Infection, Nutrition and Thyroid Disease

Choose the correct statement about community-acquired methicillin-resistant

Staphylococcus aureus (CA-MRSA).(A) Likely arose from hospital strains

that spread into the community(B) Likely arose from de novo

acquisition of resistance by a methicillin-susceptible strain

(C) Is genetically almost identical to HA-MRSA

(D) Is less susceptible to non–-lactam antibiotics than HA-MRSA

Answer

• (B) Likely arose from de novo acquisition of resistance by a methicillin-susceptible strain

Data show the majority of pregnant women who

present with CA-MRSA are nulliparous.

(A) True (B) False

Answer

• (B) False

Which of the following is the first-line treatment for

uncomplicated skin and soft tissue infection with MRSA?

(A) Incision and drainage (B) Daptomycin

(C) Linezolid (D) Tigecycline

Answer

• (A) Incision and drainage

Which of the following is considered first-line therapy for complicated skin and soft tissue

MRSA infection?(A) Co-trimoxazole (TMP/SMX)

(B) Clindamycin (C) Doxycycline (D) Vancomycin

Answer

• (D) Vancomycin

MRSA active surveillance cultures (ASC) that are required in California

• They are required within 24 hr of admission for patients scheduled for inpatient surgery, discharged from acute care hospital during past 30 days, admitted to ICU, receiving inpatient dialysis, or transferred from skilled nursing facility Rationale for ASC—prevents patient-to-patient transmission (by using contact precautions, isolation, and/or decolonization)

• prevents subsequent infection of previously colonized patients

• enables appropriate modification of perioperative prophylaxis

• conflicting data supporting ASC led professional societies to conclude evidence insufficient to warrant routine or mandated use of ASC for detection of MRSA

Contact isolation• supporting data inconclusive

• Potential adverse events associated with contact precautions (patients likely examined less frequently and for shorter periods, compared to nonisolated patients)

• patients more likely to experience preventable adverse events (eg, pressure ulcers, falls, electrolyte imbalances)

• increased rates of depression and anxiety

• trial currently ongoing to address question of whether intensive infection control strategies reduce transmission of pathogens

Origin of community-acquired MRSA (CA-MRSA)

• 4 deaths due to MRSA reported in previously healthy children in 1999• outbreaks of CA-MRSA then reported in multiple diverse populations;• 2006 paper cited CA-MRSA as predominant cause of skin and soft

tissue infection among patients presenting to 11 emergency departments

• likely arose de novo from acquisition of resistance by methicillin-susceptible strain

• CA-MRSA genetically distinct from hospital-acquired MRSA (HA-MRSA)

• Has novel staphylococcal chromosomal cassette element; lacks multiple antibiotic resistance genes

• contains other genetic elements that may contribute to virulence

Spectrum of disease• skin and soft tissue infections most common, followed by wound infections,

urinary tract infections, and bacteremia• CA-MRSA more susceptible to non–Beta-lactam antibiotics (compared to HA-

MRSA)• Cochrane Database of Systematic Reviews (2008)—reported reduction of

nosocomial S aureus infections in surgical and dialysis patients• however, most patients had methicillin- sensitive S aureus (MSSA), and those

with MRSA had HA strain• studies of nonsurgical patients and MRSA• carriers showed no benefit• 2003 review—topical mupirocin and systemic antimicrobial therapy not

effective in eradicating nasal or extranasal MRSA• adverse events and development of resistance observed with oral systemic

decolonization

MRSA carriage in pregnancy• approximately one-third of women carriers (1% colonized with MRSA; both rates consistent

with general population); 5% of infants carriers (<1% MRSA)• no evidence of maternal-infant transmission; vaginal- rectal colonization—prevalence 0.4% to

3.5%• Conflicting data on association with Group B streptococcus carriage• data looking at colonization and risk for vertical transmission showed no cases of early-onset

invasive neonatal MRSA infections• no evidence of substantial cost benefit with MRSA screening and decolonization, regardless of

success of treatment• perioperative prophylaxis—meta-analysis of cardiac surgery patients treated with vancomycin or

Beta-lactam showed no increased benefit from use of either drug• vancomycin did appear to reduce rate of surgical site infection in subgroup of patients with

MRSA• threshold prevalence of MRSA infections for changing prophylaxis regimens not yet defined• protocol at UCSF—perform ASC on selected patient group• focus on education of patient and health care personnel to reinforce standard precautions and hand

hygiene

MRSA in pregnancy• clinical presentation—data show majority of infected patients multiparous• clinical infection mostly during second trimester• mastitis and surgical site infection most common postpartum infections; skin and• soft tissue infections predominant clinical presentation;• data show no significant difference in obstetric outcomes between women with CA-MRSA and those without CA-MRSA• postpartum mastitis—data show no difference in age, pregnancy history, clinical presentation, or prenatal or intrapartum

risk factors• patients more likely multiparous (may reflect increased prevalence of MRSA among children)• no significant differences in clinical outcomes with antibiotic use• MSSA predominant organism in women without abscess• MRSA dominant organism in women with abscess• MRSA and MSSA significant pathogens in nonpuerperal mastitis• management of uncomplicated skin and soft tissue infections—incision and drainage (I and D) primary treatment• benefit of antibiotic beyond that of I and D unknown• consider empiric treatment with systemic symptoms, severe local symptoms, or immunosuppression; antibiotics may have

more important role in patients treated with minimally invasive drainage techniques• Empiric therapy—if abscess present and antibiotic therapy indicated, consider coverage for CA-MRSA (pending culture)• for mastitis without abscess, consider coverage for CA-MRSA based on local epidemiology or failure to respond to Beta-

lactam therapy

Antimicrobial therapy• co-trimoxazole (TMP/SMX)—low rate of resistance• covers MRSA and MSSA• unreliable for group A streptococcal infection; pregnancy category C or D in third trimester• clindamycin—covers MRSA, MSSA, and group A streptococci• excellent tissue and abscess penetration• potential for resistance• risk for Clostridium difficile• pregnancy category B• doxycycline—low resistance; covers MRSA and MSSA, but unreliable for group A• Streptococci• pregnancy category D• linezolid—indicated for complicated skin and soft tissue infections• Adverse events associated with long-term use (eg, potential bone marrow suppression, neurotoxicity)• pregnancy category C• inducible clindamycin resistance—not detected by standard broth microdilution testing• consider with erythromycin-resistant but clindamycin-susceptible isolate• If disk diffusion-test positive but patient improving, continue clindamycin• change therapy with failure or moderately severe infection• management of complicated skin or soft tissue infections—empiric therapy for MRSA recommended (vancomycin first-line drug)• daptomycin (pregnancy category B) and tigecycline (pregnancy category D) approved• no significant difference in primary outcome of clinical cure among these 4 drugs

MRSA and breastfeeding

• one case report of transmission of MRSA via breast milk (mother asymptomatic)

• no clear data on whether woman with postpartum mastitis should continue breastfeeding

• breast emptying mainstay of therapy

• some experts recommend continuing breastfeeding if mother on antibiotics, unless draining wound or cellulitis in area

• another recommends breastfeeding on contralateral side and expressing on infected side

Vulvar abscesses• data show MRSA dominant pathogen in

64% of women treated for vulvar abscess

• no distinguishing clinical signs or symptoms

• no difference in clinical outcomes; perform I and D

• treat with TMP/SMX (covers MRSA and majority of other pathogens)

Study: Lesser-known bug a bigger hospital threat

• March 20, 2010|By MIKE STOBBE, AP Medical Writer• 2010-03-20 06:12:00 PDT Atlanta, , United States — (03-

20) 06:12 PDT ATLANTA (AP) --• As one superbug seems to be fading as a threat in

hospitals, another is on the rise, a new study suggests.• A dangerous, drug-resistant staph infection called MRSA

is often seen as the biggest germ threat to patients in hospitals and other health care facilities.

• But infections from Clostridium difficile — known as C-diff — are surpassing MRSA infections, the study of 28 hospitals in the Southeast found.

C-Diff• "I think MRSA is almost a household name. • Everybody thinks of MRSA as a serious threat," said Dr. Becky Miller, an infectious

diseases specialist at Duke University Medical Center. She presented the research Saturday in Atlanta, at a medical conference on infection in health care facilities.

• "But C. difficile deserves more attention," she added.• MRSA, or methicillin-resistant Staphylococcus aureus, are bacteria that can't be

treated with common antibiotics. They are often harmless as they ride on the skin, but become deadly once they get in the bloodstream. They enter through wounds, intravenous lines and other paths.

• C-diff, also resistant to some antibiotics, is found in the colon and can cause diarrhea and a more serious intestinal condition known as colitis.

• It is spread by spores in feces. The spores are difficult to kill with most conventional household cleaners or alcohol-based hand sanitizers, so some of the disinfection measures against MRSA don't work on C-diff.

• Deaths from C-diff traditionally have been rare, but a more dangerous form has emerged in the last ten years.

• Still, MRSA is generally considered a more lethal threat, causing an estimated 18,000 U.S. deaths annually.

C-Diff• The new study looked at infection rates from community hospitals in Virginia,

North Carolina, South Carolina and Georgia in 2008 and 2009. • It found the rate of hospital-acquired C-diff infections was 25 percent higher than

MRSA infections.• Here are the numbers: The hospitals counted 847 infections of hospital-acquired

C-diff, and 680 cases of MRSA.• Miller also reported that C-diff was increasing at the hospitals since 2007, while

MRSA has been declining since 2005.• Last year, a government report noted a decline in MRSA infections in a study of

600 hospital intensive-care units. • MRSA bloodstream infections connected with intravenous tubes fell almost 50

percent from 1997 to 2007, according to data reported to the Centers for Disease Control and Prevention.

• C-diff has seemed to be increasing in recent years, but the trend is not uniform — some hospitals report falling rates.

• The prevalence of different infections can vary in different parts of the country, said Dr. L. Clifford McDonald, a CDC expert who was not part of the Duke study.

What is a Hospital Acquired Infection

• An infection that is not present or incubating at the time healthcare services are delivered

• IT presents symptomatically 48 hours or more after admission or provision of care

HAI Frequency

• Each year in the US, five to ten percent of all patients admitted to the hospital develop HAI’s

• This translates to almost two million cases of HAI each year, in hospitals alone.

• HAI’s may also be acquired in the Ambulatory care setting and Home care setting

Overview: thyroid nodules

• common; found in 50% of patients on ultrasonography (US)

• About 10% of patients on palpation

• thyroid dysfunction—occurs in up to 1 in 8 patients, especially in elderly population

• thyroid conditions found predominantly in women

Thyrotropin (TSH) as monitoring tool

• only 0.04% of TSH in free bioactive form

• remainder bound (ie, inactive hormone) to thyroxine-binding globulin (TBG) and albumin

• therefore, never use total T4 to assess thyroid function

Factors affecting T4 levels, Use TSH in pregnancy

• estrogen—increases TBG;

• pregnancy—total T4 can increase (to 14-16 g/dL), becauseo of increased binding proteins, and stay within normal range

• other estrogen sources—replacement therapy, contraception, and infertility treatments with follicle-stimulating hormone (FSH) injections

• long-term narcotic use—elevates T4; leuprolide (eg, Lupron)—lowers TBG and T4

• changes in pregnancy—TGB levels rise quickly at start, plateau at 20 wk, then stabilize

• 50% increase in T4 during first 20 wk (eg, from 9 to 13 μg/dL)

• estimate thyroid functions with TSH (levels decrease when thyroid hormone increases, and vice versa)

• 2-fold change in T4 levels results in 100-fold change in TSH

• TSH more sensitive, accurate, and can diagnose euthyroidism, hypothyroidism, and hyperthyroidism

Hypothyroid Prevalence

• In men it is 2% to 3% over decades,

• until >70 yr of age (increases to 10% of men)

• women—stepwise increase starting at 30 yr of age

• by >70 yr of age, 1 in 7 or 8 womem has unsuspected hypothyroidism

Screening• TSH—most sensitive and specific test for

hypothyroidism

• inexpensive

Causes• Hashimoto disease most common• other causes— radioactive iodine therapy or thyroid surgery• Hashimoto disease: ask about family history of thyroid and other

autoimmune diseases (eg, lupus erythematosus, colitis)• environmental factors include pregnancy (presence of fetus can activate

maternal immune system and initiate autoimmune disease)• thyroperoxidase (TPO) antibody rises before onset of disease; predicting

disease• measure TPO antibody levels rather than antithyroglobulin antibodies• after destruction, TSH will rise• Patient with mildly elevated TSH and positive antibody has 5% per year

chance of developing hypothyroidism

TSH and TPO antibody in diagnosis

• slightly elevated TSH does not always lead to disease

• study of elderly patients with mildly elevated TSH—in patients positive for TPO, 80% developed hypothyroidism after 4 yr (vs very few in negative TPO group)

• if hypothyroidism suspected—measure TSH; if TSH low—patient possibly hyperthyroid

• 0.3 to 3.5 g/dL considered restricted normal range

• if >9 g/dL—patient hypothyroid; requires treatment

• if 3.5 to 9 g/dL—repeat TSH 2 mo later (about 50% of patients normalize) and measure TPO antibody

• treat if positive

Treatment• levothyroxine standard treatment• structure identical to that of natural thyroid hormone• long half-life (7- 10 days)• once-daily dosing (can take 2 next day if 1 dose missed)• T3—50 to 100 times more active than T4• dose—determined by age and weight• drastic weight loss may require reduction in dose• younger patients need more thyroid hormone because of

faster metabolism

Contraindications: drugs• estrogen therapy and antiseizure drugs increase binding protein• may need more hormone to fill binding sites• pregnancy—50% to 80% of pregnant women taking thyroid

hormone require 25% to 50% increase in dose;• interference with thyroid hormone absorption • Levothyroxine locked by supplementation with iron or calcium,

and sucralfate• history of malabsorption (eg, celiac disease), and ingestion of

high-fat foods• Best time to take is on empty stomach one half hour prior to

breakfast.

Importance of thyroid hormone brand

• study of patients using 4 brands of hormone

• normal thyroid function at start of study

• change in brand (not dose) increased risk for abnormal thyroid function by 40% to 50% (50% of affected patients hyperthyroid, 50% hypothyroid)

• Take home messages—specify “no substitution of brand”

• Instruct patient to verify that same manufacturer used for each refill

• if manufacturer changes, patient must return for recheck of thyroid hormone levels after 1 mo

Maintenance of thyroid function

• study data show only 60% of patients taking thyroid hormone fall within normal range

• 20% have excess hormone; 20% undertreated

• New England Journal of Medicine (NEJM) study found after initiation of oral contraceptives in 25 women on thyroid hormone, 10 had elevated TSH levels

• Hashimoto disease—add 25 to 50 g of thyroid hormone (25% dose increase)

• no thyroid function—after, eg, radioactive iodine or thyroid surgery, 50% dose increase required

Changes in thyroid function during pregnancy

• if untreated, increases risk of worsening of hypothyroidism and for preeclampsia, anemia, postpartum hemorrhage, and cardiac ventricular dysfunction

• effects on offspring—increased risk for spontaneous abortion, low birth weight, abnormal brain development, and lower intelligence quotient (IQ)

• Controversial NEJM study—IQ <85 in 4% of children born to control women vs 13% born to women with hypothyroidism

• thyroid testing by primary care physicians recommended

• may see pregnant women earlier than obstetricians (in first trimester)

• Hypothyroidism may occur in first 20 wk (when TBGs rising)

• check TSH as soon as pregnancy confirmed

• check every 4 wk until week 20

• increase dose by 50 to 75 g/day

• after delivery, return to previous dose

Subclinical hypothyroidism

• signs and symptoms—weight gain, fatigue, or TPO antibody positivity

• treatment—L-thyroxine (brand name or consistent generic manufacturer)

• taken on empty stomach

• avoid calcium and iron at the same time

Graves disease• most common cause of thyrotoxicosis• Autoimmune disease caused by thyroid-stimulating

immunoglobulin (TSI)• occurs predominantly in women 30 to 49 yr of age• pregnancy—condition exacerbated during first trimester• improves in second and third trimesters (ie, can stop

antithyroid medicine)• worsens 1 to 6 mo postpartum• fluctuations most likely due to changes in immune status

Treatment• methimazole or propylthiouracil (PTU)—interfere with thyroid hormone synthesis

• complications—pruritus occurs in 20% of patients (treat with antihistamines)

• 3 in 1000 have agranulocytosis

• if extreme sore throat or fever >101°F develop, stop medication and obtain complete blood count; hepatitis and arthralgia (rare)

• dosage during pregnancy and breastfeeding—PTU preferred (less transfer through placenta and breast milk) to decrease likelihood of fetal goiter

• Give lowest possible dose of antithyroid drug

• T3 and T4 in pregnancy

• maintain higher limits of normal, or slightly high (studies show no negative outcomes of mild thyrotoxicosis)

• check thyroid functions monthly in pregnant women taking antithyroid drugs

• TSI—extremely high levels at end of pregnancy predict neonatal hyperthyroidism

• fetal US recommended, as large fetal goiter can cause asphyxiation during delivery

• if noncompliant or requiring high doses of antithyroid medication recommend surgery during second trimester

Alternative cause of low TSH during pregnancy

• Beta-human chorionic gonadotropin (Beta hCG) structurally similar to TSH

• Beta-hCG rises to maximal level at 12 wk, then falls to high but stable level; Beta-hCG binds to TSH receptors and causes slight increase in thyroid hormone

• therefore, TSH drops during first trimester, then rises as Beta-hCG drops;

• take-home message• low TSH during pregnancy not always indicative of hyperthyroidism• measure thyroid function at end of first trimester; if TSH suppressed

and T4 or free T4 normal or slightly elevated, do not treat• check levels next month

Which of the following statements about zinc is CORRECT?

A:Oral zinc improves healing of venous and arterial

ulcers of the legs.B:

Nasal zinc gel reduces the duration of symptoms of the common cold.

C:Most zinc is absorbed in the ileum and renally

excreted.D:

Routine zinc supplementation is necessary in healthy adults.

E:Citrus fruits are an excellent source of zinc.

Answer

• B:• Nasal zinc gel reduces the duration

of symptoms of the common cold.

Zinc•  Zinc is an essential trace element and a component of many metalloenzymes. It is involved in alcohol, carbohydrate and nucleic acids metabolism. Zinc plays a role in DNA, RNA

and protein synthesis and stabilization. It has a structural function in ribosomes and cell membranes and impacts polynucleotide transcription and genetic expression. Steroid hormone receptors depend on zinc for hormone binding. Zinc influences spermatogenesis, embryonic development and fetal growth. Additionally, zinc influences taste and smell, promotes wound healing and supports the immune system.

•  Vegetables, lean red meat, eggs, nuts and shellfish are all good sources for zinc. The recommended daily allowance (RDA) for zinc in males is 11 mg daily; females require 9 mg daily with slightly more needed during pregnancy and lactation. Children 4-8 years old require 5 mg daily, while children 9-13 years need 8 mg per day. Supplementation is not necessary in persons who eat a regular diet.

•  Zinc is absorbed in the jejunum. Both dietary fiber and phytate found in whole grain can inhibit absorption. Copper, iron and oxalate may impair uptake. Drugs that decrease zinc absorption includepenicillamine, ethambutol and sodium valproate.

• Zinc is stored intracellularly, mostly in bone and muscle, with less stored in the liver and kidneys. The majority is excreted in stool, although 10 percent is lost in urine. Sweat and desquamated epithelial cells also contain zinc.

•  Zinc deficiency is seen with diets that are low in calories and proteins. Because pancreatic enzymes are required for absorption of dietary zinc, pancreatic disease can also cause zinc deficiency. Mild zinc deficiency is sometimes seen with diabetes mellitus, cirrhosis, inflammatory bowl disease (Crohn’s) andmalabsorption syndromes. Excess renal excretion of zinc due to renal disease also causes a deficiency.Acrodermatitis enteropathica is a rare autosomal recessive condition in which zinc is not absorbed normally and results in a zinc deficit. Patients receiving total parenteral nutrition (TPN) develop zinc deficiency unless supplements are provided.

•  Clinical Findings with Zinc Deficiency•  Abdominal pAlopeciAnorexia

• Anxiety Depression• Dermatitis Diarrhea• Glossitis,, Growth delay• Impaired wound healing Night blindness• Poor concentrationStomatitis

•  Measurement of zinc level is possible using either plasma or white blood cells. Plasma levels less than60mcg/dL are considered low. Because zinc is a cofactor for alkaline phosphatase (ALP), low ALP levels are confirmatory for zinc deficiency. Zinc 60 mg given twice daily is recommended for supplementation.

•  While zinc toxicity is uncommon, it is associated with overzealous use of supplements, contamination of food or absorption of fumes while welding using zinc. Symptoms include vomiting, diarrhea, fever and renal failure. Decreased serum copper, iron and HDL levels are also seen. Welding fumes specifically cause respiratory distress, excess salivation, headaches and sweating.

•  Zinc is purported to be effective for numerous medical problems. One randomized, controlled trial (RCT) involved medicating children and adolescents with zinc lozenges to treat the common cold. The lozenges were ineffective and made most subjects feel worse. Another RCT on the effectiveness of zinc nasal gel in treating the common cold found that zinc reduced the duration of cold symptoms by 1.7 days over placebo.

•  One Cochrane review found that oral zinc sulfate did not improve healing of arterial and venous ulcers of the legs. Zinc also was not effective for preventing type 2 diabetes mellitus in overweight women in another Cochrane review.

•  While routine zinc supplementation is not currently recommended, children with stunted growth and low plasma zinc concentrations may benefit from extra zinc.  In a recent systematic review, zinc supplementation produced significant changes in height and weight in prepubertal children who were small for their age  (SOR B; Ref. 2).

•  Selected references:     • 1.Beletate V, El Dib RP, Atallah AN. Zinc supplementation for the prevention of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2007; (1):CD005525. 

http://www.cochrane.org/reviews/en/ab005525.html  Accessed April 2008• 2. Brown KH, Peerson JM, Rivera J, et al. Effect of supplemental zinc on the growth and serum zinc concentrations ofprepubertal children: a meta-analysis of randomized

controlled trials. Am J Clin Nutr 2002; 75(6):1062-1071• 3. Macknin ML, Piedmonte M, Calendine C, et al. Zinc gluconate lozenges for treating the common cold in children. A randomized controlled trial. JAMA 1998; 279:1962-67.

A 32-year-old female presents to your office after Roux-en-y gastric bypass surgery 3 months prior for morbid obesity and hypertension. She has lost weight rapidly

after the surgery, but she complains of persistent nausea and vomiting with hand tingling for the previous 2 weeks. When she called the surgeon?s office, she was prescribed metoclopramide (generic, Reglan®) and advised to see her family physician. On examination her gait is unsteady, she appears slightly confused and forgetful and nystagmus is noted; her examination is otherwise unremarkable. Select

the most appropriate next step in her management. A:

Reassurance to continue oral vitamin supplementation and oral hydration

B:Referral for endoscopy to treat likely gastric outlet stenosis

C:Routine neurology referral for gastric bypass neuropathy

D:Urine toxicology screen for illicit drug use

E:Emergent admission for parental thiamine treatment

Answer

• E:• Emergent admission for parental

thiamine treatment

Wernicke Encephalopathy Following Bariatric Surgery

• Obesity surgery provides benefits in treating the complications of obesity including diabetes, sleep apnea and hypertension. As obesity rates increase (two thirds of Americans are overweight or obese),bariatric surgery rates have increased, with more than 170,000 operations performed in 2005. Given the number of cases, family physicians are caring for these patients along with bariatric surgeons, especially after the initial 30-day postoperative period when almost 1 percent of patients die from pulmonary emboli, anastomotic leaks or respiratory failure.

•  • In the long term, however, functionally diverting food past the stomach and duodenum (except for a 20 ml stomach pouch)

predisposes patients to a host of nutritional deficiencies to include iron, thiamine (Vitamin B1), pyridoxine (Vitamin B6), folic acid (Vitamin B9) and cobalamin (Vitamin B12). Despite use of lifelong vitamin supplements, poor absorption may cause complications such as peripheral neuropathy from B12 deficiency and Wernicke encephalopathy from B1 deficiency (as seen in this case). Characterized by a classic symptom triad of confusion, ataxia and nystagmus, Wernickeencephalopathy was recently described in a systematic review of more than 30 obesity surgery cases. Most Wernicke cases were seen 1-3 months postsurgery, occurred in women and were associated with abnormal vomiting (vomiting despite appropriately sized meals) and peripheral neuropathy. Of note, the classic symptom triad may be incomplete in one third of bariatric surgical patients.

•  Clinicians need to maintain a high index of suspicion in bariatric surgery patients who present with neurological symptoms; serum thiamine levels and erythrocyte transketolase levels may be normal and characteristic radiographic findings on magnetic resonance imaging (MRI) – hyperintense signal around the thalamus and 3rd/ 4th ventricles) – may be absent. MRI has a sensitivity of 53 percent and a specificity of 93 percent for the diagnosis of Wernicke encephalopathy.

•  Patients suspected to have Wernicke encephalopathy need prompt thiamine replacement (at least 100 mg daily) to reverse symptoms and prevent long-term sequelae, such as Korsakoffsyndrome (amnesia, apathy, ataxia and confabulation). Treatment response can be dramatic, with improvement seen in the first 24 hours (SOR A; Ref. 2).

•  Urine toxicology drug screening could be helpful if the patient had no response to thiamine, but it would not be the initial indicated action, given the classic combination of Wernicke-like symptoms in a gastric bypass patient. Gastric bypass neuropathy can occur due to thiamine-deficiency-related defects in the myelin sheath, but thiamine replacement would be the best response, not delaying treatment for a neurologic consult. While nausea after obesity surgery is common, persistent vomiting is abnormal. Proceeding directly to therapeutic endoscopic dilatation would be premature without first performing a diagnostic upper gastrointestinal series.

•  Selected references:• 1. Sechi G, Serra A. Wernicke's encephalopathy: new clinical settings and recent advances in diagnosis and management.

Lancet Neurol 2007; 6(5):442-455.• 2. Singh S, Kumar A. Wernicke encephalopathy after obesity surgery: a systematic review. Neurology 2007; 68(11):807-811.• 3. Virji A, Murr MM. Caring for patients after bariatric surgery. Am Fam Physician 2006; 73(8): 1403-8.

http://www.aafp.org/afp/20060415/1403.html  Accessed March 2008

Water-soluble vitamins are absorbed, transported and quickly excreted. Because they are not stored, water-soluble vitamins must be regularly replaced. Which group of

symptoms is correctly paired with its causative vitamin deficiency?

A:Vitamin B3 (niacin) deficiency ? cheilitis,

stomatitis, glossitisB:

Vitamin B2 (riboflavin) deficiency ? scurvyC:

Vitamin B1 (thiamine) deficiency ? BeriberiD:

Vitamin B6 (pyridoxine) deficiency ? dermatitis, dementia, diarrhea

E:Vitamin C (ascorbic acid) deficiency ? elevated

homocysteine levels

Answer

• C:

• Vitamin B1 (thiamine) deficiency ? Beriber

Water Soluble Vitamins•  Vitamin B1 (thiamine) is important for normal cardiac, muscle and nervous tissue function. Thiamine deficiency is associated with

beriberi, Wernicke-Korsakoff syndrome and Leigh’s syndrome. Beriberi is a symmetric peripheral neuropathy. “Dry” beriberi is a combination sensory/motor neuropathy. “Wet” beriberi involves a combination of neuropathy and cardiac impairments (cardiomyopathy and congestive heart failure). Wernicke-Korsakoff syndrome is characterized by the triad of nystagmus,ophthalmoplegia and ataxia. Leigh’s syndrome is a form of subacute necrotizing encephalomyopathy.

•  Vitamin B3 (niacin) is metabolized to active forms that are involved in the synthesis and metabolism of carbohydrates, fatty acids and proteins. Niacin deficiency is rare but is occasionally seen withcarcinoid syndrome, Hartnup disease and prolonged use of isoniazid. Symptoms of niacin deficiency include diarrhea, dementia, delusions and dermatitis. The dermatitis is a symmetric, hyperpigmented, sunburn-like rash in sun-exposed areas.

•  Vitamin B2 (riboflavin) promotes development of skin and red blood cells through energy conversion of glucose. Riboflavin deficiency causes dry, cracked skin; cheilitis; stomatitis; and glossitis. Anormocytic-normochromic anemia is often seen. While riboflavin deficiency is rare, certain groups are at risk. Persons with anorexia nervosa, lactose intolerance, malabsorption syndromes, inborn errors of metabolism or long-term barbiturate use are at increased risk.

•  Vitamin B6 (pyridoxine) is necessary for the formation of amino acids, red blood cells and antibodies. Low levels of pyridoxine are associated with elevated homocysteine levels and increased risk for heart disease. Pyridoxine deficiency also causes stomatitis, glossitis, cheilosis, confusion and depression.

•  Vitamin C (ascorbic acid) has several important functions. It helps build and maintain collagen and connective tissue. Vitamin C enhances iron and folic acid absorption, aids in wound healing and is an antioxidant. Scurvy, ecchymoses, bleeding gums, petechiae and impaired wound healing are all associated with vitamin C deficiency. Other symptoms include weakness, malaise, joint swelling,arthralgias and neuropathy. Routine vitamin C supplementation provides a consistent, statistically significant benefit, albeit small, on the duration and severity in the common cold (SOR B; Ref. 2).

•  Selected references:• 1. Cervantes-Laurean N, McElvaney G, Moss J. Niacin. In: Shils M, ed, Modern Nutrition in Health and Medicine.Philadelphia: Lippincott,

2000:401.• 2. Douglas R, Hemila H, Chalker E, et al. Vitamin C for preventing and treating the common cold. Cochrane DatabasSyst Rev 1998;

(1):CD000980. http://www.cochrane.org/reviews/en/ab000980.html  Accessed March 2008• 3. Elsas LS, Longo N, Rosenberg LE. Inherited defects of membrane transport. In: Fauci AS, Braunwald E, IsselbacherK, et al., eds,

Harrison’s Principles of Internal Medicine. 14th ed. New York: McGraw-Hill, 1998:2203.• 4. Jacob R. Vitamin C. In: Shils M, Olson J, Shike M, et al., eds, Modern Nutrition in Health and Disease. Philadelphia:Lippincott, 2000:467.• 5. Siegfried DR, Simmons K. Vitamins & minerals. Arthritis Today. 2007; 9-10:69-71.• 6. Tanphalchitr V. In: Shils M, ed, Modern Nutrition in Health and Medicine. 9 th ed. Philadelphia: Lippincott, 2000:381.• 7. Wilson JA. Vitamin deficiency and excess. In: Fauci AS, Braunwald E, Isselbacher K,  et al., eds, Harrison’s Principles of Internal Medicine.

14th ed. New York: McGraw-Hill, 1998:481

A 75-year-old patient who resides in a nursing home has just become your patient. She states that “her

bones are brittle.” She has a family history of osteoporosis and hates taking medications,

although she has been on 1,500 milligrams of calcium citrate daily for years. She wants to know

whether vitamin D supplementation, as recommended by her grandson who is a nurse, would help her bones. Of the following options, what dose and form of vitamin D would be most likely to help prevent fractures in this patient?

A:200 IU vitamin D3

B:400 IU vitamin D2

C:800 IU 25-hydroxyvitamin D

D:800 IU vitamin D3

E:2,000 IU vitamin D of any form

Answer

•800 IU vitamin D3

A 6-month-old infant girl is being evaluated for recurrent vomiting, diarrhea and a relatively rapid fall from the 50th percentile for weight to the 10th percentile over a

period of approximately 6 weeks. She was the product of a normal term pregnancy and delivery. Both parents are healthy and have two other healthy children ages 6 and 4 years. The baby was breast-fed exclusively until very recently (after her symptoms

were noted). On examination she is hypotonic, somnolent and does not play or smile. She is pale and has fasciculations and sucking movements of the tongue. Laboratory

evaluation reveals hemoglobin, 6.8 g/dL (normal, 11.2-16.5 g/dL); hematocrit, 24 percent (normal, 35-49 percent); MCV, 102 fL (normal, 80-96 fL); MCH, 32 pg/cell

(normal, 26-34 pg/cell); MCHC, 32.8 g/dL (normal, 32-36 g/dL); platelet count, 412 x 109/L (normal, 150-400 x 109/L); and WBC, 5,500 /mm3 (normal, 4,500-11,000/mm3). The

peripheral blood film showed megaloblastic features including oval macrocytosis, anisopoikilocytosis and hypersegmented polymorphs. Additional evaluation for her

anemia reveals normal serum iron and thyroid function tests. She has a normal folate level; however, her B12 is low at 75 pg/mL (normal, 180-900 pg/mL). In a search for the cause for the vitamin B12 deficiency, additional questioning of the parents reveals that the mother has been a strict vegetarian (no animal products or byproducts) for almost 4 years. Which of the following statements regarding Vitamin B12 deficiency in infants

is CORRECT? A:

Maternal vitamin B12 serum levels normally increase during pregnancy without vitamin supplementation.

B:Guidelines recommend serum testing of vitamin B12levels in infants of pregnant women who are

strict vegetarians.C:

Pregnant vegetarians who consume milk in their diet are not at risk for low vitamin B12 levels.D:

Most infants born of mothers with low vitamin B12 levels immediately show signs of a neurological problem.

E:Intramuscular vitamin B12 injections with iron and folate supplements are the treatment of choice.

Answer

• E:• Intramuscular vitamin

B12 injections with iron and folate supplements are the treatment of choice.

B12 Deficiency In Infants 

• Although the maternal vitamin B12 level is known to fall throughout pregnancy, this is not considered to be significant. However, correlation exists between maternal and neonatal vitamin levels and corresponding neonatal homocysteine levels. With severe maternal vitamin B12 deficiency, spontaneous abortions may occur, and, if this persists, infertility may ensue. With a mild deficiency, a normal pregnancy and delivery at term may occur, but such infants have low vitamin B12 levels at birth and may also be at risk of developmental defects. The situation of vitamin deficiency is perpetuated if the vitamin B12-deficient mother breast-feeds her infant. Vitamin B12 levels are very low in the milk of these mothers.

•  One of the causes of low maternal vitamin B12 is dietary deficiency. Vegans (vegetarians without intake of any animal products) have no vitamin B12 in their diet unless there is contamination by soil or bacteria. Vegetarians who also consume milk, milk products and eggs may also have low vitamin B12 levels. Vegetarians may mask the hematological effects of vitamin B12 deficiency due to their high folate (folic acid) intake and, therefore, have normal hemoglobin levels. Oral folatesupplement in the diet and the taking of folate preparations in pregnancy to prevent neural tube defects may also have a masking effect.

•  The clinical picture of vitamin B12 deficiency may appear in the infant several months after birth and after a period of normal development. The first signs of deficiency are irritability, anorexia, apathy, vomiting, weak cry and regression of motor development. The infant then fails to thrive and may develop neurological features such as head lag, hyporeflexia, hypotonia and choreoathetoidmovements. Heart failure may eventually develop. This may be associated with macrocytic anemia (which may be severe), hypersegmented polymorphonuclear leukocytes and tissue evidence of vitamin B12 deficiency such as raised methylmalonic acid levels. Little information is available about long-term neurological sequelae. Intellectual impairment, gait disturbance and epilepsy may result.

•  can cause severe disease and since treatment is readily available and effective, screening of newborns of mothers who are vegetarian may be indicated. Guidelines for screening have not been established, although screening for increased urinary methylmalonic acid (a sign of B12 deficiency) at 3 weeks of age has been suggested but requires additional study. Treatment includes intramuscular vitamin B12administration as well as iron and folate supplementation.

•  Selected references:• 1. Campbell CD, Ganesh J, Ficicioglu C. Two newborns with nutritional vitamin B12 deficiency: challenges in newborn screening for

vitamin B12 deficiency. Haematologica 2005; 90(12 Suppl):ECR45.• 2. Casella EB, Valente M, de Navarro JM, et al. Vitamin B12 deficiency in infancy as a cause of developmental regression. Brain Dev

2005; 27(8):592-594.• 3. Simsek OP, Gonc N, Gumruk F, et al. A child with vitamin B12 deficiency presenting

with pancytopenia andhyperpigmentation. J Pediatr Hematol Oncol 2004; 26(12):834-836.•  

Ginger is a common spice and culinary herb. Which of the following statements

regarding ginger is CORRECT? A:

Ginger is approved by the U.S. Food and Drug Administration for the treatment of nausea

associated with chemotherapy.B:

At least one randomized controlled study suggests that ginger is effective in the treatment

of nausea associated with early pregnancy.C:

A common side effect of ginger is constipation.D:

Ginger tends to elevate cholesterol levels.E:

Ginger tends to promote blood clotting.

Answer

• B:• At least one randomized controlled

study suggests that ginger is effective in the treatment of nausea associated with early pregnancy.

Ginger•  Ginger has been used for its medicinal effects since ancient times. Today, it is one of the most popular herbal supplements and is purported to be

helpful for several medical conditions. The U.S. Food and Drug Administration categorizes ginger as a food additive. Ginger has been studied for the treatment for nausea and vomiting, especially during early pregnancy, and arthritis.

•  • Ginger 250 mg PO QID has been proven effective in treating nausea and vomiting of early pregnancy. Human studies show no

adverse effects on the fetus. Ginger has been found to suppress gastric contractions and increase gastrointestinal motility (SOR B; Ref. 4). Six studies involving approximately 700 patients support the effectiveness of ginger on nausea and vomiting of early pregnancy. Ginger was superior to placebo in 4 of the studies and comparable to vitamin B6(pyridoxine) in 2 studies. One possible mechanism to explain ginger’s antiemetic property is that it appears to inhibit serotonin receptors of both the gastrointestinal and central nervous systems. Ginger has also been recommended for the treatment of motion sickness and chemotherapy-induced nausea and vomiting. However, evidence has not proved its effectiveness for these conditions.

•  • Another common medicinal use of ginger is to decrease inflammation. Ginger has been shown to inhibit the activation of tumor necrosis factor

alpha and cyclooxygenase-2 expression. It is used widely today for the treatment of osteoarthritis and ulcerative colitis. Studies of its efficacy, however, have concluded shown mixed results.

•  • Ginger has also been reported to have a wide range of effects on the cardiovascular system. A few preliminary studies have suggested a

protective effect on coronary artery disease by lowering cholesterol and preventing blood from clotting. In contrast, ginger may be inotropic and has been reported to cause arrhythmias. It should be used cautiously in patients taking warfarin (generic,Coumadin®), since it may prolong bleeding time. Overall, ginger has few side effects. The most common ones are heartburn, diarrhea and irritation of the mucous membrane of the mouth.

•  • Selected references:• 1. Altman RD, Marcussen KC. Effects of a ginger extract on knee pain in patients with osteoarthritis. Arthritis Rheum 2001; 44:2531-2538.• 2. Chaiyakunapruk N, Kitikannakorn N, Nathisuwan S, et al. The efficacy of ginger for the prevention of postoperative nausea and vomiting: a

meta-analysis. Am J Obstet Gynecol 2006; 194:95-99.• 3. Frondoza CG, Sohrabi A, Polotsky A, et al. An in vitro screening assay for inhibitors of proinflammatory mediators in herbal extracts using

human synoviocyte cultures. In Vitro Cell Dev Biol Anim 2004; 40:95-101.• 4. Jewell D, Young G. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev2003;(4):CD000145. 

http://www.cochrane.org/reviews/en/ab000145.html  Accessed March 2008• 5. University of Texas at Austin. Recommendations for the evaluation and management of nausea and vomiting of early pregnancy (<20 weeks

gestation). http://www.guideline.gov/guidelines/FTNGC-2454.html  Accessed March 2008• 6. White B. Ginger: an overview. Am Fam Physician 2007; 75(11):1689-1691.http://www.aafp.org/afp/20070601/1689.html  Accessed March 2008 

Which of the following statements regarding high-density lipoprotein (HDL) cholesterol is CORRECT?

A:Low HDL cholesterol level is defined as less than 30 mg/dL.

B:The use of beta-blockers has been associated with an

increase in HDL serum levels.C:

Elimination of dietary trans fat can increase HDL serum levels.

D:The Mediterranean diet for improvement of HDL serum

levels consists of a relatively high intake of red meat and alcohol with low carbohydrate intake.

E:Thirty to 60 minutes of exercise on most days of the week will decrease LDL serum levels but should not be expected

to change HDL levels.

Answer

• C:• Elimination of dietary trans fat can

increase HDL serum levels.

HDL Diets• A low-serum high-density lipoprotein (HDL) cholesterol level has been recognized as an independent risk factor for

development of cardiovascular disease. HDL levels vary among different racial/ethnic groups, with African Americans having higher HDL levels in general than Caucasians. Up to half of the variability in HDL levels is related to genetic inheritance.

•  • Every 1mg/dL increase in HDL level is associated with a 2-3 percent decrease in coronary artery disease risk. A

low HDL is defined as <40 mg/dL and is often associated with elevated triglyceride levels, obesity, cigarette smoking, type II diabetes mellitus and ingestion of certain medications (e.g., beta-blockers, steroids and progestins). Lifestyle modification is the first line of treatment for low serum HDL levels. Thirty to 60 minutes of exercise on most days of the week can increase HDL. Elimination of dietary trans fatty acids can help decrease LDL levels and, simultaneously, increase HDL.Trans fat is monosaturated or polyunsaturated fat that has been commercially hydrogenated, making it chemically similar to saturated fats. The hydrogenation process increases the melting point, makingtrans fat easier to bake with, and the reduction in oxidation potential increases shelf life. Replacingtrans fats with healthy, monosaturated fats (canola oil, safflower oil, olive oil), polyunsaturated fats (corn oil, soybean oil) and monosaturated-rich nuts (hazelnuts, almonds, pecans, cashews, walnuts, macadamia nuts) can increase HDL levels. Although both monosaturated and polyunsaturated fats are preferred over trans fat, monosaturated fats are recommended over polyunsaturated fats (which have been associated with increased platelet aggregation and incorporation of LDL into the arterial intima, leading to plaque formation). The addition of fiber (particularly soluble) or a fish oil supplement can add further gains in HDL levels. Moderate alcohol intake (up to 1 drink daily for women and 2 drinks daily for men) has also been shown to increase HDL levels.

•  • A Mediterranean diet, one that is rich in fruits and vegetables and includes healthy fat, is the best diet

to increase HDL levels. The Mediterranean diet was first studied more than 50 years ago when it was noticed that adults on the island of Crete lived longer and had fewer cardiovascular events than adults in the United States. While this is not a specific diet, general guidelines include high intake of vegetables, fruit, nuts, legumes and grains; high intake of olive oil (but low intake of saturated fats); moderate intake of fish; low to moderate intake of dairy products (primarily cheese or yogurt); limitation of eggs; low consumption of poultry; and very low consumption of red meat. Moderate alcohol consumption, primarily wine with meals, is also part of the diet. The food pyramid in Figure 2 gives a graphic representation of one interpretation of the diet.

•  

DIRECTIONS: The following series of questions deals with primary and

secondary hyperparathyroidism. For the following four questions, select the answer

most closely associated with the statement. 

Surgery is the primary form of treatment. A:

if primary hyperparathyroidism is associated with the statement

 B:if secondary hyperparathyroidism is associated

with the statement C:

if BOTH primary hyperparathyroidism and secondary hyperparathyroidism are associated

with the statement D:

if NEITHER primary hyperparathyroidism NOR secondary hyperparathyroidism is associated

with the statement

Answer

•  A:• if primary hyperparathyroidism is

associated with the statement

Treatment with 1,25-hydroxycholecalciferol (1,25-dihydroxy

vitamin D3, calcitriol) is indicated. A:

if primary hyperparathyroidism is associated with the statement

 B:if secondary hyperparathyroidism is associated

with the statement C:

if BOTH primary hyperparathyroidism and secondary hyperparathyroidism are associated

with the statement D:

if NEITHER primary hyperparathyroidism NOR secondary hyperparathyroidism is associated

with the statement

Answer

•  B:• if secondary hyperparathyroidism

is associated with the statement

Most commonly caused by chronic kidney disease  

A:if primary hyperparathyroidism is associated

with the statement B:

if secondary hyperparathyroidism is associated with the statement

 C:if BOTH primary hyperparathyroidism and

secondary hyperparathyroidism are associated with the statement

 D:if NEITHER primary hyperparathyroidism NOR secondary hyperparathyroidism is associated

with the statement

Answer

•  B:• if secondary hyperparathyroidism

is associated with the statemen

May result in hypercalcemia  A:

if primary hyperparathyroidism is associated with the statement

 B:if secondary hyperparathyroidism is associated

with the statement C:

if BOTH primary hyperparathyroidism and secondary hyperparathyroidism are associated

with the statement D:

if NEITHER primary hyperparathyroidism NOR secondary hyperparathyroidism is associated

with the statement

Answer

•  C:• if BOTH primary

hyperparathyroidism and secondary hyperparathyroidism are associated with the statement

Hyperparathyroidism•  Four parathyroid glands are located behind the thyroid gland. Through the secretion of parathyroid hormone (PTH), these small glands regulate calcium absorption

from the gut, calcium secretion by the kidneys and calcium storage in bones. Calcium plays multiple roles within the human body including bone metabolism, nerve function and muscle activity. When serum calcium levels fall, PTH secretion increases. If serum levels of calcium are chronically low, the parathyroid glands may hypertrophy as they attempt to produce adequate amounts of PTH to maintain a normal calcium level.

•  Vitamin D also has an important role in calcium metabolism. PTH and vitamin D closely influence each other. Inadequate vitamin D leads to reduced calcium absorption, reduced serum calcium and a reactionary increase in PTH production. Vitamin D is not a true vitamin in the sense that it is not a required part of a human diet. Human skin when exposed to ultraviolet radiation creates vitamin D. In temperate climates and for those who spend most of their time indoors, dietary vitamin D or vitamin D supplements are usually necessary. Vitamin D has a confusing taxonomy. Vitamin D from dietary sources and the form of vitamin D used in nutritional supplements is cholecalciferol (vitamin D3). This form of vitamin D is metabolized in the liver to 25-hydroxycholecalciferol (25-hydroxy vitamin D 3). This in turn is metabolized by the kidney to produce 1,25-hydroxycholecalciferol (1,25-dihydroxy vitamin D 3). This form is also called calcitriol and it is the most active form of vitamin D.

•  Primary hyperparathyroidism is caused by an adenoma of usually one but sometimes more that one parathyroid gland, producing excessive amounts of PTH. This results in hypercalcemia. The hypercalcemia may initially be asymptomatic, but as the serum calcium level increases, symptoms such as proximal muscle weakness, abdominal pain and generalized fatigue may occur. The serum level at which symptoms are noted partially depends on the rate of increase. With a relatively acute rise, symptoms may be noticed at a serum level of 12 mg/dL (normal, 8.4-10.6 mg/dL). However, with a slow, chronic elevation, symptoms may not be noticed at a serum levels as high as 12-14 mg/dL. Prolonged hypercalcemia may result in nephrocalcinosis and or osteitis fibrosa cystica.

•  Primary hyperparathyroidism resulting in significant symptoms or complications is best treated by surgical excision of the hypertrophied gland. Criteria for surgery include age younger than 50 years, serum calcium >12 mg/dL, hypercalciuria (>400 mg/day), nephrolithiasis, impaired renal function, osteitis fibrosa cystica, reduced bone mass and neuromuscular symptoms including weakness, atrophy, hyperreflexia or gait disturbance. Minimally invasive procedures are now commonly used to remove parathyroid adenomas. In older patients who are asymptomatic, who have well-preserved renal function and who have no evidence of bone disease, it may be reasonable to follow the patient regularly and decide whether symptoms subsequently require surgery.

•  Secondary hyperparathyroidism is most often caused by renal disease that negatively impacts the conversion of 25-hydroxycholecalciferol to the more active 1,25-hydroxycholecalciferol. Insufficient 1,25-hydroxycholecalciferol leads initially to hypocalcemia. This results in increased PTH secretion. The increased PTH secretion often results in hypercalcemia. Supplementation with 1,25-hydroxycholecalciferol (calcitriol) is the most effective means of treatment. In most cases calcitriol (generic, Rocaltrol®) treatment results in decreased PTH levels and a normalization of serum calcium. Patients with a mild degree of renal impairment may have secondary hyperparathyroidism without their physicians being aware of it. Physicians who care for patients with renal impairment should measure 1,25-hydroxycholecalciferol intermittently. In rare circumstanceshypertrophic parathyroid tissue may not respond to treatment with calcitriol, resulting in tertiary hyperparathyroidism. This may then require surgical treatment to remove one or more hypertrophicglands.

•  Selected references:• 1. Bailie GR, Massry SG. Clinical practice guidelines for bone metabolism and disease in chronic kidney disease: an overview.  Pharmacotherapy 2005; 25(12):1687-

1707.• 2. Carroll MF, Schade DS. A practical approach to hypercalcemia. Am Fam Physician 2003; 67:1959-1966.  http://www.aafp.org/afp/20030501/1959.html  Accessed

March 2008• 3. Diaz-Corte C, Cannata-Andia J. Management of secondary hyperparathyroidism: the gap between diagnosis and treatment.  Am J Med Sci 2000; 320(2):107-111• 4. Potts JT. Parathyroid hormone: past and present. J Endocrinol 2005; 187(3):311-325.• 5. Taniegra ED. Hyperparathyroidism. Am Fam Physician 2004; 69:333-339, 340. http://www.aafp.org/afp/20040115/333.html  Accessed March 2008 •  

Many different types of infant formulas are available. Parents often have questions concerning infant formulas for their family physicians. Which of the following is TRUE concerning infant formulas?

A:Whey is the main protein source in standard cow?s milk-

based formulas (e.g., Similar®, Enfamil®).B:

Infants on formulas supplemented with docosahexaenoic acid (DHA) and arachidonic acid (ARA) have been shown to have greater growth parameters than infants on formulas

without DHA and ARA.C:

Soy protein formulas (e.g., ProSobee®, Isomil®) are hypoallergenic formulas.

D:Soy protein formulas are recommended for infants

weighing less than 1,800 grams.E:

Elemental formulas (e.g., Neocate®, EleCare®) are recommended for infants who cannot tolerate protein

hydrolysate formulas.

Answer

• E:• Elemental formulas (e.g.,

Neocate®, EleCare®) are recommended for infants who cannot tolerate protein hydrolysate formulas

Infant Formulas•  Most infant formulas are designed to approximate the nutritional value of human milk. Standard infant formulas are cow’s milk-based and are available with

(Enfamil LIPIL®, Good Start Supreme®, SimilacAdvance®) and without (Similac with Iron®, Good Start Essentials®) docosahexaenoic acid (DHA) andarachidonic acid (ARA) supplementation. DHA and ARA supplementation have been shown to improve visual acuity and cognitive development in some studies. There is no significant difference in growth parameters, however, with this supplementation. Formulas usually contain approximately 40-50 percent of calories from carbohydrates, 40-50 percent from fat and 5-10 percent of calories from protein. Casein is the main protein source in standard infant formulas. Infants who cannot tolerate casein are given whey-predominant or whey-only formulas (e.g., Good Start®). All infant formulas are also fortified with iron as recommended by the American Academy of Pediatrics (AAP). While some formulas are labeled low iron, these are not recommended by AAP (SOR C; Ref. 3).

•  Some formulas (ProSobee LIPIL®, Good Start Supreme Soy®, Similac Isomil Advance®) are designed for infants who are allergic to standard formulas. Soy protein formulas are not true hypoallergenic formulas. Formulas are defined as hypoallergenic if randomized controlled trials show that they do not cause reactions in 90 percent of infants or children with confirmed cow’s milk allergy. Although soy protein formulas are often used for infants with cow’s milk protein-induced enterocolitis, up to 60 percent of these infants will be equally sensitive to soy protein. The AAP does not recommend soy formulas for infants weighing less than 1,800 grams due to the potential for aluminum toxicity and inadequate weight gain in premature infants.

•  Protein hydrolysate formulas (Nutramigen LIPIL®, Pregestimil®, Similac Alimentum®) are hypoallergenic formulas, as 95 percent of patients with milk protein intolerance will respond well to them. These formulas are recommended for infants who cannot tolerate standard formulas or those with conditions like cystic fibrosis, autoimmune enteropathy, HIV-associated enteropathy, short bowel syndrome  and pancreatic insufficiency. Elemental formulas (free amino acid-based) are usually reserved for infants with severe protein intolerance and those who do not respond to protein hydrolysate formula. They (EleCare ®, Neocate®) are expensive and difficult to find.

•  Specialized formulas include formulas for premature infants and follow-up formulas. Formulas for preterm infants (Enfamil Premature LIPIL ®, Similac Special Care®) have higher concentrations of protein, calcium, phosphorus, sodium, potassium and chloride than standard formulas. When these preterm infants are discharged from the hospital, they may use a transitional premature formula (Enfamil EnfaCare LIPIL ®, Similar NeoSure®) that has a nutrient composition between that of premature and standard infant formulas. Follow-up formulas (Enfamil Next Step LIPIL®, Good Start Good Supreme DHA & ARA®, Similac Go and Grow®) are designed for infants 6 months or older as they begin to eat solid foods. The AAP statement concerning these formulas is that they offer “no clear advantage for infants receiving adequate amounts of iron and vitamin in their infant formula and solid food.” 

•  Lactose-free milk-based formulas (Enfamil LactoFree LIPIL®, Similac Sensitive®) are also available for infants with lactose sensitivity.•  Selected references:• 1. Akers S, Groh-Wargo S. Normal nutrition during infancy. In: Samour PQ, Helm KK, eds, Handbook of Pediatric Nutrition. 3 rd ed. Boston: Jones & Bartlett;

2005:75-106.• 2. American Academy of Pediatrics. Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics 2000; 106:346-349. 

http://pediatrics.aappublications.org/cgi/content/full/pediatrics;106/2/346  Accessed March 2008• 3. American Academy of Pediatrics Committee on Nutrition. Iron fortification of infant formulas. Pediatrics 1999; 104:119-123. 

http://aappolicy.aappublications.org/cgi/reprint/pediatrics;104/1/119.pdf  Accessed March 2008• 4. American Academy of Pediatrics. Committee on Nutrition. Soy protein-based formulas: recommendations for use in infant feeding. Pediatrics 1998; 101:148-

153. http://pediatrics.aappublications.org/cgi/content/full/101/1/148  Accessed March 2008• 5. Fleith M, Clandinin MT, Dietary PUFA for preterm and term infants. Review of clinical studies. Crit Rev Food Sci Nutr2005; 45:205-229.• 6. Johnson K, Loomis G, Flake D. Effects of soy protein-based formula in full-term infants. FPIN clinical inquiries. AmFam Physician 2008; 77(1):87.• 7. Worthington-Roberts BS. Lactation: the mother and her milk. In: Worthington-Roberts BS, Williams SR, eds, Nutrition Throughout the Life Cycle. 4 th ed. New

York: McGraw-Hill; 2000:130-161.• 8. Wright M, Lo C. Infant formulas: a practical guide. Fam Prac Recert 2007; 29(10):33-39.http://www.fpronline.com/Article.cfm?ID=411  Accessed March 2008

A 10-day-old infant is brought to the emergency department because of concerns about poor feeding and weight loss. She was full term with a normal exam and weighing 3,500 grams. There has been no vomiting or

diarrhea. No medications have been administered. She is exclusively breast-fed. Physical examination reveals a

dehydrated, cachectic infant with a weight of 2,500 grams. Laboratory evaluation shows serum sodium, 168 mEq/L (normal, 135-146 mEq/L); potassium, 5.0 mEq/L

(normal, 3.5-5.1 mEq/L); chloride, 134 mEq/L (normal, 98-106 mEq/L); BUN, 93 mg/dL (normal, 5-20 mg/dL); and

creatinine, 1.8 mg/dL (normal, 0.3-0.7 mg/dL). Which one of the following is the infant?s MOST likely diagnosis?

A:Hypernatremic dehydration from inadequate maternal milk

productionB:

Cystic fibrosisC:

Diabetes insipidusD:

Renal failureE:

Phenylketonuria

Answer

• A:• Hypernatremic dehydration from

inadequate maternal milk production

Newborn Hypernatremic Dehydration•  The development of malnutrition, dehydration and hypernatremia in a breast-fed newborn is most likely caused by inadequate maternal milk

production. Hypernatremic dehydration requiring hospitalization occurs in approximately 2 percent of otherwise healthy breast-fed infants and typically presents at 3-9 days of age. Measurement of breast milk electrolytes in this setting will typically reveal an elevated sodium concentration characteristic of colostrum instead of the normal value of 5-9 mEq/L found in mature breast milk. A fall in breast milk sodium concentration after birth is highly predictive of successful lactation, while prolonged elevation signifies impaired lactogenesis with a high risk of breast-feeding failure.

•  The infant’s hypernatremia is not due to consumption of “salty” breast milk per se. If one ingests salt with little water, intravascular volume will be expanded, not contracted. In addition, maternal breast milk sodium concentrations in this setting, although abnormally elevated, do not generally exceed the sodium concentrations found in standard oral rehydration solutions (45-75 mEq/L). To understand thepathophysiology of this disorder, one must recall that breast milk is isotonic (approximately 285mOsm/L). Lactose normally constitutes the majority of osmoles (220 mOsm/L), while electrolytes make up 45 mOsm/L. When breast milk sodium concentration is elevated (such as 60 mEq/L), the osmolalityremains constant, so there is “less room” for lactose, resulting in insufficient lactose for weight gain. The infant becomes carbohydrate-starved and must obtain glucose from gluconeogenesis andglycogenolysis. The production of glucose from body proteins generates urea. Urinary excretion of this extra urea causes an osmotic diuresis leading to dehydration and hypernatremia because the small amount of breast milk produced is not sufficient to replace this fluid loss.

•  Appropriate treatment consists of rapid restoration of effective circulating volume with 0.9 percent saline given intravenously for infants with moderate to severe dehydration (typically with bolus of 10 mL/kg over several minutes and repeated if necessary). Subsequently, rehydration should proceed cautiously, as aggressive treatment with hypotonic fluids (relative to the hyperosmoticcondition) may cause cerebral edema and lead to coma, seizures and death. Most experts recommend that serum sodium concentration be reduced by no more than 10-12 mEq/L per day to avoid this complication. The maintenance fluid for a young infant is approximately 100 mL/kg/day. Water deficit can be estimated by the following formula:

•  Water deficit = body weight x 0.6 (1-145/[current sodium])•  Generally, fluid can be replaced at a rate 20-50 percent above maintenance adjusted to limit the reduction of serum sodium as indicated above.

Typically, after initial resuscitation, intravenous fluid replacement can be accomplished with D5 ¼ NS (osmolality 355 mOsm/kg compared to a normal serumosmolality of 285-295 mOsm/kg) or D5 ¼ NS + 20 mEq/L KCL. Breast-feeding may need to be discontinued at least temporarily or supplemented with formula. Resumption of breast-feeding can only occur if lactogenesis significantly improves. 

• Measurement of the infant’s sweat chloride concentration would test for cystic fibrosis. Although this disease can cause poor weight gain and dehydration, the dehydration is typically hyponatremic due to excessive loss of electrolytes from the sweat glands. If urine output is not reduced and osmolality is very low (< 150 mOsm/L), diabetes insipidus should be suspected. The disproportionate increase in BUN compared to creatinine would indicate that dehydration is the cause of the creatinine elevation, not renal failure. Phenylketonuria does not present with symptoms in the first few months of life nor are these biochemical abnormalities noted.

•  Selected references:• 1. Halperin ML, Goldstein MB. Fluid, Electrolyte and Acid-Base Physiology. 3rd ed. Philadelphia: WB Saunders, 1999:329-367.• 2. Moritz ML, Manole MD, Bogen DL, et al. Breastfeeding-associated hypernatremia: are we missing the diagnosis?Pediatrics 2005; 116(3):e343-

e347.• 3. Morton JA. Clinical usefulness of breast milk sodium in the assessment of lactogenesis. Pediatrics 1994; 93(5):802-806.•  

A 27-year-old woman presents for her gynecologic examination. Her height is 5 feet 3 inches and her weight

is 160 pounds (BMI, 29.2 kg/m2). You advise her about weight loss. She asks you about low-carbohydrate diets

such as the Atkins Diet®. Which of the following statements is TRUE about low-carbohydrate diets?

A:The American Heart Association has supported low-carbohydrate

diets due to their effects on weight loss and lipid profile.B:

Patients on low-carbohydrate diets demonstrate worsening of lipid profiles (higher low-density lipoprotein (LDL) levels and

lower high-density lipoprotein (HDL) levels.)C:

Initial weight loss (at 6 months) with low-carbohydrate diets is greater than with low-fat diets, but no statistical difference is

noted at 1 year.D:

Long-term studies (>1 year) demonstrate the safety of low-carbohydrate diets.

E:Low-carbohydrate diets have shown no effect on hemoglobin A1C

levels in patients with diabetes 

Answer

• C:• Initial weight loss (at 6 months)

with low-carbohydrate diets is greater than with low-fat diets, but no statistical difference is noted at 1 year.

Low Carbohydrate Diets• Obesity is at epidemic levels in the American population. Sixty-five percent of the adults in the United States are overweight with a body mass

index of 25 kg/m2 or greater. Obesity has been directly related to several medical conditions, the most notable being coronary artery disease and diabetes mellitus. Traditional low-fat diets along with newer low-carbohydrate diets have become popular, and family physicians should be able to discuss the benefits and risks of these diet types with their patients.

•  Low-carbohydrate diets limit the daily consumption of carbohydrates to 20 to 60 grams (usually less than 20 percent of the total daily calories). In this manner, the calories obtained from sugar and starches are decreased. The intake of protein and fat, however, is increased. The most popular low-carbohydrate diet is the Atkins Diet®. In 1-year comparisons with patients on traditional low-fat diets, patients on low-carbohydrate diets had lower triglyceride levels, higher high-density lipoprotein (HDL) levels and lower hemoglobin A1C levels (in diabetic patients). The low-density lipoprotein levels were similar between the two diets. In 2006, a 20-year follow-up study of 80,000 women in the Nurses’ Health Study, those who self-reported following a low-carbohydrate (high-protein and high-fat) diet showed no increased cardiovascular risk. In fact, when protein and fat were from vegetable sources, cardiovascular risk was slightly lower.

•  In direct short-term (1-year) comparison studies of low-carbohydrate diets and traditional low-fat diets, neither has been shown to be more effective than the other at safely maintaining weight loss (SOR C; Ref. 5). Duration of diet compliance and degree of caloric restriction were the determinants of weight loss. Low-carbohydrate diets, however, may be more effective in very-short-term studies up to 6 months (SOR C; Ref. 5). It is the early weight loss that, in part, makes these diets popular. Some of the early weight loss in low-carbohydrate diets may be due to a significant water diuresis. This effect is most likely related to glycogenolysis from increased protein ingestion. Glycogen has a great affinity for water and, as its stores are depleted, water is shed through the urine.

•  Physicians must use caution in discussing the benefits of low-carbohydrate diets with their patients. Studies of clinical outcomes have been limited to 1 year or less. Long-term risk is unknown, and concerns have been raised about a diet that limits the intake of fruits, vegetables and legumes. The American Dietetic Association and the American Heart Association do not support low-carbohydrate diets because of their concern that they may promote cancer and cardiovascular, kidney and liver diseases. Traditionally, low-carbohydrate diets are low in some vitamins (A, B6, C and E), folate, calcium, magnesium, thiamine and potassium. Decrease in fiber is associated with constipation and, therefore, potentially colon cancer and diverticular disease. High-fat diets have been implicated in cardiac disease and breast cancer. Low-carbohydrate diets can also raise uric acid levels and, therefore, the risk of gout. Concerns also exist regarding osteoporosis due to increased calciuria and lower magnesium intake.

•  Selected references:• 1. Bravata DM, Sanders L, Huang J, et al. Efficacy and safety of low-carbohydrate diets: a systematic review. JAMA 2003; 289:1837-1850. 

http://jama.ama-assn.org/cgi/reprint/289/14/1837  Accessed March 2008• 2. Foster GD, Wyatt HR, Hill JO, et al., A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med 2003; 348(21):2082-2090.• 3. Halton TL, Willett WC, Liu S, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med 2006;

355(19):1991-2002.• 4. Kirschenbaum DS. Very-low-fat diets are superior to low-carbohydrate diets. Patient Care 2005; 39(11):47.• 5. Last AR, Wilson SA. Low-carbohydrate diets. Am Fam Physician 2006; 73(11):1942-1948.http://www.aafp.org/afp/20060601/1942.html

  Accessed March 2008• 6. Samaha FF, Iqbal N, Seshadri P, et al. A low-carbohydrate as compared to a low-fat diet in severe obesity. N Engl J Med 2003; 348(21):2074-

2081.

A 43-year-old healthy woman comes in for a well-woman examination. You discuss her diet and exercise habits

with her. She has a BMI of 28, has been on a low-carbohydrate diet for 3 months and has lost 15 lbs. She asks for you advice about low-carbohydrate diets and

future health. Which of the following is CORRECT? A:

Low-carbohydrate diets have been shown to increase cholesterol and should be avoided.

B:At 1 year, people on low-carbohydrate diets lose more weight

than people on low-fat diets.C:

In the short-term, low-carbohydrate diets are safe, but long-term studies are lacking.

D:Low-carbohydrate diets have a side effect profile identical to low-

fat diets.E:

Long-term adherence to a low-carbohydrate diet is unlikely to result in vitamin deficiencies

Answer

• C:• In the short-term, low-

carbohydrate diets are safe, but long-term studies are lacking.

Low-Carbohydrate Diets• The original Atkins Diet Revolution was published in 1973. This book espoused a low-carbohydrate diet as a means for significant

weight loss. Dr. Atkins’ 1998 book, The New Diet Revolution, sold tens of millions of copies and stimulated a popular diet trend (including the South Beach diet). The Atkins diet recommends using fat and protein as the primary energy sources. Initially, it is recommended to limit ingestion of carbohydrates to about 20 g per day. When a target weight has been achieved, carbohydrate ingestion can increase to up to 60 g per day. Many people on this diet consume high-fat protein sources such as eggs and meat as their primary foods.

•  • Several short-term studies (6-12 months) have compared low-carbohydrate diets to low-fat diets on total weight

loss and cholesterol levels. These studies show that the low-carbohydrate diets may produce greater weight loss at 6 months, but by 12 months, the differences are not significant (SOR C; Ref. 4). This initial rapid weight loss may, in fact, be one of the reasons for the diet’s popularity. Several studies show that low-carbohydrate diets produce a greater reduction in triglyceride levels, less reduction (or even improvement) in HDL levels and no difference (or slight increase) in LDL levels. Change in total cholesterol is similar in the two diets. Current studies do not show any increased cardiovascular risk associated with low-carbohydrate diets,however, long-term studies regarding adverse effects are not available.

•  • Nutritionists are concerned about people following these diets for the long term, however. Most low-carbohydrate diets recommend

complete avoidance or limited ingestion of fruits, which in the long term could cause vitamin deficiencies. Also, good evidence shows that ingestion of high-fiber complex carbohydrates can actually decrease the incidence of colon cancer. Adverse effects (constipation, headache, halitosis, diarrhea, muscle cramps, weakness) are more common in low-carbohydrate diets compared to low-fat diets. Even the 12-month studies show a high rate of noncompliance on low-carbohydrate diets, implying that a strict avoidance of carbohydrates is difficult for more than a few months.

•  • Selected references:• 1. Brehm BJ, Seeley RJ, Daniels SR, et al. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat

diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinal Metab 2003; 88(4):1617-1623.• 2. Crowe TC. Safety of low-carbohydrate diets. Obes Rev 2005; 6:235-245.• 3. Hadi S, Jensen GL. Efficacy of a low-carbohydrate diet for short-term weight loss. Nutr Clin Pract 2005; 20:17-20.• 4. Last AR, Wilson SA. Low-carbohydrate diets. Am Fam Physician 2006; 73(11):1942-1948. 

http://www.aafp.org/afp/20060601/1942.html  Accessed March 2008• 5. Yancy WS, Olsen MK, Guyton JR, et al. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity

andhyperlipidemia: a randomized, controlled trial. Ann Intern Med 2004; 140:769–777.•  

A 37-year-old morbidly obese male presents 3 months following Roux-en-Y gastric bypass surgery for weight

reduction. The patient is complaining of nausea, vomiting, weakness and a burning sensation at his feet for the past 2 months. Past medical history includes hypertension and diabetes mellitus. Other past surgical history includes a

laparoscopic cholecystectomy 6 years ago. Physical examination reveals tachycardia, distal tremor, calf muscle tenderness, diminished ankle deep tendon

reflexes, polyneuropathy in the lower extremities and peripheral edema. These symptoms most likely are

attributed to which disorder? A:

Diabetic neuropathyB:

Guillain-Barré syndromeC:

Thiamine (vitamin B1) deficiencyD:

Myasthenia gravisE:

Hypothyroidism

Answer

• C:

• Thiamine (vitamin B1) deficiency

The most appropriate intervention for this patient should include which of the

following A:

Nerve conduction studiesB:

Dietary recommendations and supplementationC:

Oral corticosteroid therapyD:

Gabapentin (generic, Neurontin®)E:

Laboratory tests including complete blood count (CBC), metabolic panel and thyroid stimulating

hormone (TSH)

Answer

• B:• Dietary recommendations and

supplementation•

Thiamine Deficiency• Nutritional deficiencies are common complications following bariatric surgery. Deficiencies can become even more pronounced when the patient is

vomiting. Thiamine (vitamin B1) deficiency has been reported as a possible consequence of restrictive (adjustable gastric banding) andmalabsorptive bariatric procedures. Thiamine is found in limited quantities in a variety of animal and vegetable products and is abundant only in a small number of foods such as yeast, whole grains, beef, lean pork and legumes. It is absent from fats, oils and refined sugars and it is rapidly destroyed in high temperature. Alcohol reduces absorption, alters metabolism and depletes body stores of thiamine.Adult populations that are considered vulnerable to the development of thiamine deficiency are those who have high carbohydrate intake derived mainly from milled rice and refined sugar and chronic ethanol abusers. Thus, although the patient described in this question is obese, his obesity does not exclude the possibility of a subclinical thiamine deficiency prior to his weight-reduction surgery. An unbalanced high-fat, high-caloric Western-style diet and increased portion sizes may lead to a variety of nutritional deficiencies including thiamine deficiency. In this patient, an increase in the vitamin requirements caused by the patient’s hypermetabolic state after surgery may accelerate the clinical manifestations of thiamine deficiency. It is well documented that strenuous physical activity, fever, pregnancy, lactation and adolescent growth as well as surgery increase thiamine requirements, while dialysis and congestive heart failure treated with furosemide induce thiamine loss in the urine.  The combination of vomiting, physiologic stress, weight loss and the nature of the surgical procedure in this patient both increase thiamine requirements and induce thiamine loss in the urine.

•  Thiamine deficiency may lead to cardiovascular and neurological derangements such as wet or dry beriberi or may involve the central nervous system in the form of Wernicke’sencephalopathy and/or Wernicke-Korsakoff syndrome.  Dry beriberi manifests predominantly as peripheral neuropathy and may include calf muscle tenderness and difficulty in rising from a squatting position. Wet beriberi is a result of cardiovascular involvement, and the physical signs include tachycardia and congestive heart failure in addition to peripheral neuropathy. The patient in this question shows signs of cardiovascular involvement (tachycardia and peripheral edema) that indicate that he may be suffering from wet beriberi. Involvement of the central nervous system will result inWernicke’s encephalopathy and is characterized by confusion, nystagmus, ophthalmoplegia and ataxia. The advanced stages of this disease include memory loss and confabulation, leading to Korsakoff’spsychosis and permanent neurological damage.  Ethanol abuse is a major cause of thiamine deficiency in Wernicke-Korsakoff syndrome, although iatrogenic causes, including parental glucose administration and chronic dialysis in patients with marginal thiamine status may cause this complication.

•  Diabetic neuropathy usually manifests as distal symmetric polyneuropathy, which often presents with distal sensory loss in a stocking-and-glove pattern. Patients often complain of numbness, tingling or a burning sensation starting in their feet and spreading proximally. Physical examination reveals sensory loss, diminished ankle reflexes and abnormal position sensation. The clinical findings of peripheral neuropathy caused both by thiamine deficiency and diabetes are often confusing, but the additional findings of tachycardia, distal tremor and peripheral edema in this patient cannot be attributed to diabetes.

•  Guillain-Barré syndrome (GBS) is an acute polyradiculoneuropathy. It usually manifests as a motor paralysis with or without sensory involvement. The patient often experiences weakness accompanied by dysesthesias in the extremities, which evolves within hours to days. This acute course does not match the patient in question. Physical examination will typically reveal involvement of the large sensory fibers, influencing deep tendon reflexes and proprioception rather than cutaneous sensory deficits such as loss of pain and temperature sensation.

•  Myasthenia gravis is a primary disorder of the neuromuscular junction. It is characterized by weakness and early fatigue of skeletal muscles, most often involving the cranial muscles, but may result in weakness of respiratory effort, requiring respiratory assistance (myasthenic crisis). The patient’s symptoms indicate peripheral neuropathy rather than motor signs.

•  Symptoms of hypothyroidism include weakness, dry skin, feeling cold, constipation and obesity. Neurological symptoms may also occur and patients may suffer from carpal tunnel syndrome,paresthesias and, rarely, polyneuropathy. On physical examination, patients with hypothyroidism may have reduced ankle reflexes and evidence of peripheral edema, but the finding of tachycardia in the patient in the question does not support hypothyroidism.

•  Selected references:• 1. Asbury AK. Approach to the patient with peripheral neuropathy. In: Kasper DL, Fauci AS, Longo DL, et al, eds,Harrison’s Principles of Internal Medicine. 16th ed. New

York: McGraw-Hill, 2004:2500-2510.• 2. Carrodeguas L, Kaidar-Person O, Szomstein A, et al. Preoperative thiamine deficiency in an obese population undergoing

laparoscopic bariatric surgery. Surg Obes Relat Dis 2005; 1(6):517-522.• 3. Escalona A, Pérez G, León F, et al. Wernicke’s encephalopathy after Roux-en-Y gastric bypass. Obes Surg 2004; 14:1135-1137.

A 25-year-old woman comes to the office for preconception counseling. She is very health

conscious and is concerned about what she has read about mercury in fish and possible effects on an

unborn child. Which of the following is FALSE regarding the consumption of fish during

pregnancy? A:

Shark and swordfish have higher levels of mercury than many other fish and should be avoided.

B:A tuna steak has higher levels of mercury than light

canned tuna.C:

Fish caught by family or friends in fresh water is safe to eat.D:

Current studies indicate that farm-raised fish have mercury levels similar to wild fish.

E:Raw fish, such as is found in some sushi, should be

avoided during pregnancy.

Answer

• C:• Fish caught by family or friends in

fresh water is safe to eat.

Mercury In Fish During Pregnancy• For the general population, the consumption of fish is recommended since fish is a good source of omega-3 fatty acids. However, it is also known that fish can be

contaminated with inorganic mercury. Mercury contamination can occur in the water, air, soil and also through natural deposits. Recognition of the adverse neurologic effects of mercury occurred in the late 1960s when the neurologic damage found in children in a town in Japan was linked to high levels of methylmercury in their mothers’ blood. The high level was from industrial contamination of the water in the nearby bay that was the main source of the fish consumed in that community.

•  Methylmercury is formed by the interaction between bacteria and mercury in the water. Fish that reside in this water can become contaminated. Larger fish that live longer and feed on other fish have the highest levels of methylmercury. The table below lists fish by mercury levels. The fish listed as having high levels of mercury should be avoided by women who could become or are pregnant. It is also recommended that these be avoided during lactation and also for children under age 6 years. Other fish considered to have much lower levels of mercury contamination may be consumed in limited amounts.  Currently the Food and Drug Administration (FDA) recommends that pregnant women limit their consumption of these fish to 12 ounces a week (equivalent to 2 average meals). Of note is that canned light tuna has lower mercury levels than canned albacore tuna or fresh or frozen tuna steaks. This is because tuna that is canned generally comes from smaller fish and light tuna is a smaller fish than albacore tuna. The recommendation is to limit albacore tuna consumption to 6 ounces per week.

•  Mercury Levels in Commercial Fish and Shellfish•  Mercury Level

Types of Fish and Shellfish• Highest levels• Tilefish (Gulf of Mexico), shark, swordfish, king mackerel• Moderate levels• Bass, bluefish, lobster (Northern/American), Spanish mackerel, orange roughy, freshwater perch, skate, snapper, tilefish (Atlantic), tuna (canned albacore, other

fresh/frozen)• Lower levels• Catfish, clams, cod, haddock, herring, lobster (spiny), Atlantic and chub mackerel, oysters, ocean perch, salmon (canned, fresh, frozen), scallops, tilapia, freshwater

trout, canned light tuna•  Raw fish should be avoided because of the risk of food-borne infection (i.e., hepatitis A, salmonella,staphylococcus). Cooked sushi, such as eel, or sushi that does

not contain raw fish, such as Californiarolls, are considered safe during pregnancy. Game fish (including bluefish, striped bass, salmon, trout and northern and walleyed pike) caught by friends or family members in fresh water may or may not be contaminated with mercury or other industrial pollutants such as polychlorinated biphenyls (PCBs). Pregnant women should not eat these fish until they have checked with their local health departments to see whether special advisories have been issued regarding the safety of fish caught in that water. If no information is available, 6 ounces may be consumed, but it is advised not to eat additional fish that week. At the present time no evidence indicates higher mercury levels in farm-raised fish.

•  Of note is that in 2007 the National Healthy Mothers, Healthy Babies Coalition made a recommendation that pregnant and breastfeeding women should consume at least 12 ounces of seafood weekly for optimal brain development. However, this recommendation has not been universally accepted, even among some of the coalition members including the March of Dimes, and American College of Obstetricians and Gynecologists.

•  Selected references:• 1. Centers for Disease Control and Prevention. Blood mercury levels in young children and childbearing-aged women – United States, 1999-2002. MMWR Morb Mort

Wkly Rep 2004; 53(43):1018-1020.http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5343a5.htm  Accessed March 2008 • 2. Frey KA. Preconception care by the nonobstetrical provider. Mayo Clin Proc 2002; 77:469-473.• 3. U.S. Department of Health and Human Services and U.S. Environmental Protection Agency. What you need to know about mercury in fish and shellfish. 

http://www.cfsan.fda.gov/~dms/admehg3.html  Accessed March 2008• 4. U.S. Food and Drug Administration. Mercury levels in seafood species. www.cfsan.fda.gov/~frf/sea-mehg.html Accessed March 2008

Which of the following is TRUE regarding the association of cancer and obesity as

defined by body mass index (BMI) in women?

A:Obesity increases the risk of lung cancer.

B:Obesity is associated with a lower risk of

endometrial cancer.C:

Obesity increases the risk of colon cancer.D:

Obesity increases the risk of breast cancer in premenopausal women.

E:Obesity lowers the risk of gall bladder cancer

associated with gallstones.

Answer

• C:• Obesity increases the risk of colon

cancer.

Obesity And Cancer Risk•  The possible association of increased cancer risk with obesity is receiving significant scrutiny. A prospective study of obese women (BMI>30) found that all cancer-related deaths were higher in the obese group than in

women with a BMI of 25 or less. All cancer-related mortality rates increased as BMI increased. In 2002 approximately 3.2 percent of all cancers (around 41,000 cases) were due to obesity. A recent report estimates that 14 percent of cancer deaths in men and 20 percent of cancer deaths in women are obesity-related. The Table shows the associations of cancer with obesity.

•  Cancers With Increased Risk Associated with Obesity Cancer Men WomEn• Breast

• Increased risk in postmenopausal women who are not taking hormonal therapy• Uterine• 4-fold greater risk regardless of menopausal status• Colon• Consistent relationship with high BMI especially associated with abdominal fat; stronger association than for women• Both obese pre- and postmenopausal women taking estrogen have increased risk; obese postmenopausal women not taking estrogen do not have increased risk; no statistically significant increase in rectal cancer• Renal• Results variable – weak association in most studies, although risk similar to women in others• 2-4 times risk of renal cell carcinoma• Esophagus/stomach• 2-fold increased risk foradenocarcinoma of the esophagus and gastric cardia; no increase in squamous cell carcinoma of esophagus• Same• Prostate• Most studies report no increased risk; may be associated with more aggressive tumors• Gallbladder• Increased risk especially with obesity compared to overweight• Even stronger association than with men• Pancreas• Studies not conclusive, but there is a trend for increased risk (2 times)• Same• Ovary• Inconclusive evidence; some evidence that there may be increased risk of premenopausalovarian cancer with increased BMI in young adulthood• Multiple myeloma• Strongest association in those with BMI>30 kg/m2 (obese)• Modest association in obese and overweight women•  A number of obesity-related factors may describe how obesity and cancer are interrelated. Obesity causes increased insulin and insulin-like growth factor production that may enhance malignant transformation and

growth. Obesity increases the peripheral estrogen production that promotes breast and endometrial cancers. Obesity increases the risk for gallstones that are a risk factor for gallbladder cancer. Diets high in simple carbohydrates and low in fruit and vegetable intake are also linked with increased cancer risk.

•  It is unclear whether losing weight lowers cancer risk. No clinical trials have been performed looking at this question for specific types of cancer. Some observational studies indicate that there is benefit in certain cancers.

•  Selected references:• 1. Birmann BM, Giovannucci E, Rosner B, et al. Body mass index, physical activity and risk of multiple myeloma. Cancer Epidemiol Biomarkers Prev 2007; 16(7):1474-1478.• 2. Fairfield KM, Willett WC, Rosner BA, et al. Obesity, weight gain and ovarian cancer. Obstet Gynecol 2002; 100:288-296.• 3. Larsson SC, Wolk A. Obesity and colon and rectal cancer: a meta-analysis of prospective studies. Am J Clin Nutr2007; 86(3):556-565.• 4. Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a meta-analysis. Brit J Cancer 2007; 86:1457-1461.• 5. Michaud DS, Giovanucci E, Willett WC, et al. Physical activity, height, and the risk of pancreatic cancer. JAMA 2001; 286:921-929.• 6. National Cancer Institute. Obesity and cancer. http://www.cancer.gov/cancertopics/factsheet/Risk/obesity  Accessed April 2008• 7. Patel AV, Rodriguez C, Bernstein L, et al. Obesity, recreational physical activity and risk of pancreatic cancer in a large U.S. cohort. Cancer Epidemiol 2005; 14:459-466.• 8. Reeves GK, Pirie K, Beral V, et al. Cancer incidence and mortality in relation to body mass index in the million women study: cohort study. BMJ 2007; 335(7630):1134. 

http://www.bmj.com/cgi/content/full/bmj.39367.495995.AEv1 Accessed April 2008• 9. Renehan HG, Tyson M, Egger M, et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371(9612):569-578.•  

A 45-year-old male with a BMI of 35 kg/m2 is seen for a follow-up visit after having fasting labs as part of an executive physical. His fasting plasma glucose was 120 mg/dL. You diagnose him with prediabetes.

Which of the following statements regarding prediabetes is TRUE?

A:Metformin is currently recommended for treatment of

patients diagnosed with prediabetes.B:

Approximately 75 percent of patients diagnosed with prediabetes will become diabetic.

C:Weight reduction of at least 20 percent is necessary to

demonstrate any risk reduction in patients with prediabetes.

D:Screening for prediabetes is strongly recommended for all overweight and obese persons (BMI ≥ 25) who are ≥ 45

years of age.E:

Measuring a hemoglobin A1C level is recommended as an additional criterion for the diagnosis of prediabetes

Answer

• D:• Screening for prediabetes is

strongly recommended for all overweight and obese persons (BMI ≥ 25) who are ≥ 45 years of age.

Prediabetes•  Prediabetes is defined as impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). In 2003, the Expert Committee on the Diagnosis and Classification

of Diabetes Mellitus recommended lowering the cutoff for impaired fasting plasma glucose values from 110 to 100 mg/dL. This redefinesIFG as a fasting plasma glucose between 100 and 125 mg/dL. The criterion for IGT has not changed and includes a 2-hour plasma glucose of 140-199 mg/dL following a 75 g oral glucose tolerance test. Changing the lower range for IFG results in about a 20 percent increase in the number of people with prediabetes. Using these criteria, 10-15 percent of American adults have prediabetes.

•  • The importance of diagnosing prediabetes is demonstrated in studies that show that about one third of patients with this condition will eventually develop diabetes

mellitus. Estimates are that about two thirds of adults with type 2 diabetes were prediabetic 5 years before their diagnosis. Another reason for diagnosing prediabetes is that clinical trials now show that more than half of new cases of diabetes are preventable with lifestyle changes.

•  • In the Diabetes Prevention Program (DPP), a 58 percent relative reduction in diabetes progression was noted in the lifestyle group after a 2.8-year follow-up. Fifty

percent of this group had a 5 percent reduction in body weight and 74 percent maintained at least 150 minutes/week of moderately intense physical activity. Lifestyle intervention worked well for men, women and all ethnic groups and in those over 60 years of age. In the Finnish Diabetes Prevention Studies, middle-age, obese patients with IGTexperienced 58 percent relative reduction in the incidence of diabetes after an average follow-up of 3.2 years if they were in the intervention group (intensive instruction on weight reduction, physical activity and food intake). It is too early to recommend drug therapy for prediabetic patients, even though 2 trials have shown risk reduction (Study to Prevent Noninsulin Dependent Diabetes Mellitus [STOP-NIDDM] and Troglitazone in Prevention of Diabetes [TRIPOD]).

•  • Many obese patients think that they need to lose massive amounts of weight before a benefit is seen. Physicians can be encouraging by telling such patients that

benefits are seen with a sustained weight reduction of even 5 percent. Patients should also be encouraged to increase their activity gradually to more than 150 minutes/week of moderate-intensity exercise (i.e., 30 minutes of brisk walk at 3 mph on most days of the week).

•  • The American Diabetes Association has recommended screening for prediabetes at 3-year intervals for all overweight and obese persons (BMI ≥

25 kg/m2) ≥45 years (SOR C; Ref. 1).Physicians should consider screening younger overweight patients who have one or more of the following risk factors: family history of diabetes, sedentary lifestyle, non-Caucasian ethnicity, history of gestational diabetes or a baby weighing >9 pounds, blood pressure >140/90 mmHg, HDL ≤35 mg/dLand/or triglycerides ≥ 250 mg/dL, syndromes of insulin resistance (e.g., polycystic ovary syndrome,acanthosis nigricans) or history of vascular disease. At this time, measuring of glycohemoglobin (A1C) is not recommended for diagnosing diabetes or prediabetes.

•  • Selected references:• 1. American Diabetes Association (<ADA). Standards of medical care in diabetes. II. Screening for diabetes. Diabetes Care 2006; 29(Suppl 1):S5-7. 

http://care.diabetesjournals.org/cgi/content/full/29/suppl_1/s4#SEC3  Accessed March 2008• 2. American Diabetes Association (ADA). Standards of medical care in diabetes. IV. Prevention/delay of type 2 diabetes.Diabetes Care 2006; 29(Suppl 1):S7-8. 

http://care.diabetesjournals.org/cgi/content/full/29/suppl_1/s4#SEC5  Accessed March 2008• 3. Benjamin SM, Valdez R, Geiss IS, et al. Estimated number of adults with prediabetes in the U.S. in 2000. Diabetes Care 2003; 26:645-649.  

http://care.diabetesjournals.org/cgi/content/full/26/3/645  Accessed March 2008• 4. Davidson JA, Hamby O. Preventing diabetes in the prediabetic. Patient Care 2004; 38(11):16-24.• 5. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Follow-up report on the diagnosis of diabetes mellitus. Diabetes Care 2003;

26:3160-3167.  http://care.diabetesjournals.org/cgi/content/full/26/11/3160 Accessed March 2008•