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UMDNJ PACE/PANRE Review Course becoming Rutgers July 1, 2013

Endocrine SystemEndocrine System

Maria Alonso, CDE, PAMaria Alonso, CDE, PA--CC

UMDNJ PANCE/PANRE Review Course UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013)(becoming Rutgers July 1, 2013)

The Endocrine SystemThe Endocrine System

Disease of the Pituitary GlandDisease of the Pituitary Gland

Diseases of the ThyroidDiseases of the Thyroid

Disease of the Adrenal GlandsDisease of the Adrenal Glands

Diabetes MellitusDiabetes Mellitus

Lipid DisordersLipid DisordersUMDNJ PANCE/PANRE Review Course

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Pituitary Gland Pituitary Gland

UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013)

Pituitary AnatomyPituitary Anatomy

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PITUITARY ANATOMYPITUITARY ANATOMY

•Small pea-sized gland at the base of brain•Located in the “Sella Turcica”•Functions as "The Master Gland" •Attached below hypothalamus by stalk•Large anterior lobe (adenohypophysis)•Smaller posterior lobe (neurohypophysis)•The optic chiasm lies directly above•Supplied by internal carotid artery



Quick ReviewQuick Review

Hypothalamus

GnRH GHRH SS TRH DA CRH

+ +++ _ _

Anterior Pituitary

ACTHProlactinTSHGH/TSH GHFSH/LH

Gonadotropin releasing hormone (GnRH). Growth hormone releasing hormone (GHRH)

Somatostatin (SS), Thyrotropin releasing hormone (TRH), Dopamine (DA)

Corticotropin releasing hormone (CRH)UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013)

Posterior PituitaryOxytocin ADH

Hypothalamus

Quick Review

+ +


Quick Review: Hypothalamic Quick Review: Hypothalamic Pituitary AxisPituitary Axis

NeurosecretoryNeurosecretory cellscells send messages from send messages from brain to brain to hypothalamushypothalamusHypothalamus sends chemical hormones Hypothalamus sends chemical hormones to the to the pituitary glandpituitary glandPituitary gland secretes hormones to the Pituitary gland secretes hormones to the thyroid gland, adrenal glands, and gonadsthyroid gland, adrenal glands, and gonadsNegative feedback mechanism finishes the Negative feedback mechanism finishes the looploop



Pituitary DisordersPituitary Disorders

HypopituitarismHypopituitarism –– Congenital causesCongenital causes

HypopituitarismHypopituitarism-- Acquired causesAcquired causes

Pituitary tumors (adenomas)Pituitary tumors (adenomas)


HypopituitarismHypopituitarism-- Congenital CausesCongenital Causes

Hypothalamic gene defectsHypothalamic gene defectsPituitary gene defectsPituitary gene defectsHormone receptor gene defectsHormone receptor gene defectsAnencephaly, neural tube defectAnencephaly, neural tube defectPituitary Pituitary aplasiaaplasia, usually fatal at birth, usually fatal at birthKallmannKallmann syndrome: xsyndrome: x--recessive recessive GnRHGnRHdefect with defect with hypogonadismhypogonadism, delayed , delayed puberty, osteoporosis, puberty, osteoporosis, anosmiaanosmia


HYPOPITUITARISM HYPOPITUITARISM ACQUIRED CAUSESACQUIRED CAUSES

TumorsTumors are the most common cause in adultsare the most common cause in adultsIrradiationIrradiation for other cranial tumorsfor other cranial tumorsVascular:Vascular: bleed, infarct, Sheehanbleed, infarct, Sheehan’’ssInflammatory:Inflammatory: sarcoidosissarcoidosis, TB, TBMetabolic:Metabolic: Fe deposits/Fe deposits/hemochromatosishemochromatosis, , amyloidosisamyloidosis, illness, malnutrition, illness, malnutrition

**Empty **Empty SellaSella Syndrome:Syndrome:unable to see gland on imaging due to any of unable to see gland on imaging due to any of above. May have shrunk or flattened above. May have shrunk or flattened



Pituitary TumorsPituitary Tumors

MicroadenomasMicroadenomas (<10 mm)(<10 mm)MacroadenomasMacroadenomas (>10mm)(>10mm)Rarely malignantRarely malignantLocally invasiveLocally invasive

destroy hormone producing cellsdestroy hormone producing cellscompresses gland or hypothalamuscompresses gland or hypothalamus


Types of AdenomasTypes of Adenomas

ProlactinomaProlactinoma prolactin/hypogonadismprolactin/hypogonadism and and galactorrheagalactorrhea(25(25--40%) (40%) (LactotrophLactotroph))

Null cell Null cell no active hormone (10no active hormone (10--25%)25%)

SomatotrophSomatotroph GH/GH/acromegalyacromegaly and gigantism (10and gigantism (10--15%)15%)

CorticotrophCorticotroph ACTH/ CushingACTH/ Cushing’’s (10s (10--15%)15%)

GonadotrophGonadotroph FSH/LH (15FSH/LH (15--20%)20%)

ThyrotrophThyrotroph TSH/ hyperthyroidism (1%)TSH/ hyperthyroidism (1%)


Clinical ManifestationsClinical Manifestations

Mass effectMass effectheadachesheadachesbitemporalbitemporal hemianopsiahemianopsiaDiplopiaDiplopia

Symptoms based on hormone involvedSymptoms based on hormone involved



TreatmentsTreatmentsMedical therapyMedical therapy--

decreases hormone and tumordecreases hormone and tumordopamine agonistdopamine agonist-- BromocriptineBromocriptinereplace hormones (thyroid/adrenal) replace hormones (thyroid/adrenal)

Surgical excisionSurgical excisionTranssphenoidalTranssphenoidalGamma Knife/ Stereotactic NonGamma Knife/ Stereotactic Non--invasive invasive Radio SurgeryRadio Surgery


ProlactinomaProlactinoma 2525--40%40%Occurs M/C 20Occurs M/C 20--50 50 yoyoHyperprolactinemiaHyperprolactinemiaHypogonadismHypogonadism

negative effect on negative effect on GnRHGnRHreduction in LH and FSHreduction in LH and FSH

Females Females -- galactorrheagalactorrhea, , oligomenorrheaoligomenorrhea, , amenorrheaamenorrheaMalesMales-- headache, visual disturbance, headache, visual disturbance, impotenceimpotence


ProlactinProlactinDopamine inhibits Dopamine inhibits prolactinprolactin secretionsecretion

Estrogen, TRH, and GHRH positively effect Estrogen, TRH, and GHRH positively effect prolactinprolactin secretionsecretion

Excess can be caused by lactation, Excess can be caused by lactation, tumors, drugs, hypothyroidism, tumors, drugs, hypothyroidism, hypothalamic dysfunctionhypothalamic dysfunction



ProlactinomaProlactinomaWork up:Work up:

BHCG, BHCG, prolactinprolactin level, TSHlevel, TSHCT/MRI of the BrainCT/MRI of the Brain

DDxDDx: : excessive exerciseexcessive exerciseHxHx chest wall surgerychest wall surgerychest trauma chest trauma renal failurerenal failurecirrhosiscirrhosis

TX : TX : dopamine agonistdopamine agonist-- BromocriptineBromocriptineSurgical excisionSurgical excision


Excessive Growth Hormone Excessive Growth Hormone SecretionSecretion

AcromegalyAcromegaly –– adultsadultsAfterAfter epiphysealepiphyseal closureclosure

Gigantism Gigantism –– childrenchildrenBeforeBefore epiphysealepiphyseal closure (excessive height)closure (excessive height)


Excessive Growth HormoneExcessive Growth Hormone

98% cases adenomas is the cause98% cases adenomas is the cause

Usually mixed cell tumorsUsually mixed cell tumors

Increase riskIncrease risk-- DM, HTN, CADDM, HTN, CAD



Physical ManifestationsPhysical Manifestations

Enlargement of extremitiesEnlargement of extremitieshands doughy / large handshands doughy / large hands

Coarse facial featuresCoarse facial featuresprominent mandible, brow, nose, prominent mandible, brow, nose, lips, tonguelips, tongue

Coarse, oily, thick skinCoarse, oily, thick skinOrganomegalyOrganomegaly


Prominent jaw/ BrowProminent jaw/ Brow

Public domain available at:http://commons.wikimedia.org/wiki/File:Acromegaly_facial_features.JPEG


Hands doughy / Large handsHands doughy / Large hands

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Related ConditionsRelated Conditions

MusclosketalMusclosketalCardiacCardiacMetabolicMetabolicSleep apneaSleep apnea


Related ConditionsRelated ConditionsMusculoskeletalMusculoskeletal

Hypertrophy of joint cartilage and Hypertrophy of joint cartilage and synovial tissuesynovial tissue

carpal tunnel syndromecarpal tunnel syndromearthritisarthritisarthralgiaarthralgia


Related ConditionsRelated Conditions

CardiacCardiacLeft ventricular hypertrophy Left ventricular hypertrophy Diastolic dysfunctionDiastolic dysfunctionDysrhythmiasDysrhythmiasHypertensionHypertension

MetabolicMetabolicInsulin resistance, glucose intolerance, DMInsulin resistance, glucose intolerance, DM



Labs/ Diagnostic TestsLabs/ Diagnostic TestsLabsLabs

GH and IGFGH and IGF--1: 5x normal in 1: 5x normal in acromegalyacromegalyProlactinProlactin, glucose, glucoseLiver enzymes, Blood urea Liver enzymes, Blood urea nitrogen(BUNnitrogen(BUN))CalciumCalciumSerum FT4 and TSHSerum FT4 and TSH

Glucose Suppression test = DiagnoseGlucose Suppression test = DiagnoseGlucose should suppress GH, in Glucose should suppress GH, in acromegalyacromegaly it it does notdoes not

Imaging: MRIImaging: MRIUMDNJ PANCE/PANRE Review Course


TreatmentTreatmentSurgical Surgical (50% success (50% success w/macroadenomasw/macroadenomas))

RadiotherapyRadiotherapy

Medical TherapyMedical TherapyDopamine AgonistDopamine Agonist-- ((brocriptinebrocriptine))

GH Receptor GH Receptor AntagnoistAntagnoist-- ((PegvisomantPegvisomant))


DwarfismDwarfismLess than 4Less than 4’’1010”” is heightis height

DisproportionateDisproportionate-- skeletal skeletal dysplasiadysplasia

AchondroplasiaAchondroplasiaShortShort--trunk dwarftrunk dwarf

ProportionateProportionate-- medical or medical or genetic conditionsgenetic conditions

Growth hormoneGrowth hormonedeficiencydeficiency


Public domain available at:http://commons.wikimedia.org/wiki/File:Paul_Steven_Miller_EEOC.jpg


AchondroplasiaAchondroplasiaMutations in the FGFR3 gene Autosomal dominantShort stature < 4Short stature < 4’’1010””OverweightOverweightShort limbsShort limbsProminent browProminent browMidfacialMidfacial hypoplasiahypoplasia

Public domain available at:http://commons.wikimedia.org/wiki/File:Jason_Acu%C3%B1a_-_Wee-Man_-_Waterfront_Marriott,_Portland,_Oregon_-_August_15,_2009_-_Full_Body.jpg


Growth Hormone DeficiencyGrowth Hormone Deficiency

Insufficient GHRH from hypothalamusInsufficient GHRH from hypothalamusInsufficient production of GH by pituitary Insufficient production of GH by pituitary Genetic MutationGenetic Mutation-- GHRHR, GH1GHRHR, GH1AcquiredAcquired-- tumors/irradiationtumors/irradiationIdiopathicIdiopathic-- M/CM/CGenetic disordersGenetic disorders-- Turner, Noonan, PWSTurner, Noonan, PWSSGASGA


Stimulation TestStimulation Test

Gold Standard Insulin Tolerance Test (ITT), then Gold Standard Insulin Tolerance Test (ITT), then another agent another agent clonidineclonidine, L, L--DopaDopa, glucagon, , glucagon, argininearginine or or GhRHGhRH should cause an increase in should cause an increase in GH levelsGH levelsStimulation test measures the level of Stimulation test measures the level of growth growth hormonehormone (GH) in the blood after stimulation (GH) in the blood after stimulation The test measures the ability of the pituitary The test measures the ability of the pituitary gland to release GH under stimulationgland to release GH under stimulation



GROWTH HORMONE GROWTH HORMONE REPLACEMENTREPLACEMENT

SomatotropinSomatotropin given as daily SQ injection given as daily SQ injection until bone fusion (Bone Age)until bone fusion (Bone Age)May not need further treatment as adults, May not need further treatment as adults, consider repeating stimulation testconsider repeating stimulation testSide effects include headaches, carpal Side effects include headaches, carpal tunnel, SKFE, tunnel, SKFE, arthralgiasarthralgias, and edema, and edemaMonitor for scoliosisMonitor for scoliosis


Diabetes Diabetes InsipidusInsipidus

Vasopressin (ADH): AntiVasopressin (ADH): Anti--Diuretic HormoneDiuretic Hormone

Synthesized in hypothalamus: stored and Synthesized in hypothalamus: stored and released from released from posterior pituitaryposterior pituitaryTwo Main forms: Two Main forms:

Central (neurogenic): Central (neurogenic): deficiency of ADH, low deficiency of ADH, low secretion, secretion, most commonly seenmost commonly seenNephrogenicNephrogenic: resistance to ADH: resistance to ADH


CentralCentral Diabetes Diabetes InsipidusInsipidus = = LOW LOW ADHADH

Disruption of the normal production, Disruption of the normal production, storage and release of ADHstorage and release of ADH

Primary:Primary: No organic lesion, autoimmuneNo organic lesion, autoimmuneSecondary:Secondary: damage to hypothalamus or damage to hypothalamus or pituitary stalkpituitary stalk

Trauma, tumor or illness Trauma, tumor or illness



NephrogenicNephrogenic DI = DI = HighHigh ADHADH

Caused by a Caused by a defectdefect in the kidney tubules in the kidney tubules interferes with water interferes with water reabsorptionreabsorption, , therefore do not respond to ADHtherefore do not respond to ADHCauses: genetic disorder (seen shortly Causes: genetic disorder (seen shortly after birth), CKD, or drugs (lithium)after birth), CKD, or drugs (lithium)


Other Rare CausesOther Rare CausesCongenital Congenital NephrogenicNephrogenic DI: defective DI: defective expression of renal vasopressin receptorsexpression of renal vasopressin receptors

Familial XFamilial X--linked traitlinked trait

DI of Pregnancy: Last trimesterDI of Pregnancy: Last trimesterOligohydramniosOligohydramniosPrePre--eclampsiaeclampsiaHepatic dysfunctionHepatic dysfunction


Clinical FeaturesClinical Features

• Polydipsia

• Polyuria (5-15L daily)

• Colorless urine (dilute)

• Dehydration and electrolyte

imbalance

Public domain available at:http://commons.wikimedia.org/wiki/File:Glass-of-water.jpg



DiagnosisDiagnosis

Fluid deprivation testFluid deprivation testexcessive intake of fluid (primary polydipsia)defect in ADH productiondefect in the kidneys' response to ADH

DesmopressinDesmopressin stimulation teststimulation testU/AU/AConsider MRIConsider MRIDiff Diff DxDx: psychogenic : psychogenic polydipsiapolydipsia


Treatment of DITreatment of DI

Central DI: Central DI: DesmopressinDesmopressin (DDAVP), (DDAVP), CarbamazipineCarbamazipine

NephrogenicNephrogenic: : ThiazideThiazide diuretics, diuretics, indomethacinindomethacin, , amilorideamiloride (combo)(combo)


HYPOTHALAMICHYPOTHALAMIC--PITUITARY PITUITARY --THYROID THYROID AXISAXIS

Public domain available at:http://commons.wikimedia.org/wiki/File:Thyroid_hormone_feedback.png



Thyroid GlandThyroid Gland

HypothyroidismHypothyroidism

HyperthyroidismHyperthyroidism

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THYROID ANATOMYTHYROID ANATOMY

Largest endocrine gland in bodyLargest endocrine gland in bodyTwo lobes connected by Two lobes connected by ““isthmusisthmus””Protected by thyroid cartilageProtected by thyroid cartilage


Public domain available at:http://upload.wikimedia.org/wikipedia/commons/3/32/Thyroid_gland-ga.svg

FUNCTIONFUNCTION

T4 is the main hormone secretedT4 is the main hormone secretedOnly 20% of T3 is secreted from thyroidOnly 20% of T3 is secreted from thyroidIodine + tyrosine makes the T3 and T4Iodine + tyrosine makes the T3 and T4T3 is 3T3 is 3--4 times as active as T44 times as active as T4T3 and T4 exist as free and protein boundT3 and T4 exist as free and protein bound



THYROID IMAGINGTHYROID IMAGING

Ultrasound (U/S) is useful to identify nodulesUltrasound (U/S) is useful to identify nodulesU/S guided Fine Needle Aspiration for U/S guided Fine Needle Aspiration for DxDx

Nuclear scans with radioactive iodineNuclear scans with radioactive iodine--123 or 123 or technetiumtechnetium--99m99mRadioactive iodine uptake test (RAIU) Radioactive iodine uptake test (RAIU)

evaluates function and helps determine amt. RAI for evaluates function and helps determine amt. RAI for txtx


Diseases of the Thyroid GlandDiseases of the Thyroid Gland

HyperthyroidismHyperthyroidismGravesGraves’’ DiseaseDiseaseThyroid stormThyroid storm

HypothryoidismHypothryoidismHashimotoHashimoto’’s s thyroiditisthyroiditis

ThyroiditisThyroiditisNeoplasticNeoplastic DiseaseDisease


HyperthyroidismHyperthyroidism

ThyrotoxicosisThyrotoxicosis is the clinical syndromeis the clinical syndromeMore common in women, 2% of societyMore common in women, 2% of societyMost common cause is Most common cause is GravesGraves’’ DiseaseDiseaseOlder patients do not show classic signsOlder patients do not show classic signs



Hyperthyroidism:Hyperthyroidism:

Other causes:Other causes:Toxic nodulesToxic nodulesThyroiditisThyroiditisIodine inducedIodine inducedExogenous hormoneExogenous hormone


Hyperthyroidism in PregnancyHyperthyroidism in Pregnancy

GravesGraves’’-- most frequent causemost frequent causeBHCGBHCG--a stimulator of thyroid a stimulator of thyroid glandglandDecrease TSH & elevated FT4Decrease TSH & elevated FT4Neonatal mortality 6%Neonatal mortality 6%

Public domain available at:http://commons.wikimedia.org/wiki/File:Pregnant_woman.jpg


GravesGraves’’ DiseaseDisease

Women > Men (8:1)Women > Men (8:1)onset 20onset 20--40 yrs.40 yrs.Autoimmune disorder Autoimmune disorder

Thyroid stimulating immunoglobulin antibodyThyroid stimulating immunoglobulin antibody

Association with other autoimmune Association with other autoimmune disordersdisorders

SLE, pernicious anemia, RA, DM type 1, MGSLE, pernicious anemia, RA, DM type 1, MGUMDNJ PANCE/PANRE Review Course



GravesGraves’’ DiseaseDisease

Affects TSH receptorsAffects TSH receptorsTSH secretionTSH secretionStimulate glandular growthStimulate glandular growthDiffuse, symmetric enlargement/goiterDiffuse, symmetric enlargement/goiterNontenderNontenderThyroid cancer can coincide w/ GravesThyroid cancer can coincide w/ Graves’’!!


Signs Specific to GravesSigns Specific to Graves’’

OphthalmopathyOphthalmopathy: : ExopthalmosExopthalmos

PretibialPretibial myxedemamyxedema

Thyroid bruitThyroid bruit


EXOPHTHALMOSEXOPHTHALMOS

MucopolysaccharidesMucopolysaccharides/lymphocytes/lymphocytesCauses protrusion of globeCauses protrusion of globeLook of astonishment Look of astonishment ““Stellwag'sStellwag's signsign””-- infrequent blinkinginfrequent blinking

Upper lid lag on downward gazeUpper lid lag on downward gazeEach eye can be affected differentlyEach eye can be affected differentlyMay see weak upward gaze, May see weak upward gaze, diplopiadiplopiaExcess tearing, photophobia, gritty feelExcess tearing, photophobia, gritty feel



Public domain available at:http://commons.wikimedia.org/wiki/File:Proptosis_and_lid_retraction_from_Graves%27_Disease.jpg


Public domain available at:http://commons.wikimedia.org/wiki/File:Myxedema.jpg


ThyrotoxicosisThyrotoxicosis Clinical FeaturesClinical FeaturesNervousness, insomnia, irritabilityNervousness, insomnia, irritabilityHand tremor, hyperactivity, tremulousnessHand tremor, hyperactivity, tremulousnessExcessive sweating, heat intoleranceExcessive sweating, heat intoleranceWt. Loss (despite Wt. Loss (despite appetite)appetite)Diarrhea, freq. defecationDiarrhea, freq. defecationPalpitations (Palpitations (tachyarrhythmiastachyarrhythmias))Muscle weaknessMuscle weaknessMenstrual irregularitiesMenstrual irregularities



Diagnosis of GravesDiagnosis of Graves’’

T3 and free T4 levels elevatedT3 and free T4 levels elevatedTSH level extremely low or undetectableTSH level extremely low or undetectableAnti-thyroglobulin antibodies (TGA)Anti-thyroid peroxidase antibodies (TPO)24 hr RAIU given orally is increased24 hr RAIU given orally is increased(T4 can be normal = T3 (T4 can be normal = T3 toxicosistoxicosis))


DonDon’’t forget false positives!t forget false positives!DrugsDrugsAuto immunityAuto immunityAcute illnessAcute illnessHigh estrogen statesHigh estrogen statesPsychiatric illnessPsychiatric illnessAIDSAIDSAcute use steroidsAcute use steroids


Treatment TypesTreatment Types

AntithyroidAntithyroid drugs drugs AblationAblationBeta blockers Beta blockers –– Used to treat symptomsUsed to treat symptoms



AntithyroidAntithyroid Drugs Drugs block conversion of T4 to T3block conversion of T4 to T3

PropylthiouracilPropylthiouracil (PTU)(PTU)taken three x dailytaken three x dailyused in severe cases, pregnancy and breast feedingused in severe cases, pregnancy and breast feedingMethimazoleMethimazole ((TapazoleTapazole) ) taken daily, slower to decrease T3taken daily, slower to decrease T3Levels checked 4 weeks after TX startedLevels checked 4 weeks after TX startedSide effects:Side effects:AgranulocytosisAgranulocytosis, thrombocytopenia, anemia, hepatitis, dermatitis, , thrombocytopenia, anemia, hepatitis, dermatitis, vasculitisvasculitis, , pneumonitispneumonitis, hypoglycemia, urticaria,, hypoglycemia, urticaria,


Radioiodine 131 (RAI)Radioiodine 131 (RAI)Used in older patientsUsed in older patientsPrior PTU/MMI Prior PTU/MMI reaction or failure, or poor compliance.reaction or failure, or poor compliance.

Not to be used in pregnancy/nursingNot to be used in pregnancy/nursingStop Stop antithyroidantithyroid meds 3meds 3--5 days prior5 days priorRAIU used to determine dosingRAIU used to determine dosingImprovement seen after 4Improvement seen after 4--6 weeks6 weeksAlmost 80% are cured with one doseAlmost 80% are cured with one doseAt least 50% will become hypothyroid in a yearAt least 50% will become hypothyroid in a year


SurgicalSurgical-- ThyroidectomyThyroidectomyIndicated for large obstructing glands, Indicated for large obstructing glands, malignant nodules, or pregnancymalignant nodules, or pregnancyMust be Must be euthyroideuthyroid before surgerybefore surgeryPotassium iodide may be given priorPotassium iodide may be given priorComplications:Complications:

recurrent laryngeal nerve damagerecurrent laryngeal nerve damagebleedingbleedinghypoparathyroidismhypoparathyroidism



Keys to Choosing Keys to Choosing TxTx

NonNon--pregnant Gravespregnant Graves’’ patientspatientsMethimazoleMethimazole + Beta blocker+ Beta blockerRAIRAI

PregPreg + Graves+ Graves’’ = PTU = PTU ((““PP’’ss””))

RAI: Elderly with GravesRAI: Elderly with Graves’’, solitary toxic , solitary toxic nodulenodule


Thyroid StormThyroid Storm

Rare complication of Rare complication of thyrotoxicosisthyrotoxicosisPrecipitating factor:Precipitating factor:Stressful illnessStressful illness thyroid surgerythyroid surgeryDKADKA infectioninfectionsevere traumasevere trauma childbirthchildbirth

High mortality rate:High mortality rate:20% pts. (coma or die)20% pts. (coma or die)


Clinical Manifestations & Clinical Manifestations & TxTx

Marked deliriumMarked deliriumSevere tachycardiaSevere tachycardiaVomitingVomitingDiarrheaDiarrheaDehydrationDehydrationHigh feverHigh fever

Supportive therapy: Supportive therapy: IVF, cooling blankets, IVF, cooling blankets, glucoseglucosePTU q 6 HPTU q 6 HMethimazoleMethimazole q 1Hq 1HBeta blockersBeta blockersIodine Iodine HydrocortisoneHydrocortisone



HypothyroidismHypothyroidism

0.80.8--1.0 % population1.0 % population3 x more common women3 x more common womenOnset adulthood and insidiousOnset adulthood and insidiousPrimary (90Primary (90--95%)95%)Autoimmune associated with other nonAutoimmune associated with other non--endocrine abnormalitiesendocrine abnormalities

pernicious anemia, RA, SLE, pernicious anemia, RA, SLE, SjogrenSjogren’’ss, and Myasthenia Gravis., and Myasthenia Gravis.


Primary HypothyroidismPrimary HypothyroidismAuto immuneAuto immune

HashimotoHashimoto’’s s thyroiditisthyroiditis

EndEnd--stage Gravesstage Graves’’ DiseaseDisease


Primary HypothyroidismPrimary HypothyroidismIatrogenic Iatrogenic

Radio Iodine therapyRadio Iodine therapyGland shrinksGland shrinks

ThyroidectomyThyroidectomy

MedicationsMedicationsLithiumLithiumAmiodoroneAmiodoroneInterferonInterferon



Other CausesOther CausesInfiltrative Process Infiltrative Process AmyloidosisAmyloidosisLymphomaLymphomaSclerodermaScleroderma

Congenital Hypothyroidism Congenital Hypothyroidism defects in enzymesdefects in enzymes


Secondary HypothyroidismSecondary Hypothyroidism

Failure of the pituitary gland or Failure of the pituitary gland or hypothalamushypothalamus

NeoplasmNeoplasmSurgerySurgerySheehanSheehan’’s syndromes syndrome

Cause deficiency in TSH or TRHCause deficiency in TSH or TRH low TSH, low FT4low TSH, low FT4


HashimotoHashimoto’’s s ThyroiditisThyroiditisChronic Lymphocyte Chronic Lymphocyte ThyroiditisThyroiditis

Most prevalent form of thyroid autoimmune diseaseMost prevalent form of thyroid autoimmune diseaseGenetic propensity Genetic propensity HLAHLA--B8B8Hypothyroidism initial manifestationHypothyroidism initial manifestationHyperthyroidism < 5% patients Hyperthyroidism < 5% patients –– self limiting or self limiting or long standinglong standing

HashitoxicosisHashitoxicosis, transient hyperthyroidism (severe), transient hyperthyroidism (severe)GravesGraves’’ TSI (thyroid stimulating TSI (thyroid stimulating immunoglobulinsimmunoglobulins))HashimotosHashimotos TSH receptor blocking antibodiesTSH receptor blocking antibodies



MyxedmaMyxedma ComaComaLifeLife--threatening hypothyroidismthreatening hypothyroidismObtundationObtundation, CO2 retention, coma, CO2 retention, comaAltered mental status is hallmarkAltered mental status is hallmarkCan be precipitated by sepsisCan be precipitated by sepsisHigh mortality, treat in ICUHigh mortality, treat in ICUThyroxineThyroxine bolus 300mcg, then 100mcg dailybolus 300mcg, then 100mcg dailyHydrocortisone 100mg IV bolusHydrocortisone 100mg IV bolus


Hypo: SignsHypo: SignsDry skinDry skinCoarse hairCoarse hairThickened puffy featuresThickened puffy featuresNonNon--pitting edemapitting edemaCarpal tunnel syndromeCarpal tunnel syndromeSlow relaxation of DTRSlow relaxation of DTRLoss lateral portions of eyebrowsLoss lateral portions of eyebrowsBradycardiaBradycardiaGoiter (Goiter (hashimotohashimoto: rubbery, : rubbery, nonnon--tender,tender, possibly possibly nodular)nodular)


Hypo: SymptomsHypo: SymptomsFatigue, lethargy, weaknessFatigue, lethargy, weaknessHeavy menstrual periods (Heavy menstrual periods (menorrhagiamenorrhagia))Slight weight gainSlight weight gainCold intoleranceCold intoleranceConstipationConstipationSlow Slow mentationmentation, inability to concentrate, inability to concentrateDepressionDepressionDiminished hearingDiminished hearing



Hypothyroidism Lab ValuesHypothyroidism Lab ValuesPrimary: Primary: HighHigh TSH, TSH, LowLow FT4FT4Secondary: Secondary: LowLow TSH or normal, TSH or normal, LowLow FT4FT4Antibody titers: Antibody titers: presentpresentAnti-thyroglobulin antibodies (TGA)Anti-thyroid peroxidase antibodies (TPO)T3 not a good testT3 not a good testSubclinical Hypothyroidism: Subclinical Hypothyroidism: mild elevated or high normal TSH, serum FT4 normalmild elevated or high normal TSH, serum FT4 normal


Hypothyroidism TreatmentHypothyroidism Treatment

••LevothyroxineLevothyroxine (T4) (T4) SynthroidSynthroid••Dose ranges 25mcg to 200 mcg dailyDose ranges 25mcg to 200 mcg daily••The T4 is converted into T3The T4 is converted into T3••Start lower in elderlyStart lower in elderly••Adjust dose every 4Adjust dose every 4--6 weeks6 weeks••Once stable, check levels twice yearlyOnce stable, check levels twice yearly


Symptoms Key WordsSymptoms Key WordsHyperHyper

Increase appetiteIncrease appetiteNervousNervousLoose stoolsLoose stoolsIrritabilityIrritabilityHeat intoleranceHeat intolerance

HypoHypo

Fatigue/LethargyFatigue/LethargyDepressedDepressedConstipationConstipationWeaknessWeaknessCold intoleranceCold intolerance



ThyroiditisThyroiditis

Acute Acute suppurativesuppurative (rare)(rare)SubacuteSubacute painful (painful (DequervainDequervain’’ss))DrugDrug--induced (induced (AmiodaroneAmiodarone))Chronic lymphocytic (HashimotoChronic lymphocytic (Hashimoto’’s)s)Fibrous Fibrous thyroiditisthyroiditis (Riedel(Riedel’’s)s)


Nontoxic GoiterNontoxic Goiter

Thyroid levels are usually normalThyroid levels are usually normalSlowly enlarging thyroid gland over yearsSlowly enlarging thyroid gland over years5% of US population5% of US populationWomen > menWomen > menUsually asymptomatic unless impingingUsually asymptomatic unless impingingEndemic in iodine deficient areasEndemic in iodine deficient areas


Solitary Thyroid NodulesSolitary Thyroid NodulesCommon in population, women>menCommon in population, women>menNodule must be over 1cm to be palpatedNodule must be over 1cm to be palpatedThyroid adenoma most common benign noduleThyroid adenoma most common benign noduleNodule of adenoma is encapsulatedNodule of adenoma is encapsulated

Follicular adenoma is most commonFollicular adenoma is most commonHürthle (oxyphil)

Papillary adenoma are very rarePapillary adenoma are very rare

Bleeding into nodule causes pain, enlargementBleeding into nodule causes pain, enlargementMost nodules are benign (95%)Most nodules are benign (95%)



Solitary Nodule Work UpSolitary Nodule Work UpHistory: Head or neck irradiationHistory: Head or neck irradiationPhysical exam: thyroid, lymph, systemicPhysical exam: thyroid, lymph, systemicTests: labs, US, RAIU, FNATests: labs, US, RAIU, FNACapsular invasion & vessel infiltration are Capsular invasion & vessel infiltration are hallmarks of malignancyhallmarks of malignancyNodules that concentrate iodine are Nodules that concentrate iodine are ““hothot””, , those that do not are those that do not are ““coldcold””Solitary nodules rarely cause extension or Solitary nodules rarely cause extension or pressure symptomspressure symptoms


Thyroid CancerThyroid Cancer

Rapid growingRapid growingPainlessPainlessSingle hard lesionSingle hard lesionMore common in women 3:1More common in women 3:1Worse in menWorse in men9% of thyroid cancers are fatal9% of thyroid cancers are fatal


Thyroid Cancer TypesThyroid Cancer Types

Papillary most common, least aggressivePapillary most common, least aggressiveFollicular type often metastasizesFollicular type often metastasizesAnaplasticAnaplastic type (bad!) mainly >60 type (bad!) mainly >60 yoyo, , least commonleast commonMedullaryMedullary typetype-- C cells, elevated C cells, elevated calcitonincalcitonin, found with MEN syndrome, found with MEN syndromeThyroid lymphoma seen in HashimotoThyroid lymphoma seen in Hashimoto’’ss



Treatment of Thyroid CancerTreatment of Thyroid Cancer

Total Total vsvs near total near total thyroidectomythyroidectomyLymph node dissection if neededLymph node dissection if neededRadiation therapyRadiation therapyRadioactive iodine therapyRadioactive iodine therapyChemotherapy as an adjunctChemotherapy as an adjunctT4 replacement will be neededT4 replacement will be needed


Parathyroid glandParathyroid gland

HypoparathyroidismHypoparathyroidism

HyperparathyroidismHyperparathyroidism

Public domain available at:http://upload.wikimedia.org/wikipedia/commons/7/75/Thyroidgland-intl.png


Review PTHReview PTHIncrease Increase osteoclasticosteoclastic activity in bone activity in bone CaCa++ into circulationinto circulationIncrease renal tubular Increase renal tubular reabsorptionreabsorption of Caof Ca++

Inhibits absorption of phosphate and Inhibits absorption of phosphate and bicarbbicarb by renal tubuleby renal tubuleSynthesis 1,25 Synthesis 1,25 dihydroxycholecalciferoldihydroxycholecalciferol by by kidney (active form of kidney (active form of Vit.DVit.D))



HypoparathyroidismHypoparathyroidismMost commonly seen following Most commonly seen following thyroidectomythyroidectomy, , surgical removal parathyroid adenomasurgical removal parathyroid adenomaDi GeorgeDi George’’s syndromes syndromeCongenital cardiac anomaliesCongenital cardiac anomaliesDamage heavy metals such as copper WilsonDamage heavy metals such as copper Wilson’’s disease s disease or iron (or iron (hemochromotosishemochromotosis, transfusion , transfusion hemosiderosishemosiderosis))GranulomasGranulomasRiedelRiedel’’s s thyroiditisthyroiditisMagnesium deficiency (Magnesium deficiency (malabsorptionmalabsorption chronic ETOH)chronic ETOH)PseudohypoparathyroidismPseudohypoparathyroidism


Clinical Features S&SClinical Features S&S

Cardiac arrhythmias, Cardiac arrhythmias, prolongprolong QT intervalQT intervalRickets, Rickets, osteomalaciaosteomalaciaNeuromuscular Neuromuscular irritabilityirritability

CircumoralCircumoral/fingers, /fingers, toes numbness, toes numbness, tinglingtinglingTetanyTetany: hyperactive : hyperactive DTR, DTR, ChovestekChovestek’’ss Sign, Sign, TrousseauTrousseau’’ss signsign

CataractsCataractsNails Nails –– thin, brittlethin, brittleSkin Skin –– dry, scalydry, scalyLoss hair Loss hair (eyebrows)(eyebrows)Defective teeth Defective teeth (childhood)(childhood)


Think Think HypocalcemiaHypocalcemia!!

ChovostekChovostek’’ss sign:sign:Tapping facial nerve elicits contraction of Tapping facial nerve elicits contraction of facial musclesfacial muscles

TrousseauTrousseau’’s sign:s sign:inflating BP cuff to pressure higher systolic inflating BP cuff to pressure higher systolic BP x 3 minutes to elicit carpal spasmsBP x 3 minutes to elicit carpal spasms



Labs and TreatmentLabs and Treatment

LabsLabsLow CalciumLow CalciumLow PTHLow PTHHigh phosphate High phosphate Alkaline Alkaline phosphatasephosphatasenormalnormal

TreatmentTreatmentIIV calcium V calcium gluconategluconateseveresevere

Calcium & Calcium & VitVit DDmaintenancemaintenance


HyperparathyroidismHyperparathyroidism

PRIMARYPRIMARY

SECONDARYSECONDARY


Primary HyperparathyroidismPrimary Hyperparathyroidism

HighHigh PTH, PTH, HighHigh CaCa++

Excessive secretion of PTH by one or more Excessive secretion of PTH by one or more glandsglandsWomen 3x more commonWomen 3x more commonPtPt’’s > 50 s > 50 yoyoSingle parathyroid adenoma (80%)Single parathyroid adenoma (80%)Hyperplasia (20%)Hyperplasia (20%)Carcinoma (<1%)Carcinoma (<1%)



Secondary Secondary HyperparathyroidismHyperparathyroidism

HighHigh PTH, PTH, LowLow or or Normal Normal CaCa++

Chronic Renal FailureChronic Renal FailureVitamin D deficiencyVitamin D deficiency


Signs and SymptomsSigns and Symptoms

BonesBonesStonesStonesGroansGroans

Psychiatric overtonesPsychiatric overtonesOther signsOther signs


BonesBones

Bone achesBone achesArthralgiaArthralgiaPathologic Pathologic fxfx’’ss ––OsteitisOsteitis fibrosafibrosa cysticacystica““brown tumorsbrown tumors”” or cysts of the jawor cysts of the jaw



StonesStones(urinary tract manifestations)(urinary tract manifestations)

Renal stonesRenal stonesNephrocalcinosisNephrocalcinosisPolydipsiaPolydipsiaPolyuriaPolyuriaHypercalcemiaHypercalcemia induced induced nephrogenicnephrogenic DIDI


GroansGroans

Muscle painMuscle painWeaknessWeaknessPancreatitisPancreatitisPUDPUDGoutGoutConstipationConstipation


Psychiatric OvertonesPsychiatric Overtones

DepressionDepressionFatigueFatigueAnorexiaAnorexiaSleep disturbanceSleep disturbanceAnxietyAnxietyLethargyLethargy



Other signsOther signs

Shortened QT interval (EKG)Shortened QT interval (EKG)

Decreased DTRDecreased DTR


Laboratory Laboratory

Elevated PTH, CaElevated PTH, Ca++ (confirms diagnosis)(confirms diagnosis)CaCa+ + > 10.5 mg/> 10.5 mg/dLdL, phosphate < 2.5 mg/, phosphate < 2.5 mg/dLdLHypercalciuriaHypercalciuria, elevated Alkaline , elevated Alkaline PhosphatasePhosphatase (bone disease)(bone disease)The best The best immunoradiometricimmunoradiometric assayassay


TreatmentTreatmentSurgerySurgery

MedicalMedicalIV hydrationIV hydrationBisphosphonatesBisphosphonatesFurosemideFurosemide



AVOID:AVOID:

Large doses ofLarge doses of…………..VitVit A, A, VitVit D and Calcium D and Calcium (Antacids/ supplements/additives)(Antacids/ supplements/additives)

ThiazideThiazide diureticsdiuretics


Adrenal GlandsAdrenal Glands

CushingCushing’’s syndromes syndrome

CorticoadrenalCorticoadrenal insufficiencyinsufficiency

NeoplasticNeoplastic Disease Disease

Public domain available at:http://commons.wikimedia.org/wiki/File:Illu_adrenal_gland.jpg


Adrenal HormonesAdrenal Hormones

GlucocorticoidsGlucocorticoids = = CortisolCortisolMineralcorticoidsMineralcorticoids = Aldosterone= AldosteroneAndrogens: precursors of sex steroidsAndrogens: precursors of sex steroidsCatecholaminesCatecholamines: epinephrine and : epinephrine and norepinephrinenorepinephrine



GlucocorticoidsGlucocorticoids = = CortisolCortisolHelp body respond to stressHelp body respond to stressMaintain BPMaintain BPCV functionCV functionSlow immune system inflammatory Slow immune system inflammatory responseresponseMaintain levels of glucoseMaintain levels of glucoseRegulate protein/fat/carbohydrate Regulate protein/fat/carbohydrate metabolismmetabolism


MineralcorticoidsMineralcorticoids = Aldosterone= Aldosterone

Maintains blood pressureMaintains blood pressureMaintains water and salt balance Maintains water and salt balance Help kidneys retain NaHelp kidneys retain Na++, excrete K, excrete K++


ACTHACTH

Public domain available at:http://commons.wikimedia.org/wiki/File:ACTH_Negative_Feedback.svg



ACTHACTHAdrenocorticotropicAdrenocorticotropic hormonehormoneHypothalamus Hypothalamus CRHCRH pituitarypituitaryPituitary Pituitary ACTH ACTH ACTH stimulates adrenal cortex ACTH stimulates adrenal cortex cortisolcortisolExcess ACTH Excess ACTH adrenal hyperplasiaadrenal hyperplasiaDeficiency ACTH Deficiency ACTH adrenal atrophyadrenal atrophyCortisolCortisol inhibits CRH & ACTH secretioninhibits CRH & ACTH secretion


CushingCushing’’s Disease s Disease Excess Excess ACTHACTH

CushingCushing’’s disease (ACTH excess) is caused s disease (ACTH excess) is caused by ACTH secreting pituitary by ACTH secreting pituitary microadenomamicroadenomaCushingCushing’’s syndrome (s syndrome (cortisolcortisol excess) is excess) is the effects of excess the effects of excess cortisolcortisol on the bodyon the bodyWomen affected 8 times more oftenWomen affected 8 times more oftenCushingCushing’’s disease accounts for 70% of s disease accounts for 70% of CushingCushing’’s syndromes syndrome


CausesCauses

Iatrogenic CushingIatrogenic Cushing’’s Syndromes Syndrome (most common(most common cause)cause)

ACTH secreting adenoma of pituitary = ACTH secreting adenoma of pituitary = CushingsCushingsDisease (43%) Disease (43%) (second most common cause)(second most common cause)

Adrenal Adenoma and Carcinoma (10Adrenal Adenoma and Carcinoma (10--15%)15%)

Ectopic ACTH (10Ectopic ACTH (10--15%)15%)



CushingCushing’’s Diseases DiseaseCentral obesityCentral obesityHirsutismHirsutismMoon faceMoon face““buffalo humpbuffalo hump””Purple Purple striaestriaeLanugoLanugo hairhairAcneAcne

Easy bruisingEasy bruisingSupraclavicularSupraclavicular fat fat padspadsProtuberant abdomenProtuberant abdomenThin extremitiesThin extremitiesHTNHTNIncrease infectionsIncrease infections


How to Diagnose How to Diagnose CushingsCushingsDisease?Disease?

Initial screening Initial screening Low dose Low dose DexamethasoneDexamethasone suppression testsuppression test24 hour free urinary 24 hour free urinary cortisolcortisol levellevel


What is my source of ACTH?What is my source of ACTH?

High dose High dose DexamethasoneDexamethasone Suppression testSuppression test> 50% suppression > 50% suppression cortisolcortisol pituitarypituitary

MRI of pituitaryMRI of pituitary

< 50% suppression < 50% suppression cortisolcortisol ectopic ectopic ACTH tumorACTH tumor

CT of appropriate regionCT of appropriate region



Ectopic ACTH producersEctopic ACTH producers

Small cell carcinoma (lung) Small cell carcinoma (lung) ““Oat cellOat cell””

Thyroid, Thyroid, thymomasthymomas

Pancreatic islet cellPancreatic islet cell


Treatment of CushingTreatment of Cushing’’ss

Iatrogenic CushingIatrogenic Cushing’’s: Taper steroidss: Taper steroids

Pituitary CushingPituitary Cushing’’s: s: transsphenoidaltranssphenoidal removal removal of pituitary adenomaof pituitary adenoma

Adrenal adenoma or carcinoma: Adrenal adenoma or carcinoma: adrenalectomyadrenalectomy


CorticoadrenalCorticoadrenal InsufficiencyInsufficiency

““AddisonAddison’’s diseases disease””

Public domain available at:http://commons.wikimedia.org/wiki/File:Illu_adrenal_gland.jpg UMDNJ PANCE/PANRE Review Course


UMDNJ PANCE/PANRE Review UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, Course (becoming Rutgers July 1,

2013)2013)


Causes of Causes of Destruction or Dysfunction Destruction or Dysfunction

of Adrenal Corticesof Adrenal Cortices

PrimaryPrimary (ACTH independent)(ACTH independent)

AutoimmuneAutoimmuneAdrenalectomyAdrenalectomyInfection (TB/fungal)Infection (TB/fungal)BleedBleedMetastaticMetastaticCongenitalCongenital

Secondary Secondary (ACTH dependent) (ACTH dependent)

SteroidsSteroidsHypopituitarismHypopituitarismTraumaTraumaACTH deficiencyACTH deficiency


CortiocadrenalCortiocadrenal Insufficiency Insufficiency ““AddisonAddison’’s diseases disease””

Autoimmune destruction Autoimmune destruction most common cause Addisonmost common cause Addison’’ss80% spontaneous cases80% spontaneous cases

Infectious diseases Infectious diseases –– tuberculosis tuberculosis most common cause worldwidemost common cause worldwide

Iatrogenic Iatrogenic B/L B/L adrenalectomyadrenalectomy

MetastaticMetastaticSecondary adrenal insufficiency Secondary adrenal insufficiency

abrupt cessation of exogenous steroidsabrupt cessation of exogenous steroids

pituitarypituitary failurefailureUMDNJ PANCE/PANRE Review Course


Clinical FeaturesClinical FeaturesGI symptomsGI symptoms: anorexia, N/V, vague : anorexia, N/V, vague abdominal pain, wt. lossabdominal pain, wt. lossMentalMental: lethargy, confusion, psychosis: lethargy, confusion, psychosisHypoglycemiaHypoglycemiaHypotensionHypotension (orthostatic)(orthostatic)HyperpigmentationHyperpigmentation –– knuckles, elbows, knuckles, elbows, knees, post. neck, knees, post. neck, palmarpalmar creases, nail creases, nail beds (primary insufficiency)beds (primary insufficiency)OtherOther: irregular or absent menses: irregular or absent menses



Diagnostic LabsDiagnostic Labs

Serum NaSerum Na++ low low (90%)(90%)

Serum KSerum K+ + high high (65% primary disease)(65% primary disease)

Fasting glucose lowFasting glucose lowLow Low levels of AM levels of AM cortisolcortisol (<3 (<3 mcg/mcg/dLdL), ), high ACTH (> 200 mg/high ACTH (> 200 mg/dLdL) = ) = diagnosticdiagnosticLow ACTH = secondaryLow ACTH = secondaryEosinophiliaEosinophilia, , neutropenianeutropenia, , lymphocytosislymphocytosis


CosyntropinCosyntropin test (stimulation)test (stimulation)

Give ACTH (Give ACTH (cosyntropincosyntropin-- parenterallyparenterally))Measure serum Measure serum cortisolcortisol 3030--60 min60 minNormal rise to at least 20 mcg/Normal rise to at least 20 mcg/dLdLLess than rise of 20 mcg/Less than rise of 20 mcg/dLdL –– suspicious suspicious for adrenal insufficiencyfor adrenal insufficiency


TreatmentTreatment

HydrocortisoneHydrocortisone -- glucocorticoidglucocorticoidPrednisone Prednisone 2020--40mg 40mg popo QD QD HydrocortisoneHydrocortisone 5050--100mg q6hr IV 100mg q6hr IV ((““stressstress””situationssituations))

FludrocortisoneFludrocortisone –– mineralocorticoidmineralocorticoidFlorinefFlorinef 0.10.1--0.2mg 0.2mg popo QDQDEnsure adequate salt intakeEnsure adequate salt intake



PheochromocytomaPheochromocytoma

Rare cause of HTN, age 40Rare cause of HTN, age 40--60 onset60 onsetMost are due to unilateral Most are due to unilateral medullarymedullary tumortumorBilateral type tends to run in familiesBilateral type tends to run in familiesRule of 10Rule of 10’’s: 10% bilateral, 10% extras: 10% bilateral, 10% extra--adrenal, adrenal, 10% malignant, 10% familial, 10% pediatric, 10% malignant, 10% familial, 10% pediatric, 10% show no HTN10% show no HTNPalpitations, diaphoresis, and headachePalpitations, diaphoresis, and headachePicture of refractory or labile HTNPicture of refractory or labile HTN


Presentation and Laboratory Presentation and Laboratory ValuesValues

Family Family HxHx of of pheochromocytomapheochromocytoma or MENor MENFirst do 24hr urine First do 24hr urine catecholaminescatecholamines (avoid (avoid caffeine, vanilla, fruits)caffeine, vanilla, fruits)False (+): shock, hypoglycemia, stress, False (+): shock, hypoglycemia, stress, clonidineclonidinewithdrawal, withdrawal, TCAsTCAs, and , and MAOIsMAOIsClonidineClonidine suppression suppression test if above equivocaltest if above equivocal


TreatmentTreatment

Adrenergic blockade for 3Adrenergic blockade for 3--4 weeks4 weeks––PhenoxybenzaminePhenoxybenzamine POPO––PhentolaminePhentolamine IVIV

Surgical laparoscopic Surgical laparoscopic adrenalectomyadrenalectomyFollow up catecholamine testing neededFollow up catecholamine testing neededAdjunctive radiation and chemotherapy Adjunctive radiation and chemotherapy



An 8 yr. old boy presents with his mother who states that he An 8 yr. old boy presents with his mother who states that he has become overweight during the past year and has little has become overweight during the past year and has little energy, sleeps more, and is cold all the time. His growth energy, sleeps more, and is cold all the time. His growth curve has fallen from the 50curve has fallen from the 50th%th% to the 5to the 5th%th% for height, but his for height, but his weight has increased from the 50weight has increased from the 50th%th% to 90to 90th%th%. On PE he is . On PE he is obese, has thin hair, immature obese, has thin hair, immature faciesfacies, and slowed reflexes. , and slowed reflexes. What is the cause of his symptoms?What is the cause of his symptoms?

1.1. AcromegalyAcromegaly2.2. CushingCushing’’s syndromes syndrome3.3. DwarfismDwarfism4.4. HypothyroidismHypothyroidism


An 8 yr. old boy presents with his mother who states that he An 8 yr. old boy presents with his mother who states that he has become overweight during the past year and has little has become overweight during the past year and has little energy, sleeps more, and is cold all the time. His growth energy, sleeps more, and is cold all the time. His growth curve has fallen from the 50curve has fallen from the 50th%th% to the 5to the 5th%th% for height, but his for height, but his weight has increased from the 50weight has increased from the 50th%th% to 90to 90th%th%. On PE he is . On PE he is obese, has thin hair, immature obese, has thin hair, immature faciesfacies, and slowed reflexes. , and slowed reflexes. What is the cause of his symptoms?What is the cause of his symptoms?

1.1. AcromegalyAcromegaly2.2. CushingCushing’’s syndromes syndrome3.3. DwarfismDwarfism4.4. HypothyroidismHypothyroidism


A 28 yr. old presents to the ED with confusion and agitation. A 28 yr. old presents to the ED with confusion and agitation. He appears intoxicated and is unable to provide a history. On He appears intoxicated and is unable to provide a history. On exam he has mild exam he has mild proptosisproptosis, is , is tachycardictachycardic with regular with regular rhythm, neck fullness, a fine tremor, and brisk reflexes. While rhythm, neck fullness, a fine tremor, and brisk reflexes. While in the ED he vomits x 3. All labs are normal.in the ED he vomits x 3. All labs are normal.What is the most likely diagnosis? What is the most likely diagnosis?

1.1. AddisonAddison’’s diseases disease2.2. Diabetic Diabetic ketoacidosisketoacidosis3.3. Thyroid stormThyroid storm4.4. Toxic adenomaToxic adenoma



A 28 yr. old presents to the ED with confusion and agitation. A 28 yr. old presents to the ED with confusion and agitation. He appears intoxicated and is unable to provide a history. On He appears intoxicated and is unable to provide a history. On exam he has mild exam he has mild proptosisproptosis, is , is tachycardictachycardic with regular with regular rhythm, neck fullness, a fine tremor, and brisk reflexes. While rhythm, neck fullness, a fine tremor, and brisk reflexes. While in the ED he vomits x 3. All labs are normal.in the ED he vomits x 3. All labs are normal.What is the most likely diagnosis? What is the most likely diagnosis?

1.1. AddisonAddison’’s diseases disease2.2. Diabetic Diabetic ketoacidosisketoacidosis3.3. Thyroid stormThyroid storm4.4. Toxic adenomaToxic adenoma


Where is thyroidWhere is thyroid--stimulating hormone stimulating hormone (TSH) produced?(TSH) produced?

1.1. Anterior pituitaryAnterior pituitary2.2. Posterior pituitary Posterior pituitary 3.3. ZonaZona fasciculatafasciculata4.4. ZonaZona glomerulosaglomerulosa


Where is thyroidWhere is thyroid--stimulating hormone stimulating hormone (TSH) produced?(TSH) produced?

1.1. Anterior pituitaryAnterior pituitary2.2. Posterior pituitary Posterior pituitary 3.3. ZonaZona fasciculatafasciculata4.4. ZonaZona glomerulosaglomerulosa



Over the past year a 21 yr. old female has developed Over the past year a 21 yr. old female has developed amenorrhea and milky nipple discharge. She is not taking any amenorrhea and milky nipple discharge. She is not taking any medications and is sexually active but doesnmedications and is sexually active but doesn’’t wish to become t wish to become pregnant. Her serum HCG is negative; pregnant. Her serum HCG is negative; prolactinprolactin 300 mg/300 mg/dLdL; ; MRI reveals a 3 mm mass in the pituitary. What is the most MRI reveals a 3 mm mass in the pituitary. What is the most appropriate therapy at this time?appropriate therapy at this time?

1.1. BromocriptineBromocriptine ((ParlodelParlodel))2.2. Monthly IM Monthly IM

medroxyprogesteronemedroxyprogesterone3.3. Sequential Sequential OCOC’’ss4.4. TransphenoidalTransphenoidal tumor tumor

resectionresection


Over the past year a 21 yr. old female has developed Over the past year a 21 yr. old female has developed amenorrhea and milky nipple discharge. She is not taking any amenorrhea and milky nipple discharge. She is not taking any medications and is sexually active but doesnmedications and is sexually active but doesn’’t wish to become t wish to become pregnant. Her serum HCG is negative; pregnant. Her serum HCG is negative; prolactinprolactin 300 mg/300 mg/dLdL; ; MRI reveals a 3 mm mass in the pituitary. What is the most MRI reveals a 3 mm mass in the pituitary. What is the most appropriate therapy at this time?appropriate therapy at this time?

1.1. BromocriptineBromocriptine ((ParlodelParlodel))2.2. Monthly IM Monthly IM

medroxyprogesteronemedroxyprogesterone3.3. Sequential Sequential OCOC’’ss4.4. TransphenoidalTransphenoidal tumor tumor

resectionresection


A 25 yr old presents with extreme weakness and A 25 yr old presents with extreme weakness and dizziness. On PE he appears depressed; BP 90/70. He dizziness. On PE he appears depressed; BP 90/70. He has dark skin and has dark skin and hyperpigmentedhyperpigmented creases on his creases on his palms. Labs: low sodium; high potassium, calcium and palms. Labs: low sodium; high potassium, calcium and urea. What is the most likely diagnosis?urea. What is the most likely diagnosis?

1.1. AddisonAddison’’s diseases disease2.2. CushingCushing’’s syndromes syndrome3.3. PheochromocytomaPheochromocytoma4.4. Primary Primary

hyperaldosteronismhyperaldosteronism



A 25 yr old presents with extreme weakness and A 25 yr old presents with extreme weakness and dizziness. On PE he appears depressed; BP 90/70. He dizziness. On PE he appears depressed; BP 90/70. He has dark skin and has dark skin and hyperpigmentedhyperpigmented creases on his creases on his palms. Labs: low sodium; high potassium, calcium and palms. Labs: low sodium; high potassium, calcium and urea. What is the most likely diagnosis?urea. What is the most likely diagnosis?

1.1. AddisonAddison’’s diseases disease2.2. CushingCushing’’s syndromes syndrome3.3. PheochromocytomaPheochromocytoma4.4. Primary Primary

hyperaldosteronismhyperaldosteronism


A 46 yr old male complains that he has developed A 46 yr old male complains that he has developed coarse facial features and a large prominent jaw. He coarse facial features and a large prominent jaw. He states that his shoe size has increased over the last states that his shoe size has increased over the last year despite no weight gain. What additional finding year despite no weight gain. What additional finding will most likely be found on PE?will most likely be found on PE?

1.1. Atrophy of the digitsAtrophy of the digits2.2. Deepening voiceDeepening voice3.3. Dry skinDry skin4.4. Enlarged testesEnlarged testes


A 46 yr old male complains that he has developed A 46 yr old male complains that he has developed coarse facial features and a large prominent jaw. He coarse facial features and a large prominent jaw. He states that his shoe size has increased over the last states that his shoe size has increased over the last year despite no weight gain. What additional finding year despite no weight gain. What additional finding will most likely be found on PE?will most likely be found on PE?

1.1. Atrophy of the digitsAtrophy of the digits2.2. Deepening voiceDeepening voice3.3. Dry skinDry skin4.4. Enlarged testesEnlarged testes



A 19 yr. old male presents to the ED with acute A 19 yr. old male presents to the ED with acute fatigue, vomiting, diarrhea, and anorexia. On PE he fatigue, vomiting, diarrhea, and anorexia. On PE he has postural dizziness and pigmented has postural dizziness and pigmented buccalbuccal mucosa. mucosa. Labs indicate Labs indicate hyponatremiahyponatremia, , hyperkalemiahyperkalemia and and glucose of 50 mg/glucose of 50 mg/dLdL. . What is the most likely diagnosis?What is the most likely diagnosis?

1.1. Adrenal insufficiencyAdrenal insufficiency2.2. DM, type 1DM, type 13.3. MyxedemaMyxedema4.4. PheochromocytomaPheochromocytoma


A 19 yr. old male presents to the ED with acute A 19 yr. old male presents to the ED with acute fatigue, vomiting, diarrhea, and anorexia. On PE he fatigue, vomiting, diarrhea, and anorexia. On PE he has postural dizziness and pigmented has postural dizziness and pigmented buccalbuccal mucosa. mucosa. Labs indicate Labs indicate hyponatremiahyponatremia, , hyperkalemiahyperkalemia and and glucose of 50 mg/glucose of 50 mg/dLdL. . What is the most likely diagnosis?What is the most likely diagnosis?

1.1. Adrenal insufficiencyAdrenal insufficiency2.2. DM, type 1DM, type 13.3. MyxedemaMyxedema4.4. PheochromocytomaPheochromocytoma


Diabetes MellitusDiabetes Mellitus



What is Diabetes Mellitus?What is Diabetes Mellitus?

A disorder of carbohydrate metabolismA disorder of carbohydrate metabolismLack of insulinLack of insulinInsulin resistanceInsulin resistanceBoth insulin deficiency and resistanceBoth insulin deficiency and resistance


ClassificationClassification

Type 1 Type 1 -- little or no endogenous insulin little or no endogenous insulin productionproductionType 2 Type 2 –– insulin resistance and/ or insulin resistance and/ or deficiencydeficiencyGestationalGestationalLADA (type 1.5)LADA (type 1.5)-- latent autoimmune diabetes in adults (+) GADMODYMODY-- maturity onset diabetes of the maturity onset diabetes of the youngyoung


EpidemiologyEpidemiologyNearly 26 million people in the US have Nearly 26 million people in the US have diabetes, 7 million of whom may be diabetes, 7 million of whom may be undiagnosed and unaware of their undiagnosed and unaware of their conditionconditionResearch examining A1C levels found that 35% of U.S. adults aged 20 years or older had pre-diabetes (50% of those aged 65 years or older are considered pre-diabetic); an estimated 79 million Americans aged 20 years or older have pre-diabetes UMDNJ PANCE/PANRE Review Course



Pathogenesis of DM type 1Pathogenesis of DM type 1

Hereditary predisposition (Hereditary predisposition (HLAHLA--DR gene)DR gene)

Autoimmune Autoimmune (90% islet cell AB)(90% islet cell AB)Islet CellIslet Cell CytoplasmicCytoplasmic AutoantibodiesAutoantibodies (ICA) (ICA) GlutamicGlutamic Acid Acid DecarboxylaseDecarboxylase AutoantibodiesAutoantibodies (GADA) (GADA) InsulinomaInsulinoma--AssociatedAssociated--2 2 AutoantibodiesAutoantibodies (IA(IA--2A) 2A) Insulin Insulin AutoantiboidiesAutoantiboidies (IAA) (IAA)

Autoimmune destruction of beta cellsAutoimmune destruction of beta cellsInfiltration of pancreas with TInfiltration of pancreas with T--lymphocyteslymphocytes


Pathogenesis of DM type 2Pathogenesis of DM type 2

Genetically linkedGenetically linkedInadequate insulin secretionInadequate insulin secretionPeripheral insulin resistancePeripheral insulin resistanceAccelerated hepatic glucose productionAccelerated hepatic glucose production


Type I vs. Type IIType I vs. Type II

Onset: SuddenOnset: SuddenAge: Typically youngAge: Typically youngBody: Usually thinBody: Usually thinKetosis: CommonKetosis: CommonAutoantibodiesAutoantibodies: : PresentPresentEndogenous insulin: Endogenous insulin: low or absentlow or absent

Onset: GradualOnset: GradualAge: Mostly adultsAge: Mostly adultsBody: usually obeseBody: usually obeseKetosis: RareKetosis: RareAutoantibodiesAutoantibodies: : AbsentAbsentEndogenous insulin: Endogenous insulin: normal, increased, normal, increased, decreaseddecreased



Risk FactorsRisk FactorsAge (> 45 years old)Age (> 45 years old)Obesity Obesity Sedentary LifestyleSedentary LifestyleEthnicity (AfricanEthnicity (African--American, Hispanic, Asian)American, Hispanic, Asian)Family history Family history HTN, hypercholesterolemia, high triglyceridesHTN, hypercholesterolemia, high triglyceridesGestational diabetes, having a child >9lbsGestational diabetes, having a child >9lbsPCOSPCOS


Diagnostic CriteriaDiagnostic Criteria

Adapted from the ADA Standards of medical care in diabetesAdapted from the ADA Standards of medical care in diabetes--2011. 2011. Diabetes CareDiabetes Care. . 2011;34 (2011;34 (supplsuppl 1):S111):S11--S61.S61.


FBS GTT A1C

Normal Blood Sugar <100 mg/dL <140 mg/dL <5.7%

Prediabetes 100-125mg/dL 140-199 mg/dL 5.7-6.4%

Diabetes >126mg/dL >200mg/dL >6.5%

Screening Guidelines Screening Guidelines Asymptomatic individuals with risk factors Asymptomatic individuals with risk factors should be screened for diabetes if they are should be screened for diabetes if they are overweight (BMI > 25 kg/m2) and have overweight (BMI > 25 kg/m2) and have additional risk factorsadditional risk factorsBeginning at age 45 for those without Beginning at age 45 for those without other risk factors other risk factors Those with normal results and low risk Those with normal results and low risk should be reshould be re--tested at threetested at three--year intervalsyear intervals

American Diabetes Association. Standards of Medical Care in DiabAmerican Diabetes Association. Standards of Medical Care in Diabetes etes -- 2010. 2010. Diabetes Care 2010:33;S11Diabetes Care 2010:33;S11--6161



Testing Recommendations: ChildTesting Recommendations: Child

OverweightOverweight, , Age 10 yrsAge 10 yrs or or onset of pubertyonset of pubertyBMI > 85BMI > 85thth percentile for age and sexpercentile for age and sexWeight for height > 85Weight for height > 85thth percentilepercentileWeight > 120% ideal for heightWeight > 120% ideal for height

Plus Plus 2 risk factors2 risk factorsFamily historyFamily historyRaceRaceAcanthosisAcanthosis nigricansnigricans, HTN, dyslipidemia, PCOS, SGA, HTN, dyslipidemia, PCOS, SGAMaternal history of DM or GDMMaternal history of DM or GDM

Frequency every Frequency every 3 years3 years


Signs & SymptomsSigns & SymptomsPolyuriaPolyuria, , polydipsiapolydipsia, , polyphagiapolyphagiaInfectionsInfectionsWeaknessWeaknessLethargyLethargyNumbness and tinglingNumbness and tinglingBlurry visionBlurry visionWeight lossWeight loss


Diabetes ComplicationsDiabetes Complications

MicrovascularMicrovascular ComplicationsComplications::RetinopathyRetinopathyNeuropathyNeuropathyNephropathyNephropathy

MacrovascularMacrovascular Complications:Complications:CVDCVD-- atherosclerosis atherosclerosis –– 110 0 cause of deathcause of death

Poor immune functionPoor immune functionComplicated infectionsComplicated infections



Morbidity and MortalityMorbidity and MortalityLeading cause of kidney failure, Leading cause of kidney failure,

nontraumaticnontraumatic lowerlower--limb amputations, and limb amputations, and new cases of blindness among adults in new cases of blindness among adults in the USthe USMajor cause of heart disease and strokeMajor cause of heart disease and stroke

1 in 3 suffer from severe periodontal 1 in 3 suffer from severe periodontal diseasediseaseSeventh leading cause of death in the USSeventh leading cause of death in the US

*CDC National diabetes fact sheet: national estimates and gener*CDC National diabetes fact sheet: national estimates and general information on al information on diabetes and diabetes and prediabetesprediabetes in the United States, 2011. Atlanta, GA: U.S. Department of in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and PreveHealth and Human Services, Centers for Disease Control and Prevention, 2011.ntion, 2011.


Diabetic RetinopathyDiabetic RetinopathyCataractsCataractsGlaucomaGlaucomaProliferative retinopathyProliferative retinopathyneovascularizationneovascularization, scarring, scarring

NonNon--Proliferative retinopathyProliferative retinopathyhemorrhages, exudates, hemorrhages, exudates, microaneursymsmicroaneursyms, venous , venous dilatationdilatation

DM leading cause of BlindnessDM leading cause of BlindnessPublic domain available at:http://commons.wikimedia.org/wiki/Eye


Diabetic NeuropathyDiabetic Neuropathy

Peripheral neuropathy ( LE > UE )Peripheral neuropathy ( LE > UE )distally distally symmetric,symmetric,““stockingstocking glove patternglove pattern”” loss sensation loss sensation

AutonomicAutonomicGastroparesisGastroparesis, urinary retention, postural hypotension, , urinary retention, postural hypotension,

impotence, fecal incontinence impotence, fecal incontinence

Silent MISilent MI

Public domain available at:http://commons.wikimedia.org/wiki/File:Derived_Neuron_schema_with_no_labels.svg



Diabetic NephropathyDiabetic NephropathyHigh glucose levels cause High glucose levels cause polyuriapolyuria--renal renal hyperfiltrationhyperfiltrationChronic Chronic hyperfiltrationhyperfiltration leads to kidney leads to kidney damagedamageProteinuriaProteinuria –– early indicator of renal early indicator of renal diseasediseaseRapid progression to dialysis once Rapid progression to dialysis once creatininecreatinine reaches 3reaches 3--4 mg/dl4 mg/dl

ESRDESRD--DM most common reason for HDDM most common reason for HDPublic domain available at:http://commons.wikimedia.org/wiki/File:Diffuse_proliferative_lupus_nephritis.jpg


Systemic Vascular ChangesSystemic Vascular Changes

AtherosclerosisAtherosclerosisHypertensionHypertensionCADCADPVDPVDStrokeStroke

Public domain available at:http://commons.wikimedia.org/wiki/File:Aorta.jpg


Poor immune functionPoor immune function

VaginitisVaginitisPeriodonitisPeriodonitisUTIUTISinusitisSinusitisOtitisOtitis externaexterna/ media/ mediaCellulitisCellulitis

Public domain available at:http://commons.wikimedia.org/wiki/File:Cellulitis_Left_Leg.JPGUMDNJ PANCE/PANRE Review Course



Complicated InfectionsComplicated InfectionsGram negative pneumoniasGram negative pneumoniasInfected ulcersInfected ulcersGram negative sepsisGram negative sepsis

Public domain available at:http://commons.wikimedia.org/wiki/File:ULCERCELLULITIS1.JPG


Diabetic Diabetic immunosuppressionimmunosuppression

Fungal infectionsFungal infectionsThrushThrushAspergilliosisAspergilliosisCholecystitisCholecystitis/ / cholangitischolangitispyelonephritispyelonephritis

Public domain available at:http://commons.wikimedia.org/wiki/File:Fungal_tounge.jpg


Hypoglycemia Hypoglycemia Signs and SymptomsSigns and Symptoms

FSFS-- < 70 mg/< 70 mg/dLdLTachycardia, sweating, tremors, nausea, Tachycardia, sweating, tremors, nausea, hunger, anxietyhunger, anxietyConfusion, coma, seizure, death Confusion, coma, seizure, death

TxTx: : 15 grams of glucose15 grams of glucose4 oz OJ or soda, 34 oz OJ or soda, 3--4 glucose tabs, 54 glucose tabs, 5--6 hard candies, 6 hard candies,

glucagon IMglucagon IM



DKADKA-- Diabetic Diabetic KetoacidosisKetoacidosis

Usually occurs in type 1Usually occurs in type 1 (insulin insufficiency)(insulin insufficiency)

Diagnostic criteriaDiagnostic criteria--PG >250PG >250Ph <7.35Ph <7.35BicarbBicarb <15<15High anion gapHigh anion gapSerum/ urine Serum/ urine ketonesketones

Signs/SymptomsSigns/Symptoms--PolyuriaPolyuria, , polydipisiapolydipisiaWeakness, stupor ( Weakness, stupor ( KussmaulKussmaul breathing)breathing)Tachycardia, Tachycardia, tachypneatachypnea (to compensate pH)(to compensate pH)Nausea/ vomitingNausea/ vomitingFruity breathFruity breath


Treatment of DKATreatment of DKA

Regular insulin IV Regular insulin IV 0.1 units/ kg bolus 0.1 units/ kg bolus -- then 0.1 then 0.1 units/kg/hrunits/kg/hr

Fluid replacement w/ normal saline Fluid replacement w/ normal saline 33--4 L/8 hrs4 L/8 hrs

Sodium Sodium bicarbbicarb if pH <7.0if pH <7.0Potassium replacement Potassium replacement ((2020--30 30 meqmeq/ 2/ 2--3 hrs after 3 hrs after therapy started)therapy started)

Glucose < 250md/dL add 5% dextrose to fluidsGlucose < 250md/dL add 5% dextrose to fluids


Hyperosmolar Hyperglycemic State (HHS)

Usually occurs in type 2Usually occurs in type 2 (osmotic (osmotic diuresisdiuresis due to due to hyperglycemia hyperglycemia --> dehydration, insulin secretion suppresses > dehydration, insulin secretion suppresses ketolysisketolysis

K+, Mg+, are lost along w/Water & Na+K+, Mg+, are lost along w/Water & Na+Severe dehydrationSevere dehydration

cardiac profusion compromise: cardiac profusion compromise: tachycaridiatachycaridia, low C.O., low Mg+ & K+, low C.O., low Mg+ & K+

Diagnostics CriteriaDiagnostics Criteria--PG >600 mg/PG >600 mg/dLdLSerum Serum osmosm >310>310No acidosisNo acidosisNo No ketonesketonesBicarbBicarb >15>15

TriggersTriggers: infection, AMI, pancreatitis, poor compliance: infection, AMI, pancreatitis, poor compliance



Treatment Treatment Hyperosmolar Hyperglycemic State

Saline replacement Saline replacement -- (6(6--10 L)10 L)

Regular Insulin IV Regular Insulin IV (15 units/ IV, 15 units SQ)(15 units/ IV, 15 units SQ)

Potassium Potassium (10 (10 meqmeq to initial fluids)to initial fluids)

Magnesium Magnesium (2 gm to initial fluids)(2 gm to initial fluids)

Once glucose <250md/dL Once glucose <250md/dL –– 5% dextrose 5% dextrose to fluidsto fluids


Dawn PhenomenonDawn PhenomenonEnd result of a combination of natural body changes that occur during sleep Between 3 AM & 8 AM, your body starts to increase the amounts of counter-regulatory hormones (GH, cortisol, & catecholamines). These combined events cause your body's blood sugar levels to rise in the morningM/C in type 1


SomogyiSomogyi EffectEffect

"rebound hyperglycemia”The cause is more "man-made" - a result of poor diabetes managementRefers to pattern of high morning sugars preceded by an episode of hypoglycemia Check blood sugars between 2-3 AM



Treatment & Management of DMTreatment & Management of DM

Self monitoringSelf monitoringInsulin/ oral medicationsInsulin/ oral medicationsDiet and exerciseDiet and exercisePatient educationPatient education


Self MonitoringSelf Monitoring

Used to adjust Used to adjust medication medication Improves glycemic Improves glycemic controlcontrolPatientPatient’’s involvement s involvement in their carein their care

Public domain available at:http://commons.wikimedia.org/wiki/File:Glucose_test.JPG


Balanced Diet Balanced Diet Moderate caloric restrictionModerate caloric restrictionModerate weight loss 5Moderate weight loss 5--9 kg goals9 kg goalsSpacing meals (especially Spacing meals (especially carbscarbs))Approach depends on lifestyleApproach depends on lifestyleVery low calorie diet usually NOT effective Very low calorie diet usually NOT effective for long term goals!for long term goals!



ExerciseExerciseImproves glucose Improves glucose tolerancetolerancePromotes good circulationPromotes good circulationMaintains good muscle Maintains good muscle tonetoneHelps maintain normal Helps maintain normal body weightbody weightReduces insulin Reduces insulin requirementsrequirementsRecommendation Recommendation 150min/week150min/week

Public domain available at:http://commons.wikimedia.org/wiki/File:Exercise_machines_(284617740).jpg


Oral AntiOral Anti--diabetic Agents (OAD)diabetic Agents (OAD)

SensitizersSensitizers-- Inhibit the release of glucose Inhibit the release of glucose from the liver; improve sensitivity to from the liver; improve sensitivity to insulininsulin

BiguanidesBiguanides-- Metformin (Metformin (GlucophageGlucophage, , FortametFortamet, , GlumetzaGlumetza, etc), etc)

* Lactic Acidosis, elderly* Lactic Acidosis, elderly

Thiazolidinediones (TZD) PPARy (gamma)Thiazolidinediones (TZD) PPARy (gamma)Rosiglitazone (Avandia),Pioglitazone (Actos)Rosiglitazone (Avandia),Pioglitazone (Actos)

*Bladder Cancer, CHF*Bladder Cancer, CHF



SecretagoguesSecretagogues-- Stimulate the release of Stimulate the release of insulin from the pancreasinsulin from the pancreas

SulfonylureasSulfonylureas (SU)(SU)Glipizide (Glipizide (GlucotrolGlucotrol), ), GlimepirideGlimepiride ((AmarylAmaryl), ), GlyburideGlyburide ((DiaBetaDiaBeta, , GlynaseGlynase))

MeglitinidesMeglitinidesRepaglinideRepaglinide ((PrandinPrandin), ), NateglinideNateglinide ((StarlixStarlix))




DipeptidylDipeptidyl peptidasepeptidase--4 inhibitors (DPP4 inhibitors (DPP--4)4)--inhibitors inhibit the degradation of incretins (GLP-

1 and GIP)SaxagliptinSaxagliptin ((OnglyzaOnglyza), ), SitagliptinSitagliptin ((JanuviaJanuvia), ), LinagliptinLinagliptin ((TradjentaTradjenta))

AlphaAlpha--glucosidaseglucosidase inhibitors (AGI)inhibitors (AGI)-- Slow Slow the breakdown of starches and some sugarsthe breakdown of starches and some sugars

AcarboseAcarbose ((PrecosePrecose), ), MiglitolMiglitol ((GlysetGlyset))


NonNon--insulin Injectablesinsulin InjectablesAmylin mimetics- It slows the rate at which It slows the rate at which glucose is absorbed from the intestine, reduces the glucose is absorbed from the intestine, reduces the production of glucose by the liver by inhibiting the action production of glucose by the liver by inhibiting the action of glucagonof glucagon

Pramlintide (Symlin)

Incretin mimetics- GLP-1 agonist- Enhances Enhances insulin secretion by the pancreatic betainsulin secretion by the pancreatic beta--cell, suppresses cell, suppresses inappropriately elevated glucagon secretion, slows inappropriately elevated glucagon secretion, slows gastric emptying which produces satietygastric emptying which produces satiety

Liraglutide (Victoza), Exenatide (Byetta), Exenatide extended-release (Bydureon)

UMDNJ PANCE/PANRE Review Course UMDNJ PANCE/PANRE Review Course UMDNJ PANCE/PANRE Review Course

(becoming Rutgers July 1, 2013)(becoming Rutgers July 1, 2013)

Human Insulin Profiles Human Insulin Profiles (Rapid and Intermediate Acting, Premix)(Rapid and Intermediate Acting, Premix)

INSULININSULIN ONSETONSET PEAKPEAK DURATIONDURATION

NovolinNovolin®® (R), (R), HumalinHumalin®® (R)(R)

Regular Regular

3030--60 min60 min 22--4 hrs4 hrs 55--8 hr8 hr

NovolinNovolin®® (N), (N), HumalinHumalin®® (N) (N)

NPH NPH

11--3 hrs3 hrs 44--10 hrs10 hrs 1818--24 hrs24 hrs

HumulinHumulin®®

70/30, 70/30, NovolinNovolin®®

70/3070/30

3030--60 min60 min VariesVaries Up to 24hrsUp to 24hrs

HumalinHumalin®® 50/5050/50 3030--60 min60 min VariesVaries Up to 24hrsUp to 24hrs



Insulin Analogs Insulin Analogs Basal (LongBasal (Long--acting) Bolus (Fastacting) Bolus (Fast--acting)acting)

INSULININSULIN ONSETONSET PEAKPEAK DURATIONDURATION

LevemirLevemir®®

(insulin (insulin detemirdetemir))1 hr1 hr Steady over Steady over

timetimeUp to 24 hrsUp to 24 hrs

LantusLantus®®

(insulin (insulin glargineglargine))1 hr1 hr Steady over Steady over

timetimeUp to 24 hrsUp to 24 hrs

NovologNovolog®®

(insulin (insulin aspartaspart))

55--15 min15 min 3030--90 min90 min 33--5 hr5 hr

ApidraApidra®®

(insulin (insulin glulisineglulisine))


HumalogHumalog®®

(insulin (insulin lisprolispro))



Treatment in DMTreatment in DM

Type I: Type I: Insulin (basal / bolus)Insulin (basal / bolus)

Type II:Type II:1.1. Diet and Exercise (First Step)Diet and Exercise (First Step)2.2. Oral medicationOral medication3.3. Insulin Insulin ((if no glycemic controlif no glycemic control, severe , severe

hyperglycemia fasting BG > 240)hyperglycemia fasting BG > 240)

***Start with one Lifestyle changes***Start with one Lifestyle changes-- then add then add Metformin Metformin (drug of choice) (drug of choice) if fails, use if fails, use second second agents different classagents different class


Preventive CarePreventive Care

HgbHgb A1C every 6 mo A1C every 6 mo (if controlled) (if controlled) FBS, AC & HS+ FBS, AC & HS+ bedtime bedtime MicroalbuminuriaMicroalbuminuriayearlyyearlyBUN/Cr yearlyBUN/Cr yearly

Dilated eye exam Dilated eye exam yearlyyearlyFoot exam each visit Foot exam each visit (yearly DPM)(yearly DPM)

Cholesterol yearlyCholesterol yearlyBP each visitBP each visitStop smokingStop smoking



Hypoglycemia Hypoglycemia

Self induced: medicationsSelf induced: medicationsImmunopathologicImmunopathologic (rare) (rare) –– antianti--insulin insulin antibodies to insulin receptorsantibodies to insulin receptorsETOH related hypoglycemiaETOH related hypoglycemiaTumors Tumors –– pancreatic Bpancreatic B--cell, extracell, extra--pancreaticpancreaticSymptoms at or below 60 mg/Symptoms at or below 60 mg/dLdL, impairment of , impairment of brain function 50 mg/brain function 50 mg/dLdLWhippleWhipple’’s Triad:s Triad: hxhx of hypoglycemic symptoms, of hypoglycemic symptoms, fasting blood glucose of 40 mg/fasting blood glucose of 40 mg/dLdL or less, or less, immediate recovery upon admin. glucoseimmediate recovery upon admin. glucose


Metabolic SyndromeMetabolic Syndrome

Need 3 of 5 to diagnoseNeed 3 of 5 to diagnoseHDL < 40 male, < 50 femaleHDL < 40 male, < 50 femaleElevated BP Elevated BP ≥≥ 135/85135/85Elevated Triglycerides Elevated Triglycerides ≥≥ 150 mg/150 mg/dLdLFasting BG 100Fasting BG 100--125 mg/125 mg/dLdLWaist CircumferenceWaist Circumference--> 35> 35"F, >40"M"F, >40"M

Public domain available at: http://upload.wikimedia.org/wikipedia/commons/9/9e/Obesity-waist_circumference.PNG


Lipid DisordersLipid DisordersHyperlipidemiaHyperlipidemia

HypertriglyceridemiaHypertriglyceridemia



HyperlipidemiaHyperlipidemia

Most important and modifiable risk factor for CAD Most important and modifiable risk factor for CAD accelerates atherosclerosisaccelerates atherosclerosis

Primary Disorder: Familial Dyslipidemia SyndromePrimary Disorder: Familial Dyslipidemia Syndrome

Secondary DisorderSecondary DisorderEndocrine: hypothyroidism, DM, Endocrine: hypothyroidism, DM, CushingsCushingsNephroticNephrotic syndrome, Chronic liver diseasesyndrome, Chronic liver diseaseMedications: steroids, estrogen, Medications: steroids, estrogen, thiazidethiazide diureticsdiureticsPregnancyPregnancy


First Step: First Step: Screening and Risk AssessmentScreening and Risk Assessment

All adults All adults ≥≥ 20 yrs. fasting lipoprotein profile 20 yrs. fasting lipoprotein profile Every five yearsEvery five years

LDL Levels aloneLDL Levels aloneCigarette smokingCigarette smokingHTN (BP HTN (BP ≥≥ 140/90 or on HTN med)140/90 or on HTN med)Low HDL < 40 mg/Low HDL < 40 mg/dLdLFamily History of premature CAD (CAD in male Family History of premature CAD (CAD in male first degree relative < 55, female first degree first degree relative < 55, female first degree relative < 65)relative < 65)Age Men > 35, women > 45Age Men > 35, women > 45


Values and Risk AssessmentValues and Risk Assessment

LDLLDL< 100 = desirable< 100 = desirable100100--129 = above optimal 129 = above optimal 130130--159 = borderline high159 = borderline high160160--189 = High189 = High≥≥ 190 very high190 very high

HDL CholesterolHDL Cholesterol< 40 Low< 40 Low≥≥ 60 High60 High

Total CholesterolTotal Cholesterol< 200 = desirable< 200 = desirable200200-- 239 = borderline high239 = borderline high≥≥ 240 = high240 = high

Total < 200Total < 200

LDL < 100 (no CAD)LDL < 100 (no CAD)

LDL < 70 (+CAD)LDL < 70 (+CAD)

Triglycerides < 125Triglycerides < 125

TC:HDL ratio < 4.5TC:HDL ratio < 4.5



Screening and Clinical FeaturesScreening and Clinical Features

No risk factors (if No risk factors (if previously not screened)previously not screened)

35 Men35 Men45 women45 women

Family Family HxHxHTNHTNSmokingSmokingDMDMLow HDLLow HDLAgeAge

AsymptomaticAsymptomaticSevere Severe hyperlipidemiahyperlipidemia

XanthelasmaXanthelasma: yellow : yellow plaques on eyelidsplaques on eyelidsXanthomaXanthoma –– hard yellow hard yellow masses on tendons masses on tendons


TreatmentsTreatments

Dietary ChangesDietary ChangesLowering fat intake Lowering fat intake (saturated fats), cholesterol(saturated fats), cholesterolFood rich Omega 3Food rich Omega 3--fatty fatty acids (fish)acids (fish)FiberFiber

Exercise: Exercise: Increase HDLIncrease HDL

Drug TherapyDrug Therapy

Public domain available at:http://commons.wikimedia.org/wiki/File:Nordic_walking_on_treadmill.jpg


Drug Treatment of Drug Treatment of HyperlipidemiaHyperlipidemia

HMG HMG CoACoA reductasereductase inhibitors (inhibitors (statinsstatins))Most potent Lower LDL ** Drug choice Lower Most potent Lower LDL ** Drug choice Lower LDLLDLMonitor Monitor LFTLFT’’ss, may elevate CPK, may elevate CPK

NiacinNiacinDecrease TG levels, Decrease LDL, Increase HDLDecrease TG levels, Decrease LDL, Increase HDLNo use in DiabeticsNo use in DiabeticsMost potent Most potent ↑↑HDL, HDL, ↓↓TG levelsTG levelsFlushing effectFlushing effectSecond line agent for LDL, First line for Second line agent for LDL, First line for hypertriglyceridemiahypertriglyceridemia

Bile acidBile acid--binding resins (binding resins (cholestyraminecholestyramine, , colestipolcolestipol))Increases TG levelsIncreases TG levelsGood for use in combo with Good for use in combo with statinsstatins or niacin in high risk pts.or niacin in high risk pts.Third line agent for LDLThird line agent for LDLGI side effectsGI side effects

FibratesFibrates ((gemfibrozilgemfibrozil))Lower VLDL, Increase HDLLower VLDL, Increase HDLUsed if above failUsed if above failGI side effects, GI side effects, gynecomastiagynecomastia, gallstones, , gallstones, wt.gainwt.gain



Treatment of Treatment of HypertriglyceridemiaHypertriglyceridemia

Reduce weightReduce weightReduce amount saturated fat, trans fat, Reduce amount saturated fat, trans fat, cholesterol in dietcholesterol in dietReduce ETOH useReduce ETOH useExerciseExerciseLower carbohydrate intakeLower carbohydrate intakeIncrease meats high in OmegaIncrease meats high in Omega--3 fatty acids3 fatty acidsLOVAZALOVAZA®® (omega(omega--33--acid ethyl esters)acid ethyl esters)

SE: burping, infection, fluSE: burping, infection, flu--like symptoms, upset like symptoms, upset stomach, and change in sense of taste stomach, and change in sense of taste


A 42 yr. old obese woman with a A 42 yr. old obese woman with a hxhx of Type 2 DM x of Type 2 DM x 4 mos. presents for follow4 mos. presents for follow--up after initial attempts at up after initial attempts at diet and exercise for control. She has gained 10 lbs diet and exercise for control. She has gained 10 lbs and her BMI is now 30.5. On this visit her HgbA1c and her BMI is now 30.5. On this visit her HgbA1c is 8; serum is 8; serum creatininecreatinine is normal. is normal. What is the best management?What is the best management?

1.1. Bedtime insulin Bedtime insulin (NPH)(NPH)

2.2. Metformin Metformin ((glucophageglucophage))

3.3. Glipizide (Glipizide (GlucotrolGlucotrol))4.4. Continue diet & Continue diet &

exercise effortsexercise effortsUMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013))

A 42 yr. old obese woman with a A 42 yr. old obese woman with a hxhx of Type 2 DM x of Type 2 DM x 4 mos. presents for follow4 mos. presents for follow--up after initial attempts at up after initial attempts at diet and exercise for control. She has gained 10 lbs diet and exercise for control. She has gained 10 lbs and her BMI is now 30.5. On this visit her HgbA1c and her BMI is now 30.5. On this visit her HgbA1c is 8; serum is 8; serum creatininecreatinine is normal. is normal. What is the best management?What is the best management?

1.1. Bedtime insulin Bedtime insulin (NPH)(NPH)

2.2. Metformin Metformin ((glucophageglucophage))

3.3. Glipizide (Glipizide (GlucotrolGlucotrol))4.4. Continue diet & Continue diet &

exercise effortsexercise effortsUMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, 2013))


A 66 yr old male was found wandering the streets by the A 66 yr old male was found wandering the streets by the police. There are no signs of trauma. Vitals: BP 90/54, P 115, police. There are no signs of trauma. Vitals: BP 90/54, P 115, R 12. PE reveals mild dehydration and mental confusion w/o R 12. PE reveals mild dehydration and mental confusion w/o focal neurological findings. Labs are: glucose 759, Na 124, focal neurological findings. Labs are: glucose 759, Na 124, K 3.0, K 3.0, ClCl 102, CO102, CO2 2 37, BUN 63, CR 1.0. What is the most 37, BUN 63, CR 1.0. What is the most appropriate first step in treatment?appropriate first step in treatment?

1.1. GlucagonGlucagon2.2. InsulinInsulin3.3. PhosphatePhosphate4.4. SalineSaline


A 66 yr old male was found wandering the streets by the A 66 yr old male was found wandering the streets by the police. There are no signs of trauma. Vitals: BP 90/54, P 115, police. There are no signs of trauma. Vitals: BP 90/54, P 115, R 12. PE reveals mild dehydration and mental confusion w/o R 12. PE reveals mild dehydration and mental confusion w/o focal neurological findings. Labs are: glucose 759, Na 124, focal neurological findings. Labs are: glucose 759, Na 124, K 3.0, K 3.0, ClCl 102, CO102, CO2 2 37, BUN 63, CR 1.0. What is the most 37, BUN 63, CR 1.0. What is the most appropriate first step in treatment?appropriate first step in treatment?

1.1. GlucagonGlucagon2.2. InsulinInsulin3.3. PhosphatePhosphate4.4. SalineSaline


Which of the following glucoseWhich of the following glucose--lowering lowering agents acts by decreasing insulin resistance agents acts by decreasing insulin resistance and increasing glucose utilization?and increasing glucose utilization?

1.1. AcorbaseAcorbase ((PrecosePrecose))

2.2. Glipizide Glipizide ((GlucotrolGlucotrol))

3.3. Metformin Metformin ((GlucophageGlucophage))

4.4. PioglitazonePioglitazone ((ActosActos))



Which of the following glucoseWhich of the following glucose--lowering lowering agents acts by decreasing insulin resistance agents acts by decreasing insulin resistance and increasing glucose utilization?and increasing glucose utilization?

1.1. AcorbaseAcorbase ((PrecosePrecose))

2.2. Glipizide Glipizide ((GlucotrolGlucotrol))

3.3. Metformin Metformin ((GlucophageGlucophage))

4.4. PioglitazonePioglitazone ((ActosActos))


A 15 yr. old male presents with extreme fatigue and A 15 yr. old male presents with extreme fatigue and frequent urination day and night which he attributes frequent urination day and night which he attributes to increased water intake to to increased water intake to ““quench his thirst.quench his thirst.”” Exam Exam indicates a slender male with postural hypotension. indicates a slender male with postural hypotension. What is the best initial step toWhat is the best initial step toestablish a diagnosis?establish a diagnosis?

1.1. ACTHACTH2.2. HgbA1CHgbA1C3.3. Plasma glucosePlasma glucose4.4. Serum AM Serum AM cortisolcortisol

A 15 yr. old male presents with extreme fatigue and A 15 yr. old male presents with extreme fatigue and frequent urination day and night which he attributes frequent urination day and night which he attributes to increased water intake to to increased water intake to ““quench his thirst.quench his thirst.”” Exam Exam indicates a slender male with postural hypotension. indicates a slender male with postural hypotension. What is the best initial step toWhat is the best initial step toestablish a diagnosis?establish a diagnosis?

1.1. ACTHACTH2.2. HgbA1CHgbA1C3.3. Plasma glucosePlasma glucose4.4. Serum AM Serum AM cortisolcortisol


A 50 yr. old male presents for a routine visit. He A 50 yr. old male presents for a routine visit. He states that he could states that he could ““stand to lose a few poundsstand to lose a few pounds”” but but is otherwise in good health. PMH and family is otherwise in good health. PMH and family hxhx reveal reveal no risk factors. Exam reveals abdominal obesity no risk factors. Exam reveals abdominal obesity (waist circumference 45 in.) and BP 142/90. What (waist circumference 45 in.) and BP 142/90. What additional finding would confirm a additional finding would confirm a dxdx of metabolic of metabolic syndrome?syndrome?

1.1. Fasting glucose 98 mg/LFasting glucose 98 mg/L2.2. HDL 45 hg/HDL 45 hg/dLdL3.3. LDL 120 mg/LDL 120 mg/dLdL4.4. Triglycerides 200 mg/Triglycerides 200 mg/dLdL


A 50 yr. old male presents for a routine visit. He A 50 yr. old male presents for a routine visit. He states that he could states that he could ““stand to lose a few poundsstand to lose a few pounds”” but but is otherwise in good health. PMH and family is otherwise in good health. PMH and family hxhx reveal reveal no risk factors. Exam reveals abdominal obesity no risk factors. Exam reveals abdominal obesity (waist circumference 45 in.) and BP 142/90. What (waist circumference 45 in.) and BP 142/90. What additional finding would confirm a additional finding would confirm a dxdx of metabolic of metabolic syndrome?syndrome?

1.1. Fasting glucose 98 mg/LFasting glucose 98 mg/L2.2. HDL 45 hg/HDL 45 hg/dLdL3.3. LDL 120 mg/LDL 120 mg/dLdL4.4. Triglycerides 200 mg/Triglycerides 200 mg/dLdL


A 49 yr. old with a A 49 yr. old with a hxhx of Type 2 DM presents after of Type 2 DM presents after receiving a nonreceiving a non--fasting cholesterol of 235 at a fasting cholesterol of 235 at a community health fair. Which of the following is community health fair. Which of the following is the best management?the best management?

1.1. Diet & exercise Diet & exercise adviceadvice

2.2. Fasting lipid profileFasting lipid profile3.3. HMG HMG Co_ACo_A

reductasereductase inhibitorinhibitor4.4. Reassurance that Reassurance that

results are OKresults are OKUMDNJ PANCE/PANRE Review Course UMDNJ PANCE/PANRE Review Course



A 49 yr. old with a A 49 yr. old with a hxhx of Type 2 DM presents after of Type 2 DM presents after receiving a nonreceiving a non--fasting cholesterol of 235 at a fasting cholesterol of 235 at a community health fair. Which of the following is community health fair. Which of the following is the best management?the best management?

1.1. Diet & exercise Diet & exercise adviceadvice

2.2. Fasting lipid profileFasting lipid profile3.3. HMG HMG Co_ACo_A

reductasereductase inhibitorinhibitor4.4. Reassurance that Reassurance that

results are OKresults are OKUMDNJ PANCE/PANRE Review Course UMDNJ PANCE/PANRE Review Course


A 52 yr old postmenopausal woman presents with A 52 yr old postmenopausal woman presents with chest pain suggestive of angina. Exercise stress test is chest pain suggestive of angina. Exercise stress test is positive. Fasting labs: glucose 92, T. positive. Fasting labs: glucose 92, T. CholChol. 271, . 271, LDL 127, HDL 31, LDL 127, HDL 31, TriglTrigl. 375. What is the best therapy . 375. What is the best therapy for this patient?for this patient?

1.1. AtorvastatinAtorvastatin (Lipitor)(Lipitor)2.2. CholestyramineCholestyramine

((QuestranQuestran))3.3. EstradiolEstradiol4.4. NiacinNiacin


A 52 yr old postmenopausal woman presents with A 52 yr old postmenopausal woman presents with chest pain suggestive of angina. Exercise stress test is chest pain suggestive of angina. Exercise stress test is positive. Fasting labs: glucose 92, T. positive. Fasting labs: glucose 92, T. CholChol. 271, . 271, LDL 127, HDL 31, LDL 127, HDL 31, TriglTrigl. 375. What is the best therapy . 375. What is the best therapy for this patient?for this patient?

1.1. AtorvastatinAtorvastatin (Lipitor)(Lipitor)2.2. CholestyramineCholestyramine

((QuestranQuestran))3.3. EstradiolEstradiol4.4. NiacinNiacin



Thank you and good luck!Thank you and good luck!

UMDNJ PANCE/PANRE Review UMDNJ PANCE/PANRE Review Course (becoming Rutgers July 1, Course (becoming Rutgers July 1,

2013)2013)

ReferencesReferencesA Compreshensive Review for the Certification and Recertification Examinations

for Physician Assistants, 3rd/4th edition. Claire Babcock O’Connell, Sarah F. Zarbock

Evidence- Base Endocrinology. 2nd edition. Pauline M. Camacho, HosseinGharib, Glen W. Sizemore.

2012 Current Medical Diagnosis and Treatment. 51th edition. Michael W. Rabow, Stephen J. McPhee, Maxine A. Papakis.

Cecil Text book of Medicine, 22nd Edition. Lee Goldman, MD, Dennis Ausiello, MD.

http://commons.wikimedia.org/wiki/Main_Page


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