Endocrinology

Pediatric Board Review

Graeme Frank, MD

Calcium

An otherwise healthy 6-week infant presents with a generalized seizure. She is exclusively breast fed. The child is somewhat sleepy with a non focal examination.Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1The most likely diagnosis is:

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1. Pseudohypoparathyroidism2. Hypoparathyroidism3. Vitamin D deficiency4. Albright’s hereditary

osteodystrophy

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Actions of PTH

1.

2.

Ca PO4

NET EFFECT

25 OH Vit D

1,25 (OH)2 Vit D1 hydroxylase

3.

Gut

This same 6-week infant with hypoparathyroidism (Glucose 88; Na 141, Ca 5.1, Phos 9.1, Mag 2.1)

What is an important diagnostic consideration (i.e. what is the underling disorder causing the hypoparathyroidism)?

DiGeorge syndrome – thymic aplasia, congenital heart

disease, immune deficiency

Biochemical changes in rickets

Ca PO4 Bone Urine

N Minimalchanges

Stage 1

N Rickets

AminoaciduriaPhosphaturiaGlycosuriaBicarbonaturia

Stage 2

Initial

Ca:PO4:Alk Phos:

9.7 3.12514

2 ½ weeks

9.8 3.52185

4 months

10.5 6.5 518

Which is consistent with vitamin D deficiency rickets?

Calcium Phos Alk Phos

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0% 0% 0%0%0%

1. Normal Normal Low2. Low Low Low3. Low High High4. Low Normal Normal5. Normal Low High

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Choose correct answer

A. Vitamin D deficiency ricketsB. Renal osteodystrophy (renal rickets)C. BothD. Neither

1. Increased phosphate level

2. Increased PTH level

3. Increased creatinine level

B

C

B

THYROID

Baby A, born on 5/27/10. Newborn screening tests, performed on 5/29/10 revealed: Normal rangeTSH 37 µIU/ml < 20T4 10.1 µg/dl 9-19Which statement is most accurate:

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1. Baby A has congenital hypothyroidism warranting urgent therapy

2. Baby A will develop mental retardation if untreated

3. Baby A likely does not have any thyroid abnormality

4. Baby A has an altered hypothalamic set-point for T4 Countdown

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Venipuncture: (1/25/10) Normal rangeTSH 488 IU/ml (0.3-5.5)T4 1.2 g/dl (4.5-12.5)

You are contacted by your state Neonatal Thyroid Screening Program. Baby X was born on 1/4/10. His newborn screening tests, performed on 1/6/10 revealed:

 Initial filter paper Normal rangeTSH >200 IU/ml < 20T4 2.1 g/dl 9-19

 

Congenital hypothyroidism

Thyroid dysgenesis/agenesis Prevalence 1 in 4,000 [Whites 1 in 2,000; Blacks

1 in 32,000] 2:1 female to male ratio Clinical features include:

hypotonia, enlarged posterior fontanelle, umbilical hernia, indirect hyperbilirubinemia

Laboratory findings: Very high TSH and low T4 Therapy: Thyroxine – keep TSH in normal range

6 month female with congenital hypothyroidism

..following 4 months therapy

A baby with gastroschisis has the following TFTs on day 5 of life:T4 2.1 μg/dL (4.5-12.5) TSH 2.3 μIU/mL (0.3-5.0)The most likely diagnosis is:

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1. Hypothyroidism due to thyroid dysgenesis

2. Central hypothyroidism3. TBG deficiency4. Hypothyroidism from

excess iodine exposure5. Normal thyroid function

(as the TSH is normal)Countdown

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Central hypothyroidism - rare

TBG deficiency1:2800

vs.

Thyroxine (T4) Major product secreted by the thyroid Circulates bound to thyroid binding proteins

- thyroid binding globulin (TBG) Only a tiny fraction (< 0.1%) is free and diffuses

into tissues When we measure T4, we measure the T4 that is

bound to protein The level of T4 is therefore largely dependent on

the amount of TBG Changes in T4 may reflect TBG variation rather

than underlying pathology

TBG deficiency

Central hypothyroidism

Free T4 Low Normal

TBG level Normal Low

T3RU Low High

Thyroid function in a 17 year old: Normal rangeTSH: 3.7 µIU/ml 0.3-5.5T4: 13.4 µg/dl 4.5-12

Which of the following medication could explain the thyroid function abnormality

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1. INH2. Retinoid acid3. Ciprofloxacin4. Ortho Tri-Cylen5. Doxycycline

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Conditions that cause alterations in TBG

Increased TBG Decreased TBGInfancy Familial deficiencyEstrogen Androgenic steroid treatment - OC Pill Glucocorticoids (large dose) - pregnancy Nephrotic syndromeFamilial excess AcromegalyHepatitisTamoxifen treatment

A 12-yr female has diffuse enlargement of the thyroid. She is asymptomatic. Her disorder is most likely associated with which of the following pathological processes

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1. Infectious2. Inflammatory3. Autoimmune4. Toxic (drug)5. Neoplastic

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Normal thyroid

Hashimoto thyroiditis

DC 16 year 7 month Growth failure x 1 1/2 years

Labs:

TSH: 1008 µIU/ ml (0.3-5.0)T4: <1.0 µg/dl (4-12)

Antithyro Ab. 232 U/ml (0-1)A-perox Ab. 592 IU/ml (<0.3)

Prolactin: 29 ng/ml (2-18)

Cholesterol: 406 mg/dl (100-170)

DC

Start of thyroxine

Background: Autoimmune destruction of the thyroid Family history in 30-40% Lymphocytic infiltration

Clinical: Growth failure, constipation, goiter, dry skin, weight gain, slow recoil of DTRLaboratory: High TSH Anti-thyroglobulin and anti-peroxidase antibodies

Therapy: Thyroxine

Hashimoto thyroiditis

15 year old female with a history of easy fatigability. Found to have an elevated pulse rate at recent MD visit 

Thyroid function: Normal rangeTSH < 0.1 IU/ml 0.3-5.5T4 14.8 g/dl 4.5-12T3 580 ng/dl 90-190

Restlessness, poor attention spanEye changes

Goiter

Tachycardia, wide pulse pressure

Increased GFR- polyuria

DiarrheaMenstrual abnormalities

Myopathy

Antithyroid medication (Methimazole or Propylthiouracil [PTU]) Pros : 25% remission rate every 2 years

Cons: Drug induced side effects - skin rashes, agranulocytosis, lupus-like reaction

Radioactive iodine (131I)Pros : Easy. Essentially free of side effectsCons: Long term hypothyroidism

Surgery

Blockers if markedly hyperthyroid

Therapy for Graves disease:

Sexual differentiation

Ambiguous genitalia is found in a newborn. The baby is noted to be hyperpigmented. Ultrasound demonstrates the presence of a uterus. The most useful test to aid in the diagnosis of this medical condition is:

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1. Testosterone2. 17-hydroxyprogesterone3. Serum sodium and

potassium4. DHEAS5. DHEAS/androstenedione

ratio

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Cholesterol

Pregnenolone

Progesterone

DOCA

Corticosterone

ALDOSTERONE

17 (OH) pregnenolone DHEA

17 (OH) progesterone Androstenedione

Compound S

CORTISOL

TESTOSTERONE

Desmolase

3--HSD 3--HSD 3--HSD

17-OH

17-OH

21-OH 21-OH

11-OH 11-OH

If she has salt wasting congenital adrenal hyperplasia, which abnormalities are likely to develop. True or False for each

a) Increased serum potassiumb) Decreased serum sodiumc) Decreased bicarbonated) Decreased plasma cortisole) Increased plasma renin activity

T

TT

T

T

A 1-year male infant has non palpable testes. Of the following, the most appropriate next step would be:

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1. Re-examination in 18 months

2. Refer the patient for an exploratory laparotomy

3. Begin therapy with LHRH

4. Measure the plasma testosterone after stimulation with HCG

5. Begin therapy with testosterone enanthate, 50 mg IM monthly for 3 months. Countdown

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History9 day old male infant 1 day history of decrease feeding, vomiting and lethargy.

ExaminationIll appearing infant with poor respiratory effortVital signs: T 99 F HR 100/min BP 61/40 RR 24/minResp: Subcostal retractions but clear to auscultationCardiac: Regular rate and rhythm. Normal S1 and S2Abdomen: Soft, non distended. Non tender. No HSMNeuro: Lethargic. No focal deficitGenitalia: Normal male. Bilateral descended testes

Laboratory data:

WBC 16.7Hb 16.4Hct 49Plt 537 K

Na 121K 9.3Cl 83CO2 6.7Glucose 163BUN/Creat 33/0.2

CSF:Chemistry: Protein 74 Glucose 82Microscopy: WBC 6 RBC 100

Emergency therapy

Fluid resuscitation:20 ml/kg Normal saline

Glucocorticoid2 mg/kg Solucortef IV

Monitor EKG

Modes of presentation

Classicalh Simple virilizingh Virilizing with salt loss

“Non classical” / Late onset

Therapy and evaluation of therapy

Glucocorticoid (Hydrocortisone)h Monitor growth, 17-OHP, urinary pregnanetriol

Fluorocortisol (Florinef 0.1 – 0.45 mg/day)h Blood pressure, plasma renin activity (PRA)

Supplemental salth Until introduction of infant food

History15 year female presents with primary amenorrheaBreast development began at 10 years

ExaminationHeight: 5 ft 7 in Weight 130 lbTanner 5 breast developmentScant pubic hair

What is your diagnosis?

XY Genotype

Testosterone

Estradiol

Androgen Receptor

EstrogenReceptor

Aromatase

Complete androgen insensitivity

15 yr female presents with primary amenorrhea.Breast development began at 10 yTanner 5 breasts, scant pubic hair

Which of the following clinical features is the most likely to give you the correct diagnosis

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1. Blood pressure in all 4 extremities

2. Careful fundoscopic examination

3. Rectal examination4. Measurement of blood

pressure with postural change

5. Cubitus valgus and shield shaped chest Countdown

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TESTIS

Leydig cells

Sertolicells

Gonadal Primordia

Testosterone

Wolfian ducts DHT

Normal maleext. genitalia

EpidymusVas deferensSeminal vesicles

Female

OVARY

No SRY

No AMH No testosterone

Mullerian ducts

Wolfian ductregression

Normal femaleexternal genitalia

Fallopian tubesUterusUpper vagina

No AMHMullerian duct

regression

nor DHT

Gonadal Primordia

Y Chromosome TESTIS

SRY

Leydig cells

Sertolicells

Testosterone AMHMullerian duct

regression Wolfian ducts DHT

EpidymusVas deferensSeminal vesicles

Normal maleext. genitalia

No AMH No testosterone

Mullerian ducts

Wolfian ductregression

Normal femaleexternal genitalia

Fallopian tubesUterusUpper vagina

nor DHT

Gonadal Primordia

Y Chromosome TESTIS

SRY

Leydig cells

Sertolicells

Testosterone AMHMullerian duct

regression Wolfian ducts DHT

EpidymusVas deferensSeminal vesicles

Normal maleext. genitalia

No AMH No testosterone

Mullerian ducts

Wolfian ductregression

Normal femaleexternal genitalia

Fallopian tubesUterusUpper vagina

nor DHT

Early Puberty

The earliest sign of puberty in a male is:

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1. Enlargement of the penis

2. Enlargement of the testes

3. Growth acceleration4. Pubic hair growth5. Axillary hair growth

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2 year old girl with breast development. No growth acceleration. No bone age advancementNo detectable estradiol, LH or FSHThe most likely diagnosis is:

1. Ingestion of her mother’s OCPs

2. Precocious puberty3. Premature

adrenarche4. Premature thelarche5. McCune Albright

Syndrome

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Benign Premature Thelarche

Isolated breast development– 80% before age 2 – Rarely after age 4

Not associated with other signs of puberty (growth acceleration, advancement of bone age)Children go on to normal timing of puberty and normal fertilityBenign processRoutine follow-up

5 year female with 6 months of pubic hair growth. Very fine axillary hair as well as adult odor to sweat.No breast development, no growth spurtThe most likely diagnosis is:

1. Precocious puberty2. Benign premature

adrenarche3. Non-classical congenital

adrenal hyperplasia4. Adrenal tumor5. Pinealoma

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0% 0% 0%0%0%

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Benign Premature Adrenarche

Production of adrenal androgens before true pubertal development beginsPresents as isolated pubic hair in mid childhood– No growth acceleration– No testicular enlargement in boys

If normal growth rate, routine follow-upIf accelerated growth and/or bone age advancement, screen for – CAH– Virilizing tumor (adrenal/gonadal)

Choose correct answer

A. Premature theralcheB. Premature adrenarcheC. BothD. Neither

1. Growth acceleration

2. Normal adolescent sexual development

3. Onset of gonadal function usually in 3-4 years

D

C

B

You suspect a 16 year female has Turner syndrome. The most definitive diagnostic test is

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1. Buccal smear2. Chromosome

analysis3. Measuring her FSH

and LH4. Determining her

bone age5. Determining her

testosterone level

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5 year old girl with pubic hair and rapid growth. She has no breast development

Possible sources of androgens:

1.Liver

2.Adrenal

3.Ovary

4.Pituitary

5.Pineal

T

F

F

F

T

5 year old girl with pubic hair and rapid growth. She has no breast development

Which of the following should be considered Answer T or F for each:

a) Central precocious puberty

b) Congenital adrenal hyperplasia

c) McCune Albright syndrome

d) Benign premature adrenarche

e) Adrenal tumor

F

T

T

F

F

When does puberty occur?

Classic teaching–8 -13 in girls (menarche ~ 2 years

after onset of puberty)

–9 -14 in boys

Case:Breast development: 6 yearsMother had menarche: 9.5 years

Why

Reactivation of hypothalamic –pituitary –gonadal axis

Gonadatropin dependent (central) precocious puberty

Clock turns on earlyIdiopathic > 95 % girls

~ 50 % boys– Hypothalamic hamartoma (Gelastic seizures)– NF (optic glioma)– Head trauma– Neurosurgery– Anoxic injury– Hydrocephalus

Treatment

Why–Psychosocial–HeightWhat–GnRH agonist

Gonadotropin independent precocious puberty

7 year male presents with 6 month history of pubic and axillary hair growth as well as adult body odor. Mother thinks he is growing faster than his peersNo exposure to androgens

PM&SH – nil of note Mother had menarche at 12 yrFather had normal timing of his pubertyMedications – none

Height 50th percentile (last height at 25th)Weight 40th percentileNo café au lait maculesNo goiterHeart and lungs: normalAbdomen: Firm hepatomegaly with irregular border

Prepubertal Asymmetric Pubertal

Adrenal source Enlarged testicle Precocious puberty

Height 50th percentile (last height at 25th)Weight 40th percentileNo café au lait maculesNo goiterHeart and lungs: normalAbdomen: Firm hepatomegaly with irregular borderGenitalia:

Pubic hair - Tanner 2Scrotal thinningTestes 5 ml bilaterally (pubertal >3 ml)

Rest unremarkable

7 year male with signs of puberty

Pubertal

Central precociouspuberty

Gonadotropins

LH

GLeydig cell

LABS:Testosterone 48 ng/dl (<10)FSH <0.1 mIU/mLLH <0.1 mIU/mL

TSH 1.0 μIU/mLT4 8.9 μg/dL

Precocious puberty in the male

Gonadotropins

Prepubertal Pubertal

Gonadotropin independent Central precociousprecocious puberty puberty

HCG LH

*McCune Albright

syndrome

G G*

Familial malePrecocious puberty(testotoxicosis)

1. Gonadotropin independent PP2. Polyostotic Fibrous Dysplasia3. Café au lait macules

Leydig cell

Final diagnosis: Gonadotropin independent precocious puberty secondary to an βHCG secreting hepatoblastoma

5 year old with breast developmentand growth acceleration - Estradiol 62 pg/ml (<10)- FSH <0.1 mIU/mL- LH <0.1 mIU/mL

Gonadotropin independent precocious puberty

McCune Albright syndrome:1. Café au lait macules 2. Gonadotropin independent

precocious puberty3. Polyostotic fibrous dysplasia

Growth disorders anddelayed puberty

Delayed puberty

Hypogonadism

HypergonadotropicHypogonadism (↑FSH, LH)

Primary gonadal failure- Chromosomal - iatrogenic (cancer therapy)- autoimmune oophoritis- galactosemia- test. biosynthetic defect

HypogonadotropicHypogonadism (FSH, LH)

Constitutionaldelay

Central Hypogonadism- Isolate gonad. def. - MPHD- Kallmann (anosmia)- Functional

A 15 yr boy has short stature and delayed puberty. He is now in early puberty (Tanner 2). His parents are of average stature. His height and weight are just below 3rd percentile.

All of the following are likely EXCEPT:

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1. A bone age of 12 ½ years2. Growth hormone

deficiency3. Adult height in the normal

range4. Acceleration of growth and

sexual maturation over the next 2 years.

5. History of normal length and weight at birth

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A 15 yr male has delayed puberty. He also has headaches, diplopia and increased urination. His height is < 3rd percentile. Which of the following is the most likely diagnosis?

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1. Diabetes mellitus2. Pinealoma3. Cerebellar tumor4. Craniopharyngioma5. Pituitary adenoma

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A 14 yr male has tender gynecomastia (3 cm in diameter bilaterally). He is in early to mid puberty. In most cases the best management for this gynecomastia is:

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1. Treatment with an anti-estrogen (e.g. Tamoxifen)

2. Treatment with an aromatase inhibitor

3. Treatment with a dopamine agonist (bromocryptine)

4. Surgery5. Reassurance

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Diabetes

A 12 year female patient presents with a 4 week history of polyuria, polydipsia, and marked weight loss. She is noted to have deep, sighing respiration. Glucose is 498 mg/dL, pH is 7.06. Her electrolytes show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9.The MOST important initial management is:

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1. insulin drip 0.1 u/kg/hr2. ½ NS with 40 meq K at 2x

maintenance3. Bicarb 1 meq/kg slowly

over 1 hour4. 20 ml/kg normal saline

bolus IV

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GTT in a 16 year obese female:Time Glucose (mg/dL)-0- 109 -120- 188 Which of the following statements are correct?

This patient has:

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1. Type 2 diabetes2. Impaired glucose

tolerance but normal fasting glucose

3. Normal glucose tolerance

4. Both impaired fasting glucose and impaired glucose tolerance

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Fasting 2 hr post load

< 100 < 140

Normal

≥ 100 ≥ 140

< 126 < 200

Pre-diabetes

≥ 126 ≥ 200Diabetes

Definition of diabetes

This obese patient with IFG and IGT is at risk for the development of all the following EXCEPT

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1. Type 2 diabetes2. Dyslipidemia3. Hypertension4. Slipped capital femoral

epiphysis5. Hashimoto thyroiditis

Metabolic syndrome

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A 13 year male has new onset type 1 diabetes mellitus. Therapy for this child may include all of the following EXCEPT:

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1. Glargine (Lantus) and Lipro insulin (Humalog)

2. Detemir (Levemir) and Aspart insulin (Novolog)

3. Metformin

4. Analog insulin administered via an insulin pump

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Miscellaneous

Side effects of corticosteroids include all of the following except

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1. hypertension2. hypoglycemia3. decrease bone

mineralization4. myopathy5. cataracts

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What is the most likely diagnosis in this newborn infant?

1 2 3 4 5

17%

27%

33%

13%10%

1. Mother has SLE2. Anasarca from cardiac

failure3. Systemic allergic

reaction 4. Congenital nephrotic

syndrome5. Turner syndrome

5 year old male with short stature

1 2 3 4 5

20%

23% 23%

10%

23%

1. Turner syndrome2. VATER syndrome3. Albright’s hereditary

osteodystrophy4. Noonan syndrome5. Goldenhar syndrome

A moderately obese adolescent female has irregular periods, hirsutism and acne. Of the following, which is the most likely diagnosis?

1 2 3 4 5

17%

23%

33%

13%13%

1. Cushing syndrome2. Polycystic ovarian

syndrome3. Virilizing adrenal tumor4. Non-classical CAH5. Hyperprolactinemia

Choose correct answer

A. Diabetes mellitusB. Diabetes insipidusC. BothD. Neither

1. Osmolality of serum > 300 Osm/L

2. Osmolality of urine > 500 mOsm/L

3. Hypernatremia

2 Na + BUN/2.8 + Gluc/18

Choose correct answer

A. Diabetes mellitusB. Diabetes insipidusC. BothD. Neither

1. Osmolality of serum > 300 Osm/L

2. Osmolality of urine > 500 mOsm/L

3. Hypernatremia

C

A

B

2 Na + BUN/2.8 + Gluc/18