1. Pediatric Board Review
Endocrinology
Graeme Frank, MD

2. Calcium

3. Pseudohypoparathyroidism Hypoparathyroidism Vitamin D deficiency
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 2.1 The most likely diagnosis is:
Pseudohypoparathyroidism
Hypoparathyroidism
Vitamin D deficiency
Albright’s hereditary osteodystrophy
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4. Actions of PTH Ca PO4 1. 2. 3. NET EFFECT 25 OH Vit D 1,25 (OH)2 Vit D
1 hydroxylase 3.
25 OH Vit D
1,25 (OH)2 Vit D
Gut
NET EFFECT

5. 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

6. Biochemical changes in rickets
Ca PO4 Bone Urine N
Minimal
changes
Stage 1 N
Rickets
Aminoaciduria
Phosphaturia Glycosuria
Bicarbonaturia
Stage 2

7. Initial
2 ½ weeks
9.8
3.5
2185
4 months
10.5
6.5
518
Ca:
PO4:
Alk Phos:
9.7
3.1
2514

8. Which is consistent with vitamin D deficiency rickets?
Calcium Phos Alk Phos
Normal Normal Low
Low Low Low
Low High High
Low Normal Normal
Normal Low High
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9. Choose correct answer Vitamin D deficiency rickets
Renal osteodystrophy (renal rickets)
Both
Neither B
1. Increased phosphate level
2. Increased PTH level
3. Increased creatinine level C B

10. THYROID

11. Baby A has congenital hypothyroidism warranting urgent therapy
Baby A, born on 5/27/10. Newborn screening tests, performed on 5/29/10 revealed: Normal range TSH µIU/ml < 20 T µg/dl Which statement is most accurate:
Baby A has congenital hypothyroidism warranting urgent therapy
Baby A will develop mental retardation if untreated
Baby A likely does not have any thyroid abnormality
Baby A has an altered hypothalamic set-point for T4
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13. You are contacted by your state Neonatal Thyroid Screening Program
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 range
TSH >200 IU/ml < 20
T g/dl 9-19
Venipuncture: (1/25/10)
Normal range
TSH 488 IU/ml ( )
T g/dl ( )

14. 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

16. ..following 4 months
therapy
6 month female with
congenital hypothyroidism

17. Hypothyroidism due to thyroid dysgenesis Central hypothyroidism
A baby with gastroschisis has the following TFTs on day 5 of life: T μg/dL ( ) TSH μIU/mL ( ) The most likely diagnosis is:
Hypothyroidism due to thyroid dysgenesis
Central hypothyroidism
TBG deficiency
Hypothyroidism from excess iodine exposure
Normal thyroid function (as the TSH is normal)
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18. Central hypothyroidism - rare
vs.
TBG deficiency 1:2800

19. 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

20. TBG deficiency
Central
hypothyroidism
Free T4 Low Normal
TBG level Normal Low
T3RU Low High

21. INH Retinoid acid Ciprofloxacin Ortho Tri-Cylen Doxycycline
Thyroid function in a 17 year old: Normal range TSH: µIU/ml T4: µg/dl Which of the following medication could explain the thyroid function abnormality
INH
Retinoid acid
Ciprofloxacin
Ortho Tri-Cylen
Doxycycline
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22. Conditions that cause alterations in TBG
Increased TBG Decreased TBG
Infancy Familial deficiency
Estrogen Androgenic steroid treatment
- OC Pill Glucocorticoids (large dose)
- pregnancy Nephrotic syndrome
Familial excess Acromegaly
Hepatitis
Tamoxifen treatment

23. Infectious Inflammatory Autoimmune Toxic (drug) Neoplastic
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
Infectious
Inflammatory
Autoimmune
Toxic (drug)
Neoplastic
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24. Normal thyroid
Hashimoto thyroiditis

25. DC 16 year 7 month Growth failure x 1 1/2 years
Labs: TSH: µIU/ ml ( ) T4: <1.0 µg/dl (4-12) Antithyro Ab U/ml (0-1) A-perox Ab IU/ml (<0.3) Prolactin: ng/ml (2-18)
Cholesterol: mg/dl ( )

26. DC
Start of thyroxine

27. Hashimoto thyroiditis
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 DTR
Laboratory:
High TSH
Anti-thyroglobulin and anti-peroxidase antibodies
Therapy:
Thyroxine

28. 15 year old female with a history of easy fatigability.
Found to have an elevated pulse rate at recent MD visit
Thyroid function: Normal range
TSH < 0.1 IU/ml
T g/dl
T ng/dl

29. Restlessness,
poor attention span
Eye changes
Goiter
Tachycardia, wide pulse
pressure
Increased GFR
- polyuria
Diarrhea
Menstrual
abnormalities
Myopathy

30. Therapy for Graves disease:
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 effects
Cons: Long term hypothyroidism
Surgery
 Blockers if markedly hyperthyroid

31. Sexual differentiation

32. 17-hydroxyprogesterone Serum sodium and potassium DHEAS
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:
Testosterone
17-hydroxyprogesterone
Serum sodium and potassium
DHEAS
DHEAS/androstenedione ratio
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33. Cholesterol Pregnenolone 17 (OH) pregnenolone DHEA Progesterone
Desmolase
17-OH
Pregnenolone
17 (OH) pregnenolone
DHEA
3--HSD
3--HSD
3--HSD
17-OH
Progesterone
17 (OH) progesterone
Androstenedione
21-OH
21-OH
DOCA
Compound S
TESTOSTERONE
11-OH
11-OH
Corticosterone
CORTISOL
ALDOSTERONE

34. If she has salt wasting congenital adrenal hyperplasia, which abnormalities are likely to develop. True or False for each
Increased serum potassium
Decreased serum sodium
Decreased bicarbonate
Decreased plasma cortisol
Increased plasma renin activity T T T T T

35. Re-examination in 18 months
A 1-year male infant has non palpable testes. Of the following, the most appropriate next step would be:
Re-examination in 18 months
Refer the patient for an exploratory laparotomy
Begin therapy with LHRH
Measure the plasma testosterone after stimulation with HCG
Begin therapy with testosterone enanthate, 50 mg IM monthly for 3 months.
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36. History
9 day old male infant
1 day history of decrease feeding, vomiting and lethargy.
Examination
Ill appearing infant with poor respiratory effort
Vital signs: T 99 F HR 100/min BP 61/40 RR 24/min
Resp: Subcostal retractions but clear to auscultation
Cardiac: Regular rate and rhythm. Normal S1 and S2
Abdomen: Soft, non distended. Non tender. No HSM
Neuro: Lethargic. No focal deficit
Genitalia: Normal male. Bilateral descended testes

37. Laboratory data: Na K Cl CO
Glucose
BUN/Creat /0.2
WBC Hb
Hct
Plt 537 K
CSF:
Chemistry: Protein 74 Glucose 82
Microscopy: WBC RBC

38. Emergency therapy Fluid resuscitation: 20 ml/kg Normal saline
Glucocorticoid 2 mg/kg Solucortef IV
Monitor EKG

39. Modes of presentation Classical “Non classical” / Late onset
Simple virilizing
Virilizing with salt loss
“Non classical” / Late onset

40. Therapy and evaluation of therapy
Glucocorticoid (Hydrocortisone)
Monitor growth, 17-OHP, urinary pregnanetriol
Fluorocortisol (Florinef 0.1 – 0.45 mg/day)
Blood pressure, plasma renin activity (PRA)
Supplemental salt
Until introduction of infant food

41. What is your diagnosis? History
15 year female presents with primary amenorrhea
Breast development began at 10 years
Examination
Height: 5 ft 7 in Weight 130 lb
Tanner 5 breast development
Scant pubic hair
What is your diagnosis?

42. Complete androgen insensitivity
XY Genotype
Testosterone
Estradiol
Androgen
Receptor
Estrogen
Aromatase

43. Blood pressure in all 4 extremities Careful fundoscopic examination
15 yr female presents with primary amenorrhea. Breast development began at 10 y Tanner 5 breasts, scant pubic hair Which of the following clinical features is the most likely to give you the correct diagnosis
Blood pressure in all 4 extremities
Careful fundoscopic examination
Rectal examination
Measurement of blood pressure with postural change
Cubitus valgus and shield shaped chest
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44. Gonadal Primordia TESTIS OVARY No SRY Female No AMH No testosterone
Sertoli
cells
Leydig
cells
Wolfian duct
regression
nor DHT
Mullerian
ducts
Normal female
external genitalia
Testosterone
No AMH
Mullerian duct
regression
Wolfian ducts
DHT
Fallopian tubes
Uterus
Upper vagina
Epidymus
Vas deferens
Seminal vesicles
Normal male
ext. genitalia

45. Gonadal Primordia TESTIS Y Chromosome SRY Leydig cells Sertoli No AMH
No testosterone
Wolfian duct
regression
nor DHT
AMH
Testosterone
Mullerian
ducts
Normal female
external genitalia
Wolfian ducts
DHT
Mullerian duct
regression
Epidymus
Vas deferens
Seminal vesicles
Normal male
ext. genitalia
Fallopian tubes
Uterus
Upper vagina

46. Gonadal Primordia TESTIS Y Chromosome SRY Leydig cells Sertoli No AMH
No testosterone
Wolfian duct
regression
nor DHT
AMH
Testosterone
Mullerian
ducts
Normal female
external genitalia
Wolfian ducts
DHT
Mullerian duct
regression
Epidymus
Vas deferens
Seminal vesicles
Normal male
ext. genitalia
Fallopian tubes
Uterus
Upper vagina

47. Early Puberty

48. The earliest sign of puberty in a male is:
Enlargement of the penis
Enlargement of the testes
Growth acceleration
Pubic hair growth
Axillary hair growth
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49. Ingestion of her mother’s OCPs Precocious puberty Premature adrenarche
2 year old girl with breast development. No growth acceleration. No bone age advancement No detectable estradiol, LH or FSH The most likely diagnosis is:
Ingestion of her mother’s OCPs
Precocious puberty
Premature adrenarche
Premature thelarche
McCune Albright Syndrome
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50. 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 fertility
Benign process
Routine follow-up

51. Benign premature adrenarche
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 spurt The most likely diagnosis is:
Precocious puberty
Benign premature adrenarche
Non-classical congenital adrenal hyperplasia
Adrenal tumor
Pinealoma
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52. Benign Premature Adrenarche
Production of adrenal androgens before true pubertal development begins
Presents as isolated pubic hair in mid childhood
No growth acceleration
No testicular enlargement in boys
If normal growth rate, routine follow-up
If accelerated growth and/or bone age advancement, screen for
CAH
Virilizing tumor (adrenal/gonadal)

53. Choose correct answer Premature theralche Premature adrenarche Both
Neither D
1. Growth acceleration
2. Normal adolescent sexual development
3. Onset of gonadal function usually in 3-4 years C B

54. Measuring her FSH and LH Determining her bone age
You suspect a 16 year female has Turner syndrome. The most definitive diagnostic test is
Buccal smear
Chromosome analysis
Measuring her FSH and LH
Determining her bone age
Determining her testosterone level
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55. 5 year old girl with pubic hair and rapid growth
5 year old girl with pubic hair and rapid growth. She has no breast development
Possible sources of androgens:
Liver
Adrenal
Ovary
Pituitary
Pineal F T T F F

56. 5 year old girl with pubic hair and rapid growth
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:
Central precocious puberty
Congenital adrenal hyperplasia
McCune Albright syndrome
Benign premature adrenarche
Adrenal tumor F T F F T

57. When does puberty occur?
Classic teaching
8 -13 in girls (menarche ~ 2 years after onset of puberty)
9 -14 in boys
Case:
Breast development: years
Mother had menarche: years

58. Why
Reactivation of hypothalamic –pituitary –gonadal axis

59. Gonadatropin dependent (central) precocious puberty
Clock turns on early
Idiopathic
> 95 % girls ~ 50 % boys
Hypothalamic hamartoma (Gelastic seizures)
NF (optic glioma)
Head trauma
Neurosurgery
Anoxic injury
Hydrocephalus

60. Treatment
Why
Psychosocial
Height
What
GnRH agonist

61. Gonadotropin independent precocious puberty

62. 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 peers
No exposure to androgens
PM&SH – nil of note Mother had menarche at 12 yr Father had normal timing of his puberty
Medications – none

63. Height 50th percentile (last height at 25th) Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border
Prepubertal Asymmetric Pubertal
Adrenal source Enlarged testicle Precocious puberty

64. Height 50th percentile (last height at 25th)
Weight 40th percentile
No café au lait macules
No goiter
Heart and lungs: normal
Abdomen: Firm hepatomegaly with irregular border
Genitalia: Pubic hair - Tanner 2 Scrotal thinning Testes 5 ml bilaterally (pubertal >3 ml)
Rest unremarkable

65. 7 year male with signs of puberty
Pubertal
Central precocious
puberty
Gonadotropins LH G
Leydig cell
LABS:
Testosterone ng/dl (<10)
FSH <0.1 mIU/mL
LH <0.1 mIU/mL
TSH 1.0 μIU/mL
T μg/dL

66. Precocious puberty in the male
Gonadotropins
Prepubertal Pubertal
Gonadotropin independent Central precocious
precocious puberty puberty
HCG LH *
Familial male
Precocious puberty
(testotoxicosis) G *
McCune Albright
syndrome G
Leydig cell
1. Gonadotropin independent PP
2. Polyostotic Fibrous Dysplasia
3. Café au lait macules

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

68. Gonadotropin independent precocious puberty
5 year old with breast development
and growth acceleration - Estradiol 62 pg/ml (<10)
FSH <0.1 mIU/mL
LH <0.1 mIU/mL
Gonadotropin independent precocious puberty

69. McCune Albright syndrome:
Café au lait macules
Gonadotropin independent precocious puberty
Polyostotic fibrous dysplasia

70. Growth disorders and delayed puberty

71. Delayed puberty Hypogonadism Hypergonadotropic Hypogonadism (↑FSH, LH)
Hypogonadotropic
Hypogonadism (FSH, LH)
Constitutional
delay
Central
Hypogonadism
- Isolate gonad. def. - MPHD
- Kallmann (anosmia) - Functional
Primary gonadal failure
- Chromosomal - iatrogenic (cancer therapy) - autoimmune oophoritis - galactosemia - test. biosynthetic defect

72. Growth hormone deficiency Adult height in the normal range
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:
A bone age of 12 ½ years
Growth hormone deficiency
Adult height in the normal range
Acceleration of growth and sexual maturation over the next 2 years.
History of normal length and weight at birth
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73. Diabetes mellitus Pinealoma Cerebellar tumor Craniopharyngioma
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?
Diabetes mellitus
Pinealoma
Cerebellar tumor
Craniopharyngioma
Pituitary adenoma
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74. Treatment with an anti-estrogen (e.g. Tamoxifen)
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:
Treatment with an anti-estrogen (e.g. Tamoxifen)
Treatment with an aromatase inhibitor
Treatment with a dopamine agonist (bromocryptine)
Surgery
Reassurance
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75. Diabetes

76. ½ NS with 40 meq K at 2x maintenance
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 Her electrolytes show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9. The MOST important initial management is:
insulin drip 0.1 u/kg/hr
½ NS with 40 meq K at 2x maintenance
Bicarb 1 meq/kg slowly over 1 hour
20 ml/kg normal saline bolus IV
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77. Impaired glucose tolerance but normal fasting glucose
GTT in a 16 year obese female: Time Glucose (mg/dL) Which of the following statements are correct? This patient has:
Type 2 diabetes
Impaired glucose tolerance but normal fasting glucose
Normal glucose tolerance
Both impaired fasting glucose and impaired glucose tolerance
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78. Definition of diabetes
≥ 126
≥ 200
Diabetes
≥ 100
≥ 140
< 126
< 200
Pre-diabetes
< 100
< 140
Normal
Fasting
2 hr post load

79. Slipped capital femoral epiphysis Hashimoto thyroiditis
This obese patient with IFG and IGT is at risk for the development of all the following EXCEPT
Type 2 diabetes
Dyslipidemia
Hypertension
Slipped capital femoral epiphysis
Hashimoto thyroiditis
Metabolic syndrome
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80. Glargine (Lantus) and Lipro insulin (Humalog)
A 13 year male has new onset type 1 diabetes mellitus. Therapy for this child may include all of the following EXCEPT:
Glargine (Lantus) and Lipro insulin (Humalog)
Detemir (Levemir) and Aspart insulin (Novolog)
Metformin
Analog insulin administered via an insulin pump
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81. Miscellaneous

82. Side effects of corticosteroids include all of the following except
hypertension
hypoglycemia
decrease bone mineralization
myopathy
cataracts
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83. What is the most likely diagnosis in this newborn infant?
Mother has SLE
Anasarca from cardiac failure
Systemic allergic reaction
Congenital nephrotic syndrome
Turner syndrome

84. 5 year old male with short stature
Turner syndrome
VATER syndrome
Albright’s hereditary osteodystrophy
Noonan syndrome
Goldenhar syndrome

85. A moderately obese adolescent female has irregular periods, hirsutism and acne. Of the following, which is the most likely diagnosis?
Cushing syndrome
Polycystic ovarian syndrome
Virilizing adrenal tumor
Non-classical CAH
Hyperprolactinemia

86. Choose correct answer Diabetes mellitus Diabetes insipidus Both
Neither
2 Na + BUN/2.8 + Gluc/18
1. Osmolality of serum > 300 Osm/L
2. Osmolality of urine > 500 mOsm/L
3. Hypernatremia

87. Choose correct answer Diabetes mellitus Diabetes insipidus Both
Neither
2 Na + BUN/2.8 + Gluc/18 C
1. Osmolality of serum > 300 Osm/L
2. Osmolality of urine > 500 mOsm/L
3. Hypernatremia A B