1. Endocrinology

2. Calcium

3. 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. • Lab data:Glucose 88 mg/dLSodium 141 mEq/LCalcium 5.1 mg/dLPhosphorus 9.1 mg/dLMagnesium 2.1 mg/dL • What is the diagnosis? • What are important considerations in this child?

4. Ca PO4 1. 2. 3. 25 OH Vit D 1,25 (OH)2 Vit D 1 hydroxylase Gut NET EFFECT Actions of PTH

5. 6-week infant presents with seizure. Calcium 5.1 mg/dLPhosphorus 9.1 mg/dL • What is the diagnosis?HYPOPARATHYROIDISM • What are important considerations in this child?Possible DiGeorge syndrome (thymic aplasia, congenital heart diseasemicrodeletion of chromosome 22)

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

7. Which is consistent with vitamin D deficiency rickets? CALCIUM PHOS ALK PHOS • Normal Normal Low • Low Low Low • Low Increased Increased • Low Normal Normal • Normal Low Increased

8. 2 ½ weeks 4 months 9.8 3.5 2185 10.5 6.5 518 Initial Ca: PO4: Alk Phos: 9.7 3.1 2514

9. Choose correct answer • Vitamin D deficiency rickets • Renal osteodystrophy (renal rickets) • Both • Neither 1. Increased phosphate level 2. Increased PTH level 3. Increased creatinine level

10. THYROID

11. You are contacted by your state Neonatal Thyroid Screening Program. Baby X was born on 1/4/01. His newborn screening tests, performed on 1/6/01 revealed: Normal range TSH 37 IU/ml< 20 T4 10.1 g/dl9-19

13. You are contacted by your state Neonatal Thyroid Screening Program. Baby X was born on 1/4/01. His newborn screening tests, performed on 1/6/01 revealed: Initial filter paper Normal range TSH >200 IU/ml < 20 T4 2.1 g/dl 9-19 Venipuncture: (1/25/01) Normal range TSH 488 IU/ml(0.3-5.5) T4 1.2 g/dl(4.5-12.5)

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. You are contacted by Newborn screening program for a baby whose newborn thyroid screen at 3 days revealed a low T4 and normal TSH. Repeat venipuncture showed:T4 2.1 μg/dL (4.5-12.5) TSH 2.3 μIU/mL (0.3-5.0) • What is the differential diagnosis?

18. Central hypothyroidism - rare vs. TBG deficiency1:2800

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. 17 year old female who complains of easy fatigability Thyroid function:Normal range TSH 3.7 IU/ml0.3-5.5 T4 13.4 g/dl4.5-12 T3RU 20 % 25-35

22. Conditions that cause alterations in TBG Increased TBGDecreased TBG Infancy Familial deficiency Estrogen Androgenic steroid treatment - OC Pill Glucocorticoids (large dose) - pregnancy Nephrotic syndrome Familial excess Acromegaly Hepatitis Tamoxifen treatment

23. 15 year old with a goiter. No family history of thyroid disease. Thyroid function:Normal range TSH 43 IU/ml0.3-5.5 T4 6.0 g/dl4.5-12 T3 140 ng/dl 90-190 Primary hypothyroidism

25. Dr. Hakaru Hashimoto

26. Hashimoto thyroiditis Normal thyroid

27. DC • 16 year 7 month • Growth failure x 1 1/2 years • Labs:TSH:1008 µIU/ ml (0.3-5.0)T4:<1.0µg/dl (4-12)A-thyro Ab.232U/ml (0-1)A-perox Ab. 592 IU/ml (<0.3)Prolactin:29ng/ml (2-18) Cholesterol:406mg/dl (100-170)

28. DC Start of thyroxine

29. 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

30. 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/ml0.3-5.5 T4 14.8 g/dl4.5-12 T3 580 ng/dl 90-190

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

32. 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

33. Sexual differentiation

34. 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

35. Cholesterol Desmolase 17-OH Pregnenolone 17 (OH) pregnenolone DHEA 3--HSD 3--HSD 3--HSD 17-OH 17 (OH) progesterone Androstenedione Progesterone 21-OH 21-OH DOCA Compound S TESTOSTERONE 11-OH 11-OH Corticosterone CORTISOL ALDOSTERONE

36. If she has salt wasting congenital adrenal hyperplasia, which abnormalities are likely to develop • Increased serum potassium • Decreased serum sodium • Decreased bicarbonate • Decreased plasma cortisol • Increased plasma renin activity

37. 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

38. Laboratory data: Na 121 K 9.3 Cl 83 CO2 6.7 Glucose 163 BUN/Creat 33/0.2 WBC 16.7 Hb 16.4 Hct 49 Plt 537 K CSF: Chemistry: Protein 74 Glucose 82 Microscopy: WBC 6 RBC 100

39. Emergency therapy • Fluid resuscitation:20 ml/kg Normal saline • Glucocorticoid2 mg/kg Solucortef IV • Monitor EKG

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

41. Therapy and evaluation of therapy • Glucocorticoid (Hydrocortisone) • Monitor growth, 17-OHP, urinary pregnanetriol • Fluorocortisol (Florinef 0.1 – 0.15 mg/day) • Blood pressure, plasma renin activity (PRA) • Supplemental salt (2.2 meq/kg/day Na) • Until introduction of infant food

42. 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?

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

44. Complete androgen insensitivity • XY genotype • Non functioning androgen receptor • Sertoli cells – AMH • Regression of Mullerian structures • Leydig cells – testosterone • No functioning receptor • Therefore Wolffian regression • Testosterone converted to DHT • No functioning receptor • Therefore normal female external genitalia

45. Puberty

46. 6 year old female with breast development • 6 yr African American female with breast development

47. History • Few months of breast development • No pubic or axillary hair • No vaginal discharge • Growth acceleration • No history of exposure to estrogen

48. Family history • Family history • Mother had menarche at 9.5 years • ROS • No Gelastic seizures

49. Ht 75 % Last height 50 % Wt 75 % No hyperpigmented lesions/ café au laitmacules Breasts T-2 PH T-1, no estrogen affect on the mucosa Growth acceleration PE • No NF or McCune Albright syndrome

50. Puberty • What First sign: • breast development • testicular enlargement, >2 cm • Isolated pubic hair is NOT puberty