Endocrinology Board Review

1. Endocrinology Board Review September 24, 2010

2. Growth

3. Growth • After 18mos of age, growth curve should be followed closely • Between 4y/o and adolescence, growth below 4-5cm/yr should be assessed • Percentiles should not be crossed • Pubertal growth spurt • Girls  early puberty • Boys  midpuberty

4. Growth Rate per Year

5. Question 1 Choose the correct statement comparing “familial or genetically determined short stature” and “constitutional delay of growth,” in regards to bone age. A. Familial = delayed/ constitutional = advanced B. Familial = equivalent/ constitutional = delayed C. Familial = delayed/ constitutional = equivalent D. Both are delayed

6. Constitutional delay of growth • Variant of normal growth and pubertal development • Period of decreased linear growth within first 3yrs of life • Downward crossing of percentiles • Linear growth resumes at normal rate • Along lower growth percentiles • Family history of “Late Bloomers”

7. Constitutional Growth Delay: Note deceleration followed by normal growth rate

8. Question 2 The physical findings depicted below corresponds to which tanner stage? A. I B. II C. III D. IV E. V

9. Tanner Staging • Boys: Staged by genital development and pubic hair – starts at 9-14 • Testis volume >= 4mL is pubertal • Mark of pubertal onset • Girls: Staged by breast development and pubic hair – starts at 10 ½ • Stage II = breast buds • Mark of pubertal onset • Stage IV = Areola elevated above breast (secondary mound)

10. Hypothalamus and Pituitary

11. Hypothalamus • Neuroectodermal tissue • Inferior third ventricle • Pituitary stalk

12. Pituitary • Anterior • Upgrowth of ectodermal cells from Rathke’s pouch • Posterior • Downgrowth of neural tissue cells from the hypothalamus

13. Question 3 You are evaluating a patient in clinic and notice the abnormality pictured. Which of the following is most likely to be affected? A. Growth hormone levels B. Aldosteronelevels C. Catecholamine levels D. Insulin levels

14. Anterior Pituitary • Growth Hormone • Secretion • GH-releasing factor • Inhibition • Somatostatin • IGF-1, IGF-BP3

15. Anterior Pituitary • Growth Hormone • Deficiency • Normal birth weight • Normal growth pattern x 1 year • “Kewpie” doll appearance, “cherubic” • Short, excess subq fat, retarded body proportion changes and high-pitched voices • Diagnosed with stimulation test

16. Anterior Pituitary • ACTH • Secretion • CRF from hypothalamus • Inhibition • Cortisol from adrenals • Prolonged steroid use

17. Anterior Pituitary • Gonadotropins • Secretion • GnRH • Hypothalamus sends pulses • Increases during puberty • Inhibition • Inhibin • FSH • Aromatase (androgen to estrogen) • Spermatogenesis • LH • Testosterone • Androstenedione (estradiol)

18. Anterior Pituitary • TSH • Secretion • TRH • Inhibition • Thyroid Hormone • Actions • Increases iodide uptake, thyroglobulin synthesis and thyroid hormone

19. Anterior Pituitary • Prolactin • Acts directly on target organ • Initiation and maintenance of lactation • Inhibited by dopamine from hypothalamus • Hyperprolactinemia • Galactorrhea • Pituitary adenomas • Medication • Neuroleptics, antipsychotics, estrogens and anti-hypertensives

20. Question 4 You are on call in the PICU and following a very sick patient admitted with meningococcal meningitis. He has not had any urine output in the last 8 hours despite fluid administration. You order a BMP and his Na is 125. What is the most likely cause of the hyponatremia in this patient? A. Diabetes insipidus B. Psychogenic polydipsia C. Inappropriate fluid administration D. SIADH

21. Posterior Pituitary • Hormones synthesized in hypothalamus and stored in posterior pituitary • Vasopressin • AVP or ADH • Released in response to increased osmotic pressure in the blood • Water balance • Increased reabsorption of water in collecting ducts of kidneys • Arteriolar vasoconstriction – HTN • Increased thirst

22. Posterior Pituitary • Vasopressin • Overproduction • Head trauma, brain tumors, encephalitis, pneumonia • SIADH • HA, apathy, nausea, vomiting, impaired consciousness • Decreased plasma osmolarity • Underproduction • Central Diabetes Insipidus (DI) • Pituitary tumors, head trauma, infiltrative diseases, autoimmune or surgical • Increased plasma osmolarity

23. Posterior Pituitary • Vasopressin • Resistant • Nephrogenic DI • Tubules in kidney cannot respond • Genetic or acquired (lithium) • Oxytocin • Released in response to nerve stimulation • Contraction of the smooth muscle of the uterus and myoepithelial cells lining the ducts of mammary glands

24. Thyroid

25. Thyroid • Location • Neck • Base of tongue • Mediastinum • Hormones • Thyroxine (T4) • Tri-iodothyronine (T3) • Need iodine for synthesis • Transported by TBG, albumin and transthyretin • Free hormone is active

26. Thyroid • Goiter • Hyper or hypo • Nodules • 70-80% benign or cystic • 1-1.5% of all childhood cancers • Neck irradiation, family history of medullary carcinoma, rapid growth, fixation to adjacent structures, enlarged lymph nodes

27. Question 5 A mother brings in her teenage daughter for hyperactivity and emotional lability. ROS is positive for diarrhea, weight loss and heat intolerance. On physical exam you notice tachycardia and a slight prominence of the eyes. A laboratory evaluation would most likely reveal: A. TSH, freeT4, + TSH receptor antibodies B. TSH, free T4, + antithyroperoxidase antibodies C. TSH, free T4, + TSH receptor antibodies D. TSH, free T4, + antithyroperoxidase antibodies

28. Thyroid • Hyperthyroid • Soft and fleshy gland • Tachycardia • Weight loss • Increased frequency of bowel movements • Heat intolerance • Nervousness • Widened pulse pressure • Tremor • Fatigue • Warm, moist skin • Fine, friable hair • Separation of distal margin of nail bed • Restlessness • Inability to sit still • Emotional lability • Short attention span • Excessive sweating

29. Thyroid • Hyperthyroidism • Graves Disease • Stimulating antibody to TSH receptor • Exopthalmos • Proptosis and lid lag • Large gland • Warm on palpation • Bruit • Labs • Increased T3 and T4 • Decreased TSH

30. Thyroid • Congenital Hypothyroidism • 1 in 4000 • Cretinism • Broad nasal bridge • Coarse facial features • Mental retardation • Short stature • Puffy hands • Protuberant tongue • Delayed skeletal maturation • Treatment within 3-4 weeks • Newborn Screening

31. Thyroid • Hypothyroid • Hypothalamic abnormalities • Pituitary abnormalities • Iodine deficiency • Chronic lymphocytic thyroiditis • Hashimoto thyroiditis • Anti-thyroid antibodies • Thyroglobulin • Thyroperoxidase • Positive FH • Increased TSH, decreased T4

32. Thyroid • Hypothyroid symptoms • Firm or bosselated gland • Congenital vs Acquired • Dry skin • Constipation • Hair loss • Fatigue • Cold intolerance • Apathy • Depressed or delayed relaxation

33. Acquired hypothyroidism: Note the sharp deceleration in growth before the onset of symptoms. Following initiation of therapy significant catch-up growth is seen.

34. Calcium and Phos Metabolism

35. PTH • Bone: • Increases release of Ca and Phos • Intestine: • Increased re-absorption of Ca and Phos • Kidney: • Increases excretion of Phos • Decreases excretion of Ca • Stimulates Synthesis of Vit D3

36. Effects of PTH

37. Vitamin D • Bone • Increases release of Ca • Increases release Ph • Intestine • Increases absorption of Ca • Increases absorption of Ph • Kidney • Improves reabsorption of Ca • Increases reabsorption of Ph

38. Vitamin D

39. Calcitonin • Bone • Inhibits reabsorption of Ca • Inhibits reabsorption of Ph • Intestine (no specific effects) • Kidney • Decreases reabsorption of Ca • Decreases reabsorption of Ph

40. Net Effect of 3 Hormones

41. Hyperparathyroidism • Results in hypercalcemia • Manifestation of multiple endocrine neoplasia I (MEN 1) • Autosomal dominant • Islet cell tumors • Zollinger-Ellison syndrome • Pituitary tumors

42. Hypocalcemia Symptoms: Paresthesias Irritability Muscle Cramps Tetany Seizures

43. Question 6 A two day old infant experiences a prolonged seizure with respiratory arrest requiring intubation. BMP reveals hypocalcemia, and CXR demonstrates absent thymic shadow. Genetic testing is likely to reveal: A. Trisomy 21 B. Trisomy 18 C. Deletion of 22q11.2 D. Deletion of 15q13.3 E.DF508 Mutation

44. Hypoparathyroidism • Idiopathic (Autoimmune) • DiGeorge Syndrome • Dysmorphic features • Cardiac defects • Immune deficiency • Thymicaplasia • Low PTH • Deletion of 22q11.2 • May present with seizures secondary to hypocalcemia Ca low P high PTH low

45. Pseudohypoparathyroidism • PTH is elevated • Unresponsiveness to PTH (Bone/Kidney/Both) • Albright hereditary osteodystrophy • Suspect in short child with hypocalcemia Ca low P high PTH high

46. Albright hereditary osteodystrophy

47. Vitamin D-Deficient Rickets • Vitamin D deficiency may result from • Inadequate sunlight exposure • Malabsorption • Drugs that affect Vit D • Phenytoin, phenobarb • Signs/Symptoms • Poor linear growth • Delayed walking • Muscle weakness • Bone pain • Hypotonia • Anorexia Ca NL/low P low PTH high AlkP high

48. Vitamin D-Deficient Rickets

49. Others • Vitamin D-Resistant Rickets • Resistance to Vit D, even when high amounts used • Findings in first months of life • Pseudovitamin D-Deficiency Rickets • AKA 1a-hydroxylase deficiency or Vit-D dependent rickets type I • Findings appear in early infancy • Autosomal recessive

50. Adrenals