Endocrinology Review Thyroid, pituitary, adrenal & bone

1. Endocrinology ReviewThyroid, pituitary, adrenal & bone Dora Liu, MD FRCPC

2. Basic thyroid physiology

3. Hypothalamic-Pituitary-Thyroid Axis

4. Thyroid hormones From UpToDate

5. Thyroid hormone transport • Three major transport proteins: • Thyroxine-binding globulin (TBG) • Thyroxine-binding prealbumin (TBPA) • Albumin • Free (unbound) hormones are active • Proportion of “free” hormones: • 0.04% of T4 • 0.4% of T3

7. Thyrotoxicosis

8. Weight loss Increased appetite Heat intolerance Anxiety, irritability Fine tremor Fatigue Thyroid stare Systolic HTN Tachycardia Palpitations Atrial fibrillation Frequent BM’s Proximal weakness Diaphoresis Moist skin Fine hair Clinical features of thyrotoxicosis

9. Thyrotoxicosis - Investigations • Primary: • Low TSH • Increased fT3 and/or fT4 • Thyroid uptake and scan to determine etiology of 1o hyperthyroidism • Secondary: • TSH elevated or not suppressed • Increased fT3 and/or fT4

10. Causes of 1o thyrotoxicosis • Graves’ disease • Toxic adenoma or toxic multinodular goitre • Thyroiditis • Jod-Basedow (iodine-induced) • Exogenous thyroid hormone • Gestational hyperthyroidism (hCG-induced)

11. Graves’ disease • Autoimmune disorder • Thyroid stimulating immunoglobulin binds TSH receptor • F > M • Any age with peak in 3rd-4th decade • Diffusely enlarged “meaty” goitre

12. Graves Hyperthyroidism

13. Graves ophthalmopathy

14. Pretibial myxedema

15. Graves diseaseIncreased homogeneous uptake

16. Treatment of Graves disease • Methimazole or propylthiouracil (PTU) • Radioactive iodine therapy • Thyroidectomy • Temporary measures: • -blockade • Steroids (decrease T4 to T3 conversion) • Iodine (Wolff-Chaikoff effect)

17. Toxic adenoma • Solitary thyroid nodule produces excess hormone • Accounts for < 5% of hyperthyroidism • Frequency increases with age • F > M • Treatment of choice: radioactive iodine therapy

18. Toxic adenoma

19. Toxic multinodular goitre

20. Toxic multinodular goitre •  2 nodules producing excess hormone • In Canada, most patients are > 50 yrs old • Younger patients in areas of iodine deficiency • Compressive symptoms can occur • Treatment of choice: I-131

21. Toxic multinodular goitre

22. Thyroiditis • Destruction of thyroid cells causes release of hormones • Autoimmune, infectious and toxic causes • Can occur in post-partum period • Can be associated with fever, painful & tender gland

23. Diagnosis & treatment of thyroiditis • Low uptake on thyroid scan • NSAIDs for painful inflammation • -blockers to control symptoms • Steroids for severe cases • Often followed by hypothyroid phase

24. Gestational hyperthyroidism • hCG mimics TSH and stimulates thyroid hormone production • Associated with hyperemesis gravidarum, multiple gestation • Improves by 2nd trimester • Must differentiate from Graves disease • -blocker & PTU can be used during pregnancy

25. Extrathyroidal sources of thyroid hormone • Exogenous sources: • Exogenous thyroid hormone • Hamburger thyrotoxicosis • Endogenous sources: • Struma ovarii • Functioning thyroid cancer

26. Other causes of hyperthyroidism • TSH-secreting tumour • Iodine load (Jod-Basedow phenomenon) • Pituitary resistance to thyroid hormone

27. Hypothyroidism

28. Hypothyroidism • 2-3% of population • F:M = 10:1 • 1o hypothyroidism (90%) • Autoimmune (e.g., Hashimoto’s) • Iatrogenic (surgery, RAI, drugs, iodine) • Congenital, intrinsic defect of hormone synthesis • Infiltrative (amyloid, progressive systemic sclerosis) • 2o hypothyroidism - TSH deficiency • 3o hypothyroidism - TRH deficiency

29. Fatigue Cold intolerance Slow mental & physical performance Hoarse voice Bradycardia Diastolic hypertension Edema Weight gain Constipation Menorrhagia Dry skin Macroglossia Muscle cramps Delayed DTR Dyslipidemia Clinical features of hypothyroidism

30. Hypothyroidism - Lab tests • 1o hypothyroidism • Elevated TSH • Low fT4 and/or fT3 • Central hypothyroidism • Low fT4 and/or fT3 • TSH not reliable

31. Treatment of hypothyroidism • Typical levothyroxine (LT4) dose 50 - 200 mcg • Start low dose (25 mcg) and titrate up slowly in elderly • R/O adrenal insufficiency • Check TSH 6-8 wk after dose change & titrate to normalize TSH for 1o hypothyroidism • Titrate to normalize fT3 for central hypothyroidism

32. Myxedema coma • Severe hypothyroidism • Precipitating event (e.g., trauma, sepsis, cold exposure, MI, narcotics) • Clinical features: Hypothermia, hypoglycemia, hypotension, bradycardia, hypoventilation • Mortality up to 60% • Treatment: • ABCs • Stress-dose steroids • L-T4 0.2-0.5 mg IV then 0.1 mg daily

33. Non-thyroidal illness“Sick euthyroid syndrome”

34. Non-thyroidal illness • Change in thyroid hormone levels related to serious illness • Abnormalities in TSH secretion, hormone binding & metabolism • Decreased T4 to T3 conversion • Typically see low fT3 & high rT3 • More severe illness: fT3, fT4 & TSH can all be low • Rx: Treat underlying illness

35. Thyroid nodules and malignancies

36. Thyroid nodules • ~ 4% prevalence • ~ 5% malignant • If nodule is identified, check TSH • Low TSH  Thyroid scan • Low probability of malignancy with hot nodules • FNAB if cold nodule is present (15-20% malignant) • Normal or high TSH  FNAB if palpable or > 1 cm in diameter

37. Thyroid malignancies • Well-differentiated thyroid carcinomas: • Papillary • Follicular • Medullary thyroid carcinoma • Familial forms: MEN IIa & IIb, familial medullary carcinoma • Calcitonin is a tumour marker • Anaplastic thyroid carcinoma • Very poor prognosis

38. Well-differentiated thyroid carcinoma • Total thyroidectomy • I-131 therapy if higher risk • Multifocal • Large tumour • Capsular invasion • Lymph node or distant metastases • TSH suppression • Follow thyroglobulin level

39. Medullary thyroid CA • Look for other features of MEN IIa & IIb • R/O pheochromocytoma • R/O 1o hyperparathyroidism • RET protooncogene mutation • Treatment • Surgical resection for cure • Some respond to MIBG or octreotide • Prophylactic thyroidectomy in affected relatives

40. MEN syndromes

41. Medullary thyroid CA • Look for other features of MEN IIa & IIb • R/O pheochromocytoma • R/O 1o hyperparathyroidism • RET proto-oncogene mutation • Treatment • Surgical resection for cure • Some respond to MIBG or octreotide • Prophylactic thyroidectomy in affected relatives

42. Pituitary - Adrenal Disorders

43. Basic pituitary & adrenal physiology

44. Hypothalamic & anterior pituitary hormones • GHRH Growth hormone (GH) • TRH TSH • Somatostatin  GH & TSH • TRH & Prolactin-releasing factors Prolactin • Dopamine Prolactin • CRH  ACTH • GnRH LH & FSH

45. Anterior Growth hormone ACTH LH FSH TSH Prolactin Posterior ADH (arginine vasopressin) Oxytocin Pituitary hormones

46. Hyperprolactinemia

47. Causes of hyperprolactinemia

48. Hyperprolactinemia • Clinical features: • Galactorrhea, gynecomastia, infertility, low bone density • Headaches, bitemporal hemianopsia (if macroadenoma affects optic chiasm) • Treat underlying cause, if present • 1o Rx for prolactinoma: • Dopamine agonist (e.g., bromocriptine or cabergoline)

49. Acromegaly

50. Coarse facial features Acral enlargement Hyperhidrosis Heat intolerance Oily skin Fatigue Weight gain HTN Goitre Cardiomegaly Insulin resistance Arthralgias Parasthesias Hypogonadism Headaches Clinical features of acromegaly