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Endocrinology Review Thyroid, pituitary, adrenal & bone

Endocrinology Review Thyroid, pituitary, adrenal & bone. Dora Liu, MD FRCPC. Basic thyroid physiology. Hypothalamic-Pituitary- Thyroid Axis. Thyroid hormones. From UpToDate. Thyroid hormone transport. Three major transport proteins: Thyroxine-binding globulin (TBG)

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Endocrinology Review Thyroid, pituitary, adrenal & bone

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  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

  6. Thyrotoxicosis

  7. 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

  8. 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

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

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

  11. Graves Hyperthyroidism

  12. Graves ophthalmopathy

  13. Pretibial myxedema

  14. Graves diseaseIncreased homogeneous uptake

  15. 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)

  16. 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

  17. Toxic adenoma

  18. Toxic multinodular goitre

  19. 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

  20. Toxic multinodular goitre

  21. 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

  22. 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

  23. 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

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

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

  26. Hypothyroidism

  27. 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

  28. 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

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

  30. 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

  31. 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

  32. Non-thyroidal illness“Sick euthyroid syndrome”

  33. 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

  34. Thyroid nodules and malignancies

  35. 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

  36. 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

  37. 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

  38. 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

  39. MEN syndromes

  40. 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

  41. Pituitary - Adrenal Disorders

  42. Basic pituitary & adrenal physiology

  43. 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

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

  45. Hyperprolactinemia

  46. Causes of hyperprolactinemia

  47. 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)

  48. Acromegaly

  49. 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

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