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Diseases of thyroid gland


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Diseases of thyroid gland

  2. 2. THYROID GLAND DISORDERS <ul><li>GENERAL ASPECTS OF THYROID GLAND </li></ul><ul><ul><li>Anatomy: weight range from 12 to 30g </li></ul></ul><ul><ul><li>Located in the neck, anterior to the traquea </li></ul></ul><ul><ul><li>Produces: T4 & T3 (active hormone) </li></ul></ul><ul><ul><li>Regulation: “negative Feed-back” axis </li></ul></ul>
  3. 3. THYROID GLAND DISORDERS <ul><ul><li>THYROID GLAND REGULATION </li></ul></ul><ul><ul><li> “ negative Feed-back” axis </li></ul></ul><ul><ul><li>Hypothalamus </li></ul></ul><ul><ul><ul><ul><li>(TRH positive effect) </li></ul></ul></ul></ul><ul><ul><li>Pituitary gland </li></ul></ul><ul><ul><ul><ul><li>(TSH, positive effect) </li></ul></ul></ul></ul><ul><ul><li>Thyroid gland </li></ul></ul><ul><ul><ul><li>T3 & T4 </li></ul></ul></ul>(negative effect)
  4. 4. THYROID GLAND DISORDERS <ul><li>Thyroid hormones: </li></ul><ul><ul><li>T4: (Thyroxine) is made exclusively in thyroid gland </li></ul></ul><ul><ul><ul><li>Ratio of T4 to T3 ; 5::1 </li></ul></ul></ul><ul><ul><ul><li>Potency of T4 to T3; 1::10 </li></ul></ul></ul><ul><ul><ul><li>T4 is the most important source of T3 by peripheral tissue deiodination “ T4 to T3 “ </li></ul></ul></ul>
  5. 5. THYROID GLAND DISORDERS <ul><li>Thyroid hormones: </li></ul><ul><ul><li>T3: (Triiodothyronine) main source is peripheral deiodination: </li></ul></ul><ul><ul><ul><li>Ratio of T3 to T4 ; 1::5 </li></ul></ul></ul><ul><ul><ul><li>Potency of T3 to T4; 10::1 </li></ul></ul></ul><ul><ul><ul><li>T3 is the most important because more than 90% of the thyroid hormones physiological effects are due to the binding of T3 to Thyroid receptors in peripheral tissues. </li></ul></ul></ul>
  7. 7. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS: </li></ul><ul><ul><li>Affects every single cell in the body </li></ul></ul><ul><ul><ul><li>Modulates: </li></ul></ul></ul><ul><ul><ul><ul><li>Oxygen consumption </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Growth rate </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Maturation and cell differentiation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Turnover of Vitamins, Hormones, Proteins, Fat, CHO </li></ul></ul></ul></ul>
  8. 8. THYROID GLAND DISORDERS <ul><li>MECHANISMS OF THYROID HORMONE ACTION </li></ul><ul><ul><li>Act by binding to Nuclear receptors, termed Thyroid Hormone Receptors (TRs), Increasing synthesis of proteins </li></ul></ul><ul><ul><li>At mitochondrial level increases number and activity to increasing ATP production </li></ul></ul><ul><ul><li>At Cell membrane increases ions and substrates transmembrane flux </li></ul></ul>
  9. 9. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>CALORIGENESIS </li></ul></ul><ul><ul><li>GROWTH & MATURATION RATE </li></ul></ul><ul><ul><li>C.N.S. DEVELOPMENT & FUNCTION </li></ul></ul><ul><ul><li>CHO, FAT & PROTEIN METABOLISM </li></ul></ul><ul><ul><li>MUSCLE METABOLISM </li></ul></ul><ul><ul><li>ELECTROLYTE BALANCE </li></ul></ul><ul><ul><li>VITAMIN METABOLISM </li></ul></ul><ul><ul><li>CARDIOVASCULAR SYSTEM </li></ul></ul><ul><ul><li>HEMATOPOIETIC SYSTEM </li></ul></ul><ul><ul><li>GASTROINTESTINAL SYSTEM </li></ul></ul><ul><ul><li>ENDOCRINE SYSTEM </li></ul></ul><ul><ul><li>PREGNANCY </li></ul></ul>
  10. 10. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>CALORIGENESIS </li></ul></ul><ul><ul><ul><li>Controls the Basal Metabolic Rate (BMR) </li></ul></ul></ul><ul><ul><li>CHO METABOLISM </li></ul></ul><ul><ul><ul><li>Increases: </li></ul></ul></ul><ul><ul><ul><ul><li>Glucose absorption of the GI tract </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Glucose consumption by peripheral tissues </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Glucose uptake by the cells </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Glycolysis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Gluconeogenesis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Insulin secretion </li></ul></ul></ul></ul>
  11. 11. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>GROWTH & MATURATION RATE </li></ul></ul><ul><ul><li>C.N.S. DEVELOPMENT & FUNTION </li></ul></ul><ul><ul><ul><li>“ ESSENTIAL” in the newborn to prevent development of “CRETINISMS” & to a normal “IQ” </li></ul></ul></ul><ul><ul><ul><li>Modulation of brain cerebration </li></ul></ul></ul><ul><ul><ul><li>Mood modulation </li></ul></ul></ul>
  12. 12. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><li>- FAT & PROTEIN METABOLISM </li></ul><ul><ul><ul><li>Increase lipolysis and lipid mobilization with: </li></ul></ul></ul><ul><ul><ul><ul><li>Cholesterol </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Triglicerides </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Free fatty acids </li></ul></ul></ul></ul><ul><ul><li>MUSCLE METABOLISM </li></ul></ul><ul><ul><ul><li>Modulates; </li></ul></ul></ul><ul><ul><ul><ul><li>Strength & velocity of contraction </li></ul></ul></ul></ul>
  13. 13. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>ELECTROLYTE BALANCE </li></ul></ul><ul><ul><ul><li>Low Thyroid hormones could induce hyponatremia </li></ul></ul></ul><ul><ul><li>VITAMIN METABOLISM </li></ul></ul><ul><ul><ul><li>Modulates vitamin consumption </li></ul></ul></ul><ul><ul><li>HEMATOPOIETIC SYSTEM </li></ul></ul><ul><ul><ul><li>Could induce anemia </li></ul></ul></ul>
  14. 14. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>CARDIOVASCULAR SYSTEM </li></ul></ul><ul><ul><ul><li>Hyperthyroidism, increases: </li></ul></ul></ul><ul><ul><ul><ul><li>Heart rate & myocardial strenght </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cardiac output </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Peripheral resistances (Vasodilatation) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Oxygen consumption </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Arterial pressure </li></ul></ul></ul></ul><ul><ul><ul><li>Hypothyroidism, reduces: </li></ul></ul></ul><ul><ul><ul><ul><li>Heart rate & myocardial strenght </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Cardiac output </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Peripheral resistances (Vasodilatation) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Oxygen consumption </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Arterial pressure </li></ul></ul></ul></ul>
  15. 15. THYROID GLAND DISORDERS <ul><li>THYROID HORMONE EFFECTS </li></ul><ul><ul><li>GASTROINTESTINAL SYSTEM </li></ul></ul><ul><ul><ul><li>Modulate bowel movements and absorption </li></ul></ul></ul><ul><ul><li>ENDOCRINE SYSTEM </li></ul></ul><ul><ul><ul><li>Modulates pituitary axis, affecting GH, ACTH, FSH, LH, so-on </li></ul></ul></ul><ul><ul><li>PREGNANCY </li></ul></ul><ul><ul><ul><li>Modulates growth rate and affects lactation </li></ul></ul></ul>
  16. 16. THYROID GLAND DISORDERS <ul><li>DIVIDED INTO: </li></ul><ul><ul><li>THYROTOXICOSIS (Hyperthyroidism) </li></ul></ul><ul><ul><ul><li>Overproduction of thyroid hormones </li></ul></ul></ul><ul><ul><li>HYPOTHYROIDISM (Gland destruction) </li></ul></ul><ul><ul><ul><li>Underproduction of thyroid hormones </li></ul></ul></ul><ul><ul><li>NEOPLASTIC PROCESSES </li></ul></ul><ul><ul><ul><li>Beningn </li></ul></ul></ul><ul><ul><ul><li>Malignant </li></ul></ul></ul>
  17. 17. THYROID GLAND DISORDERS <ul><li>LABORATORY EVALUATION </li></ul><ul><ul><li>TSH normal, practically excludes abnormality </li></ul></ul><ul><ul><li>If TSH is abnormal, next step: Total & Free T4 & T3 </li></ul></ul><ul><ul><li>TSI (Thyroid Stimulating Ig) </li></ul></ul><ul><ul><li>TPO (Thyroid Peroxidase Ab) </li></ul></ul><ul><ul><li>Antimitochondrial Ab </li></ul></ul><ul><ul><li>Serum Tg (Thyroglobulin) </li></ul></ul><ul><ul><li>Radioiodine uptake & Thyroid scaning </li></ul></ul><ul><ul><li>FNA, Fine-needle aspiration </li></ul></ul><ul><ul><li>Thyroid ultrasound </li></ul></ul>
  18. 18. THYROID GLAND DISORDERS <ul><li>TSH High usually means Hypothyroidism </li></ul><ul><ul><li>Rare causes: </li></ul></ul><ul><ul><ul><li>TSH-secreting pituitary tumor </li></ul></ul></ul><ul><ul><ul><li>Thyroid hormone resistance </li></ul></ul></ul><ul><ul><ul><li>Assay artifact </li></ul></ul></ul><ul><li>TSH low usually indicates Thyrotoxicosis </li></ul><ul><ul><li>Other causes </li></ul></ul><ul><ul><ul><li>First trimester of pregnancy </li></ul></ul></ul><ul><ul><ul><li>After treatment of hyperthyroidism </li></ul></ul></ul><ul><ul><ul><li>Some medications (Esteroids-dopamine) </li></ul></ul></ul>
  19. 19. THYROID GLAND DISORDERS <ul><li>THYROTOXICOSIS: </li></ul><ul><ul><li>is defined as the state of thyroid hormone excesss </li></ul></ul><ul><li>HYPERTHYROIDISM: </li></ul><ul><ul><li>is the result of excessive thyroid gland function </li></ul></ul>
  20. 20. THYROID GLAND DISORDERS <ul><li>Abnormalities of Thyroid Hormones </li></ul><ul><ul><li>Thyrotoxicosis </li></ul></ul><ul><ul><ul><li>Primary </li></ul></ul></ul><ul><ul><ul><li>Secondary </li></ul></ul></ul><ul><ul><ul><li>Without Hyperthyroidism </li></ul></ul></ul><ul><ul><ul><li>Exogenous or factitious </li></ul></ul></ul><ul><ul><li>Hypothyroidism </li></ul></ul><ul><ul><ul><li>Primary </li></ul></ul></ul><ul><ul><ul><li>Secondary </li></ul></ul></ul><ul><ul><ul><li>Peripheral </li></ul></ul></ul>
  21. 21. THYROID GLAND DISORDERS <ul><li>Causes of Thyrotoxicosis : </li></ul><ul><ul><li>Primary Hyperthyroidism </li></ul></ul><ul><ul><ul><li>Grave´s disease </li></ul></ul></ul><ul><ul><ul><li>Toxic Multinodular Goiter </li></ul></ul></ul><ul><ul><ul><li>Toxic adenoma </li></ul></ul></ul><ul><ul><ul><li>Functioning thyroid carcinoma metastases </li></ul></ul></ul><ul><ul><ul><li>Activating mutation of TSH receptor </li></ul></ul></ul><ul><ul><ul><li>Struma ovary </li></ul></ul></ul><ul><ul><ul><li>Drugs: Iodine excess </li></ul></ul></ul>
  22. 22. THYROID GLAND DISORDERS <ul><li>Causes of Thyrotoxicosis: </li></ul><ul><ul><li>Thyrotoxicosis without hyperthyroidism </li></ul></ul><ul><ul><ul><li>Subacute thyroiditis </li></ul></ul></ul><ul><ul><ul><li>Silent thyroiditis </li></ul></ul></ul><ul><ul><ul><li>Other causes of thyroid destruction: </li></ul></ul></ul><ul><ul><ul><ul><li>Amiodarone, radiation, infarction of an adenoma </li></ul></ul></ul></ul><ul><ul><ul><li>Exogenous/Factitia </li></ul></ul></ul><ul><ul><li>Secondary Hyperthyroidism </li></ul></ul><ul><ul><ul><li>TSH-secreting pituitary adenoma </li></ul></ul></ul><ul><ul><ul><li>Thyroid hormone resistance syndrome </li></ul></ul></ul><ul><ul><ul><li>Chorionic Gonadotropin-secreting tumor </li></ul></ul></ul><ul><ul><ul><li>Gestational thyrotoxicosis </li></ul></ul></ul>
  23. 23.
  24. 24. THYROTOXICOSIS <ul><li>Symptoms: </li></ul><ul><ul><li>Hyperactivity </li></ul></ul><ul><ul><li>Irritability </li></ul></ul><ul><ul><li>Dysphoria </li></ul></ul><ul><ul><li>Heat intolerance & sweating </li></ul></ul><ul><ul><li>Palpitations </li></ul></ul><ul><ul><li>Fatigue & weakness </li></ul></ul><ul><ul><li>Weight loss with increased appetite </li></ul></ul><ul><ul><li>Diarrhea </li></ul></ul><ul><ul><li>Polyuria </li></ul></ul><ul><ul><li>Sexual dysfunction </li></ul></ul><ul><li>Signs: </li></ul><ul><ul><li>Tachycardia </li></ul></ul><ul><ul><li>Atrial fibrillation </li></ul></ul><ul><ul><li>Tremor </li></ul></ul><ul><ul><li>Goiter </li></ul></ul><ul><ul><li>Warm, moist skin </li></ul></ul><ul><ul><li>Muscle weakness, myopathy </li></ul></ul><ul><ul><li>Lid retraction or lag </li></ul></ul><ul><ul><li>Gynecomastia </li></ul></ul><ul><ul><li>* Exophtalmus </li></ul></ul><ul><ul><li>* Pretibial myxedema </li></ul></ul>
  25. 25. THYROID GLAND DISORDERS <ul><li>Differential diagnosis: </li></ul><ul><ul><li>Panic attacks </li></ul></ul><ul><ul><li>Psychosis </li></ul></ul><ul><ul><li>Mania </li></ul></ul><ul><ul><li>Pheochromocytoma </li></ul></ul><ul><ul><li>Hypoglycemia </li></ul></ul><ul><ul><li>Occult malignancy </li></ul></ul>
  26. 26. THYROID GLAND DISORDERS <ul><li>Treatment: </li></ul><ul><ul><li>Reducing thyroid hormone synthesis: </li></ul></ul><ul><ul><ul><li>Antithyroid drugs (Methimazole, Propylthyouracil) </li></ul></ul></ul><ul><ul><ul><li>Radioiodine ( 131 I) </li></ul></ul></ul><ul><ul><ul><li>Subtotal thyroidectomy </li></ul></ul></ul><ul><ul><li>Reducing Thyroid hormone effects: </li></ul></ul><ul><ul><ul><li>Propranolol </li></ul></ul></ul><ul><ul><ul><li>Glucocorticoids </li></ul></ul></ul><ul><ul><ul><li>Benzodiazepines </li></ul></ul></ul><ul><ul><li>Reducing peripheral conversion of T4 to T3 </li></ul></ul><ul><ul><ul><li>Propylthyouracil </li></ul></ul></ul><ul><ul><ul><li>Glucocorticoids </li></ul></ul></ul><ul><ul><ul><li>Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect) </li></ul></ul></ul>
  27. 27. THYROID GLAND DISORDERS <ul><li>Treatment: Special considerations: </li></ul><ul><ul><li>Thyrotoxic crisis or Thyroid storm: </li></ul></ul><ul><ul><ul><li>It´s a life-threatening exacervation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. </li></ul></ul></ul><ul><ul><ul><li>Mortality rate reachs 30% even with treatment </li></ul></ul></ul><ul><ul><ul><li>It´s usually precipitated by acute illness, such as: </li></ul></ul></ul><ul><ul><ul><ul><li>Stroke, infection,trauma, diabeic ketoacidosis, surgery, radioiodine treatment </li></ul></ul></ul></ul><ul><ul><ul><li>Propylthyouracil IV or Nasogastric tube </li></ul></ul></ul><ul><ul><ul><li>Radioiodine ( 131 I) </li></ul></ul></ul><ul><ul><ul><li>Propranolol </li></ul></ul></ul><ul><ul><ul><li>Glucocorticoids </li></ul></ul></ul><ul><ul><ul><li>Benzodiazepines </li></ul></ul></ul><ul><ul><ul><li>Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect) </li></ul></ul></ul>
  28. 28. THYROID GLAND DISORDERS <ul><li>HYPOTHYROIDISM </li></ul><ul><ul><li>Primary </li></ul></ul><ul><ul><ul><li>Autoimmune (Hashimoto´s) </li></ul></ul></ul><ul><ul><ul><li>Iatrogenic Surgery or 131 I </li></ul></ul></ul><ul><ul><ul><li>Drugs: amiodarone, lithium </li></ul></ul></ul><ul><ul><ul><li>Congenital (1 in 3000 to 4000) </li></ul></ul></ul><ul><ul><ul><li>Iodine defficiency </li></ul></ul></ul><ul><ul><ul><li>Infiltrative disorders </li></ul></ul></ul>
  29. 29. THYROID GLAND DISORDERS <ul><li>Hashimoto´s Thyroiditis or Goitrous thyroiditis </li></ul><ul><ul><li>Mean anual incidence: </li></ul></ul><ul><ul><ul><li>Women 4:1000 Men 1:1000 </li></ul></ul></ul><ul><ul><ul><li>Risk factors; TPO antibodies (90%) Japanese, previous history, high I intake </li></ul></ul></ul><ul><ul><ul><li>Average age: 60 </li></ul></ul></ul><ul><ul><ul><li>Frequently associated to other autoimmune disorders such as: AR, SLE, Sjogren´s so-on. </li></ul></ul></ul><ul><ul><ul><li>Treatment: Levothyroxine </li></ul></ul></ul>
  30. 30. THYROID GLAND DISORDERS <ul><li>CONGENITAL HYPOTHYROIDISM </li></ul><ul><li>Prevalence: 1 in 3000 to 4000 newborns </li></ul><ul><ul><li>Cause: Dysgenesis 85% </li></ul></ul><ul><ul><li>Dx: Blood screning (TSH &/or T4) </li></ul></ul><ul><li>Treatment: </li></ul><ul><ul><li>Supplemental Tx. With Levothyroxine is “essential” for a normal C.N.S. Development and prevention of mental retardation </li></ul></ul>
  31. 31. THYROID GLAND DISORDERS <ul><li>HYPOTHYROIDISM </li></ul><ul><ul><li>Secondary </li></ul></ul><ul><ul><ul><li>Pituitary gland destruction </li></ul></ul></ul><ul><ul><ul><li>Isolated TSH deficiency </li></ul></ul></ul><ul><ul><ul><li>Bexarotene treatment </li></ul></ul></ul><ul><ul><ul><li>Hypothalamic disorders </li></ul></ul></ul><ul><ul><li>Peripheral: </li></ul></ul><ul><ul><ul><li>Rare, familial tendency </li></ul></ul></ul>
  32. 32. HYPOTHYROIDISM <ul><li>Symptoms: </li></ul><ul><ul><li>Tiredness </li></ul></ul><ul><ul><li>Weakness </li></ul></ul><ul><ul><li>Dry skin Sexual dysfunction </li></ul></ul><ul><ul><li>Dry skin </li></ul></ul><ul><ul><li>Hair loss </li></ul></ul><ul><ul><li>Difficulty concentrating </li></ul></ul><ul><li>Signs: </li></ul><ul><ul><li>Bradycardia </li></ul></ul><ul><ul><li>Dry coarse skin </li></ul></ul><ul><ul><li>Puffy face, hands and feet </li></ul></ul><ul><ul><li>Diffuse alopecia </li></ul></ul><ul><ul><li>Peripheral edema </li></ul></ul><ul><ul><li>Delayed tendon reflex relaxation </li></ul></ul><ul><ul><li>Carpal tunel syndrome </li></ul></ul><ul><ul><li>Serous cavity effusions. </li></ul></ul>
  33. 33. THYROID GLAND DISORDERS <ul><li>SPECIAL TREATMENT CONSIDERATIONS </li></ul><ul><li>Myxedema coma </li></ul><ul><ul><li>Reduced level of consciousness, seizures </li></ul></ul><ul><ul><li>Hypotension/shock </li></ul></ul><ul><ul><li>Hypothermia </li></ul></ul><ul><ul><li>Hyponatremia </li></ul></ul><ul><li>Usually in elderly hypothyroid pts. </li></ul><ul><li>Usually precipitated by intercurrent illnesses that impairs ventilation </li></ul><ul><li>It´s an Emergency with a high mortality rate </li></ul><ul><li>Treatment: Lyotironine(T3) or T4, Hydrocortisone, external warming, IV fluids </li></ul>
  34. 34. THYROID GLAND DISORDERS <ul><li>SPECIAL TREATMENT CONSIDERATIONS </li></ul><ul><li>Elderly patients </li></ul><ul><li>Coronary Artery Disease </li></ul><ul><li>Poor adrenal gland reserve </li></ul><ul><li>Childrens </li></ul><ul><li>Pregnancy </li></ul><ul><li>Emergency surgery (Non thyroid related) </li></ul>
  35. 35. THYROID GLAND DISORDERS <ul><li>THYROID GLAND NEOPLASIAS </li></ul><ul><li>Out of the focus of this lecture </li></ul>
  36. 36. <ul><li>THYROID </li></ul><ul><li>Hyperthyroidism </li></ul><ul><li>Thyrotoxicosis (most common cause) </li></ul><ul><li>a)  T 3 and T 4 </li></ul><ul><li>3 most common causes: </li></ul><ul><li>a) diffuse hyperplasia </li></ul><ul><li>i) Graves disease (~ 85% of cases) </li></ul><ul><li>b) hyperfunctional multinodular goiter </li></ul><ul><li>c) multifunctional adenoma of thyroid </li></ul>
  37. 37. <ul><li>Clinical </li></ul><ul><li>a) hypermetabolic state </li></ul><ul><li>i) skin  warm, soft and flushed </li></ul><ul><li>ii) heat intolerant </li></ul><ul><li>iii) sweating </li></ul><ul><li>iv) weight loss (despite  appetite) </li></ul><ul><li>v) cardiac  earliest S & S   HR, </li></ul><ul><li> contractility, CO, cardiomegaly, </li></ul><ul><li> arrhythmias ( A fib in older patients) </li></ul><ul><li>vi) neuromuscular  overactivity of SNS causes tremors, anxiety, inability to concentrate, muscle weakness with  muscle mass (thyroid myopathy) </li></ul>
  38. 38. vii) Ocular  wide, staring gaze and lid lag - SNS overstimulation of levator palpebrae superiosis - ptosis - true thyroid opthalmopathy seen only in Graves disease viii) GI  SNS  hypermotility, malabsorption and diarrhea ix) Skeletal system  bone resorption, osteoporosis b) thyroid storm i) abrupt onset of severe hyperthyroidism (Graves &  SNS)
  39. 39. ii) febrile,  HR (out of proportion to febrile response) iii) is a medical emergency - death from cardiac arrhythmias c) apathetic hyperthyroidism i) seen in elderly ii) age and other comorbidities blunt effects of excess thyroid hormone excess - diagnosis during work up for unexplained weight loss or worsening CV disease
  40. 40. d) Diagnosis i) measurement of serum TSH (  ) in 1 O - in 2 O  TSH may be – or  - “TRH stimulation test” excludes secondary hyperthyroidism ii)  T 4 (sometimes  T 3 ) - in some cases, T 4 may be  - T 3 may therefore be useful
  41. 41. Thyrotoxicosis results in an increase in metabolic rate. This may result in: Smooth, moist, warm skin Flushing of face and hands Overgrown nails (acropachy, clubbing), which may lift off the nail bed ( onycholysis ) Fine soft thinned scalp hair Generalized itching ( pruritus ) Urticaria Increased skin pigmentation “ Pretibial myxedema”
  42. 42. <ul><li>Hypothyroidism </li></ul><ul><li>any defect causing  thyroid hormone </li></ul><ul><li>production </li></ul><ul><li>a) anywhere in hypothalamic-pituitary- </li></ul><ul><li>thyroid axis </li></ul><ul><li>b) 1 o are most common cause </li></ul><ul><li>i) “thyroprivic” (loss of parenchyma) </li></ul><ul><li>ii) “goitrous” (due to  TSH) </li></ul><ul><li>Causes </li></ul><ul><li>a) large surgical resection </li></ul><ul><li>b) ablation (radiation) of hyperthyroidism ! </li></ul><ul><li>c) autoimmune </li></ul><ul><li>i) most common cause of goitrous hypothyroidism </li></ul>
  43. 43. ii) most are due to Hashimoto thyroiditis (later) d) drugs i) to  thyroid secretion ii) non thyroid conditions (lithium,  -aminosalicylic acid) e) inborn errors of thyroid metabolism i) uncommon ii) any step of thyroid hormone synthesis may be involved - e.g., “Pendred syndrome” failure of binding iodine in thyroglobulin
  44. 44. f) thyroid hormone resistance i) receptor mutations g) 2 O hypothyroidism i) TSH deficiency ii) any of causes of hypopituitarism (frequently  tumor). Other causes include: postpartum pituitary necrosis, trauma, nonpituitary tumors h) 3 O (central) hypothyroidism i) anything that interfere with hypothalamic-portal system ii) inadequate TRH delivery
  45. 45. <ul><li>Cretinism </li></ul><ul><li>a) hypothyroidism developing in infancy/early childhood </li></ul><ul><li>i) severe mental retardation </li></ul><ul><li>ii) occurs in iodine deficient areas of world (i.e., Himalayas, inland China, Africa) </li></ul><ul><li>iii) may also be sporadic, owing to enzyme deficiencies   thyroid hormone synthesis </li></ul>
  46. 46. b) clinical: i) impaired skeletal development ii) impaired CNS development - inadequate maternal thyroid hormone prior to fetal thyroid gland formation  SEVERE mental retardation - normal brain development if maternal thyroid deficiency occurs after fetal thyroid gland development
  47. 47.
  48. 48. <ul><li>Myxedema (i.e., Gull disease) </li></ul><ul><li>a) hypothyroidism developing in older child/adult </li></ul><ul><li>b) slowing of physical and mental activity </li></ul><ul><li>i) generalized fatigue </li></ul><ul><li>ii) apathy </li></ul><ul><li>iii) cold-intolerant </li></ul><ul><li>iv) overweight </li></ul><ul><li>v)  CO </li></ul><ul><li>- shortness of breath </li></ul><ul><li>-  exercise capacity </li></ul><ul><li>vi)  SNS activity </li></ul><ul><li>- constipation </li></ul><ul><li>-  sweating </li></ul>
  49. 49. vii) skin pale, cool (  blood flow) viii) edema, puffy face, coarse hair ix) broadening of facial features x) enlarged tongue xi) deepening of voice c) clinical: i) TSH level most sensitive screening test -  in 1 O (due to loss of feedback inhibition of TRH release) - normal or not elevated in 2 O or 3 O hypothyroidism - T 4  in all forms of hypothyroidism
  50. 50.
  51. 51.
  52. 52. <ul><li>Thyroiditis </li></ul><ul><li>inflammation of thyroid </li></ul><ul><li>a) acute illness with thyroid pain </li></ul><ul><li>b) may not significantly affect thyroid function </li></ul><ul><li>Types: </li></ul><ul><li>a) Hashimoto thyroiditis (chronic lymphocytic thyroiditis) </li></ul><ul><li>i) gradual thyroid failure due to autoimmune destruction of thyroid </li></ul><ul><li>ii) 45-65 yrs </li></ul><ul><li>iii) 10:1 female predominance </li></ul><ul><li>iv) major cause of non endemic goiter </li></ul><ul><li> in children </li></ul>
  53. 53. v) genetic component - patients with Turner syndrome have  circulating antithyroid Ab vi) Clinical: 1) progressive depletion of thyroid epithelial cells 2) replaced with mononuclear cells and fibrosis 3) comes to clinical attention as painless enlargement of thyroid with some degree of hypothyroidism 4) hypothyroidism progresses slowly 5) can be preceeded by “hashitoxicosis” 6) patients at risk in developing other autoimmune diseases 7) no CA risk
  54. 54. b) Subacute (granulomatous) thyroiditis [“aka De Quervain thyroiditis”] i) occurs less often than Hashimoto ii) 30-50 yrs iii) female preponderance 5:1 iv) caused by viral infection v) history of upper respiratory infection just prior to onset of thyroiditis vi) seasonal incidence (summer peak) vii) acute or gradual viii) painful presentation, radiating to jaw, throat, ears: especially when swallowing !!
  55. 55. ix) inflammation and hyperthyroidism are transient - followed by transient period of asymptomatic hypothyroidism x) self limited disease c) subacute lymphocytic (painless) thyroiditis i) uncommon ii) hyperthyroid presentation - may present with any of signs of hyperthyroidism (no opthalmopathy, as in Graves disease)
  56. 56. d) Riedel thyroiditis i) fibrosis of thyroid and neighboring structures ii) presents as hard and fixed thyroid which clinically is similar to CA e) Palpation thyroiditis i) vigorous clinical palpation ii) thyroid function not affected iii) usually an incidental finding.
  57. 57. <ul><li>Graves disease </li></ul><ul><li>Most common cause of endogenous </li></ul><ul><li>hyperthyroidism </li></ul><ul><li>Characteristics: </li></ul><ul><li>a) hyperthyroidism </li></ul><ul><li>i) diffuse enlargement of thyroid </li></ul><ul><li>ii) lymphocytic infiltration </li></ul><ul><li>b) infiltrative ophthalmopathy </li></ul><ul><li>i) with resultant exophthalmos </li></ul><ul><li>c) localized infiltrative dermopathy </li></ul><ul><li>i) “pretibial myxedema” </li></ul><ul><li>- present in minority of cases ! </li></ul>
  58. 58. Thyrotoxicosis results in an increase in metabolic rate. This may result in: Smooth, moist, warm skin Flushing of face and hands Overgrown nails (acropachy, clubbing), which may lift off the nail bed ( onycholysis ) Fine soft thinned scalp hair Generalised itching ( pruritus ) Urticaria Increased skin pigmentation “ Pretibial myxedema”
  59. 59. <ul><li>peak incidence 20-40 </li></ul><ul><li>female preponderance (7:1 ) </li></ul><ul><li>familial link </li></ul><ul><li>Pathogenesis: </li></ul><ul><li>a) autoimmune disorder </li></ul><ul><li>b) Ab against TSH receptor is central to disease process </li></ul><ul><li>c) retro-orbital connective tissue and ocular muscles are increased </li></ul><ul><li>i) inflammatory edema </li></ul><ul><li>ii) T-cell infiltration </li></ul><ul><li>iii) fatty infiltration </li></ul><ul><li>iv) ECM accumulation </li></ul><ul><li>v) these cause eye to bulge outward </li></ul>
  60. 60.
  61. 61.
  62. 62. <ul><li>d) Clinical: </li></ul><ul><li>i)  T 3 and T 4 </li></ul><ul><li>ii)  TSH </li></ul><ul><li>Goiter </li></ul><ul><li>Diffuse and multinodular </li></ul><ul><li>enlargement of the thyroid </li></ul><ul><li>a) most common manifestation of thyroid disease </li></ul><ul><li>b) most often caused by dietary iodine deficiency (i.e., impaired synthesis of thyroid hormone) </li></ul><ul><li>i) compensatory rise in TSH </li></ul>
  63. 63. <ul><li>ii) hyperplasia and hypertrophy compensates for hormone deficiency (via TSH) </li></ul><ul><li>- result is euthyroid state </li></ul><ul><li>iii) if response is inadequate  goitrous hypothyroid </li></ul><ul><li>- enlargement is proportional to degree and duration of thyroid hormone deficiency </li></ul><ul><li>Diffuse nontoxic goiter </li></ul><ul><li>a) diffuse goiter without nodules </li></ul><ul><li>b) thyroid follicles filled with colloid </li></ul><ul><li>i) “colloid goiter” </li></ul>
  64. 64.
  65. 65.
  66. 66. c) two types: i) endemic ii) sporadic d) endemic goiter (<10% population) i) geographic area deficient in iodine ii) mountainous areas of world - Alps, Himalayas, Andes. iii)  TSH iv) can result from ingestion of certain “goitrogens” - cabbage, cauliflower, Brussels sprouts, turnips, cassava - excessive calcium
  67. 67. <ul><li>e) Sporadic goiter </li></ul><ul><li>i) less frequent than endemic </li></ul><ul><li>ii) female preponderance </li></ul><ul><li>iii) peak incidence near puberty </li></ul><ul><li>Multinodular goiter </li></ul><ul><li>a) recurrent hyperplasia/hypertrophy </li></ul><ul><li>b) all simple nontoxic goiters evolve into multinodular goiters </li></ul><ul><li>c) produce the most extreme thyroid enlargements </li></ul><ul><li>i) often mistaken for neoplasm </li></ul><ul><li>d) asymmetrically enlarged thyroid </li></ul>
  68. 68. <ul><li>e) small % of patients may develop a hyperfunctioning thyroid (nodule) resulting in a “toxic multinodular goiter” </li></ul><ul><li>i) Plummer syndrome is example </li></ul><ul><li>- without dermopathy nor ophthalmopathy (as in Graves) </li></ul><ul><li>all goiters may cause “Mass Effects” </li></ul><ul><ul><li>a) dysphagia </li></ul></ul><ul><ul><li>b) compression of large vessels </li></ul></ul><ul><ul><li>c) airway obstruction </li></ul></ul>
  69. 69.
  70. 70.
  71. 71. <ul><li>Thyroid Neoplasms </li></ul><ul><li>Adenomas </li></ul><ul><li>discrete solitary masses </li></ul><ul><li>derived from follicular epithelium (i.e., </li></ul><ul><li>“ follicular adenomas”) </li></ul><ul><li>a) difficult to differentiate from a dominant nodule of follicular hyperplasia </li></ul><ul><li>b) NOT predecessors of malignancy </li></ul><ul><li>c) mostly nonfunctional </li></ul><ul><li>i) small % produce hormones (thyrotoxicosis) </li></ul><ul><li>ii) hormones independent of TSH </li></ul><ul><li> (thyroid “autonomy”). Similar </li></ul><ul><li> to multinodular toxic goiter </li></ul>
  72. 72. <ul><li>Pathogenesis: </li></ul><ul><li>a) toxic adenoma </li></ul><ul><li>i) TSH receptor pathway is important signaling for hormone production </li></ul><ul><li>- overproduction of cAMP </li></ul><ul><li>ii) “hot” nodules   iodine uptake </li></ul><ul><li>b) usually present as unilateral painless mass </li></ul><ul><li>c) take up less radioactive iodine compared to normal thyroid parenchymal cells </li></ul><ul><li>i) “cold” nodules </li></ul><ul><li>ii ) ~10% of cold nodules  malignant </li></ul><ul><li>iii) “hot” nodules rarely  malignant </li></ul><ul><li>d) biopsy is “gold” standard for diagnosis </li></ul>
  73. 73.
  74. 74. <ul><li>e) do not recur nor metastasize </li></ul><ul><li>other benign tumors </li></ul><ul><li>a ) cysts </li></ul><ul><li>i) usually represent cystic degeneration of thyroid follicular adenoma </li></ul><ul><li>b) lipomas </li></ul><ul><li>c) hemangiomas </li></ul><ul><li>d) dermoid cysts </li></ul><ul><li>e) teratomas (mainly in infants) </li></ul>
  75. 75. <ul><li>Thyroid Cancer typically appears as a &quot;cold nodule&quot;. That is to say, it appears as a white area or defect in an otherwise black thyroid. A &quot;cold&quot; area is NOT necessarily cancer. Indeed, most &quot;cold nodules&quot; are benign! Ultrasound, perhaps followed by biopsy, often plays an important role in differentiation </li></ul>
  76. 76. <ul><li>Thyroid Carcinomas </li></ul><ul><li>relatively uncommon in USA </li></ul><ul><li>most appear in adults </li></ul><ul><li>a) papillary CA may present in childhood </li></ul><ul><li>female predominance (early and middle </li></ul><ul><li>adult) </li></ul><ul><li>a) childhood and late adulthood have equal </li></ul><ul><li> gender distribution </li></ul><ul><li>most CA are well differentiated : </li></ul><ul><li>a) papillary CA (~80% of cases) </li></ul><ul><li>b) follicular CA ( ~15% of cases) </li></ul><ul><li>c) medullary CA (~5% of cases) </li></ul><ul><li>d) anaplastic CA (< 5% of cases) </li></ul>
  77. 77. <ul><li>genetic and environmental factors implicated </li></ul><ul><li>a) genetic factors seen in both familial and nonfamilial (sporadic) forms of CA </li></ul><ul><li>i) familial medullary CA  most inherited of thyroid CA </li></ul><ul><li>ii) papillary and follicular familial CA are very rare !! </li></ul><ul><li>b) exposure to ionizing radiation during first 2 decades of life is one of the most important factors predisposing one to thyroid cancer </li></ul>
  78. 78. i) in past, radiation of head and neck in children for a variety of problems has led to ~ 10% developing thyroid carcinoma ii) atomic bomb survivors as well as those survivors following Chernobyl incident have  thyroid carcinoma - type is papillary carcinoma c) pre-existing thyroid disease i) multi-nodular goiter have  predisposition to develop carcinoma due to areas of  iodine - type is follicular carcinoma
  79. 79. <ul><li>Papillary Carcinoma a) most common of thyroid carcinoma b) any age c) vast majority of carcinoma associated with ionizing radiation exposure d) solitary or multi-focal nodules e) are non-functional tumors i) painless masses ii) within thyroid or metastasis to cervical lymph nodes </li></ul>
  80. 80. <ul><li>Follicular Carcinoma a) second most common form of thyroid carcinoma b)  incidence in areas of dietary iodine deficiency c) do not arise from pre-existing adenomas d) present most often as solitary nodules with no iodine uptake (“cold nodules”) e) metastasize via blood to lungs, bone and liver f) unlike papillary carcinoma, regional nodal involvement is uncommon </li></ul>
  81. 81. <ul><li>Medullary Carcinoma a) secrete calcitonin from “C” cells i) calcitonin important diagnostic measurement as well as a follow-up following treatment b) may arise as solitary nodule or multiple lesions c) ”C” cell hyperplasia </li></ul><ul><li>Anaplastic Carcinoma a) most aggressive thyroid neoplasms b) predominantly in elderly patients i) areas with endemic goiter c) death in < 1 year ( compromise of neck) d) distant metastasis is common </li></ul>