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thyroid medicine-1.pdf

  1. 1. THYROID GLAND And THYROID GLAND And Diseases Of Thyroid Gland Diseases Of Thyroid Gland Thomas Leteipa Thomas Leteipa MCMFamily med, MCMFamily med, bsc clinmed,dip bsc clinmed,dip clinmed clinmed
  2. 2. Thyroid gland Thyroid gland         The thyroid gland is one of the The thyroid gland is one of the largest endocrine glands. largest endocrine glands. The thyroid gland is located The thyroid gland is located immediately below the larynx immediately below the larynx and anterior to the upper part of and anterior to the upper part of the trachea. It weighs about 15- the trachea. It weighs about 15- 20g. 20g. It consists of 2 lateral lobes It consists of 2 lateral lobes connected by a narrow band of connected by a narrow band of thyroid tissue called the isthmus. thyroid tissue called the isthmus. The isthmus usually overlies the The isthmus usually overlies the region region from the 2 from the 2nd nd to 4 to 4th th tracheal cartilage. tracheal cartilage.
  3. 3.             4 tiny parathyroid glands located 4 tiny parathyroid glands located posteriorly at each pole of posteriorly at each pole of thyroid gland. thyroid gland. Hormone secreted- Hormone secreted- Thyroxine(T4) Thyroxine(T4) Tri iodothyronine (T3) Tri iodothyronine (T3) Reverse T3 Reverse T3 Calcitonin Calcitonin
  4. 4. HISTOLOGY HISTOLOGY       The lobes of the thyroid The lobes of the thyroid contain many hollow, contain many hollow, spherical structure called spherical structure called follicles, which are the follicles, which are the functional units of the functional units of the thyroid gland. thyroid gland. Between the follicles there Between the follicles there are C cells, which secrete are C cells, which secrete calcitonin. calcitonin. Each follicle is filled with a Each follicle is filled with a thick sticky substance thick sticky substance called colloid. called colloid.
  5. 5.     The major constituent of colloid is a The major constituent of colloid is a large glycoprotein called thyroglobulin. large glycoprotein called thyroglobulin. Unlike other endocrine glands, which Unlike other endocrine glands, which secretes their hormones once they secretes their hormones once they are produced, the thyroid gland stores are produced, the thyroid gland stores considerable amount of the thyroid considerable amount of the thyroid hormones in the colloid until they are hormones in the colloid until they are needed by the body. needed by the body.
  6. 6. Iodine Iodine Metabolism Metabolism             Raw material, essential for thyroid Raw material, essential for thyroid synthesis synthesis Source- Source- Sea foods, milk, iodized salt. Sea foods, milk, iodized salt. Daily req- 100-200 microgram/day Daily req- 100-200 microgram/day From the total amount of Iodine From the total amount of Iodine entering the ECF, entering the ECF, 20% enters the 20% enters the thyroid gland and 80% excreted in urine. thyroid gland and 80% excreted in urine. Thyroid contain 95% of total iodine Thyroid contain 95% of total iodine content of body. content of body.
  7. 7.           Thyroid gland stores enough Thyroid gland stores enough hormone to maintain euthyroid state hormone to maintain euthyroid state for 3 months. for 3 months. Daily secretion- Daily secretion- 93% 93%Thyroxine (3-8 mgm/dl) Thyroxine (3-8 mgm/dl) 7% 7% T3(0.15 mgm/dl) T3(0.15 mgm/dl) T3 is 4 times more potent than T4 T3 is 4 times more potent than T4
  8. 8. REGULATION OF THYROID REGULATION OF THYROID HORMONE SECRETION HORMONE SECRETION • • • • • • Thyrotropin Releasing Hormone Thyrotropin Releasing Hormone (TRH) (TRH) A tripeptide: pyro-Glutamate- A tripeptide: pyro-Glutamate- histidine-proline-amide histidine-proline-amide Synthesized from a 29 kDa Synthesized from a 29 kDa precursor protein precursor protein Produced by hypothalamus Produced by hypothalamus Thyrotropin (TSH; Thyroid Thyrotropin (TSH; Thyroid Stimulating Hormone) Stimulating Hormone) 28 kDa glycoprotein dimer 28 kDa glycoprotein dimer composed of alpha and beta chains. composed of alpha and beta chains.
  9. 9. Autoregulatio Autoregulatio n n                 Depending upon the body Iodine Depending upon the body Iodine availability- availability- ↑ ↑ Iodine Iodine ingestion- Thyroid gland ingestion- Thyroid gland depressed depressed ↓ ↓ Iodine Iodine ingestion- Hyperactive ingestion- Hyperactive High dose of iodine High dose of iodine ↓ ↓ the formation the formation and release of thyroid hormone, and release of thyroid hormone, called called Wolff Chaikoff effect. Wolff Chaikoff effect. Done by- Done by- ↓ ↓ iodine trapping iodine trapping Preventing oxidation of Iodide to Preventing oxidation of Iodide to iodine. iodine. Preventing incorporation of iodine to Preventing incorporation of iodine to
  10. 10. SYNTHESIS, STORAGE & SYNTHESIS, STORAGE & SECRETION SECRETION               Iodine trapping Iodine trapping Synthesis and secretion of Synthesis and secretion of thyroglobulin thyroglobulin Oxidation of iodine Oxidation of iodine Organification of Organification of thyroglobulin thyroglobulin Coupling reaction Coupling reaction Storage Storage Secretion Secretion
  11. 11. Iodide Iodide trapping trapping             Plasma iodide enters through the Plasma iodide enters through the sodium iodide symporter (NIS) at the sodium iodide symporter (NIS) at the baso lateral membrane of thyrocyte baso lateral membrane of thyrocyte facing the capillaries. facing the capillaries. It transport 2 Na+, It transport 2 Na+,1 1 I- into cell, against I- into cell, against electrochemical gradient. electrochemical gradient. Energy given- Na+ K+ ATPase pump Energy given- Na+ K+ ATPase pump Process- secondary active transport Process- secondary active transport TSH promote this uptake. TSH promote this uptake. Anti thyroid drugs- Thiocynate, Anti thyroid drugs- Thiocynate, Perchlorate inhibit this Perchlorate inhibit this
  12. 12. Synthesis and Secretion of Synthesis and Secretion of Thyroglobulins Thyroglobulins       •Thyroglobulin (Tg), a large glycoprotein, •Thyroglobulin (Tg), a large glycoprotein, is synthesized within the thyroid cell by is synthesized within the thyroid cell by RE Reticulum, then modified in Golgi RE Reticulum, then modified in Golgi Apparatus and packed into secretary Apparatus and packed into secretary vesicle. vesicle. Tg released in the lumen by exocytosis. Tg released in the lumen by exocytosis. Each molecule of Tg- 123 tyrosine Each molecule of Tg- 123 tyrosine residue, which serve as subtract for residue, which serve as subtract for iodine for synthesis of hormone. iodine for synthesis of hormone.
  13. 13. Oxidation of Oxidation of iodine iodine         Once within the gland, iodide rapidly moves Once within the gland, iodide rapidly moves to apical surface of epithelial cell. to apical surface of epithelial cell. From there ,it is transported into the lumen From there ,it is transported into the lumen of follicle by Chloride Iodide ion counter of follicle by Chloride Iodide ion counter transporter Pendrin. transporter Pendrin. Thyroid peroxidase (TPO) sits on the luminal Thyroid peroxidase (TPO) sits on the luminal membrane. Iodide ion immediately oxidized membrane. Iodide ion immediately oxidized into iodine by TPO and its accompanying into iodine by TPO and its accompanying H2O2. H2O2. Anti thyroid drugs- Thiouracil,Methemazole Anti thyroid drugs- Thiouracil,Methemazole inhibit this conversion. inhibit this conversion.
  14. 14. Organification of Organification of thyroglobulin thyroglobulin         Binding of iodine with Tg molecule Binding of iodine with Tg molecule Oxidized iodine bind directly with Oxidized iodine bind directly with tyrosine. tyrosine. After release Tg into lumen, Iodine After release Tg into lumen, Iodine binds about 1/6 th tyrosine residue binds about 1/6 th tyrosine residue in Tg. in Tg. Iodinates specific tyrosines in Tg, Iodinates specific tyrosines in Tg, creating mono-and di-iodotyrosines. creating mono-and di-iodotyrosines.
  15. 15. Coupling reaction Coupling reaction           •The iodotyrosines combine to form •The iodotyrosines combine to form T3 and T4 within the Tg protein. T3 and T4 within the Tg protein. TPO(thyroid peroxidase) both involve TPO(thyroid peroxidase) both involve in iodination and coupling reaction. in iodination and coupling reaction. MIT+ DIT MIT+ DIT T3 T3 DIT+ DIT DIT+ DIT T4 T4 DIT+MIT DIT+MIT reverse T3 reverse T3
  16. 16. Storage Storage     MIT, DIT, T3,T4 are all in peptide MIT, DIT, T3,T4 are all in peptide linkage with Tg which occurs as a linkage with Tg which occurs as a colloidal aggregate with in the colloidal aggregate with in the follicle. follicle. Store is sufficient to supply for 2-3 Store is sufficient to supply for 2-3 months. months.
  17. 17. Secretion Secretion           Tg itself is not release into circulation. Tg itself is not release into circulation. T3,T4 must cleaved from Tg and release. T3,T4 must cleaved from Tg and release. The apical surface of thyroid cells send The apical surface of thyroid cells send pseudopodia which close around small pseudopodia which close around small portion of colloid to form pinocytic portion of colloid to form pinocytic vesicle that enter apex of thyroid cell by vesicle that enter apex of thyroid cell by endocytosis. endocytosis. Endocytosis facilitated by Tg receptor Endocytosis facilitated by Tg receptor Megalin on apical membrane. Megalin on apical membrane. Lysosome fuse with this vesicle to form Lysosome fuse with this vesicle to form digestive vesicle. digestive vesicle.
  18. 18.         Protease digest the Tg molecule Protease digest the Tg molecule releasing MIT, DIT, T3,T4 releasing MIT, DIT, T3,T4 As T3, T4 lipid soluble,they diffuse As T3, T4 lipid soluble,they diffuse through plasma membrane into through plasma membrane into interstitial fluid then into blood. interstitial fluid then into blood. MIT, DIT rapidly deiodinated in MIT, DIT rapidly deiodinated in follicular cell by the enzyme follicular cell by the enzyme Iodotyrosine deiodinase. Iodotyrosine deiodinase. Iodine is reutilized to produce Iodine is reutilized to produce thyroid hormone. thyroid hormone.
  19. 19.       In patient with congenital absence of In patient with congenital absence of deiodinase enzyme MIT, DIT appear in deiodinase enzyme MIT, DIT appear in urine and there are symptoms of iodine urine and there are symptoms of iodine deficiency. deficiency. Salivary gland, gastric mucosa,placenta, Salivary gland, gastric mucosa,placenta, cilliary body of eye,choroid plexus, cilliary body of eye,choroid plexus, mammary gland, post pitutary and mammary gland, post pitutary and adreanal cortex also transport iodide. adreanal cortex also transport iodide. There uptake are not dependent by TSH There uptake are not dependent by TSH and they can't form thyroid hormone. and they can't form thyroid hormone.
  20. 20. Plasma thyroid hormone binding Plasma thyroid hormone binding proteins proteins           ~99.97% of plasma T4 and 99.7% of T3 ~99.97% of plasma T4 and 99.7% of T3 are non-covalently bound to proteins. are non-covalently bound to proteins. Thyroxine Binding Globulin(TBG) is the Thyroxine Binding Globulin(TBG) is the major binding protein for T4 and T3. TBG’s major binding protein for T4 and T3. TBG’s affinity for T4 is ~10-fold greater than for affinity for T4 is ~10-fold greater than for T3. T3. Transthyretin also carries some T4. Transthyretin also carries some T4. Albumin carries small amounts of T4 and Albumin carries small amounts of T4 and T3. T3. TBG, transthyretin and albumin are made TBG, transthyretin and albumin are made
  21. 21. Importance of free Importance of free versus protein-bound versus protein-bound hormone hormone           Only free T4 and free T3 are Only free T4 and free T3 are biologically active and regulated by biologically active and regulated by feedback loops. feedback loops. Therefore conditions that alter TBG Therefore conditions that alter TBG levels alter total T4 and T3, but do not levels alter total T4 and T3, but do not alter free T4 and free T3. alter free T4 and free T3. Pregnancy Pregnancy Acute hepatitis Acute hepatitis Chronic liver failure Chronic liver failure
  22. 22. PHYSIOLOGICAL EFFECTS OF PHYSIOLOGICAL EFFECTS OF THYROID HORMONES THYROID HORMONES   ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦   ◦ ◦ Metabolic rate and heat production: Metabolic rate and heat production: ↑ ↑ metabolic activities metabolic activities ↑ ↑ O O₂ ₂ consumption to most metabolically consumption to most metabolically active tissues active tissues BMR can BMR can ↑ ↑ by 60 – 100% by 60 – 100% Since Since ↑ ↑ metabolism results in metabolism results in ↑ ↑ heat heat production production → → thyroid hormone effects is thyroid hormone effects is calorigenic calorigenic Intermediary metabolism: Intermediary metabolism: Modulates rates of many specific Modulates rates of many specific reactions involved in metabolism reactions involved in metabolism
  23. 23.           Sympathomimetic effect- Sympathomimetic effect- Sympathomimetic: any action similar to one Sympathomimetic: any action similar to one produced by the sympathetic nervous produced by the sympathetic nervous system system Thyroid hormone Thyroid hormone ↑ ↑ target cell target cell responsiveness to catecholamines responsiveness to catecholamines The cardiovascular system: The cardiovascular system: ↑ ↑ the heart’s responsiveness to circulating the heart’s responsiveness to circulating catecholamines. catecholamines. ↑ ↑ heart rate and force of contraction heart rate and force of contraction → → ↑ ↑ CO CO In response to the heat load In response to the heat load → → peripheral peripheral
  24. 24. Laboratory Evaluation and Laboratory Evaluation and Imaging Studies of Imaging Studies of Thyroid Thyroid Functio Functio n n               Serum T4 Serum T4 Serum T3 Serum T3 TSH TSH Anti-thyroid antibodies Anti-thyroid antibodies Thyroid stimulating Thyroid stimulating Immunoglobulins Immunoglobulins Thyroid uptake and scan Thyroid uptake and scan Thyroid Ultra sound Thyroid Ultra sound
  25. 25. Serum Thyroxine (T4) Serum Thyroxine (T4)     ◦ ◦ ◦ ◦ ◦ ◦   Measure free T4, not total T4 Measure free T4, not total T4 Only free T4 is biologically active Only free T4 is biologically active Conditions that alter TBG alter total T4 but Conditions that alter TBG alter total T4 but not free T4 not free T4 Pregnancy raises total T4 Pregnancy raises total T4 Chronic liver failure lowers total T4 Chronic liver failure lowers total T4 •High in hyperthyroidism •High in hyperthyroidism Low in hypothyroidism Low in hypothyroidism
  26. 26. Serum Triiodothyronine (T3) Serum Triiodothyronine (T3)         High in hyperthyroidism High in hyperthyroidism •Low in hypothyroidism •Low in hypothyroidism But generally not worth measuring in But generally not worth measuring in hypothyroidism because T3 is less hypothyroidism because T3 is less sensitive and less specific than the sensitive and less specific than the decrease in free T4 decrease in free T4 •Measurement of free T3 is preferable to •Measurement of free T3 is preferable to total T3. total T3.
  27. 27. Serum Thyrotropin (Thyroid Serum Thyrotropin (Thyroid Stimulating Hormone; TSH) Stimulating Hormone; TSH)         TSH is LOW in hyperthyroidism TSH is LOW in hyperthyroidism TSH is HIGH in hypothyroidism TSH is HIGH in hypothyroidism TSH is the most sensitive screening TSH is the most sensitive screening test for hyperthyroidism and primary test for hyperthyroidism and primary hypothyroidism hypothyroidism TSH within the normal range excludes TSH within the normal range excludes these diagnoses these diagnoses
  28. 28. Antithyroid Antithyroid Antibodies Antibodies         Antimicrosomal antibodies ( Antimicrosomal antibodies (thyroid thyroid peroxidase antibodies) peroxidase antibodies) •Anti-thyroglobulin antibodies •Anti-thyroglobulin antibodies •Present in ~95% of Hashimoto’s and •Present in ~95% of Hashimoto’s and ~60% of Graves’ patients at the time ~60% of Graves’ patients at the time of diagnosis of diagnosis •Usually not very helpful in making a •Usually not very helpful in making a diagnosis or guiding therapy diagnosis or guiding therapy
  29. 29. Thyroid Stimulating Thyroid Stimulating Immunoglobulins Immunoglobulins  Is present in Graves’ disease Is present in Graves’ disease
  30. 30. Imaging Imaging studies studies       Thyroid uptake and scan Thyroid uptake and scan •Thyroid US •Thyroid US •Neck CT •Neck CT
  31. 31. Thyroid uptake and scan Thyroid uptake and scan                   I-123 I-123 I-131 I-131 Technetium 99 Technetium 99 *Radiotracer: *Radiotracer: Injectable IV: Technetium (15 Injectable IV: Technetium (15 min later: scan) min later: scan) Oral: 131 I and 123 I;(24 h Oral: 131 I and 123 I;(24 h later: scan/uptake) later: scan/uptake) Scan: structure Scan: structure Uptake: function Uptake: function Obtain pregnancy test before Obtain pregnancy test before the test the test
  32. 32. Radioiodine Uptake Radioiodine Uptake           Used to evaluate the cause of Used to evaluate the cause of hyperthyroidism hyperthyroidism High if the thyroid is hyper-functioning, High if the thyroid is hyper-functioning, e.g. e.g. Graves’ disease Graves’ disease Low if thyroid hormone is leaking out of Low if thyroid hormone is leaking out of damaged thyroid cells (subacute thyroiditis) damaged thyroid cells (subacute thyroiditis) or the patient is taking excess exogenous or the patient is taking excess exogenous thyroid hormone thyroid hormone Expressed as a Expressed as a NUMBER(e.g., 35%) NUMBER(e.g., 35%) Used to calculate the dose of I-131 to treat Used to calculate the dose of I-131 to treat hyper-functioning thyroid tissue or cancer. hyper-functioning thyroid tissue or cancer.
  33. 33. Thyroid Scan (nuclear Thyroid Scan (nuclear medicine) medicine)         Primary use is to Primary use is to determine whether determine whether palpated nodules are palpated nodules are functional or non- functional or non- functional. functional. “Hot” nodules concentrate “Hot” nodules concentrate the radionuclide and are the radionuclide and are essentially always benign. essentially always benign. “Cold” nodules are usually “Cold” nodules are usually benign but are sometimes benign but are sometimes malignant. malignant. The majority, perhaps The majority, perhaps 90%, of palpable nodules 90%, of palpable nodules are cold. are cold.
  34. 34. Thyroid Ultra Thyroid Ultra       Sonography Sonography Painless, quick, no Painless, quick, no contrast material, no contrast material, no radiation radiation Can be used in Can be used in pregnancy, while on L- pregnancy, while on L- thyroxine therapy, after thyroxine therapy, after exogenous iodine exogenous iodine exposure exposure Can detect thyroid Can detect thyroid nodules as small as 2-3 nodules as small as 2-3 mm and provide mm and provide guidance for FNA biops guidance for FNA biopsy y
  35. 35. Indications for thyroid Indications for thyroid US US             Goiter Goiter If thyroid gland is normal on If thyroid gland is normal on physical exam: physical exam: External radiation during childhood External radiation during childhood History of familial thyroid cancer History of familial thyroid cancer Lymph node metastases Lymph node metastases Prior to parathyroid surgery Prior to parathyroid surgery
  36. 36. Diseases Of Thyroid Diseases Of Thyroid Gland Gland               DIVIDED INTO: DIVIDED INTO: HYPOTHYROIDISM HYPOTHYROIDISM (Gland destruction) (Gland destruction) Under-production of thyroid Under-production of thyroid hormones hormones Myxoedema (Gull Disease) Myxoedema (Gull Disease) Cretinism Cretinism Thyroiditis Thyroiditis HYPERTHYROIDISM HYPERTHYROIDISM (thyrotoxicosis) (thyrotoxicosis) Over-production of thyroid hormone Over-production of thyroid hormone Grave’s Disease Grave’s Disease Thyrotoxicosis Thyrotoxicosis GOITER- GOITER- Diffuse and multi-nodular Diffuse and multi-nodular NEOPLASTIC PROCESSES NEOPLASTIC PROCESSES Beningn Beningn Malignant Malignant
  37. 37. Hypothyroidism Hypothyroidism Resulting from reduced circulating level of T3 Resulting from reduced circulating level of T3 and T4 and T4
  38. 38. Causes of Causes of Hypothyroidism Hypothyroidism ◦ ◦ 1. 1. 2. 2. 3. 3. 4. 4. 5. 5. 6. 6. 7. 7. ◦ ◦ Primary Primary Dietary Iodide deficiency Dietary Iodide deficiency Iodine defficiency Iodine defficiency Autoimmune (Hashimoto´s Thyroiditis) Autoimmune (Hashimoto´s Thyroiditis) Drugs: amiodarone, lithium, thiocyanates, phenylbutazone, Drugs: amiodarone, lithium, thiocyanates, phenylbutazone, sulfonylureas sulfonylureas Iatrogenic- Surgical removal of the thyroid gland and radiation Iatrogenic- Surgical removal of the thyroid gland and radiation treatment treatment Congenital (1 in 3000 to 4000) Congenital (1 in 3000 to 4000) Infiltrative disorders Infiltrative disorders Secondary Secondary Pituitary gland destruction Pituitary gland destruction Isolated TSH deficiency Isolated TSH deficiency Bexarotene(anti cancer drug) treatment Bexarotene(anti cancer drug) treatment Hypothalamic disorders Hypothalamic disorders
  39. 39.         Hypothyroidism appears in 3 Hypothyroidism appears in 3 forms- forms- 1. Myxoedema (Gull Disease) 1. Myxoedema (Gull Disease) 2. Cretinism 2. Cretinism 3. Thyroiditis 3. Thyroiditis
  40. 40. Myxoedema (Gull Myxoedema (Gull Disease) Disease)                             hypothyroidism developing in adults, hypothyroidism developing in adults, deposition of excess mucoprotein in skin of deposition of excess mucoprotein in skin of forearm, forearm, Leg, feet Leg, feet Features- Features- Enlargement of thyroid gland (Goiter) Enlargement of thyroid gland (Goiter) Lack of interest in daily household chores. Lack of interest in daily household chores. slowing of physical and mental activity slowing of physical and mental activity generalized fatigue, dull look generalized fatigue, dull look apathy apathy overweight overweight CO CO - - shortness of breath shortness of breath - - exercise capacity exercise capacity Sympathetic activity Sympathetic activity - - constipation constipation - sweating - sweating
  41. 41.                                 Skin Skin-dry, thicken, yellow(carotinemia), cool ( blood flow) -dry, thicken, yellow(carotinemia), cool ( blood flow) edema, puffy face, periorbital swelling. edema, puffy face, periorbital swelling. Ptosis ( drooping of upper eyelid) Ptosis ( drooping of upper eyelid) coarse hair coarse hair broadening of facial features broadening of facial features enlarged tongue enlarged tongue deepening of voice (telephonic voice) deepening of voice (telephonic voice) Calorigenic action- Calorigenic action- BMR decreases to 30-40% BMR decreases to 30-40% cold-intolerant cold-intolerant Bone marrow- Bone marrow- anemia ( normocytic, normochromic) anemia ( normocytic, normochromic) Menstrual irregularities Menstrual irregularities Carbohydrate metabolism- Carbohydrate metabolism- Low blood sugar Low blood sugar Lipid metabolism- Lipid metabolism- Increased serum Cholesterols, TGs, Increased serum Cholesterols, TGs, phospholipids phospholipids CNS CNS- Myxedematous madness (psychosis) - Myxedematous madness (psychosis) Knee jerk reaction time increased Knee jerk reaction time increased Memory loss Memory loss
  42. 42. Cretinis Cretinis m m           hypothyroidism developing hypothyroidism developing in infancy/early childhood, due to in infancy/early childhood, due to maternal iodine deficiency. maternal iodine deficiency. Listless, somnolent, apathetic to play, Listless, somnolent, apathetic to play, devoid of initiatives. devoid of initiatives. Features- Features- Severe mental retardation (imbeciles- Severe mental retardation (imbeciles- IQ-25- 49) IQ-25- 49) Occurs in iodine deficient areas of world Occurs in iodine deficient areas of world (i.e. Himalayas, China, Africa) (i.e. Himalayas, China, Africa)
  43. 43.                     Clinical- Clinical- Impaired skeletal development Impaired skeletal development Impaired CNS development Impaired CNS development Inadequate maternal thyroid hormone prior to fetal thyroid Inadequate maternal thyroid hormone prior to fetal thyroid gland gland formation severe mental retardation formation severe mental retardation Often deaf and mute Often deaf and mute Dwarfism and stunted growth Dwarfism and stunted growth Thick, coars, dry skin Thick, coars, dry skin Protruded abdomen (pot belly-Splanchnomegaly) and Protruded abdomen (pot belly-Splanchnomegaly) and enlarged enlarged tongue tongue Failure of sexual developments Failure of sexual developments Delayed milestones- Delayed milestones- Length of the child fails to increase Length of the child fails to increase Dentition is delayed Dentition is delayed Delayed sitting up and head holding Delayed sitting up and head holding Delayed walking Delayed walking Delayed closure of ant fontanels Delayed closure of ant fontanels Delayed standing up and speech Delayed standing up and speech
  44. 44.       On the left, a euthyroid On the left, a euthyroid 6 year old girl at the 6 year old girl at the 50th height percentile 50th height percentile (105 cm). (105 cm). On the right, a 17 year On the right, a 17 year old girl with a height of old girl with a height of 100 cm, mental 100 cm, mental retardation, myxedema retardation, myxedema and a TSH of 288 and a TSH of 288 (normal 0.3-5.5). (normal 0.3-5.5). (Werner & Ingbar’s The Thyroid, 8th Edition, (Werner & Ingbar’s The Thyroid, 8th Edition, page 744.) page 744.)
  45. 45. Lab Findings- Lab Findings-         Increased TSH Increased TSH Decreased free T4 Decreased free T4 Decreased FT3 Decreased FT3 Anti-TPO(ant thyroid peroxidase) and Anti-TPO(ant thyroid peroxidase) and anti-Tg Abs (Hashimoto’s) anti-Tg Abs (Hashimoto’s)
  46. 46. Hypothyroidism: Therapy Hypothyroidism: Therapy         L-Thyroxine L-Thyroxine (levothyroxine; T4) (levothyroxine; T4) Goals- Goals- Alleviate Alleviate symptoms symptoms Normalize TSH Normalize TSH
  47. 47. Thyroiditis Thyroiditis Inflammation of Inflammation of thyroid thyroid Types: Types:   a) Hashimoto a) Hashimoto thyroiditis thyroiditis 1) gradual thyroid failure due 1) gradual thyroid failure due to autoimmune destruction of thyroid to autoimmune destruction of thyroid 2) 45-65 yrs 2) 45-65 yrs 3) 10:1 female predominance 3) 10:1 female predominance 4) major cause of non endemic 4) major cause of non endemic goiter in goiter in childre childre n n 5) genetic component- patients 5) genetic component- patients with Turner syndrome have circulating with Turner syndrome have circulating anti-thyroid Ab anti-thyroid Ab
  48. 48.               Clinical: Clinical: 1) 1) progressive depletion of thyroid epithelial progressive depletion of thyroid epithelial cells cells 2) 2) replaced with mononuclear cells and replaced with mononuclear cells and fibrosis fibrosis 3) 3) comes to clinical attention as painless comes to clinical attention as painless enlargement of thyroid with some degree of enlargement of thyroid with some degree of hypothyroidism hypothyroidism 4) 4) hypothyroidism progresses slowly hypothyroidism progresses slowly 5) 5) can be preceded by “hashitoxicosis” can be preceded by “hashitoxicosis” (transient hyperthyroidism caused by (transient hyperthyroidism caused by inflammation associated with Hashimoto's inflammation associated with Hashimoto's thyroiditis thyroiditis) ) 6) 6) patients at risk in developing other patients at risk in developing other
  49. 49.   b) Subacute (granulomatous) b) Subacute (granulomatous) thyroiditis thyroiditis [“ De Quervain thyroiditis”] [“ De Quervain thyroiditis”]                 i) i) occurs less often than Hashimoto occurs less often than Hashimoto ii) ii) 30-50 yrs 30-50 yrs iii) iii) female preponderance 5:1 female preponderance 5:1 iv) iv) caused by viral infection (Coxsackie virus, caused by viral infection (Coxsackie virus, mumps and adenoviruses) mumps and adenoviruses) v) v) history of upper respiratory infection just history of upper respiratory infection just prior to onset of thyroiditis prior to onset of thyroiditis vi) vi) seasonal incidence (summer peak) seasonal incidence (summer peak) vii) vii) acute or gradual acute or gradual viii) viii) painful presentation, radiating to jaw, painful presentation, radiating to jaw, throat, ears: especially when swallowing throat, ears: especially when swallowing
  50. 50.       ix) ix) inflammation and hyperthyroidism inflammation and hyperthyroidism are transient are transient x) x) self limited disease self limited disease c) Subacute lymphocytic (painless) c) Subacute lymphocytic (painless) thyroiditis thyroiditis i) i) ii) ii) uncommon uncommon hyperthyroid presentation hyperthyroid presentation - - may present with any may present with any of signs of hyperthyroidism (no of signs of hyperthyroidism (no opthalmopathy, opthalmopathy,as in Graves disease) as in Graves disease)
  51. 51.       d) Riedel thyroiditis d) Riedel thyroiditis i) i) fibrosis of thyroid and fibrosis of thyroid and neighboring structures neighboring structures ii) ii) presents as hard and fixed presents as hard and fixed thyroid which clinically is similar to thyroid which clinically is similar to CA CA
  52. 52. Congenital Congenital Hypothyroidism Hypothyroidism       ◦ ◦ Prevalence: Prevalence: 1 in 3000 to 4000 newborns 1 in 3000 to 4000 newborns Cause: Cause: Dysgenesis Dysgenesis 85% 85% Treatment: Treatment: Supplemental treatment With Levothyroxine Supplemental treatment With Levothyroxine is “essential” for a normal C.N.S. is “essential” for a normal C.N.S. Development and prevention of mental Development and prevention of mental retardation retardation
  53. 53. Hyperthyroidism Hyperthyroidism         ◦ ◦ 1) 1) 2) 2) 3) 3) 4) 4) 5) 5) 6) 6) It is a condition resulting from increased It is a condition resulting from increased level of circulating FT4 and FT3 level of circulating FT4 and FT3 Cause- Cause- Thyrotoxicosis Thyrotoxicosis Causes of Thyrotoxicosis: Causes of Thyrotoxicosis: Primary Hyperthyroidism Primary Hyperthyroidism Grave´s disease( Exopthalmic Goiter) Grave´s disease( Exopthalmic Goiter) Toxic Multinodular Goiter Toxic Multinodular Goiter Toxic adenoma Toxic adenoma Functioning thyroid carcinoma metastases Functioning thyroid carcinoma metastases Activating mutation of TSH receptor Activating mutation of TSH receptor Drugs: Iodine excess Drugs: Iodine excess
  54. 54. Graves Graves disease disease                   Most common cause of endogenous Most common cause of endogenous hyperthyroidism hyperthyroidism Characteristics: Characteristics: a) hyperthyroidism a) hyperthyroidism i) diffuse enlargement of i) diffuse enlargement of thyroid thyroid ii) lymphocytic infiltration ii) lymphocytic infiltration b) infiltrative ophthalmopathy b) infiltrative ophthalmopathy i) with resultant i) with resultant exophthalmos exophthalmos c) localized infiltrative dermopathy c) localized infiltrative dermopathy i) “pretibial myxedema” i) “pretibial myxedema”
  55. 55.             peak incidence 20-40 peak incidence 20-40 female preponderance (7:1) female preponderance (7:1) familial link familial link Pathogenesis: Pathogenesis: a) autoimmune disorder a) autoimmune disorder b)Thyroid stimulating b)Thyroid stimulating Ab (Long acting Ab (Long acting thyroid stimulator) action like TSH thyroid stimulator) action like TSH c)LATS (long acting thyroid c)LATS (long acting thyroid stimulator)protectors- prevent inactivation stimulator)protectors- prevent inactivation of LATS of LATS           LATS combine with receptors on thyroid cells LATS combine with receptors on thyroid cells plasma membrane and displace TSH from its plasma membrane and displace TSH from its binding sites. binding sites. Act via cAMP to cause prolonged action. Act via cAMP to cause prolonged action. Leads to- Leads to- Increased formation and release of T3,T4 Increased formation and release of T3,T4 Increased growth of thyroid gland Increased growth of thyroid gland
  56. 56. Feature Feature s s         Exopthalmos- Exopthalmos- Protrusion of the eye ball with visibility of sclera Protrusion of the eye ball with visibility of sclera between lower lid and cornea. between lower lid and cornea. Due to- Due to- retro-orbital connective tissue and ocular retro-orbital connective tissue and ocular muscles are increased muscles are increased   ii) ii) iii) iii) iv) iv) v) v) i) inflammatory edema (cytokines i) inflammatory edema (cytokines induced) induced) T-cell infiltration T-cell infiltration fatty infiltration fatty infiltration mucopolysaccharide and water mucopolysaccharide and water accumulation accumulation these cause eye to bulge outward these cause eye to bulge outward
  57. 57.                           Lid retraction- Lid retraction- Visibility of sclera between upper lid and cornea Visibility of sclera between upper lid and cornea Due to overstimulation of levator palpebrae Due to overstimulation of levator palpebrae superiosis superiosis Calorigenic action- Calorigenic action- BMR BMR ↑ ↑ 30%-100% 30%-100% Heat intolerance Heat intolerance Weight loss (thyrotoxic myopathy) Weight loss (thyrotoxic myopathy) Lactation Lactation ↑ ↑ Scanty periods Scanty periods Vitamine B & C deficiency Vitamine B & C deficiency CVS CVS- tachycardia, high output cardiac failure - tachycardia, high output cardiac failure Thyroid diabetes Thyroid diabetes Decreased serum lipid levels Decreased serum lipid levels
  58. 58.                 CNS CNS- overexcitibility, tremors,irritability, - overexcitibility, tremors,irritability, nervousness nervousness Smooth, moist, warm skin Smooth, moist, warm skin Flushing of face and hands Flushing of face and hands Overgrown nails ( Overgrown nails (acropachy acropachy), which may lift ), which may lift off the nail bed ( off the nail bed (onycholysis onycholysis) ) Fine soft thinned scalp hair Fine soft thinned scalp hair Generalized itching ( Generalized itching (pruritus pruritus) ) Increased skin pigmentation Increased skin pigmentation “ “Pretibial myxedema Pretibial myxedema” ”
  59. 59. Thyrotoxicosi Thyrotoxicosi s s   ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Symptoms: Symptoms: Hyperactivity Hyperactivity Irritability Irritability Dysphoria Dysphoria Heat intolerance & sweating Heat intolerance & sweating Palpitations Palpitations Fatigue & weakness Fatigue & weakness Weight loss with increased Weight loss with increased appetite appetite Diarrhea Diarrhea Polyuria Polyuria Sexual dysfunction Sexual dysfunction
  60. 60.   ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ Signs: Signs: Tachycardia Tachycardia Atrial fibrillation Atrial fibrillation Tremor Tremor Goiter Goiter Warm, moist skin Warm, moist skin Muscle weakness, Muscle weakness, myopathy myopathy Lid retraction or lag Lid retraction or lag Gynecomastia Gynecomastia * Exophtalmus * Exophtalmus * Pretibial myxedema * Pretibial myxedema
  61. 61. Lab findings- Lab findings-       Suppressed Suppressed TSH TSH Elevated Free Elevated Free T4 T4 Elevated Free Elevated Free T3 T3
  62. 62. Treatment: Treatment: ◦ ◦ ◦ ◦ ◦ ◦ Reducing thyroid hormone synthesis: Reducing thyroid hormone synthesis: Antithyroid drugs (Methimazole, Antithyroid drugs (Methimazole, Propylthyouracil) Propylthyouracil) Radioiodine ( Radioiodine (131 131I) I) Subtotal thyroidectomy Subtotal thyroidectomy Reducing Thyroid hormone effects: Reducing Thyroid hormone effects: Propranolol Propranolol Glucocorticoids Glucocorticoids Benzodiazepines Benzodiazepines Reducing peripheral conversion of T4 to T3 Reducing peripheral conversion of T4 to T3 Propylthyouracil Propylthyouracil Glucocorticoids Glucocorticoids Iodide Iodide
  63. 63. Thyrotoxic crisis or Thyroid storm: Thyrotoxic crisis or Thyroid storm: It´s a life-threatening exacerbation of It´s a life-threatening exacerbation of thyrotoxicosis, acompanied by fever, delirium, thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. seizures, coma, vomiting, diarrhea, jaundice. Mortality rate reachs 30% even with treatment Mortality rate reachs 30% even with treatment It´s usually precipitated by acute illness, such as: It´s usually precipitated by acute illness, such as: Stroke, infection,trauma, diabeic ketoacidosis, Stroke, infection,trauma, diabeic ketoacidosis, surgery, radioiodine treatment surgery, radioiodine treatment
  64. 64.       Thyroid storm Thyroid storm i) abrupt onset of severe i) abrupt onset of severe hyperthyroidism hyperthyroidism ii) febrile, tachycardia ii) febrile, tachycardia iii) is a medical emergency iii) is a medical emergency - death from cardiac arrhythmias - death from cardiac arrhythmias
  65. 65. Goiter Goiter         Diffuse and multinodular Diffuse and multinodular enlargement of the thyroid enlargement of the thyroid most common manifestation of most common manifestation of thyroid disease thyroid disease most often caused by dietary most often caused by dietary iodine deficiency (i.e., impaired iodine deficiency (i.e., impaired synthesis of thyroid hormone) synthesis of thyroid hormone)
  66. 66.   Two types: Two types: i) i) ii) ii) endemi endemi c c sporadi sporadi c c i) i) ii) ii) iii) iii) geographic area deficient in geographic area deficient in iodine iodine mountainous areas of world mountainous areas of world - Himalayas, Andes,Alps - Himalayas, Andes,Alps TSH TSH   Endemic goiter Endemic goiter (<10% (<10% population) population) iv) can result from ingestion of iv) can result from ingestion of certain certain     “ “goitrogens goitrogens”- cabbage, cauliflower, Brussels,sprouts, turnips, ”- cabbage, cauliflower, Brussels,sprouts, turnips, cassava cassava Contain Progoitrin/ Progoitrin activator( anti thyroid agent) Contain Progoitrin/ Progoitrin activator( anti thyroid agent) Prevent incorporation of iodine with Prevent incorporation of iodine with tyrosine. tyrosine.
  67. 67.   Sporadic Sporadic goiter goiter i) i) ii) ii) iii) iii) less frequent than less frequent than endemic endemic female preponderance female preponderance peak incidence near peak incidence near puberty puberty • •         Multinodular goiter Multinodular goiter a) recurrent hyperplasia/ a) recurrent hyperplasia/ hypertrophy hypertrophy b) all simple nontoxic goiters evolve b) all simple nontoxic goiters evolve into multinodular goiters into multinodular goiters c) produce the most extreme c) produce the most extreme thyroid enlargements, often thyroid enlargements, often mistaken for mistaken for neoplasm neoplasm d) asymmetrically enlarged d) asymmetrically enlarged thyroid thyroid
  68. 68.     • • ◦ ◦ ◦ ◦ ◦ ◦ small % of patients may develop a small % of patients may develop a hyperfunctioning thyroid (nodule) hyperfunctioning thyroid (nodule) resulting in a “toxic multinodular resulting in a “toxic multinodular goiter” goiter” Plummer syndrome is example Plummer syndrome is example without dermopathy, nor- without dermopathy, nor- ophthalmopathy (as in Graves) ophthalmopathy (as in Graves) All goiters may cause “Mass Effects” All goiters may cause “Mass Effects” a) dysphagia a) dysphagia b) compression of large vessels b) compression of large vessels c) airway obstruction c) airway obstruction
  69. 69. Thyroid Thyroid Neoplasms Neoplasms       Adenomas Adenomas discrete solitary masses discrete solitary masses derived from follicular epithelium (i. derived from follicular epithelium (i. e., “follicular adenomas”) e., “follicular adenomas”) NOT transform into malignancy NOT transform into malignancy
  70. 70.     Usually present as unilateral painless Usually present as unilateral painless mass mass Take up less radioactive iodine Take up less radioactive iodine compared to normal thyroid compared to normal thyroid parenchymal cells parenchymal cells i) i) ii) ii)   “cold” nodules “cold” nodules ~10% of cold nodules ~10% of cold nodules malignant malignant iii) “hot” nodules rarely iii) “hot” nodules rarely malignant malignant   Biopsy is “gold” standard for Biopsy is “gold” standard for diagnosis diagnosis
  71. 71.             Other benign tumors Other benign tumors a) cysts a) cysts b) lipomas b) lipomas c) hemangiomas c) hemangiomas d) dermoid cysts d) dermoid cysts e) teratomas (mainly in e) teratomas (mainly in infants) infants)
  72. 72. • •Thyroid Cancer typically appears as a "cold nodule". That is to say, it Thyroid Cancer typically appears as a "cold nodule". That is to say, it appears as a white area or defect in an otherwise black thyroid. A " appears as a white area or defect in an otherwise black thyroid. A " cold" area is NOT necessarily cancer. Indeed, most "cold nodules" are cold" area is NOT necessarily cancer. Indeed, most "cold nodules" are benign! Ultrasound, perhaps followed by biopsy, often plays an benign! Ultrasound, perhaps followed by biopsy, often plays an important role in differentiation important role in differentiation www.freelivedoctor. www.freelivedoctor.
  73. 73. Thyroid Carcinomas Thyroid Carcinomas                   most appear in adults most appear in adults papillary CA may present in childhood papillary CA may present in childhood female predominance (early and middle female predominance (early and middle adult) adult) childhood and late adulthood have equal childhood and late adulthood have equal gender distribution gender distribution Most CA are well differentiated: Most CA are well differentiated: a) papillary CA (~80% of cases) a) papillary CA (~80% of cases) b) follicular CA ( ~15% of cases) b) follicular CA ( ~15% of cases) c) medullary CA (~5% of cases) c) medullary CA (~5% of cases) d) anaplastic CA (< 5% of cases) d) anaplastic CA (< 5% of cases)

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