Download to read offline
Thyroiditis.ppt dg ffkjsnd.x.,jrei lvfdl
- 1. Thyroid Physiology and ThyroidPhysiology and Thyroiditis Thyroiditis Heidi Chamberlain Shea, MD Heidi Chamberlain Shea, MD Endocrine Associates of Dallas Endocrine Associates of Dallas
- 2. Case Presentation Case Presentation 23year old female 23 year old female G2P2 G2P2 6 months post partum 6 months post partum Palpitations that were Palpitations that were intermittent for a couple of intermittent for a couple of weeks and now resolved weeks and now resolved Now with 1 month of increased Now with 1 month of increased fatigue, hair loss and 10 pound fatigue, hair loss and 10 pound weight gain weight gain
- 3. Case Presentation Case Presentation Whatis her diagnosis? What is her diagnosis? Tests that should be done? Tests that should be done? Pathophysiology of her disease process? Pathophysiology of her disease process?
- 4. Thyroid Trivia Thyroid Trivia “ “Bronchocele” Bronchocele” Greekfor tracheal Greek for tracheal outpouch outpouch 1500 AD described by 1500 AD described by Leonardo da Vinci Leonardo da Vinci 1656 AD “thyroid” 1656 AD “thyroid” Thomas Wharton Thomas Wharton Shield shaped cartilage Shield shaped cartilage
- 5. Thyroid Trivia Thyroid Trivia Largestendocrine Largest endocrine gland gland 20 grams in adult 20 grams in adult Each lobe Each lobe 2-2.5cm in width and 2-2.5cm in width and thickness thickness 4cm in height 4cm in height Isthmus Isthmus 0.5cm thick 0.5cm thick 2cm height and width 2cm height and width
- 6. Thyroid Thyroid Derived from endodermat Derived from endoderm at base of tongue base of tongue Recognizable after 1 Recognizable after 1 month of fetal life month of fetal life Isthmus lies over 2 Isthmus lies over 2nd nd and and 3 3rd rd tracheal rings tracheal rings 2cm wide x 2 cm height x 2cm wide x 2 cm height x 0.5cm thick 0.5cm thick Adult 15-20 grams Adult 15-20 grams
- 7. Thyroid Thyroid Largest of theendocrine glands Largest of the endocrine glands Blood flow 5x the weight of the gland/minute Blood flow 5x the weight of the gland/minute Hormones produced Hormones produced 93% thyroxine (T4) 93% thyroxine (T4) 7% triiodothyronine (T3) 7% triiodothyronine (T3) 4x the potency of thyroxine 4x the potency of thyroxine Responsible for the basal metabolic rate Responsible for the basal metabolic rate Deficiency = 40-50% fall in metabolic rate Deficiency = 40-50% fall in metabolic rate Excess = 60-100% increase in metabolic rate Excess = 60-100% increase in metabolic rate
- 8. Thyroid Histology Thyroid Histology Multipleclosed follicles Multiple closed follicles (100-300 micrometers) (100-300 micrometers) Cuboidal epithelial cells Cuboidal epithelial cells secrete colloid into the secrete colloid into the follicles follicles Colloid = thyroglobulin Colloid = thyroglobulin Large glycoprotein with 70 Large glycoprotein with 70 tyrosine amino acids tyrosine amino acids Endoplasmic reticulum Endoplasmic reticulum and Golgi apparatus and Golgi apparatus synthesize and secrete synthesize and secrete
- 9. TRH (+) HYPOTHALAMUS ANTERIOR PITUITARY HYPOTHALAMIC- PITUITARY PORTAL SYSTEM T4, T3(T4 --> T3) THYROID GLAND TSH POSTERIOR PITUITARY (-) (-)
- 10. TRH TRH Produced by Hypothalamus Producedby Hypothalamus Release is pulsatile, circadian Release is pulsatile, circadian Downregulated by T Downregulated by T4 4, T , T3 3 Travels through portal venous system to Travels through portal venous system to adenohypophysis adenohypophysis Stimulates TSH formation Stimulates TSH formation
- 11. TSH TSH Produced by AdenohypophysisThyrotrophs Produced by Adenohypophysis Thyrotrophs Upregulated by TRH Upregulated by TRH Downregulated by T Downregulated by T4 4, T , T3 3 Travels through portal venous system to Travels through portal venous system to cavernous sinus, body. cavernous sinus, body. Stimulates several processes Stimulates several processes Iodine uptake Iodine uptake Colloid endocytosis Colloid endocytosis Growth of thyroid gland Growth of thyroid gland
- 12. Thyroid Physiology Thyroid Physiology Uptakeof Iodine by thyroid Uptake of Iodine by thyroid Coupling of Iodine to Thyroglobulin Coupling of Iodine to Thyroglobulin Storage of MIT / DIT in follicular space Storage of MIT / DIT in follicular space Re-absorption of MIT / DIT Re-absorption of MIT / DIT Formation of T Formation of T3 3, T , T4 4 from MIT / DIT from MIT / DIT Release of T Release of T3 3, T , T4 4 into serum into serum Breakdown of T Breakdown of T3 3, T , T4 4 with release of Iodine with release of Iodine
- 13. Thyroid and Iodine Thyroidand Iodine 50 mg of iodides are needed per year 50 mg of iodides are needed per year 1 mg/week 1 mg/week Iodized salt Iodized salt 1 part Na iodide to 100,000 parts NaCl 1 part Na iodide to 100,000 parts NaCl Iodides are ingested and oxidized to iodine in Iodides are ingested and oxidized to iodine in the thyroid the thyroid Nascent iodine(I Nascent iodine(Io o ) or I ) or I3 3 - - Peroxidase enzyme (hydrogen peroxide) Peroxidase enzyme (hydrogen peroxide) 1/5 of ingested iodine utilized for hormone 1/5 of ingested iodine utilized for hormone synthesis synthesis
- 14.
- 15. Iodine uptake Iodine uptake Na Na+ + /I /I- - symportprotein symport protein controls serum I controls serum I- - uptake uptake Based on Na Based on Na+ + /K /K+ + antiport potential antiport potential Stimulated by TSH Stimulated by TSH Inhibited by Inhibited by Perchlorate Perchlorate
- 16. Iodide Pump Iodide Pump Thyroidgland actively pumps iodide into Thyroid gland actively pumps iodide into the cell via the basal membrane the cell via the basal membrane (iodide trapping) (iodide trapping) Iodide 30x the concentration of blood Iodide 30x the concentration of blood Able to concentrate to 250x the concentration Able to concentrate to 250x the concentration in blood in blood Rate of iodide trapping Rate of iodide trapping TSH dependent TSH dependent
- 17. Thyroid Hormone Synthesis ThyroidHormone Synthesis Tyrosine backbone Tyrosine backbone Iodine Iodine Iodinase Iodinase enzyme (enzyme I) attaches iodine enzyme (enzyme I) attaches iodine to thyroglobulin to thyroglobulin Number of iodines determine activity of Number of iodines determine activity of thyroid hormone thyroid hormone Thyroxine (4 iodines) Thyroxine (4 iodines) Triiodothyronine (3 iodines) Triiodothyronine (3 iodines)
- 18. MIT / DITFormation MIT / DIT Formation Thyroid Peroxidase (TPO) Thyroid Peroxidase (TPO) Apical membrane protein Apical membrane protein Catalyzes iodide oxidation to reactive iodine Catalyzes iodide oxidation to reactive iodine Binds to Tyrosine residues of Thyroglobulin Binds to Tyrosine residues of Thyroglobulin Antagonized by thionamides Antagonized by thionamides Coupling enzyme Coupling enzyme MIT with DIT= T3 MIT with DIT= T3 Two DIT’s= T4 Two DIT’s= T4 Pre-hormones secreted into follicular space Pre-hormones secreted into follicular space
- 19. Transport of T3and T4 Transport of T3 and T4 When in circulation When in circulation 93% thyroxine and 7% triiodothyronine 93% thyroxine and 7% triiodothyronine Conversion to active (T3) is by slow Conversion to active (T3) is by slow deiodination process deiodination process 99% of T4 and T3 bound to plasma proteins 99% of T4 and T3 bound to plasma proteins Causes slow release of hormone to tissue Causes slow release of hormone to tissue Thyroxine-binding globulin (TBG) Thyroxine-binding globulin (TBG) Tyroxine-binding prealbumin and albumin Tyroxine-binding prealbumin and albumin
- 20. Secretion of ThyroidHormone Secretion of Thyroid Hormone Stimulated by TSH Stimulated by TSH Endocytosis of colloid on apical membrane Endocytosis of colloid on apical membrane Coupling of MIT & DIT residues Coupling of MIT & DIT residues Catalyzed by TPO Catalyzed by TPO MIT + DIT = T MIT + DIT = T3 3 DIT + DIT = T DIT + DIT = T4 4 Hydrolysis of Thyroglobulin Hydrolysis of Thyroglobulin Release of T Release of T3 3, T , T4 4 Release inhibited by Lithium Release inhibited by Lithium
- 21.
- 22. Thyroglobulin Storage Thyroglobulin Storage Thyroglobulinmolecule Thyroglobulin molecule 30 thyroxine molecules 30 thyroxine molecules Few triiodothyronine Few triiodothyronine Sufficient supply for 2-3 Sufficient supply for 2-3 months months Deiodinase enzyme Deiodinase enzyme recycles iodine when recycles iodine when thyroglobulin utilized thyroglobulin utilized
- 23. Thyroid Hormone Thyroid Hormone Metaboliceffect of thyroxine noticed 2-3 Metabolic effect of thyroxine noticed 2-3 days after release days after release Steady state of thyroid hormone 10-12 Steady state of thyroid hormone 10-12 days after ingestion days after ingestion Half life of 15 days Half life of 15 days Due to steady state, thyroid hormone is Due to steady state, thyroid hormone is typically adjusted every 4-6 weeks typically adjusted every 4-6 weeks Check T4 vs. TSH in the short term Check T4 vs. TSH in the short term assessment assessment
- 24. Thyroid Hormone Thyroid Hormone Majorityof circulating hormone is T Majority of circulating hormone is T4 4 98.5% T 98.5% T4 4 1.5% T 1.5% T3 3 Total Hormone load is influenced by serum Total Hormone load is influenced by serum binding proteins binding proteins Thyroid Binding Globulin 70% Thyroid Binding Globulin 70% Albumin 15% Albumin 15% Transthyretin 10% Transthyretin 10% Regulation is based on the free component of Regulation is based on the free component of thyroid hormone thyroid hormone
- 25. Hormone Binding Factors HormoneBinding Factors Increased TBG Increased TBG High estrogen states (pregnancy, OCP, HRT, Tamoxifen) High estrogen states (pregnancy, OCP, HRT, Tamoxifen) Liver disease (early) Liver disease (early) Decreased TBG Decreased TBG Androgens or anabolic steroids Androgens or anabolic steroids Liver disease (late) Liver disease (late) Binding Site Competition Binding Site Competition NSAID’s NSAID’s Furosemide IV Furosemide IV Anticonvulsants (Phenytoin, Carbamazepine) Anticonvulsants (Phenytoin, Carbamazepine)
- 26. Hormone Degradation Hormone Degradation T T4 4is converted to T is converted to T3 3 (active) by (active) by 5’ deiodinase 5’ deiodinase T T4 4 can be converted to rT can be converted to rT3 3 (inactive) by (inactive) by 5 deiodinase 5 deiodinase T T3 3 is converted to rT is converted to rT2 2 (inactive)by (inactive)by 5 deiodinase 5 deiodinase rT rT3 3 is inactive but measured by serum tests is inactive but measured by serum tests
- 27. Hypothyroidism Hypothyroidism Symptoms Symptoms Nervous system Nervous system Forgetfulnessand Forgetfulness and mental slowing mental slowing Paresthesias Paresthesias Carpal tunnel Carpal tunnel Ataxia and decreased Ataxia and decreased hearing hearing Tendon jerk slowed Tendon jerk slowed with prolonged with prolonged relaxation phase relaxation phase Cardiovascular Cardiovascular Bradycardia Bradycardia Decreased cardiac Decreased cardiac output output Pericardial effusion Pericardial effusion Reduced voltage on Reduced voltage on EKG and flat T waves EKG and flat T waves Dependent edema Dependent edema
- 28. Hypothyroidism Hypothyroidism Symptoms Symptoms Gastrointestinal Gastrointestinal Constipation Constipation Achlorhydria with Achlorhydria with perniciousanemia pernicious anemia Ascitic fluid with high Ascitic fluid with high protein protein Renal Renal Reduced excretion of Reduced excretion of water load water load Hyponatremia Hyponatremia Decreased renal blood Decreased renal blood flow and glomerular flow and glomerular filtration filtration Pulmonary Pulmonary Responses to hypoxia and Responses to hypoxia and hypercapnia are decreased hypercapnia are decreased Pleural effusions high Pleural effusions high protein protein Musculoskeletal Musculoskeletal Arthralgia Arthralgia Joint effusions Joint effusions Muscle cramps Muscle cramps CK can be elevated CK can be elevated Anemia Anemia Normochromic normocytic Normochromic normocytic Megaloblastic Megaloblastic Pernicious anemia Pernicious anemia
- 29. Hypothyroidism Hypothyroidism Symptoms Symptoms Skin and hair Skinand hair Loss of lateral eye brows Loss of lateral eye brows Dry, cool skin Dry, cool skin Facial features Facial features Coarse and puffy Coarse and puffy Orange skin Orange skin Carotene Carotene Reproductive system Reproductive system Menorrhagia from Menorrhagia from anovulatory cycles anovulatory cycles Hyperprolactinemia Hyperprolactinemia No inhibition of thyroid No inhibition of thyroid hormone hormone Metabolism Metabolism Hypothermia Hypothermia Intolerance to cold Intolerance to cold Increased cholesterol Increased cholesterol and triglyceride and triglyceride Decreased lipoprotein Decreased lipoprotein receptors receptors Weight gain Weight gain
- 30. Thyroid Hormone Thyroid Hormone Metaboliceffect of thyroxine noticed 2-3 Metabolic effect of thyroxine noticed 2-3 days after release days after release Steady state of thyroid hormone 10-12 Steady state of thyroid hormone 10-12 days after ingestion days after ingestion Half life of 15 days Half life of 15 days Due to steady state, thyroid hormone is Due to steady state, thyroid hormone is typically adjusted every 4-6 weeks typically adjusted every 4-6 weeks Check T4 vs TSH in the short term Check T4 vs TSH in the short term assessment assessment
- 31. Hypothyroidism Hypothyroidism Etiologies Etiologies Thyroiditis Thyroiditis Thyroid ablation Thyroid ablation Externalradiotherapy External radiotherapy Pharmacologic agents Pharmacologic agents Infiltrative disorders Infiltrative disorders Embryologic variants Embryologic variants
- 32. Thyroiditis Thyroiditis Decreased uptake on Decreaseduptake on uptake scan uptake scan Transient Transient Euthyroidism returns with Euthyroidism returns with time time Lead to chronic thyroid Lead to chronic thyroid dysfunction dysfunction Etiology Etiology Infectious Infectious Post-partum Post-partum Auto-immune Auto-immune Transient Transient Chronic Chronic Drug Drug
- 33. Thyroiditis Thyroiditis Thyrotoxic phase Thyrotoxic phase Shortphase Short phase Increased T3 and T4 Increased T3 and T4 Symptoms of Symptoms of hyperthyroidism hyperthyroidism Thionamides not Thionamides not effective effective Thyroid synthesis low Thyroid synthesis low Can use beta-blockers Can use beta-blockers Hypothyroid phase Hypothyroid phase Transient or permanent Transient or permanent Symptomatic patients Symptomatic patients need replacement need replacement Can check for recovery Can check for recovery with stopping after 3-6 with stopping after 3-6 months months
- 34. Thyroiditis Thyroiditis Time Course Time Course WilliamsText of Endocrinology, Fig 11.50
- 35. Infectious Thyroiditis Infectious Thyroiditis Etiology Etiology Bacterial90% Bacterial 90% Fungal Fungal Mycobacterial Mycobacterial Parasitic Parasitic Syphilitic Syphilitic Symptoms Symptoms Thyroid pain and Thyroid pain and tenderness tenderness Fever Fever Dysphagia Dysphagia Dysphonia Dysphonia Treatment Treatment Treat the infection Treat the infection
- 36. Autoimmune Thyroiditis Autoimmune Thyroiditis ChronicLymphocytic Chronic Lymphocytic Silent Thyroiditis Silent Thyroiditis Hashimoto’s Hashimoto’s Women 3.5/1000 Women 3.5/1000 Men 0.8/1000 Men 0.8/1000 Frequency increases with Frequency increases with age age Familial history Familial history Associated with Associated with autoimmune diseases autoimmune diseases Antibodies Antibodies Thyroid peroxidase Thyroid peroxidase More specific More specific Thyroglobulin Thyroglobulin Elevated in many types of Elevated in many types of thyroid inflammation thyroid inflammation
- 37. Thyroiditis Thyroiditis Postpartum thyroiditis Postpartum thyroiditis 2-21%of pregnancies 2-21% of pregnancies Can occur up to one Can occur up to one year post partum year post partum Usually transient and Usually transient and returns to euthyroid returns to euthyroid state state Treat Treat Hypothyroidism Hypothyroidism Symptoms with Symptoms with ‘hyperthyroidism’ ‘hyperthyroidism’ Presence of TPO AB Presence of TPO AB increases risk of long increases risk of long term hypothyroidism term hypothyroidism
- 38. Transient/Destructive Thyroiditis Transient/Destructive Thyroiditis Subacute Subacute 20%of thyrotoxic cases 20% of thyrotoxic cases De Quervain’s thyroiditis De Quervain’s thyroiditis Giant cell thyroiditis Giant cell thyroiditis Pseudogranulomatous Pseudogranulomatous thyroiditis thyroiditis Subacute painful thyroiditis Subacute painful thyroiditis Symptoms Symptoms Pain Pain Fever Fever Increased ESR Increased ESR Hoarseness or dysphagia Hoarseness or dysphagia Treatment Treatment ASA, NSAID ASA, NSAID Steroid rarely Steroid rarely
- 39. Comparison of Thyroiditis Comparisonof Thyroiditis Characteristic Characteristic Silent thyroiditis Silent thyroiditis Subacute thyroiditis Subacute thyroiditis Age of onset (yr) Age of onset (yr) 5-93 5-93 20-60 20-60 Sex ratio (F:M) Sex ratio (F:M) 2:1 2:1 5:1 5:1 Etiology Etiology Autoimmune Autoimmune Viral Viral Pathology Pathology Lymphocytic infiltration Lymphocytic infiltration Giant cells, granulomas Giant cells, granulomas Prodrome Prodrome Pregnancy Pregnancy Viral illness Viral illness Goiter Goiter Non-painful Non-painful Painful Painful Fever/malaise Fever/malaise No No Yes Yes TPO/thyroglobulin AB TPO/thyroglobulin AB High and rising High and rising Low, absent or transient Low, absent or transient ESR ESR Normal Normal High High RAIU RAIU <5% <5% <5% <5% Relapse Relapse Common Common Rare Rare Permanent Permanent hypothyroidism hypothyroidism Common Common Infrequent Infrequent
- 40. Drug Induced ThyroidDysfunction Drug Induced Thyroid Dysfunction Lithium Lithium Inhibits thyroid hormone Inhibits thyroid hormone secretion secretion Hypothyroidism Hypothyroidism 3.4% prevalence 3.4% prevalence Interferon- Interferon-α α Hyper/Hypothyroidism Hyper/Hypothyroidism Transient thyroiditis Transient thyroiditis TPO AB increases risk of TPO AB increases risk of thyroid dysfunction thyroid dysfunction Interleukin-2 Interleukin-2 Aminoglutethimide Aminoglutethimide Ethionamide Ethionamide Sulfonamides Sulfonamides
- 41. Drug Induced ThyroidDysfunction Drug Induced Thyroid Dysfunction Amiodarone Amiodarone 75 mg iodine/200 mg 75 mg iodine/200 mg Hypothyroidism Hypothyroidism Thyrotoxicosis Thyrotoxicosis Type I and Type II Type I and Type II Increased blood flow vs. Increased blood flow vs. decreased blood flow decreased blood flow Not responsive to thionamides Not responsive to thionamides
- 42. Hypothyroidism Hypothyroidism Infiltrative Disorders Infiltrative Disorders Riedel’sthyroiditis Riedel’s thyroiditis Invasive Fibrous Thyroiditis Invasive Fibrous Thyroiditis Thyroid tissue replaced by Thyroid tissue replaced by fibrous tissue fibrous tissue Rapidly enlarging neck Rapidly enlarging neck mass mass Compressive symptoms Compressive symptoms Surgical removal Surgical removal Steroids and tamoxifen Steroids and tamoxifen Amyloidosis Amyloidosis Sarcoidosis Sarcoidosis Hemochromatosis Hemochromatosis Cystinosis Cystinosis Pneumocystis carinii Pneumocystis carinii Lymphoma Lymphoma
- 43. Thyroid Hormone Replacement ThyroidHormone Replacement 1.3 ug/kg/day 1.3 ug/kg/day 75-100 ug per day 75-100 ug per day Elderly or patients with Elderly or patients with angina angina 12.5-25 ug/day 12.5-25 ug/day Carefully increase every Carefully increase every month month IV dosing IV dosing Use 60% of oral dose Use 60% of oral dose Levothyroxine Levothyroxine Synthroid Synthroid Levoxyl Levoxyl Unithroid Unithroid Armour Thyroid Armour Thyroid T3/T4 preparation T3/T4 preparation Dessicated pig thyroid Dessicated pig thyroid Not a consistent amount of Not a consistent amount of T3/T4 T3/T4 Most T3 preparations give Most T3 preparations give higher than 1:11 ratio of higher than 1:11 ratio of T3:T4 T3:T4
- 44. Case Presentation Case Presentation 23year old female 23 year old female G1P1 G1P1 6 months post partum 6 months post partum Palpitations that were Palpitations that were intermittent for a intermittent for a couple of weeks and couple of weeks and now resolved now resolved Now with 1 month of Now with 1 month of increased fatigue, hair increased fatigue, hair loss and 10 pound loss and 10 pound weight gain weight gain
- 45. Case Presentation Case Presentation Whatis her diagnosis? What is her diagnosis? Post partum thyroiditis Post partum thyroiditis Tests that should be done? Tests that should be done? TSH 15 uIU/ml, Free T4 1.2 ng/dl TSH 15 uIU/ml, Free T4 1.2 ng/dl TPO AB negative TPO AB negative Pathophysiology of her disease process? Pathophysiology of her disease process? Transient Transient Treatment Treatment Levothyroxine therapy Levothyroxine therapy Recheck every 6-8 months Recheck every 6-8 months After 3-6 months may be able to wean replacement After 3-6 months may be able to wean replacement
- 46. Post Partum Thyroiditis PostPartum Thyroiditis Time Course Time Course Williams Text of Endocrinology, Fig 11.51 Changes in free T4
- 47. Williams Text ofEndocrinology, Fig 12.6
Editor's Notes
- #8 Colloid contains thyroid hormones. Colloid is stored in the follicles and then reabsorbed back through the follicular epithelium and into the blood stream to be utilized.
- #13 1Na Iodide to 100,000 parts of
- #16 Refer you to pg 859 and Figure 76-2 shows iodine transport Thus, decreasing TSH (will decrease the iodide pump)
- #17 Without oxidation of iodide, iodine is not placed onto thyroglobulin and hormone formation ceases Organification is a rapid process occurs minutes/seconds
- #29 Glycosaminoglycans accumulate in skin