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Thyroid assessment & thyroid DZ.ppt
- 1. Thyroid function &thyroid diseases Presenter: Mohamed Ali (PGY1) Moderator: Dr. Abdulaziz (internist at Haramaya university)
- 3. Thyroid assessment • TSH,FT3/4 • RIU • FNA • U/S • CT • MRI
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- 6. Overview • Introduction • Causes •Congenital Hypothyroidism • Prevalence • Clinical Features • Diagnosis & Treatment • Autoimmune Hypothyroidism • Classification • Prevalence • Pathogenesis • Clinical Manifestations • Laboratory Evaluation • Differential Diagnosis • Other Causes • Treatment • Clinical Hypothyroidism • Subclinical Hypothyroidism • Special Considerations • Pregnancy • Elderly • Myxedema Coma
- 7. Introduction • 2nd MCendocrine disorder after Diabetes Mellitus • MC cause of hypothyroidism worldwide - Iodine Deficiency • MCC in Iodine sufficient areas- Hashimoto’s Thyroiditis • 99% cases- Primary Hypothyroidism • <1% cases- Secondary Hypothyroidism • Easy to diagnose & gratifying to treat
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- 9. Transient and secondarycauses
- 10. CONGENITAL HYPOTHYROIDISM PREVALENCE •1 in 4000 newborns • Can be • Transient - if the mother has TSH-R blocking antibodies • Permanent- majority • Causes • 80-85% cases - Thyroid gland dysgenesis • 10-15% cases- Inborn errors of Thyroid hormone synthesis • 5% cases- TSH-R antibody mediated • Gene Mutations include: • PROP-1, PIT-1, TSH-receptor, TSH beta, Thyroid Peroxidase, Thyroglobulin, Pendrin
- 11. Clinical manifestation • Majority-appear normal at birth • Few cases are diagnosed on the basis of clinical features & biochemical screening • Clinical Features include: • Prolonged jaundice • Feeding problems • Hyotonia • Enlarged tongue, Umblical hernia • Delayed bone maturation • Complications: • Congenital malformations (Cardiac) • Permanent neurological damage
- 12. DIAGNOSIS & TREATMENT •Neonatal Screening programs • Measurement of TSH or T4 • Heel prick blood sample • Treatment dose: T4 10-15 ug/kg per day • Early treatment- normal IQ levels
- 13. AUTOIMMUNE HYPOTHYROIDISM • Classification: •Hashimoto’s or Goitrous Thyroiditis • Atrophic Thyroiditis • Prevalence • 4 per 1000 women, 1 per 1000 men • Mean age ~ 60 years • Subclinical hypothyroidism prevalence • 6-8% women • 3% men
- 14. PATHOGENESIS GENETIC ENVIRONMENTAL • HLA-DR3,DR4 and DR5 • CTLA-4 • Association with Down’s Syndrome • Association with Turner’s Syndrome • Other asso. autoimmune diseases • High iodine intake • Low selenium intake • Decreased exposure to microbes in childhood • Smoking cessation • Alcohol- protective HASHIMOTO’S THYROIDITIS ATROPHIC THYROIDITIS • Marked lymphocytic infiltration • Germinal center formation • Atrophy of thyroid follicles, oxyphil metaplasia • Absence of colloid • Mild to moderate fibrosis • Extensive fibrosis • Lymphocyte infiltration- Less • Thyroid follicles- completely absent • Usually the end stage of Hashimoto’s
- 15. ANTIBODIES CYTOKINES • 20%Patients- TSH-R antibody- Blocking type • Responsible for transient neonatal hypohyroidism • TBII assays • Anti TPO • Anti Tg • Lymphocytic infiltrate- T cells & B cells • CD8+ cytotoxic T cells • TNF, IL-1, IGN gamma
- 16. Clinical manifestation • Onset-usuallyinsidious • Hashimoto’s- Goitre rather than other features • Irregular & firm in consistency • Atrophic thyroiditis or late stages of Hashimoto’s- Present with symptoms & signs of Hypothyroidism
- 18. • Hashimoto’s encepalopathy •signs or symptoms of other autoimmune diseases • Thyroid asso. ophthalmopathy- 5% patients • Children - autoimmune hypothyroidism • Uncommon • Slow growth, delayed facial & dental maturation • Myopathy, muscle swelling • Delayed puberty • Intellectual disability
- 20. Other causes • Iatrogenic •Radioiodine treatment • Subtotal Thyroidectomy • Iodine Deficiency • Endemic goitre & cretinism • Uncommon in adults • Public health measures avoid this condition • Iodine excess • Chronic excess can induce goitre & hypothyroidism • Amiodarne, Lithium • Secondary Hypothyroidism • Ant pituiary hormone deficiencies • TSH levels can be low, normal or even slightly increased
- 21. TREATMENT - CLINICALHYPOTHYROIDISM • Dose of Levothyroxine (T4) ? • Ideal time of taking? • Goal of treatment? • TSH monitoring? • Symptom relief? • Risk of overtreatment? • Issues with adherence? • Don’t feel any difference after missing few doses • If misses single dose? • Increased requirements?
- 23. SUBCLINICAL HYPOTHYROIDISM Indications oftreatment • TSH > 10 mIU/L • TSH 4.5-10 mIU/L • Symptoms, Goitre • F?H?O autoimmune thyroid disease • Planning pregnancy or pregnant • TPO antibody positive • Evidence of heart disease, dyslipidemia • Infertility • Psychiatric disorders • Dose • Start with low dose- 25-50 ug/day
- 24. SPECIAL CONSIDERATIONS • Pregnancy •Thyroid function should be monitored • Before conception- therapy to target TSH in normal range • TFT • Every 4 weeks in first half of pregnancy • every 6-8 weks after 20 weeks • Levothyroxine dose is increased by 45% • After delivery dose- Pre pregnancy levels • Elderly • Require 20% less dose than younger specially cardiac patients • Starting dose 12.5 to 2 ug/day • Gradual increments in 2-3 months • Surgery?
- 25. • Myxedema coma •20-40% mortality • Almost always - Elderly patient • Precipitating conditions- That impair respiration • Drugs, Pneumonia, CHF, MI • CVA , GI bleed • Levothyroxine • Initial- 200-400 ug IV bolus or through Nasogastric tube f/b • Daily oral dose 1.6 ug/kg • Liothyronine (T3) • Since T4->T3 conversion is impaired • 5-20 ug f/b 2.5 -10 ug 8 hrly • Supportive therapy • External warming • Parenteral Hydrocortisone (50 mg every 6 hrly) • Treat precipitating factor • Ventilatory support , ABG • Hypertonic saline or IV det©roMseedi
- 26. Subclinical hypothyroidism • Overview •Subclinical hypothyroidism is defined as an increased serum TSH in the presence of normal serum T4. • Prevalent in Women and Elderly
- 27. CAUSES • Iatrogenic • Hashimoto’sThyroiditis • Postpartum thyroiditis • Thyroid Infiltration • Medications • Partial Thyroidectomy • Head and Neck radiation
- 28. CLINICAL CONSEQUENCES • OvertHypothyroidism • Cardiovascular Disease • Diastolic Dysfunction • Diastolic Hypertension • Increase in LDL-C, CRP • Aternation in coagulation parameters, endothelial dysfunction • Decreased Fertility • Nonalcoholic Fatty Liver Disease (NAFLD) • Neuropsychiatric manifestations
- 29. INDICATION OF TREATMENT •Patients with serum TSH >10.0 mU/L • Patients <65 yrs, Asymptomatic • Infertile, Ovulatory dysfunction or planning for pregnancy • Symptoms or signs of hypothyroidism • Goitre • High serum anti-TPO antibodies • Comorbidities- IHD, DM, Dyslipidemia
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- 32. Overview • Thyrotoxicosis • Graves’Disease • Epidemiology • Pathogenesis • Clinical Manifestations • Lab Evaluation • Differential Diagnosis • Clinical Course • Treatment
- 34. GRAVES’ DISEASE -EPIDEMIOLOGY •60-80% cases of thyrotoxicosis •F:M = 10:1 •20-50 yrs of age
- 35. ETIOPATHOGENESIS Genetic factors Environmental •HLA-DR, CTLA-4, PTPN22, TSH-R gene • Conordance - Monozygotic (20-30%), Dizygotic (<5%) • Stress • Smoking - Ophthalmopathy • Increased Iodine intake • Postpartum • HIV- ater HAART (IR disease) Autoantibodies Cytokines • Thyroid Stimulating Ig (TSI) • Anti TPO • Anti Tg • EOM infiltrated by T cells • IFN γ, TNF, Il-1 - Fibroblast activation • Increased synthesis of GAGs- >trap water->muscle swelling • Irreversible fibrosis of muscles
- 36. Clinical manifestation • Featurescommon to Thyrotoxicosis • Specific for Graves’ Disease • Clinical presentation depends upon: • Severity • Duration • Age • Individual responsiveness to excess thyroid hormone • Apathetic Thyrotoxicosis?
- 38. Specific for gravesdisease Gland is diffusely enlarged, 2-3 times normal size, consistency is firm, thrill or bruit can be heard at the inferolateral borders of the gland. Opthalmopathy Dermopathy Acrophathy • Thyroid asso. ophthalmopathy • 75% cases- Onset 1 yr before or after the onset of Graves • Euthyroid ophthalmopathy • 10% patients- Unilateral • Earliest symptoms-Gritty sensation, eye discomfort, excess tearing • Severe cases- Corneal damage, periorbital edema, scleral injecion, chemosis, Diplopia(5%) • Most serious manifestation- Optic nerve compression • <5% patients • Always occurs in presence of moderate to severe ophthalmopathy • Most frequent location? • Non inflames, indurated plaque, deep pink to purple, Orange skin appearance • <5% patients • Always occurs in presence of moderate to severe ophthalmopathy • Most frequent location? • Non inflames, indurated plaque, deep pink to purple, Orange skin appearance
- 40. Laboratory evaluation • TSHlevel is suppressed, total & free T3, T4 are increased • T3 toxicosis? • T4 toxicosis? • Associated abnormalities: • Elevation of Bilirubin • Liver enzymes • Ferritin • Microcytic anemia • Thrombocytopenia
- 42. Clinical course • Clinicalfeatures worsen without treatment • Mortality 10-30% without treatment • 15% patients- Develop Hypothyroidism 10-15 years later • Ophthalmopathy • Worsens over initial 3-6 months-->Plateau phase 12-18 months -> Improves spontaneously • Radioiodine treatment- worsens ophthalmopathy • Dermopathy • appears after 1-2 years • may improve spontaneously
- 43. Treatment • Treatment Approach •Rapid amelioration of symptoms • Decreasing Thyroid Hormone synthesis • Symptom Control: Beta blocker • Propanolol (DOC)-20-40 mg 6 hrly or Atenolol • Relief from sympathetic overactivity (Anxiety, Palpitations, increased bowel activity, lid retraction, tremors) • Decrease thyroid hormone synthesis • Antithyroid Drugs (Thionamides) • Radioiodine • Surgery
- 44. ANTITHYROID DRUGS (THIONAMIDES •Used for 1-2 years prior to definitive therapy (surgery or radioablation) • Indications: • Pregnancy • Children & Adolescent • Severe Graves’ disease with eye changes • MOA: Inhibit TPO enzyme & iodination & organification
- 45. METHIMAZOLE CARBIMEZOLE PTU FreeT4 •1-1.5 times ULN •1.5-2 times ULN •2-3 times ULN Tapering • Additinal immunosuppressive action • Dose- 20-60 mg-->5-15 mg • Total duration- 18-24 months • Adverse effects- Rashes,Urticaria, Fever, Athralgia, Agranulocytosis, hepatotoxicity, aplasia cutis (neonates • Preferred during first trimester of pregnacy (donot cross placenta) • Additionally inhibits peripheral T4->T3 conversion • Dose- 100 mg TDS->50 mg TDS ADVANTAGES DISADVANTAGES No surgical scar, Chances of injury,Hypothyroidism if induced is reversible, Can be used in children and young. Prolonged treatment, High relapse, impractical in huubnhacmooUppaedhryaatyive patient
- 46. Radioiodine ablation • Definitetherapy in non-pregnant patients • Strictly avoided in smokers & those with moderate - severe ophthalmopathy • Indications 1. Patients >40 years of age 2. Young individuals who are sterilized 3. Young patients with short life span • I131 capule -> emits gamma radiation -> ablation of thyroid gland within 6-18 weeks • Dose- 185-555 MBq • Complications- Hypothyroidism, Infertlity, Secondary cancers
- 47. Surgery • Subtotal Thyroidectomy •Indications • Severe hyperthyroidism in children • Pregnant women who cannot tolerate thionamides • Large goitre with severe ophthalmopathy or pressure symptoms • Who require quick normalization of thyroid function • Preparation: Propanolol, Methimazole, Potassium Iodide • Complications • Hypothyroidism • Hypoparathyroidism • Hypocalcemia • RLN damage
- 48. ADJUNCTIVE THERAPIES • OralRadio-contrast Agents: Sodium Ipodate, Iopanoic acid • Iodine elixirs: 10 drops of SSKI • Glucocorticoids • Cholestyramine: 4 gm four times a day • Potassium perchlorate • Lithium • Calcium: for skeletal health 1 gm per day
- 49. Treatment for graves disease •Reversal of Hyperthyroidism • Smoking cessation • Local measures: Eyes shades, artificial tears & lubricants Drugs • Selenium - Antioxidant • Glucocorticoids - Anti inflammatory • Teprotumumab - IGF-1 receptor inhibitor • Mycophenolate moetil • Tocilizumab - Anti IL6 • Rituximab - Anti CD 20 Surgery • Orbital decompression • Fat decompression • Bilateral lateral tarsorrhaphy • resection of Muller’s muscle Treatment of dermopathy • Usually asymptomatic- Treatment is not necessary • Indications: Pruritus, Local discomfort, Unsightly appearance, progression of lesions Non Pharmacological • Avoid tobacco • Reduce weight • Normalize thyroid function Pharmacological • Topical Fluocinolon acetonide • Intralesional Triamcinolone acetate • Pentoxiphylline
- 50. ACUTE THYRODITIS SUBACUTETHYRODITIS CHRONIC THYRODITIS DEF Suppurative infxn of thyroid gland Infiltrative DZ of thyroid gland Infiltrative DZ of the thyroid gland ETIO Bacterial/fungal Viral/ TPO A/B Autoimmune/TPO A/B GOIT Small, tender asymmetric Small, exquisitely tender Firm, hard, with variable sizes CLIN Febrile illness with LAP, dysphagia and erythema around the gland Fever, +/- hypo/hyperthyroid signs /symptoms Local compressive symptoms, Hashimoto Dx Elevated WBC AND ESR, FNA shows PMN infiltration, gram stain and Cx TFT, FNA to R/O bleeding into cyst or CA Open Bx Rx ABX • ASPRIN( 600MG Q4-6HR) • PREDNISOLONE(14-40MG) • PHASE Tx Surgical decompression, tamoxifen
- 52. Phase Tx • Thyrotoxicosisimprove spontaneously but may be ameliorated by β-adrenergic blockers; antithyroid drugs play no role in treatment of the thyrotoxic phase. • Levothyroxine replacement may be needed if the hypothyroid phase is prolonged, but doses should be low enough (50–100 μg daily) to allow TSH-mediated recovery.
- 53. Amiodarone induced thyroditis •Amiodarone (iodine in sheeps clothing) contains 39% iodine by weight. Pathophysiology Clinical manifestation • Acute/transient suppression of thyroid function • Hypothyroidism in pts susceptible to inhibitory effects of high iodine load. • Thyrotoxicosis(Jod-basedow effect, in MNG,Graves or thyroiditis) • Hypothyroidism • Thyrotoxicosis Diagnosis & Treatment • Color-flow U/S is used to differentiate type 1 AIT from type 2 AIT. • D/C if possible • Potassium percholorate (200mg Q6hrs), R/F of agranulocytosis. • GC have modest effect on type 2 AIT • Lithium has some benefit • Near total thyroidectomy is the most effective long-term sol’n if it can be performed safely.
- 54. Thyroid nodular DZ& thyroid CA
- 55. DIFFUSE NON-TOXIC (SIMPLE)GOITER Etiopathogenesis Clinical manifestations & DX • Iodine deficiency(MCC) • Environmental goitrogens(e.g cassava roots) • Inherited defects in thyroid hormone synthesis. • Mostly ASX • P/E diffuse, nontender, soft symmetrically enlarged. • Substernal goiter(blocks thoracic inlet, pemberton’s sign) • CT/MRI if obstructive features present in substernal goiter • TFT’s Treatment • Iodine replacement induces variable regression. • Surgery is indicated if compression of trachea or thoracic inlet occurs. • Cosmetic surgery
- 56. Nontoxic MNG Etiopathogenesis Clinicalmanifestations & DX • Occurs in up to 12% of adults • Females > Males • MC in areas of iron defeciency, but also occurs in areas of iron excess. • Polyclonal/ monoclonal hypercellular/hyerplastic regions to cystic areas of hemmorhage may be seen. • Extensive fibrosis • ASX & euthyroid • Compressive SX( rare) • SX if extremely large and fibrotic. • Pain suggests hemorrhage into nodule or suggest malignancy • Hoarseness, also suggests malignancy
- 57. Diagnosis Treatment • P/Ethyroid architecture is distorted and multiple nodules ov varying size are present. • Pamberton’s sign could be positive • TSH (usually normal) • Tracheal deviationand airway compromise (>70% of tracheal diameter), inspiratory stridor. • PFT to assess respiratory function. • CT/MRI • Barium swallow may reveal extent of tracheal compression. • U/S for which nodules to be Bx • Conservative management • Avoid contrast agents, iodine containing substances (Jod-Basedow effect) • Radioiodine ablation(3.7MBq per gram tissue, enganced by rTSH 0.1 IM) • GC along with surgery in acute compression • Surgery remains the definitve Tx
- 59. Toxic MNG Pathogenesis andDiagnosis Clinical manifestations • Autonomous toxic nodules are present. • Molecular bases for autonomy is unknown. • TSH is low, T4 level is normal or minimally increased, T3 is elevated often to greater degree than T4. • Thyroid scan shows heterogenous uptake • U/S for cold nodules, then FNA may be indicated based on sonographic pattern. • Surgery if CA on cytology • Subclical/ overt hyperthyroidism • AFIB, palpitation, tachycardia, nervousness, tremor, and weight loss in elderly. Treatment • Antithyroid drugs elderly/paliative) • Radioiodine is the Tx of choice • Surgery is definitive Tx • Tx hypothyroidism afterwards.
- 60. Toxic adenoma Pathogenesis &clinical manifestation Diagnosis • Acquired, somatic mutation in TSH-R pathway leading to enhanced thyroid follicular cell proliferation and function. • Mild thyrotoxicosis, only detected when nodule >3cm • Subnormal TSH level • P/E presence of nodule, absence of graves specific signs, • Thyroid scan is definitive (increased uptake by the toxic adenoma) Treatment • Radioiodine ablation is the Tx of choice (large doses are used) • Surgical resection(lobectomy) • Antithyroid drugs and BB for short term. • U/S guidance, repeated percutaneous radiofreaquency thermal ablation. • Hypothyroidism occurs in <10%
- 61. Thyroid growths • Benign •Malignant
- 63. Thyroid cancer • Mostcommon malignancy in endocrine system. • Malignant tumors derived from the follicular epithelium are classified according to histologic features. – Differentiated tumors, such as papillary thyroid cancer (PTC) or follicular thyroid cancer (FTC), are often curable, and the prognosis is good for patients identified with early-stage disease. – In contrast, anaplastic thyroid cancer (ATC) is aggressive, responds poorly to treatment, and is associated with a bleak prognosis.
- 67. Papillary Follicular AnapalasticMedullary • Well differentiated • MC(80-85%) • FNA(orphan annie eye appearance) • Can infiltrate adjacent structures of the neck • Spreads lymphatically • Have excellent prognosis • Tx • TSH suppression • Radioiodine • Well differentiated • Accounts for 5% of thyroid CA • Difficult to DX by FNA • Dx by capsular and/or vascular invasion • Spreads hematogenously • Poor prgnosis if hematogenously spread. • Tx • TSH suppression • radioiodine • Poorly differentiated aggressive cancer. • Poor prognosis(pts die with in 6 months of Dx) • Chemotherapy is ineffective. • External beam therapy • Immune checkpoint inhibition therapy may beneficial (recent data) • Sporadic or familial • Associated with MEN • More aggressive when associated with MEN 2B • Elevated serum calcitonin provides a marker for residual or recurrent DZ • Tx is surgical
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