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Thyroid Disorders Hasan AYDIN, MD Yeditepe University Medical Faculty Department of Endocrinology and Metabolism Thyroid Regulation HYPOTHALAMUS - TRH ANT. PITUITARY - TSH TSH -R THYROID T4 and T3 PLASMA T4 + FT4 PLASMA T3 + FT3 TISSUES FT4 to FT3 Thyroid Hormones THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE EXTREMELY HELPFUL THYROID GLAND DISORDERS THYROID HORMONE EFFECTS: Affects every single cell in the body Modulates: Oxygen consumption Growth rate Maturation and cell differentiation Turnover of Vitamins, Hormones, Proteins, Fat, CHO Thyroid Gland Disorders Overproduction of thyroid hormones Underproduction of thyroid hormones Thyroid nodules Thyroiditis Thyroid neoplasms Hyperthyroidism Thyroid Gland Disorders TSH High usually means Hypothyroidism Rare causes: TSH-secreting pituitary tumor Thyroid hormone resistance Assay artifact TSH low usually indicates Thyrotoxicosis Other causes First trimester of pregnancy After treatment of hyperthyroidism Some medications (Steroids-dopamine) Thyroid Gland Disorders THYROTOXICOSIS: is defined as the state of thyroid hormone excesss HYPERTHYROIDISM: is the result of excessive thyroid gland function Abnormalities of Thyroid Hormones Thyrotoxicosis Primary Secondary Without Hyperthyroidism Exogenous or factitious Hypothyroidism Primary Secondary Peripheral Causes of Thyrotoxicosis Primary Hyperthyroidism Grave´s disease Toxic Multinodular Goiter Toxic adenoma Functioning thyroid carcinoma metastases Activating mutation of TSH receptor Struma ovary Drugs: Iodine excess Causes of Thyrotoxicosis Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction: Amiodarone, radiation, infarction of an adenoma Exogenous/Factitia Secondary Hyperthyroidism TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome Chorionic Gonadotropin-secreting tumor Gestational thyrotoxicosis Thyrotoxicosis Symptoms: Hyperactivity Irritability Dysphoria Heat intolerance & sweating Palpitations Fatigue & weakness Weight loss with increased appetite Diarrhea Polyuria Sexual dysfunction Signs: Tachycardia Atrial fibrillation Tremor Goiter Warm, moist skin Muscle weakness, myopathy Lid retraction or lag Gynecomastia Exophtalmus Pretibial myxedema Manifestations of Thyrotoxicosis Differential Diagnosis Panic attacks Psychosis Mania Pheochromocytoma Hypoglycemia Occult malignancy Treatment Reducing thyroid hormone synthesis: Antithyroid drugs (Methimazole, Propylthyouracil) Radioiodine (131I) Subtotal thyroidectomy Reducing Thyroid hormone effects: Propranolol Glucocorticoids Benzodiazepines Reducing peripheral conversion of T4 to T3 Propylthyouracil Glucocorticoids Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect) Treatment: Special Considerations Thyrotoxic crisis or Thyroid storm: It´s a life-threatening exacerbation of thyrotoxicosis, acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice. Mortality rate reachs 30% even with treatment It´s usually precipitated by acute illness, such as: Stroke, infection,trauma, diabetic ketoacidosis, surgery, radioiodine treatment Propylthyouracil IV or Nasogastric tube Radioiodine (131I) Propranolol Glucocorticoids Benzodiazepines Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect) HYPOTHYROIDISM Definition A deficiency of thyroid hormones, which in turn results in a generalized slowing down of metabolic processes. In infants and children => marked slowing of growth and development, with serious permanent consequences including mental retardation. In adulthood => a generalized slowing down of the organism, with the clinical picture of myxedema. Causes of Hypothyroidism Primary Congenital Acquired Transient Secondary Pituitary Hypothalamic Hypothyroidism Symptoms: Tiredness Weakness Dry skin Sexual dysfunction Hair loss Difficulty concentrating Signs: Bradycardia Dry coarse skin Puffy face, hands and feet Diffuse alopecia Peripheral edema Delayed tendon reflex relaxation Carpal tunel syndrome Serous cavity effusions. Hypothyroidism Special Considerations Myxedema coma Reduced level of consciousness, seizures Hypotension/shock Hypothermia Hyponatremia Usually in elderly hypothyroid pts. Usually precipitated by intercurrent illnesses that impairs ventilation It´s an Emergency with a high mortality rate Treatment: Lyotironine(T3) or T4, Hydrocortisone, external warming, IV fluids Many Causes, One Treatment Goal : Normalize TSH level regardless of cause of hypothyroidism Treatment : Once daily dosing with Levothyroxine sodium (1.6 µg/kg/day) Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage change Treatment: Special Considerations Elderly patients Coronary Artery Disease Poor adrenal gland reserve Childrens Pregnancy Emergency surgery (Non thyroid related) Goiter and Thyroid Cancer Definitions Goiter is a diffuse or nodular enlargement of the thyroid gland resulting from excessive replication of benign thyroid epithelial cells. A thyroid nodule is a discrete lesion within the thyroid gland that is palpably and/or ultrasonog- raphically distinct from the surrounding thyroid parenchyma Etiology of Nontoxic Goiter Iodine deficiency Goitrogen in the diet Hashimoto's thyroiditis Subacute thyroiditis Inherited defect in thyroidal enzymes necessary for T 4 and T 3 biosynthesis Generalized resistance to thyroid hormone (rare) Neoplasm, benign or malignant Multinodular Goiter Clinical Issues Hyperthyroidism Suspicion of malignancy Compressive/obstructive symptoms Cosmetic concerns MULTINODULAR GOITER Presentation Asymptomatic Neck mass discovered by patient or physician Abnormal CXR Symptomatic Pressure symptoms Hoarseness Thyrotoxicosis NODULAR GOITER Suspicious Nodule or Goiter High suspicion Family history of medullary thyroid carcinoma Rapid tumor growth A nodule that is very firm or hard Fixation of the nodule to the adjacent structures Paralysis of the vocal cord Regional lymphadenopathy Distant metastasis Moderate suspicion Age of either<20 or >70 years Male sex History of head and neck irradiation A nodule >4 cm in diameter or partially cystic Symptoms of compression, including dysphagia, dysphonia, hoarseness, dyspnea, and cough Ultrasound Ultrasonographic Cancer Risk Factors for a Thyroid Nodule hypoechogenicity, microcalcifications, irregular margins, increased nodular flow visualized by Doppler, the evidence of invasion or regional lymphadenopathy Multinodular Goiter : Evaluation TSH FT4, T3 Radionuclide Scan / RAIU US CT Scan (without contrast) FNA biopsy Multinodular Goiter Fine Needle Aspiration Evaluation Biopsy all accessible nodule(s) Biopsy suspicious nodule(s) cold on scan; firm by palpation; growing in size Results less reliable in large goiters Most common diagnosis is “colloid nodule” Fine Needle Aspiration Evaluation FNA results Malignant- pt needs to have surgical management Benign- observation with interval ultrasounds and clinical examinations Indeterminate- radioisotope scan- perform suppression scan and if cold proceed to surgical management- if hot nodule consider observation Non diagnostic- repeat FNA or U/S guided FNA Thyroid Cancers Benign Neoplasms of the Thyroid Thyroid adenoma is a benign neoplastic growth contained within a capsule. Embrional adenoma Fetal adenoma Microfollicular adenoma Macrofollicular adenoma Papillary cystadenoma Hurtle cell adenoma Thyroid Cancer Papillary (mixed papillary and follicular) 75% Follicular carcinoma 16% Medullary carcinoma 5% Undifferentiated carcinomas 3% Miscellaneous (lymphoma, fibrosarcoma, squamous cell carcinoma, malignant hemangioendothelioma, teratomas, and metastatic carcinomas) 1% Papillary Carcinoma very slowly grow and remain confined to the thyroid gland and local lymph nodes for many years. In older patients, more aggressive and invade locally into muscles and trachea. in later stages, they can spread to the lung. Death is usually due to local disease, with invasion of deep tissues in the neck less commonly, death may be due to extensive pulmonary metastases.. Follicular Carcinoma is characterized by the presence of small follicles, colloid formation is poor. capsular or vascular invasion. more aggressive and local invasion of lymph nodes or by blood vessel invasion with distant metastases to bone or lung. often retain the ability to concentrate radioactive iodine, to form thyroglobulin, and, rarely, to synthesize T3 and T4. Follicular Carcinoma rare ''functioning thyroid cancer'' is almost always a follicular carcinoma. more likely to respond to radioactive iodine therapy. In untreated patients, death is due to local extension or to distant bloodstream metastasis with extensive involvement of bone, lungs, and viscera. Medullary Carcinoma a disease of the C cells (parafollicular cells) derived calcitonin, histamin, prostaglandins, serotonin, other peptides more aggressive , but not undifferentiated thyroid cancer. locally into lymph nodes and into surrounding muscle and trachea. lymphatics and blood vessels and metastasize to lungs and viscera. Calcitonin and CEA clinically useful markers for diagnosis and follow-up. Medullary Carcinoma About 80% are sporadic the remainder are familial. four familial patterns: without associated endocrine disease (FMTC); MEN 2a medullary carcinoma, pheochromocytoma, and hyperparathyroidism; MEN 2B, medullary carcinoma, pheochromocytoma, and multiple mucosal neuromas; MEN 3 : with cutaneous lichen amyloidosis, a pruritic skin lesion located on the upper back. Undifferentiated (Anaplastic) Carcinoma small cell, giant cell, and spindle cell carcinomas. usually occur in older patients with a long history of goiter in whom the gland suddenly -over weeks or months- begins to enlarge and produce pressure symptoms, dysphagia, or vocal cord paralysis. Death from massive local extension usually occurs within 6-36 months These tumors are very resistant to therapy . Lymphoma only type of rapidly growing thyroid cancer that is responsive to therapy as part of a generalized lymphoma or may be primary in the thyroid gland. occasionally with long-standing Hashimoto's thyroiditis characterized by lymphocyte invasion of thyroid follicles and blood vessel walls, which helps to differentiate thyroid lymphoma from chronic thyroiditis. If there is no systemic involvement, the tumor may respond dramatically to radiation therapy Cancer metastatic to the thyroid Cancers of the breast and kidney, bronchogenic carcinoma, and malignant melanoma. The primary site of involvement is usually obvious, Occasionally , the diagnosis is made by needle biopsy or open biopsy of a rapidly enlarging cold thyroid nodule. The prognosis is that of the primary tumor, Management of Thyroid Cancer Papillary and Follicular Carcinoma: Low-risk group under age 45 with primary lesions under 1 cm and no evidence of intra- or extraglandular spread. For these patients, lobectomy is adequate therapy All other patients high-risk, and for these total thyroidectomy and-if there is evidence of lymphatic spread -a modified neck dissection are indicated. Prophylactic neck dissection is not necessary. For the high-risk group, postoperative radioiodine ablation Management of Thyroid Cancer Follow-up at intervals of 6-12 months should include careful examination of the neck for recurrent masses. If a lump is noted, needle biopsy is indicated to confirm or rule out cancer. Serum TSH should be checked Serum Tg should be < 1 ng/ml . Thyroiditis Definition Infectious or autoimmune inflammatory diseases of thyroid gland Classification • Hashimoto thyroiditis • Subacute granulomatous thyroiditis • Infectious thyroiditis • Radiation & Trauma induced thyroiditis • Subacute Lymphocytic thyroiditis • Postpartum thyroiditis • Drug induced thyroiditis • Riedel’s thyroiditis HASHIMOTO’s THYROIDITIS Chronic Lymphocytic Thyroiditis •Is the most prevalent form of thyroid autoimmune disease (3-4 % of popul.) and most common cause of hypothyroidism •Is characterized by gradual thyroid failure, goitre or both •Is more common in middle age •Clusters in families •May be associated with other autoimmune disorders Dr. Hakaru Hashimoto Subacute Granulomatous (de Quervain’s) Thyroiditis •Most frequent cause of thyroid pain and tenderness •Postviral inflammatory process (Coxsackievirus, mumps, measles, adenovirus, other) •Strongly associated with HLA-B35, most common in 40-50 years old women •Transient thyroiditis (thyrotoxic for 2-6 wks) Clinical Presentation •Previous viral infection (in 1-3 weeks) •Pain over thyroid,upper neck, jaw, throat,ears •Hoarseness,dysphagia •Fever, palpitation, nervousness, lassitude •Tender, enlarged, firm and often nodular Treatment of DeQuervain’s Thyroiditis A nonsteroidal antiinflammatory drug Aspirin: 2.4-3.6 g in divided doses Naproxen: 1.0-1.5 g in divided doses Prednisone : 30-40 mg qd A beta blocker Propranolol : 40-120 mg Atenolol : 25-50 mg Infectious Thyroiditis Acute (with abscess formation) Gram-positive or negative organisms (via blood or a fistula from the piriform sinus adjacent to the larynx) Chronic Mycobacterial Fungal Pneumocystis Infectious Thyroiditis Acute Usually unilateral neck pain and tenderness Fever, chills, a unilateral neck mass (fluctuant) USG, FNAB, drainage and antibiotics Chronic Bilateral, less prominent neck pain Some patients have hypothyroidism FNAB Radiation and Trauma-Induced Thyroiditis Radiation Thyroiditis Radioiodine treatment of Graves disease Develops 5-10 days later and is mild Trauma-induced Thyroiditis Palpation, thyroid biopsy, surgery, car seat belt Subacute Lymphocytic Thyroiditis (Painless, Silent, Lymphocytic) A variant form of Hashimoto’s thyroiditis Associated with HLA-DR3 Postulated initiating factors : Excess iodine intake Various cytokines Treatment of Subacute Lymphocytic Thyroiditis Most patients need no treatment Symptomatic treatment during the hyperthyroid phase : propranolol or atenolol T4 ( 50-100 µg daily) given for 8-12 wks, discontinued and reevaluated 4-6 wks later Postpartum Thyroiditis •Occurs in 3-16% of pregnancies (25 % in T1DM) •Is seen within 1 year after parturition •Is likely to recur after subsequent pregnancies •Thyrotoxicosis is mild and transient •Antithyroid antibodies are elevated •RAIU is low •Slightly increased ESR Presentation of Postpartum Thyroiditis Transient hyperthyroidism (2-8 wks) followed by hypothyroidism (2-8 wks) and then recovery 2030 % Transient hyperthyroidism alone 20-40 % Transient hypothyroidism alone 40-50 % Drug-Induced Thyroiditis Interferon-alpha thyroiditis Interleukin-2 thyroiditis Amiodarone Riedel’s Thyroditis Is a fibrotic process associated with a mononuclear cell inflammation that extends beyond the thyroid into soft tissue Can involve the parathyroids, the recurrent laryngeal nerve, trachea, mediastinum, ant. chest wall Fibrosclerosis may involve the retroperitoneal space, mediastinum, retroorbital space, the biliary tract Treatment of Riedel’s Thyroiditis Thyroxine Surgery Glucocorticoids Tamoxifen Methylprednisone pulse therapy + azathioprine or penicillamine