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Thyroid Disease: Diagnosis and Management Internal Medicine Resident Lecture Series Michael Pascolini D.O. 8/18/2004 Goal The residents will understand how to diagnose and manage thyroid disease Objectives The residents will: – understand the basic hormonal actions of the thyroid gland – evaluate and diagnose a patient with thyroid disease using clinical skills and lab work – understand the four different types of Malignant thyroid tumors Question #1 In X-linked TBG deficiency, the TSH level is: – A. increased – B. decreased – C. normal Thyroid Axis Hypothalamus TRH Pituitary TSH Thyroid T3 and T4 Dopamine Glucocorticoids Somatostatin Thyroid Axis Thyroid hormones (T3 and T4) are the dominant regulator of TSH & TRH production TSH production – pulsatile; diurnal (highest levels at night) – long plasma 1/2 life (50 min) Iodine Iodine transport is a critical first step in thyroid hormone synthesis Normal thyroid extracts 10-25% radioactive iodine trace over 24 hrs. – Thyroid of Graves disease can extract 70-90% Areas of iodine deficiency have increased incidence of Goiter Oversupply of iodine is associated with increased incidence of autoimmune thyroid disease Decreased iodine increases thyroid bloodflow Excess iodine inhibits thyroid iodide organification (Wolff-Chaikoff effect) Thyroid hormones T4 is secreted 20x in excess of T3 from thyroid gland – both are bound to plasma proteins thyroxinebinding thyroglobulin(TBG), transthyretin (TTR) and Albumin (99.98% T4 and 99.7% T3) – Free T3 > Free T4 (only free hormone is available to tissues) Thyroid hormones Homeostatic mechanisms maintain normal concentration of free hormones – X-linked TBG deficiency - There are low levels of total T3 & T4, however free hormone levels are normal. • patients are euthyroid, TSH levels are normal – TBG are increased by estrogen (pregnancy, estrogen birth control pills) TBG, total T3 & T4 are increased. Free T3 and T4 are normal. – Do not try to normalize the total hormone levels Question #1 In X-linked TBG deficiency, the TSH level is: – A. increased – B. decreased – C. normal Question #1 In X-linked TBG deficiency, the TSH level is: – A. increased – B. decreased – C. normal Question #2 Which of the following can cause a decreased TSH level? – A. severe non thyroid illness – B. medications (increased levels of dopamine and glucocorticoids) – C. TSH secreting pituitary tumor – D. Thyroid hormone resistance (increased free T4 & T3 with normal TSH) Physical Exam Extrathyroid features: Opthalmopathy and Dermopathy Inspect pt from front and side Palpate thyroid from behind pt – note tenderness, fixation, nodularity, masses Bruit over gland suggests increased vascularity (hyperthyroidism) Physical Exam Physical Exam If low boarders are not clearly felt, pt may have retrosternal goiter – Venous distention, difficulty breathing, especially when arms are raised (Pemberton’s sign) Central Masses - have pt stick out tongue, thyroglossal cysts will move upward Asses lymphadenopathy in supraclavicular and cervical regions Lab Eval First determine TSH level – normal TSH level excludes primary abnormalities of thyroid function, with rare exceptions – Abnormal TSH, next get a free T4 and T3 resin uptake tests • Resin uptake test - compares amount of T3 bound to Resin as opposed to unoccupied thyroid hormone binding proteins – uptake increased when proteins are low or Thyroid hormone levels are increased Lab Eval TSH as screening test may be misleading (especially without Free T4) – Increased TSH level • severe non thyroid illness • TSH secreting pituitary tumor • Thyroid hormone resistance (increased free T4 & T3 with normal TSH) • Artifact – Decreased TSH level • 1st trimester of pregnancy (2o hCG secretion) • Treatment of hyperthyroidism (suppression lasts several weeks) • medications (increased levels of dopamine and glucocorticoids) TSH should not be used to assess a patient with known pituitary disease. Hypothyroidism - signs and symptoms (decreasing order of frequency) Signs – – – – – – Dry coarse skin Puffy face, hands and feet Diffuse alopecia Bradycardia Peripheral edema Delayed tendon reflex relaxation – Carpal tunnel syndrome – Serous cavity effusion Symptoms – Tiredness, weakness – Feeling cold – Difficulty concentrating and poor memory – Constipation – Weight gain with poor apatite – Dyspnea – Hoarse voice – Menorrhagia – Parasthesias – Impaired hearing Hypothyroidism increased TSH and a decreased free T4 Congenital Autoimmune Iatrogenic Hypothyroidism Congenital – 1 in 3000-4000 newborns – <10% are diagnosed with clinical features • prolonged jaundice, feeding problems, hypotonia, enlarged tongue, delayed bone maturation. – permanent neurological damage could occur if treatment is delayed – Treatment is levothyroxine at 10-15 mcg/kg/day, monitoring effects by TSH levels Hypothyroidism Autoimmune – may be associated with goiter (Hashimoto’s) or minimal residual thyroid tissue (atrophic thyroiditis), later in the disease. – patients present with typical signs and symptoms Hypothyroidism Iatrogenic – may be caused by radioiodide treatment (in the 1st 3-4 months after treatment) Hypothyroidism Treatment – Start daily replacement dose of levothyroxine at 1.5 mcg/kg of body weight – adjust the dose based on TSH levels – once replacement is achieved, annual TSH are recommended to follow Thyrotoxicosis - signs and symptoms (decreasing order of frequency) Signs – Tachycardia; A-fib in the elderly – Tremor – Goiter – Warm, moist skin – Muscle weakness, proximal myopathy – Lid retraction or lag – Gynecomastia Symptoms – Hyperactivity, irritability, dysphoria – Heat intolerance and sweating – Palpitations – Fatigue and weakness – Weight loss with increased apatite – Diarrhea – Polyuria – Oligomenorrhea Thyrotoxicosis Thyrotoxicosis - the state of thyroid hormone excess Hyperthyroidism - result of excessive thyroid function Labs: Decreased TSH and increased free T3 & T4 Etiologies – Graves’ disease – Thyroiditis – Toxic Adenoma Thyrotoxicosis Graves’ disease – 60-80% of thyrotoxicosis, depending on iodine intake (increased intake= increased prevalence) – Diagnosis can be excluded if TSH is normal – clinical features worsen without treatment; mortality 10-30% Thyrotoxicosis Graves’ disease – Treatment goal is to reduce thyroid hormone synthesis using antithyroid drugs • Thionamides – Propylthiouracil 100-200mg q 6-8 hours – Carbimazole 10-20 mg BID or TID – Methimazole 10-20 mg BID or TID Thyrotoxicosis Thyroiditis – Acute • pt presents in thyroid pain • infection of thyroid, rare, usually secondary to presence of piriform sinus • Treatment guided by Gram stain and culture of FNA biopsy – Subacute (deQuervain’s thyroiditis) • many viruses implicated as cause; peak incidence 30-50 yrs F>M • Treat with relatively large doses of Aspirin or other NSAIDs.(600mg q4-6 hrs) Thyrotoxicosis Thyroiditis – Silent (painless thyroiditis) • usually pts have underlying autoimmune thyroid disease • clinical course same as subacute thyroiditis without the pain • glucocorticoids are not indicated • Propranolol may be used to treat sever thyrotoxicosis Thyrotoxicosis Toxic adenoma • autonomously functioning thyroid nodule – hypersecretion of T4 and T3; leads to thyrotoxicosis • etiology related to iodine deficiency • Always greater than 3cm in diameter • Labs: decreased TSH and marked elevation of T3 levels, borderline elevation of T4 • Almost never malignant • May treat with antithyroid drugs but if size continues to increase, then surgery or I-131 therapy Sick Euthyroid Syndrome Any acute, severe illness can cause abnormalities in TSH of thyroid hormone levels in the absence of underlying disease. These measurements can be misleading Common pattern: Decreased Total and Free T3 with normal levels of T4 and TSH Amiodarone effects on Thyroid Amiodarone is structurally related to thyroid hormone and contains 39% iodine by weight increased iodine levels for >6 months after discontinuation of drug Multiple effects on thyroid function: – acute, transient changes in thyroid function – hypothyroidism in susceptible patients with increased iodine – thyrotoxicosis, possibly by induction of autoimmune Graves’ disease Question #2 Which of the following can cause a decreased TSH level? – A. severe non thyroid illness – B. medications (increased levels of dopamine and glucocorticoids) – C. TSH secreting pituitary tumor – D. Thyroid hormone resistance (increased free T4 & T3 with normal TSH) Question #2 Which of the following can cause a decreased TSH level? – A. severe non thyroid illness – B. medications (increased levels of dopamine and glucocorticoids) – C. TSH secreting pituitary tumor – D. Thyroid hormone resistance (increased free T4 & T3 with normal TSH) Question #3 Which of the following malignant tumors has the poorest prognosis? – A. Anaplastic carcinoma – B. Follicular (well-differentiated thyroid carcinomas) – C. Papillary – D. Medullary thyroid carcinoma Benign lesions Can be categorized into: – nontoxic - diffuse and multinodular goiter – toxic - toxic multinodular goiter, solitary toxic adenoma, and diffuse toxic goiter (Graves’ disease) – inflammatory - Thyroiditis: acute, subacute and chronic Benign thyroid diseases are significant to the surgeon because: – mechanical constraint on the upper aerodigestive structures – it’s not possible to rule out carcinoma within a nodular lesion of the thyroid gland Malignant tumors Primary epithelial tumors, they account for 1.5% of all cancer in the US – – – – Papillary Follicular (well-differentiated thyroid carcinomas) Medullary thyroid carcinoma Anaplastic carcinoma Papillary Adenocarcinomas 80% of all thyroid carcinomas incidence in the 3rd and 4th decade both lobes involved in 80% of the cases; often multicentric tumor spreads by regional lymphatics to paratracheal or lateral cervical lymph nodes locoregional metastasis is high from 37-65% 5-year survival rates range from 70-95% with mortality of 10-20% over 10-20 year period – significant mortality occurs from intrathyroidal lesions > 5cm in diameter or extracapsular spread Follicular Carcinomas 10% of all thyroid cancers more prevalent in areas of endemic goiter occurs exclusively in patients older than 40 years Multicentricity is uncommon as is lymph node metastasis tumor spreads by angioinvasion; distant mets to lungs or bone in 65%of patients 5-year survival rate is about 70%, decreasing to 40% at 10 years. – if distant mets present, 5-year survival is 20% Medullary Thyroid Carcinoma 5-7% of thyroid carcinomas originate from parafollicular cells (neural crest cells) calcified areas in the thyroid is a radiological feature of this tumor 60-80% are sporadic cases;10-40% are familial. sporadic case is unilateral; familial cases are bilateral Familial cases occur in the MEN syndrome type II – better prognosis than the sporadic cases 5- and 10-year survival rates range from 88% and 78%, respectively – cervical lymph node mets affects 10 year rate down to 46% Anaplastic Carcinoma one of the most lethal carcinomas; 1-5% of thyroid malignancies mainly affects patients older than 65 years. only small-cell type responds to radiation therapy Approximately 10% of patients will survive 1 year. – Average duration of survival after diagnosis is 3-6 months Effective treatment is rarely feasible. Thyroid Ultrasound Can differentiate cystic from solid thyroid nodules in >80% cases used increasingly in the diagnosis of thyroid disease 10MHz instruments with detection of nodules >3mm Can also be used to monitor nodular sizes, guide FNA biopsies and aspiration of cystic lesions Thyroid scanning Radioisotopes of iodine can be used to trace the fractional uptake into the gland – Graves’ disease - shows and enlarged thyroid with homogenous tracer uptake – Toxic Adenoma - shows areas of increased uptake with suppressed tracer uptake in remainder of gland – Toxic Multinodular goiter - Enlarged gland with multiple areas of increased and decreased uptake Thyroid scanning – Subacute thyroiditis - very low uptake due to cell damage – Thyrotoxicosis factitia (self-administration of thyroid hormone) - low uptake Cold nodules are usually benign, but have 5-10% chance of being malignant Hot nodules are almost never malignant Scans are also used to follow up on thyroid cancer. Uptake in the thyroid bed after surgery may show metastatic thyroid cancer deposits. Thyroid scanning Fine Needle Aspiration most accurate preop diagnostic modality for evaluation of thyroid nodules Has decreased the need for thyroid surgeries by 50% and increased yield of thyroid malignancies by 50% reports classified as benign, indeterminate or malignant – fewer than 5% false-positives on malignancies Indications for Operation Scan Needle Bx Cystic Solid Neg Pos. or ? Rapid recurrence Surgery Surgery growth or failure to suppress Surgery Suppression cont. disappearance Treatment Thyroidectomy – hemithyroidectomy - half of the thyroid is removed, parathyroids preserved – total thyroidectomy - entire thyroid is removed, parathyroids preserved Complications of Surgery complication rate is low reported complications with surgery – transient hypocalcemia (7.1%) – permanent hypocalcemia (0.4%) – Vocal cord paralysis (1.2%) Further management 131I thyroid ablation and treatment should be coordinated with the surgical approach – ablation is much more effective when there is less normal thyroid tissue in the thyroid bed. – Patient is kept on thyroid treatment for a few weeks post op, then withdrawn. – TSH rise correlates to the amount of normal tissue left. – The residual tissue is then ablated with 131I Further management An initial whole-body scan should be performed about 6 months after surgery and thyroid ablation for more residual tissue. – if positive another larger ablative dose is given – if negative and thyroglobulin (Tg) levels are low, a repeat scan should be done 1 year later – if negative again, then patient can be managed with suppressive therapy and Tg levels every 6 to 12 months Question #3 Which of the following malignant tumors has the poorest prognosis? – A. Anaplastic carcinoma – B. Follicular (well-differentiated thyroid carcinomas) – C. Papillary – D. Medullary thyroid carcinoma Question #3 Which of the following malignant tumors has the poorest prognosis? – A. Anaplastic carcinoma – B. Follicular (well-differentiated thyroid carcinomas) – C. Papillary – D. Medullary thyroid carcinoma