Medical School · Year 3 · Internal Medicine · includes a discussion video

Seminar 15: Thyroid Disorders

Internal Medicine Clerkship

Learning Objectives

By the end of this seminar, students will be able to:

1. Describe thyroid physiology including the hypothalamic-pituitary-thyroid axis, hormone synthesis, and the clinical interpretation of thyroid function tests
2. Recognize the clinical features of hypothyroidism and hyperthyroidism across multiple organ systems and identify atypical presentations
3. Differentiate the causes of thyroid dysfunction using laboratory studies, antibody testing, and radioactive iodine uptake scanning
4. Apply appropriate treatment strategies for hypothyroidism and hyperthyroidism including medication dosing, monitoring, and management of complications
5. Manage thyroid emergencies including thyroid storm and myxedema coma using stepwise pharmacological and supportive approaches
6. Describe the systematic approach to thyroid nodules including ultrasound characterization, fine-needle aspiration indications, and thyroid cancer classification

Seminar Outline

Section 1: Thyroid Physiology

The hypothalamic-pituitary-thyroid axis is a classic neuroendocrine feedback loop that maintains thyroid hormone levels within a narrow physiological range. The hypothalamus secretes thyrotropin-releasing hormone, which travels through the hypothalamic-hypophyseal portal system to stimulate the anterior pituitary thyrotroph cells to secrete thyroid-stimulating hormone. TSH is the primary regulator of thyroid gland function, stimulating iodide uptake, thyroid hormone synthesis, and thyroid hormone secretion through binding to TSH receptors on thyroid follicular cells. The thyroid gland produces and secretes thyroxine (T4) and triiodothyronine (T3), which circulate in the blood and exert negative feedback on both the hypothalamus and anterior pituitary, suppressing further TRH and TSH secretion. This negative feedback loop ensures that thyroid hormone levels are tightly regulated, with TSH serving as the most sensitive indicator of thyroid status because even small changes in thyroid hormone levels produce large, amplified changes in TSH secretion.

Thyroid hormones are essential for normal growth, development, and metabolism. Thyroxine (T4) is the major hormone produced by the thyroid gland but is largely a prohormone that requires peripheral conversion to triiodothyronine (T3) by deiodinase enzymes to become biologically active. T3 is the primary active thyroid hormone and exerts its effects by binding to nuclear thyroid hormone receptors, which regulate gene transcription affecting virtually every organ system. Greater than ninety-nine percent of circulating thyroid hormones are bound to transport proteins, predominantly thyroxine-binding globulin, but also albumin and transthyretin; only the unbound free fraction is biologically active and available to enter cells. This distinction between total and free hormone levels is clinically important because conditions that alter binding protein concentrations (pregnancy, oral contraceptive use, liver disease) will change total hormone levels without affecting free hormone levels or the patient's thyroid status.

The laboratory assessment of thyroid function relies primarily on TSH and free T4 measurements. TSH is the single most sensitive and specific screening test for thyroid dysfunction because the logarithmic-linear relationship between TSH and free T4 means that small changes in free T4 produce large changes in TSH, making TSH abnormalities detectable before free T4 moves outside the normal range. Free T4 measures the biologically active unbound fraction and is the primary confirmatory test when TSH is abnormal. Free T3 is useful in the evaluation of hyperthyroidism (where T3 may be elevated before T4 or where T3-predominant thyrotoxicosis occurs) and in distinguishing sick euthyroid syndrome from true hypothyroidism. Total T4 and total T3 levels are affected by binding protein concentrations and are less useful than free hormone levels in most clinical situations. Thyroid antibody testing, including anti-thyroid peroxidase antibodies and thyroid-stimulating immunoglobulins, helps identify autoimmune causes of thyroid disease.

The interpretation of thyroid function tests follows a logical algorithm based on the pattern of TSH and free T4. An elevated TSH with a low free T4 indicates primary hypothyroidism, the most common pattern of thyroid dysfunction, where the thyroid gland fails and the pituitary increases TSH secretion in an attempt to stimulate more hormone production. An elevated TSH with a normal free T4 represents subclinical hypothyroidism, where the TSH elevation detects early thyroid failure before free T4 falls below the normal range. A low or suppressed TSH with an elevated free T4 indicates hyperthyroidism, where excess thyroid hormone suppresses pituitary TSH secretion. A low TSH with a normal free T4 and free T3 represents subclinical hyperthyroidism, where the TSH suppression detects mild thyroid hormone excess before free hormone levels rise above the normal range. A low TSH with a low free T4 suggests secondary (central) hypothyroidism from pituitary or hypothalamic disease, where the diseased pituitary cannot produce adequate TSH despite low thyroid hormone levels.

<image>Panel A: Hypothalamic-pituitary-thyroid axis diagram showing the hypothalamus secreting TRH, the anterior pituitary secreting TSH, and the thyroid gland producing T4 and T3, with negative feedback loops from T4/T3 back to both hypothalamus and pituitary illustrated with inhibitory arrows. Panel B: Thyroid hormone physiology showing T4 as the major product (prohormone), peripheral conversion by deiodinases to active T3, protein binding (99%+ bound to TBG, albumin, transthyretin) with only the free fraction being biologically active, and T3 binding to nuclear receptors affecting gene transcription. Panel C: Laboratory test hierarchy showing TSH as the most sensitive screening test (amplified response to small T4 changes), free T4 as the confirmatory test, free T3 for hyperthyroidism and sick euthyroid, and antibodies (anti-TPO, TSI) for autoimmune etiology, arranged in diagnostic order. Panel D: TSH and free T4 interpretation matrix showing five patterns: high TSH/low T4 (primary hypothyroidism), high TSH/normal T4 (subclinical hypothyroidism), low TSH/high T4 (hyperthyroidism), low TSH/normal T4 (subclinical hyperthyroidism), and low TSH/low T4 (secondary hypothyroidism), each with diagnostic arrows.</image>

Section 2: Hypothyroidism

Hypothyroidism results from insufficient thyroid hormone production or action and is classified by the level of the endocrine axis affected. Primary hypothyroidism, accounting for over ninety-five percent of cases, results from intrinsic thyroid gland failure. Hashimoto thyroiditis (chronic lymphocytic thyroiditis) is the most common cause in iodine-sufficient regions and involves autoimmune destruction of the thyroid gland. Iatrogenic causes include thyroidectomy, radioactive iodine therapy, and external beam radiation to the neck. Medications, particularly amiodarone and lithium, can cause hypothyroidism through direct toxic effects on thyroid follicular cells or interference with hormone synthesis. Iodine deficiency remains the most common cause worldwide but is rare in developed countries with iodized salt programs. Secondary hypothyroidism results from pituitary disease (TSH deficiency) and tertiary hypothyroidism from hypothalamic disease (TRH deficiency), both of which are uncommon. Transient hypothyroidism occurs during the recovery phase of subacute thyroiditis and postpartum thyroiditis.

Hashimoto thyroiditis deserves particular attention as the most common cause of hypothyroidism in the developed world. The pathogenesis involves autoimmune destruction of thyroid follicular cells by cytotoxic T lymphocytes and antibody-dependent cell-mediated cytotoxicity. The characteristic autoantibodies are anti-thyroid peroxidase antibodies (present in over ninety percent of cases and the most commonly tested) and anti-thyroglobulin antibodies (present in approximately fifty percent). The histological hallmark is dense lymphocytic infiltration of the thyroid gland with germinal center formation and progressive fibrosis. Hashimoto thyroiditis is associated with other autoimmune conditions including type 1 diabetes mellitus, vitiligo, Addison disease, pernicious anemia, celiac disease, and autoimmune hepatitis, forming part of the autoimmune polyendocrine syndromes. The clinical course is typically progressive, with gradual decline in thyroid function over months to years, although some patients may experience a transient thyrotoxic phase (hashitoxicosis) early in the disease when stored hormone is released from the damaged gland.

The clinical features of hypothyroidism affect virtually every organ system and reflect the widespread metabolic effects of thyroid hormone deficiency. General symptoms include fatigue, cold intolerance, and weight gain (typically modest, five to ten pounds, primarily from fluid retention rather than fat accumulation). Dermatologic findings include dry, coarse, cool skin, brittle nails and hair, and non-pitting myxedema (a waxy, dough-like swelling of the skin resulting from glycosaminoglycan deposition in the dermis). Cardiovascular effects include bradycardia, diastolic hypertension (from increased systemic vascular resistance), and pericardial effusion. Gastrointestinal manifestations include constipation from decreased gut motility. Neurologic findings include slow mentation, impaired concentration, delayed relaxation phase of deep tendon reflexes, and carpal tunnel syndrome. Reproductive effects include menorrhagia and infertility in women. The presentation is often insidious, and patients may attribute their symptoms to aging or other conditions, leading to significant diagnostic delay.

Laboratory findings in hypothyroidism extend beyond the thyroid function tests. An elevated TSH with a low free T4 confirms primary hypothyroidism, and positive anti-thyroid peroxidase antibodies establish Hashimoto thyroiditis as the etiology. Hyperlipidemia, particularly elevated LDL cholesterol, is common because thyroid hormone is required for hepatic LDL receptor expression, and thyroid hormone deficiency reduces LDL clearance. A mild normocytic or macrocytic anemia may be present. An elevated creatine kinase reflects decreased skeletal muscle metabolism and may be dramatic, occasionally raising concern for rhabdomyolysis. Hyponatremia from impaired free water excretion occurs in moderate to severe hypothyroidism. Mild elevation of liver transaminases may be observed. These associated laboratory abnormalities typically normalize with thyroid hormone replacement and do not require separate treatment.

<image>Panel A: Hypothyroidism etiology hierarchy showing primary causes (Hashimoto's as most common, iatrogenic from thyroidectomy and RAI, medications including amiodarone and lithium, iodine deficiency worldwide), secondary (pituitary TSH deficiency), and tertiary (hypothalamic TRH deficiency), with relative frequencies annotated. Panel B: Hashimoto thyroiditis detail showing autoimmune pathogenesis (cytotoxic T cells attacking follicular cells), characteristic antibodies (anti-TPO >90%, anti-thyroglobulin ~50%), histology (lymphocytic infiltration with germinal centers), associated autoimmune conditions (type 1 DM, vitiligo, Addison, pernicious anemia), and clinical course (progressive decline with possible early hashitoxicosis). Panel C: Clinical features by organ system showing general (fatigue, cold intolerance, weight gain), skin (dry, coarse, non-pitting myxedema), cardiovascular (bradycardia, diastolic HTN), GI (constipation), neurologic (slow mentation, delayed reflexes, carpal tunnel), and reproductive (menorrhagia, infertility), illustrated on a full-body diagram. Panel D: Laboratory profile showing elevated TSH, low free T4, positive anti-TPO antibodies confirming Hashimoto's, alongside associated findings: hyperlipidemia (elevated LDL), anemia (normocytic or macrocytic), elevated CK, hyponatremia, and mildly elevated transaminases.</image>

Section 3: Hypothyroidism Treatment

Levothyroxine, synthetic thyroxine (T4), is the standard treatment for hypothyroidism and represents one of the most commonly prescribed medications worldwide. The full replacement dose for most adults is approximately 1.6 micrograms per kilogram per day, which translates to doses typically ranging from 75 to 150 micrograms daily. The starting dose should be lower in elderly patients and those with cardiovascular disease to avoid precipitating angina, myocardial infarction, or arrhythmias from the sudden increase in metabolic demand. Levothyroxine has a long half-life of approximately seven days, which allows once-daily dosing and produces stable serum levels, and it should be taken on an empty stomach, ideally thirty to sixty minutes before breakfast, to maximize absorption. The oral bioavailability is approximately seventy to eighty percent, and consistent timing relative to meals is important for maintaining stable levels.

Dose adjustments follow specific guidelines based on the patient population and clinical scenario. Elderly patients and those with known coronary artery disease should be started at 25 to 50 micrograms daily, with gradual increases of 12.5 to 25 micrograms every four to six weeks, to allow the cardiovascular system to adapt to the increased metabolic demand. Patients with severe cardiac disease may need to start at even lower doses of 12.5 to 25 micrograms. Young, otherwise healthy patients can often be started on the full replacement dose without gradual titration. Pregnancy requires special attention: thyroid hormone requirements increase by approximately thirty percent during pregnancy, typically necessitating a dose increase that should be made as early as possible, ideally within the first four to six weeks of gestation, with TSH monitored every four weeks during the first and second trimesters. Patients planning pregnancy should be counseled to contact their provider immediately upon learning they are pregnant for prompt dose adjustment.

Monitoring of levothyroxine therapy requires patience because the full effect of a dose change takes six to eight weeks to be reflected in the TSH level due to the long half-life of thyroxine and the slow response time of the hypothalamic-pituitary axis. TSH should be checked six to eight weeks after initiating therapy or making a dose adjustment, and the dose should be titrated to achieve a TSH within the normal range, with most guidelines recommending a target of 0.5 to 2.5 milliunits per liter for the general population. Once a stable dose is achieved and the TSH is within the target range, annual monitoring with a TSH level is sufficient. Elderly patients may tolerate and benefit from a slightly higher TSH target (up to 4-5 milliunits per liter), as overtreating elderly patients with subclinical hyperthyroidism increases the risk of atrial fibrillation, osteoporosis, and cardiovascular events.

Several factors can interfere with levothyroxine absorption or metabolism and necessitate dose adjustments. Medications that reduce gastrointestinal absorption include iron supplements, calcium supplements, aluminum-containing antacids, cholestyramine, and sucralfate, all of which should be separated from levothyroxine administration by at least four hours. Proton pump inhibitors may reduce absorption by increasing gastric pH and should be taken at a separate time. Medications that increase thyroid hormone metabolism include carbamazepine, phenytoin, phenobarbital, and rifampin, which induce hepatic enzymes that accelerate T4 clearance and may necessitate higher levothyroxine doses. Estrogen therapy (including oral contraceptive pills and hormone replacement therapy) increases thyroxine-binding globulin production, which increases total T4 levels but does not affect free T4 in patients with an intact hypothalamic-pituitary-thyroid axis; however, patients on fixed-dose levothyroxine replacement may require dose increases when starting estrogen because the increased TBG binds more of the exogenous T4, reducing the free fraction. The consistent recommendation to take levothyroxine on an empty stomach aims to minimize variability in absorption and maintain stable hormone levels.

<image>Panel A: Levothyroxine dosing guide showing full replacement dose (1.6 mcg/kg/day), typical dose range (75-150 mcg/day), administration instructions (empty stomach, 30-60 minutes before breakfast), and half-life (7 days allowing once-daily dosing), with a dose calculator illustration. Panel B: Starting dose selection flowchart: young healthy patient (full dose), elderly patient (25-50 mcg, increase every 4-6 weeks), severe cardiac disease (12.5-25 mcg, very slow titration), and pregnancy (increase by 30%, monitor TSH every 4 weeks), with safety rationale annotations. Panel C: Monitoring timeline showing initial TSH check at 6-8 weeks after starting or dose change, dose titration to target TSH 0.5-2.5 mU/L, transition to annual monitoring once stable, and elderly target consideration (higher TSH acceptable), displayed as a calendar timeline. Panel D: Drug interactions and absorption factors showing medications reducing absorption (iron, calcium, antacids, cholestyramine, PPIs with 4-hour separation rule), medications increasing metabolism (carbamazepine, phenytoin, rifampin requiring dose increase), and estrogen effect (increased TBG binding requiring dose adjustment), with timing recommendations.</image>

Section 4: Hyperthyroidism

Hyperthyroidism results from excessive thyroid hormone production or release and has multiple etiologies with distinct pathophysiological mechanisms. Graves disease is the most common cause of hyperthyroidism and is an autoimmune disorder in which thyroid-stimulating immunoglobulins bind to and activate TSH receptors on thyroid follicular cells, causing unregulated hormone production. Toxic multinodular goiter occurs predominantly in elderly patients and results from autonomously functioning nodules that produce thyroid hormone independent of TSH regulation. Toxic adenoma involves a single hyperfunctioning thyroid nodule that produces excess hormone, usually caused by activating mutations in the TSH receptor or the G-protein signaling pathway. Thyroiditis causes transient thyrotoxicosis from the release of preformed hormone from the damaged gland rather than from new hormone synthesis. Exogenous thyrotoxicosis results from excessive ingestion of thyroid hormone, whether intentional or inadvertent. TSH-secreting pituitary adenoma is a rare cause of central hyperthyroidism characterized by an elevated TSH with elevated free T4, which is the opposite of the expected pattern.

Graves disease warrants detailed discussion as the most common cause of hyperthyroidism, particularly in younger patients. The pathogenesis involves thyroid-stimulating immunoglobulins, which are IgG autoantibodies that bind to and activate the TSH receptor, mimicking the action of TSH and stimulating thyroid hormone synthesis and secretion. Graves disease is five to ten times more common in women than men and has a peak incidence in the third to fifth decades. Three unique extrathyroidal manifestations distinguish Graves disease from other causes of hyperthyroidism: ophthalmopathy (proptosis, periorbital edema, lid retraction, and diplopia from inflammatory infiltration and glycosaminoglycan deposition in the extraocular muscles and orbital fat), dermopathy (pretibial myxedema, characterized by localized waxy, indurated skin lesions on the anterior shins), and acropachy (digital clubbing). The thyroid-stimulating immunoglobulin test is the most specific serologic marker, and radioactive iodine-123 uptake scan demonstrates diffusely increased uptake throughout the gland, distinguishing Graves disease from thyroiditis (which shows low or absent uptake).

The clinical features of hyperthyroidism reflect the systemic effects of excess thyroid hormone on metabolism, the cardiovascular system, and the nervous system. General symptoms include unintentional weight loss despite increased appetite, heat intolerance, and excessive sweating. Cardiovascular manifestations are often the most prominent and include tachycardia (frequently the first noted finding), palpitations, and atrial fibrillation (occurring in ten to fifteen percent of hyperthyroid patients, particularly the elderly). Neurologic features include tremor (typically a fine, rapid tremor of the outstretched hands), anxiety, emotional lability, insomnia, and hyperreflexia. Gastrointestinal effects include increased bowel frequency and hyperdefecation (not true diarrhea). Dermatologic findings include warm, moist skin, hair thinning, and onycholysis. Ocular findings common to all forms of hyperthyroidism include lid lag (the upper eyelid fails to keep pace with the globe during downward gaze) and stare (wide palpebral fissures from sympathetic activation of Mueller muscle), while true proptosis and inflammatory eye disease are specific to Graves disease.

Laboratory findings in hyperthyroidism demonstrate a suppressed TSH (typically below 0.01 milliunits per liter) with elevated free T4 and/or free T3. In some patients, particularly those with early Graves disease or toxic nodular disease, the free T3 may be disproportionately elevated with a normal free T4, a pattern called T3 thyrotoxicosis, which occurs because the hyperactive thyroid gland preferentially synthesizes T3. Radioactive iodine uptake scanning using iodine-123 is essential for determining the etiology of hyperthyroidism: diffusely increased uptake indicates Graves disease, one or more focal areas of increased uptake ("hot nodules") indicate toxic multinodular goiter or toxic adenoma, and low or absent uptake indicates thyroiditis or exogenous thyroid hormone intake. This distinction is critical because the treatment approach differs significantly based on the etiology: antithyroid drugs and radioactive iodine are effective for Graves disease and toxic nodular disease (which produce new hormone) but are contraindicated or ineffective in thyroiditis (which releases preformed hormone).

<image>Panel A: Hyperthyroidism etiology comparison showing Graves disease (most common, TSI autoantibodies activating TSH receptor), toxic multinodular goiter (elderly, multiple autonomous nodules), toxic adenoma (single hyperfunctioning nodule), thyroiditis (transient, hormone release from destruction), exogenous (excessive hormone intake), and TSH-secreting adenoma (rare, elevated TSH with elevated T4). Panel B: Graves disease features showing pathogenesis (TSI binding and activating TSH receptor), female predominance (5-10x), three unique extrathyroidal manifestations (ophthalmopathy with proptosis diagram, pretibial dermopathy with shin lesion, and acropachy with clubbed digits), and diagnostic tests (TSI positive, I-123 scan showing diffuse uptake). Panel C: Clinical features by organ system on a body diagram: general (weight loss, heat intolerance, sweating), cardiovascular (tachycardia, palpitations, atrial fibrillation), neurologic (tremor, anxiety, hyperreflexia), GI (hyperdefecation), skin (warm, moist, hair thinning), and eyes (lid lag, stare, proptosis in Graves), with symptom frequency annotations. Panel D: Diagnostic laboratory and imaging panel showing suppressed TSH below 0.01, elevated free T4 and T3, T3 thyrotoxicosis pattern, and I-123 uptake scan comparison: diffuse uptake (Graves), focal hot nodules (toxic nodular), and low/absent uptake (thyroiditis or exogenous).</image>

Section 5: Hyperthyroidism Treatment

The treatment of hyperthyroidism involves three primary modalities: antithyroid drugs, radioactive iodine ablation, and surgery, with the choice depending on the etiology, patient preferences, and clinical circumstances. Antithyroid drugs are the first-line treatment in many cases of Graves disease, particularly in younger patients, those with mild disease, or those who prefer to avoid radiation or surgery. Radioactive iodine ablation provides definitive treatment by destroying thyroid tissue and is widely used, but it results in permanent hypothyroidism requiring lifelong levothyroxine replacement in most patients. Thyroidectomy is preferred in patients with large goiters causing compressive symptoms, suspicious or malignant thyroid nodules, moderate to severe Graves ophthalmopathy (where RAI may worsen eye disease), and pregnant patients in the second trimester who cannot tolerate antithyroid medications. The choice among these three options should involve shared decision-making with the patient, considering efficacy, risks, convenience, and long-term outcomes.

Antithyroid drugs, methimazole and propylthiouracil, inhibit thyroid hormone synthesis by blocking the thyroid peroxidase enzyme that catalyzes the organification and coupling reactions in hormone production. Methimazole is the preferred agent due to its longer half-life allowing once-daily dosing, faster onset of action, and lower incidence of serious adverse effects compared to propylthiouracil. Propylthiouracil is preferred in two specific situations: the first trimester of pregnancy (because methimazole is associated with rare but serious embryopathy including aplasia cutis and choanal atresia) and thyroid storm (because PTU uniquely inhibits peripheral T4-to-T3 conversion in addition to blocking thyroid hormone synthesis). Common adverse effects include rash, urticaria, and arthralgia. The most serious adverse effect is agranulocytosis, occurring in approximately 0.2 to 0.5 percent of patients, which presents with fever, sore throat, and markedly depressed neutrophil count and requires immediate drug discontinuation and supportive care. Hepatotoxicity is another rare but serious complication, more common with propylthiouracil than methimazole.

Radioactive iodine therapy with iodine-131 provides definitive treatment of hyperthyroidism by delivering targeted radiation to thyroid follicular cells, producing cellular necrosis and gradual thyroid gland destruction. The therapeutic effect develops over weeks to months, during which the patient may remain hyperthyroid and should continue beta-blocker therapy for symptom control. The expected outcome is permanent hypothyroidism, which occurs in the majority of patients and requires lifelong levothyroxine replacement. Contraindications include pregnancy (absolute), breastfeeding, and moderate to severe Graves ophthalmopathy, where RAI may exacerbate eye disease by releasing thyroid antigens that cross-react with orbital tissue, stimulating the orbital inflammatory process. Patients should be counseled to avoid pregnancy for at least six months after RAI treatment and to avoid close contact with young children and pregnant women for several days after treatment due to radiation exposure.

Beta-blockers are an essential adjunctive therapy for symptomatic relief in all forms of hyperthyroidism, regardless of the definitive treatment chosen. Propranolol is the preferred beta-blocker because, in addition to its non-selective beta-adrenergic blockade that controls tachycardia, palpitations, tremor, and anxiety, it also inhibits the peripheral conversion of T4 to T3, providing a modest additional therapeutic effect. Beta-blockers provide rapid symptomatic relief within hours to days and serve as a critical bridge while awaiting the onset of action of antithyroid drugs (which take two to four weeks to produce significant hormone reduction) or radioactive iodine (which takes weeks to months). All patients with symptomatic hyperthyroidism should receive beta-blocker therapy unless contraindicated by asthma, decompensated heart failure, or significant bradycardia. Beta-blockers are particularly important in elderly patients and those with cardiovascular disease, where uncontrolled tachycardia poses the greatest risk of complications including atrial fibrillation with rapid ventricular response.

<image>Panel A: Three treatment modalities comparison showing antithyroid drugs (first-line for many Graves patients, blocks TPO enzyme), radioactive iodine (definitive, causes hypothyroidism, I-131 destroys thyroid tissue), and surgery (for large goiters, suspicious nodules, severe ophthalmopathy, pregnancy), with indications and outcomes for each. Panel B: Antithyroid drug comparison showing methimazole (preferred, once-daily, fewer side effects) versus PTU (first trimester pregnancy, thyroid storm, also blocks T4-to-T3 conversion), with shared adverse effects (rash, arthralgia) and serious risks (agranulocytosis 0.2-0.5%, hepatotoxicity) highlighted. Panel C: Radioactive iodine therapy diagram showing I-131 uptake by thyroid follicular cells, cellular necrosis and gland destruction over weeks to months, expected outcome of permanent hypothyroidism, and contraindications (pregnancy, breastfeeding, severe ophthalmopathy), with post-treatment precautions. Panel D: Beta-blocker role illustration showing propranolol as preferred agent with dual mechanism (beta-blockade for symptom control plus inhibition of T4-to-T3 conversion), rapid onset providing bridge therapy, and symptom targets (tachycardia, palpitations, tremor, anxiety), with contraindications noted.</image>

Section 6: Thyroid Emergencies

Thyroid storm is a life-threatening exacerbation of hyperthyroidism characterized by multisystem decompensation that carries high mortality if not promptly recognized and treated. Precipitating factors include surgery, infection, trauma, radioactive iodine therapy, iodinated contrast administration, and discontinuation of antithyroid medications, all of which can trigger a massive release or peripheral effect of thyroid hormones. The clinical presentation features extreme manifestations of thyrotoxicosis: high fever (often exceeding 104 degrees Fahrenheit or 40 degrees Celsius), severe tachycardia (often with atrial fibrillation and rapid ventricular response), altered mental status ranging from agitation and delirium to obtundation and coma, and gastrointestinal manifestations including nausea, vomiting, diarrhea, and jaundice from hepatic dysfunction. The diagnosis is clinical, as thyroid hormone levels cannot distinguish thyroid storm from uncomplicated thyrotoxicosis; the Burch-Wartofsky Point Scale is a validated clinical scoring system that quantifies the probability of thyroid storm based on temperature, cardiovascular function, CNS effects, and gastrointestinal-hepatic dysfunction.

The treatment of thyroid storm requires a multifaceted pharmacological approach that addresses hormone synthesis, hormone release, peripheral conversion, and systemic effects simultaneously. Step one is the administration of propylthiouracil (preferred over methimazole in this setting because it blocks both hormone synthesis and peripheral T4-to-T3 conversion), given as a loading dose of 500 to 1000 milligrams followed by 250 milligrams every four hours. Step two is the administration of iodine (either potassium iodide solution or Lugol solution), which must be given at least one hour after PTU to ensure that the excess iodide is not used as substrate for new hormone synthesis; the iodine blocks further thyroid hormone release through the Wolff-Chaikoff effect. Step three is aggressive beta-blockade with propranolol (60 to 80 milligrams orally every four hours) or esmolol infusion for intravenous control. Step four is corticosteroid administration (hydrocortisone 300 milligrams IV loading dose followed by 100 milligrams every eight hours or dexamethasone 2 milligrams every six hours), which blocks peripheral T4-to-T3 conversion and provides adrenal support. Step five is aggressive supportive care including active cooling (avoiding aspirin, which displaces thyroid hormone from binding proteins), intravenous fluids, treatment of the precipitating factor, and intensive care unit monitoring.

Myxedema coma is the most extreme and life-threatening manifestation of hypothyroidism, characterized by severe decompensation of multiple organ systems in the setting of profoundly deficient thyroid hormone levels. Precipitating factors include infection (the most common trigger), surgery, cold exposure, medications (sedatives, opioids, anesthetics), and non-compliance with thyroid hormone replacement. The clinical presentation features hypothermia (often the most striking finding, with core temperature below 95 degrees Fahrenheit or 35 degrees Celsius), altered mental status ranging from confusion to frank coma, hypotension from decreased cardiac output and peripheral vascular tone, hypoventilation with hypercapnia and hypoxemia, and hyponatremia from impaired free water excretion. Laboratory findings include markedly elevated TSH (often above 50 milliunits per liter), very low free T4, and evidence of precipitating illness. Despite its name, true coma is not required for the diagnosis, and clinicians should have a low threshold for initiating treatment when clinical suspicion is high.

Treatment of myxedema coma requires aggressive thyroid hormone replacement, corticosteroid coverage, and comprehensive supportive care. Intravenous levothyroxine is administered as a loading dose of 200 to 500 micrograms, which rapidly repletes depleted body stores, followed by a daily maintenance dose of 50 to 100 micrograms intravenously until the patient can take oral medication. Intravenous liothyronine (T3) may be added to the regimen because peripheral conversion of T4 to T3 may be impaired in critical illness, and T3 provides a more rapid onset of action at the cellular level. Intravenous hydrocortisone (100 milligrams every eight hours) must be administered concomitantly until adrenal insufficiency is excluded, because thyroid hormone replacement in a patient with concurrent undiagnosed adrenal insufficiency can precipitate adrenal crisis by increasing cortisol metabolism. Supportive care includes passive rewarming (active external warming should be avoided because it can cause peripheral vasodilation and cardiovascular collapse), cautious intravenous fluid administration, mechanical ventilation if needed, treatment of the precipitating illness with appropriate antibiotics, and intensive care unit monitoring with close attention to hemodynamic status.

<image>Panel A: Thyroid storm presentation showing precipitating factors (surgery, infection, trauma, RAI, contrast), clinical features (fever >104F, severe tachycardia with AF, altered mental status from agitation to coma, GI/hepatic dysfunction with jaundice), Burch-Wartofsky scoring elements, and mortality risk annotation. Panel B: Thyroid storm five-step treatment protocol displayed as a sequential ladder: Step 1 PTU (blocks synthesis and conversion, 500-1000 mg load), Step 2 iodine 1 hour after PTU (blocks release via Wolff-Chaikoff), Step 3 beta-blocker (propranolol 60-80 mg q4h or esmolol drip), Step 4 corticosteroids (hydrocortisone 300 mg IV load, blocks conversion), Step 5 supportive care (cooling avoiding aspirin, fluids, treat precipitant, ICU). Panel C: Myxedema coma presentation showing precipitants (infection, surgery, cold, sedatives), clinical features (hypothermia <95F, altered mental status, hypotension, hypoventilation), laboratory findings (TSH >50, very low T4), and the clarification that true coma is not required for diagnosis. Panel D: Myxedema coma treatment showing IV levothyroxine (200-500 mcg loading, 50-100 mcg daily maintenance), IV T3 consideration (faster onset), IV hydrocortisone (100 mg q8h until adrenal insufficiency excluded), and supportive measures (passive rewarming only, cautious fluids, ventilatory support, treat precipitant, ICU monitoring).</image>

Section 7: Thyroid Nodules

Thyroid nodules are extremely common, with a prevalence of fifty to sixty percent on high-resolution ultrasound in the general adult population, and the vast majority are benign. The clinically important question is whether a nodule harbors thyroid cancer, which occurs in five to fifteen percent of nodules that come to clinical attention. The evaluation of thyroid nodules begins with a thorough clinical history, focusing on risk factors for malignancy including prior radiation exposure to the head and neck (particularly during childhood), family history of thyroid cancer or multiple endocrine neoplasia syndromes, rapid nodule growth, compressive symptoms (dysphagia, dysphonia, dyspnea), and male sex (which confers a relatively higher risk of malignancy per nodule). Physical examination should assess nodule size, consistency (firm or hard nodules are more concerning), fixation to surrounding structures, and the presence of palpable cervical lymphadenopathy, all of which raise concern for malignancy.

The initial laboratory evaluation of a thyroid nodule should include a TSH measurement. If the TSH is low, suggesting hyperthyroidism, a radioactive iodine uptake scan should be performed to determine whether the nodule is hyperfunctioning ("hot"), which virtually excludes malignancy and does not require biopsy. If the TSH is normal or elevated, the nodule should be evaluated with thyroid ultrasound. Thyroid ultrasound is the single most important imaging modality for characterizing nodules and determining which nodules require fine-needle aspiration biopsy. Ultrasound provides detailed information about nodule size, composition, echogenicity, margins, calcifications, and relationship to surrounding structures, all of which contribute to the risk stratification that guides the decision to biopsy.

Ultrasound features are categorized into those that suggest benign versus suspicious lesions. Features suggesting a benign nodule include a purely cystic composition (virtually zero malignancy risk), a spongiform appearance (multiple small cystic spaces comprising more than fifty percent of the nodule), and regular, smooth margins. Suspicious features that raise concern for malignancy include a solid hypoechoic composition, a taller-than-wide shape (anteroposterior diameter greater than transverse diameter), irregular or infiltrative margins suggesting invasion of surrounding tissue, microcalcifications (tiny punctate echogenic foci without acoustic shadowing, representing psammoma bodies characteristic of papillary thyroid cancer), and extrathyroidal extension. The American College of Radiology Thyroid Imaging Reporting and Data System (TI-RADS) provides a standardized scoring system that integrates these features and assigns a risk level to guide biopsy decisions.

Fine-needle aspiration biopsy is the gold standard for evaluating thyroid nodules and determining the need for surgical intervention. The size threshold for biopsy depends on the ultrasound risk assessment: highly suspicious nodules should be biopsied at one centimeter or larger, intermediate suspicion nodules at one centimeter or larger, low suspicion nodules at 1.5 centimeters or larger, and very low suspicion nodules at two centimeters or larger (or may be observed). The Bethesda System for Reporting Thyroid Cytopathology provides a standardized six-category classification of fine-needle aspiration results: Category I (nondiagnostic/unsatisfactory), Category II (benign), Category III (atypia of undetermined significance), Category IV (follicular neoplasm), Category V (suspicious for malignancy), and Category VI (malignant). Each category carries a defined risk of malignancy and a recommended management pathway, ranging from repeat biopsy or surveillance for low-risk categories to surgical excision for high-risk categories.

<image>Panel A: Thyroid nodule epidemiology and risk factors showing prevalence (50-60% on ultrasound), malignancy rate (5-15%), and risk factors for malignancy (prior radiation, family history, rapid growth, compressive symptoms, male sex, firm consistency, fixed mass, cervical lymphadenopathy), displayed as a risk assessment checklist. Panel B: Initial evaluation algorithm showing TSH measurement as first step: low TSH leads to I-123 scan (hot nodule excludes malignancy, no biopsy needed), normal or elevated TSH leads to thyroid ultrasound for characterization, with branching pathways for each scenario. Panel C: Ultrasound feature comparison showing benign features (purely cystic, spongiform, smooth margins) versus suspicious features (solid hypoechoic, taller-than-wide, irregular margins, microcalcifications, extrathyroidal extension), with ultrasound image examples and risk level annotations. Panel D: FNA biopsy decision guide showing size thresholds by suspicion level (high suspicion at 1 cm, intermediate at 1 cm, low at 1.5 cm, very low at 2 cm), and the Bethesda System six categories (I-nondiagnostic through VI-malignant) with malignancy risk percentages and recommended management at each level.</image>

Section 8: Thyroid Cancer

Thyroid cancer encompasses four major histological types with dramatically different clinical behaviors and prognoses. Papillary thyroid cancer is the most common type, accounting for approximately eighty percent of thyroid malignancies, and has an excellent prognosis with ten-year survival rates exceeding ninety-five percent. Follicular thyroid cancer accounts for ten to fifteen percent of cases and tends to spread hematogenously to distant sites including bone and lung rather than to regional lymph nodes. Medullary thyroid cancer accounts for approximately five percent of cases and arises from parafollicular C-cells rather than follicular cells, with calcitonin serving as a specific tumor marker. Anaplastic thyroid cancer accounts for less than two percent of cases but is one of the most aggressive malignancies in all of oncology, with a median survival of only three to six months from diagnosis. The vast majority of patients diagnosed with thyroid cancer will have well-differentiated disease (papillary or follicular) with an excellent long-term prognosis.

Papillary thyroid cancer is the prototypical well-differentiated thyroid cancer and deserves detailed discussion due to its high prevalence. It occurs with peak incidence between thirty and fifty years of age, is two to three times more common in women, and is strongly associated with prior radiation exposure. The prognosis is excellent, with greater than ninety-five percent ten-year survival for most patients, even those with regional lymph node metastases, which are present in approximately thirty percent of patients at diagnosis. The characteristic spread pattern is through the lymphatic system to regional cervical lymph nodes, distinguishing it from follicular cancer, which preferentially spreads hematogenously. Histological features include papillary architecture, Orphan Annie eye nuclei (optically clear nuclei), psammoma bodies (concentric calcified lamellated structures corresponding to the microcalcifications seen on ultrasound), and nuclear grooves. Multifocality within the thyroid gland is common, occurring in twenty to eighty percent of cases.

Treatment of thyroid cancer is determined by the histological type, stage, and risk stratification. Low-risk papillary thyroid cancer (unifocal, intrathyroidal, less than four centimeters, no extrathyroidal extension, no vascular invasion, no aggressive histological variant) may be adequately treated with lobectomy alone, avoiding the complications of total thyroidectomy including hypoparathyroidism and recurrent laryngeal nerve injury. Higher-risk differentiated thyroid cancer (large tumors, extrathyroidal extension, vascular invasion, clinically significant lymph node metastases, aggressive histological variants) is treated with total thyroidectomy, often followed by radioactive iodine-131 ablation to destroy residual thyroid tissue and any iodine-avid metastases. Long-term follow-up involves surveillance with serum thyroglobulin levels (which serve as a tumor marker for differentiated thyroid cancer and should be undetectable after total thyroidectomy and RAI ablation), thyroglobulin antibody levels, and periodic neck ultrasound. TSH suppression therapy with supraphysiologic levothyroxine doses may be used in high-risk patients to suppress any TSH-dependent residual cancer growth.

Medullary thyroid cancer arises from the parafollicular C-cells and has unique features that distinguish it from well-differentiated thyroid cancers. The tumor produces calcitonin, which serves as a highly specific and sensitive tumor marker for diagnosis, monitoring, and detection of recurrence. Approximately twenty-five percent of medullary thyroid cancers are hereditary, caused by activating germline mutations in the RET proto-oncogene, and are associated with multiple endocrine neoplasia type 2 syndromes: MEN 2A (medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism) and MEN 2B (medullary thyroid cancer, pheochromocytoma, and mucosal neuromas with a marfanoid habitus). All patients diagnosed with medullary thyroid cancer should undergo genetic testing for RET mutations, and family members of patients with hereditary disease should be screened with genetic testing and offered prophylactic thyroidectomy if they carry the mutation. Treatment is total thyroidectomy with central lymph node dissection, and radioactive iodine is not effective because C-cells do not concentrate iodine.

<image>Panel A: Thyroid cancer type comparison showing four types in descending frequency: papillary (80%, excellent prognosis, lymphatic spread), follicular (10-15%, hematogenous spread to bone and lung), medullary (5%, C-cell origin, calcitonin marker), and anaplastic (<2%, extremely aggressive, median survival 3-6 months), with survival data for each type. Panel B: Papillary thyroid cancer detail showing peak age 30-50, female predominance, radiation association, 95%+ ten-year survival, lymphatic spread to cervical nodes, histological features (papillary architecture, Orphan Annie nuclei, psammoma bodies, nuclear grooves), and multifocality. Panel C: Treatment algorithm showing low-risk DTC (lobectomy sufficient) versus high-risk DTC (total thyroidectomy plus RAI ablation), followed by surveillance with thyroglobulin monitoring, neck ultrasound, and TSH suppression in high-risk patients, with risk stratification criteria at the branch point. Panel D: Medullary thyroid cancer features showing C-cell origin, calcitonin as tumor marker, 25% hereditary with RET mutations, MEN 2A (MTC plus pheochromocytoma plus hyperparathyroidism) and MEN 2B (MTC plus pheochromocytoma plus mucosal neuromas), genetic testing recommendation, and treatment (total thyroidectomy plus node dissection, RAI not effective).</image>

Section 9: Subclinical Thyroid Disease

Subclinical hypothyroidism is defined by an elevated TSH with a normal free T4 and represents the earliest stage of thyroid failure before overt hypothyroidism develops. Many patients with subclinical hypothyroidism are asymptomatic, although some report subtle symptoms of fatigue, mild cognitive impairment, or weight gain that may be attributed to the mild thyroid hormone deficiency. The rate of progression to overt hypothyroidism is approximately two to five percent per year, with higher progression rates in patients with positive anti-thyroid peroxidase antibodies and higher initial TSH levels. The decision to treat subclinical hypothyroidism with levothyroxine is individualized: treatment is generally recommended when the TSH exceeds 10 milliunits per liter, when symptoms are present and potentially attributable to thyroid dysfunction, or when anti-TPO antibodies are positive (indicating autoimmune thyroiditis with a high likelihood of progression).

Subclinical hyperthyroidism is defined by a low or suppressed TSH with normal free T4 and free T3 levels and may represent early or mild autonomous thyroid hormone production. Unlike subclinical hypothyroidism, subclinical hyperthyroidism carries definable risks even in the absence of overt symptoms, including an increased risk of atrial fibrillation (particularly in patients over sixty-five years), accelerated bone loss with increased fracture risk (particularly in postmenopausal women), and potentially increased cardiovascular mortality. Treatment is generally recommended when the TSH is persistently below 0.1 milliunits per liter, particularly in elderly patients and those with cardiovascular disease or osteoporosis. When the TSH is mildly suppressed (0.1 to 0.4 milliunits per liter), close monitoring with repeat testing in three to six months is appropriate, with treatment reserved for patients who develop symptoms, persistent TSH suppression, or progression to overt hyperthyroidism.

Sick euthyroid syndrome, also known as non-thyroidal illness syndrome, describes the characteristic changes in thyroid function tests that occur during acute and chronic non-thyroidal illness. The most common finding is a low total T3 and low free T3, which results from decreased peripheral conversion of T4 to T3 by type 1 deiodinase, with preferential conversion to the metabolically inactive reverse T3. In more severe illness, total T4 and free T4 may also fall, and TSH may be low, normal, or mildly elevated during the recovery phase. The thyroid function test pattern in sick euthyroid syndrome can mimic central (secondary) hypothyroidism, creating a diagnostic challenge. Current evidence supports the interpretation that these changes represent an adaptive response to illness that conserves energy by reducing metabolic rate, and treatment with thyroid hormone is not recommended because randomized trials have not demonstrated benefit and potential harm exists from increasing metabolic demand in a critically ill patient. Thyroid function tests normalize during recovery from the underlying illness.

Special populations require modified approaches to thyroid disease management. During pregnancy, TSH reference ranges change by trimester: first-trimester TSH is typically lower than the non-pregnant range due to the thyroid-stimulating effect of human chorionic gonadotropin, which shares structural homology with TSH. Overt hypothyroidism during pregnancy must be treated promptly due to risks of preeclampsia, placental abruption, and impaired fetal neurodevelopment. Elderly patients may have an appropriately higher TSH that does not require treatment, as population studies demonstrate that TSH distributions shift rightward with aging; overtreating elderly patients to achieve younger-adult TSH targets may cause subclinical hyperthyroidism with its attendant risks. Patients with cardiac disease should be treated with lower starting doses of levothyroxine and slower titration to avoid precipitating angina or arrhythmias. Postpartum women should be screened for thyroiditis, which can present with transient hyperthyroidism, hypothyroidism, or the classic biphasic pattern of hyperthyroidism followed by hypothyroidism.

<image>Panel A: Subclinical hypothyroidism definition and management showing elevated TSH with normal free T4, progression rate (2-5% per year to overt hypothyroidism), factors increasing progression (positive anti-TPO, higher TSH), and treatment indications (TSH >10, symptoms present, positive anti-TPO), displayed as a decision algorithm. Panel B: Subclinical hyperthyroidism showing low TSH with normal free hormones, associated risks (atrial fibrillation especially in elderly, bone loss in postmenopausal women, cardiovascular mortality), treatment indications (persistent TSH <0.1, elderly, cardiovascular disease, osteoporosis), and monitoring strategy (repeat testing in 3-6 months if mildly suppressed TSH). Panel C: Sick euthyroid syndrome showing the characteristic laboratory pattern (low T3 from decreased conversion, possible low T4 in severe illness, variable TSH), the adaptive response interpretation (energy conservation, no treatment recommended), differential from central hypothyroidism, and the expectation of normalization during recovery. Panel D: Special populations panel showing pregnancy (trimester-specific TSH ranges, hCG-mediated TSH suppression, risks of untreated hypothyroidism), elderly (rightward TSH shift with aging, higher target acceptable, avoid overtreatment), cardiac disease (low starting dose, slow titration), and postpartum (screen for thyroiditis, biphasic pattern).</image>

Section 10: Thyroiditis

Thyroiditis encompasses a group of inflammatory thyroid disorders with diverse etiologies, clinical presentations, and outcomes. Hashimoto thyroiditis (chronic lymphocytic thyroiditis) is the most common form and produces chronic, progressive hypothyroidism through autoimmune destruction of the thyroid gland, as discussed in detail in Section 2. Subacute thyroiditis (de Quervain thyroiditis) is a self-limited inflammatory condition thought to be triggered by viral infection, presenting with a painful, tender thyroid gland and transient thyrotoxicosis. Postpartum thyroiditis is an autoimmune condition occurring in five to ten percent of women within the first year after delivery, presenting with a characteristic biphasic pattern. Silent (painless) thyroiditis is clinically similar to postpartum thyroiditis but occurs outside the postpartum period. Drug-induced thyroiditis is increasingly recognized, particularly with amiodarone and immune checkpoint inhibitor therapy used in cancer treatment.

Subacute thyroiditis follows a characteristic triphasic clinical course that is important to recognize. The initial thyrotoxic phase, lasting four to eight weeks, results from the release of preformed thyroid hormone from the inflamed and damaged gland; during this phase, the radioactive iodine uptake is low (because new hormone is not being synthesized, and the TSH is suppressed). The hypothyroid phase follows, lasting two to four months, as the depleted thyroid gland cannot produce adequate hormone while it heals. The recovery phase then ensues as the gland regenerates, and most patients return to normal thyroid function, although approximately five to fifteen percent develop permanent hypothyroidism. Treatment during the thyrotoxic phase targets symptoms with nonsteroidal anti-inflammatory drugs for pain (or corticosteroids for severe pain not responding to NSAIDs) and beta-blockers for thyrotoxic symptoms. Antithyroid drugs are not indicated because the thyrotoxicosis results from hormone release rather than new synthesis.

Amiodarone-induced thyroid dysfunction is a common clinical problem because amiodarone contains approximately thirty-seven percent iodine by weight and has complex effects on thyroid physiology. Amiodarone-induced thyrotoxicosis is classified into two types with different mechanisms and treatments. Type 1 occurs in patients with underlying thyroid disease (Graves disease or multinodular goiter) where the excess iodine provides substrate for increased hormone synthesis, and the radioactive iodine uptake is typically normal or elevated; treatment is with antithyroid drugs. Type 2 occurs in patients with a previously normal thyroid gland, where amiodarone causes a destructive thyroiditis with release of preformed hormone, and the radioactive iodine uptake is typically low or absent; treatment is with corticosteroids. In practice, mixed forms are common and may require combined therapy. Amiodarone-induced hypothyroidism is more common than thyrotoxicosis and is treated with levothyroxine, often at higher-than-usual doses because of amiodarone's inhibitory effects on T4-to-T3 conversion.

Postpartum thyroiditis is an autoimmune condition that occurs in five to ten percent of women within two to six months after delivery and follows a characteristic biphasic course similar to subacute thyroiditis but without pain. The initial thyrotoxic phase (lasting weeks to months) results from immune-mediated thyroid destruction with hormone release, followed by a hypothyroid phase (lasting months) as the damaged gland recovers. Many patients experience only one phase (either thyrotoxicosis or hypothyroidism). Approximately fifty percent of women with postpartum thyroiditis develop permanent hypothyroidism within seven years, making long-term follow-up essential. The strongest risk factor is the presence of anti-thyroid peroxidase antibodies, which are present in the majority of affected women and can be used to identify women at risk prior to delivery. Treatment is supportive: beta-blockers during the thyrotoxic phase and levothyroxine during the hypothyroid phase if symptomatic. Women with postpartum thyroiditis have a high recurrence rate with subsequent pregnancies and should be counseled about this risk.

<image>Panel A: Thyroiditis classification showing five types: Hashimoto (chronic autoimmune, progressive hypothyroidism), subacute de Quervain (viral trigger, painful, triphasic), postpartum (autoimmune, biphasic, 5-10% of women), silent/painless (autoimmune, biphasic, non-postpartum), and drug-induced (amiodarone, checkpoint inhibitors), with key distinguishing features for each. Panel B: Subacute thyroiditis triphasic course shown as a timeline graph: thyrotoxic phase (4-8 weeks, hormone release, low RAI uptake), hypothyroid phase (2-4 months, depleted stores), and recovery (return to normal, 5-15% permanent hypothyroidism), with treatment at each phase annotated (NSAIDs/steroids for pain, beta-blockers for symptoms, levothyroxine if needed). Panel C: Amiodarone-induced thyroid dysfunction showing Type 1 (underlying thyroid disease, iodine excess providing substrate, normal/high uptake, treat with antithyroid drugs) versus Type 2 (normal thyroid, destructive thyroiditis, low uptake, treat with corticosteroids), with note about mixed forms requiring combined therapy, and amiodarone-induced hypothyroidism (more common, treat with levothyroxine). Panel D: Postpartum thyroiditis showing timeline (2-6 months postpartum), biphasic pattern (thyrotoxic then hypothyroid), anti-TPO antibodies as risk factor, treatment (beta-blockers for thyrotoxicosis, levothyroxine for hypothyroidism), long-term outcome (50% permanent hypothyroidism within 7 years), and recurrence risk with future pregnancies.</image>

Summary

• TSH is the most sensitive screening test for thyroid dysfunction; interpret with free T4 to identify the pattern
• Hypothyroidism: Hashimoto thyroiditis is the most common cause; treat with levothyroxine at 1.6 mcg/kg/day, starting lower in elderly and cardiac patients
• Hyperthyroidism: Graves disease is the most common cause; treatment options include antithyroid drugs, radioactive iodine, and surgery
• Thyroid storm: fever, tachycardia, altered mental status; treat with PTU, then iodine 1 hour later, beta-blocker, corticosteroids, and supportive care
• Myxedema coma: hypothermia, altered mental status, hypotension; treat with IV levothyroxine, consider IV T3, IV hydrocortisone, and supportive care
• Thyroid nodules: ultrasound characterization with FNA biopsy based on size and suspicion level using TI-RADS or equivalent
• Papillary thyroid cancer is the most common type with excellent prognosis; medullary cancer requires RET testing
• Subclinical hypothyroidism: treat if TSH >10 or symptoms present; subclinical hyperthyroidism: treat if TSH <0.1 persistently with risk factors
• Sick euthyroid syndrome: low T3 in non-thyroidal illness; do not treat, as thyroid function normalizes with recovery
• Subacute thyroiditis follows a triphasic course (hyperthyroid, hypothyroid, recovery); postpartum thyroiditis has 50% risk of permanent hypothyroidism

Key Terms

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