Hyperthyroidism Review Notes

Hyperthyroidism: A Review

Overt hyperthyroidism is defined by suppressed thyrotropin (TSH) and elevated triiodothyronine (T3) and/or free thyroxine (FT4). Subclinical hyperthyroidism involves low TSH with normal T3 and FT4. Untreated hyperthyroidism can lead to cardiac issues, osteoporosis, adverse pregnancy outcomes, and metabolic abnormalities, increasing mortality.

Common Causes & Symptoms

Graves’ disease is the most common cause, with toxic nodules and thyroiditis also contributing. Symptoms include anxiety, insomnia, palpitations, weight loss, diarrhea, and heat intolerance. Graves’ disease may present with enlarged thyroid glands and exophthalmos. Toxic nodules can cause compression symptoms like dysphagia. Diagnosis involves clinical evaluation, thyroid function tests, and TSH-receptor antibody status. Thyroid scintigraphy is useful for nodule evaluation or unclear etiology.

Thyrotoxicosis & Struma Ovarii

Thyrotoxicosis can arise from increased thyroid hormone production, hormone release due to inflammation, or extrathyroidal thyroid hormone availability (e.g., struma ovarii). Untreated hyperthyroidism may result in cardiac arrhythmias, heart failure, osteoporosis, and metabolic disturbances.

Prevalence & Definitions

Hyperthyroidism affects approximately 2.5% of adults globally. Overt hyperthyroidism prevalence is 0.2-1.4%, while subclinical hyperthyroidism is 0.7-1.4%. Thyrotoxicosis encompasses all conditions with elevated thyroid hormone levels.

Pathophysiology

Graves’ disease is an autoimmune disorder where TSH receptor autoantibodies increase thyroid hormone synthesis. Toxic nodular disease involves autonomous hormone secretion from thyroid nodules. hCG in early pregnancy can stimulate thyroid hormone synthesis. Thyroiditis, caused by autoimmunity or infection, leads to hormone release without increased synthesis. Amiodarone-induced thyrotoxicosis (AIT) has two types: Type 1 from increased hormone synthesis due to iodine, and Type 2 from destructive thyroiditis.

Clinical Presentation

Symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, weight loss, diarrhea, heat intolerance, and irregular menses. Some older adults may present with apathetic hyperthyroidism. Graves’ disease or toxic nodules may cause neck enlargement and compressive symptoms. Subclinical hyperthyroidism can be asymptomatic or have milder symptoms. COVID-19 has been linked to increased cases of Graves’ disease and subacute thyroiditis.

Assessment and Diagnosis

Physical exam may reveal tachycardia, systolic hypertension, stare, tremor, and muscle weakness. Graves’ disease can manifest as orbitopathy and pretibial myxedema. Low serum TSH is the best initial test for thyroid dysfunction. Free T4 levels and T3 levels help in assessing hyperthyroidism. The total T3:T4 ratio is typically >20:1 in Graves’ disease or toxic nodules, and <20:1 in thyroiditis. TRAb measurement differentiates Graves’ disease. False hyperthyroidism diagnoses can occur due to biotin interference in immunoassays. Thyroid scintigraphy is recommended for palpable nodules or unclear etiology.

Treatment Overview

Untreated thyrotoxicosis can cause osteoporosis and atrial fibrillation. Treatment is patient-centered, considering age, comorbidities, and preferences. Graves’ disease treatment aims for remission, while toxic nodular disease requires indefinite treatment. Beta-blockers manage hyperadrenergic symptoms. Overt hyperthyroidism from nodules or Graves’ disease is treated with antithyroid drugs (ATD), radioactive iodine (RAI) ablation, or surgery.

Antithyroid Drugs (ATD)

Thionamides (methimazole [MMI], carbimazole, propylthiouracil [PTU]) reduce thyroid hormone synthesis. MMI is generally the first-line agent, except in the first trimester of pregnancy. Dosing is based on FT4 levels. For Graves’ disease, ATD treatment may be discontinued after 12-18 months if TSH normalizes and TRAb is negative. Remission rates are 30-50%. Adverse effects occur in approximately 13% of patients, including pruritus and agranulocytosis.

Radioactive Iodine (RAI) Treatment

RAI cures hyperthyroidism in over 90% of patients with Graves’ disease or autonomous nodules. Pre-treatment with beta-blockers and MMI is recommended in older patients. The goal is hypothyroidism in Graves’ disease and alleviating hyperthyroidism in toxic nodular goiter. Hypothyroidism is a common outcome. RAI may worsen eye disease in Graves’ patients. Recent studies show no significant association between RAI therapy and overall cancer risk, although there was a linear dose-response association with mortality due to breast cancer.

Thyroid Surgery

Thyroidectomy is indicated for compressive symptoms, suspicious nodules, or Graves’ ophthalmopathy. Total thyroidectomy is preferred for Graves’ disease. Complications include recurrent laryngeal nerve damage and hypoparathyroidism. Pre-treatment with ATD and iodine reduces risks.

Subclinical Hyperthyroidism

Subclinical hyperthyroidism may progress to overt hyperthyroidism. It is associated with increased risks of atrial fibrillation, heart failure, and mortality. Treatment is recommended for patients >65 years or those with TSH <0.1 mIU/L and cardiovascular risks.

Pregnancy and Lactation

Gestational transient thyrotoxicosis, linked to elevated hCG, often resolves without ATD treatment. Overt hyperthyroidism requires treatment due to risks. PTU is preferred in the first trimester due to lower teratogenic risks compared to MMI. ATDs are secreted in breast milk at low levels and are considered safe during lactation. RAI is contraindicated in pregnancy and lactation.

Thyroid Storm

Thyroid storm involves severe hyperthyroidism with multi-organ failure and high mortality. Management includes ATDs, glucocorticoids, beta-blockers, and iodide.

Prognosis

Overt hyperthyroidism is associated with increased mortality. Surgery may offer greater benefits than ATD or RAI in reducing cardiovascular risks.