Thyroid Disorders for ABIM

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Thyroid Disorders for the American Board of Internal Medicine Exam

Hyperthyoridism

Hyperthyroidism is characterized by excessive production and release of thyroid hormones (T3 and T4), leading to a hypermetabolic state.
Causes:
Graves’ Disease: The most common cause of hyperthyroidism, it is an autoimmune disorder where thyroid-stimulating immunoglobulins (TSI) activate the thyroid-stimulating hormone (TSH) receptor, causing thyroid enlargement and overproduction of thyroid hormones.
Toxic Multinodular Goiter (Plummer’s Disease): Hyperfunctioning thyroid nodules that produce excess thyroid hormones independently of TSH regulation.
Toxic Adenoma: A single autonomously functioning thyroid nodule that produces thyroid hormones without TSH stimulation.
Thyroiditis: Inflammation of the thyroid gland (e.g., subacute, silent, or postpartum thyroiditis), causing the release of stored thyroid hormones.
Iatrogenic Hyperthyroidism: Excessive thyroid hormone replacement therapy or iodine-induced hyperthyroidism (Jod-Basedow phenomenon).

General Symptoms: Weight loss despite increased appetite, heat intolerance, sweating, and palpitations.
Cardiovascular: Tachycardia, atrial fibrillation, palpitations, and increased pulse pressure.
Neurologic: Tremor, anxiety, irritability, insomnia, and hyperreflexia.
Gastrointestinal: Increased bowel movements, diarrhea, and abdominal pain.
Dermatologic: Warm, moist skin; fine hair; and onycholysis.
Graves’ Disease-Specific Features:
Exophthalmos: Proptosis and lid lag due to retro-orbital tissue inflammation.
Pretibial Myxedema: Localized thickening of the skin on the shins.
Thyroid Bruit: Due to increased vascularity of the gland.

Laboratory Tests:
Thyroid Function Tests:
Low TSH: A hallmark of primary hyperthyroidism.
Elevated Free T3 and T4: Confirm the diagnosis of hyperthyroidism.
Autoantibodies: TSI or thyroid peroxidase (TPO) antibodies are commonly elevated in Graves' disease.
Imaging:
Radioactive Iodine Uptake (RAIU) Scan: Differentiates causes:
Graves’ Disease: Diffuse high uptake.
Toxic Multinodular Goiter/Toxic Adenoma: Focal areas of high uptake.
Thyroiditis: Low uptake due to thyroid hormone leakage.
Ultrasound: May reveal nodules in toxic multinodular goiter or toxic adenoma.

Antithyroid Medications:
Methimazole: The first-line medication for most patients; inhibits thyroid hormone synthesis.
Propylthiouracil (PTU): Used in pregnancy (especially the first trimester) and thyroid storm; inhibits peripheral conversion of T4 to T3.
Beta-Blockers: Used to control adrenergic symptoms such as tachycardia and tremors (e.g., propranolol or atenolol).
Radioactive Iodine Ablation: Destroys overactive thyroid tissue. Contraindicated in pregnancy and may cause hypothyroidism.
Surgery (Thyroidectomy): Indicated in cases of large goiter, thyroid cancer, or failure of other treatments. Complications include hypocalcemia (due to injury to the parathyroid glands) and recurrent laryngeal nerve damage.

Thyroid Storm: A life-threatening exacerbation of hyperthyroidism characterized by hyperpyrexia, tachycardia, altered mental status, and cardiovascular collapse. Immediate treatment with antithyroid drugs, beta-blockers, and corticosteroids is required.

Hypothyroidism

Hypothyroidism is characterized by insufficient production of thyroid hormones (T3 and T4), leading to a hypometabolic state.
Causes:
Hashimoto’s Thyroiditis: The most common cause of primary hypothyroidism, it is an autoimmune disorder where antibodies (anti-thyroid peroxidase [TPO] and anti-thyroglobulin [Tg]) attack the thyroid gland, leading to gradual destruction.
Iatrogenic: Post-thyroidectomy, radioactive iodine ablation, or neck radiation.
Medications: Lithium, amiodarone, and interferon-alpha may interfere with thyroid function.
Iodine Deficiency: Common in regions with low dietary iodine.
Central Hypothyroidism: Secondary to hypothalamic or pituitary disease (e.g., pituitary adenoma) that impairs TSH or thyrotropin-releasing hormone (TRH) secretion.

General Symptoms: Fatigue, weight gain, cold intolerance, and decreased appetite.
Dermatologic: Dry skin, brittle hair, alopecia, and non-pitting edema (myxedema).
Cardiovascular: Bradycardia, hypertension (due to increased peripheral vascular resistance), and hypercholesterolemia.
Neurologic: Depression, memory impairment, lethargy, and slow reflexes.
Gastrointestinal: Constipation and delayed gastric emptying.
Reproductive: Menorrhagia or oligomenorrhea, and infertility.
Myxedema Coma: A severe form of hypothyroidism, characterized by hypothermia, altered mental status, and cardiovascular collapse.

Laboratory Tests:
Thyroid Function Tests:
Elevated TSH: Indicates primary hypothyroidism.
Low Free T4: Confirms the diagnosis.
Low TSH and low T4: Suggest central hypothyroidism (secondary or tertiary).
Autoantibodies: Elevated anti-TPO and anti-thyroglobulin antibodies confirm Hashimoto’s thyroiditis.
Imaging:
Ultrasound: May reveal diffuse heterogeneity of the thyroid in Hashimoto’s disease.

Levothyroxine (Synthetic T4): The mainstay of treatment for hypothyroidism. Doses are titrated based on TSH levels, typically measured every 6-8 weeks until stable. The target TSH is generally within the normal range.
Central Hypothyroidism: Levothyroxine dosing is adjusted based on free T4 rather than TSH due to pituitary dysfunction.
Myxedema Coma: An endocrine emergency requiring high-dose IV levothyroxine, supportive care, and corticosteroids to treat potential adrenal insufficiency.

Myxedema Coma: A life-threatening condition triggered by infections, trauma, or sedatives. It presents with severe hypothyroidism, hypothermia, and altered mental status. Treatment requires aggressive supportive care and IV hormone replacement.
Cardiovascular Disease: Untreated hypothyroidism can lead to atherosclerosis and coronary artery disease due to hypercholesterolemia.

Key Points

Hyperthyroidism is most commonly caused by Graves' disease, toxic multinodular goiter, and toxic adenomas. Symptoms include weight loss, heat intolerance, palpitations, and tremors. Diagnosis is confirmed by low TSH and elevated free T3/T4. Treatment options include antithyroid drugs, radioactive iodine, and surgery.
Thyroid Storm is a life-threatening complication of untreated hyperthyroidism, requiring urgent treatment with beta-blockers, antithyroid medications, and supportive care.
Hypothyroidism is most commonly caused by Hashimoto’s thyroiditis. Symptoms include fatigue, weight gain, cold intolerance, and bradycardia. Diagnosis is based on elevated TSH and low free T4. Levothyroxine is the treatment of choice.
Myxedema Coma is a severe, life-threatening form of hypothyroidism requiring IV levothyroxine and corticosteroids.
Long-term complications of untreated thyroid disorders include cardiovascular disease, osteoporosis (in hyperthyroidism), and dyslipidemia (in hypothyroidism).