Thyroid Disorders (Clinical)
From TSH-driven titration to storm, nodules, cancer, and pregnancy
Hypothyroidism
Primary hypothyroidism shows an elevated TSH with a low free T4. Hashimoto thyroiditis (anti-TPO antibodies) is the most common cause in iodine-sufficient areas; worldwide, iodine deficiency dominates. Patients have fatigue, cold intolerance, weight gain, constipation, dry skin, and bradycardia, with delayed relaxation of deep tendon reflexes; labs may show hyperlipidemia, hyponatremia, and a raised CK. Treat with levothyroxine (T4).
Subclinical hypothyroidism is an elevated TSH with a NORMAL free T4. Treat with levothyroxine if TSH ≥10 or if the patient is pregnant or trying to conceive. With TSH between the upper limit and 10, consider treatment in a younger adult with symptoms or positive anti-TPO, but not in an older adult; otherwise monitor. Overtreatment risks atrial fibrillation and bone loss.
Levothyroxine management. Titrate to TSH, rechecking every 6–8 weeks, since T4's long half-life means a new steady state takes about that long. Take it on an empty stomach and separate it from calcium, iron, and PPIs, which impair absorption. Start low (12.5–25 mcg) in the elderly or those with coronary disease to avoid precipitating angina or arrhythmia.
A rising levothyroxine requirement can mean malabsorption, pregnancy, or a new interfering medication. In central (pituitary) hypothyroidism the TSH is low or inappropriately normal, so follow free T4 instead.
Hyperthyroidism
Confirm, then localize. Hyperthyroidism shows a low TSH with high free T4/T3 and causes heat intolerance, weight loss, tremor, palpitations, and atrial fibrillation. Radioactive iodine uptake separates a gland that is overproducing hormone (high uptake) from a gland leaking preformed hormone or hormone taken exogenously (low uptake).
| Cause | Uptake | Distinguishing features |
|---|---|---|
| Graves disease | Diffuse high | TSH-receptor stimulating antibodies (TSI), ophthalmopathy, pretibial myxedema, diffuse goiter with bruit |
| Toxic multinodular goiter | Patchy | Older patient, nodular gland |
| Toxic adenoma | Single hot spot | One autonomous nodule; rest of gland suppressed |
| Thyroiditis | Low | Preformed hormone leaking out; transient |
| Exogenous hormone | Low | Low serum thyroglobulin, no goiter |
Antithyroid drugs. Methimazole is the first-line antithyroid drug (once daily, fewer hepatic effects); PTU is preferred only in first-trimester pregnancy and thyroid storm. A β-blocker (propranolol) controls adrenergic symptoms while hormone levels fall. Radioactive iodine ablation or surgery is definitive.
| Feature | Methimazole | PTU |
|---|---|---|
| Role | First-line | First-trimester pregnancy, thyroid storm |
| Mechanism | Blocks thyroid peroxidase | Blocks thyroid peroxidase and peripheral T4→T3 conversion |
| Signature toxicity | Teratogen: aplasia cutis | Hepatotoxicity |
| Shared risk | Agranulocytosis | Agranulocytosis |
Warn every patient on an antithyroid drug to report fever or sore throat, which can signal agranulocytosis.
Definitive therapy. Radioactive iodine is contraindicated in pregnancy and breastfeeding, can worsen Graves ophthalmopathy, and usually leaves the patient hypothyroid and on lifelong levothyroxine. Thyroidectomy risks hypoparathyroidism (hypocalcemia) and recurrent laryngeal nerve injury (hoarseness).
Thyroid emergencies
Thyroid storm is decompensated thyrotoxicosis with fever, tachyarrhythmia, and agitation or delirium, often precipitated by surgery or infection. The order of drugs decides the outcome.
- β-blocker (propranolol)Controls adrenergic effects; also blocks peripheral T4→T3 conversion
- PTUStops new hormone synthesis
- Iodine (SSKI or Lugol)At least 1 hour AFTER PTU; blocks release of stored hormone
- GlucocorticoidsFurther reduce T4→T3 conversion
Iodine given before PTU would fuel hormone synthesis. Treat the fever with acetaminophen rather than aspirin, which displaces T4 from binding proteins.
Myxedema coma is decompensated hypothyroidism, usually in an elderly patient after infection, cold exposure, or sedatives: altered mental status, hypothermia, bradycardia, hypoventilation, and hyponatremia. Treat with IV levothyroxine plus stress-dose hydrocortisone until coexisting adrenal insufficiency is excluded, with supportive care.
Thyroid nodules and cancer
Check TSH first. A low TSH leads to a radionuclide scan; a hot (autonomous) nodule is almost never malignant. A normal or high TSH leads to ultrasound, then FNA based on size and suspicious features: microcalcifications, hypoechogenicity, irregular margins, and a taller-than-wide shape.
- Check TSHFirst step for every nodule
- Low TSHRadionuclide scan; hot nodule is almost never cancer
- Normal or high TSHUltrasound
- FNABy size and suspicious features
Bethesda I–VI. FNA cytology is graded I nondiagnostic, II benign, III/IV indeterminate, V suspicious, and VI malignant. The category guides management, from repeat FNA or molecular testing for indeterminate results to lobectomy or total thyroidectomy for suspicious or malignant ones.
| Type | Hallmarks | Behavior | Marker |
|---|---|---|---|
| Papillary | Most common; psammoma bodies, Orphan Annie eye nuclei, nuclear grooves; BRAF, RET | Lymphatic spread; excellent prognosis | Thyroglobulin |
| Follicular | Diagnosis needs capsular or vascular invasion, so FNA cannot separate it from adenoma | Hematogenous spread | Thyroglobulin |
| Medullary | Parafollicular C cells; MEN2 (RET) | Does not take up radioiodine | Calcitonin, CEA |
| Anaplastic | Elderly; rapidly enlarging invasive mass | Rapidly fatal | — |
Treatment. Differentiated (papillary or follicular) cancer is treated with thyroidectomy, radioiodine ablation for higher-risk disease, then TSH suppression with levothyroxine; thyroglobulin is the recurrence marker. Medullary cancer needs total thyroidectomy with calcitonin and CEA as markers; screen for RET and rule out pheochromocytoma (MEN2) before surgery.
Always exclude a pheochromocytoma before operating on medullary thyroid cancer or MEN2, or an intraoperative hypertensive crisis may follow.
Thyroiditis and pregnancy
Subacute granulomatous (de Quervain) thyroiditis causes a painful, tender gland after a viral illness with an elevated ESR. It runs a transient hyperthyroid phase, then hypothyroidism, then recovery, with low radioiodine uptake. Silent and postpartum thyroiditis are painless versions; postpartum thyroiditis arises within a year of delivery. All are self-limited: treat symptoms with NSAIDs and β-blockers, adding prednisone for severe de Quervain pain or NSAID failure. Antithyroid drugs do not help because no new hormone is being made.
Thyroiditis causes a thyrotoxic phase with LOW radioiodine uptake (preformed hormone leaking out), unlike Graves.
Pregnancy. Estrogen raises thyroid-binding globulin (higher total T4), and hCG mildly stimulates the thyroid, so TSH may dip in the first trimester. Hypothyroid women need their levothyroxine dose increased about 30% (roughly 2 extra doses per week) once pregnant, targeting trimester-specific TSH, because the fetus depends on maternal T4 early in gestation. For hyperthyroidism, use PTU in the first trimester; after it, either continue PTU or switch to methimazole (ATA 2017); radioactive iodine is contraindicated.