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BASICS

Description

  • Hyperthyroidism: Excess thyroid hormone production from the thyroid gland.
  • Thyrotoxicosis: Clinical syndrome of thyroid hormone excess; may be from thyroid or other sources.
  • Causes include Graves disease (GD), toxic multinodular goiter (TMNG), toxic adenoma, thyroiditis, iodine-induced, drug-induced, and subclinical forms.
  • Thyroid storm: Severe thyrotoxicosis with fever, tachycardia, GI symptoms, CNS dysfunction; ~50% mortality.

Geriatric Considerations

  • Symptoms may be atypical or absent.
  • Atrial fibrillation common when TSH <0.1 mIU/L.

Pediatric Considerations

  • Treated with antithyroid drugs for 12-24 months.
  • Radioactive iodine therapy controversial.

Pregnancy Considerations

  • PTU preferred in 1st trimester; methimazole in 2nd/3rd trimesters.
  • Use lowest effective dose; avoid treatment-induced hypothyroidism.
  • Radioiodine contraindicated.

EPIDEMIOLOGY

  • Prevalence: 1.3% of population.
  • Female > male (7–10:1 ratio).
  • GD common in 2nd-3rd decades; TMNG in >40 years.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Graves disease: Autoimmune with TSH receptor antibodies.
  • TMNG: TSH receptor gene abnormalities (60%).
  • Toxic adenoma: TSH receptor mutation.
  • Hashitoxicosis: Autoimmune thyroiditis with antimicrosomal antibodies.
  • Subacute thyroiditis: Viral granulomatous inflammation.
  • Drug-induced: Amiodarone, lithium, interferon-Ξ±, interleukin-2.
  • Postpartum thyroiditis: Autoimmune; hypothyroidism in 60%.

Genetics

  • GD concordance ~35% in monozygotic twins.

RISK FACTORS

  • Positive maternal family history.
  • Other autoimmune diseases.
  • Iodide repletion after deprivation.

COMMONLY ASSOCIATED CONDITIONS

  • Autoimmune disorders.
  • Down syndrome.

DIAGNOSIS

History

  • Hypermetabolic symptoms: fatigue, weakness, weight loss, heat intolerance.
  • Neuropsychiatric: agitation, anxiety, psychosis, poor concentration.
  • GI: increased appetite, hyperdefecation.
  • Gynecologic: oligomenorrhea, amenorrhea.
  • Cardiovascular: tachycardia, chest discomfort.
  • Geriatric: apathetic hyperthyroidism.

Physical Exam

  • Skin: warm, moist; pretibial myxedema (GD).
  • Eyes: exophthalmos, lid lag.
  • Endocrine: goiter, gynecomastia, hyperhidrosis.
  • Cardiovascular: tachycardia, atrial fibrillation.
  • Neurologic: tremor, proximal muscle weakness.

Differential Diagnosis

  • Anxiety, depression.
  • Diabetes mellitus.
  • Pregnancy, menopause.
  • Pheochromocytoma, carcinoid syndrome.

Diagnostic Tests

  • Suppressed TSH, elevated free T4 (95% cases).
  • T3 elevated in T3 toxicosis or amiodarone-induced thyrotoxicosis.
  • TSH receptor antibodies diagnostic for GD.
  • Nuclear medicine uptake: GD shows diffuse uptake; TMNG heterogeneous; toxic nodule focal "hot" nodule.
  • Neck ultrasound: increased vascularity in GD.

TREATMENT

Observation

  • Mild hyperthyroidism may be observed, especially in young low-risk patients.

Medications

  • Antithyroid drugs: Methimazole preferred, PTU in thyroid storm and 1st trimester pregnancy.
  • Duration: 12-18 months; relapse common after cessation.
  • Side effects: hepatitis, agranulocytosis.
  • Beta blockers: Symptom control; propranolol inhibits T4 to T3 conversion.
  • Glucocorticoids: Reduce T4 to T3 conversion; used in thyroid storm and Graves ophthalmopathy.
  • Cholestyramine: Reduces thyroid hormone reabsorption.
  • Other: Lithium, iodine solutions (SSKI), with careful timing to avoid Jod-Basedow.

Radioactive iodine therapy (RAIT)

  • Used in GD, TMNG.
  • Pretreat with antithyroid drugs.
  • Hypothyroidism common post-RAIT.

Surgery

  • Indicated for compressive symptoms, malignancy, or contraindications to other therapies.
  • Preferred in 2nd trimester pregnancy.

ISSUES FOR REFERRAL

  • Graves ophthalmopathy to ophthalmology.

ONGOING CARE

Monitoring

  • Thyroid function tests q3 months.
  • CBC and LFTs during antithyroid therapy.
  • Post-RAIT: thyroid tests at 6, 12, 24 weeks, then annually.
  • Smoking cessation in GD.

Diet

  • Maintain sufficient calories.

PROGNOSIS

  • Good with early diagnosis and treatment.
  • High relapse rates with antithyroid drugs alone in GD.

COMPLICATIONS

  • Surgery: hypoparathyroidism, recurrent laryngeal nerve injury, hypothyroidism.
  • RAIT: postablation hypothyroidism.
  • GD: relapse, ophthalmopathy, atrial fibrillation, heart failure, CVA.

REFERENCES

  1. Cappola AR, Fried LP, Arnold AM, et al. Thyroid status, cardiovascular risk, and mortality in older adults. JAMA. 2006;295(9):1033-1041.
  2. Bahn RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Endocr Pract. 2011;17(3):456-520.
  3. Bahn Chair RS, Burch HB, Cooper DS, et al. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011;21(6):593-646.

Clinical Pearls

  • Not all thyrotoxicoses are due to hyperthyroidism.
  • Graves disease typically presents with hyperthyroidism, ophthalmopathy, and goiter.
  • Thyroid storm is a medical emergency.
  • TSH levels may lag in normalization after treatment despite decreasing T3/T4.