Diagnosis

Hyperthyroidism

Etiology

Cause [kc1]

1. Graves autoimmune hyperthyroidism (most common in younger population)

   • Autoimmune disease with antibodies against the TSH receptor

   • Trophic effect --> thyroid gland hypertrophy

2. Toxic multinodular goiter (common in older population)

   • Nodular disease --> nodules develop autonomy for thyroid hormone production

3. Toxic adenoma:

   • Solitary nodules with autonomous thyroid hormone production due to somatic mutations in the TSH receptor

4. Iodine-induced hyperthyroidism (iodinated contrast, amiodarone, iodine supplements)

5. TSH-secreting pituitary adenoma

6. Conditions with high hCG levels:

   • Choriocarcinomas

   • Hydatiform moles in females

   • Germ cell tumors in males

7. Ovarian teratoma with ectopic thyroid hormone production

8. Extensive metastasis from functionally differentiated thyroid carcinoma

9. Drug-induced thyroiditis: amiodarone, lithium, tyrosine kinase inhibitors, interferon-alpha, immune checkpoint inhibitor therapy

10. Other thyroiditis: Hashitoxicosis, painless thyroiditis, painful subacute thyroiditis, suppurative thyroiditis, and Riedel thyroiditis

11. Factitious thyroiditis (due to excess exogenous thyroid hormone use)

Pathophysiology

1. Thyroid stimulating hormone (TSH) --> triiodothyronine (T3) and thyroxine (T4)

2. Excessive thyroid hormone:

   • Hyperadrenergic and hypermetabolic state

   • weight loss, palpitation, tremor, heat intolerance, anxiety, irritability, fatigue, muscle weakness, diarrhea, hair loss, loss of libido, and oligomenorrhea or amenorrhea

Complications [kc1]

• Thyroid storm - an extreme case of hyperthyroidism

• Cardiovascular events: atrial fibrillation, ischemic stroke

• Osteoporosis

• Infertility, abnormalities of menstrual cycles

Epidemiology

Incidence per 100.000 [kc1][uiu][vsu]

Approach

• Blood test: TSH, free T4, total T3, thyrotropin receptor antibody (anti-TR/TRAb is elevated at Graves disease)

• PET-scan with radioiodine thyroid uptake

• Thyroid ultrasound

Treatment

Treatment of hyperthyroidism depends on the underlying etiology and severity: [kc1]

• Overt hyperthyroidism

• Subclinical hyperthyroidism (TSH <0.1)

1. Symptomatic treatment (palpitations, anxiety, and tremor):

   • Beta-adrenergic antagonist (or Calcium channel blockers)

2. Definitive treatments:

   • Antithyroid Drugs (Thionamide) block thyroid hormone synthesis:

     • Methimazole: 5-10mg/day (FT4 1-1.5 times of normal limit), 10-20 mg/day (FT4 1.5-2 times of normal limit), 30-40 mg/day (FT4 2-3 times of normal limit)

     • Carbimazole, Propylthiouracil (preferred during pregnancy)

     • Risk of remission: 20-50%

   • Radioactive iodine therapy: destruction of thyroid follicular cells

     • Contraindications for the use of thionamides and surgery (high-risk comorbidities)

     • Cannot be used during pregnancy and breast feeding

   • Subtotal thyroidectomy:

     • Indications: Pregnancy, Graves orbitopathy, side effects to thionamides, thyroid malignancy, large compressive goiters, co-existing hyperparathyroidism needing surgery

     • Graves disease and Toxic multinodular goiter: Near-total or total thyroidectomy

     • Toxic adenoma: Ipsilateral thyroid lobectomy or isthmusectomy

Differential diagnoses

Anxiety, Atrial fibrillation, Cocaine toxicity, Diarrhea, Graves disease, Hashimotos thyroiditis, Pheochromocytoma, Pituitary adenoma, Postpartum thyroiditis, Radiation, Struma ovarii, Subacute thyroiditis, Thyroid cancer, Toxic nodular goiter, Toxic thyroid adenoma, Wolff-Parkinson-White Syndrome