Thyrotoxicosis and Hyperthyroidism

Summary

Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves’ disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Subacute thyroiditis is an example of thyrotoxicosis without hyperthyroidism, and a pituitary adenoma , which secretes thyroid-stimulating hormone (TSH) is an example of secondary hyperthyroidism. Clinical features of thyrotoxicosis are mostly due to an increase in the metabolic rate and overactivity of the sympathetic nervous system (i.e., an increase in the β-adrenergic “tone”). Thyrotoxicosis is diagnosed by measuring the levels of TSH produced by the anterior pituitary gland and unbound T4 and T3. Depending on the etiology and clinical presentation, it may be treated pharmacologically, surgically, or with radioiodine.

Overview

• Hyperthyroidism is a condition characterized by the overproduction of thyroid hormones by the thyroid gland; can cause thyrotoxicosis.
• Much more common in women than in men (5:1)
• Age range at presentation
  • Graves disease: 20–30 years of age
  • Toxic adenoma: 30–50 years of age
  • Toxic MNG: peak incidence > 50 years of age

Causes

• Hyperfunctioning thyroid gland
  • Graves’ disease (∼ 60–80% of cases) ➜ Most common cause
  • Toxic multinodular goiter (∼ 15–20% of cases)
  • Toxic adenoma (3–5% of cases)
  • TSH-producing pituitary adenoma (thyrotropic adenoma)
  • β-hCG-mediated hyperthyroidism (hydatidiform mole, choriocarcinoma)
• Destruction of the thyroid gland
  • Thyroiditis (see “Subacute thyroiditis”)
    • Subacute granulomatous thyroiditis (de Quervain thyroiditis)
    • Subacute lymphocytic thyroiditis (e.g., postpartum thyroiditis)
  • Drug-induced thyroiditis (e.g., amiodarone, lithium)
    • Amiodarone can cause hyper and hypothyroidism
  • Contrast-induced thyroiditis (Jod-Basedow phenomenon)
  • Hashitoxicosis (see "Hashimoto thyroiditis")
  • Radiation thyroiditis
  • Palpation thyroiditis: due to thyroid gland manipulation during parathyroid surgery.
• Exogenous thyrotoxicosis
• Ectopic (extrathyroidal) hormone production
  • Struma ovarii
  • Metastatic follicular thyroid carcinoma

Clinical features

Diagnosis

• Thyroid-stimulating hormone (TSH) level (initial screening test): Typically low/undetectable
  • TSH could be high in case of pituitary adenoma or thyroid hormone resistance
• Free T4 (FT4) and total T3 levels: Typically both elevated.
• TSH receptor antibody (TRAb) ➜ for Grave’s disease
  • Positive: Diagnosis of Graves disease is established.
  • Negative: Further investigation is necessary.
• Thyroglobulin antibodies (TgAb): not routinely indicated but can be elevated in Grave’s disease, autoimmune conditions, and thyroid cancer
• Serum thyroglobulin (Tg): indicated for suspected exogenous hyperthyroidism with unclear history
  • Low: Exogenous hyperthyroidism
  • Normal/Increased: Endogenous hyperthyroidism

Thyroid antibodies

Treatment

1. Symptomatic therapy for thyrotoxicosis

• Beta blocker
  • Beta blockers (eg, propranolol, atenolol) are recommended as initial therapy to control heart rate and hyperadrenergic symptoms.
  • In addition, propranolol decreases conversion of T4 to T3 in peripheral tissues.
  • Should be initiated as soon as hyperthyroidism is diagnosed and should be continued until the hyperthyroidism is adequately treated with thionamides, radioiodine, and/or surgery

2. Medical therapy

• Antithyroid drugs for thyrotoxicosis (thionamides) à inhibits thyroid hormone synthesis
  • Thionamides
    • Propylthiouracil (PTU)
      • Can be used in the 1^st trimester of pregnancy due to fetal teratogenicity with methimazole
      • Usually not the preferred drug due to the risk of severe liver injury and acute liver failure
      • Preferred drug for thyroid storm
    • Methimazole (MMI)
      • Associated with less side effects than propylthiouracil.
      • Not used in the 1^st trimester of pregnancy but can be used in the 2^nd and 3^rd
    • Side effects
      • Propylthiouracil: Agranulocytosis, Hepatic failure, ANCA-associated vasculitis
      • Methimazole: Agranulocytosis, 1st-trimester teratogen, cholestasis

3. Radioactive iodine ablation (RAIA)

• Destruction of thyroid tissue via radioactive iodine (iodine-131) through a sodium/iodine symporter

4. Surgical therapy

Complications of Graves disease treatment

Thyroid Storm

• Thyroid storm is a rare, acute complication of thyrotoxicosis that constitutes a life-threatening emergency with a high mortality rate.
• Mortality:
  • 10%–20% with treatment
  • 100% if left untreated
• Precipitated by:
  • Infection, trauma, surgical emergencies, or planned surgeries
  • Less commonly by radiation thyroiditis, diabetic ketoacidosis, toxemia of pregnancy

Clinical features

• Fever as high as 40-41 C
• Tachycardia, hypertension, congestive heart failure, cardiac arrythmias, (eg, atrial fibrillation)
• Agitation, delirium, seizure, coma
• Goiter, lid lag, tremor, warm & moist skin
• Nausea, vomiting, diarrhea, jaundice

Treatment

• Beta blocker (eg, propranolol) to decrease adrenergic manifestations
• Propylthiouracil followed by iodine solution (potassium iodide solution) to decrease hormone synthesis and release
  • Propylthiouracil is preferred over methimazole
• Glucocorticoids (eg, hydrocortisone) to decrease peripheral T4 to T3 conversion
• Identify trigger & treat, supportive care

Quick Quiz

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