Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders


Hyperthyroidism, or thyrotoxicosis, is a metabolic imbalance that results from the overproduction of thyroid hormone. The most common form is Graves' disease, an autoimmune disorder that increases thyroxine (T4) production, enlarges the thyroid gland (goiter), and causes multiple system changes.

Age Alert

Incidence of Graves' disease is greatest in women between ages 30 and 60, especially those with a family history of thyroid abnormalities; only 5% of patients are younger than age 15.


·   Inherited predisposition, probably autosomal recessive gene

·   Other endocrine abnormalities

·   Defect in suppressor T-lymphocyte function and consequent production of autoantibodies

·   Excessive dietary intake of iodine

·   Stress, such as surgery, infection, toxemia of pregnancy, or diabetic ketoacidosis—can precipitate thyroid storm

·   Medications, such as lithium and amiodarone

·   Toxic nodules or tumors


The thyroid gland secretes the thyroid precursor T4, the thyroid hormone triiodothyronine (T3), and thyrocalcitonin. T4 and T3 stimulate protein, lipid, and carbohydrate metabolism primarily through catabolic pathways. Thyrocalcitonin removes calcium from the blood and incorporates it into bone. Biosynthesis, storage, and release of thyroid hormones are controlled by the hypothalamic-pituitary axis through a negative-feedback loop.

Thyrotropin-releasing hormone (TRH) from the hypothalamus stimulates the release of thyroid-stimulating-hormone (TSH) by the pituitary. Circulating T3 levels provide negative feedback through the hypothalamus to decrease TRH levels, and through the pituitary to decrease TSH levels.

In Graves' disease, autoantibodies are produced that attach to and then stimulate TSH receptors on the thyroid gland. This process leads to increased stimulation of the gland and increased hormone production.

Signs and symptoms

·   Enlarged thyroid (goiter)

·   Nervousness, tremor, and palpitations

·   Heat intolerance, sweating

·   Weight loss despite increased appetite

·   Frequent bowel movements

·   Exophthalmos (characteristic, but absent in many patients with thyrotoxicosis)

Other signs and symptoms, common because thyrotoxicosis profoundly affects virtually every body system

·   Difficulty concentrating; fine tremor, shaky handwriting, and clumsiness; emotional instability and mood swings ranging from occasional outbursts to overt psychosis

·   Moist, smooth, warm, flushed skin; fine, soft hair; premature patchy graying and increased hair loss in both sexes; friable nails and onycholysis; pretibial myxedema, producing thickened skin; accentuated hair follicles; sometimes itchy or painful raised red patches of skin with occasional nodule formation; microscopic examination showing increased mucin deposits

·   Systolic hypertension, tachycardia, full bounding pulse, wide pulse pressure, cardiomegaly, increased cardiac output and blood volume, visible point of maximal impulse, paroxysmal supraventricular tachycardia and atrial fibrillation (especially in elderly people), and occasional systolic murmur at the left sternal border

·   Increased respiratory rate, dyspnea on exertion and at rest; nausea and vomiting; soft stools or diarrhea; liver enlargement

·   Weakness, fatigue, and muscle atrophy; rare coexistence with myasthenia gravis; possibly generalized or localized paralysis associated with hypokalemia and, rarely, acropachy

·   Oligomenorrhea or amenorrhea, decreased fertility, increased incidence of spontaneous abortion (females), gynecomastia (males), diminished libido (both sexes)

Thyroid storm

·   Extreme irritability, hypertension, tachycardia, vomiting, temperature up to 106 F (41.1 C), delirium, and coma

Diagnostic test results

·   Radioimmunoassay shows increased serum T4 and T3 levels.

·   Laboratory studies reveal low TSH levels.

·   Thyroid scan shows increased uptake of radioactive iodine (131I) in Graves' disease and, usually, in toxic multinodular goiter and toxic adenoma; low radioactive uptake in thyroiditis and thyrotoxic factitia (test contraindicated in pregnancy).

·   Ultrasonography confirms subclinical ophthalmopathy.


·   Antithyroid drugs—thyroid hormone antagonists, including propylthiouracil and methimazole, to block thyroid hormone synthesis; propranolol until antithyroid drugs reach their full effect—to manage tachycardia and other peripheral effects of excessive hypersympathetic activity

·   Single oral dose of 131I

·   Surgery and lifelong regular medical supervision—most patients become hypothyroid, sometimes as long as several years after surgery

Clinical Tip

With treatment, most patients with hyperthyroidism can lead normal lives. However, thyroid storm—an acute, severe exacerbation of thyrotoxicosis—is a medical emergency that may have life-threatening cardiac, hepatic, or renal consequences.







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