Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Hypothyroidism

Hypothyroidism results from hypothalamic, pituitary, or thyroid insufficiency or resistance to thyroid hormone. The disorder can progress to life-threatening myxedema coma. Hypothyroidism is more prevalent in women than men; in the United States, the incidence is increasing significantly in people ages 40 to 50.

Age Alert

Hypothyroidism occurs primarily after age 40 and is particularly underdiagnosed in elderly persons. After age 65, prevalence increases to as much as 10% in females and 3% in males.

A deficiency of thyroid hormone secretion during fetal development and early infancy results in infantile cretinism (congenital hypothyroidism). Subacute thyroiditis, painless thyroiditis, and postpartum thyroiditis are self-limited conditions that may follow an episode of hyperthyroidism.

Causes

Primary (disorder of thyroid gland)

·   Thyroidectomy or radiation therapy (particularly with radioactive iodine)

·   Inflammation, chronic autoimmune thyroiditis (Hashimoto's thyroiditis), or such conditions as amyloidosis and sarcoidosis (rare)

Secondary (failure to stimulate normal thyroid function)

·   Inadequate production of thyroid hormone

·   Use of such antithyroid medications as propylthiouracil

·   Pituitary failure to produce thyroid-stimulating hormone (TSH)

·   Inborn errors of thyroid hormone synthesis

·   Iodine deficiency (usually dietary)

·   Hypothalamic failure to produce thyrotropin-releasing hormone.

Pathophysiology

Hypothyroidism may reflect a malfunction of the hypothalamus, pituitary, or thyroid gland, all of which are part of the same negative-feedback mechanism. However, disorders of the hypothalamus and pituitary rarely cause hypothyroidism. Primary hypothyroidism is most common.

Chronic autoimmune thyroiditis, also called chronic lymphocytic thyroiditis, occurs when autoantibodies destroy thyroid gland tissue. Chronic autoimmune thyroiditis associated with goiter is called Hashimoto's thyroiditis. The cause of this autoimmune process is unknown, although heredity plays a role, and specific human leukocyte antigen subtypes are associated with greater risk.

Outside the thyroid, antibodies can reduce the effect of thyroid hormone in two ways. First, antibodies can block the TSH receptor and prevent the production of TSH. Second, cytotoxic antithyroid antibodies may trigger thyroid destruction.

Signs and symptoms

·   Typical, vague, early clinical features—weakness, fatigue, forgetfulness, sensitivity to cold, unexplained weight gain, constipation

·   Myxedema—decreasing mental stability; coarse, dry, flaky, inelastic skin; puffy face, hands, and feet; hoarseness; periorbital edema; upper eyelid droop; dry, sparse hair; thick, brittle nails (as disorder progresses)

·   Cardiovascular involvement—decreased cardiac output, slow pulse rate, signs of poor peripheral circulation, congestive heart failure, cardiomegaly (occasionally)

Other common effects

·   Anorexia, abdominal distention, menorrhagia, decreased libido, infertility, ataxia, and nystagmus; reflexes with delayed relaxation time (especially Achilles' tendon)

·   Progression to myxedema coma—usually gradual but may develop abruptly when stress aggravates severe or prolonged hypothyroidism—progressive stupor, hypoventilation, hypoglycemia, hyponatremia, hypotension, hypothermia

Diagnostic test results

·   Radioimmunoassay shows decreased serum levels of triiodothyronin (T3) and thyroxine (T4).

·   Serum TSH level is increased with thyroid insufficiency; decreased with hypothalamic or pituitary insufficiency.

·   Serum cholesterol, alkaline phosphatase, and triglycerides levels are elevated.

·   Blood chemistry shows low serum sodium levels in myxedema coma.

·   Arterial blood gases show decreased pH and increased partial pressure of carbon dioxide in myxedema coma.

·   Skull X-ray, computed tomography scan, and magnetic resonance imaging may show pituitary or hypothalamic lesions.

·   Chest X-ray detects cardiomegaly.

Treatment

·   Gradual lifelong thyroid hormone replacement with T4 and, occasionally, T3

·   Surgery for underlying cause such as pituitary tumor

Age Alert

Elderly patients should be started on a very low dose of T4, such as 25 mcg every morning, to avoid cardiac problems. TSH levels guide gradual increases in dosage.

P.291

HISTOLOGIC CHANGES IN HASHIMOTO'S THYROIDITIS

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Clinical Tip

Facial Manifestations of Myxedema

Before the era of rapid laboratory diagnosis and hormone replacement therapy, severe hypothyroidism was diagnosed by typical facial features.

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