Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Hypopituitarism

Hypopituitarism, also known as panhypopituitarism, is a complex syndrome marked by metabolic dysfunction, sexual immaturity, and growth retardation (when it occurs in childhood). The cause is a deficiency of the hormones secreted by the anterior pituitary gland. Panhypopituitarism is a partial or total failure of all six of this gland's vital hormones—adrenocorticotropin (ACTH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), growth hormone (GH), and prolactin.

Age Alert

Partial and complete forms of hypopituitarism affect adults and children; in children, these diseases may cause dwarfism and delayed puberty. The prognosis may be good with adequate replacement therapy and correction of the underlying causes.

Primary hypopituitarism usually develops in a predictable pattern. It generally begins with decreased gonadotropin (FSH and LH) levels and consequent hypogonadism, reflected by cessation of menses in women and impotence in men. GH deficiency follows, causing short stature, delayed growth, and delayed puberty in children. Subsequent decreased TSH levels cause hypothyroidism and, finally, decreased ACTH levels result in adrenal insufficiency, possibly leading to adrenal crisis. When hypopituitarism follows surgical ablation or trauma, the pattern of hormonal events may not necessarily follow that sequence. Damage to the hypothalamus or neurohypophysis may cause diabetes insipidus.

Causes

Primary hypopituitarism

·   Tumor of the pituitary gland

·   Congenital defect (hypoplasia or aplasia of the pituitary gland)

·   Pituitary infarction (most often from postpartum hemorrhage)

·   Partial or total hypophysectomy by surgery, irradiation, or chemical agents

·   Granulomatous disease such as tuberculosis

·   Idiopathic or autoimmune origin (occasionally)

Secondary hypopituitarism

·   Deficiency of releasing hormones produced by the hypothalamus, either idiopathic or resulting from infection, trauma, or a tumor

Pathophysiology

The pituitary gland is highly vascular and therefore extremely vulnerable to ischemia and infarction. Any event that leads to circulatory collapse and compensatory vasospasm may result in gland ischemia, tissue necrosis, or edema. Expansion of the pituitary gland within the fixed compartment of the sella turcica further impedes its blood supply. An absence or decrease of one or more pituitary hormones leads to a loss of function in the gland or organ that it controls.

Signs and symptoms

·   ACTH deficiency: weakness, fatigue, weight loss, fasting hypoglycemia, and altered mental function; loss of axillary and pubic hair; orthostatic hypotension and hyponatremia

·   TSH deficiency: weight gain, constipation, cold intolerance, fatigue, and coarse hair

·   Gonadotropin deficiency: sexual dysfunction, infertility

·   Antidiuretic hormone deficiency: diabetes insipidus

·   Prolactin deficiency: lactation dysfunction or gynecomastia

Diagnostic test results

·   Blood test reveals decreased serum thyroxin levels in diminished thyroid gland function due to lack of TSH.

·   Radioimmunoassay shows decreased plasma levels of some or all of the pituitary hormones.

·   Increased prolactin levels possibly indicating a lesion in the hypothalamus or pituitary stalk.

·   Computed tomography scans, magnetic resonance imaging, or cerebral angiography may show the presence of intrasellar or extrasellar tumors.

·   Oral administration of metyrapone shows the source of low hydroxycorticosteroid levels.

·   Insulin administration shows low levels of corticotropin, indicating pituitary or hypothalamic failure.

·   Dopamine antagonist administration evaluates prolactin secretory reserve.

·   I.V. administration of gonadotropin releasing hormone distinguishes pituitary and hypothalamic causes of gonadotropin deficiency.

·   Provocative testing shows persistently low GH and insulin-like growth factor-1 levels confirming GH deficiency.

Treatment

·   Replacement of hormones (cortisol, thyroxine, androgen or cyclic estrogen) secreted by the target glands; prolactin not replaced

·   Clomiphene or cyclic gonadotropin-releasing hormone to induce ovulation in female patient of reproductive age

·   Surgery for pituitary tumor

P.289

REGULATION OF PITUITARY FUNCTION

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