Hypopituitarism

Hypopituitarism, also known as panhypopituitarism, is a complex syndrome marked by metabolic dysfunction, sexual immaturity, and growth retardation (when it occurs in childhood), resulting from a deficiency of the hormones secreted by the anterior pituitary gland. Panhypopituitarism refers to a generalized condition caused by partial or total failure of all six of this gland's vital hormones - corticotropin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle-stimulating hormone(FSH), human growth hormone (HGH)
and prolactin. Partial hypopituitarism and complete hypopituitarism occur in 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.

Causes

The most common cause of primary hypopituitarism is a tumor. Other causes include congenital defects (hypoplasia or aplasia of the pituitary gland); pituitary infarction (most often from postpartum hemorrhage); partial or total hypophysectomy by surgery, irradiation,
or chemical agents; and, rarely, granulomatous disease (tuberculosis, for example). Occasionally, hypopituitarism may have no identifiable cause, or it may be related to autoimmune destruction of the gland. Secondary hypopituitarism stems from a deficiency of releasing hormones produced by the hypothalamuseither idiopathic or possibly resulting from infection, trauma, or a tumor.

Primary hypopituitarism usually develops in a predictable pattern of hormonal failures. It generally starts with hypogonadism from gonadotropin failure (decreased FSH and LH levels). In adults, it causes cessation of menses in women and impotence in men. GH deficiency follows; in children, this causes short stature, delayed growth, and delayed puberty. Subsequent failure of thyrotropin (decreased TSH levels) causes hypothyroidism; finally, adrenocortical failure (decreased corticotropin levels) results in adrenal insufficiency. When hypopituitarism follows surgical ablation or trauma, the pattern of hormonal events may not necessarily follow this sequence.

Signs and symptoms

The symptoms of hypopituitarism vary depending on which hormones are insufficiently produced by the pituitary gland. In addition, the symptoms of hypopituitarism in children will vary depending on their age. Each child may also experience symptoms differently. The following are common symptoms associated with reduced production of certain hormones:

• insufficient growth hormone production - this deficiency can lead to stunted growth and dwarfism in children.
• insufficient luteinizing hormone production - this deficiency can cause the insufficient production of testosterone by a boy's testes, resulting in undeveloped male secondary sexual characteristics.

The symptoms of hypopituitarism may resemble other conditions or medical problems. Always consult your child's physician for a diagnosis.

Diagnosis

Children suffering from growth failure are typically diagnosed by the end of the first year after birth. To diagnose GHD, previous growth measurements are evaluated, a bone age (x-ray of a child's hand and wrist) is taken and blood samples are assessed for possible thyroid hormone deficiency. Testing for GHD will occur when other possibilities of short stature have been ruled out. A child's growth hormone secretion will be stimulated and measured over a period of 8-12 hours, since growth hormone secretion varies throughout the day and is greatest after falling asleep.

Treatment

Replacement of hormones secreted by the target glands is the most effective treatment for hypopituitarism. Hormone replacement therapy includes cortisol, T4 and androgen or cyclic estrogen. Prolactin need not be replaced. The patient of reproductive age may benefit from cyclic administration of FSH and human chorionic gonadotropin to induce ovulation.

CLINICAL TIP

In hypopituitarism, the TSH levels become an unreliable marker for thyroid hormone replacement. Therefore, follow free T4 levels in this patient.

Somatrem, identical to GH but the product of recombinant deoxyribonucleic acid technology, has replaced growth hormones derived from human sources. It's effective for treating dwarfism and stimulates growth increases as great as 6" (15 cm) in the 1st year of treatment. The growth rate tapers off in subsequent years. After pubertal changes have occurred, the effects of somatrem therapy are limited. Occasionally, a child becomes unresponsive to somatrem therapy, even with larger doses, perhaps because antibodies have formed against it. In such refractory patients, small doses of androgen may again stimulate growth, but extreme caution is necessary to prevent premature closure of the epiphyses. Children with hypopituitarism may also need replacement of adrenal and thyroid hormones and, as they approach puberty, sex hormones.

Prevention

There is no known prevention of hypopituitarism, except for prevention of damage to the pituitary/hypothalamic area from injury.