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Treatment of hypopituitarism

Peter J Snyder, MD


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INTRODUCTION — Treatment of patients with hypopituitarism is the sum of the treatments of each of the individual pituitary hormonal deficiencies detected when a patient with a pituitary or hypothalamic disease is tested. The treatments of corticotropin (ACTH), thyroid-stimulating hormone (TSH), and luteinizing hormone (LH) and follicle-stimulating hormone (FSH) deficiencies are in many ways the same as the treatments of primary deficiencies of the respective target glands, but in other ways they differ. Both the similarities and differences will be highlighted below. Treatment of growth hormone (GH) deficiency is unique to hypopituitarism.

One reason to optimize treatment is that in a retrospective study of 344 patients who had hypopituitarism after pituitary surgery, the long-term mortality was about double that of the general population [1]. Most of the excess mortality was due to cerebrovascular disease. The relationship between the hypopituitarism and the excess mortality remains unknown.

The specifics of therapy for hypopituitarism will be reviewed here. The causes, clinical manifestations, and diagnosis of hypopituitarism, are discussed elsewhere. Growth hormone deficiency in adults is also discussed in more detail elsewhere. (See "Causes of hypopituitarism" and see "Clinical manifestations of hypopituitarism" and see "Diagnosis of hypopituitarism" and see "Growth hormone deficiency in adults").

ACTH DEFICIENCY — Lack of ACTH primarily induces cortisol deficiency. As a result, treatment consists of the administration of hydrocortisone or other glucocorticoid in an amount and timing to mimic the normal pattern of cortisol secretion. Because there is no test to assess the adequacy of the replacement, the optimal replacement glucocorticoid and the optimal doses are not known. The author's practice is to use hydrocortisone, because that is the glucocorticoid the adrenals make, in a daily dose according to the patient's weight; suitable doses are approximately 20 mg/day for a patient who weighs 55 kg and 30 mg/day for a patient who weighs 80 kg. Although it would make sense physiologically to give two-thirds of the dose on arising and one-third in the early afternoon, many patients cannot remember the latter dose, so it more practical to give the entire dose on arising.

Some authorities, however, prefer dexamethasone or prednisone because of their longer durations of action. (See "Treatment of adrenal insufficiency"). Others use hydrocortisone but in lower doses, eg, 15 to 20 mg a day, because that is closer to the daily production rate of hydrocortisone [2]. Whatever the preparation and dose, the patient should be instructed in the need for larger doses in times of illness and other stresses.

An inadequate dose may result in persistence (or recurrence) of the symptoms of cortisol deficiency, while an excessive dose can lead to symptoms of cortisol excess and to bone loss. (See "Glucocorticoids and osteoporosis: Pathogenesis and clinical features"). Small deviations from the optimal dose are usually not detected, and there are no established biochemical tests for determining the adequacy of the dose. Plasma ACTH measurements cannot be used, because the values are low or normal before treatment. Serum cortisol values vary greatly depending upon when a dose of hydrocortisone was taken. Urinary cortisol values are also unreliable.

Unlike the situation in primary adrenal insufficiency, mineralocorticoid replacement is rarely necessary in hypopituitarism. Angiotensin II and potassium, not ACTH, are the major regulators of aldosterone secretion. (See "Chapter 6C: Aldosterone").

An unusual side effect of glucocorticoid replacement is the unmasking of underlying central diabetes insipidus, leading to marked polyuria [3]. Correction of cortisol deficiency can increase the blood pressure and renal blood flow, and, in patients with partial diabetes insipidus, reduce the secretion of vasopressin. All of these effects increase urine output. (See "Urine output in diabetes insipidus").

TSH DEFICIENCY — TSH deficiency results in thyroxine (T4) deficiency, and is treated with L-thyroxine. The goal of therapy should be a normal serum T4 value. The factors that influence dosing are similar to those of primary hypothyroidism (See "Treatment of hypothyroidism"), but treatment of secondary hypothyroidism differs in two ways:

T4 should not be administered until adrenal function, including ACTH reserve, has been evaluated and either found to be normal or treated. In a patient with coexisting hypothyroidism and hypoadrenalism, treatment of the hypothyroidism alone may increase the clearance of the little cortisol that is produced, thereby increasing the severity of the cortisol deficiency.
Measurement of serum TSH cannot be used as a guide to the adequacy of L-thyroxine replacement therapy. The treatment goal should be a serum T4 concentration in the middle of the normal range.
LH AND FSH DEFICIENCY — Treatment of LH and FSH deficiency depends upon gender and whether or not fertility is desired.

Men — Testosterone replacement is sufficient in men who have hypogonadism and who are not interested in fertility. The choice of treatment does not differ from that in men with primary hypogonadism, but serum LH measurements cannot be used to monitor the adequacy of therapy. This can be achieved by measurements of serum testosterone. (See "Testosterone treatment of male hypogonadism").

Men with secondary hypogonadism who wish to become fertile can be treated with gonadotropins, if they have pituitary disease or with either gonadotropins or gonadotropin-releasing hormone (GnRH) if they have hypothalamic disease. (See "Induction of fertility in men with secondary hypogonadism").