panhypopit

INTRODUCTION — The presentation of hypopituitarism can be considered as the presentation of deficiency of each anterior pituitary hormone. The presentations of patients with deficiencies of those hormones that control target glands are often similar to the presentations of patients with primary deficiencies of the target gland hormones they control, with some notable exceptions.

An overview of the hormonal abnormalities that can occur in patients with hypopituitarism and of their clinical consequences will be provided here. The clinical manifestations and the specific diagnostic approaches to establishing the presence of hormone deficiency due to hypothalamic or pituitary disease are discussed separately as are the diagnosis and treatment of hypopituitarism. (See "Diagnosis of hypopituitarism" and see "Treatment of hypopituitarism").

Patients in whom the hypopituitarism is due to a pituitary or sellar mass may also have symptoms related to the mass, such as headache, visual loss, or diplopia. (See "Causes; presentation; and evaluation of sellar masses").

GENERAL PRINCIPLES — Damage to the anterior pituitary can occur suddenly or slowly, can be mild or severe, and can affect the secretion of one, several, or all of its hormones. As a result, the clinical presentation of anterior pituitary hormone deficiencies varies, depending upon the following factors:

* The rapidity with which a disease affects anterior pituitary cells. Some diseases, such as pituitary apoplexy, develop rapidly, causing sudden impairment of ACTH (corticotropin) secretion and, consequently, sudden onset of symptoms of cortisol deficiency. Other insults, such as radiation therapy to the pituitary or hypothalamus, usually act slowly, causing symptoms many months or, more likely, years later. (See "Causes of hypopituitarism").

* The severity of the hormonal deficiency. Complete ACTH and cortisol deficiency, as an example, can cause symptoms under basal circumstances, while partial ACTH deficiency may cause symptoms only during times of physical stress.

* How many kinds of anterior pituitary cells are affected, leading to impairment in the secretion of one, a few, or all the pituitary hormones (called panhypopituitarism). As a general rule, the secretion of gonadotropins and growth hormone is more likely to be affected than ACTH and thyroid-stimulating hormone (TSH). Many exceptions occur, however, so that one may see a patient who has only isolated ACTH deficiency. Thus, one cannot make an assumption about the status of one pituitary hormone from the status of another; if the physician judges that it is clinically important to know the status of a particular pituitary hormone, the status of that hormone must be tested directly.

ACTH deficiency — The presentation of ACTH deficiency is almost exclusively that of the resulting cortisol deficiency. In its most severe form, cortisol deficiency leads to death due to vascular collapse, because cortisol is necessary for maintenance of peripheral vascular tone. A less severe form of the same phenomenon is postural hypotension and tachycardia. Mild, chronic deficiency may result in lassitude, fatigue, anorexia, weight loss, decreased libido, hypoglycemia, and eosinophilia. (See "Clinical manifestations of adrenal insufficiency in adults").

There are two important clinical distinctions between ACTH deficiency and primary adrenal insufficiency with a secondary increase in ACTH release:

* ACTH deficiency does not cause salt wasting, volume contraction, and hyperkalemia, because it does not result in clinically important deficiency of aldosterone.

* ACTH deficiency does not result in hyperpigmentation.

Both forms of adrenal insufficiency can cause hyponatremia. This abnormality is due to inappropriate secretion of antidiuretic hormone (vasopressin) that is caused by cortisol (not aldosterone) deficiency [1]. (See "Hyponatremia and hyperkalemia in adrenal insufficiency").

It is important to realize that moderately severe ACTH and cortisol deficiency may cause few or no symptoms and no physical findings. Consequently, the adequacy of ACTH secretion should be evaluated biochemically in all patients who have pituitary or hypothalamic disease. (See "Diagnosis of adrenal insufficiency in adults").

TSH deficiency — The clinical presentation of TSH deficiency is exclusively that of thyroxine deficiency, which might include fatigue, lethargy, cold intolerance, decreased appetite, constipation, facial puffiness, dry skin, bradycardia, delayed relaxation phase of the deep tendon reflexes, and anemia. The degree of symptoms and abnormal physical findings usually parallels the degree of thyroxine deficiency, but, as the case with ACTH deficiency, some patients with marked TSH deficiency have few or no symptoms. (See "Clinical manifestations of hypothyroidism").

Gonadotropin deficiency — Deficient secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) causes hypogonadism in both women and men.

* In women, hypogonadism means ovarian hypofunction, which results in the inability to ovulate, infertility, and decreased estradiol secretion. The latter may be responsible for a variety of symptoms including oligo- or amenorrhea, vaginal dryness and atrophy, and fatigue. Estradiol deficiency due to hypopituitarism causes hot flashes, like estradiol deficiency due to ovarian disease. No physical findings of hypogonadism are detectable initially, but after several years, breast tissue decreases, fine facial wrinkles appear, and bone mineral density declines. (See "Evaluation of spontaneous premature ovarian failure").

Serum androgen concentrations in women with hypopituitarism (particularly those with both gonadotropin and ACTH deficiency) are lower than those in normal control women [2], and appear to be correlated with bone mineral density [3]. The clinical significance of this decrease has yet to be determined.

* In men, hypogonadism means testicular hypofunction, which results in infertility and decreased testosterone secretion. The latter causes decreased energy and libido, and hot flashes if sufficiently severe, within weeks to months, but does not cause decreased muscle mass (and perhaps strength) for several years. Testosterone deficiency also causes decreased bone mineral density [4]. (See "Clinical features and diagnosis of male hypogonadism").

Growth hormone deficiency — Growth hormone deficiency in children typically presents as short stature. (See "Causes of short stature"). For many years, growth hormone deficiency beginning in adulthood was not thought to have any adverse consequences. However, evidence suggests that lack of growth hormone in adults might have a number of adverse effects [5]. The evidence is of two kinds. (See "Growth hormone deficiency in adults").

* The demonstration that patients who have growth hormone deficiency have a greater frequency of certain diseases than expected. Interpretation of this kind of evidence is confounded by the simultaneous deficiencies of other pituitary hormones and the variability of their replacement.

* The improvement these patients experience when they are treated with growth hormone. Interpretation of this kind of evidence is made difficult by the lack of placebo controls in most studies of growth hormone treatment.

With the above qualifications, we should consider the possibility that growth hormone deficiency may result in the following:

* Diminished muscle mass and increased fat mass [6-9].
* Increased serum low-density-lipoprotein (LDL) cholesterol.
* Decreased bone mineral density [10,11].
* Diminished sense of well being [12-14].
* Increased risk of cardiovascular disease [15] and increased inflammatory cardiovascular risk markers (IL-6 and C-reactive protein). (See "Screening for cardiovascular risk with C-reactive protein" and see "C-reactive protein in cardiovascular disease") [16].

Of the above possible effects of GH deficiency, only the effect on muscle and fat mass is well documented in GH-deficient men and women by improvements during GH replacement in placebo-controlled, double-blind studies. A beneficial effect of GH replacement on bone mineral density has also been demonstrated in men, but not in women. None of the other possible effects has been consistently demonstrated in randomized, placebo-controlled, double-blind studies. (See "Growth hormone deficiency in adults").

Prolactin deficiency — The only known presentation of prolactin deficiency is the inability to lactate after delivery.