Body organs affected by stimulatory hormones from the pituitary include the thyroid, adrenals, and gonads. Bone growth in childhood is dependent on pituitary GH. Pituitary failure does not produce a clear-cut syndrome analogous to syndromes produced by failure of pituitary-controlled organs (“end organs”) such as the thyroid. Therefore, pituitary hormone deficiency is considered only when there is deficiency-type malfunction in one or more end organs or metabolic processes such as growth that are dependent on pituitary hormones. Diagnosis is complicated by the fact that primary end organ failure is much more common than pituitary hormone deficiency. Another source of confusion is that most abnormal effects that can be produced by pituitary dysfunction can also be produced or simulated by nonpituitary etiologies. In addition, the hypothalamus controls pituitary secretion of several hormones, so that hypothalamic abnormality (e.g., defects produced by a craniopharyngioma or other hypothalamic tumor) can result in pituitary dysfunction.

Pituitary insufficiency in adults most commonly results in deficiency of more than one pituitary hormone and is most frequently caused by postpartum hemorrhage (Sheehan’s syndrome). Pituitary tumor is also an important cause. Gonadal failure is ordinarily the first clinical deficiency to appear. It is followed some time later by hypothyroidism. The first laboratory abnormality is usually failure of the GH level to rise normally in response to stimulation.


Diagnosis of pituitary insufficiency can be made by direct or indirect testing methods. Indirect methods demonstrate that a hypofunctioning organ that is pituitary dependent shows normal function after stimulation by injection of the appropriate pituitary hormone. Direct methods consist of blood level assays of pituitary hormones. Another direct method is injection of a substance that directly stimulates the pituitary. Now that pituitary hormone assays are available in most medical centers and sizable reference laboratories, indirect tests are much less frequently needed.

Assay of pituitary hormones. Pituitary hormones are peptide hormones rather than steroid hormones. Currently available immunoassays are a great improvement over original bioassays and even the first-generation radioimmunoassays (RIAs). However, with the exception of thyroid-stimulating hormone (TSH), pituitary hormone assays are still ordered infrequently, so that most physician’s offices and ordinary hospital laboratories do not find it economically worthwhile to perform the tests. The assays for TSH and adrenal cortex stimulating hormone (adrenocorticotropin; ACTH) are discussed in the chapters on thyroid and adrenal function. Pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH) assay are discussed later. GH deficiency is probably the most frequent pituitary hormone deficiency, either in overall pituitary failure or as an isolated defect leading to growth retardation in childhood. GH assay will be discussed in detail in relation to childhood growth disorders. GH assay has been used as an overall screen for pituitary insufficiency, but not all cases of pituitary hormone secretion deficiency have associated GH secretion deficiency. Prolactin is another pituitary hormone, but prolactin secretion is one of the last pituitary functions to disappear when the pituitary is injured.

In primary end organ failure the blood level of stimulating hormone from the pituitary is usually elevated, as the pituitary attempts to get the last possible activity from the damaged organ. Therefore, in the presence of end organ failure, if values for the pituitary hormone that stimulates the organ are in the upper half of the reference range or are elevated, this is strong evidence against deficiency of that pituitary hormone. Theoretically, inadequate pituitary hormone secretion should result in serum assay values less than the reference range for that pituitary hormone. Unfortunately, low-normal or decreased values of some pituitary hormones may overlap with values found in normal persons, at least using many of the present-day commercial assay kits. In that situation, stimulation or suppression testing may be necessary for more definitive assessment of pituitary function.

Stimulation and suppression tests. Pituitary suppression and stimulation tests available for diagnosis of pituitary hormone secretion deficiency include the following:

1. Metyrapone (Metopirone) test based on the adrenal cortex-pituitary feedback mechanism involving ACTH and cortisol but dependent also on hypothalamic function.
2. Thyrotropin-releasing hormone (TRH) test involving the ability of synthetic TRH to stimulate the pituitary by direct action to release TSH and prolactin.
3. Tests involving pituitary gonadotropins (LH and FSH) such as clomiphene stimulation (involving the hypothalamic-pituitary axis) or LH-releasing hormone (LHRH) administration (direct pituitary stimulation).
4. Tests of hypothalamic function, usually based on establishing pituitary normality by direct stimulation of the pituitary (TRH stimulation of TSH and prolactin, LHRH stimulation of LH secretion, etc.) followed by use of a test that depends on intact hypothalamic function to stimulate pituitary secretion of the same hormone. An example is the use of TRH to stimulate prolactin secretion by the pituitary, followed by chlorpromazine administration, which blocks normal hypothalamic mechanisms that inhibit hypothalamic stimulation of pituitary prolactin secretion and which leads to increased prolactin secretion if the hypothalamus is still capable of stimulating prolactin release.