Clinical manifestations of hypopituitarism

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 clinical manifestations in patients with hypopituitarism will be provided here. The causes, diagnosis, and treatment of hypopituitarism are reviewed separately. (See "Diagnostic testing for hypopituitarism" and "Treatment of hypopituitarism".)

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 (see "Causes of hypopituitarism"):

●The rapidity with which a disease affects anterior pituitary cells. Some diseases, such as pituitary apoplexy, develop rapidly, causing sudden impairment of corticotropin (ACTH) 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.

●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.

●The number of different anterior pituitary cells that 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.

Patients in whom the hypopituitarism is due to a 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".)

HORMONE DEFICIENCIES

ACTH — The presentation of corticotropin (ACTH) deficiency (secondary adrenal insufficiency) 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 cortisol deficiency due to ACTH deficiency and cortisol deficiency due to primary adrenal disease, which is also associated with aldosterone deficiency and secondary increases in pro-opiomelanocortin (POMC) and ACTH release (see "Clinical manifestations of adrenal insufficiency in adults"):

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

●Cortisol deficiency due to ACTH deficiency does not result in hyperpigmentation. In contrast, primary adrenal insufficiency, which is associated with secondary increases in POMC and ACTH, does 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 "Determining the etiology of adrenal insufficiency in adults" and "Clinical manifestations of adrenal insufficiency in adults", section on 'Secondary/tertiary adrenal insufficiency'.)

TSH — Common symptoms and signs of thyroid-stimulating hormone (TSH) deficiency include fatigue, 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" and "Central hypothyroidism", section on 'Clinical manifestations'.)

Gonadotropins — Deficient secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) results in hypogonadotropic hypogonadism (secondary hypogonadism) in both males and females.

●In women, hypogonadism means ovarian hypofunction, which results in anovulation and decreased estradiol secretion. The clinical consequences of estradiol deficiency in women with secondary hypogonadism are similar to those seen in women with primary hypogonadism (primary ovarian insufficiency [premature ovarian failure]). Findings in premenopausal women include irregular periods or amenorrhea, anovulatory infertility, hot flashes, and, eventually, vaginal atrophy. No physical findings of hypogonadism are detectable initially, but after several years, if estrogen therapy is not provided, breast tissue decreases and bone mineral density (BMD) declines. (See "Clinical manifestations and diagnosis of primary ovarian insufficiency (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 BMD [3]. The clinical significance of this decrease has yet to be determined. (See "Overview of androgen deficiency and therapy in females", section on 'Androgen deficiency'.)

●In men, hypogonadism means testicular hypofunction, which results in decreased spermatogenesis 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 BMD [4]. (See "Clinical features and diagnosis of male hypogonadism".)

Growth hormone — Growth hormone deficiency in children typically presents as short stature (see "Causes of short stature"). Likely clinical manifestations of growth hormone deficiency in adults are changes in body composition (increased fat mass and decreased lean body mass) and decreased BMD in men. Also possible, but not yet confirmed, are decreased BMD in women, dyslipidemia, cardiovascular disease, impaired psychological function, and an increase in mortality.

Adults with growth hormone deficiency may also be more likely to have dyslipidemia and increased inflammatory markers and biochemical markers of endothelial function. The clinical manifestations of growth hormone deficiency in adults are reviewed in more detail separately. (See "Growth hormone deficiency in adults", section on 'Clinical manifestations'.)

Prolactin — The only known clinical manifestation of prolactin deficiency is the inability to lactate after delivery. Isolated prolactin deficiency is rare; most patients with acquired prolactin deficiency have evidence of other pituitary hormone deficiencies [5].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Pituitary tumors and hypopituitarism".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Panhypopituitarism (The Basics)")

SUMMARY

●General principles – The clinical presentation of anterior pituitary hormone deficiencies varies, depending upon the rapidity with which a disease affects anterior pituitary cells, the severity of the hormonal deficiency, and the number of hormone deficiencies. (See 'General principles' above.)

●Hormonal deficiencies

•ACTH – The presentation of corticotropin (ACTH) deficiency is almost exclusively that of the resulting cortisol deficiency. There are two important clinical distinctions between cortisol deficiency due to ACTH deficiency (secondary adrenal deficiency) and cortisol deficiency due to adrenal disease (primary adrenal insufficiency) with a secondary increase in ACTH release (see 'ACTH' above):

-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.

•TSH – The clinical manifestations of thyroid-stimulating hormone (TSH) deficiency (secondary/central hypothyroidism) are similar to those of primary hypothyroidism for similar degrees of deficiency. (See 'TSH' above.)

•Gonadotropins – Deficient secretion of the gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) results in hypogonadotropic (secondary) hypogonadism in both females and males. (See 'Gonadotropins' above.)

•Growth hormone – Growth hormone deficiency in children typically presents as short stature. Likely clinical manifestations of growth hormone deficiency in adults are changes in body composition (increased fat mass with a decrease in lean body mass) and decreased bone mineral density (BMD) in men. Also possible, but not yet confirmed, are decreased BMD in women, dyslipidemia, cardiovascular disease, impaired psychological function, and an increase in mortality. (See 'Growth hormone' above.)

•Prolactin – The only known clinical manifestation of prolactin deficiency is the inability to lactate after delivery. (See 'Prolactin' above.)