Hypopituitarism

Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain.

[4] The signs and symptoms of hypopituitarism vary, depending on which hormones are undersecreted and on the underlying cause of the abnormality.

The diagnosis of hypopituitarism is made by blood tests, but often specific scans and other investigations are needed to find the underlying cause, such as tumors of the pituitary, and the ideal treatment.

Hypopituitarism is a rare disease, but may be significantly underdiagnosed in people with previous traumatic brain injury.

[1][7] Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly (enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve or optic chiasm, there may be visual field defects.

[8] Apoplexy, in addition to sudden headaches and rapidly worsening visual loss, may also be associated with double vision that results from compression of the nerves in the adjacent cavernous sinus that control the eye muscles.

Both sexes may experience a decrease in libido and loss of sexual function, and have an increased risk of osteoporosis (bone fragility).

[1][6] Growth hormone (GH) deficiency leads to a decrease in muscle mass, central obesity (increase in body fat around the waist) and impaired attention and memory.

[11] Thyroid-stimulating hormone (TSH) deficiency leads to hypothyroidism (lack of production of thyroxine (T4) and triiodothyronine (T3) in the thyroid).

In children, hypothyroidism leads to delayed growth and in extreme inborn forms to a syndrome called cretinism.

[8] Antidiuretic hormone (ADH) deficiency leads to the syndrome of diabetes insipidus (unrelated to diabetes mellitus): inability to concentrate the urine, leading to polyuria (production of large amounts of clear urine) that is low in solutes, dehydration and—in compensation—extreme thirst and constant need to drink (polydipsia), as well as hypernatremia (high sodium levels in the blood).

The posterior pituitary secretes antidiuretic hormone, which regulates osmolarity of the blood, and oxytocin, which causes contractions of the uterus in childbirth and participates in breastfeeding.

[14] The pituitary develops in the third week of embryogenesis from interactions between the diencephalon part of the brain and the nasal cavity.

Together, these cellular signals stimulate a group of cells from the oral cavity to form Rathke's pouch, which becomes independent of the nasal cavity and develops into the anterior pituitary; this process includes the suppression of production of a protein called Sonic hedgehog by the cells of Rathke's pouch.

[14][16][17] In addition to the pituitary, some of the transcription factors are also required for the development of other organs; some of these mutations are therefore also associated with specific birth defects.

[8] Prolactin can be measured by basal level, and is required for the interpretation of LH and FSH results in addition to the confirmation of hypopituitarism or diagnosis of a prolactin-secreting tumor.

[20] If GH deficiency is suspected, and all other pituitary hormones are normal, two different stimulation tests are needed for confirmation.

[1] Symptoms of diabetes insipidus should prompt a formal fluid deprivation test to assess the body's response to dehydration, which normally causes concentration of the urine and increasing osmolarity of the blood.

In contrast, there is no change if the kidneys are unresponsive to ADH due to a different problem ("nephrogenic diabetes insipidus").

[8] Formal visual field testing by perimetry is recommended, as this would show evidence of optic nerve compression by a tumor.

[1] Pituitary tumors require treatment when they are causing specific symptoms, such as headaches, visual field defects or excessive hormone secretion.

This approach may improve pituitary hormone secretion in more than half the cases, and make supplementary treatment unnecessary.

[23] Most pituitary hormones can be replaced indirectly by administering the products of the effector glands: hydrocortisone (cortisol) for adrenal insufficiency, levothyroxine for hypothyroidism, testosterone for male hypogonadism, and estradiol for female hypogonadism (usually with a progestogen to inhibit unwanted effects on the uterus).

[8] The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population.

[1][7] Recent studies have shown that people with a previous traumatic brain injury, spontaneous subarachnoid hemorrhage (a type of stroke) or radiation therapy involving the head have a higher risk of hypopituitarism.

[26] Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition.

He described the condition on autopsy in a 46-year-old woman who had had severe puerperal fever eleven years earlier, and subsequently had amenorrhea, weakness, signs of rapid aging, and anemia.

[1][5] The eponym Simmonds' syndrome is used infrequently for acquired hypopituitarism, especially when cachexia (general ill health and malnutrition) predominates.

[1] Until the 1950s, the diagnosis of pituitary disease remained based on clinical features and visual field examination, sometimes aided by pneumoencephalography and X-ray tomography.

The major breakthrough in diagnosis came with the discovery of radioimmunoassay by Rosalyn Yalow and Solomon Berson in the late 1950s.

The major endocrine glands of the body. Pituitary hormones control the function of the adrenal gland, thyroid gland and the gonads (testes and ovaries).
CT scan of the brain showing a craniopharyngioma (white structure in the center of the image). This tumor may cause hypopituitarism and requires surgical removal.