Hypopituitarism refers to the inadequate production of one or more anterior pituitary hormones as a result of damage to the pituitary gland and/or hypothalamus. These hormones include growth hormone (GH), prolactin, thyroid stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), follicle stimulating hormone (FSH), and luteinizing hormone (LH). In some cases, the posterior pituitary hormones (e.g., ADH) may also be affected, which is known as panhypopituitarism. The most common cause of hypopituitarism is compression of the pituitary gland by a non-secretory pituitary macroadenoma. Other common causes include postpartum pituitary necrosis (Sheehan syndrome), traumatic brain injury, hypophysectomy, and/or irradiation of the pituitary gland. Clinical manifestations vary significantly and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism: Growth hormone deficiency during childhood presents with growth retardation, while prolactin deficiency manifests as lactation failure among women. Deficiencies of other anterior pituitary hormones, on the other hand, manifest with clinical features of hypogonadotropic hypogonadism, secondary hypothyroidism, and/or secondary adrenal insufficiency. Severe pituitary damage can also result in central diabetes insipidus as a result of ADH deficiency. Diagnosis of hypopituitarism involves measuring specific hormone levels (depending on the underlying hormone deficiency) and cranial imaging (in order to identify damage to the pituitary gland and/or hypothalamus). Treatment of hypopituitarism consists of hormone replacement therapy and treatment of the underlying disorder (e.g., transsphenoidal resection of pituitary adenomas).
- Intrasellar/parasellar masses
- Infarction of the pituitary gland as a result of ischemia and/or hemorrhage.
- Most commonly occurs in patients with a pre-existing pituitary adenoma
- Primarily affects the anterior pituitary gland because it receives its blood supply from a relatively low-pressure arterial system and is, therefore, vulnerable to ischemia and infarction.
- Sheehan syndrome: postpartum necrosis of the pituitary gland. Usually occurs following postpartum hemorrhage, but can also occur even without clinical evidence of hemorrhage.
- Traumatic brain injury (especially around the skull base)
- Iatrogenic causes (e.g., hypophysectomy, pituitary irradiation)
- Infiltration of the pituitary and/or hypothalamus
- Empty sella syndrome
- Congenital deficiency of hypothalamic hormones
- GnRH deficiency ( )
- Hypopituitarism becomes symptomatic when more than 80% of pituitary cells are damaged.
- Hypopituitarism refers to deficiency of one or more anterior pituitary hormones (see for their physiological effects)
- In addition to the aforementioned hormone deficiencies, patients with severe pituitary damage (panhypopituitarism) also present with deficiencies of posterior pituitary hormones:
Symptoms are variable and depend on the specific hormone deficiency, the age of disease onset, the rate at which hypopituitarism develops, and the underlying cause of hypopituitarism.
- During childhood:
- During adulthood: usually asymptomatic; subtle findings include weight gain, weakness, and depression
- Females: lactation failure following delivery
- Males: asymptomatic
- FSH/LH deficiency
- TSH deficiency: weight gain, cold intolerance, lethargy, constipation, dry skin (see )
- ACTH deficiency: weight loss, weakness, hypotension, chronic hyponatremia, hypoglycemia (see )
- Central diabetes insipidus: : polyuria, polydipsia
- Intrasellar/parasellar masses (e.g., pituitary macroadenomas, craniopharyngiomas) can present with headache, visual field defects (bitemporal hemianopsia), and/or diplopia.
- Pituitary apoplexy: manifests with acute onset of
- GH deficiency
- Prolactin deficiency: No routine test is available
Females: the presence of regular menstrual cycles effectively rules out gonadotropin deficiency; no further diagnostic test is required.
- ↓ FSH and ↓ LH and do not rise after a GnRH stimulation test
- ↓ Estradiol
- Lack of withdrawal bleeding after administering medroxyprogesterone acetate for 10 days (progesterone challenge test)
- However, withdrawal bleeding occurs after administering an estrogen preparation for 21 days followed by a progesterone preparation for 7 days (estrogen/progesterone challenge test)
- TSH deficiency: ↓ T3, ↓ T4, ↓ or normal TSH (see secondary )
- ACTH deficiency (see )
- Central diabetes insipidus: low urine osmolality (< 300 mOsmol/L); which persists despite water deprivation; but increases once exogenous desmopressin is administered (see )
- If a pituitary hormone deficiency is identified: perform cranial imaging (preferably MRI) to identify pituitary adenomas
- Growth hormone deficiency
- TSH deficiency: : administration of levothyroxine (see )
Patients with TSH deficiency should not be treated with levothyroxine until ACTH deficiency has been ruled out and/or treated because levothyroxine increases the clearance of cortisol and may precipitate an adrenal crisis!
- ACTH deficiency: glucocorticoid; replacement therapy with increased dosage during periods of stress (see )
Immediate treatment with glucocorticoids, without waiting for diagnostic confirmation, is required when acute ACTH deficiency is suspected (e.g., following pituitary apoplexy) to prevent an adrenal crisis!
- Gonadotropin deficiency
- Prolactin deficiency: no treatment is required
- Central diabetes insipidus: