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 nonsecretory 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 manifests with delayed growth, while prolactin deficiency in women can manifest as lactation failure. Deficiencies of other anterior pituitary hormones, on the other hand, manifest with clinical features of hypogonadotropic hypogonadism, secondary hypothyroidism, and/or secondary adrenal insufficiency (AI). Severe pituitary damage can also result in central diabetes insipidus as a result of ADH deficiency. Hypopituitarism is diagnosed by measuring specific hormone levels (depending on the underlying hormone deficiency) and with cranial imaging (in order to identify damage to the pituitary gland and/or hypothalamus). Treatment consists of hormone replacement therapy and treatment of the underlying disorder (e.g., transsphenoidal resection of pituitary adenomas).
- Intrasellar/parasellar masses
- Nonsecretory pituitary macroadenomas (≥ 10 mm in diameter) are the most common cause of hypopituitarism among adults.
- Less common: meningiomas, craniopharyngiomas, internal carotid artery aneurysms, Rathke cleft cyst (a benign, intrasellar/suprasellar cyst that arises from the remnants of the Rathke pouch)
- Infarction of the pituitary gland as a result of ischemia and/or hemorrhage
- Most commonly occurs in patients with a preexisting 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. 
- During pregnancy, hypertrophy of prolactin-producing regions increases the size of the pituitary gland, making it very sensitive to ischemia.
- Blood loss during delivery/postpartum hemorrhage; → hypovolemia → vasospasm of hypophyseal vessels → ischemia of the pituitary gland → empty sella turcica on imaging 
- Traumatic brain injury (especially around the skull base)
- Infiltration of the pituitary and/or hypothalamus
- Infections: meningitis, TB, tertiary syphilis, toxoplasmosis, fungi (e.g., histoplasmosis)
- Empty sella syndrome
- Congenital deficiency of hypothalamic hormones
- Hypopituitarism becomes symptomatic when more than 80% of pituitary cells are damaged. 
Hypopituitarism refers to deficiency of one or more anterior pituitary hormones (see ““)
- GH deficiency → growth retardation (during childhood), ↓ bone density, muscle atrophy, hypercholesterolemia
- Prolactin deficiency → lactation failure following delivery
- FSH/LH deficiency → hypogonadotropic hypogonadism (secondary hypogonadism)
- TSH deficiency → secondary hypothyroidism
- ACTH deficiency →
- 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.
- General symptoms: Intrasellar/parasellar masses (e.g., pituitary macroadenomas, craniopharyngiomas) can manifest with headache, visual field defects (bitemporal hemianopsia), and/or diplopia.
- Pituitary apoplexy manifests with acute onset of:
- During childhood:
- During adulthood
- Usually asymptomatic
- Subtle findings include weight gain, weakness, and depression.
- Women: lactation failure following delivery
- Men: 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
Each hormone deficiency must be tested individually because the pattern of hormone deficiency may vary.
- All patients: Assess for deficiencies of ACTH, TSH, LH/FSH, and ADH.
- GH deficiency testing: Perform if treatment is indicated (e.g., in children) or if < 3 of the other deficiency tests are positive.
- Prolactin testing: not routinely performed for hypopituitarism
- Melanocyte stimulating hormone (MSH) and oxytocin levels: not used in the diagnosis of hypopituitarism
- If a hormone deficiency is identified, cranial imaging (preferably MRI) is indicated to identify the cause (e.g., pituitary adenoma).
- In an emergency setting (e.g., adrenal crisis, myxedema coma), treatment is indicated prior to biochemical testing.
ACTH deficiency (central/secondary adrenal insufficiency) 
- First line: morning cortisol level
- For further information on the diagnosis of secondary adrenal insufficiency, see “Endocrine testing for adrenal insufficiency.”
TSH deficiency (secondary hypothyroidism)
- First line: thyroid function tests (both TSH and free T4 are required)
- Supportive findings: ↓ or normal TSH with ↓ serum free T4 and ↓ serum free T3
- For further information on the diagnosis of secondary hypothyroidism, see “Diagnostics” in “Hypothyroidism.”
LH/FSH deficiency (secondary hypogonadism)
- Patients with regular menstrual cycles: confirms normal gonadotropin function; no further diagnostic testing required
- Routine testing in oligomenorrhea, amenorrhea, or postmenopause if secondary hypogonadism is suspected:
- For further information on the diagnosis of secondary hypogonadism, see “Diagnostics” in “Hypogonadism.”
- Testing is required if treatment is planned and optional if treatment is not planned and hormonal deficiencies exist in ≥ 3 pituitary axes.
- IGF-1 level: typically ↓; may be normal 
- Confirmatory testing: GH stimulation test 
- Routine testing is not performed in the investigation of hypopituitarism.
- Prolactin levels may be tested in:
- Supportive finding: low-normal to low prolactin level, which does not increase with stimulation testing 
Posterior pituitary hormones: ADH deficiency (central diabetes insipidus)
- First-line: urine and plasma osmolality 
- If urine and plasma osmolality are abnormal: water deprivation test
- For further information, see “Diagnostics” in “Diabetes Insipidus.”
Imaging of the pituitary is indicated in all patients to determine the underlying cause.
- MRI brain
- CT Head (without IV contrast): used if there are contraindications to MRI or in patients requiring rapid evaluation, e.g., after suspected TBI or SAH
- Assess patients for signs of clinical instability and, if present, initiate emergency management.
- All patients require pituitary hormone replacement to treat the conditions that result from hypopituitarism.
- Identify and treat the underlying cause (e.g., transsphenoidal resection in some cases of pituitary macroadenomas).
- Ensure patients receive appropriate education on the following aspects:
- Importance of treatment adherence
- Effects of intercurrent illness (e.g., sick days rules in adrenal insufficiency)
- Need for an emergency bracelet or necklace
- Adrenal crisis: Give immediate IV hydrocortisone without waiting for diagnostic confirmation (see “Adrenal crisis” for dosage information).
- Myxedema coma
- Once stabilized, patients should be started on maintenance pituitary hormone replacement.
Maintenance therapy for pituitary hormone deficiencies
|Hormone replacement in hypopituitarism |
|Secondary adrenal insufficiency|| |
|Growth hormone deficiency |
|Central diabetes insipidus|| |
Hypopituitarism 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.