History
Assessment of pituitary function, history of:

• Pituitary or hypothalamic lesions
• Cranial radiation
• Head trauma or head surgery
• Gonadal dysfunction
• Craniofacial abnormalities
• Empty sella
• Inflammatory or granulomatous disease
• Pregnancy-related hemorrhage or hypotension
• Initial symptoms may be nonspecific and of insidious onset, depending on severity of hormone deficiency: Fatigue, hypotension, cold intolerance
• Pituitary failure secondary to tumors may present with symptoms related to mass effect: Headache, visual impairment, hypothalamic dysfunction
• Symptoms are related to specific hormone deficiency:
  • Corticotropin (ACTH): Hypotension, hypoglycemia, nausea, vomiting, extreme fatigue, asthenia, anorexia, pallor, weight loss:
    • In children: Failure to thrive, hypoglycemia
  • Thyrotropin: Tiredness, cold intolerance, constipation, weight gain, hair loss, dry skin, bradycardia, hoarseness, mental lethargy
  • Gonadotropin: Sexual dysfunction, loss of libido, infertility:
    • In men: Impotence, decreased muscle and bone mass
    • In women: Amenorrhea, dyspareunia
    • In children: Delayed puberty
  • Growth hormone: Commonly deficient when other hormones are deficient. Fatigue, decreased muscle mass and strength, increased visceral fat, general malaise:
    • In children: Growth retardation
  • Prolactin: Inability to lactate

Physical Exam

• Hypotension
• Pituitary failure secondary to tumors: Visual impairment:
  • Corticotropin (ACTH): Hypotension, anorexia, pallor, weight loss
  • Thyrotropin: Weight gain, hair loss, dry skin, bradycardia, hoarseness
  • Gonadotropin: Delayed puberty
  • Growth hormone: Decreased muscle mass and strength, increased visceral fat, growth retardation

• Stigmata specific to hormone deficiencies
• Visual field defects
• Children:
  • Congenital malformations and syndromes, especially malformations of the head and genitalia
  • Growth retardation and delayed puberty

Lab

• Documentation of >1 deficiencies of pituitary hormones: Hormones are tested individually.
• Deficiencies may be single or multiple
• Laboratory measurement of basal and stimulated hormone levels, and levels of their target hormones.
• Corticotropin:
  • Basal ACTH at 8–9 AM, low level is positive test
  • Metapyrone test: Induced reduction in serum cortisol should cause increase in ACTH secretion.
  • Corticotropin stimulation test: Administration of synthetic ACTH should stimulate adrenal cortisol production, unless adrenal atrophy is present.
• Thyrotropin:
  • Secondary hypothyroidism, rare in absence of other pituitary hormone deficiencies
  • Low free T4 with inappropriately normal or low TSH suggests TSH deficiency
  • TSH not a reliable screening test
  • Thyroid-releasing hormone (TRH) stimulation: Blunted response in secondary hypothyroidism
• Gonadotropins:
  • Men: Serum testosterone is surrogate for LH deficiency in patients with known hypothalamic or pituitary disease. LH is elevated in primary hypogonadism, and normal or low in secondary hypogonadism.
  • Women: In women with known pituitary disease, LH and FSH testing not necessary in the presence of normal menses.
  • In the presence of oligomenorrhea or amenorrhea, measure FSH and LH levels.
  • Serum estradiol is low in hypogonadotropic hypogonadism.
  • Vaginal cytology for estrogenization index
  • Exclude hyperprolactinemia
• Prolactin:
  • Isolated hypoprolactinemia is rare.
  • Prolactin deficiency prevents lactation.
  • In prolactin deficiency, basal plasma levels are low, and fail to rise after injection of TRH.
  • Elevated prolactin may accompany hypopituitarism due to the disruption of hypothalamic inhibitory influences.
• Growth hormone:
  • Growth hormone deficiency highly likely if >2 other pituitary hormones deficient.
  • Low serum IGF-1.
  • Provocative tests include insulin-induced hypoglycemia, and arginine plus arginine-growth hormone-releasing hormone. Positive tests show deficient serum growth hormone response.
• Genetic testing if indicated

Imaging

• MRI of hypothalamic-pituitary region
• Radiographs: Chest, skull, hands, wrists (for bone age)
• Gonadotropin deficiency may result in osteoporosis

Pathological Findings

• Destruction of anterior pituitary
• Atrophy of adrenal cortex, thyroid, gonads

• Primary hypothyroidism
• Primary hypogonadism
• Addison disease, primary adrenal insufficiency
• Hypothalamic insufficiency
• Kallmann syndrome
• Chronic liver disease
• Constitutional short stature

ALERT
Geriatric Considerations
More difficult to diagnose in elderly

Pediatric Considerations

• Congenital malformations, genetic conditions may warrant screening for hypopituitarism.
• Growth hormone deficiency may result in growth retardation.
• Hypogonadism in prenatal pituitary failure
• Delayed puberty

Pregnancy Considerations

• Pregnancy-associated hemorrhage or hypotension may result in pituitary hypoperfusion and subsequent partial or complete pituitary failure (Sheehan syndrome)
• Lymphocytic hypophysitis may be triggered by pregnancy.