History and exam
Key diagnostic factors
common
history of pituitary or hypothalamic disease
Key risk factors for hypopituitarism include pituitary tumors, apoplexy, surgery, or radiation; genetic disorders such as mutations of the PROP1 gene that cause familial hormone deficiencies; and hypothalamic disease.
history of traumatic brain injury
headaches
Often develop due to raised intracranial pressure from a space-occupying lesion in the sellar or parasellar region.
In patients who develop a sudden severe headache, the possibility of pituitary apoplexy needs to be considered.
faltering growth or short stature
Growth hormone deficiency in children.
infertility
Gonadotropin deficiency.
hypoglycemia
Adrenal insufficiency.
amenorrhea/oligomenorrhea
Suggests gonadotropin deficiency and occurs early in the sequence of pituitary hormone loss. Patients can also present with prolactin excess causing functional suppression of the pituitary gonadal axis.
galactorrhea
Seen in patients with elevated prolactin levels from stalk effect or a prolactinoma.
May be spontaneous or expressible.
delayed puberty
Absence of facial and body hair, gynecomastia, and small undeveloped testes due to gonadotropin deficiency in childhood.
uncommon
family history of pituitary hormone deficiencies
Family members may have required multiple hormone replacement therapies from childhood.
hypotension
Acute adrenal insufficiency.
visual field defects
Patients will complain of difficulty seeing into the periphery, sometimes described as tunnel vision.
ophthalmoplegia
Associated with cranial nerve invasion or impingement by a sellar or parasellar process. Patients characteristically complain of diplopia.
Other diagnostic factors
common
cardiovascular events
Attributable to relative insulin resistance and chronic growth hormone deficiency (leading to obesity, hyperlipidemia, and hypertension).[4]
cold intolerance
Thyroid hormone deficiency.
weight gain
Thyroid hormone deficiency.
erectile dysfunction and reduced libido
Seen in males with low testosterone from hypogonadotropic hypogonadism.
nausea
Adrenal insufficiency.
vomiting
Adrenal insufficiency.
fatigue
Adrenal insufficiency.
weakness
Adrenal insufficiency.
dizziness
Adrenal insufficiency.
constipation
Thyroid hormone deficiency results in reduced gastrointestinal motility.
dry skin
Thyroid hormone deficiency.
delayed relaxation of reflexes
Thyroid hormone deficiency.
uncommon
hypoactive sexual desire
Gonadotropin deficiency.
hot flashes
Gonadotropin deficiency.
nocturia and polyuria
Antidiuretic hormone insufficiency leading to diabetes insipidus.
breast atrophy
Gonadotropin deficiency.
reduced bone and muscle mass
Due to gonadotropin deficiency in both sexes. Osteoporosis may present as an atraumatic fracture or as an incidental finding on radiologic tests.
loss of axillary and pubic hair
Chronic cases of adrenal insufficiency.
Risk factors
strong
pituitary tumor
Typical clinical syndrome such as acromegaly, resulting from hypersecretion of one or more anterior pituitary hormones. Alternatively, they may present more insidiously with mass effect, with tumor expansion leading to compression of surrounding structures.[8]
Hypopituitarism resulting from pituitary adenomas is related to impaired blood flow to the normal pituitary tissue, compression of normal tissue, or interference with the delivery of hypothalamic hormones via the hypothalamus-hypophyseal portal system.
Craniopharyngiomas arise in Rathke pouch and may be cystic or solid and are commonly calcified. They commonly present with growth hormone deficiency and diabetes insipidus, with or without visual field defects.[10]
pituitary apoplexy
Denotes the sudden hemorrhagic destruction of a pre-existing pituitary adenoma. It presents with the sudden onset of an excruciating headache, visual disturbance, or ophthalmoplegia due to cranial nerve palsies (III, IV, VI).[35]
Sudden onset of adrenocorticotropic hormone deficiency and subsequent cortisol deficiency is the most serious complication and can lead to life-threatening hypotension, hyponatremia, and hypoglycemia.
Hypopituitarism caused by pituitary infarction may develop immediately or after a delay of several years, depending on the degree of tissue destruction.[15] Apoplexy usually spares the posterior pituitary. Associated risk factors for pituitary apoplexy include brain trauma, diabetes mellitus, pregnancy, anticoagulants, and blood dyscrasias.
pituitary surgery
Prompt postoperative assessment of pituitary function should be performed following surgery for pituitary adenomas.[36] Prognostic indicators for good recovery include smaller tumor size and less severe hypopituitarism prior to the surgery. At least partial recovery of pituitary function in up to 50% of patients has been reported after surgery.[37]
cranial radiation
The degree of hormonal deficits caused by radiation therapy is related to the age of exposure of the patient, the radiation dose received, and the time elapsed since the radiation exposure to the hypothalamic-pituitary axis.[34][38][39] Isolated growth hormone deficiency ensues after lower doses, whereas panhypopituitarism occurs after higher doses.
traumatic brain injury
genetic defects
May be of either pituitary or hypothalamic origin. Congenital deficiencies may be of isolated hormones or multiple pituitary hormones. Transcription factor defects including Pit-1, PROP1, HESX1, LHX3, LHX4, and TPIT are all associated with multiple hormone deficiencies and varying degrees of inherited hypopituitarism.[26][27] These transcription factors are responsible for organogenesis and early differentiation of pituicytes. Mutations in the PROP1 gene are the most common cause of familial and sporadic congenital pituitary hormone deficiencies.
hypothalamic disease
Unlike diseases that affect the pituitary directly, hypothalamic conditions can also diminish secretion of vasopressin and cause diabetes insipidus (DI). Typically, pituitary lesions alone do not cause DI, because some vasopressin-producing neurons terminate in the median eminence. Mass lesions such as craniopharyngiomas, malignant tumors, and metastasis; hypothalamic radiation; and infiltrative lesions such as sarcoidosis and more commonly Langerhans cell histiocytosis X have been associated with the development of DI.
weak
inflammatory disorders
May clinically and radiologically mimic pituitary adenomas with mass effect leading to headaches, visual impairment, and variable degrees of hypopituitarism.
Lymphocytic hypophysitis commonly results in adrenocorticotropic hormone and thyroid-stimulating hormone deficiency; however, diabetes insipidus and hyperprolactinemia have also been described. Hereditary hemochromatosis commonly results in gonadotropin deficiency.
severe postpartum hemorrhage (Sheehan syndrome)
During pregnancy, the pituitary gland enlarges due to hyperplasia and hypertrophy of the lactotroph cells, which produce prolactin. During a severe postpartum hemorrhage, the hypophyseal vessels, which supply the pituitary, constrict in response to decreasing blood volume, and subsequent vasospasm occurs leading to necrosis of the pituitary gland and hypopituitarism. The degree of necrosis correlates with the severity of the hemorrhage. Anterior pituitary hormone deficits may be single or multiple, depending on the degree of necrosis. Classically, it is associated with inability to lactate post delivery.[41]
empty sella syndrome
Empty sella refers to an enlarged sella turcica, which is not entirely filled with pituitary tissue. Primary empty sella is a defect in the diaphragm sella, which allows the cerebrospinal fluid (CSF) pressure to enlarge the sella and is typically not associated with hypopituitarism.[22]
In secondary empty sella, a mass such as an adenoma enlarges the sella and is later removed by surgery, radiation, or infarction and subsequently leaves a CSF vacuum. Most patients have no pituitary hormone dysfunction; however, hypopituitarism can result from mass effect of the adenoma, surgery, radiation, or infarction of the tumor.[42][43]
tuberculous meningitis
May cause hypopituitarism years after the original infection.
syphilis
May cause hypopituitarism in congenital syphilis and adult infection.
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