Hypopituitarism (Panhypopituitarism)



Hypopituitarism is a clinical syndrome of deficiency in pituitary hormone production.[1] This may result from disorders involving the pituitary gland, hypothalamus, or surrounding structures. Panhypopituitarism refers to involvement of all pituitary hormones; however, only 1 or more pituitary hormones are often involved, resulting in isolated or partial hypopituitarism.[2] (See Pathophysiology and Etiology.)

Pituitary gland physiology

The pituitary gland has 2 parts: the anterior pituitary (adenohypophysis) and the posterior pituitary (neurohypophysis). The anterior pituitary receives signals from the hypothalamus that either stimulate or inhibit secretion of pituitary hormones. These hormones are secreted directly into the systemic circulation, where they act on specific organs.

The actions of the pituitary gland can be modulated at many stages. The pituitary hormones, or target organ hormones, can influence the hypothalamus and the pituitary to decrease or increase pituitary hormone secretion through long and short feedback loops. Hormones secreted by the anterior pituitary include the following:

The posterior pituitary does not produce its own hormones. The hypothalamus produces 2 hormones, vasopressin (VP) and oxytocin (OXT), that are secreted from the nerve axons into the capillary beds that supply the posterior pituitary, where they are stored in cells and ultimately released into the circulation.

Vasopressin, also called antidiuretic hormone (ADH), primarily acts on the V2 receptors of the distal tubules of the kidney to reabsorb water, which increases total body water and urine osmolality and decreases urine volume. Vasopressin, at high levels, also acts as a pressor on the V1 receptors of vascular smooth muscle. Oxytocin induces labor in pregnant women, causing contraction of uterine smooth muscle; the hormone also initiates the mechanics of breastfeeding.

Adrenal crisis

An adrenal crisis (acute cortisol insufficiency) is life threatening and should be treated promptly. When hypothyroidism occurs concurrently with cortisol insufficiency, glucocorticoid replacement should precede thyroid hormone replacement. This reduces the likelihood of possible cortisol insufficiency resulting from increased demands due to enhanced metabolism. (See Treatment and Medication.)

Hormone replacement

Patients with hypopituitarism are maintained on hormone replacement therapies for life, unless the causative disorder is reversed by treatment or by natural history. These medically replaced patients are generally asymptomatic but require increased doses of glucocorticoids following any form of stress, emotional or physical. The most common stressor is infection. Not matching glucocorticoid dose to stress causes acute decompensation. These patients present with nausea and vomiting and may be hypotensive and ill-appearing. A patient's initial presentation of undiagnosed hypopituitarism may be with this life-threatening decompensated state under stress.

Patient education

Education emphasizes the need for lifelong hormone replacement, increased glucocorticoid replacement during stress, and prompt medical attention as appropriate. Regular monitoring to avoid excessive hormone replacement is important.

All patients with hypopituitarism should carry some identification. This is often in the form of an identification bracelet worn on the wrist or neck. Some vendors include more than 20 lines of information in a tiny pendant. Some may need to have a vial of hydrocortisone (Solu-Cortef) 100 mg and a syringe for emergency purposes at home and while travelling.


When pituitary hormone production is impaired, target gland hormone production is reduced because of a lack of trophic stimulus. Normally, subphysiologic target hormone levels stimulate the pituitary gland to increase trophic hormone production; however, in hypopituitarism, the pituitary gland response is absent, suboptimal, or inappropriate (with biologically inert hormone production). This results in progressive secondary failure of the target glands. Patients with hypopituitarism typically present with low target hormone levels accompanied by low or inappropriately normal levels of the corresponding trophic hormone.

The tropic hormone level may appear to be within the reference range with a corresponding subphysiologic target hormone level. Such a tropic hormone level would be inappropriately low for the subphysiologic target hormone level. Sometimes, the assayed tropic hormone level may be biologically inert.

Thus, pituitary function is assessed by the target gland function, not by measuring the pituitary hormone as an isolated event. This is in contrast to target gland function being assessed by the pituitary hormone. For example, adequate pituitary thyrotropin secretion is best assessed by the serum free thyroxin. Primary thyroid gland hypofunction is best assessed by the serum thyrotropin. A low serum free thyroxin yet normal serum thyrotropin indicates pituitary, not thyroid, disease, and central hypothyroidism would be missed by only measuring serum thyrotropin.


Causes of pituitary insufficiency include pituitary adenomas or other intrasellar and parasellar tumors, inflammatory and infectious destruction, surgical removal, radiation-induced destruction of pituitary tissue, traumatic brain injury (TBI), subarachnoid hemorrhage, and postpartum pituitary necrosis (Sheehan syndrome). Similar diseases originating in the hypothalamus or pituitary stalk may also result in pituitary insufficiency. Children may have a genetic cause of transcription factor deficiency, resulting in trophic hormone hyposecretion.

Pituitary tumors, or adenomas, are the most common cause of hypopituitarism in adults, although traumatic brain injury as a cause is being more frequently recognized.

Hypopituitarism resulting from pituitary adenomas is due to impaired blood flow to the normal tissue, compression of normal tissue, or interference with the delivery of hypothalamic hormones via the hypothalamus-hypophysial portal system.

In primary pituitary destruction, the anterior pituitary is destroyed, causing a deficiency in some or all pituitary hormones, including prolactin. Disease involving the hypothalamus or pituitary stalk may cause pituitary hormone deficiency with an elevated serum prolactin. This prolactin elevation may suggest the possibility of recovery of function if the offending mass is debulked. Pituitary tumors, or adenomas, can be secretory or nonsecretory. Approximately 30% of all macroadenomas larger than 10 mm produce at least 1 hormone. In such cases, the most common phenomenon is prolactin hypersecretion.

Hypothalamic disease involves destruction of the hypothalamus. This causes a deficiency or loss of hypothalamic regulatory hormone input to the pituitary, which leads to the loss of anterior pituitary hormone secretion, with an elevated serum prolactin level. Loss of antidiuretic hormone (ADH) from hypothalamic disease may have concomitant diabetes insipidus.

Hypersecretion of a pituitary hormone is suggestive of a secretory adenoma. Some pituitary adenomas may result in a deficiency in some pituitary hormones, but with concomitant hyperprolactinemia. Normally, dopamine, produced in the hypothalamus, inhibits prolactin secretion by the anterior pituitary. Compressing the pituitary stalk decreases the inhibitory effect of dopamine and increases prolactin levels.

Longstanding target gland hyposecretion may result in hyperplasia of the relevant pituitary cell secreting the tropic hormone, the level of which would be elevated. With an enlarged pituitary gland from the hyperplasia, a mass is simulated. Although uncommon, this may appear to be a pituitary adenoma, but the target gland is not hyperfunctioning.

Another common intracranial tumor is craniopharyngioma, a squamous cell tumor that arises from remnants of the Rathke pouch. One third of these tumors extend into the sella, while approximately two thirds remain suprasellar.

Sheehan syndrome occurs with a large volume of postpartum hemorrhage. During pregnancy, the pituitary gland enlarges due to hyperplasia and hypertrophy of the lactotroph cells, which produce prolactin. The hypophyseal vessels, which supply the pituitary, constrict in response to decreasing blood volume, and subsequent vasospasm occurs, causing necrosis of the pituitary gland. The degree of necrosis correlates with the severity of the hemorrhage. As many as 30% of women experiencing postpartum hemorrhage with hemodynamic instability may develop some degree of hypopituitarism. These patients can develop adrenal insufficiency, hypothyroidism, amenorrhea, diabetes insipidus, and an inability to breastfeed (an early symptom). Lymphocytic hypophysitis occurs most commonly in the postpartum state and may appear as Sheehan syndrome due to the resulting postpartum hypopituitarism.

Pituitary apoplexy denotes the sudden destruction of the pituitary tissue resulting from infarction or hemorrhage into the pituitary. The most likely cause of the apoplexy is brain trauma; however, it can occur in patients with diabetes mellitus, pregnancy, sickle cell anemia, blood dyscrasias or anticoagulation, or increased intracranial pressure. Apoplexy usually spares the posterior pituitary and solely affects the anterior pituitary. In patients with such underlying diseases, Sheehan syndrome can occur with lesser degrees of postpartum hemorrhage or hypotension.

Head trauma from a motor vehicle accident, a fall, or a projectile can cause hypopituitarism by direct damage to the pituitary or by injuring the pituitary stalk or the hypothalamus. Hypopituitarism may occur immediately, or it may develop months or years later. Recovery can occur from regeneration. Many studies show an incidence of 15-40%,[3] but a study by Kokshoorn et al found the incidence of clinically significant posttraumatic hypopituitarism to be low.[4]

In a study by Giuliano et al of hypopituitarism in adults associated with complicated mild traumatic brain injury, consequent growth hormone deficiency existed in a subset of patients even several years postinjury. Visceral adiposity and metabolic changes were associated with the deficiency.[5]

Other causes of hypopituitarism include empty sella syndrome and infiltrative diseases. Empty sella syndrome occurs when the arachnoid herniates into the sella turcica through an incompetent sellar diaphragm and flattens the pituitary against bone, but resulting pituitary insufficiency is uncommon. Infiltrative diseases, such as Wegener granulomatosis and sarcoidosis, can cause destruction of the anterior pituitary. Lymphocytic hypophysitis is an autoimmune destructive disease that may be directed towards the pituitary or its stalk.

Physiologic or psychological states can influence the hypothalamus by impairing synthesis and secretion of regulating hormones. For example, poor nutrition may impair the hypothalamic secretion of gonadotropin-releasing hormone (GnRH), resulting in reversible pituitary gonadotropin deficiency. Medications may affect measured hormone levels, such as opioids decreasing serum LH, testosterone, and cortisol.

The degree of hormone deficiency varies greatly and depends on the extent of the process and its location. Some functional causes include emotional disorders, changes in body weight, habitual exercise, anorexia, bulimia, congestive heart failure (CHF), renal failure, and certain medications.

Hypopituitarism can occur in adult patients after cranial radiotherapy performed to treat nonpituitary tumors. Thus, patients who undergo cranial radiotherapy should be periodically assessed over a period of years for pituitary functions.[6]

Additional causes of hypopituitarism include the following:

  1. Histiocytosis X
  2. Hemochromatosis
  3. Tuberculosis
  4. Syphilis
  5. Meningitis
  6. Iatrogenic causes - Radiation,[6, 7] surgery, and withholding of chronic glucocorticoid replacement
  7. Kallmann syndrome
  8. Lymphocytic hypophysitis
  9. Transsphenoidal adenomectomy
  10. Congenital - Usually presents in childhood, but can present later with features such as delayed puberty; heritable pituitary disease usually involves homeodomain transcription factors

With regard to item 9 above, in a study of 435 patients, Fatemi et al found evidence that the likelihood of hypopituitarism development after transsphenoidal adenoma removal is higher when the tumor is larger than 20 mm.[8] In contrast, some with hypopituitarism prior to adenomectomy may have improved pituitary function following surgery, if the cause of the hypopituitarism was increased suprasellar pressure resulting from the mass itself.


Hypopituitarism is listed as a rare disorder by the National Institutes of Health (NIH), affecting less than 200,000 individuals in the United States. Internationally, hypopituitarism has an estimated incidence of 4.2 cases per 100,000 per year and an estimated prevalence of 45.5 cases per 100,000 without gender difference.

Regal et al reported the first study detailing prevalence and incidence of hypopituitarism in a population in northwestern Spain. They studied an adult population of 146,000 and found a prevalence of 45.5 cases per 100,000 population.[9]

The incidence of permanent pituitary deficiency following traumatic brain injury has yet to be determined.


Stable patients who are diagnosed with hypopituitarism have a favorable prognosis with replacement hormone therapy. Patients with acute decompensation are in critical condition and may have a high mortality rate.


Four retrospective studies from the United Kingdom and Sweden showed that mortality is increased by 1.3- to 2.2-fold in patients with hypopituitarism, compared with age- and sex-matched cohorts.[10] Morbidity is variable and may result from hormone deficiency, from the underlying disease, or from inadequate long-term replacement therapy. The systemic effects of pituitary hormone deficiencies vary depending on the extent of pituitary involvement. Given that the pituitary acts on numerous endocrine sites, the consequences of pituitary dysfunction range from subclinical disease to panhypopituitarism. Underlying disorders, such as tumors, intracranial lesions, or systemic disease, may be asymptomatic or may cause morbidity that masks the hormone deficiency. Note the following:

A study by O’Reilly et al indicated that in patients with hypopituitarism resulting from nonfunctioning pituitary adenomas, deficiencies of ACTH and gonadotropin increase mortality rates, as do excessive doses of hydrocortisone and suboptimal replacement of levothyroxine. The study included 519 patients, with a median followup of 7.0 years.[11]

Cardiovascular disease is significantly higher among hypopituitary patients.[12] Female patients with hypopituitarism who are receiving controlled thyroid and steroid hormone substitution, but without GH replacement, have a more than 2-fold increase in cardiovascular mortality compared with the general population.[12] Hypopituitary patients have a lower high-density lipoprotein cholesterol level and a higher low-density/high-density lipoprotein ratio.[12]

However, a literature review by Giagulli et al indicated that neither short- nor long-term GH supplementation significantly reduces cardiovascular risk in adults with a GH deficit resulting from either isolated GH deficiency or compensated panhypopituitarism. Nonetheless, both groups of patients in the study did show an increase in fat-free mass, a decrease in fat mass, and a reduction in low-density lipoprotein cholesterol.[13]

There is a higher incidence of cerebrovascular morbidity and mortality following pituitary radiotherapy.

Other complications of hypopituitarism include visual deficits and, due to a limited ability of the endocrine system to respond appropriately, susceptibility to infection and other stressors. Decreased quality of life has been documented by standardized questionnaires.


Presentation varies from asymptomatic to acute collapse, depending on the etiology, rapidity of onset, and predominant hormones involved. Initially, a patient with any hormone deficiency may be asymptomatic. Individuals with the following deficiencies present with the indicated condition:

Other presenting features may be attributable to the underlying cause. A patient with a space-occupying lesion may present with headaches, double-vision, or visual-field deficits. A patient with large lesions involving the hypothalamus may present with polydipsia/polyuria or, rarely, syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Physical Examination

Physical examination findings may be normal in subtle presentations. Patients may present with features attributable to deficiency of target hormones, including hypothyroidism (with a small, soft thyroid gland), adrenal insufficiency, hypogonadism (with small, soft testes in men), and failure to thrive. In women, loss of adrenal and ovarian function results in loss of all androgens; loss of axillary and pubic hair may result.

In the stable patient, with the diverse complaints associated with hypopituitarism, a complete physical examination, including thyroid palpation, genital inspection, and ophthalmic examination, can support the diagnosis of hypopituitarism. During the neurologic and ophthalmic examinations, check specifically for visual acuity, extraocular movements, and bitemporal hemianopsia. Also look for evidence of hormonal hypersecretion due to a large functioning adenoma, such as signs of Cushing disease, acromegaly, or galactorrhea.

Approach Considerations

Hormonal studies should be performed in pairs of target gland and their respective stimulatory pituitary hormone for proper interpretation, as follows:[14]

Corticotropin deficiency may be evident with the finding of a decreased serum cortisol level. However, a low cortisol level may not help to distinguish primary adrenal insufficiency from secondary adrenal insufficiency due to hypopituitarism. The conditions can be differentiated on clinical grounds. A patient with secondary causes due to pituitary dysfunction has a relatively pale complexion (not hyperpigmented), a normal aldosterone response, normal serum potassium, and low/normal morning ACTH level, measured in the morning due to its highest circadian levels. Hyponatremia may occur.

The opposite is true for primary adrenal insufficiency. Hyperpigmentation in primary adrenal insufficiency is due to increased ACTH production with concomitant overproduction of melanocyte-stimulating hormone, which is coupled with ACTH in a mutual precursor. ACTH elevation, measured any time, suggests an adrenal etiology. Hyperkalemia may be present, owing to concomitant aldosterone deficiency, which does not occur with ACTH insufficiency. Hyponatremia may result from cortisol insufficiency, and thus does not separate pituitary from adrenal disease.

Histologic findings in hypopituitarism depend on etiology (eg, tumors, infiltrations, infections, empty sella). Other tests to ascertain the likely underlying etiology are indicated by the patient's presentation.

ACTH (Cortrosyn) Stimulation Test

The ACTH stimulation test, which evaluates the hypothalamic-pituitary-adrenal axis, is a superior tool in the diagnosis of adrenal insufficiency, but it does not generally separate pituitary from adrenal causation. This dynamic test measures serum cortisol levels before and after a 1- or 250-mcg dose of ACTH. The cortisol level should be greater than 500 pmol/L (may be  less in some assays) 30 minutes after ACTH administration in patients with normal adrenal function.

A low cortisol level that fails to rise after ACTH administration represents an abnormal cortisol response, a response seen in primary adrenal insufficiency. However, because of adrenal atrophy with chronic ACTH insufficiency, the cortisol response is often abnormal in patients with hypopituitarism. A poor response requires the serum ACTH, or other clinical clues, to separate pituitary from primary adrenal disease.

Other provocative tests for ACTH/cortisol function are the insulin-induced hypoglycemia test and the glucagon stimulation test. These may be needed within the acute stage of ACTH deficiency, such as following pituitary surgery.

TSH and Thyroxine

Assessment of thyroid function is important in the evaluation of ACTH deficiency. In a hypothyroid state, cortisol clearance decreases, causing an increase in the serum cortisol level. If thyroid replacement is initiated, the cortisol level may be inappropriate to the new state, initiating an adrenocortical crisis.

In suspected TSH deficiency, measure serum TSH and thyroxine. A normal level of total free T4 rules out hypothyroidism. A low thyroxine and low/normal serum TSH and a small, soft thyroid gland confirm the diagnosis of TSH deficiency.

FSH, LH, and Estradiol or Testosterone

LH and FSH deficiencies may indicate secondary hypogonadism. Elevated FSH and LH levels differentiate primary hypogonadism from secondary hypogonadism. A low testosterone level in a man, or an amenorrheic woman with low estradiol and low/normal serum FSH/LH, indicates secondary hypogonadism.

In men, measuring testosterone levels is useful, if properly performed. A decreased testosterone level should be associated with an increase in FSH and LH levels if pituitary function is normal. Low or normal FSH or LH levels in the face of low testosterone indicate hypopituitarism. Serum testosterone is best measured early in the morning owing to a diurnal rhythm that falls through the day. There may be other causes of a low testosterone level, such as poor nutrition, stress, hyperprolactinemia, or chronic opioid use. A low level of sex hormone binding protein may give a low total testosterone level (but with the free testosterone level being normal). A finding of low total testosterone needs to be confirmed with a repeat test, which should include a measurement of non-protein-bound (free) testosterone.

Semen analysis also may be performed. A normal semen sample usually excludes hypogonadism from a primary or secondary source. Semen analysis is performed only if fertility is being considered.

GH provocative testing and prolactin testing

Given that GH secretion is pulsatile and low in most adults through most of the day, a single low serum level cannot be interpreted, whereas a single elevated or normal serum GH level can exclude the diagnosis of GH deficiency. Best is a provocative test for GH secretion. The serum IGF-1 may be useful for GH deficiency in children but not in adults, as up to a third of adults with proven GH deficiency by provocative testing may have a normal serum IGF-1. There are various GH stimulation tests, with glucagon and hypoglycemia being the most definitive. GH-releasing hormone (GHRH) for such testing is difficult to obtain.

Prolactin deficiency can also be verified by directly measuring serum levels. As with most other pituitary hormones, secretion of prolactin is episodic; more than 1 value is necessary for diagnosis. However, testing is rarely necessary since most patients are asymptomatic, and the results are not clinically relevant unless a woman wishes to lactate.

Water Deprivation Test and Vasopressin Stimulation Test

A water deprivation test can help to differentiate psychogenic polydipsia from diabetes insipidus and nephrogenic diabetes insipidus. Supervise patients constantly to inhibit water intake, as patients with psychogenic polydipsia often use any means possible to consume water (eg, drinking from a toilet bowl). While withholding water, take urine samples hourly to measure urine osmolalities, with serum osmolarity measured at the beginning and end.

If the cause is psychogenic, urine osmolality increases while serum osmolality remains normal. If urinary concentrations do not increase in a water deprivation test, despite the rise in serum osmolarity, the diagnosis of diabetes insipidus is established (central or nephrogenic).

At the time of stability of the urine osmolarity, a vasopressin stimulation test may assist in discriminating between central and nephrogenic diabetes insipidus. Administer either 5 units of aqueous vasopressin or 1-2 mcg of desmopressin (DDAVP) subcutaneously. After 1 hour, acquire an additional set of serum and urine specimens. An increase in urine osmolality and a decrease in serum osmolality support a central cause of diabetes insipidus and a lack of arginine vasopressin (AVP). If osmolalities remain unchanged, the patient has nephrogenic diabetes insipidus (resistance to AVP).

This test is with some limitations in interpretation, so added serum measurements of AVP or copeptin (the C terminus of the vasopressin precursor) may improve test interpretation.

Magnetic Resonance Imaging

A study by Li et al concluded that magnetic resonance imaging (MRI) findings can be correlated with pituitary function and can provide evidence of multiple pituitary hormone deficiencies. The study included 96 pituitary hormone ̶ deficient children and 90 controls. The authors used MRI findings from the hypothalamic-pituitary region to divide the hormone-deficient patients into 5 stages. Based on serum concentrations of ACTH, cortisol, GH, insulinlike growth factor-1 (IGF-1), free T4, TSH, FSH, LH, testosterone, estradiol, and prolactin in the patients and controls, a positive correlation was found between the MRI-based stages and the number of pituitary hormone deficiencies in patients.[15, 16]  However, MRI does not eliminate the need for appropriate biochemical testing.

In the presence of clinical or biochemical evidence of hypopituitarism, visualization of the sella/suprasella areas is needed to identify the nature of the causative disease process. This is best assessed by CT scanning or MRI. The presence of a mass with hormonal hypersecretion indicates that it is likely a secretory pituitary adenoma. In the absence of hypersecretion, any mass/infiltrate may be of unknown etiology, but certain characteristics on CT scanning/MRI may suggest the pathological cause in some cases. The presence of a lesion requires correlation with the clinical/biochemical data, and the absence of any visible lesion suggests a nonorganic cause in most cases.

Approach Considerations

Missed or delayed diagnosis of hypopituitarism could potentially lead to permanent disability or death. Medical care consists of hormone replacement as appropriate and treatment of the underlying cause. Glucocorticoids are required if the ACTH-adrenal axis is impaired. This is particularly important in sudden collapse due to pituitary apoplexy or acute obstetric hemorrhage with pituitary insufficiency. In such circumstances, do not delay initiation of a possibly lifesaving treatment pending a definitive diagnosis. Treat secondary hypothyroidism with thyroid hormone replacement.

Treat gonadotropin deficiency with sex-appropriate hormones. In men, testosterone replacement is used and substituted with HCG injections if the patient desires fertility. In women, estrogen replacement is used with or without progesterone as appropriate.

GH is replaced in children as appropriate. GH is not routinely replaced in adults unless the patient is symptomatic of GH deficiency, after all other pituitary hormones have been replaced. Then, a 6-month trial of replacement GH therapy may be considered.

Surgical care depends on the underlying cause and clinical state. In pituitary apoplexy, prompt surgical decompression may be lifesaving if head imaging reveals clinically significant tumor mass effect. Microadenomas do not need surgical treatment, unless GH or ACTH hypersecretion is present. Prolactinomas, small and large, generally respond to medical therapy with tumor shrinkage and alleviation of mass symptoms. Debulk macroadenomas with mass symptoms that do not respond to medical therapy or are not expected to respond to medical therapy. Some asymptomatic nonsecreting macroadenomas may have an option of close clinical/radiologic observation. If radiotherapy is used, long-term new-onset hypopituitarism may occur and must be monitored.

The most common causes of nonsecreting pituitary adenomas are variants of gonadotropin-secreting tumors. In perhaps a third of these lesions, treatment with the potent dopamine agonist cabergoline may result in some decrease in mass or prevention of recurrence.[17]

A retrospective study by Graffeo et al indicated that in radiation-naïve patients receiving single-fraction stereotactic radiosurgery for pituitary adenoma, a mean gland dose of less than 11.0 Gy may reduce the likelihood of posttreatment hypopituitarism. The investigators found that in patients who received this lower dose, the rates of hypopituitarism at 2 and 5 years were 2% and 5%, respectively, compared with 31% and 51%, respectively, for those who received a mean dose of 11.0 Gy or higher.[18]

A study by Lee et al found that in patients with nonfunctioning pituitary adenomas, gross-total resection and/or adjuvant radiotherapy appear to prevent tumor recurrence or regrowth. The study involved 289 patients, 193 of whom had gross-total resection, 53 of whom had near-total resection, and 43 of whom had subtotal resection.[19]

A literature review by Li et al indicated that in the surgical treatment of pituitary adenomas, endoscopic transsphenoidal surgery is more successful than microscopic transsphenoidal surgery in gross tumor removal and, unlike the microscopic technique, does not significantly affect cerebrospinal fluid leak risk. Moreover, the endoscopic surgery significantly decreases septal perforation risk and is not linked to an increased risk for meningitis, epistaxis, hematoma, hypopituitarism, hypothyroidism, hypocortisolism, total mortality, or recurrence.[20]

In very ill hospitalized patients or in patients undergoing major procedures, stress-dose steroids are required and are quickly tapered to a maintenance schedule after the procedure. Minor procedures or illnesses may not necessitate a change in steroid dose or may require a simple doubling of the usual daily dose until the illness resolves. Other hormone replacements are continued at their usual maintenance doses as appropriate.

No special diet is necessary in patients with hypopituitarism unless dictated by an underlying disease process. Also, no activity restrictions are necessary unless dictated by an underlying disease process. Include an endocrinologist, a neurosurgeon, and a radiologist in consultations, as appropriate.

The World Health Organization's 2017 classification of pituitary tumors lists adenoma subtypes that may be more aggressive and likely to recur, requiring additional therapy.[21]


Good obstetric care has reduced the incidence of postpartum hypopituitarism. Radiation therapy that minimizes exposure of the pituitary reduces the time of onset of hypopituitarism. Experienced neurosurgeons employing high-resolution microscopic hypophyseal surgery may reduce the likelihood of subsequent hypopituitarism.

Long-Term Monitoring

Provide long-term follow-up care for complications of underreplacement or overreplacement. Stressful situations warrant an adjustment in therapy. Unlike adults, children require GH replacement.

Follow-up care also involves adjusting hormone replacement to physiologic maintenance levels using the lowest dose. Monitor the patient to avoid overreplacement. The incidence of new neoplasms is increased in young people treated with growth hormone who had previous tumor treatment.[22]  This does not appear to be the case in adult patients. Excessive glucocorticoid or thyroid doses, or inadequate sex steroid doses, have been associated with decreased bone mineral density.

Medication Summary

The goal of pharmacotherapy is to restore target hormones to physiologic levels. Medications used in hypopituitarism vary depending on the specific hormone deficiency that exists. As previously stated, patients with hypopituitarism are usually maintained on hormone replacement therapies for life. These patients are generally asymptomatic but require increased doses of glucocorticoids following any form of stress, emotional or physical. The most common stressor is infection. Not matching glucocorticoid dose to stress causes acute decompensation.

Hydrocortisone (Hydrocortone, A-Hydrocort, Solu-Cortef, Cortef)

Clinical Context:  Hydrocortisone is used as replacement therapy in adrenocortical deficiency states and may be used for its anti-inflammatory effects. For hypotensive patients and acute management, use intravenous (IV) preparation.


Clinical Context:  This is an alternative to hydrocortisone in patients with adrenal insufficiency.

Class Summary

These agents are used in adrenal insufficiency. They cause profound and varied metabolic effects in addition to modifying the body's immune response to diverse stimuli. The naturally occurring glucocorticoids and many synthetic steroids have glucocorticoid and mineralocorticoid activity.[22] In the past, these agents were used in a higher-than-physiological dose. Presently, a dose equivalent to 15-20 mg/day of hydrocortisone is recommended in adults.

Levothyroxine (Synthroid, Levoxyl, Levothroid, Tirosint, Unithroid)

Clinical Context:  In active form, levothyroxine influences the growth and maturation of tissues. It is involved in normal growth, metabolism, and development. Endocrinologists can monitor and adjust the doses to optimal effect. A serum free thyroxine value in the upper third of normal range is the goal.

Class Summary

These agents are used in hypothyroidism.

Vasopressin (Pitressin)

Clinical Context:  This is an intramuscular or subcutaneous injection of an ADH analog that has vasopressor and ADH activity. It increases water resorption at the distal renal tubular epithelium (ADH effect) and promotes smooth-muscle contraction throughout the vascular bed of the renal tubular epithelium (vasopressor effects). It is rarely used today for long-term therapy.

Desmopressin acetate (DDAVP, Stimate)

Clinical Context:  This agent is a longer-acting ADH derivative that can be used intranasally (also orally and sublingually); it increases the cellular permeability of the collecting ducts, resulting in the resorption of water by the kidneys.

Class Summary

These agents are used for the replacement of vasopressin.

Human growth hormone; somatropin (Humatrope, Genotropin, Saizen)

Clinical Context:  This is produced by recombinant deoxyribonucleic acid (DNA) technology. It stimulates the growth of linear bone, skeletal muscle, and organs and stimulates erythropoietin, increasing red blood cell mass. Actions are either direct or from the hepatic production of IGF-1.

Class Summary

These agents are used in the treatment of children who have growth failure associated with chronic renal insufficiency up to the time of renal transplantation. Use in conjunction with optimal management of chronic renal insufficiency.

Estrogens, conjugated (Premarin)

Clinical Context:  Estrogen is important in the development and maintenance of the female reproductive system and secondary sex characteristics, promoting the growth and development of the vagina, uterus, fallopian tubes, and breasts. It affects the release of pituitary gonadotropins; causes capillary dilatation, fluid retention, and protein anabolism; increases the water content of cervical mucus; and inhibits ovulation. Metabolic effects include maintenance of bone density. Estrogen is predominantly produced by the ovaries.

Estradiol (Alora, Climara, Elestrin, Vivelle-Dot, Estrace, Estraderm, EstroGel)

Clinical Context:  Estradiol increases synthesis of DNA, RNA, and many proteins in target tissues. It may be given transdermally by patch or gel, or orally in micronized form.

Medroxyprogesterone (Provera, Depo-Provera)

Clinical Context:  Administer cyclically 12 d/mo to prevent endometrial hyperplasia that unopposed estrogen may cause. In young women, regular withdrawal bleeding is preferable because even young women with premature ovarian failure have a 5-10% chance of spontaneous pregnancy (unlike postmenopausal women). If an expected withdrawal bleeding is absent, perform a pregnancy test (and a timely diagnosis of pregnancy will not be missed). Other causes of amenorrhea may also remit spontaneously and result in an unexpected pregnancy.

Progesterone (Prometrium)

Clinical Context:  This agent is used to prevent endometrial hyperplasia.

Desogestrel and ethinyl estradiol (Desogen, Ortho-Cept, Velivet, Azurette, Cyclessa)

Clinical Context:  The combination of desogestrel and ethinyl estradiol reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing the amount of gonadotropin-releasing hormones (GnRHs). This is one example of an oral contraceptive pill (OCP). All the modern formulations are equally efficacious, although some of the newer (so-called third-generation) pills have a larger progestin effect and may offer greater efficacy.

Norgestimate and ethinyl estradiol (Ortho Cyclen, Sprintec, TriNessa, Ortho Tri-Cyclen)

Clinical Context:  The combination of norgestimate and ethinyl estradiol reduces the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary by decreasing the amount of gonadotropin-releasing hormones (GnRHs).

Class Summary

These hormones are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone or estrogen.

Testosterone (Depo-Testosterone, Androderm, AndroGel, Testim, Andriol)

Clinical Context:  Testosterone is an anabolic steroid that promotes and maintains secondary sex characteristics in androgen-deficient males. Physiological amounts may be given by intramuscular injection every 1-2 weeks, daily by transdermal patch or gel, or several times daily by oral testosterone undecanoate, the latter of which is not available in all countries.

Class Summary

Androgens are used for replacement therapy in hypogonadism associated with a deficiency or absence of endogenous testosterone.

What is hypopituitarism (panhypopituitarism)?What is the physiology of the pituitary gland relative to hypopituitarism (panhypopituitarism)?How is hypopituitarism (panhypopituitarism) treated in an adrenal crisis?What is the role of glucocorticoids in the treatment of hypopituitarism (panhypopituitarism)?What is included in patient education about hypopituitarism (panhypopituitarism)?What is the pathophysiology of hypopituitarism (panhypopituitarism)?What causes hypopituitarism (panhypopituitarism)?What causes hypopituitarism (panhypopituitarism) in pregnant women?What is the role of traumatic brain injury (TBI) in the etiology of hypopituitarism (panhypopituitarism)?What are less common causes of hypopituitarism (panhypopituitarism)?What is the prevalence of hypopituitarism (panhypopituitarism)?What is the prognosis of hypopituitarism (panhypopituitarism)?Which factors increase the risk of mortality from hypopituitarism (panhypopituitarism) cause morbidity?What are the cardiovascular complications of with hypopituitarism (panhypopituitarism)?What are the noncardiovascular complications of hypopituitarism (panhypopituitarism)?Which clinical history findings are characteristic of hypopituitarism (panhypopituitarism)?Which physical findings are characteristic of hypopituitarism (panhypopituitarism)?How is an acute cortisol insufficiency state prevented in hypopituitarism (panhypopituitarism)?When is the ACTH stimulation test normal in patients with hypopituitarism (panhypopituitarism)?What are the differential diagnoses for Hypopituitarism (Panhypopituitarism)?What is the role of lab testing in the workup of hypopituitarism (panhypopituitarism)?Which histologic findings are characteristic of hypopituitarism (panhypopituitarism)?What is the role of adrenocorticotropic hormone (ACTH) stimulation test in the diagnosis of hypopituitarism (panhypopituitarism)?What is the role thyroid function testing in the diagnosis of hypopituitarism (panhypopituitarism)?What is the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) assessment in the diagnosis of hypopituitarism (panhypopituitarism)?Which lab tests should be performed in the evaluation of hypopituitarism (panhypopituitarism) in men?What is the role of growth hormone (GH) provocative testing and prolactin testing in the diagnosis of hypopituitarism (panhypopituitarism)?What is the role of a vasopressin stimulation test in the diagnosis of hypopituitarism (panhypopituitarism)?What is the role of a water deprivation test in the diagnosis of hypopituitarism (panhypopituitarism)?What is the role of imaging studies in the diagnosis of hypopituitarism (panhypopituitarism)?How is hypopituitarism (panhypopituitarism) treated?How are pituitary adenomas treated in patients with hypopituitarism (panhypopituitarism)?How is hypopituitarism (panhypopituitarism) prevented?What is included in long-term monitoring of hypopituitarism (panhypopituitarism)?What is the role of drug treatment for hypopituitarism (panhypopituitarism)?Which medications in the drug class Androgens are used in the treatment of Hypopituitarism (Panhypopituitarism)?Which medications in the drug class Estrogens/Progestins are used in the treatment of Hypopituitarism (Panhypopituitarism)?Which medications in the drug class Growth hormones are used in the treatment of Hypopituitarism (Panhypopituitarism)?Which medications in the drug class Antidiuretic hormone replacements are used in the treatment of Hypopituitarism (Panhypopituitarism)?Which medications in the drug class Thyroid hormones are used in the treatment of Hypopituitarism (Panhypopituitarism)?Which medications in the drug class Corticosteroids are used in the treatment of Hypopituitarism (Panhypopituitarism)?


Bernard Corenblum, MD, FRCPC, Professor of Medicine, Director, Endocrine-Metabolic Testing and Treatment Unit, Ovulation Induction Program, Department of Internal Medicine, Division of Endocrinology, University of Calgary Faculty of Medicine, Canada

Disclosure: Nothing to disclose.


James R Mulinda, MD, FACP, Consulting Staff, Department of Endocrinology, Endocrinology Associates, Inc

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP, Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Disclosure: Nothing to disclose.


David S Schade, MD Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center

David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, and Society for Experimental Biology and Medicine

Disclosure: Nothing to disclose.

Don S Schalch, MD Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics

Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment


  1. Kim SY. Diagnosis and Treatment of Hypopituitarism. Endocrinol Metab (Seoul). 2015 Dec. 30(4):443-55. [View Abstract]
  2. Gounden V, Jialal I. Hypopituitarism (Panhypopituitarism). 2018 Jan. [View Abstract]
  3. Schneider HJ, Schneider M, Saller B, et al. Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol. 2006 Feb. 154(2):259-65. [View Abstract]
  4. Kokshoorn NE, Smit JW, Nieuwlaat WA, et al. Low prevalence of hypopituitarism after traumatic brain injury: a multicenter study. Eur J Endocrinol. 2011 Aug. 165(2):225-31. [View Abstract]
  5. Giuliano S, Talarico S, Bruno L, Nicoletti FB, Ceccotti C, Belfiore A. Growth hormone deficiency and hypopituitarism in adults after complicated mild traumatic brain injury. Endocrine. 2016 Nov 23. [View Abstract]
  6. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. 2011 Aug. 96(8):2330-40. [View Abstract]
  7. Fernandez A, Brada M, Zabuliene L, Karavitaki N, Wass JA. Radiation-induced hypopituitarism. Endocr Relat Cancer. 2009 Sep. 16(3):733-72. [View Abstract]
  8. Fatemi N, Dusick JR, Mattozo C, et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. 2008 Oct. 63(4):709-18; discussion 718-9. [View Abstract]
  9. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001 Dec. 55(6):735-40. [View Abstract]
  10. Clayton RN. Mortality, cardiovascular events and risk factors in hypopituitarism. Growth Horm IGF Res. 1998 Feb. 8 Suppl A:69-76. [View Abstract]
  11. O'Reilly MW, Reulen RC, Gupta S, et al. ACTH and gonadotropin deficiency predict mortality in patients treated for nonfunctioning pituitary adenoma (NFPA): long-term follow-up of 519 patients in two large European centres. Clin Endocrinol (Oxf). 2016 Jun 21. [View Abstract]
  12. Bulow B, Hagmar L, Eskilsson J, Erfurth EM. Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors. J Clin Endocrinol Metab. 2000 Feb. 85(2):574-84. [View Abstract]
  13. Giagulli VA, Castellana M, Perrone R, Guastamacchia E, Iacoviello M, Triggiani V. GH Supplementation Effects on Cardiovascular Risk in GH Deficient Adult Patients: A Systematic Review and Meta-analysis. Endocr Metab Immune Disord Drug Targets. 2017 Nov 16. 17 (4):285-96. [View Abstract]
  14. Nakamoto J. Laboratory diagnosis of multiple pituitary hormone deficiencies: issues with testing of the growth and thyroid axes. Pediatr Endocrinol Rev. 2009 Jan. 6 Suppl 2:291-7. [View Abstract]
  15. Li G, Shao P, Sun X, Wang Q, Zhang L. Magnetic resonance imaging and pituitary function in children with panhypopituitarism. Horm Res Paediatr. 2010. 73(3):205-9. [View Abstract]
  16. Child CJ, Zimmermann AG, Woodmansee WW, et al. Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study. Eur J Endocrinol. 2011 Aug. 165(2):217-223. [View Abstract]
  17. Greenman Y, Cooper O, Yaish I, et al. Treatment of clinically nonfunctioning pituitary adenomas with dopamine agonists. Eur J Endocrinol. 2016 Jul. 175 (1):63-72. [View Abstract]
  18. Graffeo CS, Link MJ, Brown PD, Young WF Jr., Pollock BE. Hypopituitarism After Single-Fraction Pituitary Adenoma Radiosurgery: Dosimetric Analysis Based on Patients Treated Using Contemporary Techniques. Int J Radiat Oncol Biol Phys. 2018 Mar 8. [View Abstract]
  19. Lee MH, Lee JH, Seol HJ, et al. Clinical Concerns about Recurrence of Non-Functioning Pituitary Adenoma. Brain Tumor Res Treat. 2016 Apr. 4(1):1-7. [View Abstract]
  20. Li A, Liu W, Cao P, Zheng Y, Bu Z, Zhou T. Endoscopic versus microscopic transsphenoidal surgery in the treatment of pituitary adenoma: a systematic review and meta-analysis. World Neurosurg. 2017 Jan 16. [View Abstract]
  21. Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017 Oct. 134 (4):521-35. [View Abstract]
  22. Harsch IA, Schuller A, Hahn EG, Hensen J. Cortisone replacement therapy in endocrine disorders - quality of self-care. J Eval Clin Pract. 2010 Jun. 16(3):492-8. [View Abstract]
  23. Welsh J. Managing hypopituitarism in emergency departments. Emerg Nurse. 2015 Oct 9. 23 (6):32-7. [View Abstract]
  24. Silva PP, Bhatnagar S, Herman SD, Zafonte R, Klibanski A, Miller KK, et al. Predictors of Hypopituitarism in Patients with Traumatic Brain Injury. J Neurotrauma. 2015 Sep 29. [View Abstract]
  25. Klose M, Feldt-Rasmussen U. Hypopituitarism in Traumatic Brain Injury-A Critical Note. J Clin Med. 2015 Jul 14. 4 (7):1480-97. [View Abstract]
  26. Crespo I, Santos A, Webb SM. Quality of life in patients with hypopituitarism. Curr Opin Endocrinol Diabetes Obes. 2015 Aug. 22 (4):306-12. [View Abstract]