eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic

Hypopituitarism

Lisa Diane Mills, MD, Assistant Professor of Emergency Medicine, Director, Section of Emergency Medicine Ultrasound, Louisiana State University at New Orleans

Updated: Aug 14, 2008

Introduction

Background

Hypopituitarism may present as an acutely decompensated patient or in a patient who is stable but with symptoms of the disorder. The diagnosis of hypopituitarism is easily overlooked as the symptoms and signs are frequently protean and nonspecific, including abnormalities in electrolyte levels, mental status, glucose levels, body temperature, and heart rate. The setting is not uncommon in which an emergency physician is evaluating a patient with complaints of weakness, fatigue, or altered mental status without a clear diagnosis. Subtle, but still abnormal vital signs, such as slightly reduced blood pressure or heart rate, may be the only initial clues to suggest a pituitary deficiency rather than a relatively benign etiology.

Emergency physicians frequently provide care to patients at risk of developing hypopituitarism. These risks include, but are not limited to, traumatic brain injury (TBI), cocaine use, subarachnoid hemorrhage, and postpartum hypotension (Sheehan syndrome).

Establish a broad differential diagnosis in the initial evaluation of patients with abnormal vital signs. Include hypopituitarism as a cause for these abnormalities.  Also consider hypopituitarism as the cause for abnormal laboratory values.

The pituitary gland was first called "hypophysis" by Thomas Soemmering in 1778. Hypophysis is a Greek term that describes how the pituitary appears to "grow beneath the brain." The pituitary gland carries the respectable sobriquet "master gland" because it produces hormones that regulate growth, development, and reproduction. Despite its vital role, the pituitary gland is only the size of a pea. It is located in the middle cranial fossa within a recess of the sphenoid bone called the sella turcica ("Turks saddle").

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 upon specific organs.

The actions of the pituitary gland can be modulated at many stages. The pituitary hormones, or target organ hormones, can influence both 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:

• Thyrotropin, or thyroid-stimulating hormone (TSH)
• Gonadotropins, or follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
• Growth hormone (GH)
• Corticotropin, or adrenocorticotropic hormone (ACTH)
• Prolactin hormone (PRL)

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

Vasopressin primarily acts on the V₂ receptors of the distal tubules of the kidney to reabsorb water, which increases total body water and urine osmolality. Vasopressin 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.

Pathophysiology

Patients with hypopituitarism are 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. These patients present hypotensive and ill-appearing. A patient's initial presentation of undiagnosed hypopituitarism may be with this life-threatening decompensated state. 

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).

Pituitary tumors, or adenomas, are the most common cause of hypopituitarism in adults. Depletion of pituitary function by tumors occurs via the following mechanisms: 

• In primary pituitary destruction, the anterior pituitary is destroyed. The result is deficiency in some or all pituitary hormones. Pituitary tumors, or adenomas, can be secretory or nonsecretory. Approximately 30% of all macroadenomas larger than 10 mm will produce at least one hormone.
• Hypothalamic disease involves destruction of the hypothalamus. This causes a deficiency or loss of hypothalamic regulatory hormone input to the pituitary, resulting in loss of anterior pituitary hormone secretion.

Frequency

United States

Although the prevalence of pituitary adenomas is strikingly high (10-20%) in autopsy and MRI studies, the actual presence of clinical disease is quite uncommon. 

Approximately 2-8 in 100,000 persons per year present with symptoms attributed to pituitary tumors.

International

International estimates of hypopituitarism are an incidence of 4.2 cases per 100,000 per year and a prevalence of 45.5 per 100,000 without gender difference.¹

Mortality/Morbidity

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.

• Missed or delayed diagnosis could potentially lead to permanent disability or death.
• Female patients with hypopituitarism who are receiving controlled thyroid and steroid hormone substitution, but without growth hormone replacement, have more than a 2-fold increase in cardiovascular mortality compared with the general population.²
• Cardiovascular disease is significantly higher among hypopituitary patients (incidence ratio, 3.7; 95% confidence interval, 1.2–11.3).²
• Hypopituitary patients have lower high-density lipoprotein cholesterol (P = 0.002) and higher low-density/high-density lipoprotein ratio (P = 0.009).²

Race

• Little data exist on the incidence of hypopituitarism based on ethnicity.

Sex

• The most frequent etiologies of hypopituitarism do not demonstrate a significant disparity in incidence between genders. Postpartum pituitary necrosis (Sheehan syndrome) occurs only in women.

Clinical

History

The history in an acutely decompensated patient with hypopituitarism should be aimed at identifying the stressor that caused decompensation. Most commonly trauma or infectious disease cause the change from compensated to decompensated disease. Patients may also have discontinued medication or have emotional stressors. These conditions should be evaluated and treated concurrently with the pituitary emergency.

Symptom presence and severity depend on the amount of and rapidity of hormone depletion. Clinical manifestations closely match those of primary deficiency or hypofunctioning of target glands. Hypopituitarism is usually a combination of several hormonal deficiencies and rarely involves all pituitary hormones. End-organ hormonal insufficiencies are referred to as secondary deficiencies of the target organ (eg, hypothyroidism caused by a decrease in TSH will be termed secondary hypothyroidism).

The presence of an antecedent closed-head injury may be elicited. Patients with traumatic brain injury can have some degree of hypopituitarism as soon as 3 months and typically by 12 months following the injury. Nearly all patients with resultant pituitary deficiency will have experienced loss of consciousness following the trauma, and approximately half have a skull fracture.

• The onset of hypopituitarism is often gradual over a period of years, but in some conditions, rapid onset is seen. The insidious decline in health is often attributed to other medical conditions prior to recognition.
• Adrenocorticotropic hormone deficiency  
  • Deficiency in corticotropin is characterized by a decrease in adrenal androgens and production of cortisol.
  • Acute loss of adrenal function is a medical emergency and may lead to hypotension and death if not treated.
  • Signs and symptoms of ACTH deficiency may be profound and potentially fatal and include myalgias, arthralgias, fatigue, headache, weight loss, anorexia, nausea, vomiting, abdominal pain, altered mentation or altered consciousness, dry wrinkled skin, decreased axillary and pubic hair, anemia of chronic disease, dilutional hyponatremia, hypoglycemia, hypotension, and shock.
  • Symptoms are nearly identical to those of primary adrenal insufficiency but can be differentiated by lack of hyperpigmentation. Hyperpigmentation occurs in a long feedback loop in which a cortisol deficiency results in increased production of ACTH by the pituitary. The ACTH precursor coupled to melanocyte-stimulating hormone is not produced in those with pituitary disease, and therefore hyperpigmentation does not take place.
  • Patients with secondary adrenal insufficiency usually are eukalemic. This differs from primary adrenal insufficiency, in which patients develop hyponatremia and hyperkalemia.
  • Aldosterone secretion is not affected, as it does not depend on corticotropin but instead on the renin-angiotensin axis.
• Thyrotropin deficiency  
  • Secondary thyrotropin deficiency (ie, hypothyroidism) due to decreased TSH exhibits identical symptoms to primary thyroid disease, only typically less severe.
  • Signs and symptoms of secondary hypothyroidism include fatigue, weakness, weight gain, thickened subcutaneous tissues, constipation, cold intolerance, altered mental status, impaired memory, and anemia.
  • Physical examination may reveal bradycardia, delayed relaxation of the deep tendon reflexes, and periorbital edema.
• Gonadotropin deficiency  
  • Low FSH and LH levels increase risk of osteoporosis due to decreased bone density and result in hypogonadism in both men and women.
  • In men, symptoms include decreased libido, varying degrees of erectile dysfunction, decreased ejaculate, muscle weakness, and fatigue.
  • Men with long-standing hypogonadism have decreased hair growth, soft testes, and gynecomastia. (For a related CME activity, see Diagnosis and Evaluation of Male Hypogonadism.)
  • Patients may be anemic due to decreased erythropoietin production, which causes a normochromic, normocytic anemia.
  • Premenopausal women present with altered menstrual function, ranging from regular anovulatory periods to amenorrhea, hot flashes, decreased libido, breast atrophy, vaginal dryness, and dyspareunia.
  • Pubic and axillary hair growth is usually normal unless a concomitant ACTH deficiency exists.
  • Postmenopausal women usually present with headache or visual abnormalities due to other hormonal deficiencies or mass lesions.
  • In children, FSH and LH deficiency can cause eunuchoidism and lack of sexual development.
    • FSH and LH have an indirect effect on bone growth by causing closure of the epiphysis.
    • Characteristics of eunuchoidism are due to delay in closure of the epiphysis, resulting in long extremities.
• Growth hormone deficiency  
  • In children, GH deficiency presents as growth retardation and delayed sexual maturation.
  • Patients may present with fasting hypoglycemia due to loss of the gluconeogenic effect of GH, which counteracts the effect of insulin.
  • In adults, GH deficiency presents as weakness, poor wound healing, decreased exercise tolerance, and decreased social functioning.
• Prolactin deficiency  
  • Tumor growth that decreases PRL production affects the process of lactation; these tumors become evident only in the postpartum state.
  • PRL deficiency is very rare; any process that affects the hypothalamus and the pituitary stalk decreases the normal inhibitory effect of dopamine from the hypothalamus on the pituitary, causing a rebound increase in PRL.
• Antidiuretic hormone deficiency 
  • Antidiuretic hormone (ADH) deficiency causes polyuria and polydipsia (diabetes insipidus).
  • When deficient in ADH, the distal tubules of the kidney are unable to absorb water, producing very dilute urine and increasing serum osmolality.
  • If water excretion exceeds oral intake, a patient may become hypotensive and hypovolemic with hypernatremia and elevated serum osmolality.
  • If fluid intake matches fluid output, serum sodium and osmolality may remain normal.
  • Central diabetes insipidus is caused by a decrease in ADH secretion, in contrast to nephrogenic diabetes insipidus, in which the kidney is ADH resistant.
• Oxytocin deficiency  
  • Deficiency in oxytocin is characterized by a decrease in milk ejection during lactation. Interestingly, women with known oxytocin deficiency undergo normal labor and delivery despite the lack of hormone.
  • One of the initial clues to the presence of Sheehan syndrome should be the lack of lactation secondary to oxytocin deficiency.

Physical

• In the stable patient, with the diverse complaints associated with hypopituitarism, a complete physical examination including thyroid palpation, genital inspection, and ophthalmologic examination can support the diagnosis of hypopituitarism. During the neurologic and ophthalmic examinations, check specifically for visual acuity, extraocular movements, and bitemporal hemianopsia. (See the above discussion for signs that are consistent with each of the abnormal hormonal states.)
• In the acutely decompensated patient with hypopituitarism, expect to find an ill-appearing patient with hypotension and signs of dehydration.

Causes

• 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.
  • Hypersecretion of the secretory pituitary tumor hormone is suggestive of an adenoma.
  • Another indication of a pituitary adenoma is a deficiency in some pituitary hormones 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.
• 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 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.
• 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, and increased intracranial pressure.
  • Apoplexy usually spares the posterior pituitary and solely affects the anterior pituitary.
• 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 is uncommon.
• 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.
  • Infiltrative diseases, such as Wegener granulomatosis and sarcoidosis, can cause destruction of the anterior pituitary.
• Physiologic or psychological states can influence the hypothalamic-pituitary stalk by impairing synthesis and secretion of regulating hormones.
  • The degree of the 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.

Differential Diagnoses

Adrenal Insufficiency and Adrenal Crisis
Hypothyroidism and Myxedema Coma
Shock, Cardiogenic
Shock, Septic

Other Problems to Be Considered

Chronic liver disease
Myotonia dystrophica
Primary psychosis
Primary hypogonadism

Workup

Laboratory Studies

In the emergency department, routine laboratory results will not diagnose hypopituitarism. The diagnosis of decompensated hypopituitarism is clinical. In patients in whom nondecompensated hypopituitarism is suspected, the laboratory testing is not part of emergency care.

Laboratory and radiographic tests are necessary to confirm the diagnosis. A variety of diagnostic laboratory tests can be used, but significant controversy exists regarding which tests are ideal. Because many specific endocrine tests are not rapidly available in the ED setting, immediate confirmation of hypopituitarism may not be practical. Clinical suspicion by history and clinical examination may be the only tools to reveal the etiology and to guide appropriate endocrine follow-up care. Expensive, time-consuming tests, which may be performed and interpreted upon follow-up by endocrinologists, are listed below.

• Corticotropin deficiency may be evident with the finding of a decreased serum cortisol level.  
  • 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 will have a relatively pale complexion, a normal aldosterone response, and low ACTH level.
  • 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 ACTH in a mutual precursor.
  • ACTH deficiency in the morning during its highest circadian levels suggests a pituitary/hypothalamic etiology.
• The corticotropin stimulation test, which evaluates the hypothalamic-pituitary-adrenal axis, is a superior tool in distinguishing hypopituitarism from primary adrenal insufficiency.  
  • This dynamic test measures serum cortisol level before and after a 250-mcg dose of ACTH.
  • The cortisol level should at least double 30-60 minutes after ACTH administration in those 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, cortisol response is often slightly blunted in patients with hypopituitarism.
• Assessment of thyroid function is important in the evaluation of ACTH deficiency.  
  • In a hypothyroid state, cortisol clearance decreases, causing an increase in serum cortisol level.
  • If thyroid replacement is initiated, cortisol level drops acutely, initiating an adrenocortical crisis.
• In suspected thyrotropin deficiency, measure serum thyrotropin (TSH) and thyroxine (T4).  
  • A normal level of total free T4 rules out hypothyroidism.
  • Low serum TSH and a small, atrophic thyroid gland confirm the diagnosis of thyrotropin deficiency.
• LH and FSH deficiencies may indicate secondary hypogonadism.  
  • Measuring LH and FSH is possible, but values range widely throughout the day and are therefore unreliable. Measure multiple samples, and calculate a mean value before establishing gonadotropin deficiency.
  • In men, measuring serum testosterone levels is useful.
    • 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 indicates hypopituitarism.
    • Semen analysis also may be performed. A normal semen sample excludes hypogonadism of a primary or secondary source.
  • Elevated FSH and LH levels differentiate primary hypogonadism from secondary hypogonadism.
• GH deficiency can be confirmed by directly measuring serum levels. 
  • Given that GH secretion is pulsatile, a single low serum level must be repeated for confirmation, whereas a single elevated or normal serum GH level can exclude the diagnosis of GH deficiency.
• PRL deficiency can also be verified by directly measuring serum levels.  
  • As with most other pituitary hormones, secretion of PRL is episodic; more than one value is necessary for diagnosis.
  • Testing is rarely necessary since most patients are asymptomatic.
• A water deprivation test can help differentiate psychogenic polydipsia from diabetes insipidus.  
  • Supervise patients constantly to calculate 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 blood and urine samples hourly to measure serum and urine osmolalities.
  • If the cause is psychogenic, urine osmolality increases while serum osmolality remains normal.
• If urinary concentrations do not increase in a water deprivation test, the diagnosis of diabetes insipidus is established. Subsequently, an aqueous 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 and record the results.
  • An increase in urine osmolality and a decrease in serum osmolality support a central cause of diabetes insipidus and a lack of ADH.
  • If osmolalities remain unchanged, the patient has nephrogenic diabetes insipidus.

Imaging Studies

• Radiographic studies of the head (eg, MRI, CT scan) can be performed for patients with a history and physical examination suggestive of an intracranial lesion. Both MRI and CT scans should be obtained with intravenous contrast to increase sensitivity of the tests.
• MRI is superior in localizing and characterizing intracranial lesions; however, CT scan may be more readily accessible.
• A lateral skull film can delineate contours of the sella turcica but are otherwise very unlikely to provide any beneficial information.

Procedures

• There is no emergent procedure to diagnose hypopituitarism.

Treatment

Prehospital Care

Vital sign abnormalities and life-threatening concerns should be managed according to prehospital protocols, such as those for hypoglycemia, altered mental status, bradycardia, hypothermia, or seizures.

Emergency Department Care

The ED treatment of hypopituitarism is 3-fold. Missing hormones must be replaced coincidentally with treatment of electrolyte and cardiovascular effects of the missing hormones being treated. In addition, the stressor that caused decompensation should be treated. For instance, administer antibiotics in a patient with coincident urosepsis or pneumonia.

Standard acute resuscitation principles apply to patients who have hypotension or cardiovascular instability. Intravenous saline boluses are the first-line therapy. Vasopressors are used according to standard recommendations. 

Electrolyte disorders are common. The combination of hypovolemia and hyponatremia are addressed with normal saline boluses. Hyperkalemia is usually mild and does not require acute intervention. It corrects with replacement of aldosterone. 

Test for hypoglycemia and treat. Retest glucose level frequently. Begin continuous intravenous dextrose infusions in a patient with a single episode of recurrent hypoglycemia during the ED stay.

The supportive measures above are standard for all patients. If the emergency physician suspects hypopituitarism based on clinical presentation or knows that the patient has a prior diagnosis of hypopituitarism, emergent intervention is warranted.

Hormone replacement in hypopituitarism varies with the patient's diagnosis. In the emergency department, the single most important agent to replace emergently is the glucocorticoid. Hydrocortisone in a stress dose is the standard choice for replacement. Early thyroxine replacement is the second most important treatment. Intravenous levothyroxine is the preferential thyroid hormone to administer. Triiodothyroxine is associated with cardiovascular complications.

Consultations

• Patients with a hypopituitarism crisis will be admitted to the intensive care unit. 
• In the setting of a newly diagnosed brain mass, a neurosurgeon may need to be emergently consulted. 
• Other consultants who may be involved in the case, but are not emergently consulted from the ED, include an endocrinologist, oncologist, and radiation oncologist.
• Patients in whom the emergency physician suspects nondecompensated, undiagnosed hypopituitarism can be referred to an endocrinologist on an outpatient basis.

Medication

Medications used in hypopituitarism vary depending on the specific hormone deficiency that exists.

Agents for hormone replacement

These drugs are either synthetic or natural agents used to supplement hormone deficiencies resulting from hypopituitarism.

Hydrocortisone (Solu-Cortef, Westcort)

Used as steroid replacement in patients who have adrenal insufficiency. For hypotensive patients and acute management, use IV preparation.

Dosing

Adult

Outpatient: 10 mg PO qam, 5 mg PO qpm
Inpatient: 100-250 mg IV initial bolus, followed by 100 mg IV q8h until patient is hemodynamically stable and able to take PO

Pediatric

0.5-0.75 mg/kg/d or 20-25 mg/m²/d PO divided q8h

Interactions

Clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia

Contraindications

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis

Prednisone (Deltasone, Orasone, Sterapred)

Alternative to hydrocortisone in patients with adrenal insufficiency. Medication of choice for maintenance therapy.

Dosing

Adult

5 mg PO divided bid

Pediatric

4-5 mg/m²/d PO
Alternatively, administer 1-2 mg/kg PO qd

Interactions

Estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with concurrent diuretics

Contraindications

Documented hypersensitivity; viral, fungal, tubercular skin, or connective tissue infections; peptic ulcer disease; hepatic dysfunction; connective tissue infections; GI disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Abrupt discontinuation may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur

Thyroxine products

These agents are used for the treatment of hypothyroidism.

Levothyroxine (Synthroid, Levoxyl)

Thyroid supplement whose active form influences tissue growth and maturation. Involved in normal growth, metabolism, and development. Endocrinologists can monitor and adjust doses to optimal effect.

Dosing

Adult

12.5-50 mcg/d PO initially; increase by 25-50 mcg/d q2-4wk; not to exceed 100-200 mcg/d

Pediatric

Neonate to 6 months: 25 mcg/d PO
6-12 months: 50 mcg/d PO
1-5 years: 75 mcg/d PO
6-12 years: 100 mcg/d PO
>12 years: 150 mcg/d PO

Interactions

Cholestyramine may decrease absorption; estrogens may decrease response to thyroid hormone therapy in patients with nonfunctioning thyroid glands; increases effects of anticoagulants; activity of some beta-blockers may decrease when hypothyroid patient is converted to a euthyroid state

Contraindications

Documented hypersensitivity; uncorrected adrenal insufficiency

Precautions

Pregnancy

A - Fetal risk not revealed in controlled studies in humans

Precautions

Caution in angina pectoris or cardiovascular disease; monitor thyroid status periodically

Antidiuretic hormone replacement

These agents are used for the replacement of vasopressin.

Vasopressin (Pitressin)

IM or SC injection of ADH analog that has vasopressor and ADH activity. Increases water resorption at distal renal tubular epithelium (ADH effect). Promotes smooth-muscle contraction throughout vascular bed of renal tubular epithelium (vasopressor effects).

Dosing

Adult

5-10 U IM/SC q6h

Pediatric

2.5-10 U IM/SC bid/qid

Interactions

Lithium, epinephrine, demeclocycline, heparin, and alcohol may decrease effects; chlorpropamide, urea, fludrocortisone, and carbamazepine may potentiate effects

Contraindications

Documented hypersensitivity; coronary artery disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in cardiovascular disease, seizure disorders, nitrogen retention, asthma, or migraine; excessive doses may result in hyponatremia

Desmopressin acetate (DDAVP, Stimate)

Longer-acting ADH derivative that can be used intranasally; increases cellular permeability of collecting ducts, resulting in resorption of water by kidneys.

Dosing

Adult

150 mcg intranasally q12-24h; endocrinologist should follow effects to adjust dose and timing

Pediatric

<3 months: Not established
3 months to 12 years: 5-30 mcg/d intranasally qd or divided bid
>12 years: Administer as in adults

Interactions

Demeclocycline and lithium decrease effects; fludrocortisone and chlorpropamide increase effects

Contraindications

Documented hypersensitivity; patients with platelet-type von Willebrand disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Avoid overhydration in patients using desmopressin to benefit from its hemostatic effects

Follow-up

Further Inpatient Care

• Acutely decompensated hypopituitarism requires admission.
• Once diagnosed, hypopituitarism due to pituitary adenomas may be entirely reversible by means of tumor resection or by shrinking it with pharmacologic therapy or radiation.
• Pituitary surgery is an option, depending on the size of the tumor, the degree of destruction of adjacent tissue, and the ability of the neurosurgeon to remove the tumor without disturbing the normal pituitary tissue. If the tumor can be removed selectively, hormone secretion may return to normal.
• Recovery of baseline pituitary function is unlikely if hypothalamic or pituitary tissue has been destroyed by radiation, surgery (total hypophysectomy), or hemorrhage. Life-long hormone replacement will be required.
• Hormone replacement is the treatment option. Initiation of this treatment is outside the purview of emergency medicine, but an overview is provided below.   
• Thyroxine deficiency is resolved easily with once-a-day replacement. Administer levothyroxine (Synthroid) at an initial dose of 25 mcg, then increase as needed to a maintenance dose.
  • Hypothyroidism can mask a hypocortisol state.
  • Upon initiating thyroid replacement, a patient's cortisol level drops acutely, creating an adrenocortical crisis.
  • Prior to replacement of thyroid hormone, patients should be treated empirically with glucocorticoids if adrenal insufficiency is potentially present.
• Maintenance treatment of adrenal insufficiency consists of 10-20 mg of hydrocortisone daily, often with a dose of 10 mg every morning and 5 mg every evening.  
  • A similar treatment comprises 5 mg of prednisone each morning and 2.5 mg each evening.
  • In acute adrenal insufficiency, a bolus of hydrocortisone 100-250 mg IV, followed by hydrocortisone 100 mg IV every 8 hours, would sustain a patient through physiologic stress (eg, infection, injury).
• Treat FSH and LH deficiency in premenopausal women with oral contraceptive pills containing estrogen and progesterone.  
  • The pills provide a cyclical release of hormone and stimulate normal endometrial growth and shedding.
  • In males, testosterone can be given orally as a testosterone enanthate patch 200-300 mg every 2-3 weeks or as a depot injection 300 mg IM every 3 weeks.
• Recombinant GH has had tremendous significance for children. Growth hormone replacement in adults can be initiated at a recommended dose of 300 mcg/day or lower and titrated according to IGF-1 levels and tolerance to side effects.
• Prolactin deficiency rarely is present and is only of significance in lactating, postpartum women. However, no replacement is currently available for prolactin deficiency.
• Treat ADH deficiency with vasopressin in doses of 5-10 units given IM or SC every 6 hours. Desmopressin (DDAVP), a synthetic form of vasopressin, can be given intranasally and can last up to 12-24 hours.

Further Outpatient Care

• Patients with hypopituitarism who are seen in the ED for nonendocrinologic reasons should be reminded to increase their baseline steroids in response to the stress. They should follow up with their primary doctor or endocrinologist as previously directed by the physician.
• Outpatient evaluation of patients for hypopituitarism in a well-appearing patient can be orchestrated by the primary doctor in consultation with appropriate specialists.

Inpatient & Outpatient Medications

• Previous sections discuss the treatment options (see Emergency Department Care and Further Inpatient Care).

Deterrence/Prevention

• Prevention of hypopituitarism is a complex sociomedical process outside the purview of the clinical practice of emergency medicine.
• Prevention of acute decompensation can be accomplished by reminding patients to increase the hydrocortisone dose in response to stress.

Complications

• Visual deficit
• Adrenal crisis
• Long-term hormone replacement therapy
• Susceptibility to infection and other stressors due to limited ability of the endocrine system to respond appropriately

Prognosis

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

Patient Education

• Patients should wear a medical identification bracelet or necklace.
• In patients with documented ACTH deficiency, stress doses of corticosteroids may be needed in times of major physical stress (eg, fever, trauma, surgery).
• For excellent patient education resources, visit eMedicine's Endocrine System Center. Also, see eMedicine's patient education articles Hypopituitarism in Children, Hypopituitary, and Anatomy of the Endocrine System.

Miscellaneous

Medicolegal Pitfalls

• Patients with acutely decompensated hypopituitarism require early administration of stress doses of glucocorticoids. Failure to administer glucocorticoids is not practicing to the standard of care.
• The initial presentation of hypopituitarism is a difficult diagnosis in the acutely decompensated or the stable patient. The emergency physician should keep these diagnoses in mind but can not be expected to make this diagnosis in the ED.

References

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Keywords

hypopituitarism, pituitary apoplexy, Sheehan's syndrome, Sheehan syndrome, pituitary hormone deficiencies, thyrotropin, thyroid-stimulating hormone, TSH, gonadotropins, follicle-stimulating hormone, FSH, luteinizing hormone, LH, growth hormone, GH, corticotropin, adrenocorticotropic hormone, ACTH, prolactin hormone, PRL, traumatic brain injury, TBI, cocaine snorting, subarachnoid hemorrhage, postpartum hypotension, pituitary insufficiency

Contributor Information and Disclosures

Author

Lisa Diane Mills, MD, Assistant Professor of Emergency Medicine, Director, Section of Emergency Medicine Ultrasound, Louisiana State University at New Orleans
Lisa Diane Mills, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, Society for Academic Emergency Medicine, and Southern Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Erik D Schraga, MD, Consulting Staff, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates; Consulting Staff, Permanente Medical Group, Kaiser Permanente, Santa Clara Medical Center
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Howard A Bessen, MD, Professor of Medicine, Department of Emergency Medicine, UCLA School of Medicine; Program Director, Harbor-UCLA Medical Center
Howard A Bessen, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors, Jerome FX Naradzay, MD, and Stuart A Brilliant, MD, to the development and writing of this article.

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