Disorders of the Hypothalamus and Pituitary Gland

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[edit] Disorders of the Hypothalamus and Pituitary Gland

Janet Schlechte

Hyperprolactinemia, acromegaly, and hypopituitarism are common neuroendocrine disorders that are likely to be encountered in the primary care setting. Although all will be managed in conjunction with an endocrinologist, the primary care physician needs to be familiar with the clinical presentation, appropriate screening tests, and treatment options for these disorders.

[edit] HYPERPROLACTINEMIA

Although most anterior pituitary hormones, including growth hormone (GH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH), and thyroid stimulating hormone (TSH), are stimulated by hypothalamic releasing factors, the secretion of prolactin (PRL) is under inhibitory hypothalamic control. Dopamine is the predominant PRL inhibitory factor and disruption of hypothalamic dopaminergic pathways or alteration of dopamine synthesis leads to hypersecretion of PRL. The primary action of PRL is to stimulate lactation and growth of mammary tissue. PRL levels gradually increase throughout pregnancy, with a tenfold elevation at term. Four to 12 weeks after delivery PRL levels return to normal unless breastfeeding occurs. Serum levels of PRL are usually under 20 ng/ml in females and under 10 ng/ml in males.

[edit] Clinical Presentation

The major consequence of hyperprolactinemia is reproductive dysfunction. High levels of PRL suppress the pulsatile secretion of gonadotropin releasing hormone, leading to low LH and follicle stimulating hormone (FSH) secretion and impaired production of estradiol and testosterone. In women the classic symptoms of hyperprolactinemia are amenorrhea, galactorrhea, and infertility. However, amenorrhea may occur without galactorrhea, galactorrhea may occur alone, and some women with hyperprolactinemia have regular menses. The hypogonadism induced by PRL excess also leads to dyspareunia or hot flashes. Hyperprolactinemia in males causes impotence, decreased libido, infertility, and gynecomastia. Galactorrhea is present in only 10% to 20% of men with hyperprolactinemia.

[edit] Causes

Although PRL-secreting pituitary tumors are the most common cause of hyperprolactinemia, the first step in evaluating a patient is to rule out causes unrelated to the pituitary or hypothalamus (Box 99-1). A variety of medications cause hyperprolactinemia by altering hypothalamic dopamine levels. Dopamine receptor antagonists such as neuroleptic agents and metoclopramide may be associated with PRL levels that exceed 200 ng/ml. Histamine type 2 receptor blockers cause hyperprolactinemia through centrally mediated mechanisms, and peripheral decarboxylase inhibitors like carbidopa interfere with dopamine biosynthesis. Verapamil may raise PRL levels in about 10% of patients taking the drug. PRL levels usually return to normal 48 to 96 hours after the medication is discontinued.

PRL levels rise during the menstrual cycle, and oral contraceptives cause a mild elevation of PRL. In patients with renal insufficiency the clearance of PRL is decreased. Chronic nipple stimulation and chest trauma increase PRL secretion and psychic stress has a variable effect. Primary hypothyroidism may be associated with an elevated PRL, and the pituitary enlargement that may accompany longstanding primary hypothyroidism mimics the presentation of a prolactinoma. A careful history and physical examination, measurement of thyroid function, and a pregnancy test will rule out most causes of hyperprolactinemia. Stimulation or suppression tests of PRL secretion using thyrotropin releasing hormone,l-dopa, or insulin-induced hypoglycemia are not valuable in the differential diagnosis of hyperprolactinemia.

[edit] Prolactinomas

Prolactinomas account for over 80% of all functioning pituitary tumors. In women prolactinomas are usually microadenomas (less than 10 mm) and are rarely associated with visual loss or hypopituitarism (Fig. 99-1). Fewer than 30% of women with hyperprolactinemia will have a macroadenoma (greater than 10 mm), but the majority of prolactinomas in men are large tumors (Fig. 99-2). PRL-secreting macroadenomas are more likely to be associated with visual loss, neurologic deficits, and loss of anterior pituitary hormones. Although males with prolactinomas develop impotence and decreased libido due to hyperprolactinemia, they usually seek medical attention because of headaches or visual loss.

Figure 99-1 Coronal T₁-weighted images before (left) and after (right) administration of gadolinium. After administration of contrast the pituitary microadenoma is hypodense compared with surrounding pituitary tissue.

Figure 99-2 Coronal T₁-weighted image of a pituitary macroadenoma extending into the cavernous sinus and displacing the optic chiasm.

[edit] Diagnosis.

The diagnosis of a prolactinoma is confirmed by demonstration of sustained hyperprolactinemia and radiographic evidence of a pituitary tumor. Because PRL secretion is episodic and PRL levels can be increased with stress, minimally elevated levels (20 to 30 ng/ml) should be confirmed by obtaining several samples.

When no obvious cause of an elevated PRL is apparent the hypothalamus and pituitary should be imaged. Magnetic resonance imaging (MRI) is superior to computed tomography (CT) in delineating tumor size and evaluating suprasellar or lateral tumor extension. PRL-secreting macroadenomas are virtually always accompanied by marked elevations of PRL (over 1000 ng/ml). In fact, a large pituitary tumor that is associated with a PRL of less than 200 ng/ml is unlikely to be a prolactinoma. Formal testing of visual fields and assessment of anterior pituitary function should always be undertaken when a macroadenoma is detected. Small prolactinomas are so rarely associated with hypopituitarism or visual loss that formal visual field testing and tests of anterior pituitary function are not necessary.

[edit] Management.

The two established indications for treatment of a prolactinoma are infertility and the presence of a macroadenoma. The goals of therapy are to normalize PRL, restore menses or erectile function, and decrease tumor size. The treatment of choice, regardless of tumor size, is a dopamine agonist. Pituitary surgery is not generally recommended because it is associated with a high rate of recurrence of hyperprolactinemia. Radiation is not used as primary therapy because of the time required to normalize PRL and gonadal function and because it may lead to hypopituitarism.

In the majority of cases treatment should be initiated with bromocriptine. This dopamine agonist causes rapid normalization of PRL and restoration of menses in 80% to 90% of patients. Treatment is usually started with a bedtime dose of 1.25 mg, which is slowly increased to 5 mg daily. A PRL level should be checked 3 to 4 weeks after reaching the target dose. If the PRL has not normalized, the dose should be increased slowly and the level should be repeated. Most women with a microadenoma will require 5 to 7.5 mg of bromocriptine daily. Gonadal function usually normalizes within 3 months, and after 4 to 6 weeks of therapy there will be a reduction in tumor size. Women with macroadenomas and men may require higher doses of bromocriptine to normalize PRL and cause tumor shrinkage.

Bromocriptine may be associated with nausea, nasal stuffiness, and orthostatic hypotension. All of these symptoms can be reduced if the drug is started at a low dose and increased slowly. If bromocriptine is not effective or is not well tolerated, another dopamine agonist such as pergolide (Permax) or cabergoline (Dostinex) may be substituted. Cabergoline has a high specificity for the dopamine D2 receptor and a long half-life and can be given twice weekly. Doses of cabergoline ranging from 0.5 to 2 mg weekly are as efficacious as 5 to 7.5 mg of bromocriptine and may be associated with fewer side effects. However, cabergoline is expensive and should be reserved for patients with resistant tumors or for those who cannot take bromocriptine. All dopamine agonists must be taken regularly to be effective. Discontinuation leads to a rapid return to pretreatment PRL levels and tumor regrowth (Box 99-2).

When treatment with bromocriptine is initiated, mechanical contraception should be used until two to three menstrual cycles have occurred. When pregnancy is documented, the dopamine agonist should be discontinued. Although dopamine agonists are not associated with an increased rate of spontaneous abortion or congenital defects, fetal exposure should be limited. PRL normally rises after conception, and it is not necessary or cost-effective to monitor levels throughout pregnancy. The pituitary gland will increase in size during pregnancy and the high estrogen levels achieved during pregnancy will stimulate lactotroph hyperplasia, but pregnant women with PRL microadenomas rarely develop symptomatic tumor enlargement. A pregnant woman with a macroadenoma, however, should have a formal visual field examination each trimester and MRI scanning if symptoms of tumor expansion occur. The primary care physician may institute and manage dopamine agonist therapy for a microadenoma but treatment of a PRL-secreting macroadenoma will require a multidisciplinary approach involving an endocrinologist, neuro-ophthalmologist, and neurosurgeon.

[edit] Management of Prolactinomas When Pregnancy Is Not an Issue.

When a prolactinoma is small and fertility is not an issue, there is no clear consensus on whether to treat the hyperprolactinemia or to monitor the patient without therapy. PRL-secreting microadenomas have a benign natural history and do not progressively increase in size over time. Elevated PRL levels do, however, suppress production of estradiol and testosterone and may place these patients at risk for premature bone loss. Women with hyperprolactinemic amenorrhea have been shown to have 25% lower spinal bone mass than women with regular menses but do not have an increased fracture rate. The use of dual-energy x-ray absorptiometry to quantitate bone mass in hyperprolactinemic women may help with treatment decisions in individual patients. An amenorrheic woman with elevated PRL who is not desirous of pregnancy or a postmenopausal woman with hyperprolactinemia may be treated with estrogen. Since estrogen may induce pituitary enlargement, these women should be monitored closely for clinical signs of tumor growth. Alternatively, they can be treated with a combination of estrogen and bromocriptine.

[edit] Idiopathic Hyperprolactinemia.

Some women with amenorrhea, galactorrhea, and hyperprolactinemia have no evidence of a tumor on MRI, and this condition is termed idiopathic hyperprolactinemia. A tumor may actually be present but is too small to be detected radiographically. In most of these patients PRL levels remain stable and progression toward a macroadenoma or microadenoma is uncommon.

[edit] ACROMEGALY

Secretion of GH is regulated by two hypothalamic peptides, GH releasing factor and somatostatin. The releasing factor stimulates synthesis and release of GH, while somatostatin is inhibitory and maintains low levels of GH secretion. Insulin-like growth factor (IGF-1) is the peripheral target for GH and the anabolic effects of GH are mediated through IGF-1, which is produced in the liver. GH secretion is pulsatile and is stimulated by exercise, stress, and estrogen.

GH secreting tumors account for 10% to 15% of pituitary adenomas and are usually discovered in the third to fifth decade. GH secreting tumors grow slowly, and about 80% of patients have tumors larger than 10 mm on presentation (Fig. 99-3). Headache is present in about 50% of patients at diagnosis, and a patient with a rapidly enlarging tumor may present with a visual field defect or cranial nerve palsy. Primary care physicians need to be aware of the clinical presentation of acromegaly and how to screen for GH hypersecretion.

Figure 99-3 Computed tomography (CT) scan of large pituitary tumor in a patient with acromegaly.

[edit] Clinical Presentation

Typical findings of GH excess include coarsening of facial features, increasing hand and foot size, frontal bossing, oily skin, and hyperhidrosis (Fig. 99-4). With enlargement of the mandible, malocclusion of the jaw may occur, and the diagnosis of acromegaly may first be considered during a dental evaluation. Sleep apnea occurs in 50% of patients with acromegaly and degenerative arthritis is common. Diabetes mellitus occurs in 10% to 25%. Cardiovascular disease is prevalent and is the most common cause of death in patients with acromegaly. Acromegaly is associated with an increased frequency of colonic polyps, uterine leiomyomata, and gastrointestinal malignancies. Early recognition of GH excess is important since patients with acromegaly have two to three times the expected mortality rate, which decreases after GH levels return to normal.

Figure 99-4 Typical facial features of acromegaly.

[edit] Diagnosis

GH secretion is pulsatile with undetectable levels between pulses. Because of this pulsatility random measurement of GH will not suffice to make the diagnosis of acromegaly. The diagnosis of GH excess can be confirmed by measurement of IGF-1 or by measurement of GH during a glucose tolerance test. After the oral administration of 75 or 100 grams of glucose, GH levels in healthy individuals will fall to less than 2 ng/ml, whereas patients with acromegaly will show no suppression or may show a paradoxical increase in GH (Fig. 99-5). The best single test for diagnosis of acromegaly is measurement of IGF-1. IGF-1 values are not affected by exercise and reflect integrated GH secretion over the previous 24 hours (see Fig. 99-5). Other laboratory abnormalities in patients with acromegaly include elevated triglycerides, hyperglycemia, and hyperphosphatemia. The elevated phosphate may be due to direct stimulation of renal tubular phosphate reabsorption by IGF-1. One third of individuals with GH excess will have hyperprolactinemia due to co-secretion of GH and PRL by the tumor. When GH excess is confirmed, a MRI of the pituitary should be done and the patient should be referred to an endocrinologist for treatment.

Figure 99-5 A, Lack of suppression of GH after oral administration of glucose in patient with acromegaly. Levels less than 2 ng/ml are normal. B, IGF-1 levels in normal subjects and patients with acromegaly.

[edit] Management

The treatment of choice for a GH-secreting tumor is transsphenoidal surgery. This procedure should be performed by an experienced neurosurgeon, and preoperative and postoperative care should be coordinated by the primary care physician, endocrinologist, and neurosurgeon. Surgical success rates range from 78% to 90% for small GH-secreting tumors and from 33% to 80% for macroadenomas. Unsuccessful surgery may necessitate treatment with a dopamine agonist, a long-acting analog of somatostatin, or radiation therapy.

[edit] HYPOPITUITARISM

Hypopituitarism results from failure of all or portions of the anterior pituitary. The clinical manifestations of pituitary insufficiency depend on the process responsible for the hormone loss and the type and number of hormones that are absent. Hormone loss may be total (panhypopituitarism) or partial, and in some cases hormone deficiency is due to loss of a single hypothalamic releasing hormone. In a patient with a large pituitary mass, visual loss or headache may bring the patient to medical attention before the hormone loss becomes clinically apparent. In contrast, a patient with a slow-growing pituitary tumor may present with nonspecific symptoms such as fatigue.

[edit] Causes

The most common cause of hypopituitarism is a hypothalamic or pituitary tumor. Infiltrative processes such as sarcoidosis account for only 1% of cases of pituitary dysfunction, and postpartum hemorrhage (Sheehan's syndrome) leading to hypopituitarism is rare. Hormone loss can occur from a few months to years after radiation therapy. Sudden hemorrhage into a large pituitary tumor may lead to headache, diplopia, and acute pituitary failure (pituitary apoplexy). Head trauma may lead to direct fracture of the sella turcica, causing hemorrhage within the gland or rupture of the pituitary stalk. In older subjects a rare cause of hypopituitarism is vascular insufficiency sustained during coronary artery bypass surgery (Box 99-3).

[edit] Clinical Presentation

The endocrine symptoms that accompany pituitary failure mimic the symptoms that develop with the loss of the target organs (thyroid, ovary, testes, adrenal). Although there is no fixed order in which anterior pituitary hormones are lost, GH, LH, and FSH usually disappear before ACTH or TSH. The clinical manifestations that accompany loss of the anterior pituitary hormones are discussed below. When hormone deficiency is due to failure of the target organ the disorder is termed primary hormone insufficiency. When the hormone deficiency is due to loss of a hypothalamic or pituitary hormone it is termed secondary hormone insufficiency.

[edit] LH and FSH.

Loss of gonadal function is perhaps the most common presentation of hypopituitarism in adults. Attention to clinical symptoms is important, since normal semen analysis in a male and regular menstrual function in a female make hypogonadotropic hypogonadism extremely unlikely. In premenopausal women loss of LH and FSH leads to oligomenorrhea, amenorrhea, infertility, dyspareunia, and decreased libido. In males, decreased testicular function is manifested by decreased libido, decrease in ejaculate volume, infertility, and change in beard and body hair growth.

Evaluation of the pituitary-gonadal axis involves measurement of LH, FSH, and testosterone or estradiol. Patients with ovarian or testicular failure will have low testosterone and estradiol levels with an elevated FSH and LH, whereas those with hypogonadotropic hypogonadism will have low LH and FSH levels and low sex steroid levels.

[edit] TSH.

Secondary hypothyroidism that develops due to loss of TSH is less common than thyroid failure and accounts for less than 5% of all cases of hypothyroidism. It is not possible to distinguish primary and secondary hypothyroidism on clinical symptomatology alone, and common findings include cold intolerance, constipation, dry skin, myalgias, delayed deep tendon reflexes, and bradycardia.

The most reliable test to document secondary hypothyroidism is measurement of free thyroxine, and a normal serum thyroxine indicates that the pituitary-thyroid axis is intact. A TSH alone should not be used as a screening test in patients with pituitary disease because most patients with secondary hypothyroidism will have a TSH within the normal range. With symptoms of hypothyroidism a subnormal serum thyroxine and a low or normal TSH should suggest pituitary insufficiency.

[edit] ACTH.

ACTH deficiency is potentially the most serious outcome of pituitary hormone loss. The symptoms associated with loss of ACTH usually occur gradually, and patients who develop secondary adrenal insufficiency usually present with fatigue, weight loss, and lassitude. Patients with secondary adrenal insufficiency do not develop hyperpigmentation and rarely have the salt wasting, volume contraction, or hypokalemia that is seen in patients with primary adrenal failure. Hypotension and electrolyte abnormalities are absent in secondary adrenal insufficiency because the renin-angiotensin-aldosterone system in the adrenal glands remains intact. Patients with ACTH deficiency do not develop hyperpigmentation because the pituitary cannot produce ACTH or other components of the proopiomelanocortin molecule, which is responsible for skin darkening in primary adrenal insufficiency. Patients with severe ACTH deficiency may develop hypoglycemia after a prolonged fast and some patients may present with abdominal pain, arthralgias, and myalgias. Patients with ACTH deficiency occasionally develop hyponatremia as a consequence of inappropriately elevated levels of antidiuretic hormone (ADH). Since ACTH stimulates production of adrenal androgens, ACTH deficiency may also lead to loss of axillary and pubic hair. This is more likely to occur in women where it may also contribute to decreased libido. In some cases impairment of ACTH secretion is only partial and patients may be asymptomatic unless they become severely ill or have surgery. Long-term administration of glucocorticoids is a common cause of secondary adrenal insufficiency. Any glucocorticoid given in supraphysiologic doses or over a prolonged period of time will suppress hypothalamic production of corticotropin releasing factor and lead to decreased ACTH secretion.

When ACTH deficiency is suspected it is important to determine whether the hypothalamic-pituitary-adrenal axis is intact and whether it can respond to stress. A plasma cortisol greater than 18 mg/dl excludes adrenal insufficiency but a normal cortisol does not exclude partial ACTH deficiency. Provocative testing may be needed to document adrenal cortical reserve. A normal cortisol response to the administration of Cortrosyn indicates that the adrenal cortex can respond and excludes primary adrenal insufficiency but does not exclude partial ACTH deficiency (Fig. 99-6). A patient with low serum cortisol or an inadequate response to Cortrosyn should be referred to an endocrinologist for provocative testing of the pituitary-adrenal axis.

Figure 99-6 Cortisol response to ACTH in healthy subjects and patients with primary and secondary adrenal insufficiency. The flat response in primary adrenal insufficiency is due to adrenal failure. The blunted response in secondary adrenal insufficiency is due to insufficient stimulation of the adrenals by ACTH.

[edit] Growth Hormone Deficiency.

For many years GH deficiency was not thought to have any adverse effects in adults. Recent studies suggest that lack of GH may lead to decreased muscle mass, increased fat mass, decreased muscle strength, reduced aerobic exercise capacity, low bone density, and increased low-density lipoprotein (LDL) cholesterol. Patients with GH deficiency have also been shown to have a higher mortality rate than age-and sex-matched subjects.

Measurement of IGF-1 and random GH cannot be used to diagnose GH deficiency. The diagnosis can only be made when a patient has a subnormal response to a test of GH reserve. Provocative tests to assess GH reserve include insulin-induced hypoglycemia,l-dopa, clonidine, or arginine, and all should be performed in consultation with an endocrinologist.

[edit] Management of Hypopituitarism

[edit] Hypogonadism.

The treatment of hypopituitarism requires replacement of hormones normally produced by the target organs (Box 99-4). Treatment of gonadotropin deficiency is accomplished by replacing gonadal steroids except when fertility is an issue. Estrogen is indicated for maintenance of secondary sex characteristics and prevention of osteoporosis. A variety of estrogen preparations are available. Postmenopausal women can be adequately treated with estrogen and progesterone, but it may be more convenient to treat a premenopausal woman with an oral contraceptive. In women with an intact uterus estrogen should be used in conjunction with a progestational agent like medroxyprogesterone acetate to avoid the development of endometrial hyperplasia. In women with gonadal dysfunction due to loss of gonadotropins the response to therapy cannot be monitored by changes in LH and FSH.

Parenteral testosterone preparations are the agents of choice for androgen replacement therapy and can be administered intramuscularly every 2 to 4 weeks. The consequences of androgen therapy include salt and fluid retention, edema, gynecomastia, and occasional aggressive behavior. Worsening of benign prostatic hypertrophy in middle-aged and elderly men may also occur. Oral testosterone preparations are not recommended because of low potency and an association with peliosis hepatitis and hepatoma.

[edit] Hypoadrenalism.

The cortisol deficiency induced by loss of ACTH can be effectively treated with hydrocortisone, cortisone acetate, or prednisone. Since the renin-angiotensin-aldosterone system is intact in patients with secondary adrenal insufficiency, mineralocorticoid replacement is usually not required. Serum and urine cortisol and ACTH levels cannot be used to monitor the efficacy of replacement, and assessment of electrolytes and clinical symptoms will be used to guide therapy. In patients with partial ACTH deficiency enough cortisol may be secreted to take care of daily needs but secretion may be inadequate in times of stress. Patients must be alert to the requirement for additional glucocorticoids during periods of illness. Occasionally administration of glucocorticoid replacement will unmask central diabetes insipidus leading to polyuria (see Diabetes Insipidus). In patients with pituitary disease it is important to establish that ACTH secretion is normal prior to initiating thyroid hormone therapy. Treatment with thyroid hormone accelerates cortisol metabolism and could precipitate an adrenal crisis.

[edit] Hypothyroidism.

The goal of therapy in patients with TSH deficiency is to restore the euthyroid state. Synthetic levothyroxine preparations should be used because of their uniform potency, and the usual replacement dose is 0.1 to 0.15 mg daily. Elderly patients and those with cardiovascular diseases should be started on lower doses (0.025 to 0.05 mg daily) and the dose should be increased slowly. Measurement of TSH cannot be used to confirm the euthyroid state, and free T4 levels should be used to monitor therapy.

[edit] Growth Hormone Deficiency.

Recombinant GH therapy is only indicated for select patients with GH deficiency. In order to qualify for GH therapy an adult must have a subnormal GH response to a standard stimulation test (see above) and evidence of hypopituitarism secondary to pituitary or hypothalamic disease. The optimal dose of recombinant GH for adults has not been determined and the drug should be administered by an endocrinologist. Side effects include edema, arthralgias, carpal tunnel syndrome, and glucose intolerance.

[edit] Disorders of the Posterior Pituitary

[edit] Diabetes Insipidus.

Diabetes insipidus develops when the posterior pituitary cannot produce adequate amounts of ADH. The principal manifestation of diabetes insipidus is polyuria and some patients may excrete more than 15 liters of urine daily. Central diabetes insipidus is caused by any process that damages the hypothalamic nuclei that synthesize ADH or the axons extending into the pituitary, and about one third of cases of central diabetes insipidus are idiopathic. Other patients develop diabetes insipidus because the kidneys are incapable of responding to ADH (nephrogenic diabetes insipidus). Common causes of nephrogenic diabetes insipidus include hypokalemia, hypercalcemia, and the use of lithium and demeclocycline.

The diagnosis of diabetes insipidus requires the demonstration of an inability to concentrate the urine. The second step in the evaluation is to determine whether the inability to concentrate the urine is due to deficient production of ADH from the pituitary or hypothalamus or is due to insensitivity of the kidney to the hormone. A formal water deprivation test measuring pituitary and kidney responses to exogenous ADH is usually required to make the diagnosis. A water deprivation test should be done under close medical supervision and in consultation with an endocrinologist.

Desmopressin is an analog of ADH with a prolonged half-life and is the primary therapy for central diabetes insipidus. Two daily doses are usually efficacious. Patients who require long-term use of ADH should be cautioned about the potential for water intoxication and hyponatremia.

[edit] EMPTY SELLA

During radiographic evaluation of the central nervous system it is not uncommon to discover an enlarged sella that is not completely filled with pituitary tissue. An empty sella may result from herniation of the suprasellar cistern through an incompetent diaphragm sella, and the pituitary gland may be flattened on the floor of the sella. A partial empty sella occurs in obese and multiparous middle-aged women who are often hypertensive. An empty sella alone is not an indication for therapy and clinical symptoms should determine the need for tests of hormone function. In general pituitary function remains normal in patients with the empty sella syndrome.

[edit] PITUITARY INCIDENTALOMA

With the widespread use of MRI to evaluate central nervous system disorders it is not unusual to detect unsuspected abnormalities in the pituitary glands of patients who have no symptoms of pituitary disease (pituitary incidentaloma). Asymptomatic patients with an incidentally diagnosed pituitary adenoma that is less than 10 mm will not require extensive tests of hormone function if there is no clinical evidence of hormone hypersecretion. In the absence of clinical signs of hormone excess a single measurement of serum PRL is a cost-effective approach. An MRI can be repeated in 1 to 2 years. If the adenoma has not changed in size, no further testing is required. Patients with an incidentaloma larger than 10 mm should be evaluated for hormone excess and should have formal visual field testing. In general, incidentally discovered pituitary adenomas do not progressively increase in size or become hormonally active over time.

[edit] ADDITIONAL READINGS

• WA Hall,et al.: Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 1994; 120:817 - 820.
• S Melmed: Acromegaly. New Engl J Med 1990;966 - 977.
• ME Molitch, MO Thorner, C Wilson: Therapeutic controversy: management of prolactinomas. J Clin Endocrinol Metab 1997; 82:996 - 1000.
• J Schlechte,et al.: The natural history of untreated hyperprolactinemia: a prospective analysis. J Clin Endocrinol Metab 1989; 68:412 - 418.
• I Shimon, S Melmed: Management of pituitary tumors. Ann Intern Med 1998; 129:472 - 483.
• ME Vance: Hypopituitarism. New Engl J Med 1994; 330:1651 - 1662.