Hypopituitarism

Hypopituitarism may be either partial or complete and may result from either pituitary or hypothalamic disease. Its clinical manifestations vary, depending on the extent and severity of the pituitary hormone deficiency. Thus, a patient may present in extremis with acute adrenal insufficiency or profound hypothyroidism, with symptoms indicating a pituitary mass lesion, or with nonspecific symptoms of fatigue and malaise. Most of the hypothalamic-pituitary-target-organ axes are tightly coordinated systems in which hormonal signals from the hypothalamus stimulate or inhibit secretion of anterior pituitary hormones; these hormones, in turn, act on specific organs. These axes are frequently described as closed-loop or negative-feedback systems, since circulating hormones secreted by target organs modulate hypothalamic and pituitary activity (Figure 1. Interactions among the Hypothalamus, Pituitary, and Target Glands.). The anterior pituitary is composed of distinct cell types, each of which secretes a specific hormone in response to unique hypothalamic stimulatory or inhibitory hormones; the target-gland hormone then modulates hypothalamic or pituitary activity or both. For example, hypothalamic corticotropin-releasing hormone (CRH) stimulates pituitary corticotropin secretion, which stimulates adrenal cortisol secretion, which in turn inhibits CRH and corticotropin secretion. The hypothalamic, pituitary, and target-organ hormones are listed in Table 1. Hypothalamic and Pituitary Hormones and Their Actions.. Although the secretion of most anterior pituitary hormones is regulated primarily by stimulating hormones, prolactin secretion is tonically inhibited by dopamine. A hormone deficiency is primary or secondary; a primary deficiency refers to target-gland failure, a secondary deficiency to target-gland failure caused by lack of stimulation by the specific pituitary hormone. A pituitary hormone deficiency may result from either a deficiency of the hypothalamic-releasing hormone or intrinsic pituitary disease. This review discusses the prevalence and causes of acquired pituitary insufficiency, the clinical features of pituitary hormone deficiency, biochemical and anatomical evaluation, and hormone-replacement therapy. CAUSES OF HYPOPITUITARISM The causes of acquired hypopituitarism are listed in Table 2. Causes of Hypopituitarism.. Although a pituitary tumor is the most common cause, a tumor or cyst in the hypothalamus or infundibulum; infiltrative, vascular, and other disorders; and pituitary or cranial radiation therapy may also cause hypopituitarism. The reported annual incidence of pituitary tumors of all sizes, types, and secretory activities in the United States ranges from 0.2 to 2.8 per 100,000 population1-3. The prevalence of all types of symptomatic pituitary tumors, based on the U.S. population in 1950 (151 million), was 8.9 per 100,000,4 for a total prevalence of 13,439. If this rate is applied to the current U.S. population (253 million), the estimated current prevalence of symptomatic pituitary tumors is 22,517. This is probably an underestimation, since the studies that formed the basis for the estimated prevalence in 1950 preceded the development of contemporary hormone assays and imaging techniques.

Pituitary Adenoma Hypopituitarism may occur in patients with either secretory or nonsecretory pituitary adenomas. Among patients with macroadenomas ( 10 mm), 30 percent or more have one or more hormone deficiencies; the most common is growth hormone deficiency (100 percent in some series). In contrast, patients with microadenomas (<10 mm) usually have disordered gonadotropin secretion and gonadal dysfunction5,6. A patient may have a deficiency of one hormone or any combination of hormones, although deficiencies of corticotropin and thyrotropin may be the least common7-12. The mechanisms by which pituitary tumors cause hypopituitarism include mechanical compression of normal pituitary tissue by the tumor, impaired blood flow to the normal tissue, and interference with the delivery of hypothalamic regulating hormones through the hypothalamic-hypophysial portal system. Hypopituitarism may be reversible; removal of the tumor or shrinkage by means of drug therapy (for example, the shrinkage of large prolactinomas with dopamine-agonist drugs) is often accompanied by the return of normal function13-15. If hypothalamic or pituitary tissue has been destroyed, however (e.g., by radiation therapy, hemorrhage, or surgery), recovery of normal function is unlikely, and lifelong hormone-replacement therapy is required. Pituitary Surgery The development of postoperative pituitary deficiency depends on at least three factors: the size of the tumor, the degree of destruction of adjacent normal tissue, and the ability of the neurosurgeon to remove the tumor without disturbing the normal pituitary tissue. If a total hypophysectomy is performed, panhypopituitarism, often including diabetes insipidus, results. If the tumor is selectively removed, secretion may return to normal. Postoperative studies are therefore necessary to determine changes in function. In a study of 26 patients with pituitary macroadenomas, all the patients had deficient secretion of growth hormone before surgery, and 15 percent continued to have deficient secretion after surgery. Gonadotropin was deficient in 96 percent of the patients before surgery and in 35 percent afterward, thyrotropin was deficient in 81 percent before surgery and in 65 percent afterward, and corticotropin was deficient in 62 percent before surgery and in 39 percent afterward16. In a study of 28 patients with macroadenomas, 85 percent had deficient growth hormone and 68 percent had another hormone deficiency before surgery; after surgery, 100 percent had deficient growth hormone and 82 percent had at least one other deficiency17. Thus, patients about to undergo surgery for a pituitary tumor should be told not only that their hormone deficiencies may be corrected but also that hormone-replacement therapy may be required after surgery and that fertility cannot be ensured. Pituitary Radiation Therapy Pituitary radiation by the conventional method, proton beam, gamma knife (focused in a single treatment), or yttrium-90 or gold-198 implants is now commonly used as adjunctive therapy after an incomplete surgical resection or as primary therapy if the patient is not a candidate for surgery. The primary objectives of radiation therapy are to prevent continued tumor growth and arrest any hormonal hypersecretion. In the process of radiation, normal hypothalamic and pituitary tissue may be damaged. Patients with brain tumors treated with radiation have damage to the hypothalamus and, less often, to the pituitary gland18. Most, if

not all, patients undergoing pituitary radiation eventually have either partial or complete hypopituitarism, and the hormone deficiencies may occur before hormonal hypersecretion is inhibited. The clinical challenge is to detect deficiencies before unnecessary morbidity occurs. How soon after radiation should pituitary insufficiency be expected? Prospective studies of pituitary function after radiotherapy indicate that the onset of pituitary hormone deficiencies is highly variable. In a study of 22 patients, conventional pituitary radiation, which is usually given in a dose of 50 Gy over four weeks, caused corticotropin, gonadotropin, and thyrotropin deficiencies in over 50 percent of the patients a mean of 4.2 years after treatment19. Similarly, in 66 patients evaluated five years after pituitary radiation therapy, 100 percent had deficient growth hormone, 91 percent had deficient gonadotropin, 77 percent had deficient corticotropin, and 42 percent had deficient thyrotropin20. The less frequently used pituitary radiation techniques, such as proton-beam radiation and yttrium-90 or gold-198 implants, usually cause substantial pituitary hormone deficiencies21-24. Whether the gamma-knife method of radiation therapy causes a similar degree of pituitary insufficiency is not known but should be anticipated. Patients with nasopharyngeal or head and neck cancer who receive radiation therapy are also at risk for endocrine deficiencies, because the treatment field often includes the hypothalamus, pituitary, and thyroid gland. Two years after cranial radiation for nasopharyngeal carcinoma, 19 percent of patients had a deficiency of one or more anterior pituitary hormones25. The onset of pituitary or thyroid failure occurred from 1 to 26 years after head and neck radiation26. Although pituitary insufficiency is almost certain to develop after cranial or pituitary radiation, it is impossible to predict when the insufficiency will occur. Thus, lifelong follow-up at regular intervals is necessary. Some investigators suggest an endocrine evaluation three months after the completion of treatment and then yearly. Patients should be informed of the symptoms associated with pituitary failure and instructed to seek medical attention if any of these symptoms develop. Pituitary Apoplexy Pituitary apoplexy is the abrupt destruction of pituitary tissue resulting from infarction or hemorrhage into the pituitary, usually into an undiagnosed tumor. The clinical features of pituitary apoplexy include the sudden onset of severe headache, visual loss, cranial-nerve palsy (cranial nerves III, IV, or VI or any combination thereof), and a variably depressed sensorium. Secondary adrenal insufficiency, if not recognized and treated, may lead to hypotension and shock. A recent hemorrhage is easily identifiable with an unenhanced coronal computed tomographic (CT) scan or a magnetic resonance imaging (MRI) scan. The prevalence of pituitary hemorrhage is not known, and it may not be accompanied by any symptoms. Among 560 patients undergoing surgery for a pituitary tumor, 93 (17 percent) had some hemorrhage into their tumors. Of these 93 patients, 42 had no symptoms that could be related to the hemorrhage, 38 had neurologic or ophthalmologic deficits, and 13 had headache, nausea, vomiting, and vertigo27. In a study of 27 patients with macroprolactinomas treated with a

dopamine-agonist drug for one year, serial MRI scans revealed small areas of hemorrhage in 9 of the patients (33 percent), 1 of whom had a transient corticotropin deficiency28. In addition to a pituitary tumor, predisposing factors for pituitary apoplexy include diabetes mellitus, radiation therapy, anticoagulant therapy or bleeding disorders, head trauma, sudden changes in arterial or intracranial pressure (for example, during carotid angiography), and postpartum hemorrhage (Sheehan's syndrome)29. In a study of 66 patients with pituitary apoplexy, secretion of growth hormone was abnormal in 88 percent of the patients, and secretion of corticotropin, thyrotropin, luteinizing hormone, and follicle-stimulating hormone (FSH) was abnormal in 66, 42, 76, and 58 percent, respectively; 2 to 3 percent of the patients had diabetes insipidus30. Sheehan's syndrome, which is pituitary necrosis after postpartum hemorrhage and hypovolemia, may cause hypopituitarism (either immediately or after a delay of several years), depending on the amount of tissue destruction31. Adrenal insufficiency, hypothyroidism, amenorrhea, and an inability to breast-feed are classic features of the syndrome; diabetes insipidus may also occur. High-resolution CT scans in 57 women with Sheehan's syndrome demonstrated that the sellar volume was 39 percent smaller than in normal women; 20 percent of the women with Sheehan's syndrome had an empty sella32. Less Common Causes of Pituitary Insufficiency Empty Sella Syndrome An empty sella refers to an enlarged pituitary fossa resulting from arachnoid herniation through an incomplete sellar diaphragm. An empty sella may result from a congenital diaphragmatic defect (primary empty sella) or damage to the diaphragm by surgery, radiation therapy, or tumor infarction (secondary empty sella). The prevalence of primary empty sella in a study of adults with normal pituitary function being evaluated for ophthalmologic or otolaryngeal disease ranged from 39 to 43 percent33,34. Most patients with a primary empty sella have normal pituitary function, and approximately 15 percent have mild hyperprolactinemia. The pituitary gland is usually flattened against the floor of the sella, and the pituitary stalk may be deviated laterally. The development of pituitary dysfunction appears to be related to the degree of sellar enlargement, as demonstrated by CT scans in 56 adults with normal pituitary function and 11 patients with hypopituitarism33. The empty sella syndrome can also occur in children, with an incidence of 48 percent in children with either an isolated growth hormone deficiency or a combination of pituitary hormone deficiencies; only 2 percent of children with normal pituitary function have an empty sella35. Head Trauma Hypothalamic or pituitary injury may occur after any type of head trauma, including trauma as a result of a motor vehicle accident, fall, explosion, or injury from a bullet or shrapnel. The injury can occur without a basilar skull fracture. The clinical manifestations of pituitary dysfunction may be evident immediately after the injury or not until months or even years later. Of 20 patients with post-traumatic hypopituitarism, 100 percent had deficient growth hormone and gonadotropins, 95 percent had deficient corticotropin, and 85 percent had deficient thyrotropin; 63 percent had an increased serum prolactin concentration. Only 40

percent of the patients had either transient or permanent diabetes insipidus36. Although recovery of anterior pituitary function is uncommon, it was reported to have occurred 12 years after injury in one patient37. Infiltrative Disease Granulomatous diseases that affect the hypothalamus or pituitary and therefore cause hypopituitarism include sarcoidosis, giant-cell granuloma, eosinophilic granuloma (which is more common in children than in adults), and Wegener's granulomatosis. Lymphocytic hypophysitis, a diffuse infiltration of the anterior pituitary, occurs predominantly in women and is often first evident during pregnancy or after delivery. Pathological examination reveals infiltration with lymphocytes and plasma cells; some patients have evidence of another autoimmune endocrine disease38. Lymphocytic hypophysitis has also been reported in a postmenopausal woman39. In hemochromatosis, iron infiltration of the pituitary, as well as other endocrine glands, may result in one or more hormonal deficiencies. Repeated phlebotomy may reverse the abnormality40. Several types of infections cause hypopituitarism by infiltrating the hypothalamus or pituitary. Many types of cancer metastasize to the hypothalamus or pituitary and cause hypopituitarism; the most common types are breast and lung cancers. Symptoms or signs of hypopituitarism may occur before a mass is evident on an MRI or CT scan. The anatomical characteristics of infiltrative lesions, which are not distinctive on imaging scans, often mimic the features of pituitary tumors. Metastases tend to occur initially in the posterior pituitary, thus causing diabetes insipidus. Internal-Carotid-Artery Aneurysm Atherosclerotic involvement of the intracavernous portion of the internal carotid artery may cause aneurysmal dilatation into the pituitary fossa. Hypopituitarism may result from pressure exerted by the mass itself or from aneurysmal leakage and hemorrhagic destruction of the gland41. CT scans (unenhanced and enhanced) demonstrate a homogeneous pituitary mass that may be indistinguishable from a pituitary tumor, and MRI scans show an area of signal void (black) on T- and T-weighted images that is more marked on the latter. Partial thrombosis in the aneurysm appears as an area of high signal intensity (white) interspersed with a signal void on T-weighted images. Carotid or MRI angiography is necessary to confirm the presence of an aneurysm and to determine the feasibility of surgery or endovascular repair. The diagnosis is important, since transsphenoidal surgery would be likely to cause uncontrollable hemorrhage. CLINICAL FEATURES OF HYPOPITUITARISM The clinical manifestations of hypopituitarism depend on the type and degree of hormone deficiency and the rapidity of its onset. For example, if corticotropin deficiency is partial, basal cortisol secretion is normal. During an intercurrent illness or surgery, however, corticotropin secretion may not increase to normal levels, in which case adrenal insufficiency may develop. If corticotropin deficiency is complete, cortisol secretion is subnormal at all times. The diagnosis of a complete deficiency is straightforward; most patients have symptoms, and the serum concentrations of both the target-organ hormone (e.g., cortisol, thyroxine, and testosterone in men) and the pituitary hormone (e.g., corticotropin, thyrotropin, and luteinizing hormone, respectively) are low. Dynamic tests are usually necessary to detect partial deficiencies. With the exception of growth hormone, which is deficient in most patients with hypopituitarism, it is

impossible to predict which, if any, pituitary hormones will be deficient in a patient with hypopituitarism from a particular cause or a tumor of a particular size. Similarly, the absence of a lesion on an MRI or CT scan does not exclude pituitary failure. Pituitary hormone secretion can often be evaluated adequately in the outpatient setting by measurements of basal serum hormone concentrations, particularly if they are inappropriately low. Most of the symptoms and signs of a pituitary hormone deficiency are similar to those that occur in patients with a primary deficiency of the target gland, except as noted below. The symptoms of corticotropin deficiency include fatigue, weakness, headache, anorexia, weight loss, nausea, vomiting, abdominal pain, and altered mental activity. Physical examination is notable for lack of the hyperpigmentation that occurs in patients with primary adrenal insufficiency. Supine blood pressure is usually normal, but orthostatic hypotension may occur. Women with long-standing adrenal insufficiency often have loss of axillary and pubic hair. Hyponatremia may occur as a result of increased vasopressin secretion, but the serum potassium concentration is usually normal, since adrenal production of aldosterone is not dependent on corticotropin. In contrast, both hyponatremia and hyperkalemia are common in patients with primary adrenal insufficiency. Normochromic, normocytic anemia and eosinophilia may also occur with corticotropin deficiency. Symptoms of thyrotropin deficiency include fatigue, weakness, inability to lose weight (or weight gain), puffiness, constipation, and cold intolerance. Impaired memory or altered mental activity is characteristic of severe hypothyroidism. Physical examination may reveal bradycardia, periorbital puffiness, and delayed relaxation of tendon reflexes. Other findings include mild hyponatremia and normochromic, normocytic anemia. Luteinizing hormone and FSH are produced by the same pituitary cell type. Men with hypogonadism have decreased libido and erectile dysfunction ranging from decreased tumescence to complete impotence; the volume of ejaculate may be decreased and hot flashes may occur. The patient's sexual partner may be the one to report sexual dysfunction. The physical examination is usually normal if hypogonadism is of recent onset. Diminished facial and body hair, fine facial wrinkles, gynecomastia, and soft testes are characteristic of long-standing (years) hypogonadism. Women of reproductive age with gonadotropin deficiency have alterations in menstrual function ranging from regular but anovulatory cycles to oligomenorrhea or amenorrhea. Other symptoms of ovarian failure include hot flashes, decreased libido, vaginal dryness, and dyspareunia. Pubic and axillary hair is present unless there is concomitant adrenal failure. Postmenopausal women usually present with symptoms of other hormonal deficiencies or a mass lesion (headache or visual abnormalities). Symptoms attributed to growth hormone deficiency in adults include lack of vigor, decreased tolerance of exercise, and decreased social functioning42. The percentage of body fat is higher in growth hormone-deficient adults than in age-matched normal subjects (Thorner MO: personal communication). Fine facial wrinkles may result from a deficiency of growth hormone as well as from hypogonadism. Prolactin is the only pituitary hormone whose secretion is tonically inhibited under normal circumstances; dopamine is the inhibitory hormone. Hyperprolactinemia occurs with a

prolactin-secreting tumor or any process that interferes with the transport of dopamine from the hypothalamus to the pituitary. The characteristic feature of hyperprolactinemia is galactorrhea, but it is not as common as hypogonadism -- in particular, amenorrhea. Hyperprolactinemia of any cause interferes with normal pulsatile secretion of luteinizing hormone and FSH5,6. A high serum prolactin concentration is a useful marker of hypothalamic or pituitary dysfunction, even if the concentration is not sufficiently elevated to cause hypogonadism or galactorrhea. Polyuria and polydipsia with nocturia are the classic features of diabetes insipidus, resulting from a deficiency of vasopressin (from the posterior pituitary). Characteristically, cold water is preferred. If water excretion exceeds intake, the patient will become hypovolemic and hypotensive. Serum sodium concentrations and serum osmolality may be normal if the fluid intake is adequate or increased if the fluid intake is not adequate. Oxytocin deficiency (from the posterior pituitary) is characterized by decreased milk ejection during lactation. ENDOCRINE AND IMAGING STUDIES Although basal serum hormone measurements may be all that is needed to confirm pituitary insufficiency, dynamic tests are used if the results of serum hormone tests are equivocal or to diagnose partial deficiencies. Both the target hormone concentration and the pituitary hormone concentration should be measured to assess the appropriateness of both values. The uses and limitations of single and dynamic endocrine tests are listed in Table 3. Use and Limitations of Single Hormone Measurements in Patients with Suspected Pituitary Disease. andTable 4. Use and Limitations of Dynamic Tests in Patients with Suspected Pituitary Disease., respectively. Endocrine Studies Corticotroph (Corticotropin) Deficiency An undetectable or subnormal morning serum cortisol concentration, in the absence of steroid therapy, indicates adrenal insufficiency. Glucocorticoid therapy should be initiated immediately; dynamic tests can be performed later if there is any question about the diagnosis. A normal serum corticotropin concentration in a patient who has a low serum cortisol concentration indicates a deficiency of corticotropin. Of the several dynamic tests of hypothalamic-pituitary-adrenal function that have been developed, the easiest and most common is the corticotropin stimulation test. In this test, serum cortisol concentrations are measured before and 30 and 60 minutes after a single intravenous injection of 250 g of corticotropin. If corticotropin and adrenal secretion are normal, the serum cortisol concentration should increase to 20 g per deciliter (552 nmol per liter) or higher 43. In patients with severe corticotropin deficiency for more than a few weeks, the serum cortisol response will be lower, or even absent, as a result of the adrenal atrophy that occurs in the absence of corticotropin secretion. This test does not assess whether corticotropin secretion can increase, and some patients have a normal serum cortisol response despite corticotropin deficiency, as demonstrated by the lack of serum corticotropin and cortisol responses to insulin-induced hypoglycemia (even though the serum cortisol response to exogenous corticotropin is normal).

These findings occur in patients with pituitary failure of recent onset in whom there has been insufficient time for adrenal atrophy to develop and in patients with a partial deficiency of corticotropin. Tests of the function of the whole axis include insulin-induced hypoglycemia and the metyrapone test. Insulin-induced hypoglycemia increases CRH secretion directly, thereby increasing serum corticotropin (and growth hormone) and cortisol concentrations. Serum glucose and cortisol (and growth hormone) are measured before and 30, 60, and 90 minutes after the intravenous administration of 0.15 U of regular insulin per kilogram of body weight. The serum glucose concentration should decrease to less than 50 percent of the base-line value or less than 40 mg per deciliter (2.2 mmol per liter) for adequate hypothalamic-pituitary stimulation. Because of the risks associated with hypoglycemia, this test must be performed under a physician's supervision. If the morning serum cortisol concentration is less than 5 g per deciliter (138 nmol per liter), a normal response is highly unlikely and the test is probably not necessary. Contraindications to this test include a history of a seizure disorder, angina, an altered mental status, and generalized debility. The serum cortisol concentration should increase to 20 g per deciliter (552 nmol per liter) or higher (a normal serum growth hormone response is an increase to 10 ng per milliliter or higher). Metyrapone inhibits cortisol synthesis, leading to increased secretion of corticotropin and therefore of 11-deoxycortisol. The test is performed by administering one or several doses of metyrapone and measuring serum 11-deoxycortisol concentrations several hours later; in normal subjects the concentrations rise, whereas in patients with corticotropin deficiency they do not rise. A recently developed test of pituitary-adrenal function is the stimulation of corticotropin and cortisol secretion with CRH. CRH is currently available only as an experimental drug, and since the test has been performed in only a small number of patients with pituitary disease, its role is uncertain44,45. In a study of patients receiving steroid therapy, the results of tests with CRH and insulin-induced hypoglycemia were comparable46. Thyrotroph (Thyrotropin) Deficiency Both serum thyrotropin and thyroxine concentrations should be measured in a patient with suspected hypothalamic or pituitary disease. Patients with secondary hypothyroidism usually have a normal or low serum thyrotropin concentration, either of which is inappropriate if the serum thyroxine concentration is low. Occasionally, however, a patient has an elevated serum thyrotropin concentration because the hypothalamic or pituitary disease has resulted in the secretion of thyrotropin that has diminished biologic activity but retains immunologic activity. Failure of the serum thyrotropin concentration to increase after the administration of thyrotropin-releasing hormone confirms secondary hypothyroidism but is not necessary to make the diagnosis. Gonadotroph (Luteinizing Hormone and FSH) Deficiency The best test of gonadotroph deficiency in premenopausal women is the menstrual history, because regular menses indicate at least some gonadotroph function. Since luteinizing hormone and FSH are secreted in a pulsatile manner, a single measurement may be in the

normal range even in women who have amenorrhea, but even normal values are inappropriate in women with amenorrhea. The serum estradiol concentration, which may be normal or low in women with gonadotropin deficiency, provides little information beyond that which can be obtained from the menstrual history. Men with gonadal failure may have normal or low serum luteinizing hormone and FSH concentrations, but normal values are inappropriate if the serum testosterone concentration is decreased. Somatotroph (Growth Hormone) Deficiency A single measurement of serum growth hormone is rarely useful, since the serum concentration is normally low most of the day and growth hormone is also secreted in a pulsatile fashion. A stimulatory test (Table 4) is therefore required to assess the somatotroph reserve. Measurement of serum insulin-like growth factor I, which is dependent on growth hormone, may indicate a deficiency of the hormone, if the patient is not malnourished, chronically ill, or elderly, all of which decrease the production of insulin-like growth factor I. Lactotroph (Prolactin) Deficiency The serum prolactin concentration is rarely low and may be increased in patients with hypothalamic-pituitary disease of almost any cause. Serum prolactin should always be measured, because it may provide information about the location of the disorder causing hypopituitarism, as well as the cause of hypogonadism. Dynamic testing of the lactotroph reserve with thyrotropin-releasing hormone is not useful, because it does not differentiate among the various causes of hyperprolactinemia. Imaging Studies After the clinical and biochemical diagnosis of hypopituitarism has been made, an imaging study of the hypothalamic-pituitary region should be performed to determine whether a mass is present. The most informative image is an MRI scan with intravenous gadolinium. MRI is superior to CT because the optic chiasm, pituitary stalk, and cavernous sinuses -- all of which may be affected by a hypothalamic or pituitary mass -- can normally be seen on an MRI scan (Figure 2. MRI Scans and Drawings of the Scans of a Normal Pituitary Gland (Panel A) and a Pituitary Macroadenoma That Resulted in Panhypopituitarism (Panel B).). If it is not possible to obtain an MRI scan because of claustrophobia or ferrous metal in the body, a high-resolution CT scan with contrast administration is an adequate alternative. If possible, the CT scan should be obtained in the coronal plane with thin sections (1.5 mm) through the pituitary fossa. If the patient is unable to hyperextend his or her neck, axial sections with sagittal reconstruction will provide adequate visualization of the pituitary. Although an MRI scan is more expensive than a CT scan (approximately $300 more at the University of Virginia), the additional anatomical information provided by the MRI scan is worth the higher cost. Skull and sellar x-ray films have no role in the evaluation of patients with a possible hypothalamic or pituitary mass, since a tumor may extend superiorly or laterally without enlarging the sella. If a patient undergoes surgery, a second scan should be obtained two to three months later to assess the amount of residual pituitary or tumor tissue. This interval between surgery and a subsequent evaluation is necessary to allow for resolution of postoperative edema and inflammation, which make it impossible to determine the amount of residual tumor

immediately after surgery. Many neurosurgeons obtain a CT scan a few days after surgery to determine whether a hemorrhage has occurred, but this scan should not be used to assess the adequacy of tumor resection. CONSEQUENCES OF UNTREATED HYPOPITUITARISM Cortisol and thyroxine are necessary for life, and a deficiency of corticotropin or thyrotropin may therefore result in death. Gonadotropin deficiency in premenopausal women and in men causes infertility and sexual dysfunction. Although fertility or sexual function may not be important to a particular patient, replacement of sex steroids is clinically important. The consequences of untreated hypogonadism in both men and women include a decrease in bone density and an increase in the risk of osteoporosis47,48. Estrogen deficiency in women may result in an increased risk of coronary artery disease49. Testosterone deficiency in men is thought to cause a decrease in muscle mass, strength, and a sense of well-being, all of which may improve with hormone replacement. The polyuria and polydipsia caused by vasopressin deficiency can be extremely inconvenient, because some patients need to drink up to 10 liters of water a day. If fluid intake is inadequate, dehydration, hypovolemia, and hypernatremia occur. Prolactin deficiency is not known to cause any problems except deficient lactation. There are no studies reporting the medical consequences of growth hormone deficiency in adults. However, an absence of growth hormone may have adverse effects on the vascular system, resulting in premature death from cardiovascular disease. In a study of 333 patients with hypopituitarism, 104 patients (31 percent) died (expected mortality, 57 patients, or 17 percent); 60 percent of the deaths were attributed to cardiovascular events. All 53 patients tested for growth hormone had deficient concentrations, and all the patients with cortisol or thyroid hormone deficiency had undergone replacement therapy. Only 76 percent of the men had received testosterone, and only 40 percent of the women under 50 years of age had received estrogen50. Although gonadal steroid deficiency may have contributed to the excess mortality (most likely in the women), the patients with deficient growth hormone may have had increased serum cholesterol and triglyceride concentrations -- an additional risk factor for cardiovascular disease51,52. HORMONE-REPLACEMENT THERAPY Hormone-replacement therapy should be considered by patients and physicians as just that: replacement of the hormones that the endocrine glands are no longer capable of producing. This is an important concept, since patients often resist long-term therapy because of publicity about the adverse effects of medications. The judicious use of hormone replacement is both necessary and beneficial. The goals of hormone-replacement therapy are to raise circulating hormone concentrations to levels that are within the normal range, with normal daily variation taken into account when appropriate, and to ameliorate the symptoms of the hormone deficiency. Adrenal insufficiency should be treated with hydrocortisone (20 mg on awakening and 10 mg in the early evening) or prednisone (5 mg on awakening and 2.5 mg in the early evening) to simulate the normal circadian rhythm of cortisol secretion. Thyroxine can be given once daily, because there is little, if any, variation in its secretion. Premenopausal women should be treated with estrogen and progesterone, given in a cyclic pattern that reproduces the normal process of endometrial

growth and sloughing; an oral contraceptive may also be used. Testosterone must be given in the form of long-acting testosterone esters, which usually result in normal serum testosterone concentrations during much of the recommended interval between doses but cannot be considered the same as physiologic concentrations. The most commonly used preparation, testosterone enanthate, is administered every two or three weeks in a dose of 200 or 300 mg, respectively. This regimen transiently increases serum testosterone concentrations to levels that are higher than normal, raising the possibility of adverse effects on serum lipid concentrations, particularly high-density lipoprotein (HDL) cholesterol. Transdermal administration of testosterone, which is currently being tested, may result in concentrations that are closer to the physiologic values53,54. Growth hormone has a beneficial effect on body composition, reducing the adipose mass and increasing the muscle mass,55,56 and also improves exercise tolerance, muscle strength, and bone density,57-59 but whether these effects provide a long-term benefit is not known. Growth hormone is not currently approved in the United States for use in adults. Assessment of the efficacy of hormone replacement involves both clinical and biochemical evaluation. Although twice daily administration of hydrocortisone or prednisone in the recommended doses is suitable for most patients, some have mild cushingoid symptoms. Conversely, some patients have fatigue or headache, often in the afternoon, which may indicate accelerated clearance of hydrocortisone or prednisone; such patients should be given the same total dose but in three doses each day. Measurement of the serum or urinary cortisol concentration (which is possible only in patients treated with hydrocortisone) is usually not helpful in assessing the adequacy of hormone replacement, although the serum or urinary cortisol concentration may be measured to confirm suspected overreplacement. Because aldosterone secretion is not dependent on corticotropin, mineralocorticoid replacement is not required. A patient who requires glucocorticoid therapy should wear an identification bracelet or necklace stating the need for this therapy. The patient's symptoms are monitored, and the serum free or total thyroxine concentration is measured to assess the adequacy of thyroxine therapy. Gonadal steroid therapy is adequate in women when cyclic menses occur and there are no menopausal symptoms. In men, replacement therapy is adequate when well-being, libido, and potency are restored and hot flashes disappear. These symptoms may recur if the interval between injections is too long. The serum testosterone concentration can be measured just before an injection if there is a suspicion that the dose is inadequate. Serum cholesterol and HDL cholesterol concentrations should be measured periodically, and the dose decreased if the HDL cholesterol level is lower than normal. CONCLUSIONS Hypopituitarism is treatable, and a patient with this condition should be able to perform normal activities as long as the appropriate hormonal therapy is used consistently and properly. Once the proper replacement regimen has been determined, the doses usually do not need to be changed except for an increase in the glucocorticoid dose (which is generally doubled) during intercurrent illness. Even after the proper regimen has been established, however, a patient with hypopituitarism requires lifelong medical follow-up Sumber : http://www.nejm.org/doi/full/10.1056/NEJM199406093302306

hypopituitarism Hypopituitarism dapat berupa sebagian atau lengkap dan dapat berakibat baik dari penyakit hipofisis hipotalamus atau . Manifestasi klinis bervariasi , tergantung pada tingkat keparahan kekurangan hormon hipofisis . Dengan demikian , pasien mungkin hadir dalam extremis dengan insufisiensi adrenal akut atau hipotiroidisme mendalam , dengan gejala yang menunjukkan lesi massa hipofisis , atau dengan gejala nonspesifik kelelahan dan malaise . Sebagian dari sumbu hipotalamus-hipofisis -target - organ erat dikoordinasikan sistem di mana sinyal hormonal dari hipotalamus merangsang atau menghambat sekresi hormon hipofisis anterior , hormon ini , pada gilirannya , bertindak atas organ tertentu . Ini sumbu sering digambarkan sebagai sistem loop tertutup atau umpan balik negatif , karena beredar hormon yang disekresi oleh organ sasaran memodulasi aktivitas hipotalamus dan hipofisis ( Gambar 1 . Interaksi antara hipotalamus ini, hipofisis , dan Kelenjar Target. ) . Hipofisis anterior terdiri dari jenis sel yang berbeda , masing-masing mengeluarkan hormon tertentu dalam menanggapi stimulasi hipotalamus unik atau hormon penghambat , hormon kelenjar target kemudian memodulasi aktivitas hipotalamus atau hipofisis atau keduanya . Misalnya , hipotalamus corticotropin - releasing hormone ( CRH ) merangsang hipofisis corticotropin sekresi , yang merangsang sekresi kortisol adrenal , yang pada gilirannya menghambat CRH dan sekresi kortikotropin . Hipotalamus , hipofisis , dan target organ hormon yang tercantum dalam Tabel 1 . Hormon hipotalamus dan hipofisis dan Tindakan mereka .. Meskipun sekresi hormon hipofisis anterior yang paling diatur terutama dengan merangsang hormon , sekresi prolaktin dihambat oleh dopamin tonically . Kekurangan hormon primer atau sekunder , kekurangan utama mengacu pada kegagalan target kelenjar , kekurangan sekunder untuk kegagalan target kelenjar yang disebabkan oleh kurangnya stimulasi oleh hormon hipofisis tertentu. Sebuah kekurangan hormon hipofisis dapat mengakibatkan baik dari kekurangan hormon hipotalamushipofisis melepaskan atau penyakit intrinsik . Ulasan ini membahas prevalensi dan penyebab diperoleh insufisiensi hipofisis , fitur klinis defisiensi hormon hipofisis , evaluasi biokimia dan anatomi , dan terapi hormon pengganti . PENYEBAB hypopituitarism Penyebab hypopituitarism diakuisisi tercantum dalam Tabel 2 . Penyebab hypopituitarism .. Meskipun tumor hipofisis adalah penyebab paling umum , tumor atau kista di hipotalamus atau infundibulum , infiltratif , pembuluh darah , dan gangguan lain , dan terapi radiasi hipofisis atau tengkorak juga dapat menyebabkan hypopituitarism . Melaporkan kejadian tahunan tumor hipofisis dari semua ukuran , jenis , dan kegiatan sekretorik di Amerika Serikat berkisar 0,2-2,8 per 100.000 population1 - 3 . Prevalensi semua jenis tumor hipofisis gejala , berdasarkan populasi AS pada 1950 (151 juta) adalah 8,9 per 100,000,4 untuk prevalensi total 13.439 . Jika tingkat ini diterapkan pada penduduk AS saat ini ( 253 juta ) , prevalensi saat ini diperkirakan tumor hipofisis gejala adalah 22.517 . Ini mungkin merupakan meremehkan , karena studi yang membentuk dasar untuk estimasi prevalensi pada tahun 1950 mendahului pengembangan tes hormon kontemporer dan teknik pencitraan .

pituitary Adenoma Hypopituitarism dapat terjadi pada pasien dengan baik sekresi atau adenoma hipofisis nonsecretory . Di antara pasien dengan macroadenomas ( 10 mm ) , 30 persen atau lebih memiliki satu atau lebih kekurangan hormon , yang paling umum adalah kekurangan hormon pertumbuhan ( 100 persen dalam beberapa seri ) . Sebaliknya, pasien dengan mikroadenoma ( < 10 mm ) biasanya memiliki sekresi gonadotropin teratur dan gonad dysfunction5 , 6 . Seorang pasien mungkin memiliki kekurangan satu hormon atau kombinasi dari hormon , meskipun kekurangan kortikotropin dan thyrotropin mungkin paling common7 - 12 . Mekanisme yang tumor hipofisis menyebabkan hypopituitarism termasuk kompresi mekanik jaringan hipofisis normal dengan tumor , gangguan aliran darah ke jaringan normal , dan gangguan pada pengiriman hormon pengatur hipotalamus melalui sistem portal hipotalamus - hypophysial . Hypopituitarism mungkin reversibel , pengangkatan tumor atau penyusutan dengan cara terapi obat ( misalnya, penyusutan Prolaktinoma besar dengan obat - dopamin agonis ) sering disertai dengan kembalinya normal function13 - 15 . Jika jaringan hipotalamus atau hipofisis telah dihancurkan , namun ( misalnya , dengan terapi radiasi , perdarahan , atau operasi ) , pemulihan fungsi normal tidak mungkin , dan terapi penggantian hormon seumur hidup diperlukan . Bedah pituitary Pengembangan defisiensi hipofisis pascaoperasi tergantung pada setidaknya tiga faktor : ukuran tumor , tingkat kerusakan jaringan normal yang berdekatan , dan kemampuan ahli bedah saraf untuk menghilangkan tumor tanpa mengganggu jaringan hipofisis normal. Jika hipofisektomi total dilakukan , panhypopituitarism , sering termasuk diabetes insipidus , hasil . Jika tumor selektif dihapus , sekresi dapat kembali normal . Studi pascaoperasi karena itu diperlukan untuk menentukan perubahan fungsi . Dalam sebuah penelitian terhadap 26 pasien dengan macroadenomas hipofisis , semua pasien memiliki kekurangan sekresi hormon pertumbuhan sebelum operasi , dan 15 persen terus memiliki kekurangan sekresi setelah operasi . Gonadotropin adalah kekurangan 96 persen dari pasien sebelum operasi dan dalam 35 persen sesudahnya , thyrotropin adalah kekurangan 81 persen sebelum operasi dan dalam 65 persen sesudahnya , dan corticotropin adalah kekurangan 62 persen sebelum operasi dan dalam 39 persen afterward16 . Dalam sebuah penelitian terhadap 28 pasien dengan macroadenomas , 85 persen memiliki kekurangan hormon pertumbuhan dan 68 persen mengalami defisiensi hormon lain sebelum operasi, setelah operasi , 100 persen memiliki kekurangan hormon pertumbuhan dan 82 persen memiliki setidaknya satu deficiency17 lainnya . Dengan demikian , pasien akan menjalani operasi tumor hipofisis harus diberitahu bahwa tidak hanya kekurangan hormon mereka dapat dikoreksi tetapi juga bahwa terapi hormon pengganti mungkin diperlukan setelah operasi dan kesuburan yang tidak dapat dipastikan . Terapi Radiasi Pituitary Radiasi hipofisis dengan metode konvensional , proton beam , pisau ( fokus dalam pengobatan tunggal ) gamma , atau yttrium - 90 atau emas - 198 implan sekarang umum digunakan sebagai terapi tambahan setelah reseksi bedah lengkap atau sebagai terapi utama jika pasien tidak calon untuk operasi . Tujuan utama dari terapi radiasi untuk mencegah pertumbuhan tumor lanjutan dan menangkap setiap hipersekresi hormon . Dalam proses radiasi , jaringan hipotalamus dan hipofisis normal dapat rusak. Pasien dengan tumor otak

diobati dengan radiasi mengalami kerusakan pada hipotalamus dan , lebih jarang , ke pituitari gland18 . Kebanyakan , jika tidak semua , pasien yang menjalani radiasi hipofisis akhirnya memiliki baik hypopituitarism sebagian atau lengkap , dan kekurangan hormon dapat terjadi sebelum hipersekresi hormon terhambat. Tantangan klinis adalah untuk mendeteksi kekurangan sebelum morbiditas yang tidak perlu terjadi . Berapa lama setelah radiasi harus insufisiensi hipofisis diharapkan? Studi prospektif fungsi hipofisis setelah radioterapi menunjukkan bahwa terjadinya kekurangan hormon hipofisis sangat bervariasi . Dalam sebuah penelitian terhadap 22 pasien , radiasi hipofisis konvensional , yang biasanya diberikan dalam dosis 50 Gy selama empat minggu , disebabkan corticotropin , gonadotropin , dan thyrotropin kekurangan dalam lebih dari 50 persen dari pasien rata-rata 4,2 tahun setelah treatment19 . Demikian pula, pada 66 pasien dievaluasi lima tahun setelah terapi radiasi hipofisis , 100 persen memiliki kekurangan hormon pertumbuhan , 91 persen memiliki kekurangan gonadotropin , 77 persen memiliki corticotropin kekurangan , dan 42 persen memiliki thyrotropin20 kekurangan . Semakin sedikit sering digunakan teknik radiasi hipofisis , seperti proton - balok radiasi dan yttrium - 90 atau emas - 198 implan , biasanya menyebabkan hormon hipofisis substansial deficiencies21 - 24 . Apakah metode gamma - pisau terapi radiasi menyebabkan gelar serupa dari insufisiensi hipofisis tidak diketahui, tetapi harus diantisipasi . Pasien dengan kanker nasofaring atau kepala dan leher yang menerima terapi radiasi juga berisiko untuk kekurangan endokrin , karena bidang pengobatan sering mencakup hipotalamus , hipofisis , dan kelenjar tiroid . Dua tahun setelah radiasi kranial untuk karsinoma nasofaring , 19 persen pasien memiliki kekurangan satu atau lebih hipofisis anterior hormones25 . Terjadinya kegagalan hipofisis atau tiroid terjadi 1-26 tahun setelah kepala dan leher radiation26 . Meskipun insufisiensi hipofisis hampir pasti berkembang setelah radiasi kranial atau hipofisis , adalah mustahil untuk memprediksi kapan kekurangan akan terjadi . Dengan demikian , seumur hidup tindak lanjut secara berkala diperlukan . Beberapa peneliti menyarankan evaluasi endokrin tiga bulan setelah selesainya pengobatan dan kemudian tahunan. Pasien harus diberitahu tentang gejala yang terkait dengan kegagalan hipofisis dan diperintahkan untuk mencari bantuan medis jika gejala-gejala tersebut berkembang. pituitary pitam Hipofisis pitam adalah kerusakan mendadak jaringan hipofisis akibat infark atau perdarahan ke dalam hipofisis , biasanya menjadi tumor terdiagnosis . Gambaran klinis pitam hipofisis meliputi mendadak sakit kepala parah, kehilangan penglihatan , kelumpuhan saraf kranial - ( saraf kranial III , IV , atau VI atau kombinasi dari semuanya ) , dan sensorium bervariasi tertekan . Insufisiensi adrenal sekunder , jika tidak diakui dan diperlakukan , dapat menyebabkan hipotensi dan shock . Sebuah perdarahan baru-baru ini mudah diidentifikasi dengan unenhanced koronal dihitung tomografi ( CT ) scan atau pencitraan resonansi magnetik ( MRI ) scan . Prevalensi perdarahan hipofisis tidak diketahui , dan mungkin tidak disertai dengan gejala apapun . Di antara 560 pasien yang menjalani operasi untuk tumor hipofisis , 93 ( 17 persen ) memiliki beberapa perdarahan ke dalam tumor mereka . Dari jumlah tersebut 93 pasien , 42 tidak memiliki gejala yang dapat berhubungan dengan pendarahan , 38 memiliki defisit

neurologis atau oftalmologi , dan 13 sakit kepala , mual, muntah , dan vertigo27 . Dalam sebuah penelitian terhadap 27 pasien dengan macroprolactinomas diobati dengan obat dopamin agonis selama satu tahun , MRI scan mengungkapkan seri daerah kecil perdarahan di 9 besar pasien ( 33 persen ) , 1 di antaranya memiliki corticotropin transien deficiency28 . Selain tumor hipofisis , faktor predisposisi untuk hipofisis pitam termasuk diabetes mellitus , terapi radiasi , terapi antikoagulan atau gangguan perdarahan , trauma kepala , perubahan mendadak dalam arteri atau intrakranial tekanan ( misalnya, selama karotis angiografi ) , dan perdarahan postpartum ( sindrom Sheehan ) 29 . Dalam sebuah penelitian terhadap 66 pasien dengan hipofisis pitam, sekresi hormon pertumbuhan tidak normal di 88 persen pasien , dan sekresi kortikotropin , tirotropin , hormon luteinizing , dan follicle-stimulating hormone ( FSH ) adalah normal pada 66 , 42 , 76 , dan 58 persen , masing-masing; 2 sampai 3 persen pasien memiliki diabetes insipidus30 . Sindrom Sheehan , yang nekrosis hipofisis setelah perdarahan postpartum dan hipovolemia , dapat menyebabkan hypopituitarism (baik langsung atau setelah penundaan beberapa tahun ) , tergantung pada jumlah jaringan destruction31 . Insufisiensi adrenal , hipotiroidisme , amenore , dan ketidakmampuan untuk menyusui adalah fitur klasik sindrom , diabetes insipidus juga dapat terjadi . Resolusi tinggi CT scan pada 57 wanita dengan sindrom Sheehan menunjukkan bahwa volume sellar adalah 39 persen lebih kecil dibandingkan pada wanita normal, 20 persen dari wanita dengan sindrom Sheehan memiliki sella32 kosong. Penyebab Kurang umum Insufficiency hipofisis Sindrom Sella kosong Sebuah sella kosong mengacu pada fossa hipofisis membesar akibat arachnoid herniasi melalui diafragma sellar lengkap . Sebuah sella kosong mungkin akibat dari cacat bawaan diafragma ( sella kosong primer) atau kerusakan pada diafragma dengan pembedahan , terapi radiasi , atau infark tumor ( sella kosong sekunder ) . Prevalensi sella kosong utama dalam studi orang dewasa dengan fungsi hipofisis yang normal sedang dievaluasi untuk penyakit oftalmologi atau otolaryngeal berkisar 39-43 percent33 , 34 . Kebanyakan pasien dengan sella kosong utama memiliki fungsi hipofisis normal, dan sekitar 15 persen memiliki hiperprolaktinemia ringan. Kelenjar pituitari biasanya diratakan terhadap lantai sella , dan tangkai hipofisis dapat menyimpang lateral . Perkembangan disfungsi hipofisis tampaknya terkait dengan tingkat pembesaran sellar , seperti yang ditunjukkan oleh CT scan pada 56 orang dewasa dengan fungsi hipofisis normal dan 11 pasien dengan hypopituitarism33 . Sindrom sella kosong juga bisa terjadi pada anak-anak , dengan kejadian 48 persen pada anak-anak dengan baik sebagai kekurangan hormon pertumbuhan terisolasi atau kombinasi dari kekurangan hormon hipofisis , hanya 2 persen anak-anak dengan fungsi hipofisis yang normal memiliki sella35 kosong. kepala Trauma Cedera hipotalamus atau hipofisis mungkin terjadi setelah semua jenis trauma kepala , termasuk trauma akibat kecelakaan kendaraan bermotor , jatuh , ledakan, atau cedera akibat peluru atau pecahan peluru . Cedera dapat terjadi tanpa patah tulang tengkorak basilar . Manifestasi klinis disfungsi hipofisis mungkin jelas segera setelah cedera atau tidak sampai

berbulan-bulan atau bahkan bertahun-tahun kemudian. Dari 20 pasien dengan hypopituitarism pasca-trauma , 100 persen memiliki kekurangan hormon pertumbuhan dan gonadotropin , 95 persen memiliki corticotropin kekurangan , dan 85 persen memiliki thyrotropin kekurangan , 63 persen memiliki peningkatan konsentrasi prolaktin serum . Hanya 40 persen dari pasien telah baik sementara atau permanen diabetes insipidus36 . Meskipun pemulihan fungsi hipofisis anterior jarang , dilaporkan telah terjadi 12 tahun setelah cedera dalam satu patient37 . Penyakit infiltratif Penyakit granulomatosa yang mempengaruhi hipotalamus atau hipofisis dan karena itu menyebabkan hypopituitarism termasuk sarkoidosis , granuloma raksasa - sel , eosinophilic granuloma (yang lebih sering terjadi pada anak-anak dibandingkan pada orang dewasa ) , dan granulomatosis Wegener . Hypophysitis limfositik , infiltrasi difus dari hipofisis anterior , terjadi terutama pada wanita dan sering pertama terlihat selama kehamilan atau setelah melahirkan . Pemeriksaan patologis menunjukkan infiltrasi dengan limfosit dan sel plasma , beberapa pasien memiliki bukti lain endokrin autoimun disease38 . Hypophysitis Lymphocytic juga telah dilaporkan dalam woman39 pascamenopause . Pada hemochromatosis , infiltrasi besi hipofisis , serta kelenjar endokrin lainnya , dapat menyebabkan satu atau lebih kekurangan hormon . Phlebotomy berulang dapat membalikkan abnormality40 tersebut . Beberapa jenis infeksi menyebabkan hypopituitarism dengan infiltrasi hipotalamus atau hipofisis . Banyak jenis kanker bermetastasis ke hipotalamus atau hipofisis dan menyebabkan hypopituitarism , jenis yang paling umum adalah kanker payudara dan paru-paru . Gejala atau tanda-tanda hypopituitarism mungkin terjadi sebelum massa jelas pada MRI atau CT scan . Karakteristik anatomi lesi infiltratif , yang tidak berbeda pada pencitraan scan , sering meniru fitur dari tumor hipofisis . Metastasis cenderung terjadi awalnya di hipofisis posterior , sehingga menyebabkan diabetes insipidus . Internal- karotis Arteri - Aneurysm Keterlibatan aterosklerotik dari bagian intracavernous dari arteri karotis interna dapat menyebabkan dilatasi aneurisma ke fossa hipofisis . Hypopituitarism mungkin hasil dari tekanan yang diberikan oleh massa itu sendiri atau dari kebocoran aneurisma dan kehancuran hemorrhagic gland41 tersebut . CT scan ( unenhanced dan ditingkatkan ) menunjukkan massa hipofisis homogen yang dapat dibedakan dari tumor hipofisis , dan MRI scan menunjukkan area void sinyal ( hitam) pada T - dan gambar T - tertimbang yang lebih ditandai pada yang terakhir . Trombosis parsial dalam aneurisma muncul sebagai daerah intensitas sinyal tinggi ( putih) diselingi dengan kekosongan sinyal gambar T - tertimbang . Karotis atau MRI angiography diperlukan untuk mengkonfirmasi adanya aneurisma dan untuk menentukan kelayakan operasi atau perbaikan endovascular . Diagnosis ini penting, karena transsphenoidal operasi akan cenderung menyebabkan perdarahan tak terkendali . FITUR KLINIS hypopituitarism Manifestasi klinis hypopituitarism tergantung pada jenis dan derajat kekurangan hormon dan kecepatan onset nya . Misalnya, jika kekurangan kortikotropin parsial , sekresi kortisol basal adalah normal . Selama penyakit kambuhan atau operasi , namun, sekresi kortikotropin mungkin tidak meningkat ke tingkat normal , dalam hal insufisiensi adrenal dapat berkembang . Jika kekurangan corticotropin selesai , sekresi kortisol adalah subnormal setiap saat . Diagnosis

kekurangan lengkap mudah, kebanyakan pasien memiliki gejala , dan konsentrasi serum dari kedua hormon target organ (misalnya , kortisol , tiroksin , dan testosteron pada pria ) dan hormon hipofisis ( misalnya , kortikotropin , tirotropin , dan luteinizing hormon , masingmasing) yang rendah . Tes dinamis biasanya diperlukan untuk mendeteksi kekurangan parsial . Dengan pengecualian dari hormon pertumbuhan , yang kekurangan pada kebanyakan pasien dengan hypopituitarism , adalah mustahil untuk memprediksi , jika ada , hormon hipofisis akan kekurangan pasien dengan hypopituitarism dari penyebab tertentu atau tumor dengan ukuran tertentu. Demikian pula , tidak adanya lesi pada MRI atau CT scan tidak mengecualikan kegagalan hipofisis . Sekresi hormon hipofisis sering dapat dievaluasi secara memadai pada pasien rawat jalan dengan pengukuran konsentrasi hormon serum basal , terutama jika mereka tidak tepat rendah. Sebagian besar gejala dan tanda-tanda kekurangan hormon hipofisis yang mirip dengan yang terjadi pada pasien dengan defisiensi utama dari kelenjar sasaran , kecuali seperti yang tercantum di bawah ini . Gejala-gejala defisiensi corticotropin termasuk kelelahan , lemah, sakit kepala , anoreksia , penurunan berat badan , mual, muntah , sakit perut , dan aktivitas mental. Pemeriksaan fisik adalah penting untuk kurangnya hiperpigmentasi yang terjadi pada pasien dengan insufisiensi adrenal primer . Tekanan darah terlentang biasanya normal , tetapi hipotensi ortostatik dapat terjadi . Wanita dengan insufisiensi adrenal lama sering memiliki hilangnya rambut ketiak dan kemaluan . Hiponatremia dapat terjadi sebagai akibat dari peningkatan sekresi vasopresin , tetapi konsentrasi kalium serum biasanya normal , karena produksi adrenal aldosteron tidak tergantung pada corticotropin . Sebaliknya , baik hiponatremia dan hiperkalemia adalah umum pada pasien dengan insufisiensi adrenal primer . Normokromik , anemia normositik dan eosinofilia juga dapat terjadi dengan kekurangan corticotropin . Gejala defisiensi thyrotropin termasuk kelelahan , kelemahan, ketidakmampuan untuk menurunkan berat badan ( atau berat badan ) , bengkak , sembelit , dan intoleransi dingin. Gangguan memori atau kegiatan mental yang berubah adalah karakteristik dari hipotiroidisme parah. Pemeriksaan fisik mungkin mengungkap bradikardia , bengkak periorbital , dan relaksasi tertunda refleks tendon . Temuan lainnya termasuk hiponatremia ringan dan normokromik , anemia normositik . Hormon luteinizing dan FSH diproduksi oleh jenis sel pituitari yang sama . Pria dengan hipogonadisme mengalami penurunan libido dan disfungsi ereksi mulai dari penurunan ereksi impotensi lengkap, volume ejakulasi mungkin akan menurun dan hot flashes dapat terjadi . Pasangan seksual pasien mungkin menjadi orang yang melaporkan disfungsi seksual . Pemeriksaan fisik biasanya normal jika hipogonadisme yang baru mulai . Wajah dan rambut tubuh berkurang , wajah keriput halus, ginekomastia , dan testis lembut merupakan ciri khas dari lama ( tahun ) hipogonadisme . Wanita usia reproduksi dengan defisiensi gonadotropin memiliki perubahan dalam fungsi menstruasi mulai dari siklus teratur namun anovulasi dengan oligomenore atau amenore . Gejala lain dari kegagalan ovarium meliputi hot flashes , penurunan libido , vagina kering , dan dispareunia . Rambut kemaluan dan ketiak hadir kecuali ada kegagalan adrenal bersamaan .

Wanita postmenopause biasanya hadir dengan gejala kekurangan hormon lain atau lesi massa ( sakit kepala atau kelainan visual) . Gejala dikaitkan dengan kekurangan hormon pertumbuhan pada orang dewasa meliputi kurangnya semangat , penurunan toleransi latihan , dan penurunan functioning42 sosial. Persentase lemak tubuh lebih tinggi pada pertumbuhan dewasa hormon - kekurangan dari pada subjek normal usia cocok ( Thorner MO : komunikasi pribadi ) . Kerutan halus wajah mungkin akibat dari kekurangan hormon pertumbuhan serta dari hipogonadisme . Prolaktin adalah satu-satunya hormon hipofisis yang sekresi tonically dihambat dalam keadaan normal , dopamin adalah hormon penghambat . Hiperprolaktinemia terjadi dengan tumor yang mensekresi prolaktin atau proses yang mengganggu pengangkutan dopamin dari hipotalamus ke hipofisis . Gambaran karakteristik hyperprolactinemia galaktorea , tetapi tidak biasa seperti hipogonadisme - khususnya, amenore . Hiperprolaktinemia akibat penyebab apapun mengganggu sekresi berdenyut normal hormon luteinizing dan FSH5 , 6 . Konsentrasi prolaktin serum yang tinggi adalah penanda yang berguna disfungsi hipotalamus atau hipofisis , bahkan jika konsentrasi tidak cukup meningkat menyebabkan hipogonadisme atau galaktorea . Poliuria dan polidipsia dengan nokturia adalah fitur klasik diabetes insipidus , akibat kekurangan vasopressin ( dari hipofisis posterior ) . Secara karakteristik , air dingin lebih disukai . Jika ekskresi air melebihi asupan , pasien akan menjadi hipovolemik dan hipotensi . Konsentrasi natrium serum dan osmolalitas serum mungkin normal jika asupan cairan memadai atau meningkat jika asupan cairan yang tidak memadai . Defisiensi Oksitosin ( dari hipofisis posterior ) ditandai dengan penurunan ejeksi susu selama menyusui . ENDOKRIN DAN STUDI PENCITRAAN Meskipun basal pengukuran hormon serum mungkin semua yang diperlukan untuk mengkonfirmasi insufisiensi hipofisis , tes dinamis digunakan jika hasil tes hormon serum yang samar-samar atau untuk mendiagnosa kekurangan parsial . Kedua konsentrasi hormon target dan konsentrasi hormon hipofisis harus diukur untuk menilai kelayakan kedua nilai . Penggunaan dan keterbatasan tes endokrin tunggal dan dinamis tercantum dalam Tabel 3 . Penggunaan dan Keterbatasan Pengukuran Hormon tunggal pada pasien dengan penyakit hipofisis Dugaan . andTable 4 . Penggunaan dan Keterbatasan Tes Dinamis pada pasien dengan penyakit hipofisis Diduga . , Masing-masing. Studi endokrin Corticotroph ( kortikotropin ) Defisiensi Sebuah pagi konsentrasi serum kortisol tidak terdeteksi atau subnormal , dalam ketiadaan terapi steroid , menunjukkan insufisiensi adrenal . Terapi glukokortikoid harus dimulai segera, tes dinamis dapat dilakukan nanti jika ada pertanyaan tentang diagnosis . Konsentrasi corticotropin serum yang normal pada pasien yang memiliki kadar kortisol serum rendah menunjukkan kekurangan kortikotropin . Dari beberapa tes dinamis fungsi hipotalamushipofisis - adrenal yang telah dikembangkan , yang paling mudah dan paling umum adalah tes stimulasi kortikotropin . Dalam tes ini , konsentrasi kortisol serum diukur sebelum dan 30 dan 60 menit setelah injeksi intravena tunggal 250 ug corticotropin . Jika corticotropin dan sekresi

adrenal normal , konsentrasi kortisol serum harus meningkat menjadi 20 mg per desiliter ( 552 nmol per liter ) atau higher43 . Pada pasien dengan defisiensi corticotropin parah selama lebih dari beberapa minggu , respon kortisol serum akan lebih rendah , atau bahkan tidak ada , sebagai akibat dari atrofi adrenal yang terjadi tanpa adanya sekresi kortikotropin . Tes ini tidak menilai apakah sekresi kortikotropin dapat meningkatkan , dan beberapa pasien memiliki respon kortisol serum yang normal meskipun kekurangan kortikotropin , seperti yang ditunjukkan oleh kurangnya serum corticotropin dan tanggapan kortisol terhadap insulin induced hypoglycemia ( meskipun respon kortisol serum eksogen corticotropin adalah normal ) . Temuan ini terjadi pada pasien dengan gagal hipofisis yang baru mulai di antaranya telah ada waktu yang cukup untuk atrofi adrenal untuk mengembangkan dan pada pasien dengan defisiensi parsial corticotropin . Tes fungsi seluruh sumbu termasuk insulin -induced hipoglikemia dan uji metyrapone . Insulin -induced hipoglikemia meningkatkan sekresi CRH langsung , sehingga meningkatkan serum kortikotropin ( dan hormon pertumbuhan ) dan konsentrasi kortisol . Glukosa serum dan kortisol ( hormon pertumbuhan dan ) diukur sebelum dan 30 , 60 , dan 90 menit setelah pemberian intravena 0,15 U insulin reguler per kilogram berat badan . Konsentrasi glukosa serum harus menurun menjadi kurang dari 50 persen dari nilai dasar - line atau kurang dari 40 mg per desiliter ( 2,2 mmol per liter ) untuk stimulasi hipotalamus-hipofisis yang memadai . Karena risiko yang terkait dengan hipoglikemia , tes ini harus dilakukan di bawah pengawasan dokter . Jika pagi konsentrasi serum kortisol kurang dari 5 mg per desiliter ( 138 nmol per liter ) , respon normal sangat tidak mungkin dan tes ini mungkin tidak diperlukan . Kontraindikasi untuk tes ini termasuk riwayat gangguan kejang , angina , status mental berubah , dan kelemahan umum . Konsentrasi serum kortisol harus meningkat menjadi 20 mg per desiliter ( 552 nmol per liter ) atau lebih tinggi ( respon hormon pertumbuhan serum normal adalah peningkatan menjadi 10 ng per mililiter atau lebih tinggi ) . Metyrapone menghambat sintesis kortisol , yang menyebabkan peningkatan sekresi kortikotropin dan karena dari 11 - deoxycortisol . Pengujian ini dilakukan dengan pemberian dosis satu atau beberapa metyrapone dan mengukur konsentrasi 11 - deoxycortisol serum beberapa jam kemudian , pada subjek normal konsentrasi kenaikan , sedangkan pada pasien dengan defisiensi corticotropin mereka tidak naik. Sebuah tes baru dikembangkan fungsi hipofisis-adrenal adalah stimulasi kortikotropin dan sekresi kortisol dengan CRH . CRH saat ini tersedia hanya sebagai obat percobaan , dan karena tes telah dilakukan hanya dalam sejumlah kecil pasien dengan penyakit hipofisis , perannya adalah uncertain44 , 45 . Dalam sebuah penelitian terhadap pasien yang menerima terapi steroid , hasil tes dengan CRH dan insulin -induced hipoglikemia adalah comparable46 . Thyrotroph ( Thyrotropin ) Defisiensi Kedua thyrotropin serum dan konsentrasi tiroksin harus diukur pada pasien dengan dugaan hipotalamus atau penyakit hipofisis . Pasien dengan hipotiroidisme sekunder biasanya memiliki konsentrasi serum thyrotropin normal atau rendah , baik dari yang pantas jika konsentrasi tiroksin serum rendah . Kadang-kadang, bagaimanapun, pasien memiliki konsentrasi serum thyrotropin karena penyakit hipofisis hipotalamus atau telah menghasilkan sekresi thyrotropin yang memiliki aktivitas biologis berkurang tetapi mempertahankan aktivitas imunologi .

Kegagalan konsentrasi serum Thyrotropin meningkat setelah pemberian thyrotropin - releasing hormone menegaskan hipotiroidisme sekunder tetapi tidak diperlukan untuk membuat diagnosis . Gonadotroph ( Luteinizing Hormone dan FSH ) Defisiensi Tes terbaik defisiensi gonadotroph pada wanita premenopause adalah riwayat menstruasi , karena menstruasi teratur menunjukkan setidaknya beberapa fungsi gonadotroph . Karena hormon luteinizing dan FSH disekresikan secara berdenyut , pengukuran tunggal mungkin dalam batas normal bahkan pada wanita yang memiliki amenore , tetapi bahkan nilai normal yang tidak pantas pada wanita dengan amenore . Konsentrasi serum estradiol , yang mungkin normal atau rendah pada wanita dengan defisiensi gonadotropin , memberikan sedikit informasi melebihi apa yang dapat diperoleh dari riwayat menstruasi . Pria dengan kegagalan gonad mungkin memiliki luteinizing hormone serum normal atau rendah dan konsentrasi FSH , tetapi nilai normal tidak sesuai jika konsentrasi serum testosteron menurun . Somatotroph ( Growth Hormone ) Defisiensi Sebuah pengukuran tunggal hormon pertumbuhan serum jarang berguna, karena konsentrasi serum biasanya rendah sebagian besar hari dan hormon pertumbuhan juga disekresikan secara berdenyut . Sebuah tes stimulasi ( Tabel 4 ) Oleh karena itu diperlukan untuk menilai cadangan somatotroph . Pengukuran serum insulin - like growth factor I , yang tergantung pada hormon pertumbuhan , mungkin menunjukkan kekurangan hormon , jika pasien tidak kekurangan gizi , sakit kronis , atau tua , yang semuanya menurunkan produksi faktor pertumbuhan insulin-seperti I. Lactotroph ( Prolaktin ) Defisiensi Konsentrasi serum prolaktin jarang rendah dan dapat ditingkatkan pada pasien dengan penyakit hipotalamus-hipofisis hampir setiap penyebab . Serum prolaktin harus selalu diukur , karena dapat memberikan informasi tentang lokasi dari gangguan yang menyebabkan hypopituitarism , serta penyebab hipogonadisme . Pengujian dinamis dari cadangan lactotroph dengan hormon thyrotropin -pelepas tidak berguna , karena tidak membedakan antara berbagai penyebab hiperprolaktinemia . pencitraan Setelah diagnosis klinis dan biokimia hypopituitarism telah dibuat , sebuah studi pencitraan daerah hipotalamus - hipofisis harus dilakukan untuk menentukan apakah massa hadir . Citra yang paling informatif adalah MRI scan dengan gadolinium intravena . MRI lebih unggul CT karena Chiasm optik , tangkai hipofisis , dan sinus kavernosa - yang semuanya dapat dipengaruhi oleh massa hipotalamus atau hipofisis - biasanya bisa dilihat pada scan MRI ( Gambar 2 Scan MRI dan Gambar dari . memindai dari Gland normal hipofisis ( Panel A ) dan macroadenoma hipofisis Itu Menghasilkan Panhypopituitarism ( Panel B ) . ) . Jika tidak mungkin untuk mendapatkan scan MRI karena claustrophobia atau logam besi dalam tubuh , CT scan resolusi tinggi dengan pemberian kontras merupakan alternatif yang memadai . Jika memungkinkan, CT scan harus diperoleh pada bidang koronal dengan bagian tipis ( 1,5 mm ) melalui fossa hipofisis . Jika pasien tidak dapat hyperextend leher nya , bagian aksial dengan rekonstruksi sagital akan memberikan visualisasi yang memadai dari hipofisis . Meskipun MRI

scan lebih mahal daripada CT scan ( sekitar $ 300 lebih di University of Virginia ) , informasi anatomi tambahan yang disediakan oleh scan MRI adalah senilai biaya yang lebih tinggi . Skull and film x - ray sellar tidak memiliki peran dalam evaluasi pasien dengan massa hipotalamus atau hipofisis mungkin, karena tumor dapat memperpanjang superior atau lateral tanpa memperbesar sella tersebut . Jika seorang pasien menjalani operasi , scan kedua harus memperoleh dua sampai tiga bulan kemudian untuk menilai jumlah jaringan hipofisis atau tumor sisa . Ini interval antara operasi dan evaluasi selanjutnya diperlukan untuk memungkinkan resolusi edema pasca operasi dan peradangan, yang membuat tidak mungkin untuk menentukan jumlah sisa tumor segera setelah operasi . KESIMPULAN Hypopituitarism dapat disembuhkan, dan pasien dengan kondisi ini harus mampu melakukan kegiatan normal selama terapi hormonal yang sesuai digunakan secara konsisten dan benar. Setelah penggantian rejimen yang tepat telah ditentukan, dosis biasanya tidak perlu diubah kecuali untuk peningkatan dosis glukokortikoid (yang umumnya dua kali lipat) selama kambuhan sakit. Bahkan setelah rejimen yang tepat telah ditetapkan, namun, pasien dengan hypopituitarism membutuhkan seumur hidup medis tindak lanjut