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CMDT 2008
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ops in patients receiving high-dose methadone or chronic intrathecal infusion of opioids; both GH deficiency and secondary adrenal insufficiency occur in 15% of such patients Secondary adrenal insufficiency may persist for many months following high-dose corticosteroid therapy Severe illness causes functional suppression of TSH and T4 Hyperthyroxinemia reversibly suppresses TSH Administration of triiodothyronine (Cytomel) suppresses TSH and T4 Bexarotene, used to treat cutaneous T cell lymphoma, suppresses TSH secretion, resulting in temporary central hypothyroidism Corticosteroids or megestrol treatment reversibly suppresses endogenous ACTH and cortisol secretion
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Patients with destructive lesions (eg, tumors) may develop complications related to them or to surgery or radiation therapy Among patients with craniopharyngiomas, diabetes insipidus is found in 16% preoperatively and in 60% postoperatively Hyponatremia often presents abruptly during the first 2 weeks following pituitary surgery Visual field impairment may occur Hypothalamic damage may result in morbid obesity as well as cognitive and emotional problems Conventional radiation therapy results in an increased incidence of small vessel ischemic strokes and second tumors Patients with untreated hypoadrenalism and a stressful illness may become febrile and die in shock and coma Adults with GH deficiency have experienced an increased cardiovascular morbidity Rarely, acute hemorrhage may occur in large pituitary tumors, manifested by rapid loss of vision, headache, and evidence of acute pituitary failure (pituitary apoplexy) requiring emergency decompression of the sella
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Transsphenoidal removal of pituitary tumors will sometimes reverse hypopituitarism Postoperative hyponatremia often occurs; serum sodium must be checked frequently for 2 weeks after pituitary surgery Hypogonadism due to PRL excess usually resolves during treatment with dopamine agonists Endocrine substitution therapy must be given before, during, and, often, permanently after such procedures GH-secreting tumors may respond to octreotide (see section on acromegaly) Radiation therapy with x-ray, gamma knife, or heavy particles may be necessary but increases the likelihood of hypopituitarism The mainstay of substitution therapy for pituitary insufficiency remains lifetime hormone replacement
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MRI provides the best visualization of pituitary tumors Thickening of the pituitary stalk can also be caused by sarcoidosis or hypophysitis
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Reversible hypogonadotropic hypogonadism may occur with serious illness, malnutrition, or anorexia nervosa The clinical situation and the presence of normal adrenal and thyroid function allow ready distinction from hypopituitarism Profound hypogonadotropic hypogonadism develops in men who receive gonadotropin-releasing hormone (GnRH) therapy for prostate cancer; it usually persists following cessation of therapy Hypogonadotropic hypogonadism usually devel-
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A Corticosteroids
Hydrocortisone tablets, 15 30 mg/d orally in divided doses, should be given Most patients do well with 15 mg in the morning and 5 10 mg in the late afternoon Patients with partial ACTH deficiency (basal morning serum cortisol above 8 mg/dL [220 mmol/L]) require hydrocortisone replacement in lower doses of about 5 mg orally twice daily Some patients feel better taking prednisone, 3 75 mg/d orally A mineralocorticoid is rarely needed To determine the optimal cortico-
CMDT 2008
persistent treatment and the help of intracytoplasmic sperm injection for some cases, the total pregnancy success rate is about 70% Clomiphene, 25 50 mg orally daily, can sometimes stimulate a man s own pituitary gonadotropins (when his pituitary is intact), thereby increasing testosterone and sperm production For fertility induction in females, ovulation may be induced with clomiphene, 50 mg daily for 5 days every 2 months Follitropins and hCG can induce multiple births and should be used only by those experienced with their administration (See Hypogonadism and 17)
steroid replacement dosage, it is necessary to monitor patients carefully for manifestations of overreplacement (Cushing s syndrome) or underreplacement A serum white blood cell count (WBC) with a relative differential can be useful, since a relative neutrophilia and lymphopenia can indicate overreplacement with corticosteroid, and vice versa Additional corticosteroids must be given during states of stress, eg, during infection, trauma, or surgical procedures For mild illness, corticosteroid doses are doubled or tripled For trauma or surgical stress, hydrocortisone is given in doses of 50 mg intramuscularly or intravenously every 6 hours and then reduced to normal doses as the stress subsides Patients with adrenal insufficiency are advised to wear a medical alert bracelet describing their condition and treatment Patients with secondary adrenal insufficiency due to treatment with corticosteroids at supraphysiologic doses require their usual daily dose of corticosteroid during surgery and acute illness; supplemental hydrocortisone is not usually required
D Human Growth Hormone (hGH)
Recombinant human growth hormone (rhGH) has been synthesized as a 191-amino acid sequence (somatropin) identical to hGH; an rhGH of 192 amino acids (somatrem) is also available and is of equal potency Symptomatic adults with severe GH deficiency (serum IGF-I below 85 mcg/L) may be treated with a subcutaneous rhGH injection starting at a dosage of about 02 mg (06 IU)/day, administered three or four times weekly The dosage of rhGH is increased every 2 4 weeks by increments of 01 mg (03 IU) until side effects occur or a sufficient salutary response and a normal serum IGF-I level are achieved A sustained-release injectable suspension of GH is available (somatropin depot) It can be given once monthly and is therefore more convenient than standard rhGH preparations; however, its safety and dosing in adults remain to be established If the desired effects (eg, improved energy and mentation, reduction in visceral adiposity) are not seen within 3 6 months at maximum tolerated dosage, rhGH therapy is discontinued During pregnancy, rhGH may be safely administered to women with hypopituitarism at their usual pregestational dose during the first trimester, tapering the dose during the second trimester, and discontinuing rhGH during the third trimester Oral estrogen replacement reduces hepatic IGF-I production Therefore, prior to commencing rhGH therapy, oral estrogen is changed to a transdermal or transvaginal estradiol Side effects of rhGH therapy may include peripheral edema, hand stiffness, arthralgias, myalgias, headache, pseudotumor cerebri, gynecomastia, carpal tunnel syndrome, tarsal tunnel syndrome, hypertension, and proliferative retinopathy Side effects are more common in older patients, those with greater weight and higher BMI, and those with adult-onset GH deficiency Such symptoms usually remit promptly after a sufficient reduction in dosage Excessive doses of rhGH could cause acromegaly; patients receiving long-term therapy require careful clinical monitoring Serum IGF-I levels should be kept in the normal range and periodic determinations of serum IGF-I levels are helpful in guiding therapeutic dosing GH should not be administered during critical illness since, in one study, administration of very high doses of rhGH to patients in an intensive care unit was shown to increase overall mortality There is no role for GH replacement in the somatopause of aging Patients with resistance to GH have severe short stature and IGF-I deficiency IGF-I (mecasermin) is available to treat such patients
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