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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-

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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)

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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)

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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.

Levothyroxine is given to correct hypothyroidism only after the patient is assessed for cortisol deficiency or is already receiving corticosteroids (See Hypothyroidism) The typical maintenance dose is about 16 mcg/kg body weight However, dosage requirements vary widely, averaging 0125 mg daily with a range of 0025 03 mg daily The optimal replacement dose of thyroxine for each patient must be carefully assessed clinically on an individual basis Serum free thyroxine (FT4) levels usually need to be in the high-normal range for adequate replacement Assessment of serum TSH is useless for monitoring patients, since levels are always low with TSH deficiency

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