endocrine and metabolic disorders
Cushing Syndrome
Treatment of Cushing Syndrome
High protein intake, and potassium administration (or potassium-sparing drugs such asspironolactone) Adrenal inhibitors such asmetyraponeorketoconazoleand rarelymitotane, or newer drugs such asosilodrostatandlevoketoconazole Surgery or radiation therapy to remove pituitary, adrenal, or ectopic ACTH-producing tumors Sometimes somatostatin analogs ordopamineagonists to block ACTH secretion, or the glucocorticoid receptor antagonistmifepristone Initially, the patient’s general condition should be supported by high protein intake and appropriate administration of potassium. If clinical manifestations of hypercortisolism are severe, it may be reasonable to block corticosteroid secretion withmetyrapone250 mg to 1 g orally 3 times a day orketoconazole400 mg orally once a day, increasing to a maximum of 400 mg 3 times a day.Ketoconazoleis probably slower in onset and sometimes hepatotoxic. Alternatives includemitotaneand the newer drugslevoketoconazoleandosilodrostat, which block steroidogenesis, ormifepristonewhich is a receptor antagonist. Parenteraletomidate(an intravenous anesthetic that also blocks cortisol production) may be life-saving for patients with fulminant symptoms; it is given as an intravenous infusion: the starting dose is usually 1 to 2 mg/hour, increasing as necessary, with frequent assessments of cortisol levels and the dose titrated accordingly. Pituitary tumors that produce excessive ACTH are removed surgically or extirpated with radiation therapy. If no tumor is shown on imaging but a pituitary source is likely, total hypophysectomy may be attempted, particularly in older patients. Younger patients may receive supervoltage irradiation of the pituitary, delivering 45 Gy (Gray). However, in children, irradiation may reduce secretion of growth hormone and occasionally cause precocious puberty. In special centers, a focused beam of radiation therapy may be given as a single dose (radiosurgery). Alternatively, proton beam therapy can be used if available. Response to irradiation occasionally requires several years, but response is more rapid in children. Studies suggest that mild cases of persistent or recurrent disease may benefit from drugs that suppress ACTH secretion, including the somatostatin analogpasireotideand thedopamineagonistcabergoline. However, hyperglycemia is a significant adverse effect ofpasireotide. Alternatively, the corticosteroid receptors can be blocked withmifepristone. The glucocorticoid receptor antagonistmifepristoneincreases serum cortisol but blocks the effects of the corticosteroid and may cause hypokalemia. Bilateral adrenalectomy is reserved for patients with pituitary hyperadrenocorticism who do not respond to both pituitary exploration (with possible adenomectomy) and irradiation, or in patients in whom surgery was unsuccessful and radiotherapy is contraindicated. Adrenalectomy requires life-long corticosteroid replacement. Adrenocortical tumors are removed surgically. Patients must receive cortisol during the surgical and postoperative periods because their nontumorous adrenal cortex will be atrophic and suppressed. Benign adenomas can be removed laparoscopically. With multinodular adrenal hyperplasia, bilateral adrenalectomy may be necessary. Even after a presumed total adrenalectomy, functional regrowth occurs in a few patients. 0.5 g orally once a day, increasing to a maximum of 3 to 4 g a day, usually control severe metabolic disturbances (eg, Hypokalemia ). When Sometimes ectopic ACTH-secreting tumors respond to long-acting somatostatin analogs (eg,octreotideand/or others), although administration for>2 years requires close follow-up because mild gastritis, gallstones, cholangitis, and malabsorption may develop. Nelson syndrome occurs when the pituitary gland continues to expand after bilateral adrenalectomy, causing a marked increase in the secretion of ACTH and its precursors and resulting in severe hyperpigmentation. It occurs in about 20 to 25% of patients who undergo adrenalectomy. The risk is probably reduced if the patient undergoes prophylactic pituitary radiation therapy at the time of adrenalectomy. Although irradiation may arrest continued pituitary growth, many patients also require hypophysectomy. The indications for hypophysectomy are the same as for any pituitary tumor: an increase in size such that the tumor encroaches on surrounding structures, causing visual field defects, pressure on the hypothalamus, or other complications. Radiation therapy may be given, e if it was not given at the time of bilateral adrenalectomy. Radiosurgery, or focused radiation therapy, can be given in a single fraction when standard external beam radiation therapy has already been done, as long as the lesion is at a reasonable distance from the optic nerve and chiasm. 