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Patients with Cushing s syndrome from a benign adrenal adenoma experience a 5-year survival of 95% and a 10-year survival of 90%, following a successful adrenalectomy Patients with Cushing s disease from a pituitary adenoma experience a similar survival if their pituitary surgery is successful However, transsphenoidal surgery incurs a failure rate of about 10 20%, often due to the adenoma s ectopic position or invasion of the cavernous sinus Those patients who have a complete remission after transsphenoidal surgery have about a 15 20% chance of recurrence over the next 10 years Patients with failed pituitary surgery may require pituitary radiation therapy, which has its own morbidity Bilateral adrenalectomy is often complicated by infection; recurrence of hypercortisolism may occur as a result of growth of an adrenal remnant stimulated by high levels of ACTH The prognosis for patients with ectopic ACTH-producing tumors depends on the aggressiveness and stage of the particular tumor Patients with ACTH of unknown source have a 5-year survival rate of 65% and a 10-year survival rate of 55% Patients with adrenal carcinoma have a median survival of 7 months
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Findling JW et al Cushing s Syndrome: important issues in diagnosis and management J Clin Endocrinol Metab 2006 Oct;91(10):3746 53 [PMID: 16868050] Ilias I et al Cushing s syndrome due to ectopic corticotropin secretion: twenty years experience at the National Institutes of Health J Clin Endocrinol Metab 2005 Aug;90(8):4955 62 [PMID: 15914534]
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Cushing s syndrome, if untreated, produces serious morbidity and even death The patient may suffer from any of the complications of hypertension or of diabetes Susceptibility to infections is increased Compression fractures of the osteoporotic spine and aseptic necrosis of the femoral head may cause marked disability Nephrolithiasis and psychosis may occur Following bilateral adrenalectomy for Cushing s disease, a pituitary adenoma may enlarge progressively, causing local destruction (eg, visual field impairment) and hyperpigmentation; this complication is known as Nelson s syndrome
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Cushing s disease is best treated by transsphenoidal selective resection of the pituitary adenoma After pituitary surgery, the rest of the pituitary usually returns to normal function; however, the pituitary corticotrophs remain suppressed and
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the presence of ovarian cysts is not helpful diagnostically, since about 30% of women with PCOS do not have cystic ovaries and 25 30% of normal menstruating women have cystic ovaries Obesity and high serum insulin levels (due to insulin resistance) contribute to the syndrome in 70% of women The serum LH:FSH ratio is often greater than 20 Both adrenal and ovarian androgen hypersecretion are commonly present Women with PCOS have a 35% risk of depression, compared with 107% in age-matched controls Diabetes mellitus is present in about 13% of cases Untreated women with amenorrhea have a slightly increased risk of endometrial carcinoma Hypertension and hyperlipidemia are often present, increasing the risk of cardiovascular disease Women frequently regain normal menstrual cycles with aging
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Viardot A et al Reproducibility of nighttime salivary cortisol and its use in the diagnosis of hypercortisolism compared with urinary free cortisol and overnight dexamethasone suppression test J Clin Endocrinol Metab 2005 Oct;90(10): 5730 6 [PMID: 16014408]
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HIRSUTISM & VIRILIZATION
ESSENTIALS OF DIAGNOSIS
Hirsutism, acne, menstrual disorders Virilization: increased muscularity, androgenic alopecia, deepening of the voice, clitoromegaly Rarely, a palpable pelvic tumor Urinary 17-ketosteroids and serum DHEAS and androstenedione elevated in adrenal disorders; variable in others Serum testosterone is often elevated
C Steroidogenic Enzyme Defects
Baby girls with classic 21-hydroxylase deficiency have ambiguous genitalia and may become virilized unless treated with corticosteroid replacement; about 50% of such patients have clinically evident mineralocorticoid deficiency (saltwasting) as well About 2% of patients with adult-onset hirsutism have been found to have a partial defect in adrenal 21-hydroxylase, whose phenotypic expression is delayed until adolescence or adulthood; such patients do not have salt-wasting Polycystic ovaries and adrenal adenomas are more likely to develop in these women Some rare patients with hyperandrogenism and hypertension have 11-hydroxylase deficiency This is distinguished from cortisol resistance by high cortisol serum levels in the latter and by high serum 11-deoxycortisol levels in the former Patients with an XY karyotype and a deficiency in 17 hydroxysteroid dehydrogenase-3 or a deficiency in 5 -reductase-2 may present as phenotypic girls in whom virilization develops at puberty
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