Midnight serum cortisol level 100 77 Used mainly for inpatients with special precautions
Low-dose dexamethasone suppression test 100 90 Used mainly for equivocal cases
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mediastinum, and abdomen with gadolinium; ultrasonography of the neck; and octreotide body scan. About 80% of the carcinoid tumors that cause ectopic ACTH syndrome are found above the diaphragm.12,23
When an imaging study localized a presumed tumor, fine-needle aspiration cytology with immuno-assay of ACTH may confirm the diagnosis.17
Treatment. Optimal treatment involves resection or complete destruction of the ACTH-secreting tumor. However, most carcinoid tumors that cause ectopic ACTH syndrome remain occult even after multiple imaging studies,66,67 so medical or surgical adrenalectomy is usually required to control hyper-cortisolism. The longer the expected survival, the more important it is to control hypercortisolism. Bilateral adrenalectomy is superior to medical therapy in controlling hypercortisolism caused by disseminated cancer or occult ACTH-secreting tumors.68 Severe ectopic Cushing's syndrome is associated with poor prognosis over and above that attributable to the tumor itself.
ACTH-Independent Causes of Cushing's Syndrome
About 25% of patients with Cushing's syndrome have adrenal tumors.
About 10 to 15% of patients with Cushing's syndrome have an autonomously functioning benign adrenal adenoma. These adenomas are usually less than 5 cm in diameter (Figure 11-4). Adrenalectomy is curative, and the prognosis is excellent.21 Postop-eratively, glucocorticoid should be replaced until complete recovery of the hypothalamus-pituitary-adrenal axis, which usually takes several months but may take as long as 2 years. Mineralocorticoid replacement is rarely needed after unilateral adrena-lectomy because the secretion of mineralocorticoid does not depend on the recovery of the pituitary ACTH secretion, and hydrocortisone has some min-eralocorticoid effects.
Adrenocortical carcinoma causes 5 to 10% of Cushing's syndrome (or 40% of ACTH-indepen-dent Cushing's patients, owing to primary adrenal pathology). Adrenocortical carcinoma is rare, with a bimodal age distribution with an initial peak before age 5 years and the second peak at the fourth and fifth decades.69-71 It occurs rarely as part of multiple endocrine neoplasia type I (parathyroid, pancreatic islet cell, and pituitary neoplasms).72 It also may occur as part of Li-Frau-meni syndrome (germline mutation of P53).8 Adrenocortical carcinomas are usually larger than 6 cm in diameter and weigh 100 to 5,000 g.17,73-75 Virilization can occur because of the relatively inefficient cortisol synthesis, resulting in overproduction of androgenic precursors.76 The only reli-
able criteria to differentiate adrenocortical carcinoma from adrenocortical adenoma are nodal or distant metastasis and direct invasion into the adjacent tissues. Carcinomas also tend to be larger and have more mitoses. The mainstay of treatment is an initial complete resection.77-79 The prognosis of patients with adrenocortical carcinomas is generally poor. The overall mean survival is 18 months, but for untreated patients, it is only 3 months.80 Tumor stage and completeness of resection are the most important prognostic factors.80-82 It is controversial whether mitotane therapy improves long-term survival.83-85 Similar to other hormone-secreting tumors, debulking may be attempted even if complete resection cannot be achieved to minimize the complications caused by hypercortisolism. Prolonged remission has been reported after resection of metastasis or regional recurrences.86-88
Primary adrenocortical hyperplasia causes 5% of Cushing's syndrome. In contrast to patients with adrenocortical hyperplasia secondary to ACTH secretion by a pituitary tumor or ectopic source, these patients almost always have a very low level of or undetectable plasma ACTH.
Primary adrenocortical hyperplasia may be macronodular or micronodular.
1. The adrenal glands in patients with bilateral macronodular adrenal hyperplasia are very large, with multiple nodules. In contrast, patients with micronodular primary adrenal hyperplasia may have normal or slightly abnormal adrenal glands on CT and MRI.89-91
2. Primary pigmented micronodular hyperplasia occurs mainly in children and may have a familial pattern. It may be attributable to a circulating immunoglobulin that stimulates the adrenal gland. Half of these occur as an autosomal dominant disorder known as Carney's complex that is associated with atrial myxoma, blue nevi, and schwannomas.92-95
3. Rare patients may have adrenocortical hyperpla-sia owing to an abnormal or ectopic expression of receptors for various hormones, such as gastric inhibitory polypeptide or P-adrenergic receptors.96-98
Bilateral adrenalectomy is required for the treatment of primary adrenocortical hyperplasia.
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