Porth's Essentials of Pathophysiology, 4e

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Endocrine System

U N I T 9

Other tests include measurement of the plasma lev- els of ACTH. 39,40,47,48 Adrenocorticotropic hormone lev- els should be normal or elevated in ACTH-dependent Cushing syndrome (Cushing disease and ectopic ACTH), and low in non–ACTH-dependent Cushing syndrome (adrenal tumors). Various suppression or stimulation tests of the HPA system are performed to delineate the cause further. MRI or CT scans afford a means for locat- ing adrenal or pituitary tumors. Untreated, Cushing syndrome produces serious mor- bidity and even death. The choice of surgery, irradiation, or pharmacologic treatment is determined largely by the cause of the hypercortisolism. The goal of treatment for Cushing syndrome is to remove or correct the source of hypercortisolism without causing permanent pituitary or adrenal damage. 40,48 Transsphenoidal removal of a pitu- itary adenoma or a hemihypophysectomy is the preferred method of treatment for Cushing disease. This allows removal of only the tumor rather than the entire pituitary gland. After successful removal, the person must receive cortisol replacement therapy for 6 to 12 months or until adrenal function returns. Pituitary radiation therapy may also be used, but the full effects of treatment may not be realized for 3 to 12 months. Unilateral or bilateral adre- nalectomy may be done in the case of adrenal adenoma. When possible, ectopic ACTH-producing tumors are removed. Pharmacologic agents that block steroid syn- thesis (i.e., mitotane, ketoconazole, and metyrapone) may be used to treat persons with ectopic tumors or adre- nal carcinomas that cannot be resected. 39,40 Many of these patients also require Pneumocystis jiroveci (formerly known as Pneumocystis carinii ) pneumonia prophylaxis because of the profound immunosuppression caused by the excessive glucocorticoid levels. Incidental Adrenal Mass An incidentaloma is a mass lesion found unexpectedly in an adrenal gland by an imaging procedure (done for other reasons), most commonly CT (but also MRI and ultrasonography). 49 It has been increasingly recognized since the early 1980s. 50 The prevalence of adrenal inci- dentalomas at autopsy is approximately 10 to 100 per 1000. In CT series, 0.6% to 4.4% are the usual figures published. Incidentalomas also can occur in other organs (e.g., pituitary, thyroid). The two most important ques- tions are (1) is the mass malignant, and (2) is the mass hormonally active (i.e., is it functioning)? Primary adrenal carcinoma is quite rare, but other cancers, particularly lung cancers, commonly metasta- size to the adrenal gland (other cancers include breast, stomach, pancreas, colon, kidney, melanomas, and lymphomas). The size and imaging characteristics of the mass may help determine whether the tumor is benign or malignant. The risk of cancer is high in adre- nal masses larger than 6 cm. Many experts recommend surgical removal of masses larger than 4 cm, particu- larly in younger patients. 49,50 Appropriate screening to exclude a hormonally active lesion includes tests to rule out pheochromocytoma, Cushing syndrome, and Conn syndrome (mineralocorticoid excess).

SUMMARY CONCEPTS

■■ The adrenal cortex produces three types of hormones: mineralocorticoids, glucocorticoids, and adrenal androgens.The mineralocorticoids, along with the renin–angiotensin mechanism, aid in controlling body levels of sodium and potassium.The glucocorticoids have anti- inflammatory actions and aid in regulating glucose, protein, and fat metabolism during periods of stress.The adrenal androgens exert little effect on daily control of body function, but they probably contribute to the development of body hair in women. Disorders of the adrenal cortex include those that produce adrenocortical hormone insufficiency or excess. ■■ Congenital adrenal hyperplasia describes a genetic defect in the cortisol pathway resulting from a deficiency of one of the enzymes needed for its synthesis. Depending on the enzyme involved, the disorder causes virilization of female infants and, in some instances, fluid and electrolyte disturbances because of impaired mineralocorticoid synthesis. ■■ Primary adrenal cortical insufficiency, which can be caused by destruction of the adrenal gland (Addison disease) or by dysfunction of the HPA system, is manifested by signs of a mineralocorticoid deficiency (impaired ability to regulate salt and water elimination) and a glucocorticoid deficiency (impaired ability to regulate blood glucose and control the effects of the immune and inflammatory responses). Adrenal insufficiency requires replacement therapy with adrenal cortical hormones. Acute adrenal insufficiency is a life-threatening situation. ■■ Adrenal corticosteroid excess, or Cushing syndrome, results in derangements in glucose metabolism, disorders of sodium and potassium regulation (increased sodium retention and potassium loss), impaired ability to respond to stress because of inhibition of inflammatory and immune responses, and signs of increased androgen levels such as hirsutism.This syndrome may result from pharmacologic doses of glucocorticoids, a pituitary or adrenal tumor, or an ectopic tumor that produces ACTH. ■■ An incidentaloma is a mass lesion found unexpectedly in an adrenal gland (and other glands) by an imaging procedure done for other reasons. Incidentalomas are being recognized with increasing frequency, emphasizing the need for correct diagnosis and treatment.