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Carcinoma Of The Adrenal Cortex, Iatrogenic Cushing’s Syndrome And Ectopic ACTH Secretion

Updated on February 11, 2014

The Adrenal Gland

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A General Overview

Carcinoma of the Adrenal cortex, Iatrogenic Cushing’s syndrome and ectopic adrenocorticotropic hormone secretion are major pathologies affecting the adrenal gland.

Carcinoma Of The Adrenal Cortex

These tumours are rapidly progressive with local invasion and distant metastases early in their course. Some tumours do not produce hormones whereas others produce both cortisol and sex hormones. Over 80% of estrogen producing tumours are malignant.

Iatrogenic Cushing’s Syndrome

This may occur at all ages in both sexes but it is more prominent in young adults. Daily administration of 10mg or more prednisolone or its equivalent can give rise to Cushing’s syndrome. The full-fledged case resembles classical Cushing’s syndrome. The clinical features are variable in many cases. Regression of symptoms occurs within months of withdrawal of the drug, but established diabetes may not clear up.

Ectopic ACTH Secretion

Carcinomas of the bronchus, neural tissue, ovaries and gastrointestinal tract may give rise to ACTH-like substances. This syndrome is seen more in older age groups. It is characterized by rapidly developing pigmentation, hypokalemia and marked alkalosis. In many, the complete picture of Cushing’s syndrome may not develop. Clinical features produced by the primary lesion may be evident. In any case of Cushing’s syndrome, the presence of digital clubbing and osteoarthropathy should suggest pulmonary malignancy as the underlying causes.

Cushings Hirsuitism

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Diagnosis And Prognosis

Clinical diagnosis is easy in florid cases. It has to be supported by biochemical investigations. Cushing’s syndrome has to be differentiated from simple obesity, hirsuitism, functional ovarian tumours, diabetes mellitus, and hypertension. In borderline cases, continued observation and repitation of tests may be required before the diagnosis is established.

Etiology is suggested by the following tests. Failure of dexamethasone to suppress cortisol production should suggest the possibility of adrenal tumours or ectopic ACTH production. Positive response to ACTH infusion suggests benign hyperplasia, whereas failure of stimulation is suggestive of tumours. The secretion of cortisol can be estimated isotopically. The normal range is 250- 840 mol in 24 hours. Serum hormone levels and urinary metabolites can be estimated. Raised levels of ACTH are suggestive of pituitary adenomas or ectopic foci.

The ACTH levels are low in adrenal tumours. Marked increase of urinary 17-KS is suggestive of adrenal carcinomas.

The site of tumour or hyperplasia is identified by radiological studies, CT scan, ultrasonography and estimation of cortisol levels in the adrenal veins.

Course and prognosis

Cushing’s syndrome due to primary adrenal disease or pituitary lesions is fatal if left untreated, though rarely spontaneous remissions may occur. Death is due to diabetic complications, hypertension, hypokalemia, infections or the effect of the underlying neoplasm.

Treatment Of Adrenal Disorders

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Treatment

Surgical removal of the adrenal tumour is the treatment of choice. Since the normal portions of the glands may be atrophic, substitution therapy is needed in the post-operative period to prevent adrenal crisis. A course of ACTH helps in stimulating the residual tissue to activity. Cushing’s syndrome due to pituitary adenoma resolves after surgical removal of the microadenomas. An alternative is to do bilateral adrenalectomy and lifelong hormone replacement.

Medical management: Symptomatic management of diabetes, hypertension and electrolyte disturbances is indicated as the conditions warrant.

Specific Drugs: Metyrapone in a dose of 250- 750 mg thrice daily blocks the synthesis of cortisol and abolishes the effects of hypercortisolism. Medical therapy is indicated if the primary cause is not correctable surgically. Aminoglutethimide and O-P’DDD are the drugs which block the synthesis of cortisol. Aminoglutethimide given orally in a total daily dose of 0.75g daily, blocks the synthesis of aldosterone, cortisol and other adrenal hormones. It may cause side effects such as ataxia, rashes, fever and drowsiness.

O,P’DDD [2,2-bis-(2-chlorophenyl-4 chlorophenyl-1, 1-dichloroethane)] given orally in divided doses to a total of 10-15 g/day causes atrophy and necrosis of the adrenal cortex and adrenal metastases. This drug may prolong life by a few months to years.

Irradiation: Pituitary tumour may respond to local irradiation with 4,500- 5,000 rads using a cobalt-60 source or 90Yttrium implantation. Cushing’s syndrome seen as a paraneoplastic manifestation of advanced malignancy does not generally respond to surgery. In such cases, metyrapone is worth a trial to give symptomatic relief.

Increased Pigmentation Of Skin In Nelson's Syndrome

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Nelson's Syndrome

Some patients who undergo bilateral adrenalectomy develop enlargement of the pituitary, pressure effects on the optic chiasma and raised intracranial tension. They also show increased pigmentation due to hypersecretion of MSH. This syndrome follows bilateral adrenalectomy after a few years.

© 2014 Funom Theophilus Makama

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