Hyperplasia of any tissue or organ means that there is an abnormal increase in the number of normal cells in the organ. Hyperplasia of a tissue is not a carcinoma, a malignant tumor, or an adenoma, a benign tumor, although hyperplasia in some tissues is considered precancerous. In the adrenal glands, hyperplasia of the cortex, the outer surface of the gland, is a common cause of Cushing’s syndrome, and would usually only be diagnosed when doctors are working up a case of this syndrome. The normal adrenal glands are small structures lying on top of the kidneys on both sides of the body.
Cushing’s syndrome, named after Dr. Harvey Cushing who described it, occurs when the adrenal glands secrete excessive amounts of the hormone hydrocortisone that they normally make. The adrenal gland is an endocrine gland, meaning that it makes hormones which it releases into the blood stream for distribution to all the cells of the body. The pituitary gland, the thyroid, ovary and parathyroid glands are other examples of endocrine glands and hyperplasia, adenomas or carcinomas of all of them can result in the production of excessive amounts of hormone.
Hydrocortisone is one of several hormones that the adrenal glands normally produce, and when made in excess it causes Cushing’s syndrome. The typical symptoms are weight gain with fat particularly in the face, neck and across the shoulders; high blood pressure; fatigue and weakness; the development or worsening of diabetes; abnormal hair growth in women; the development of purple stretch marks called striae; and osteoporosis. Cushing’s syndrome can develop from taking prednisone, a commonly prescribed cortisone type drug, for prolonged periods, and this side effect is the reason doctors are so unwilling to prescribe it for more than a few weeks.
When adrenal hyperplasia is the cause of the excessive hydrocortisone production, it is almost always due to an increase in ACTH, the pituitary hormone which stimulates the adrenal cortex. Excessive ACTH may be produced by a benign pituitary adenoma, or occasionally by malignant tumors arising elsewhere. An adenoma or carcinoma of the adrenal gland may also produce excess hydrocortisone without any ACTH stimulation.
Distinguishing between these various causes of Cushing’s syndrome can occasionally be difficult. It is usually obvious if someone is taking too much prednisone, although cases where a person has deliberately taken large doses for prolonged periods and denied it have been reported. Distinguishing between the pituitary and adrenal causes of the syndrome requires some fairly sophisticated testing and diagnosing a non-pituitary tumor that is producing ACTH can be particularly difficult. CT scans of the adrenal glands will usually pick up adenomas or carcinomas without difficulty, but in about 50 percent of cases of adrenal hyperplasia the glands do not appear enlarged on a CT scan. An MRI scan of the pituitary gland will often show an adenoma there, but unfortunately a normal MRI of the pituitary does not rule out that gland as the source of excessive ACTH, nor of course would it rule out the presence of a different tumor elsewhere which is producing ACTH.
If a clear cut adenoma is found in the pituitary gland, then it is usually removed surgically through the nose, a procedure known as trans-sphenoidal hypophysectomy. An adenoma or carcinoma of the adrenal glands causing Cushing’s syndrome must also be removed surgically. When none of those clear causes of the syndrome are found, then often the only option is to remove both the adrenal glands completely, which removes the source of the hydrocortisone causing the syndrome. After such a bilateral adrenalectomy a person must take replacement adrenal hormones for life.