The adrenal glands are the major source in the body of the steroid hormones. In normal physiology, the pituitary hormone ACTH regulates the secretion of glucocorticoids, while the secretion of mineralocorticoids is controlled by the renin-angiotensin system. In addition to these two steroids, the adrenal gland secretes lesser amounts of intermediate metabolites of these steroids, as well as the sex-steroids DHEA, DHEAS, androstenedione, testosterone, estrogen, and estrone. Dysregulated secretion of any of these hormones can be caused by sporadic adrenocortical adenomas or carcinomas, with the development of specific clinical syndromes depending on the identity of the hormones secreted. Similar clinical phenomena can also occur in the setting of a primary, bilateral hyperplasia of the adrenal cortex. In at least a subset of cortisol-producing adrenocortical neoplasms, the presence of ectopic or abnormal receptors has been described, resulting in the regulation of cortisol by non-physiologic stimuli. The present study will serve as a mechanism to investigate individuals with steroid hormone-secreting adrenocortical tumors of all types for the purpose of identifying hereditary, congenital, or acquired defects leading not only to hormone oversecretion, but also to tumor formation. The first goal of the study will be to examine the prevalence of ectopic receptor expression in hormone secreting adrenocortical tumors. This aim will aid in the understanding of the ontogeny of these tumors, as well as lead to the development of novel therapeutic strategies (e.g., receptor antagonists) to control hormone oversecretion. The second goal of the study will be to perform a comparative analysis of the expression of large sets of genes using the emerging technology of gene array/gene chip analysis. This study will generate important diagnostic information about the malignant potential of adrenocortical neoplasms, information which at present can only be obtained through follow-up of patients and retrospective analysis. This information may help to identify patients who would benefit from more aggressive intervention strategies. Thirdly, this study will also provide for the establishment of a bank of tissues of varying malignant potential from the adrenal cortex, which may serve in the future as an experimental resource to test new diagnostic and therapeutic methods.

• INCLUSION CRITERIA:

Patients are adults or children with evidence for the existence of a tumor of the adrenal glands, as indicated by previously obtained imaging studies and/or biochemical investigation of hormonal secretion.

Patients must be willing to return to the NIH for follow-up evaluation.

Patients may withdraw from the study at any time.

EXCLUSION CRITERIA:

Children less than 3 years old will be excluded.

Individuals over the age of 70 years of age will be excluded.

Individuals whose medical status will not allow them, for safety reasons, to participate in the provocative testing or who have unacceptably high risk for surgical morbidity and mortality will be excluded.

Individuals found to have a known inherited syndrome as the cause for hormone oversecretion will be excluded.

Specific examples of syndromes to may be excluded from this protocol include individuals with Carney Complex, McCune-Albright syndrome, and MEN-1.

Individuals with a diagnosis of glucocorticoid-remediable aldosteronism (GRA) are excluded from participation in this protocol.

For family members studied for linkage analysis, the following criteria must be met:

These individuals can be of any age. Each must be a member of a kindred suspected of having an inherited form of adrenal neoplasia, as evidenced by results of a patient studied under above eligibility criteria.