The adrenal glands, located atop the kidneys, normally produce several types of hormones. Tumors of these glands may or may not secrete hormones. It is not known what causes these tumors or why some secrete hormones and others do not. Some of the tumors are benign and confined to the adrenal gland, and others are malignant (cancerous), and can spread to other parts of the body. This study will investigate how adrenal gland tumors develop, why some secrete steroid hormones and others do not, and why some are benign and others malignant.

Patients between 3 and 70 years old with a known or suspected adrenal gland tumor may be eligible for this study. Participants will be hospitalized for 7 to 10 days for various tests and procedures that may include the following:

1. Medical history and physical examination, including body measurements, as appropriate. Children and adolescents will have Tanner staging, including examination of the genitals, to determine the extent of sexual maturity.
2. 24-hour urine collection to measure hormones in the urine.
3. Imaging studies, including magnetic resonance imaging (MRI) of the brain, computed tomography (CT) and other X-ray studies.
4. Blood tests to see if the tumor secretes hormones in response to specific stimuli, including exercise, food, and various hormones. The hormones are given through an intravenous catheter, or IV-a thin plastic tube inserted into an arm vein. After the stimulus, blood is drawn through the same IV every 30 minutes for up to 3 hours to measure hormone levels. Based on the results of these tests, some patients may have additional blood tests to check hormone response to special foods, an IV salt solution, or other hormones or drugs given either IV or by mouth (in pill form).
5. Photographs to document the effects on the body of abnormal hormone secretion from the adrenal tumor.
6. Small samples of blood and tumor tissue for research and DNA (genetic) analysis.

A discussion of treatment options will be based on the results of tests. If surgery to remove the tumor is recommended, the procedure can be done at NIH under this study protocol. If a malignant tumor is found that cannot be treated surgically, chemotherapy or radiation therapy may be recommended. These options are not offered under this protocol, but may be available under a different NIH study (for example, at the National Cancer Institute). Referrals will be made at the patient's request.

Patients who had surgery may be followed at the NIH outpatient clinic for 1 year after surgery. Patients with certain types of tumors may continue to be followed at NIH once a year for up to 5 years.

A registry of study participants will be created to keep records and correlate medical histories with tissues kept at NIH. The registry will also be used to inform participants of research studies they may be interested in. No individuals or organizations outside of NIH will have access to the registry.

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.

• Dluhy RG, Lifton RP. Glucocorticoid-remediable aldosteronism. J Clin Endocrinol Metab. 1999 Dec;84(12):4341-4. Review. No abstract available.
• Torpy DJ, Stratakis CA, Chrousos GP. Hyper- and hypoaldosteronism. Vitam Horm. 1999;57:177-216. Review.
• Torpy DJ, Gordon RD, Lin JP, Huggard PR, Taymans SE, Stowasser M, Chrousos GP, Stratakis CA. Familial hyperaldosteronism type II: description of a large kindred and exclusion of the aldosterone synthase (CYP11B2) gene. J Clin Endocrinol Metab. 1998 Sep;83(9):3214-8.

• 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.

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.

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.