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
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 such as aldosterone is controlled by the renin-angiotensin
system. In addition to these two classes of steroids, the adrenal gland secretes lesser
amounts of intermediate metabolites as well as dehydroepiandrosterone (DHEA) and its sulfated
product (DHEAS) and 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. 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 and/or aldosterone 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. One of the first goals of the
study was (until very recently) to examine the prevalence of ectopic receptor expression in
cortisol- and/or aldosterone- hormone secreting adrenocortical tumors. This led to the
understanding of the ontogeny of these tumors and the development of novel therapeutic
strategies (e.g., receptor antagonists) to control hormone oversecretion. We currently use
this information for the evaluation and treatment of our patients. An important research goal
of the study is to identify novel genetic defects leading to tumors of the adrenal gland.
This is done through a set of methods, from sequencing of the collected DNA to analysis of
the expression of large sets of genes using gene array/gene chip analysis. This information
may help to identify patients who would benefit from more aggressive intervention strategies,
especially those with potentially malignant tumors. This study also provides the patient
cohort necessary for the establishment of a bank of tissues of varying tumors of the adrenal
cortex, which may serve in the future as an experimental resource to test new diagnostic and
therapeutic methods. Finally, an important and more recent goal of this study is to
investigate the effects of excess aldosterone on renal, cardiac, metabolic, and bone systems
in patients with primary hyperaldosteronism, an important subgroup of patients with
adrenocortical tumors. Patients with hyperaldosetronism have not been studied with the same
rigor as patients with hypercortisolism in the past; this study aims at investigating the
relative contribution of hyperaldosteronism in the etiopathogenesis of a number of clinical
problems in patients with adrenocortical lesions and hypertension.
- 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. This condition is meant to include the possibility of
individuals with "sub-clinical" hormone secretion syndromes, which may be detectable at the
biochemical level even in the absence of frank clinical signs/symptoms.
All eligible patients are invited to participate in this protocol, regardless of sex, race
or ethnic origin. All populations appear at risk for adrenal tumors, and therefore the
subject population can include Native Americans, Asian/Pacific Islanders, Caucasian,
Hispanic, and Black individuals. Patients will be accepted for evaluation based on referral
from clinicians, or may be self-referred, if they can provide evidence supportive of the
diagnosis of hormone over-secretion.
Patients must be willing to return to the NIH for follow-up evaluation.
Patients may withdraw from the study at any time.
1. Children less than 3 years old will be excluded from the protocol because of the
limited resources available at the NIH for the care of infants of this age.
2. Individuals over the age of 70 years of age will be excluded because of the
possibility of comorbidities that may significantly affect appropriate initial work-up
and post-operative management. In addition, research data may be compromised by the
inability to interpret data collected from patients over the age of 70 years that may
be on multiple medications for a variety for reasons.
3. Women who are pregnant or nursing will be excluded from the hyperaldosteronism arm of
the protocol. Women with adrenal tumors secreting cortisol or other adrenal hormones
may benefit clinically from evaluation and treatment of their tumor, and will be
considered for enrollment when clinically indicated.
4. 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 from the protocol, as they will not be able
to participate profitably in the research aspects of this protocol.
5. Individuals found to have an known inherited syndrome as the cause for hormone
oversecretion will be excluded from participation in this protocol, as the mechanisms
of hormone oversecretion and tumorigenesis is likely to be distinct in these
individuals. Specific examples of syndromes to may be excluded from this protocol
include individuals with Carney Complex, McCune-Albright syndrome, and MEN-1. If
inquiries are received from such patients, they will be referred to the appropriate
ongoing protocols, if possible.