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Clinical and Molecular Analysis of ACTH-Independent Steroid Hormone Production in Adrenocortical Tissue

3 Years
70 Years
Open (Enrolling)
Adrenal Gland Neoplasm

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Trial Information

Clinical and Molecular Analysis of ACTH-Independent Steroid Hormone Production in Adrenocortical Tissue

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.

Type of Study:


Study Design:


Principal Investigator

Constantine A Stratakis, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)


United States: Federal Government

Study ID:




Start Date:

June 2000

Completion Date:

Related Keywords:

  • Adrenal Gland Neoplasm
  • Adrenal Adenoma
  • Adrenal Cancer
  • Macronodular Adrenals
  • Ectopic Receptors
  • Gene Profiling
  • Adrenocortical Carcinoma
  • Cushing Syndrome
  • Virilizing Adrenal Tumor
  • Feminizing Adrenal Tumor
  • Massive Macronodular Adrenocortical Disease
  • Adrenal Gland Tumor
  • Adrenal Gland Neoplasms
  • Neoplasms



National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, Maryland  20892