Cushing's SyndromeNCT00001452
Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex
An observational study of Cushing's Syndrome and Pituitary Adenoma, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
Lentiginosis refers to groups of diseases marked by the presence of pigmented spots on the skin. These conditions are most commonly associated with multiple tumors and changes in hormone producing glands. Read more about this study
- Who is it for?
- Ages 3 to 70 years
- Conditions the study is for
- Cushing's Syndrome, Pituitary Adenoma, Carney Complex
- What is being tested?
- oCRH
- How many people
- 1,387 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 1995to not given
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Research subjects who present with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions. Research subjects who need screening based on clinical and biochemical data for PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Who may be able to join
- All patients with PPNAD and/or Carney Complex by history and their siblings, children and parents. Additional relatives and their families that are suspected to have the same disorder on clinical grounds will be recruited:
- PPNAD patients will be included if their diagnosis is fully documented. First-degree relatives of patients with the disease will be accepted also for evaluation, or if already conclusively evaluated elsewhere, for DNA linkage analysis only.
- Patients with suspected Carney complex will be accepted for evaluation and/or DNA analysis for linkage, if they have at least two of the following:
- <!-- -->
- cardiac myxoma
- cutaneous myxoma
Show all 15Show fewer
- breast myxoma
- oral myxoma
- myxoma of the external ear
- spotty mucocutaneous pigmentation (lentigines)
- testicular tumor
- pituitary growth hormone secreting adenoma
- nerve tumor, such as psammomatous melanotic schwannoma
- first-, second-, or third-degree relatives with Carney complex
- Patients with one of the familial lentiginosis syndromes: Peutz-Jeghers and LEOPARD syndrome, other forms of familial lentiginosis.
Who cannot join
- For DNA analysis and linkage study:
- 1. Unwillingness to participate.
- For clinical evaluation and DNA analysis/linkage study:
- Patients with major illnesses, such as severe renal failure, restrictive or obstructive lung disease, cardiac disease, anemia and/or terminal cancer that will not be able to undergo appropriate testing or the stress of hospitalization. Also, patients with Carney complex and a known heart tumor (heart myxoma) will not be able to enter the clinical part of the study until after surgical treatment of their tumor. These patients, however, will be asked to participate in the DNA analysis study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Definition of the Genotype and Clinical Phenotype of Primary Pigmented Nodular Adrenocortical Disease (PPNAD), Carney Complex, Peutz-Jeghers Syndrome and Related Conditions
Lentiginosis refers to groups of diseases marked by the presence of pigmented spots on the skin. These conditions are most commonly associated with multiple tumors and changes in hormone producing glands. The cause of these diseases is unknown, but researchers suggest there may be a level of inheritance involved in their development. Meaning to say that some of these diseases may "run in the family" and be passed down form generation to generation.
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by;
Read more
- Resistance to suppression by the drug dexamethasone
- The body is unable to secrete cortisol in a normal rhythm
- Distinct microscopic changes of both adrenal glands
PPNAD can be associated with tumors (myxomas) of the skin, heart, breast, tumors (swannomas) of the nerve sheaths, pigmented spots (nevi and lentigines) of the skin, growth hormone (GH) producing tumors of the pituitary gland, and tumors of the testicles, ovaries, and thyroid gland. In the presence of these associations the condition is referred to as the Carney Complex. Presently there are no tests for screening of PPNAD and the Carney Complex. In addition, it is unknown how these conditions are genetically transferred from generation to generation.
This study proposes to use standard methods of clinical testing for endocrine and nonendocrine diseases and genetic testing in order to;
- Define the genetic basis for PPNAD and/or the Carney Complex.
- Determine the molecular changes associated with the development of the tumors.
- Identify carriers of the disease.
- Determine the prognosis for carriers and affected individuals.
- Provide sufficient data for genetic counseling of families with PPNAD and/or Carney Complex.<TAB>
Read the detailed description
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by (a) resistance to suppression by dexamethasone and abolition of the normal diurnal rhythm of cortisol secretion, and (b) distinctive, bilateral, histopathologic changes of the adrenal glands, such as the formation of variably sized, pigmented nodular adenomas, loss of normal zonation and atrophy of the extranodular cortex. PPNAD can be associated with a variety of other manifestations, such as myxomas of the skin, heart, breast and other sites, psammomatous melanotic swannomas involving the peripheral nervous system (PNS), lentigines and blue nevi of the skin and mucosae, growth hormone (GH)-producing adenomas of the pituitary, testicular Sertoli cell tumors, and possibly other neoplasms (adrenocortical and thyroid follicular carcinoma, and ovarian cysts). These associations constitute a distinct clinical syndrome, Carney complex, a genetic syndrome. At present, there are no standardized screening tests for the members of families with affected individuals and the molecular mechanism(s) of this hereditary single and/or multiple neoplasia syndrome have not been completely elucidated (e.g. patients who meet clinical criteria for Carney complex but test negative for PRKAR1A mutation . This study seeks to define the genetic basis of PPNAD and/or Carney complex in sporadic and familial cases and the molecular pathogenesis of their tumors, to identify the carriers of the familial forms of the disease, and to determine the prognosis for carriers and affected individuals. The methods include standard clinical testing for endocrine and nonendocrine pathologic conditions of the subjects of the study, linkage analysis with DNA markers from areas of the genome likely to harbor the responsible gene(s), and finally genetic screening of these genes. Molecular studies of the tumors of the patients will provide additional clues for the pathophysiologic mechanisms leading to PPNAD/Carney complex. The study will ultimately provide sufficient data for genetic counseling of families with PPNAD and/or Carney complex, and, ultimately, the means for genetic screening and prenatal testing.
- Conditions
- Cushing's Syndrome, Pituitary Adenoma, Carney Complex, Primary Pigmented Nodular Adrenocortical Disease, Peutz-Jeghers Syndrome
- Being tested
- oCRH
- Keywords
- Cushing's Syndrome, Genetics, Pituitary Adenoma, PPNAD, Carney Complex, Natural History
- Medical subject headings
- Cushing Syndrome, Pituitary Neoplasms, Carney Complex, Peutz-Jeghers Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oCRHDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | families with PPNAD and/or Carney complex Receives: Drug: oCRH |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genotype and clinical phenotype correlation in patients with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Genotype and clinical phenotype correlation in patients with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Measured: This is an ongoing project
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study start14 Dec 1995
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cushing's SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 1,387 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Deborah P Merke, M.D., Principal investigator, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001452
- Sponsor's protocol ID
- 950059
- Other IDs
- 95-CH-0059
- Status last verified
- 17 Aug 2026
- First submitted
- 3 Nov 1999
- Last updated
- 5 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lodish MB, Yuan B, Levy I, Braunstein GD, Lyssikatos C, Salpea P, Szarek E, Karageorgiadis AS, Belyavskaya E, Raygada M, Faucz FR, Izzat L, Brain C, Gardner J, Quezado M, Carney JA, Lupski JR, Stratakis CA. Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations. Eur J Endocrinol. 2015 Jun;172(6):803-11. doi: 10.1530/EJE-14-1154.
PubMed 25924874Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985 Jul;64(4):270-83. doi: 10.1097/00005792-198507000-00007.
PubMed 4010501Young WF Jr, Carney JA, Musa BU, Wulffraat NM, Lens JW, Drexhage HA. Familial Cushing's syndrome due to primary pigmented nodular adrenocortical disease. Reinvestigation 50 years later. N Engl J Med. 1989 Dec 14;321(24):1659-64. doi: 10.1056/NEJM198912143212407. No abstract available.
PubMed 2586567Pitsava G, Zhu C, Sundaram R, Mills JL, Stratakis CA. Predicting the risk of cardiac myxoma in Carney complex. Genet Med. 2021 Jan;23(1):80-85. doi: 10.1038/s41436-020-00956-3. Epub 2020 Sep 7.
PubMed 32893266Keil MF, Graf J, Gokarn N, Stratakis CA. Anthropometric measures and fasting insulin levels in children before and after cure of Cushing syndrome. Clin Nutr. 2012 Jun;31(3):359-63. doi: 10.1016/j.clnu.2011.11.007. Epub 2011 Dec 7.
PubMed 22154461
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Definition of the Genotype and Clinical Phenotype of Primary Pigmented Nodular Adrenocortical Disease (PPNAD), Carney Complex, Peutz-Jeghers Syndrome and Related Conditions
- ClinicalTrials.gov ID
- NCT00001452
- Acronym / sponsor ID
- 950059
- Conditions
- Cushing's Syndrome, Pituitary Adenoma, Carney Complex, Primary Pigmented Nodular Adrenocortical Disease, Peutz-Jeghers Syndrome
- Keywords
- Cushing's Syndrome, Genetics, Pituitary Adenoma, PPNAD, Carney Complex, Natural History
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 1,387 participants (actual)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- 14 Dec 1995 (actual)
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lentiginosis refers to groups of diseases marked by the presence of pigmented spots on the skin. These conditions are most commonly associated with multiple tumors and changes in hormone producing glands. The cause of these diseases is unknown, but researchers suggest there may be a level of inheritance involved in their development. Meaning to say that some of these diseases may "run in the family" and be passed down form generation to generation.
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by;
- Resistance to suppression by the drug dexamethasone
- The body is unable to secrete cortisol in a normal rhythm
- Distinct microscopic changes of both adrenal glands
PPNAD can be associated with tumors (myxomas) of the skin, heart, breast, tumors (swannomas) of the nerve sheaths, pigmented spots (nevi and lentigines) of the skin, growth hormone (GH) producing tumors of the pituitary gland, and tumors of the testicles, ovaries, and thyroid gland. In the presence of these associations the condition is referred to as the Carney Complex. Presently there are no tests for screening of PPNAD and the Carney Complex. In addition, it is unknown how these conditions are genetically transferred from generation to generation.
This study proposes to use standard methods of clinical testing for endocrine and nonendocrine diseases and genetic testing in order to;
- Define the genetic basis for PPNAD and/or the Carney Complex.
- Determine the molecular changes associated with the development of the tumors.
- Identify carriers of the disease.
- Determine the prognosis for carriers and affected individuals.
- Provide sufficient data for genetic counseling of families with PPNAD and/or Carney Complex.<TAB>
Detailed description
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by (a) resistance to suppression by dexamethasone and abolition of the normal diurnal rhythm of cortisol secretion, and (b) distinctive, bilateral, histopathologic changes of the adrenal glands, such as the formation of variably sized, pigmented nodular adenomas, loss of normal zonation and atrophy of the extranodular cortex. PPNAD can be associated with a variety of other manifestations, such as myxomas of the skin, heart, breast and other sites, psammomatous melanotic swannomas involving the peripheral nervous system (PNS), lentigines and blue nevi of the skin and mucosae, growth hormone (GH)-producing adenomas of the pituitary, testicular Sertoli cell tumors, and possibly other neoplasms (adrenocortical and thyroid follicular carcinoma, and ovarian cysts). These associations constitute a distinct clinical syndrome, Carney complex, a genetic syndrome. At present, there are no standardized screening tests for the members of families with affected individuals and the molecular mechanism(s) of this hereditary single and/or multiple neoplasia syndrome have not been completely elucidated (e.g. patients who meet clinical criteria for Carney complex but test negative for PRKAR1A mutation . This study seeks to define the genetic basis of PPNAD and/or Carney complex in sporadic and familial cases and the molecular pathogenesis of their tumors, to identify the carriers of the familial forms of the disease, and to determine the prognosis for carriers and affected individuals. The methods include standard clinical testing for endocrine and nonendocrine pathologic conditions of the subjects of the study, linkage analysis with DNA markers from areas of the genome likely to harbor the responsible gene(s), and finally genetic screening of these genes. Molecular studies of the tumors of the patients will provide additional clues for the pathophysiologic mechanisms leading to PPNAD/Carney complex. The study will ultimately provide sufficient data for genetic counseling of families with PPNAD and/or Carney complex, and, ultimately, the means for genetic screening and prenatal testing.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | – | Drug: oCRHfamilies with PPNAD and/or Carney complex |
Who may qualify
- Ages
- 3 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Research subjects who present with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions. Research subjects who need screening based on clinical and biochemical data for PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Key inclusion criteria (15 listed)
- <!-- -->
Key exclusion criteria (4 listed)
- For DNA analysis and linkage study:
- 1. Unwillingness to participate.
- For clinical evaluation and DNA analysis/linkage study:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| oCRH | Drug | 1 |
Primary outcome
Genotype and clinical phenotype correlation in patients with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Time frame: This is an ongoing project
Genotype and clinical phenotype correlation in patients with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.
- Background: PubMed 25924874Lodish MB, Yuan B, Levy I, Braunstein GD, Lyssikatos C, Salpea P, Szarek E, Karageorgiadis AS, Belyavskaya E, Raygada M, Faucz FR, Izzat L, Brain C, Gardner J, Quezado M, Carney JA, Lupski JR, Stratakis CA. Germline PRKACA amplification causes variable phenotypes that may depend on the extent of the genomic defect: molecular mechanisms and clinical presentations. Eur J Endocrinol. 2015 Jun;172(6):803-11. doi: 10.1530/EJE-14-1154.
- Background: PubMed 4010501Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore). 1985 Jul;64(4):270-83. doi: 10.1097/00005792-198507000-00007.
- Background: PubMed 2586567Young WF Jr, Carney JA, Musa BU, Wulffraat NM, Lens JW, Drexhage HA. Familial Cushing's syndrome due to primary pigmented nodular adrenocortical disease. Reinvestigation 50 years later. N Engl J Med. 1989 Dec 14;321(24):1659-64. doi: 10.1056/NEJM198912143212407. No abstract available.
- Derived from this study: PubMed 32893266Pitsava G, Zhu C, Sundaram R, Mills JL, Stratakis CA. Predicting the risk of cardiac myxoma in Carney complex. Genet Med. 2021 Jan;23(1):80-85. doi: 10.1038/s41436-020-00956-3. Epub 2020 Sep 7.
- Derived from this study: PubMed 22154461Keil MF, Graf J, Gokarn N, Stratakis CA. Anthropometric measures and fasting insulin levels in children before and after cure of Cushing syndrome. Clin Nutr. 2012 Jun;31(3):359-63. doi: 10.1016/j.clnu.2011.11.007. Epub 2011 Dec 7.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah P Merke, M.D. principal investigator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cushing's Syndrome and Pituitary Adenoma, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genotype and clinical phenotype correlation in patients with PPNAD, Carney Complex, Peutz-Jeghers Syndrome and related conditions. (time frame: This is an ongoing project). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001452, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.