Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease (PPNAD) and the Carney Complex

NCT00001452 | Completed

• 2 other identifiers: 95005995-CH-0059
• Study Type: observational
• Target: 1,387
• Locations: 1 country
• Sites: 1

Brief 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. 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;

1. 1.Resistance to suppression by the drug dexamethasone
2. 2.The body is unable to secrete cortisol in a normal rhythm
3. 3.Distinct microscopic changes of both adrenal glands
4. 4.Define the genetic basis for PPNAD and/or the Carney Complex.
5. 5.Determine the molecular changes associated with the development of the tumors.
6. 6.Identify carriers of the disease.
7. 7.Determine the prognosis for carriers and affected individuals.
8. 8.Provide sufficient data for genetic counseling of families with PPNAD and/or Carney Complex.\<TAB\>

Conditions

Cushing's Syndrome; Peutz-Jeghers Syndrome; Pituitary Adenoma; Carney Complex; Primary Pigmented Nodular Adrenocortical Disease

Keywords

Cushing's Syndrome; Genetics; Pituitary Adenoma; PPNAD; Carney Complex; Natural History

Outcome Measures

Primary Outcomes (1)

• 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.

  This is an ongoing project

Study Arms (1)

1

families with PPNAD and/or Carney complex

Drug: oCRH

Interventions

oCRH DRUG

1

Eligibility Criteria

• Age: 3 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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:
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• cardiac myxoma
• cutaneous myxoma
• 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
• (c) Patients with one of the familial lentiginosis syndromes: Peutz-Jeghers and LEOPARD syndrome, other forms of familial lentiginosis.

You may not qualify if:

• For DNA analysis and linkage study:
• \. 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.

Sponsors & Collaborators

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

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• 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.

  PMID: 25924874 BACKGROUND

• Carney 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.

  PMID: 4010501 BACKGROUND

• Young 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.

  PMID: 2586567 BACKGROUND

• Pitsava 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.

  PMID: 32893266 DERIVED

• Keil 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.

  PMID: 22154461 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cushing Syndrome; Pituitary Neoplasms; Carney Complex; Peutz-Jeghers Syndrome

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Myxoma; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Heart Neoplasms; Thoracic Neoplasms; Heart Diseases; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Abnormalities; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Intestinal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Genetic Diseases, Inborn; Lentigo; Melanosis; Hyperpigmentation; Pigmentation Disorders; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Deborah P Merke, M.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: December 14, 1995
• Last Updated: May 1, 2026

Record last verified: 2025-10-01

Locations

US (1)