Trial record 8 of 14 for:    nichd Cushing's Syndrome

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001452
First received: November 3, 1999
Last updated: April 3, 2014
Last verified: March 2014
  Purpose

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. < TAB> Resistance to suppression by the drug dexamethasone
  2. < TAB> The body is unable to secrete cortisol in a normal rhythm
  3. < TAB> 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;

  1. < TAB> Define the genetic basis for PPNAD and/or the Carney Complex.
  2. < TAB> Determine the molecular changes associated with the development of the tumors.
  3. < TAB> Identify carriers of the disease.
  4. < TAB> Determine the prognosis for carriers and affected individuals.
  5. < TAB> Provide sufficient data for genetic counseling of families with PPNAD and/or Carney Complex.< TAB>

Condition
Cushing's Syndrome
Hereditary Neoplastic Syndrome
Lentigo
Neoplasm
Testicular Neoplasm

Study Type: Observational
Official Title: Definition of the Genotype and Clinical Phenotype of Primary Pigmented Nodular Adrenocortical Disease (PPNAD), Carney Complex, Peutz-Jeghers Syndrome and Related Conditions

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 99999999
Study Start Date: January 1995
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.

  Eligibility

Ages Eligible for Study:   3 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. 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:

    1. 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.
    2. 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:

      1. cardiac myxoma
      2. cutaneous myxoma
      3. breast myxoma
      4. oral myxoma
      5. myxoma of the external ear
      6. spotty mucocutaneous pigmentation (lentigines)
      7. testicular tumor
      8. pituitary growth hormone secreting adenoma
      9. nerve tumor, such as psammomatous melanotic schwannoma
      10. first-, second-, or third-degree relatives with Carney complex
    3. Patients with one of the familial lentiginosis syndromes: Peutz-Jeghers and LEOPARD syndrome, other forms of familial lentiginosis.

      2. Informed consent, and for children and/ or mentally impaired, parental or legal custodian's consent and subject assent.

      EXCLUSION CRITERIA:

    1. For DNA analysis and linkage study:

      1. Unwillingness to participate.

    2. For clinical evaluation and DNA analysis/linkage study:

      1. 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001452

Contacts
Contact: Constantine A Stratakis, M.D. (301) 594-5984 stratakc@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Constantine A Stratakis, M.D. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00001452     History of Changes
Other Study ID Numbers: 950059, 95-CH-0059
Study First Received: November 3, 1999
Last Updated: April 3, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cushing Syndrome
Gene Mapping
Linkage
Oncogene
Linkage Analysis
Gene Identification
Tumors
Familial Neoplasia
Adrenal Gland
Lentigines
Carney Complex

Additional relevant MeSH terms:
Cushing Syndrome
Neoplastic Syndromes, Hereditary
Peutz-Jeghers Syndrome
Neoplasms
Lentigo
Testicular Neoplasms
Carney Complex
Adrenocortical Hyperfunction
Adrenal Gland Diseases
Endocrine System Diseases
Melanosis
Hyperpigmentation
Pigmentation Disorders
Skin Diseases
Genetic Diseases, Inborn
Intestinal Polyposis
Intestinal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Testicular Diseases
Gonadal Disorders
Myxoma
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 22, 2014