Ignite Creation Date:
2024-05-05 @ 11:21 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001452
Status:
COMPLETED
Last Update Posted:
2024-06-28
First Post:
1999-11-03
Brief Title:
Defining the Genetic Basis for the Development of Primary Pigmented Nodular Adrenocortical Disease PPNAD and the Carney Complex
Sponsor:
Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Definition of the Genotype and Clinical Phenotype of Primary Pigmented Nodular Adrenocortical Disease PPNAD Carney Complex Peutz-Jeghers Syndrome and Related Conditions
Status:
COMPLETED
Status Verified Date:
2024-09-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Resistance to suppression by the drug dexamethasone
2 The body is unable to secrete cortisol in a normal rhythm
3 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 Define the genetic basis for PPNAD andor the Carney Complex
2 Determine the molecular changes associated with the development of the tumors
3 Identify carriers of the disease
4 Determine the prognosis for carriers and affected individuals
5 Provide sufficient data for genetic counseling of families with PPNAD andor Carney ComplexTAB
Primary pigmented nodular adrenocortical disease PPNAD is a pituitary-independent primary adrenal form of hypercortisolism characterized by
1 Resistance to suppression by the drug dexamethasone
2 The body is unable to secrete cortisol in a normal rhythm
3 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 Define the genetic basis for PPNAD andor the Carney Complex
2 Determine the molecular changes associated with the development of the tumors
3 Identify carriers of the disease
4 Determine the prognosis for carriers and affected individuals
5 Provide sufficient data for genetic counseling of families with PPNAD andor Carney ComplexTAB
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 mechanisms of this hereditary single andor multiple neoplasia syndrome have not been completely elucidated eg patients who meet clinical criteria for Carney complex but test negative for PRKAR1A mutation This study seeks to define the genetic basis of PPNAD andor 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 genes 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 PPNADCarney complex The study will ultimately provide sufficient data for genetic counseling of families with PPNAD andor Carney complex and ultimately the means for genetic screening and prenatal testing
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 95-CH-0059 | None | None | None |