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 and/or 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 and/or Carney Complex.

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.

Brief Title

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

Official Title

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

Brief Summary

Lentiginosis refers to groups of diseases marked by the presence of pigmented spots on the <br /> skin. These conditions are most commonly associated with multiple tumors and changes in <br /> hormone producing glands. The cause of these diseases is unknown, but researchers suggest <br /> there may be a level of inheritance involved in their development. Meaning to say that some <br /> of these diseases may "run in the family" and be passed down form generation to generation. <br /> <br /> Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary <br /> adrenal form of hypercortisolism characterized by; <br /> <br /> 1. Resistance to suppression by the drug dexamethasone <br /> <br /> 2. The body is unable to secrete cortisol in a normal rhythm <br /> <br /> 3. Distinct microscopic changes of both adrenal glands <br /> <br /> PPNAD can be associated with tumors (myxomas) of the skin, heart, breast, tumors (swannomas) <br /> of the nerve sheaths, pigmented spots (nevi and lentigines) of the skin, growth hormone (GH) <br /> producing tumors of the pituitary gland, and tumors of the testicles, ovaries, and thyroid <br /> gland. In the presence of these associations the condition is referred to as the Carney <br /> Complex. Presently there are no tests for screening of PPNAD and the Carney Complex. In <br /> addition, it is unknown how these conditions are genetically transferred from generation to <br /> generation. <br /> <br /> This study proposes to use standard methods of clinical testing for endocrine and <br /> nonendocrine diseases and genetic testing in order to; <br /> <br /> 1. Define the genetic basis for PPNAD and/or the Carney Complex. <br /> <br /> 2. Determine the molecular changes associated with the development of the tumors. <br /> <br /> 3. Identify carriers of the disease. <br /> <br /> 4. Determine the prognosis for carriers and affected individuals. <br /> <br /> 5. Provide sufficient data for genetic counseling of families with PPNAD and/or Carney <br /> 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.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.