Evidence for a second genetic locus in Carney complex

Irvine, Alan D.; Armstrong, Steven R.; Bingham,; Hadden,; Nevin, Austin; Hughes, H. Velocity

doi:10.1046/j.1365-2133.1998.02450.x

Cited by 19 publications

(10 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Among the other conditions listed in Table 1, pilonidal cyst, which was present in patients 1 and 2 (brother and sister), has been reported in 4 members of a family with CNC (28), making the condition almost certainly a rare manifestation of the syndrome. Also, in patient 11, the follicular thyroid carcinoma, which was bilateral with cervical lymph node metastasis, is a very unusual presentation of the tumor, and this lesion may be another rare constituent of CNC.…”

Section: Discussionmentioning

confidence: 99%

Cushing Syndrome in Carney Complex

Lowe¹,

Young

Lyssikatos

et al. 2017

American Journal of Surgical Pathology

View full text Add to dashboard Cite

Carney complex (CNC) is a rare dominantly inherited multiorgan tumoral disorder that includes Cushing syndrome (CS). To establish the Mayo Clinic experience with the CS component, including its clinical, laboratory, and pathological findings, we performed a retrospective search of the patient and pathological databases of Mayo Clinic in Rochester, Minnesota, for patients with CNC and clinical or laboratory findings of CS. Thirty-seven patients with CNC were identified. Twenty-nine had clinical, pathological, or laboratory evidence of an adrenocortical disorder. Seventeen had classic CS; 15 underwent bilateral, subtotal, or partial unilateral adrenalectomy, and 2 had no treatment. Pathologically, the glands were normal sized or slightly enlarged with multiple small (1–4 mm), brown, black, and yellow micronodules (primary pigmented nodular adrenocortical disease) (PPNAD). Three glands each had a mass: a 2-cm adenoma, a 1.5-cm macronodule, and an unencapsulated 1.8-cm myelolipoma. Fourteen of the patients were alive at follow-up and 3 were deceased; 2 of the latter had PPNAD at autopsy, and the third had PPNAD at surgery. Twelve patients without clinical features of classic CS had abnormal adrenocortical testing results; none developed classic CS during follow-up (mean, 10 years). Autopsy findings in 1 showed bilateral vacuolated cell cortical hyperplasia.

show abstract

Section: Discussionmentioning

confidence: 99%

Cushing Syndrome in Carney Complex

Lowe¹,

Young

Lyssikatos

et al. 2017

American Journal of Surgical Pathology

View full text Add to dashboard Cite

show abstract

“…Carney complex (CNC), a rare condition, has been described in about 500 people to date and is caused in more than 60% of the cases that meet diagnostic criteria by an inactivating mutation in the gene encoding protein kinase A (PKA) type 1A regulatory (R1α) subunit (PRKAR1A) at 17q22-24; a second, as yet uncharacterized, locus at 2p16 has also been implicated in some families [6,7]. The pituitary gland is frequently affected in CNC and the clinical features are reminiscent of McCune-Albright syndrome (MAS) [8][9][10][11]: despite frequent abnormalities of growth hormone (GH), insulinlike growth factor 1 (IGF-1), and prolactin (PRL) secretion, clinical acromegaly or significant hyperprolactinaemia and growing GH-or PRL-producing tumors are rare [12][13][14][15]. Mouse models of R1α deficiency have been created but they failed to reproduce a specific or a significant pituitary phenotype, although mild abnormalities were seen.…”

Section: Introductionmentioning

confidence: 99%

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Boikos

Stratakis

2006

Pituitary

View full text Add to dashboard Cite

First described in the mid 80's, Carney Complex (CNC) is a rare, dominantly heritable disorder with features overlapping those of McCune-Albright syndrome (MAS) and other multiple endocrine neoplasia (MEN) syndromes like MEN type 1 (MEN 1). Pituitary tumors have been described in a number of patients with CNC; they present with elevated growth hormone (GH) levels and mild hyperprolactinemia. However, most patients with CNC have mild hypersomatomammotropinemia starting in adolescence; this is similar to the situation in MAS patients: in both disorders, pituitary hyperplasia appears to precede tumor development. Familial pituitary tumor syndromes such as CNC provide an important insight into the genetics and molecular pathology of pituitary and other endocrine tumors. Our understanding of these conditions is expanding rapidly due to the identification of the causative genes and the availability of murine disease models. The present report reviews the clinical findings related to pituitary tumor development among patients with CNC and provides an update on murine models of the complex.

show abstract

“…Although growth hormone (GH) and prolactin (PRL) secretion are frequently abnormal in affected patients [9,10], clinical acromegaly or significant hyperprolactinemia and GH-or PRL-producing tumors, respectively, have been detected in less than one fifth of them [11,12]. The pattern of biochemical abnormalities of GH and PRL secretion without pituitary tumors that are detectable by common imaging modalities, and infrequent development of clinically significant acromegaly is reminiscent of the situation in McCune-Albright syndrome (MAS) [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Pituitary Pathology in Carney Complex Patients

et al. 2004

View full text Add to dashboard Cite

Carney complex (CNC) is a familial multiple neoplasia syndrome with features overlapping those of McCune-Albright syndrome (MAS) and multiple endocrine neoplasia (MEN) type 1 (MEN 1). Like MAS and MEN 1 patients, patients with CNC develop growth hormone (GH)-producing pituitary tumors. Occasionally, these tumors are also prolactin-producing, but there are no isolated pro-lactinomas or other types of pituitary tumors. In at least some patients with CNC, the pituitary gland is characterized by hyperplastic areas; hyperplasia appears to involve somatomammotrophs only. Hyperplasia most likely precedes the formation of GH-producing adenomas in CNC, as has been suggested in MAS-related somatotropinomas, but has never been seen in MEN 1 patients. In at least one case of a patient with CNC and advanced acromegaly, a GH-producing macroadenoma showed extensive genetic changes at the chromosomal level. So far, half of the patients with CNC have germline inactivating mutations in the PRKAR1A gene; in their pituitary tumors, the normal allele of the PRKAR1A gene is lost. Loss-of-hererozygosity suggests that PRKAR1A, which codes for the regulatory subunit type 1α of the cAMP-dependent protein kinase A (PKA) may act as a tumor-suppressor gene in CNC somatomammotrophs. These data provide evidence for a PRKAR1A-induced somatomammotroph hyperpasia in the pituitary tissue of CNC patients; hyperplasia, in turn may lead to additional genetic changes at the somatic level, which then cause the formation of adenomas in some, but not all, patients.

show abstract

Evidence for a second genetic locus in Carney complex

Cited by 19 publications

References 17 publications

Cushing Syndrome in Carney Complex

Cushing Syndrome in Carney Complex

Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities

Pituitary Pathology in Carney Complex Patients

Contact Info

Product

Resources

About