Cushing Syndrome in Carney Complex

Lowe, Kathleen M.; Young, William F.; Lyssikatos, Charalampos; Stratakis, Constantine A.; Carney, J. Aidan

doi:10.1097/pas.0000000000000748

Cited by 39 publications

(25 citation statements)

References 27 publications

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“…Unlike hyperplastic processes, neoplastic proliferations are considered to represent cellular proliferations originating from genetically transformed cells. Therefore, in adrenal Cushing syndrome, diagnostic entities falling into the spectrum of primary bilateral nodular (micronodular or macronodular) adrenal cortical hyperplasia do not represent true hyperplastic phenomenon because these nodular proliferations generally include genetically transformed cells ( 6 , 36 , 42 – 45 ). Consequently, these lesions should be regarded as multiple benign cortical neoplasms.…”

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

“…Primary bilateral micronodular adrenocortical disease frequently presents at a younger age and results in Cushing syndrome. Traditionally, it is divided into two subgroups: (i) a pigmented subtype, which is also referred to as primary pigmented nodular adrenocortical disease (PPNAD), and (ii) a non-pigmented or scarcely pigmented subtype, which is also known as isolated micronodular adrenocortical disease (i-MAD) ( 36 , 45 – 50 ). The association between inherited genetic predisposition and the pathogenesis of primary bilateral micronodular adrenocortical disease has been well characterized (see Molecular Characteristics and Pathogenesis ) ( 36 , 45 ).…”

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

“…Traditionally, it is divided into two subgroups: (i) a pigmented subtype, which is also referred to as primary pigmented nodular adrenocortical disease (PPNAD), and (ii) a non-pigmented or scarcely pigmented subtype, which is also known as isolated micronodular adrenocortical disease (i-MAD) ( 36 , 45 – 50 ). The association between inherited genetic predisposition and the pathogenesis of primary bilateral micronodular adrenocortical disease has been well characterized (see Molecular Characteristics and Pathogenesis ) ( 36 , 45 ). Consequently, PPNAD is further subdivided based on its association with Carney complex: (i) c-PPNAD for those associated with Carney complex, and (ii) i-PPNAD for isolated cases with may be either familial (due to germline mutations) or sporadic (due to somatic alterations) ( 36 , 45 , 50 ).…”

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

“…The association between inherited genetic predisposition and the pathogenesis of primary bilateral micronodular adrenocortical disease has been well characterized (see Molecular Characteristics and Pathogenesis ) ( 36 , 45 ). Consequently, PPNAD is further subdivided based on its association with Carney complex: (i) c-PPNAD for those associated with Carney complex, and (ii) i-PPNAD for isolated cases with may be either familial (due to germline mutations) or sporadic (due to somatic alterations) ( 36 , 45 , 50 ). Unlike PBMAH, primary bilateral micronodular adrenocortical disease presents with normal size or slightly enlarged adrenal glands ( 36 , 45 – 48 ).…”

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

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The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

Mete

Duan

2018

Front. Med.

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Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

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Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

Section: Heterogeneity In Glucocorticoid-producing Benign Adrenal Cormentioning

confidence: 99%

See 2 more Smart Citations

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

Mete

Duan

2018

Front. Med.

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“…Rarely medical treatment with ketoconazole or mitotane has been used [29]. In a recent retrospective study of 15 patients with CNC and classic CS who underwent surgical treatment, cure was achieved with bilateral adrenalectomy (12 patients), subtotal adrenalectomy (2 patients), and partial unilateral adrenalectomy (1 patient), whereas CS regressed spontaneously in 1 patient and persisted untreated for almost 3 decades in another [30]. These data highlight the possible need for reconsideration of less than total bilateral adrenalectomy in patients with CNC and CS.…”

Section: Endocrine Manifestationsmentioning

confidence: 99%

Carney Complex

Kamilaris

Faucz

Voutetakis

et al. 2018

Exp Clin Endocrinol Diabetes

104

103

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Carney complex is a rare, autosomal dominant, multiple endocrine neoplasia and lentiginosis syndrome, caused in most patients by defects in the PRKAR1A gene, which encodes the regulatory subunit type 1α of protein kinase A. Inactivating defects of PRKAR1A lead to aberrant cyclic-AMP-protein kinase A signaling. Patients may develop multiple skin abnormalities and a variety of endocrine and non-endocrine tumors. Endocrine manifestations include primary pigmented nodular adrenocortical disease, that may cause Cushing syndrome, growth-hormone secreting pituitary adenoma or pituitary somatotropic hyperplasia which can result in acromegaly, as well as gonadal and thyroid tumors. Non-endocrine tumors associated with Carney complex include myxomas of the heart, breast, and other sites, psamommatous melanotic schwannomas, breast ductal adenomas, osteochondromyxomas, and a predisposition to a number of malignancies from adrenal to pancreatic and liver cancer.

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Cushing Syndrome

Reincke

Fleseriu

2023

JAMA

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ImportanceCushing syndrome is defined as a prolonged increase in plasma cortisol levels that is not due to a physiological etiology. Although the most frequent cause of Cushing syndrome is exogenous steroid use, the estimated incidence of Cushing syndrome due to endogenous overproduction of cortisol ranges from 2 to 8 per million people annually. Cushing syndrome is associated with hyperglycemia, protein catabolism, immunosuppression, hypertension, weight gain, neurocognitive changes, and mood disorders.ObservationsCushing syndrome characteristically presents with skin changes such as facial plethora, easy bruising, and purple striae and with metabolic manifestations such as hyperglycemia, hypertension, and excess fat deposition in the face, back of the neck, and visceral organs. Cushing disease, in which corticotropin excess is produced by a benign pituitary tumor, occurs in approximately 60% to 70% of patients with Cushing syndrome due to endogenous cortisol production. Evaluation of patients with possible Cushing syndrome begins with ruling out exogenous steroid use. Screening for elevated cortisol is performed with a 24-hour urinary free cortisol test or late-night salivary cortisol test or by evaluating whether cortisol is suppressed the morning after an evening dexamethasone dose. Plasma corticotropin levels can help distinguish between adrenal causes of hypercortisolism (suppressed corticotropin) and corticotropin-dependent forms of hypercortisolism (midnormal to elevated corticotropin levels). Pituitary magnetic resonance imaging, bilateral inferior petrosal sinus sampling, and adrenal or whole-body imaging can help identify tumor sources of hypercortisolism. Management of Cushing syndrome begins with surgery to remove the source of excess endogenous cortisol production followed by medication that includes adrenal steroidogenesis inhibitors, pituitary-targeted drugs, or glucocorticoid receptor blockers. For patients not responsive to surgery and medication, radiation therapy and bilateral adrenalectomy may be appropriate.Conclusions and RelevanceThe incidence of Cushing syndrome due to endogenous overproduction of cortisol is 2 to 8 people per million annually. First-line therapy for Cushing syndrome due to endogenous overproduction of cortisol is surgery to remove the causative tumor. Many patients will require additional treatment with medications, radiation, or bilateral adrenalectomy.

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Cushing Syndrome in Carney Complex

Cited by 39 publications

References 27 publications

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

Carney Complex

Cushing Syndrome

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