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Primary pigmented nodular adrenocortical disease

MedGen UID:
930501
•Concept ID:
C4304832
•
Disease or Syndrome
Synonyms: pigmented nodular adrenocortical disease; pigmented nodular adrenocortical disease, primary; PPNAD; Primary pigmented nodular adrenal dysplasia; primary pigmented nodular adrenal dysplasia; primary pigmented nodular adrenocortical disease
SNOMED CT: Primary pigmented nodular adrenocortical disease (719274008)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Monarch Initiative: MONDO:0015999
OMIM® Phenotypic series: PS610489
Orphanet: ORPHA189439

Definition

Primary pigmented nodular adrenocortical disease (PPNAD) is a form of bilateral adrenocortical hyperplasia that is often associated with adrenocorticotrophin hormone (ACTH) independent Cushing syndrome (see this term) and is characterized by small to normal sized adrenal glands containing multiple small cortical pigmented nodules (less than 1 cm in diameter). [from ORDO]

Professional guidelines

PubMed

Treatment of Primary Pigmented Nodular Adrenocortical Disease.
Liu X, Zhang S, Guo Y, Gang X, Wang G
Horm Metab Res 2022 Nov;54(11):721-730. Epub 2022 Sep 21 doi: 10.1055/a-1948-6990. PMID: 36130700Free PMC Article
MANAGEMENT OF ENDOCRINE DISEASE: Carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene.
Bouys L, Bertherat J
Eur J Endocrinol 2021 Mar;184(3):R99-R109. doi: 10.1530/EJE-20-1120. PMID: 33444222
Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease.
Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, Chrousos GP, Papanicolaou DA
Ann Intern Med 1999 Oct 19;131(8):585-91. doi: 10.7326/0003-4819-131-8-199910190-00006. PMID: 10523219

Recent clinical studies

Etiology

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review.
Sun J, Ding L, He L, Fu H, Li R, Feng J, Dong J, Liao L
Front Endocrinol (Lausanne) 2024;15:1356870. Epub 2024 Jun 26 doi: 10.3389/fendo.2024.1356870. PMID: 39006359Free PMC Article
Update on primary micronodular bilateral adrenocortical diseases.
Maillet M, Bourdeau I, Lacroix A
Curr Opin Endocrinol Diabetes Obes 2020 Jun;27(3):132-139. doi: 10.1097/MED.0000000000000538. PMID: 32209819
Adrenal tumors: when to search for a germline abnormality?
Gimenez-Roqueplo AP
Curr Opin Oncol 2019 May;31(3):230-235. doi: 10.1097/CCO.0000000000000525. PMID: 30985498
Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience.
Memon SS, Thakkar K, Patil V, Jadhav S, Lila AR, Fernandes G, Bandgar TR, Shah NS
J Pediatr Endocrinol Metab 2019 Apr 24;32(4):391-397. doi: 10.1515/jpem-2018-0413. PMID: 30875328
Laparoscopic unilateral adrenalectomy in children for isolated primary pigmented nodular adrenocortical disease (PPNAD): case report and literature review.
Guanà R, Gesmundo R, Morino M, Matarazzo P, Pucci A, Pasini B, Lala R, Fiore L, Repici M, Canavese F
Eur J Pediatr Surg 2010 Jul;20(4):273-5. Epub 2010 Jan 22 doi: 10.1055/s-0029-1243203. PMID: 20099223

Diagnosis

Bilateral Adrenocortical Nodular Disease and Cushing's Syndrome.
Bouys L, Violon F, Louiset E, Sibony M, Lefebvre H, Bertherat J
J Clin Endocrinol Metab 2024 Sep 16;109(10):2422-2432. doi: 10.1210/clinem/dgae419. PMID: 38888184
Cushing Syndrome in Childhood.
Parish A, Cheung C, Ryabets-Lienhard A, Zamiara P, Kim MS
Pediatr Rev 2024 Jan 1;45(1):14-25. doi: 10.1542/pir.2022-005732. PMID: 38161162
Adrenocortical hyperplasia: A multifaceted disease.
Bourdeau I, Parisien-La Salle S, Lacroix A
Best Pract Res Clin Endocrinol Metab 2020 May;34(3):101386. Epub 2020 Feb 4 doi: 10.1016/j.beem.2020.101386. PMID: 32115357
Carney complex review: Genetic features.
Bosco Schamun MB, Correa R, Graffigna P, de Miguel V, Fainstein Day P
Endocrinol Diabetes Nutr (Engl Ed) 2018 Jan;65(1):52-59. Epub 2017 Nov 20 doi: 10.1016/j.endinu.2017.09.006. PMID: 29162369
Rare syndromes.
Jabbour SA, Davidovici BB, Wolf R
Clin Dermatol 2006 Jul-Aug;24(4):299-316. doi: 10.1016/j.clindermatol.2006.04.005. PMID: 16828412

Therapy

Germline PRKACA amplification-associated primary pigmented nodular adrenocortical disease: a case report and literature review.
Yang WR, Liang XH, Qin YF, Yang HY, He SZ, Huang ZX, Liu YP, Luo ZJ
Arch Endocrinol Metab 2023 Nov 17;68:e220491. doi: 10.20945/2359-4292-2022-0491. PMID: 37988664Free PMC Article
Predicting the risk of cardiac myxoma in Carney complex.
Pitsava G, Zhu C, Sundaram R, Mills JL, Stratakis CA
Genet Med 2021 Jan;23(1):80-85. Epub 2020 Sep 7 doi: 10.1038/s41436-020-00956-3. PMID: 32893266Free PMC Article
c-KIT oncogene expression in PRKAR1A-mutant adrenal cortex.
Nadella K, Faucz FR, Stratakis CA
Endocr Relat Cancer 2020 Oct;27(10):591-599. doi: 10.1530/ERC-20-0270. PMID: 32738126Free PMC Article
Update on primary micronodular bilateral adrenocortical diseases.
Maillet M, Bourdeau I, Lacroix A
Curr Opin Endocrinol Diabetes Obes 2020 Jun;27(3):132-139. doi: 10.1097/MED.0000000000000538. PMID: 32209819
Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience.
Memon SS, Thakkar K, Patil V, Jadhav S, Lila AR, Fernandes G, Bandgar TR, Shah NS
J Pediatr Endocrinol Metab 2019 Apr 24;32(4):391-397. doi: 10.1515/jpem-2018-0413. PMID: 30875328

Prognosis

Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome.
Berthon A, Bertherat J
Horm Metab Res 2020 Aug;52(8):598-606. Epub 2020 Feb 25 doi: 10.1055/a-1061-7349. PMID: 32097969
Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience.
Memon SS, Thakkar K, Patil V, Jadhav S, Lila AR, Fernandes G, Bandgar TR, Shah NS
J Pediatr Endocrinol Metab 2019 Apr 24;32(4):391-397. doi: 10.1515/jpem-2018-0413. PMID: 30875328
Primary pigmented nodular adrenocortical disease: literature review and case report of a 6-year-old boy.
Katanić D, Kafka D, Živojinov M, Vlaški J, Budakov Z, Knežević Pogančev M, Vorgučin I, Ćuk T
J Pediatr Endocrinol Metab 2017 May 1;30(5):603-609. doi: 10.1515/jpem-2016-0249. PMID: 28391254
Laparoscopic unilateral adrenalectomy in children for isolated primary pigmented nodular adrenocortical disease (PPNAD): case report and literature review.
Guanà R, Gesmundo R, Morino M, Matarazzo P, Pucci A, Pasini B, Lala R, Fiore L, Repici M, Canavese F
Eur J Pediatr Surg 2010 Jul;20(4):273-5. Epub 2010 Jan 22 doi: 10.1055/s-0029-1243203. PMID: 20099223
Adrenocorticotropic hormone-independent Cushing's syndrome.
Bourdeau I, Lampron A, Costa MH, Tadjine M, Lacroix A
Curr Opin Endocrinol Diabetes Obes 2007 Jun;14(3):219-25. doi: 10.1097/MED.0b013e32814db842. PMID: 17940443

Clinical prediction guides

Bilateral Adrenocortical Nodular Disease and Cushing's Syndrome.
Bouys L, Violon F, Louiset E, Sibony M, Lefebvre H, Bertherat J
J Clin Endocrinol Metab 2024 Sep 16;109(10):2422-2432. doi: 10.1210/clinem/dgae419. PMID: 38888184
Update of Genetic and Molecular Causes of Adrenocortical Hyperplasias Causing Cushing Syndrome.
Berthon A, Bertherat J
Horm Metab Res 2020 Aug;52(8):598-606. Epub 2020 Feb 25 doi: 10.1055/a-1061-7349. PMID: 32097969
PRKAR1A mutations in primary pigmented nodular adrenocortical disease.
Cazabat L, Ragazzon B, Groussin L, Bertherat J
Pituitary 2006;9(3):211-9. doi: 10.1007/s11102-006-0266-1. PMID: 17036196
Carney complex (CNC).
Bertherat J
Orphanet J Rare Dis 2006 Jun 6;1:21. doi: 10.1186/1750-1172-1-21. PMID: 16756677Free PMC Article
Primary pigmented nodular adrenocortical disease. A light and electron microscopic study of eight cases.
Travis WD, Tsokos M, Doppman JL, Nieman L, Chrousos GP, Cutler GB Jr, Loriaux DL, Norton JA
Am J Surg Pathol 1989 Nov;13(11):921-30. PMID: 2679153

Recent systematic reviews

The clinical characteristics and pathogenic variants of primary pigmented nodular adrenocortical disease in 210 patients: a systematic review.
Sun J, Ding L, He L, Fu H, Li R, Feng J, Dong J, Liao L
Front Endocrinol (Lausanne) 2024;15:1356870. Epub 2024 Jun 26 doi: 10.3389/fendo.2024.1356870. PMID: 39006359Free PMC Article

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