pigmented nodular adrenocortical disease
Definition: Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushing’s syndrome.
Even though primary pigmented nodular adrenocortical disease is a rare cause of Cushing’s syndrome, it should be included in the differential diagnosis of adrenocorticotropic hormone-independent Cushing’s syndrome, especially because adrenal imaging can be misleading mimicking other adrenocortical diseases.
Bilateral laparoscopic adrenalectomy is the preferred treatment in these subjects.
Association
Carney complex
- Cushing disease, spotty cutaneous pigmentation, cutaneous and cardiac myxomas, growth hormone secreting pituitary adenomas, psammomatous melanotic schwannomas, multiple myxoid fibroadenomas of breast in females, large cell calcifying Sertoli tumors of testis in males
Macroscopy
variable sized adrenal glands with multiple brown-black pigmented cortical nodules
possible unilateral adrenocortical nodule (#20670433#)
Microscopy
sharply circumscribed nodules composed of eosinophilic lipid-poor cells similar to normal zone reticularis
growth pattern: trabecular
prominent lipofuscin deposits in zona fasciculata
focal necrosis
mitotic activity
Etiology
mutations in the PRKAR1A gene coding for the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (#12424709#)
Open Access References
Primary pigmented nodular adrenocortical disease. Ngow HA, Khairina WM. Endokrynol Pol. 2011;62(3):268-70. PMID: #21717412# [Free]
Primary pigmented nodular adrenocortical disease presenting with a unilateral adrenocortical nodule treated with bilateral laparoscopic adrenalectomy: a case report. Zografos GN, Pappa T, Avlonitis S, Markou A, Chrysikos DT, Kaltsas G, Aggeli C, Piaditis G. J Med Case Reports. 2010 Jul 29;4:230.PMID: #20670433# [Free]
Cushing’s syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice. Sahut-Barnola I, de Joussineau C, Val P, Lambert-Langlais S, Damon C, Lefrançois-Martinez AM, Pointud JC, Marceau G, Sapin V, Tissier F, Ragazzon B, Bertherat J, Kirschner LS, Stratakis CA, Martinez A. PLoS Genet. 2010 Jun 10;6(6):e1000980. PMID: #20548949# [Free]
Association of the M1V PRKAR1A mutation with primary pigmented nodular adrenocortical disease in two large families. Pereira AM, Hes FJ, Horvath A, Woortman S, Greene E, Bimpaki E, Alatsatianos A, Boikos S, Smit JW, Romijn JA, Nesterova M, Stratakis CA. J Clin Endocrinol Metab. 2010 Jan;95(1):338-42. PMID: #19915019# [Free]
Inactivation of the Carney complex gene 1 (protein kinase A regulatory subunit 1A) inhibits SMAD3 expression and TGF beta-stimulated apoptosis in adrenocortical cells. Ragazzon B, Cazabat L, Rizk-Rabin M, Assie G, Groussin L, Fierrard H, Perlemoine K, Martinez A, Bertherat J. Cancer Res. 2009 Sep 15;69(18):7278-84. PMID: #19738044# [Free]
The paradoxical increase in cortisol secretion induced by dexamethasone in primary pigmented nodular adrenocortical disease involves a glucocorticoid receptor-mediated effect of dexamethasone on protein kinase A catalytic subunits. Louiset E, Stratakis CA, Perraudin V, Griffin KJ, Libé R, Cabrol S, Fève B, Young J, Groussin L, Bertherat J, Lefebvre H. J Clin Endocrinol Metab. 2009 Jul;94(7):2406-13. PMID: #19383776# [Free]
MicroRNA signature of primary pigmented nodular adrenocortical disease: clinical correlations and regulation of Wnt signaling. Iliopoulos D, Bimpaki EI, Nesterova M, Stratakis CA. Cancer Res. 2009 Apr 15;69(8):3278-82. PMID: #19351815# [Free]
Mutations in regulatory subunit type 1A of cyclic adenosine 5’-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. Bertherat J, Horvath A, Groussin L, Grabar S, Boikos S, Cazabat L, Libe R, René-Corail F, Stergiopoulos S, Bourdeau I, Bei T, Clauser E, Calender A, Kirschner LS, Bertagna X, Carney JA, Stratakis CA. J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91. PMID: #19293268# [Free]
New genes and/or molecular pathways associated with adrenal hyperplasias and related adrenocortical tumors. Stratakis CA. Mol Cell Endocrinol. 2009 Mar 5;300(1-2):152-7. PMID: #19063937# [Free]
Operative management of Cushing syndrome secondary to micronodular adrenal hyperplasia. Powell AC, Stratakis CA, Patronas NJ, Steinberg SM, Batista D, Alexander HR, Pingpank JF, Keil M, Bartlett DL, Libutti SK. Surgery. 2008 Jun;143(6):750-8. PMID: #18549891# [Free]
Expression of progesterone and estradiol receptors in normal adrenal cortex, adrenocortical tumors, and primary pigmented nodular adrenocortical disease. de Cremoux P, Rosenberg D, Goussard J, Brémont-Weil C, Tissier F, Tran-Perennou C, Groussin L, Bertagna X, Bertherat J, Raffin-Sanson ML. Endocr Relat Cancer. 2008 Jun;15(2):465-74. PMID: #18508999# [Free]
Phosphodiesterase 11A expression in the adrenal cortex, primary pigmented nodular adrenocortical disease, and other corticotropin-independent lesions. Boikos SA, Horvath A, Heyerdahl S, Stein E, Robinson-White A, Bossis I, Bertherat J, Carney JA, Stratakis CA. Horm Metab Res. 2008 May;40(5):347-53. PMID: #18491255# [Free]
Primary pigmented nodular adrenocortical disease and Cushing’s syndrome. Horvath A, Stratakis C. Arq Bras Endocrinol Metabol. 2007 Nov;51(8):1238-44. Review. PMID: #18209861# [Free]
Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review. Gonçalves FT, Feibelmann TC, Mendes CM, Fernandes ML, Miranda GH, Gouvêa AP, Jorge PT. Sao Paulo Med J. 2006 Nov 7;124(6):336-9. PMID: #17322955# [Free]
Primary pigmented nodular adrenocortical disease reveals insulin-like growth factor binding protein-2 regulation by protein kinase A. Shi Z, Henwood MJ, Bannerman P, Batista D, Horvath A, Guttenberg M, Stratakis CA, Grimberg A. Growth Horm IGF Res. 2007 Apr;17(2):113-21. Epub 2007 Feb 5. PMID: #17280861# [Free]
Unravelling the mystery in a case of persistent ACTH-independent Cushing’s syndrome. Lim LC, Tan LH, Rajasoorya C. Ann Acad Med Singapore. 2006 Dec;35(12):892-6. PMID: #17219002# [Free]
References
Familial micronodular adrenocortical disease, Cushing syndrome, and mutations of the gene encoding phosphodiesterase 11A4 (PDE11A). Carney JA, Gaillard RC, Bertherat J, Stratakis CA. Am J Surg Pathol. 2010 Apr;34(4):547-55. PMID: #20351491#
Primary pigmented nodular adrenocortical disease: a case report in a 7-year-old girl. Leka S, Kousta E, Anyfandakis K, Dolianiti M, Vakaki M, Linos D, Chrousos GP, Papathanasiou A. J Pediatr Endocrinol Metab. 2011;24(3-4):197-202. PMID: #21648292#