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CC BY-NC-ND 4.0 · Horm Metab Res 2022; 54(11): 721-730
DOI: 10.1055/a-1948-6990
Review

Treatment of Primary Pigmented Nodular Adrenocortical Disease

Xinming Liu
1   Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
,
Siwen Zhang
1   Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
,
Yunran Guo
1   Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
,
Xiaokun Gang‡
1   Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
,
Guixia Wang‡
1   Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, China
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Abstract

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of adrenocorticotropin hormone (ACTH)-independent Cushing’s syndrome (CS), which mainly occurs in children and young adults. Treatment options with proven clinical efficacy for PPNAD include adrenalectomy (bilateral or unilateral adrenalectomy) and drug treatment to control hypercortisolemia. Previously, the main treatment of PPNAD is bilateral adrenal resection and long-term hormone replacement after surgery. In recent years, cases reports suggest that unilateral or subtotal adrenal resection can also lead to long-term remission in some patients without the need for long-term hormone replacement therapy. Medications for hypercortisolemia, such as Ketoconazole, Metyrapone and Mitotane et.al, have been reported as a preoperative transition for in some patients with severe hypercortisolism. In addition, tryptophan hydroxylase inhibitor, COX2 inhibitor Celecoxib, somatostatin and other drugs targeting the possible pathogenic mechanisms of the disease are under study, which are expected to be applied to the clinical treatment of PPNAD in the future. In this review, we summarize the recent progress on treatment of PPNAD, in which options of surgical methods, research results of drugs acting on possible pathogenic mechanisms, and the management during gestation are described in order to provide new ideas for clinical treatment.

Key words

primary pigmented nodular adrenocortical disease (PPNAD) - adrenocorticotropin hormone (ACTH)-independent Cushing’s syndrome (CS) - hypercortisolemia - Carney complex (CNC) - adrenalectomy


Publication History

Received: 21 December 2021

Accepted after revision: 14 September 2022

Accepted Manuscript online:
21 September 2022

Article published online:
10 November 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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  • References

  • 1 Shenoy BV, Carpenter PC, Carney JA. Bilateral primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol 1984; 8: 335-344
    CrossrefPubMedGoogle Scholar
  • 2 Ammini AC, Tandon N, Gupta N. et al. Etiology and clinical profile of patients with Cushing’s syndrome: a single center experience. Indian J Endocrinol Metab 2014; 18: 99-105
    CrossrefPubMedGoogle Scholar
  • 3 Zhou J, Zhang M, Bai X. et al. Demographic characteristics, etiology, and comorbidities of patients with Cushing’s syndrome: a 10-year retrospective study at a large general hospital in China. Int J Endocrinol 2019; 7159696
    PubMedGoogle Scholar
  • 4 Stratakis CA. Adrenocortical tumors, primary pigmented adrenocortical disease (PPNAD)/Carney complex, and other bilateral hyperplasias: the NIH studies. Horm Metab Res 2007; 39: 467-473
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Carney JA, Gordon H, Carpenter PC. et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine 1985; 64: 270-283
    CrossrefPubMedGoogle Scholar
  • 6 Bertherat J. Carney complex (CNC). Orphanet J Rare Dis 2006; 1: 21
    CrossrefPubMedGoogle Scholar
  • 7 Correa R, Salpea P, Stratakis CA. Carney complex: an update. Eur J Endocrinol 2015; 173: M85-M97
    CrossrefPubMedGoogle Scholar
  • 8 Memon SS, Thakkar K, Patil V. et al. Primary pigmented nodular adrenocortical disease (PPNAD): single centre experience. J Pediatr Endocrinol Metab 2019; 32: 391-397
    CrossrefPubMedGoogle Scholar
  • 9 Chen S, Li R, Lu L. et al. Efficacy of dexamethasone suppression test during the diagnosis of primary pigmented nodular adrenocortical disease in Chinese adrenocorticotropic hormone-independent Cushing syndrome. Endocrine 2018; 59: 183-190
    CrossrefPubMedGoogle Scholar
  • 10 Lowe KM, Young WF, Lyssikatos C. et al. Cushing syndrome in Carney complex: clinical, pathologic, and molecular genetic findings in the 17 affected Mayo clinic patients. Am J Surg Pathol 2017; 41: 171-181
    CrossrefPubMedGoogle Scholar
  • 11 Gunther DF, Bourdeau I, Matyakhina L. et al. Cyclical Cushing syndrome presenting in infancy: an early form of primary pigmented nodular adrenocortical disease, or a new entity?. J Clin Endocrinol Metab 2004; 89: 3173-3182
    CrossrefPubMedGoogle Scholar
  • 12 Powell AC, Stratakis CA, Patronas NJ. et al. Operative management of Cushing syndrome secondary to micronodular adrenal hyperplasia. Surgery 2008; 143: 750-758
    CrossrefPubMedGoogle Scholar
  • 13 Xu Y, Rui W, Qi Y. et al. The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias. World J Surg 2013; 37: 1626-1632
    CrossrefPubMedGoogle Scholar
  • 14 Kyrilli A, Lytrivi M, Bouquegneau MS. et al. Unilateral adrenalectomy could be a valid öption for primary nodular adrenal disease: evidence from twins. J Endocr Soc 2019; 3: 129-134
    CrossrefPubMedGoogle Scholar
  • 15 Sarlis NJ, Chrousos GP, Doppman JL. et al. Primary pigmented nodular adrenocortical disease: reevaluation of a patient with carney complex 27 years after unilateral adrenalectomy. J Clin Endocrinol Metab 1997; 82: 1274-1278
    CrossrefPubMedGoogle Scholar
  • 16 Campo MR, Lamacchia O, Farese A. et al. Mitotane and Carney complex: ten years follow-up of a low-dose mitotane regimen inducing a sustained correction of hypercortisolism. Hormones (Athens, Greece) 2015; 14: 300-304
    PubMedGoogle Scholar
  • 17 Bram Z, Louiset E, Ragazzon B. et al. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease. JCI Insight 2016; 1: e87958
    CrossrefPubMedGoogle Scholar
  • 18 Bram Z, Xekouki P, Louiset E. et al. Does somatostatin have a role in the regulation of cortisol secretion in primary pigmented nodular adrenocortical disease (ppnad)? a clinical and in vitro investigation. J Clin Endocrinol Metab 2014; 99: E891-E901
    CrossrefPubMedGoogle Scholar
  • 19 Kurtova AV, Xiao J, Mo Q. et al. Blocking PGE2-induced tumour repopulation abrogates bladder cancer chemoresistance. Nature 2015; 517: 209-213
    CrossrefPubMedGoogle Scholar
  • 20 Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 2001; 86: 4041-4046
    CrossrefPubMedGoogle Scholar
  • 21 Bertherat J, Horvath A, Groussin L. et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5’-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab 2009; 94: 2085-2091
    CrossrefPubMedGoogle Scholar
  • 22 Lacroix A, Feelders RA, Stratakis CA. et al. Cushing’s syndrome. Lancet 2015; 386: 913-927
    CrossrefPubMedGoogle Scholar
  • 23 Boscaro M, Barzon L, Fallo F. et al. Cushing’s syndrome. Lancet 2001; 357: 783-791
    CrossrefPubMedGoogle Scholar
  • 24 Groussin L, Jullian E, Perlemoine K. et al. Mutations of the PRKAR1A gene in Cushing’s syndrome due to sporadic primary pigmented nodular adrenocortical disease. J Clin Endocrinol Metab 2002; 87: 4324-4329
    CrossrefPubMedGoogle Scholar
  • 25 Cyranska-Chyrek E, Filipowicz D, Szczepanek-Parulska E. et al. Primary pigmented nodular adrenocortical disease (PPNAD) as an underlying cause of symptoms in a patient presenting with hirsutism and secondary amenorrhea: case report and literature review. Gynecol Endocrinol 2018; 34: 1022-1026
    CrossrefPubMedGoogle Scholar
  • 26 Stratakis CA, Carney JA, Lin JP. et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996; 97: 699-705
    CrossrefPubMedGoogle Scholar
  • 27 Stratakis CA. Diagnosis and clinical genetics of Cushing syndrome in pediatrics. Endocrinol Metab Clin North Am 2016; 45: 311-328
    Google Scholar
  • 28 Attri B, Aggarwal A, Mattoo S. et al. Cushing’s syndrome due to primary pigmented nodular adrenal disease in two brothers with Carney complex. Pediatr Endocrinol Diabetes Metab 2020; 26: 155-158
    CrossrefPubMedGoogle Scholar
  • 29 da Silva RM, Pinto E, Goldman SM. et al. Children with Cushing’s syndrome: primary pigmented nodular adrenocortical disease should always be suspected. Pituitary 2011; 14: 61-67
    CrossrefPubMedGoogle Scholar
  • 30 Storr HL, Chan LF, Grossman AB. et al. Paediatric Cushing’s syndrome: epidemiology, investigation and therapeutic advances. Trends Endocrinol Metab 2007; 18: 167-174
    CrossrefPubMedGoogle Scholar
  • 31 Lumbroso S, Paris F, Sultan C. Activating Gsalpha mutations: analysis of 113 patients with signs of McCune-Albright syndrome – a European collaborative study. J Clin Endocrinol Metab 2004; 89: 2107-2113
    CrossrefPubMedGoogle Scholar
  • 32 Brown RJ, Kelly MH, Collins MT. Cushing syndrome in the McCune-Albright syndrome. J Clin Endocrinol Metab 2010; 95: 1508-1515
    CrossrefPubMedGoogle Scholar
  • 33 El Ghorayeb N, Bourdeau I, Lacroix A. Multiple aberrant hormone receptors in Cushing’s syndrome. Eur J Endocrinol 2015; 173: M45-M60
    CrossrefPubMedGoogle Scholar
  • 34 Nieman LK, Biller BM, Findling JW. et al. The diagnosis of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
    Google Scholar
  • 35 Carney JA, Young WFJ. Primary pigmented nodular adrenocortical disease and its associated conditions. Endocrinologist 1992; 2: 6-21
    CrossrefPubMedGoogle Scholar
  • 36 Courcoutsakis NA, Tatsi C, Patronas NJ. et al. The complex of myxomas, spotty skin pigmentation and endocrine overactivity (Carney complex): imaging findings with clinical and pathological correlation. Insights Imaging 2013; 4: 119-133
    CrossrefPubMedGoogle Scholar
  • 37 Vezzosi D, Tenenbaum F, Cazabat L. et al. Hormonal, radiological, NP-59 scintigraphy, and pathological correlations in patients with Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). J Clin Endocrinol Metab 2015; 100: 4332-4338
    CrossrefPubMedGoogle Scholar
  • 38 Defilippi C, Chiappetta D, Marzari D. et al. Image diagnosis in McCune-Albright syndrome. J Pediatr Endocrinol Metab 2006; 19: 561-570
    CrossrefPubMedGoogle Scholar
  • 39 Stratakis CA, Sarlis N, Kirschner LS. et al. Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999; 131: 585-591
    CrossrefPubMedGoogle Scholar
  • 40 Espiard S, Vantyghem MC, Assié G. et al. Frequency and incidence of Carney complex manifestations: a prospective multicenter study with a three-year follow-up. J Clin Endocrinol Metab 2020; 105 dgaa002 DOI: 10.1210/clinem/dgaa002.
    CrossrefPubMedGoogle Scholar
  • 41 Bourdeau I, Parisien-La Salle S, Lacroix A. Adrenocortical hyperplasia: a multifaceted disease. Best Pract Res Clin Endocrinol Metab 2020; 34: 101386
    CrossrefPubMedGoogle Scholar
  • 42 Morio H, Terano T, Yamamoto K. et al. Serum levels of dehydroepiandrosterone sulfate in patients with asymptomatic cortisol producing adrenal adenoma: comparison with adrenal Cushing’s syndrome and non-functional adrenal tumor. Endocri J 1996; 43: 387-396
    CrossrefPubMedGoogle Scholar
  • 43 Hofland J, de Herder WW, Derks L. et al. Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing’s syndrome. Eur J Endocrinol 2013; 168: 67-74
    CrossrefPubMedGoogle Scholar
  • 44 Navarro Moreno C, Delestienne A, Marbaix E. et al. Familial forms of Cushing syndrome in primary pigmented nodular adrenocortical disease presenting with short stature and insidious symptoms: a clinical series. Horm Res Paediatr 2018; 89: 423-433
    CrossrefPubMedGoogle Scholar
  • 45 Horvath A, Boikos S, Giatzakis C. et al. A genome-wide scan identifies mutations in the gene encoding phosphodiesterase 11A4 (PDE11A) in individuals with adrenocortical hyperplasia. Nat Genet 2006; 38: 794-800
    CrossrefPubMedGoogle Scholar
  • 46 Horvath A, Giatzakis C, Tsang K. et al. A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex. Eur J Hum Genet 2008; 16: 1245-1253
    CrossrefPubMedGoogle Scholar
  • 47 Kamilaris CDC, Faucz FR, Andriessen VC. et al. First somatic PRKAR1A defect associated with mosaicism for another PRKAR1A mutation in a patient with Cushing syndrome. J Endocr Soc 2021; 5 bvab007
    PubMedGoogle Scholar
  • 48 Tadjine M, Lampron A, Ouadi L. et al. Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD). Clin Endocrinol 2008; 69: 367-373
    CrossrefPubMedGoogle Scholar
  • 49 Storr HL, Mitchell H, Swords FM. et al. Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing’s syndrome due to primary nodular adrenocortical hyperplasia. Clin Endocrinol 2004; 61: 553-559
    CrossrefPubMedGoogle Scholar
  • 50 Kumorowicz-Czoch M, Dolezal-Oltarzewska K, Roztoczynska D. et al. Causes and consequences of abandoning one-stage bilateral adrenalectomy recommended in primary pigmented nodular adrenocortical disease – case presentation. J Pediatr Endocrinol Metab 2011; 24: 565-567
    CrossrefPubMedGoogle Scholar
  • 51 Ferreira SH, Costa MM, Rios E. et al. Carney complex due to a novel pathogenic variant in the PRKAR1A gene – a case report. J Pediatr Endocrinol Metab 2019; 32: 197-202
    CrossrefPubMedGoogle Scholar
  • 52 Nieman LK, Biller BM, Findling JW. et al. Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100: 2807-2831
    CrossrefPubMedGoogle Scholar
  • 53 Madani A, Lee JA. Surgical approaches to the adrenal gland. Surg Clin North Am 2019; 99: 773-791
    CrossrefPubMedGoogle Scholar
  • 54 Kiriakopoulos A, Linos D. Carney syndrome presented as a pathological spine fracture in a 35-year-old male. Am J Case Rep 2018; 19: 1366-1369
    CrossrefPubMedGoogle Scholar
  • 55 Yoshiaki Tanno F, Srougi V, Almeida MQ. et al. A new insight into the surgical treatment of primary macronodular adrenal hyperplasia. J Endocr Soc 2020; 4 bvaa083
    PubMedGoogle Scholar
  • 56 Zhang Y, Li H. Classification and surgical treatment for 180 cases of adrenocortical hyperplastic disease. Int J Clin Exp Med 2015; 8: 19311-19317
    PubMedGoogle Scholar
  • 57 Zhang CD, Pichurin PN, Bobr A. et al. Cushing syndrome: uncovering Carney complex due to novel PRKAR1A mutation. Endocrinol Diabetes Metab Case Rep 2019; 18-0150 DOI: 10.1530/EDM-18-0150. Online ahead of print
    CrossrefPubMedGoogle Scholar
  • 58 Guanà R, Gesmundo R, Morino M. et al. Laparoscopic unilateral adrenalectomy in children for isolated primary pigmented nodular adrenocortical disease (PPNAD): case report and literature review. Eur J Pediatr Surg 2010; 20: 273-275
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 Cohen O, Bogat S, Dolitzki M. et al. Successful pregnancy after unilateral adrenalectomy in a case of primary pigmented adrenocortical disease. J Matern-Fetal Neonat Med 2005; 17: 161-163
    CrossrefPubMedGoogle Scholar
  • 60 Zhu Y, Wu YX, Rui WB. et al. Primary pigmented nodular adrenocortical disease report of 5 cases. Zhonghua wai ke za zhi [Chin J Surg] 2005; 43: 944-947
    PubMedGoogle Scholar
  • 61 Pasternak-Pietrzak K, Stratakis CA, Moszczyńska E. et al. Detection of new potentially pathogenic mutations in two patients with primary pigmented nodular adrenocortical disease (PPNAD) – case reports with literature review. Endokrynol Pol 2018; 69: 675-681
    CrossrefPubMedGoogle Scholar
  • 62 Iacobone M, Albiger N, Scaroni C. et al. The role of unilateral adrenalectomy in ACTH-independent macronodular adrenal hyperplasia (AIMAH). World J Surg 2008; 32: 882-889
    CrossrefPubMedGoogle Scholar
  • 63 Vezzosi D, Cartier D, Régnier C. et al. Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors. Eur J Endocrinol 2007; 156: 21-31
    CrossrefPubMedGoogle Scholar
  • 64 Lamas C, Alfaro JJ, Lucas T. et al. Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases. Eur J Endocrinol 2002; 146: 237-240
    CrossrefPubMedGoogle Scholar
  • 65 van der Pas R, de Herder WW, Hofland LJ. et al. New developments in the medical treatment of Cushing’s syndrome. Endocr Relat Cancer 2012; 19: R205-R223
    CrossrefPubMedGoogle Scholar
  • 66 Varlamov EV, Han AJ, Fleseriu M. Updates in adrenal steroidogenesis inhibitors for Cushing’s syndrome – a practical guide. Best Pract Res Clin Endocrinol Metab 2021; 35: 101490
    CrossrefPubMedGoogle Scholar
  • 67 Castinetti F, Guignat L, Giraud P. et al. Ketoconazole in Cushing’s disease: is it worth a try?. J Clin Endocrinol Metab 2014; 99: 1623-1630
    CrossrefPubMedGoogle Scholar
  • 68 Costenaro F, Rodrigues TC, de Lima PB. et al. A successful case of Cushing’s disease pregnancy treated with ketoconazole. Gynecol Endocrinol 2015; 31: 176-178
    CrossrefPubMedGoogle Scholar
  • 69 Boronat M, Marrero D, López-Plasencia Y. et al. Successful outcome of pregnancy in a patient with Cushing’s disease under treatment with ketoconazole during the first trimester of gestation. Gynecol Endocrinol 2011; 27: 675-677
    CrossrefPubMedGoogle Scholar
  • 70 Riedl M, Maier C, Zettinig G. et al. Long term control of hypercortisolism with fluconazole: case report and in vitro studies. Eur J Endocrinol 2006; 154: 519-524
    CrossrefPubMedGoogle Scholar
  • 71 Bertagna X, Pivonello R, Fleseriu M. et al. LCI699, a potent 11β-hydroxylase inhibitor, normalizes urinary cortisol in patients with Cushing’s disease: results from a multicenter, proof-of-concept study. J Clin Endocrinol Metab 2014; 99: 1375-1383
    CrossrefPubMedGoogle Scholar
  • 72 Fleseriu M, Pivonello R, Young J. et al. Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, phase II study in Cushing’s disease. Pituitary 2016; 19: 138-148
    CrossrefPubMedGoogle Scholar
  • 73 Skalhegg BS, Tasken K. Specificity in the cAMP/PKA signaling pathway. Differential expression,regulation, and subcellular localization of subunits of PKA. Front Biosc 2000; 5: D678-D693
    PubMedGoogle Scholar
  • 74 Kirschner LS, Sandrini F, Monbo J. et al. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the carney complex. Hum Mol Genet 2000; 9: 3037-3046
    CrossrefPubMedGoogle Scholar
  • 75 Casey M, Vaughan CJ, He J. et al. Mutations in the protein kinase A R1alpha regulatory subunit cause familial cardiac myxomas and Carney complex. J Clin Invest 2000; 106: R31-R38
    CrossrefPubMedGoogle Scholar
  • 76 Kirschner LS, Carney JA, Pack SD. et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet 2000; 26: 89-92
    CrossrefPubMedGoogle Scholar
  • 77 Berthon AS, Szarek E, Stratakis CA. PRKACA: the catalytic subunit of protein kinase A and adrenocortical tumors. Front Cell Develop Biol 2015; 3: 26
    CrossrefPubMedGoogle Scholar
  • 78 de Joussineau C, Sahut-Barnola I, Tissier F. et al. mTOR pathway is activated by PKA in adrenocortical cells and participates in vivo to apoptosis resistance in primary pigmented nodular adrenocortical disease (PPNAD). Hum Mol Gen 2014; 23: 5418-5428
    CrossrefPubMedGoogle Scholar
  • 79 Mavrakis M, Lippincott-Schwartz J, Stratakis CA. et al. Depletion of type IA regulatory subunit (RIalpha) of protein kinase A (PKA) in mammalian cells and tissues activates mTOR and causes autophagic deficiency. Hum Mol Gen 2006; 15: 2962-2971
    CrossrefPubMedGoogle Scholar
  • 80 Sahut-Barnola I, de Joussineau C, Val P. et al. Cushing’s syndrome and fetal features resurgence in adrenal cortex-specific Prkar1a knockout mice. PLoS Genet 2010; 6: e1000980
    CrossrefPubMedGoogle Scholar
  • 81 Liu S, Saloustros E, Berthon A. et al. Celecoxib reduces glucocorticoids in vitro and in a mouse model with adrenocortical hyperplasia. Endocri Relat Cancer 2016; 23: 15-25
    CrossrefPubMedGoogle Scholar
  • 82 Le Mestre J, Duparc C, Reznik Y. et al. Illicit upregulation of serotonin signaling pathway in adrenals of patients with high plasma or intra-adrenal ACTH levels. J Clin Endocrinol Metab 2019; 104: 4967-4980
    CrossrefPubMedGoogle Scholar
  • 83 Ralser DJ, Strizek B, Kupczyk P. et al. Obstetric and neonatal outcome of pregnancy in Carney complex: a case report. Front Endocrinol 2020; 11: 296
    CrossrefPubMedGoogle Scholar
  • 84 Spaniol A, Mulla BM, Daily JG. et al. Carney complex: a rare cause of Cushing syndrome in pregnancy. Obstetr Gynecol. 2014; 124: 426-428
    PubMedGoogle Scholar
  • 85 Schulz S, Redlich A, Köppe I. et al. Carney complex – an unexpected finding during puerperium. Gynecol Obstetr Invest 2001; 51: 211-213
    CrossrefPubMedGoogle Scholar
  • 86 Caticha O, Odell WD, Wilson DE. et al. Estradiol stimulates cortisol production by adrenal cells in estrogen-dependent primary adrenocortical nodular dysplasia. J Clin Endocrinol Metab 1993; 77: 494-497
    PubMedGoogle Scholar
  • 87 Brue T, Amodru V, Castinetti F. Management of endocrine disease: management of Cushing’s syndrome during pregnancy: solved and unsolved questions. Eur J Endocrinol 2018; 178: R259-R266
    CrossrefPubMedGoogle Scholar
  • 88 Caimari F, Valassi E, Garbayo P. et al. Cushing’s syndrome and pregnancy outcomes: a systematic review of published cases. Endocrine 2017; 55: 555-563
    CrossrefPubMedGoogle Scholar
  • 89 Lim WH, Torpy DJ, Jeffries WS. The medical management of Cushing’s syndrome during pregnancy. Eur J Obstetr Gynecol Reprod Biol 2013; 168: 1-6
    CrossrefPubMedGoogle Scholar