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Horm Metab Res 2016; 48(04): 242-246
DOI: 10.1055/s-0042-103686
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Use of 3-Dimensional Volumetric Modeling of Adrenal Gland Size in Patients with Primary Pigmented Nodular Adrenocortical Disease

P. P. Chrysostomou
1   Program on Developmental Endocrinology and Genetics, Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA
,
M. B. Lodish
1   Program on Developmental Endocrinology and Genetics, Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA
,
E. B. Turkbey
2   Radiology and Imaging Sciences, Clinical Center, and National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA
,
G. Z. Papadakis
3   Department of Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA
,
C. A. Stratakis
1   Program on Developmental Endocrinology and Genetics, Section on Endocrinology & Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA
› Author Affiliations
Further Information

Publication History

received 24 July 2015

accepted 15 February 2016

Publication Date:
11 April 2016 (online)

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Abstract

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare type of bilateral adrenal hyperplasia leading to hypercortisolemia. Adrenal nodularity is often appreciable with computed tomography (CT); however, accurate radiologic characterization of adrenal size in PPNAD has not been studied well. We used 3-dimensional (3D) volumetric analysis to characterize and compare adrenal size in PPNAD patients, with and without Cushing’s syndrome (CS). Patients diagnosed with PPNAD and their family members with known mutations in PRKAR1A were screened. CT scans were used to create 3D models of each adrenal. Criteria for biochemical diagnosis of CS included loss of diurnal variation and/or elevated midnight cortisol levels, and paradoxical increase in urinary free cortisol and/or urinary 17-hydroxysteroids after dexamethasone administration. Forty-five patients with PPNAD (24 females, 27.8±17.6 years) and 8 controls (19±3 years) were evaluated. 3D volumetric modeling of adrenal glands was performed in all. Thirty-eight patients out of 45 (84.4%) had CS. Their mean adrenal volume was 8.1 cc±4.1, 7.2 cc±4.5 (p=0.643) for non-CS, and 8.0cc±1.6 for controls. Mean values were corrected for body surface area; 4.7 cc/kg/m2±2.2 for CS, and 3.9 cc/kg/m2±1.3 for non-CS (p=0.189). Adrenal volume and midnight cortisol in both groups was positively correlated, r=0.35, p=0.03. We conclude that adrenal volume measured by 3D CT in patients with PPNAD and CS was similar to those without CS, confirming empirical CT imaging-based observations. However, the association between adrenal volume and midnight cortisol levels may be used as a marker of who among patients with PPNAD may develop CS, something that routine CT cannot do.

Key words

PPNAD - 3D imaging - CT - adrenals - cushing’s syndrome
 

  • References

  • 1 Lacroix A, Feelders RA, Stratakis CA, Nieman LK. Cushing’s syndrome. Lancet 2015; 386: 913-927
    CrossrefPubMedSearch in Google Scholar
  • 2 Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the Carney complex. Hum Mol Genet 2000; 9: 3037-3046
    CrossrefPubMedSearch in Google Scholar
  • 3 Groussin L, Jullian E, Perlemoine K, Louvel A, Leheup B, Luton JP, Bertagna X, Bertherat J. 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
    Search in Google Scholar
  • 4 Louiset E, Stratakis CA, Perraudin V, Griffin KJ, Libé R, Cabrol S, Fève B, Young J, Groussin L, Bertherat J, Lefebvre H. 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. J Clin Endocrinol Metab 2009; 94: 2406-2413
    CrossrefPubMedSearch in Google Scholar
  • 5 Stratakis CA, Boikos SA. Genetics of adrenal tumors associated with Cushing’s syndrome: a new classification for bilateral adrenocortical hyperplasias. Nat Clin Pract End Met 2007; 3: 748-757
    CrossrefPubMedSearch in Google Scholar
  • 6 Stratakis CA, Sarlis N, Kirschner LS, Carney JA, Doppman JL, Nieman LK, Chrousos GP, Papanicolaou DA. Paradoxical response to dexamethasone in the diagnosis of primary pigmented nodular adrenocortical disease. Ann Intern Med 1999; 131: 585-591
    PubMedSearch in Google Scholar
  • 7 Powell AC, Stratakis CA, Patronas NJ, Steinberg SM, Batista D, Alexander HR, Pingpank JF, Keil M, Bartlett DL, Libutti SK. Operative management of Cushing Syndrome secondary to micronodular adrenal hyperplasia. Surgery 2008; 143: 750-758
    CrossrefPubMedSearch in Google Scholar
  • 8 Horvath A, Stratakis C. Primary pigmented nodular adrenocortical disease and Cushing’s syndrome. Arquiv Brasil Endocrinol Metab 2007; 51: 1238-1244
    PubMedSearch in Google Scholar
  • 9 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Storr HL, Mitchell H, Swords FM, Main KM, Hindmarsh PC, Betts PR, Shaw NJ, Johnston DI, Clark AJL, Reznek RH, Grossman AB, Savage MO. Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing’s syndrome due to primary nodular adrenocortical hyperplasia. Clinical Endocrinology 2004; 61: 553-559
    CrossrefPubMedSearch in Google Scholar
  • 11 Dunnick NR, Doppman JL, Gill JR, Strott CA, Keiser HR, Brennan MF. Localization of functional adrenal tumors by computed tomography and venous sampling. Radiology 1982; 142: 429-433
    CrossrefPubMedSearch in Google Scholar
  • 12 Reincke M. Subclinical Cushing’s Syndrome. Endocrinol Metab Clin North Am 2000; 29: 43-56
    CrossrefPubMedSearch in Google Scholar
  • 13 Batista DL, Riar J, Keil M, Stratakis CA. Diagnostic tests for children who are referred for the investigation of Cushing syndrome. Pediatrics 2007; 120: 576-586
    CrossrefPubMedSearch in Google Scholar
  • 14 Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing’s syndrome. The Journal of Clinical Endocrinology & Metabolism 1960; 20: 1539-1560
    CrossrefPubMedSearch in Google Scholar
  • 15 Rockall AG, Babar SA, Sohaib SAA, Isidori AM, Diaz-Cano S, Monson JP, Grossman AB, Reznek RH. CT and MR Imaging of the Adrenal Glands in ACTH-independent Cushing Syndrome. RadioGraphics 2004; 24: 435-452
    CrossrefPubMedSearch in Google Scholar
  • 16 Meier JM, Alavi A, Iruvuri S, Alzeair S, Parker R, Houseni M, Hernandez-Pampaloni M, Mong A, Torigian DA. Assessment of Age-Related Changes in Abdominal Organ Structure and Function With Computed Tomography and Positron Emission Tomography. Semin Nucl Med 2007; 37: 154-172
    CrossrefPubMedSearch in Google Scholar
  • 17 Kempná P, Flück CE. Adrenal gland development and defects. Best Prac Res Clin Endocrinol Metab 2008; 22: 77-93
    CrossrefPubMedSearch in Google Scholar