Abstract
OBJECTIVE
Primary pigmented nodular adrenocortical disease (PPNAD), an uncommon cause of Cushing’s syndrome, is frequently associated with a wider clinical spectrum, the Carney complex (CC), a multiple endocrine neoplasia syndrome.
DESIGN
We evaluated a low-dose mitotane regimen for treating severe hypercortisolism in a 27-year-old woman with CC. She presented with severe hypercortisolism and a history of surgeries for breast ductal adenoma, atrial cardiac myxomas with cerebral and peripheral arterial embolism, and near-total thyroidectomy because of an oxyphilic adenoma. The patient refused further surgery for adrenalectomy.
RESULTS
During the first 7 months of mitotane (Lysodren, HRA Pharma, Paris, France), the daily oral dose was progressively increased from 0.5 to 4 g/day and then stopped because of the appearance of sustained signs of hypoadrenalism, that required a replacement therapy with 5 mg of prednisone o.d. A 10-month mitotane off-therapy follow-up was performed and when an increase in urine free Cortisol (UFC) was noted, the mitotane regimen was restarted at lower doses (0.750–1 g/day). Serum morning Cortisol levels and UFC were then maintained within the normal range, with plasma mitotane ranging between 2 and 4 mg/L. A sustained regression of Cushing’s features without inducing hypoadrenalism was achieved, which still persists after 122 months of follow-up. Minimal initial gastric discomfort was the only side effect of which the patient complained and only during the first higher dose mitotane course.
CONCLUSIONS
Long-term administration of a low maintenance dose of mitotane may be suggested as treatment for hypercortisolism in CC patients who refuse or are at high risk for surgical adrenalectomy.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Shenoy BV, Carpenter PC, Carney JA, 1984 Bilateral Primary pigmented nodular adrenocortical disease. Rare cause of the Cushing syndrome. Am J Surg Pathol 8: 335–344.
Salpea P, Stratakis CA, 2013 Carney complex and McCune Albright syndrome: An overview of clinical manifestations and human molecular genetics. Mol Cell Endocrinol 386: 85–91.
Stratakis CA, Jenkins RB, Pras E, et al, 1996 Cytogenetic and micro satellite alterations in tumors from patients with the syndrome of myxomas, spotted skin pigmentation, and endocrine overactivity (Carney complex). J Clin Endocrinol Metab 81: 3607–3614.
Horvath A, Bertherat J, Groussin L, et al, 2010 Mutations and polymorphisms in the gene encoding regulatory subunit type 1-alpha of protein kinase A (PRKAR1 A): an update. Hum Mutat 31: 369–379.
Stratakis CA, Kirschner LS, Carney JA, 2001 Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab 86: 4041–4046.
Louiset E, Stratakis CA, Perraudin V, et al, 2009 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 94: 2406–2413.
Biller BM, Grossman AB, Stewart PM, et al, 2008 Treatment of adrenocorticotropin-dependent Cushing’s syndrome: a consensus statement. J Clin Endocrinol Metab 93: 2454–2462.
Benecke R, Keller E, Vetter B, de Zeeuw RA, 1991 Plasma level monitoring of MT (o,p’-DDD) and its metabolite (o,p’-DDE) during long-term treatment of Cushing’s disease with low doses. Eur J Clin Pharmacol 41: 259–261.
Terzolo M, Daffara F, Ardito A, 2014 Management of adrenal cancer: a 2013 update. J Endocrinol Invest 37: 207–217.
Kerkhofs TM, Baudin E, Terzolo M, et al, 2013 Comparison of two mitotane starting dose regimens in patients with advanced adrenocortical carcinoma. J Clin Endocrinol Metab 98: 4759–4767.
Terzolo M, Baudin AE, Ardito A, et al, 2013 Mitotane levels predict the outcome of patients with adrenocortical carcinoma treated adjuvantly following radical resection. Eur J Endocrinol 169: 263–270.
Cignarelli M, Picca G, Campo M, et al, 2005 Six months mitotane course induced sustained correction of hypercortisolism in a young woman with PPNAD and Carney Complex. J Endocrinol Invest 28: 54–60.
Donadille B, Groussin L, Waintrop C, et al, 2010 Management of Cushing’s syndrome due to ectopic adrenocorticotropin secretion with ortho-1-para-dichlorodiphenyl-dichloro-ethane: findings in 23 patients from a single center. J Clin Endocrinol Metab 95: 537–544.
Baudin E, Pellegriti G, Bonnay M, et al, 2001 Impact of monitoring plasma 1,1-dichlorodiphenyldichloroethane (o,p’DDD) levels on the treatment of patients with adrenocortical carcinoma. Cancer 92: 1385–1392.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Campo, M.R., 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 14, 300–304 (2015). https://doi.org/10.14310/horm.2002.1514
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.14310/horm.2002.1514