Mitotane and Carney Complex: ten years follow-up of a low-dose mitotane regimen inducing a sustained correction of hypercortisolism.
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.


METHODS
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.
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Michela Rosaria
MR
Campo
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Olga
O
Lamacchia
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Anna
A
Farese
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Antonella
A
Conserva
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Giuseppe
G
Picca
Radiodiagnostic Unit, "Ospedali Riuniti" University Hospital; Foggia, Italy.
Gianpaolo
G
Grilli
Unit of Endocrinology and Metabolic Diseases, Department of Medical and Surgical Sciences, University of Foggia, Italy.
Mauro
M
Cignarelli
D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D056733:Carney Complex / Q000188:drug therapy*; D003480:Cushing Syndrome / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008939:Mitotane / Q000494:pharmacology / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D008939:Mitotane