A 27-year-old woman with Carney Complex, with inactivating mutation of the PRKAR1α gene [(a 2-bp deletion of nucleotides T and G at positions 576 and 577 with frame-shift mutation beginning with aminoacid residue threonine 163 (ΔFSterThr163)], bearing a GH secreting microadenoma, Cushing syndrome from PPNAD and with high operatory risk because of the neurological sequelae of cerebral embolism from atrial myxomas, underwent a low-dose mitotane (MT) regimen.
In the first 12 weeks period, the MT daily dose was progressively increased from 0.5 to 4.0 g/day. This dosage was maintained for additional 16 weeks (cumulative dose 602 g, plasma MT 12 μg/ml) and then stopped because of sustained signs of hypoadrenalism requiring prednisone replacement. Profound decrease of both serum cortisol (from 615 to 220 nmol/l) and urinary free cortisol (UFC) values (from 1498 to 477 nmol/day) was noted after 16 weeks of treatment (cumulative dose 314 g, plasma MT 8 μg/ml). MT treatment was associated with mild gastric discomfort and reversible increase of cholesterol plasma levels. Normal serum cortisol and UFC were still observed 57 weeks after MT was discontinued (plasma MT 0.2 μg/ml), although cortisol bio-rhythm was still abnormal. 60 weeks after discontinuation, mitotane treatment was replaced because of mild increase of serum cortisol and DHEAS levels and onset of oligomenorrea. Now we achieve normal serum cortisol and UFC levels with a MT daily dose of 750 mg, not requiring prednisone replacement, without any side effects.
Our report demonstrates that low dose MT treatment may be a safe and effective modality for a sustained correction of hypercortisolism by PPNAD in subjects with CNC with high risk for both adrenalectomy and the consequent trouble from total dependency on corticosteroid substitutive therapy.
01 - 05 Apr 2006
European Society of Endocrinology