Mitotane, 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane is the most effective medical therapy for adrenocortical carcinoma, but its molecular mechanism of action remains poorly understood. Although mitotane is known to have mitochondrial (mt) effects, a direct link to mt dysfunction has never been established. We examined the functional consequences of mitotane exposure on proliferation, steroidogenesis, and mt respiratory chain, biogenesis and morphology, in two human adrenocortical cell lines, the steroid-secreting H295R line and the non-secreting SW13 line. Mitotane inhibited cell proliferation in a dose-and a time-dependent manner. At the concentration of 50 mM (14 mg/l), which corresponds to the threshold for therapeutic efficacy, mitotane drastically reduced cortisol and 17-hydroxyprogesterone secretions by 70%. This was accompanied by significant decreases in the expression of genes encoding mt proteins involved in steroidogenesis (STAR, CYP11B1, and CYP11B2). In both H295R and SW13 cells, 50 mM mitotane significantly inhibited (50%) the maximum velocity of the activity of the respiratory chain complex IV (cytochrome c oxidase (COX)). This effect was associated with a drastic reduction in steady-state levels of the whole COX complex as revealed by blue native PAGE and reduced mRNA expression of both mtDNA-encoded COX2 (MT-CO2) and nuclear DNA-encoded COX4 (COX4I1) subunits. In contrast, the activity and expression of respiratory chain complexes II and III were unaffected by mitotane treatment. Lastly, mitotane exposure enhanced mt biogenesis (increase in mtDNA content and PGC1a (PPARGC1A) expression) and triggered fragmentation of the mt network. Altogether, our results provide first evidence that mitotane induced a mt respiratory chain defect in human adrenocortical cells.

131 I treatment in thyroid cancer patients may induce side effects, including extrathyroidal cancer and leukemia. There are still some uncertainties concerning parameters that may influence the effective half-life of 131 I and the absorbed doses by extrathyroidal organs. Methods: Whole-body retention of radioiodine was measured in 254 patients, and repeated quantitative whole-body scans and measurements of the urinary excretion of 131 I were performed on 30 of these patients. Results: The mean effective half-life (10.5 h) was shorter by 31%, with little difference between patients, in the 36 patients who received recombinant human thyroid-stimulating hormone than in the 218 patients who underwent thyroid hormone withdrawal (15.7 h). The residence times in the stomach and in the rest of the body were significantly shorter in patients who received recombinant human thyroid-stimulating hormone than in patients who underwent withdrawal, but the residence times were similar in the colon and bladder. Conclusion: In patients who undergo thyroid hormone withdrawal, the longer mean effective half-life is mainly due to delayed renal excretion of 131 I and results in dose estimates higher than the data in report 53 of the International Commission on Radiological Protection, which were obtained from healthy, euthyroid subjects.

F-FCH PET/CT is a promising modality in challenging pre-surgical localization of hyper-functioning parathyroid glands, such as inconclusive standard imaging, recurrence after surgery, or suspected multiple gland disease.

By increasing the iodine excretion, rhTSH allows a shorter hospitalization length, which partially compensates its acquisition cost.

With our current practice, radiation doses to relatives are low and well below international recommendations.