Central Hypothyroidism is Frequent During Mitotane Therapy in Adrenocortical Cancer Patients: Prevalence and Timeline

Abstract

Context Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence is limited. Objective To better characterize thyroid hormone insufficiency in patients exposed to mitotane. Methods We reviewed medical records of patients from two academic centers in Montreal (Canada) and Toulouse (France) with exposure to mitotane therapy for ACC between 1995 and 2020. We analysed the thyroid function parameters during and after treatment. Results In our cohort of 83 patients, 17 were excluded because of pre-existing primary hypothyroidism or drug-induced hypothyroidism. During follow-up, 3/66 patients maintained a normal thyroid function and 63/66 developed central hypothyroidism. Among those 63 patients, 56 presented with an inappropriately normal or low TSH and 7 with a mildly elevated TSH. The onset of hypothyroidism was: < 3 months in 33.3%, 3-6 months in 19.1%, 6-9 months in 14.3% and 9-12 months in 9.5%. At least 14.3% of cases occurred after 12 months of exposure and 6 patients had an undetermined time of occurrence. Over time, 27 patients stopped mitotane and partial (42.3%) or complete (23.1%) recovery from hypothyroidism was observed mainly in the first 2 years after mitotane discontinuation. Conclusion Mitotane therapy is frequently associated with new onset of central hypothyroidism with a prevalence of 95.5%. Most cases occurred in the first year of treatment. Partial or full recovery of thyroid function occurs in 65.4% of cases. This study supports the importance of systematic monitoring of TSH and free T4 levels during and following discontinuation of mitotane therapy.

Precocious puberty and other endocrine disorders during mitotane treatment for paediatric adrenocortical carcinoma – case series and literature review

“…According to Poirier et al ., mitotane therapy is frequently associated with the new onset of central hypothyroidism, with a prevalence of 95.5%; the study included 66 adult patients treated with mitotane for ACC [ 43 ]. Most of the cases occurred in the first year of treatment, 33.3% during the first 3 months of treatment, 3–6 months in 19.1%, 6–9 months in 14.3%, and 9–12 months in 9.5%; at least 14.3% of cases occurred after 12 months of exposure.…”

“…Most of the cases occurred in the first year of treatment, 33.3% during the first 3 months of treatment, 3–6 months in 19.1%, 6–9 months in 14.3%, and 9–12 months in 9.5%; at least 14.3% of cases occurred after 12 months of exposure. Partial or full recovery of thyroid function occurred in 65.4% of cases, mainly in the first 2 years after mitotane discontinuation [ 43 ].…”