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

Author:

Poirier Jonathan1ORCID,Godemel Sophie2,Mourot Aurélie1ORCID,Grunenwald Solange2ORCID,Olney Harold J3,Le Xuan Kim1,Lacroix André1ORCID,Caron Philippe2ORCID,Bourdeau Isabelle1ORCID

Affiliation:

1. Division of Endocrinology, Department of Medicine and Research Center, Centre hospitalier de l’Université de Montréal (CRCHUM) , Montreal, Quebec, H2X 3E4 , Canada

2. Service d'Endocrinologie, Maladies métaboliques et Nutrition, Pôle Cardio-Vasculaire et Métabolique, Centre Hospitalo-Universitaire de Toulouse , 31059 Toulouse Cedex , France

3. Oncology Division, Department of Medicine and Research Center, Centre hospitalier de l’Université de Montréal (CRCHUM) , Montreal, Quebec, H2X 3E4 , Canada

Abstract

Abstract Context Central hypothyroidism was described previously in mitotane-treated patients but data on its prevalence and time of occurrence are limited. Objective To better characterize thyroid hormone insufficiency in patients exposed to mitotane. Methods We reviewed medical records of patients from 2 academic centers in Montreal (Canada) and Toulouse (France) with exposure to mitotane therapy for adrenocortical cancer between 1995 and 2020. We analyzed the thyroid function parameters during and after treatment. Results In our cohort of 83 patients, 17 were excluded because of preexisting 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 to 6 months in 19.1%, 6 to 9 months in 14.3%, and 9 to 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.

Publisher

The Endocrine Society

Subject

Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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1. Mitotane;Reactions Weekly;2024-04-06

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