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

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.

Chiari Malformation and Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition characterized by inattention, hyperactivity, and impulsivity. Chiari malformations (CM), first described approximately a hundred years ago, refer to a spectrum of hindbrain malformations characterized by cerebellar herniation through the foramen magnum. We present the case of a 28-year-old woman with ADHD and concurrent Chiari malformation type I (CM-I) that was diagnosed by CT scan. There is growing evidence supporting the role of the cerebellum and its associated structures in the pathophysiology of ADHD. Thus, a cerebellar malformation such as CM may impact neurological circuitry in a manner favoring the development of a neuropsychiatric disorder such as ADHD. Our case highlights the need for further studies pertaining to the role of the cerebellum in the pathophysiology of ADHD and the importance of considering the presence of CM when evaluating a patient with ADHD.