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.

Lenvatinib Therapy for Advanced Thyroid Cancer: Real-Life Data on Safety, Efficacy, and Some Rare Side Effects.

Context: The SELECT trial led to the approval of lenvatinib for the treatment of advanced radioiodine-refractory differentiated thyroid carcinomas (DTCs) but also revealed an important adverse event (AE) profile which may limit its use in clinical practice. Objective: We aim to describe the efficacy and toxicity profiles of lenvatinib in real life. Methods: We included all patients who received lenvatinib for an advanced DTC at our institution, enrolling 27 patients. We reviewed retrospectively electronic medical records to assess efficacy and AEs. Results: Among the 24 patients with evaluation of tumor response during treatment, overall response rate (ORR) was 37.0% (95% CI, 19.4%-57.6%), and disease control rate was 85.2% (95% CI, 66.3%-95.8%). The median progression-free survival (PFS) was 12 months (95% CI, 7.5-16.5]. The most prevalent AEs were hypertension (77.8%), fatigue (55.6%), and weight loss (51.9%). At least one grade ≥ 3 AE was experienced by 25/27 patients (92.6%), mostly hypertension (59.3%). Lenvatinib was discontinued due to AEs in 13/27 patients (48.1%). Interestingly, 1 patient experienced a grade 4 posterior reversible encephalopathy syndrome, and another developed a Takotsubo cardiomyopathy. Conclusion: The safety profile of lenvatinib in our cohort was similar to that reported in the literature, with a predominance of hypertension. Rigorous blood pressure control is therefore essential to avoid discontinuing therapy. We also report 2 severe and rarely described AEs that physicians should watch for. As for efficacy, although less than in the SELECT trial, ORR and PFS were similar to other real-life studies.

Postoperative Recurrences in Patients Operated for Pheochromocytomas and Paragangliomas: New Data Supporting Lifelong Surveillance.

At least 10% of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs) may recur after the initial surgery. Guidelines recommend annual screening for recurrence in non-metastatic tumors for at least 10 years after the initial surgical resection and lifelong screening in high-risk patients. However, recent data suggest that a shorter follow-up might be appropriate. We performed a retrospective analysis on patients with PPGLs who had local and/or metastatic recurrences between 1995 and 2020 in our center. Data were available for 39 cases of recurrence (69.2% female) including 20 PHEOs (51.3%) and 19 PGLs (48.7%) (13 head and neck (HNPGL) and 6 thoracoabdominal (TAPGL)). The overall average delay of recurrence was 116.6 months (14-584 months) or 9.7 years and the median was 71 months or 5.9 years. One-third of the cohort had a recurrence more than 10 years after the initial surgery (10-48.7 years). The average tumor size at initial diagnosis was 8.2 cm for PHEOs, 2.7 cm for HNPGLs, and 9.6 cm for TAPGLs. Interestingly, 17.6% of PHEOs were under 5 cm at the initial diagnosis. Metastatic recurrence was identified in 75% of PHEOs, 15.4% of HNPGLs, and 66.7% of TAPGLs. Finally, 12/23 (52.2%) patients with recurrence who underwent genetic testing carried a germline mutation. Overall, the safest option remains a lifelong follow-up.