Objective. Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods. We conducted a retrospective study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. Results. The levels of thyroid hormones were lower in subjects treated compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P<0.05 at each time). The time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 120 days in untreated patients (P<0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (P=0.89). Conclusions. Our preliminary data suggest that in patients with a poor performance status experiencing a severe destructive thyrotoxicosis induced by PD-1 blockade, a short period of administration of oral prednisone is effective in obtaining a quick reduction of the levels of thyroid hormones.

The WNT1 gene is crucial for bone development and homeostasis. Homozygous mutations in WNT1 cause severe bone fragility known as osteogenesis imperfecta type XV. Moreover, heterozygous WNT1 mutations have been found in adults with early-onset osteoporosis. We identified a 35 year-old Caucasian woman who experienced multiple vertebral fractures two months after her second pregnancy. There was no history of risk factors for secondary osteoporosis or family history of osteoporosis. Dual-energy X-ray absorptiometry confirmed a marked reduction of bone mineral density (BMD) at the lumbar spine (0.734 g/cm2, Z-score -2.8), femoral neck (0.48 g/cm2, Z-score -3.5), and total hip (0.589 g/cm2, Z-score -3.0). Blood tests excluded secondary causes of bone fragility. Genetic analysis revealed a heterozygous missense mutation (p.Leu370Val) in the WNT1 gene. Varsome classified it as a variant of uncertain significance. However, the fact that the Leucine residue at position 370 is highly conserved among vertebrate species and the variant has a very low allelic frequency in the general population would exclude the possibility of a polymorphism. The patient was treated for two years with teriparatide therapy associated with calcium and vitamin D supplements. During the follow-up period she did not report further clinical fractures. After 24 months of teriparatide, BMD increased at lumbar spine (+14.6%), femoral neck (+8.3%) and total hip (+4.9%) compared to baseline. We confirm that the heterozygous WNT1 mutation could cause a variable bone fragility and low turnover osteoporosis. We suggest that teriparatide is one of the most appropriate available therapies for this case.

Background Destructive thyroiditis is the most common endocrine immune related adverse event (iRAEs) in patients treated with anti-PD1/PD-L1 agents. Given its self-limited course, current guidelines recommend no treatment for this iRAE. Nevertheless in patients with enlarged thyroid volume and a poor performance status, thyrotoxicosis may be particularly severe and harmful. Aim of the study is to evaluate if steroid treatment might be useful in improving thyrotoxicosis in subjects with a poor performance status. Methods We conducted a case-control study, comparing the course of thyrotoxicosis of 4 patients treated with oral prednisone at the dosage of 25 mg/d (tapered to discontinuation in three weeks) and an enlarged thyroid volume to that of 8 patients with similar thyroid volume who were left untreated. Results No difference was found between the two groups at the onset of thyrotoxicosis (time 0) in demographic characteristics and in the levels of thyroid hormones. The levels of thyroid hormones were lower in subjects treated with prednisone compared to those untreated at time 7, 14, 21, 28, 35, 42, 60 and 90 days (P&lt;0.05 at each time). The median time to remission of thyrotoxicosis was 24 days in patients treated with steroids and 92 days in untreated patients (P&lt;0.001). At 6 months, the rate of evolution to hypothyroidism was similar in the 2 groups (4/4 in steroid group vs 7/8 in untreated group, P=0.74) and no difference was found in tumor progression (Progression free survival in treated group 5.1 months vs 5.0 months in untreated patients, P=0.89). Conclusion A short period of prednisone therapy is useful to restore more quickly euthyroidism in patients with a poor performance status and a severe destructive thyrotoxicosis induced by PD-1 blockade. This treatment does not impair the efficacy of immunotherapy. Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.

No abstract

No abstract