SAT-502 Clinical Hypothyroidism Associated with Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma: A Novel Adverse Effect of Peptide Receptor Radionuclide Therapy

Background: Peptide receptor radionuclide therapy (PRRT) is a relatively novel, emerging therapy for the treatment of metastatic pheochromocytoma and paraganglioma (PPGL). Lutetium 177 ((177)Lu)-DOTATATE (Lutathera ®) is a form of PRRT that is currently being evaluated for its treatment efficacy in metastatic PPGL. It acts by binding to somatostatin receptors 2 (SSTR2) which are present on PPGL and other tissues of neuroendocrine origin. Although subclinical thyroid dysfunction has been previously noted, development of clinical hypothyroidism post (177)Lu-DOTATATE therapy has not been reported to date. Case: A 29-year-old male with Beckwith-Weidemann syndrome and metastatic, succinate dehydrogenase subunit B (SDHB) germline mutation-positive paraganglioma with normal metanephrines was enrolled at our center under the (177)Lu-DOTATATE trial for the treatment of inoperable, metastatic PPGL (ClinicalTrials.gov NCT03206060). Prior to the first cycle of therapy, the patient underwent endocrine evaluation per protocol. He was noted to have suppressed thyroid stimulating hormone (TSH) of <0.01 mcIU/mL (normal: 0.27 - 4.2 mcIU/mL), and a normal free thyroxine (FT4) of 1.3 ng/dL (0.9 - 1.7 ng/dL), indicating subclinical hyperthyroidism. Thyroid auto-antibodies were not measured at that time point. The patient denied symptoms of hyper- or hypothyroidism. On physical examination, there was no thyromegaly or cervical lymphadenopathy. Serial monitoring of thyroid function tests (TFTs) was pursued. One month after the first cycle of (177)Lu-DOTATATE therapy, the patient complained of new onset fatigue and weight gain. The TSH had markedly increased (73.04 mcIU/mL), along with a reduction in FT4 levels (0.3 mg/dL). Mass spectrometry measures revealed a low total T4 (1.3 ng/dL; 4.9 - 10.5 ng/dL), and a low total T3 (57 ng/dL; 87 - 169 ng/dL). Thyroid peroxidase antibodies were >1000 IU/mL (0.0 - 34.9 IU/mL), and anti-thyroglobulin antibodies were 668 IU/mL (0.0-40.0 IU/mL). Weight-based levothyroxine therapy was initiated and the follow-up TFTs normalized. The baseline diagnostic Gallium 68-DOTATATE scan performed prior to PRRT demonstrated an increased diffuse uptake in the entire thyroid gland (maximum standardized uptake value: 14.3) and post-treatment SPECT-CT scan revealed similar increased, diffuse (177)Lu-DOTATATE uptake in the thyroid gland. The patient currently has stable metastatic disease and continues to be under (177)Lu-DOTATATE therapy. Conclusion: We report the first known case of clinical hypothyroidism post (177)Lu-DOTATATE therapy in a patient who likely had subclinical hyperthyroidism prior to treatment. The possible mechanism was development of thyroiditis. Further studies are necessary to evaluate the mechanisms of PRRT-induced endocrine abnormalities and their clinical implications.