Dataset Information

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma.

ABSTRACT:

Background

Lutetium 177 (¹⁷⁷Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on ¹⁷⁷Lu-DOTATATE-induced thyroid dysfunction is limited.

Case description

A 29-year-old male with SDHB positive metastatic paraganglioma enrolled under the ¹⁷⁷Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) and free thyroxine (FT4) immunoassay measurements per protocol prior to ¹⁷⁷Lu-DOTATATE therapy. The TSH was suppressed [<0.01 µIU/ml (0.27-4.2 µIU/ml)], and FT4 was normal [1.3 ng/dl (0.9-1.7 ng/dl)]. The TSH receptor antibody and thyroid stimulating immunoglobulin index were undetectable [<1 IU/L (?1.75 IU/L), and <1 (?1.3) respectively], while the anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies were elevated [605 IU/ml (0.0-34.9 IU/ml), and 178 IU/ml (0.0-40.0 IU/ml) respectively]. Mass spectrometry on a stored (-80°C) plasma sample obtained one-month pre-PRRT revealed elevated total triiodothyronine (TT3) [235 ng/dl (65-193 ng/dl)] and FT4 [3.9 ng/dl (1.2-2.9 ng/dl)] levels. The patient was diagnosed with Hashimoto's thyrotoxicosis. However, the patient was asymptomatic. One month after the first dose of 200mCi ¹⁷⁷Lu-DOTATATE, the patient noted fatigue and a 2.6 Kg weight gain. The TSH (73.04 µIU/ml), anti-TPO antibodies (>1,000 IU/ml), and anti-Tg antibodies (668 IU/ml) had substantially increased, with reductions in FT4 (0.3 ng/dl) and TT3 [54 ng/dl (87-169 ng/dl)]. Diagnostic gallium 68 - DOTATATE positron emission tomography-computed tomography performed prior to ¹⁷⁷Lu-DOTATATE treatment revealed diffuse thyroid uptake. Post-therapy single-photon emission computed tomography also revealed diffuse uptake of ¹⁷⁷Lu-DOTATATE in the thyroid gland. Levothyroxine therapy was initiated, and the patient's symptoms resolved.

Summary

We report, for the first time, a patient with asymptomatic primary hyperthyroidism who rapidly developed symptomatic primary hypothyroidism 1 month after ¹⁷⁷Lu-DOTATATE therapy, accompanied by marked changes in TFTs and thyroid auto-antibody titers, with functional imaging evidence of diffuse uptake of ¹⁷⁷Lu-DOTATATE in the thyroid gland.

Conclusions

Thyroid dysfunction can be associated with PRRT. Thyroid uptake patterns on pre-treatment diagnostic somatostatin analog scans might predict individual susceptibility to PRRT-associated TFT disruption. Therefore, periodic evaluation of TFTs should be considered in patients receiving PRRT.

SUBMITTER: Gubbi S

PROVIDER: S-EPMC7859638 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma.

Gubbi Sriram S Al-Jundi Mohammad M Del Rivero Jaydira J Jha Abhishek A Jha Abhishek A Knue Marianne M Zou Joy J Turkbey Baris B Carrasquillo Jorge Amilcar JA Lin Emily E Pacak Karel K Klubo-Gwiezdzinska Joanna J Lin Frank I-Kai FI

Frontiers in endocrinology 20210121

<h4>Background</h4>Lutetium 177 (<sup>177</sup>Lu) - DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) utilized in the treatment of neuroendocrine tumors. Data on <sup>177</sup>Lu-DOTATATE-induced thyroid dysfunction is limited.<h4>Case description</h4>A 29-year-old male with <i>SDHB</i> positive metastatic paraganglioma enrolled under the <sup>177</sup>Lu-DOTATATE trial (NCT03206060) underwent thyroid function test (TFT) evaluation comprised of thyroid stimulating hormone (TSH) ...[more]

PMID: 33551992

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Project description:Abstract Background: Peptide receptor radionuclide therapy (PRRT) is a relatively novel, emerging therapy for the treatment of metastatic pheochromocytoma and paraganglioma (PPGL). Lutetium 177 (177Lu)-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 177Lu-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 177Lu-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 177Lu-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 177Lu-DOTATATE uptake in the thyroid gland. The patient currently has stable metastatic disease and continues to be under 177Lu-DOTATATE therapy. Conclusion: We report the first known case of clinical hypothyroidism post 177Lu-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.

Project description:BackgroundMetastatic castration-resistant prostate cancer remains fatal despite recent advances. Prostate-specific membrane antigen (PSMA) is highly expressed in metastatic castration-resistant prostate cancer. Lutetium-177 (177Lu)-PSMA-617 is a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.MethodsWe conducted an international, open-label, phase 3 trial evaluating 177Lu-PSMA-617 in patients who had metastatic castration-resistant prostate cancer previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)-labeled PSMA-11 positron-emission tomographic-computed tomographic scans. Patients were randomly assigned in a 2:1 ratio to receive either 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. The alternate primary end points were imaging-based progression-free survival and overall survival, which were powered for hazard ratios of 0.67 and 0.73, respectively. Key secondary end points were objective response, disease control, and time to symptomatic skeletal events. Adverse events during treatment were those occurring no more than 30 days after the last dose and before subsequent anticancer treatment.ResultsFrom June 2018 to mid-October 2019, a total of 831 of 1179 screened patients underwent randomization. The baseline characteristics of the patients were balanced between the groups. The median follow-up was 20.9 months. 177Lu-PSMA-617 plus standard care significantly prolonged, as compared with standard care, both imaging-based progression-free survival (median, 8.7 vs. 3.4 months; hazard ratio for progression or death, 0.40; 99.2% confidence interval [CI], 0.29 to 0.57; P<0.001) and overall survival (median, 15.3 vs. 11.3 months; hazard ratio for death, 0.62; 95% CI, 0.52 to 0.74; P<0.001). All the key secondary end points significantly favored 177Lu-PSMA-617. The incidence of adverse events of grade 3 or above was higher with 177Lu-PSMA-617 than without (52.7% vs. 38.0%), but quality of life was not adversely affected.ConclusionsRadioligand therapy with 177Lu-PSMA-617 prolonged imaging-based progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer. (Funded by Endocyte, a Novartis company; VISION ClinicalTrials.gov number, NCT03511664.).

Project description:BackgroundGastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland.MethodsCost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes.ResultsFor unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained. In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus.ConclusionsCost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.

Dataset Information

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma.

Background

Case description

Summary

Conclusions

Publications

Case Report: Primary Hypothyroidism Associated With Lutetium 177-DOTATATE Therapy for Metastatic Paraganglioma.

Similar Datasets

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