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

Sriram Gubbi, Mohammad Al-Jundi, Jaydira Del Rivero, Abhishek Jha, Marianne Knue, Joy Zou, Baris Turkbey, Jorge Amilcar Carrasquillo, Emily Lin, Karel Pacak, Joanna Klubo-Gwiezdzinska, Frank I-Kai Lin, Sriram Gubbi, Mohammad Al-Jundi, Jaydira Del Rivero, Abhishek Jha, Marianne Knue, Joy Zou, Baris Turkbey, Jorge Amilcar Carrasquillo, Emily Lin, Karel Pacak, Joanna Klubo-Gwiezdzinska, Frank I-Kai Lin

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.

Keywords: DOTATATE; Lutathera; hypothyroidism; paraganglioma; peptide receptor radionuclide therapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Gubbi, Al-Jundi, Del Rivero, Jha, Knue, Zou, Turkbey, Carrasquillo, Lin, Pacak, Klubo-Gwiezdzinska and Lin.

Figures

Figure 1
Figure 1
Thyroid uptake patterns in the patient before and after 177Lu-DOTATATE therapy. (A) A whole body (maximum intensity projection) view on the diagnostic 68Ga-DOTATATE scan demonstrating multiple paragangliomas as well as a diffuse uptake in the thyroid gland with a maximum standardized uptake value (SUVmax) of 14.3. (B–D) Axial slices at the thyroid level: (B) Positron emission tomography (PET) scan only. (C) Computed tomography (CT) scan only. (D) Fused PET and CT images. Images (B, D) demonstrate diffuse uptake in the thyroid gland. (E, F) The 24-h post-treatment whole body single-photon emission computed tomography (SPECT) scans demonstrating diffuse uptake of 177Lu-DOTATATE in the thyroid gland (E) After the first cycle of therapy, and (F) after the second cycle of therapy.

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