Subclinical hyperthyroidism in post immunotherapy lung cancer on FDG PET/CT: an incidental observation : Indian Journal of Cancer

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Subclinical hyperthyroidism in post immunotherapy lung cancer on FDG PET/CT

an incidental observation

Jain, Pallavi; Sharma, Nagender; Sahoo, Manas K

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Indian Journal of Cancer 59(3):p 428-429, Jul–Sep 2022. | DOI: 10.4103/ijc.IJC_758_20
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We report a case of a 65-year-old man who presented with hoarseness of voice. Contrast enhanced Computed tomography (CECT) chest showed a heterogenously enhancing mass in left lung, which on biopsy revealed squamous cell carcinoma. PET/CECT (positron emission tomography/contrast enhanced computed tomography) revealed a hypermetabolic mass in the left upper lobar main bronchus with a few enlarged FDG (fluoro-deoxyglucose) avid metastatic precarinal lymph nodes [Figure A1, A2]. There was no increased FDG uptake in thyroid gland [Figure A3]. Maximum-intensity-projection (MIP) image showed increased metabolic activity in left lung mass along with mediastinal lymphnodes [Figure A4].

F1-22
Figure 1:
A1,A2: positron emission tomography/contrast enhanced computed tomography (PET/CECT) shows a hypermetabolic mass in the left upper lobar main bronchus; A3: FDG PET/CT does not show any increased uptake in the thyroid gland (Pre-treatment);A4: Maximum intensity projection (MIP) image showed increased metabolic activity in left lung mass (pre-treatment);B1,B2: Post immunotherapy, PET/CECT showed near complete response of primary lung mass; B3:Bulky thyroid gland with interval appearance of increased FDG uptake in both lobes; B4: Reduction in size and metabolic activity of the primary lung lesion along with interval appearance of thyroid hypermetabolism (Post-Treatment)

The disease was staged as metastatic nonsmall cell lung carcinoma cT4N3M1 (M1a pleura) on TNM staging. EGFR on the biopsy specimen was negative and immunohistochemistry for programmed death ligand-1 (PD-L1) showed a positivity of 60%. Palliative chemoimmunotherapy was started with pembrolizumab, nab-Paclitaxel, and carboplatin. Post immunotherapy, PET/CECT showed near complete response of primary lung mass [Figure B1, B2]. Incidentally, thyroid gland appeared bulky with interval appearance of increased FDG uptake (SUV max-14.9) seen in both lobes [Figure B3] suggestive of inflammatory activity in thyroid gland. Follow-up MIP image [Figure B4] showed a reduction in size and metabolic activity of the primary lung lesion along with interval appearance of thyroid hypermetabolism. Biochemical picture of normal FT3, FT4 and suppressed TSH value <0.015 confirmed a state of subclinical hyperthyroidism with no clinical symptoms of hyperthyroidism. Possibility of thyroiditis on the PET scan along with suppressed TSH could be attributed to a post immunotherapy response as is seen in the other quoted studies. Subclinical hyperthyroidism, though, can be manifested during the post immunotherapy phase, but to our knowledge, has not been reported in literature in such a clinical scenario that was incidentally detected on the follow-up PET/CT scan as diffusely increased FDG uptake in the thyroid gland. This observation should be kept in mind while interpreting follow-up PET/CT of such patients post immunotherapy.

Thyroid immune-related adverse events (irAEs) in patients treated with PD-L1 blockade are recognized as common adverse effects. Thyroid irAEs manifest as thyroiditis, hypothyroidism or subclinical hypothyroidism. Hyperthyroidism is a rarely encountered thyroid irAE. A retrospective study conducted on 93 patients with advanced cancer on at least a single dose of pembrolizumab infusion revealed that thirteen (14%) patients had thyroid irAEs out of which thyroiditis occurred in seven (54%) patients.[1] However, reversible destructive thyroiditis and overt hypothyroidism were the most common clinical presentations. In another study conducted on patients with advanced melanoma on pembrolizumab, a diffuse increase of FDG uptake in the thyroid gland was found in all patients.[2] However, all seven thyrotoxic patients progressed to hypothyroidism in the follow-up.

Eshghi et al. had mentioned the role of FDG PET/CT in prediction of thyroiditis due to immune therapy for lung cancer.[3] Serial measurements of thyroid function should be carried during anti-PD-L1 monoclonal antibody therapy to detect early onset of thyroiditis. Due emphasis should be given to the pattern of FDG uptake in the thyroid gland in post immunotherapy PET/CT which may detect underlying thyroid defect at the earliest.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

REFERENCES

1. Delivanis DA, Gustafson MP, Bornschlegl S, Merten MM, Kottschade L, Withers S, et al Pembrolizumab-induced thyroiditis: Comprehensive clinical review and insights into underlying involved mechanisms J Clin Endocrinol Metab. 2017;102:2770–80
2. de Filette J, Jansen Y, Schreuer M, Everaert H, Velkeniers B, Neyns B, et al Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab J Clin Endocrinol Metab. 2016;101:4431–9
3. Eshghi N, Garland LL, Nia E, Betancourt R, Krupinski E, Kuo PH. 18F-FDG PET/CT can predict development of thyroiditis due to immunotherapy for lung cancer J Nucl Med Technol. 2018;46:260–4
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