A Rare Case of Painless Destructive Thyroiditis Resulting in Thyroid Storm.

Thyroid storm is a life-threatening clinical condition that is usually triggered by untreated or interrupted treatment of Graves' disease, leading to the sudden onset of severe thyrotoxicosis, which requires an immediate diagnosis and treatment based on diagnostic criteria. Cases of thyroid storm caused by painless/painless subacute thyroiditis are very rare. We herein report an 85-year-old man with features of severe thyrotoxicosis caused by painless/painless subacute thyroiditis who had no uptake of 99mTcO4 and was negative for thyroid-stimulating hormone receptor antibodies. In thyroid storm patients in whom the findings are inconsistent with Graves' disease, careful follow-up and management are necessary, assuming the possibility of painless or painless subacute thyroiditis.

Sub-Acute Thyroiditis presenting as pyrexia of unknown origin: A rare case with literature review.

Pyrexia of unknown origin (PUO) is a challenging entity in medical practice from a diagnostic point of view. Sub-Acute Thyroiditis (SAT), that is an inflammatory condition of thyroid, self-limiting and easily treatable, is a very rare cause for PUO with a few published cases and unfortunately not considered in routine for the differential diagnosis (DD) of PUO. Usually, it presents with mild thyrotoxicosis signs and symptoms, painful goiter, and rarely with cervical Lymph adenopathy. Thyroid antibodies might be negative, but inflammatory markers are usually raised. Anti-inflammatory drugs (NSAID) and steroids are a simple but very effective treatment. We present our experience for diagnosing and treating a female patient presenting with PUO. She was diagnosed as a case of sub-acute Thyroiditis on nuclear thyroid scan, High resolution ultrasound (HR-USG) of Thyroid and radioimmunoassay (RIA) for thyroid hormones and thyroid antibodies. The Patient was successfully treated with NSAIDs and steroids. The consent of the patient was taken to publish her case.

68Ga-FAPI Uptake of Thyroiditis in a Patient With Breast Cancer.

ABSTRACT: 68Ga-fibroblast activation protein-specific inhibitor (FAPI)-04 PET/CT was performed in a 49-year-old woman diagnosed with breast cancer. In PET/CT imaging, intense 68Ga-FAPI uptake was observed in the primary tumor, axillary lymph nodes, and also in the thyroid gland, whereas pathological 18F-FDG uptake was not observed in the thyroid gland. On thyroid ultrasonography, parenchyma was heterogeneous, and an area of focal thyroiditis was observed in the superior part of the right lobe. Biochemical parameters were found to be consistent with thyroiditis. This case shows that FAPI uptake in the thyroid gland may be associated with thyroiditis and should be evaluated clinically.

Multiple endocrinopathies, hypercalcaemia and pancreatitis following combined immune checkpoint inhibitor use- case report and review of literature.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of oncological agents which are used to treat a number of malignancies. To date seven agents have been approved by the Food and Drug Administration (FDA) to treat both solid and haematological malignancies. Despite their efficacy they have been associated with a number of endocrinopathies. We report a unique case of hypophysitis, thyroiditis, severe hypercalcaemia and pancreatitis following combined ICI therapy. CASE PRESENTATION: A 46-year old Caucasian female with a background history of malignant melanoma and lung metastases presented to the emergency department with lethargy, nausea, palpitations and tremors. She had been started on a combination of nivolumab and ipilimumab 24 weeks earlier. Initial investigations revealed thyrotoxicosis with a thyroid stimulating hormone (TSH) of < 0.01 (0.38-5.33) mIU/L, free T4 of 66.9 (7-16) pmol/.L. TSH receptor and thyroperoxidase antibodies were negative. She was diagnosed with thyroiditis and treated with a beta blocker. Six weeks later she represented with polyuria and polydipsia. A corrected calcium of 3.54 (2.2-2.5) mmol/l and parathyroid hormone (PTH) of 9 (10-65) pg/ml confirmed a diagnosis of non-PTH mediated hypercalcaemia. PTH-related peptide and 1, 25-dihydroxycholecalciferol levels were within the normal range. Cross-sectional imaging and a bone scan out ruled bone metastases but did reveal an incidental finding of acute pancreatitis - both glucose and amylase levels were normal. The patient was treated with intravenous hydration and zoledronic acid. Assessment of the hypothalamic-pituitary-adrenal (HPA) axis uncovered adrenocorticotrophic hormone (ACTH) deficiency with a morning cortisol of 17 nmol/L. A pituitary Magnetic Resonance Image (MRI) was unremarkable. Given her excellent response to ICI therapy she remained on ipilimumab and nivolumab. On follow-up this patient's thyrotoxicosis had resolved without anti-thyroid mediations - consistent with a diagnosis of thyroiditis secondary to nivolumab use. Calcium levels normalised rapidly and remained normal. ACTH deficiency persisted, and she is maintained on oral prednisolone. CONCLUSION: This is a remarkable case in which ACTH deficiency due to hypophysitis; thyroiditis; hypercalcaemia and pancreatitis developed in the same patient on ipilimumab and nivolumab combination therapy. We postulate that hypercalcaemia in this case was secondary to a combination of hyperthyroidism and secondary adrenal insufficiency.

Pembrolizumab-Induced Thyroiditis and Colitis-Presentation and Resolution on Serial FDG PET/CT.

ABSTRACT: A 58-year-old man with previous melanoma of the left leg underwent whole-body 18F-FDG PET/CT to stage metastatic disease prior to commencing pembrolizumab. Follow-up FDG PET/CT after 3 months of treatment showed partial metabolic response of soft tissue and nodal metastases and diffuse increased thyroid and colonic uptake, suggestive of thyroiditis and colitis. Pembrolizumab was ceased, and a repeat FDG PET/CT scan showed regression of uptake in the thyroid gland and colon, in keeping with resolution of inflammatory change. Immune-related adverse events induced by Immune checkpoint inhibitors, such as pembrolizumab, should be recognized-cessation of treatment often leads to resolution.

Imaging spectrum of adverse events of immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs), a form of immunotherapy, are increasingly used for a variety of malignancies and have been linked to numerous treatment-related side effects known as immune-related adverse events (irAEs). IrAEs can affect multiple organ systems and are important to recognise in order to avoid misinterpretation as progressive tumour and to ensure appropriate management. In this pictorial review, we will briefly discuss radiological response criteria of immunotherapy and describe the imaging appearances of the wide spectrum of these ICI-associated toxicities.

Pembrolizumab Exacerbates Thyroid Diseases Shown on FDG PET/CT.

A 51-year-old woman with a history of sarcomatoid hepatocellular carcinoma, status post resection, underwent FDG PET/CT. In addition to abnormal activity elsewhere, the images showed focal activity in the isthmus of the thyroid, suggestive of malignant involvement, and diffuse mild activity in the left lobe of the thyroid, suggestive of thyroiditis. After a 10-week anti-PD-1 pembrolizumab therapy, the follow-up FDG PET/CT scan demonstrated much more intense activity in both the isthmus and the left lobe of the thyroid. Pathological examination revealed papillary thyroid cancer in the isthmus and thyroiditis in the left lobe of the thyroid.

Qualitative analysis of contrast-enhanced ultrasound in the diagnosis of small, TR3-5 benign and malignant thyroid nodules measuring ≤1 cm.

OBJECTIVE: To evaluate the performance of contrast-enhanced ultrasound in the diagnosis of small, solid, TR3-5 benign and malignant thyroid nodules (≤1 cm). METHODS: From January 2016 to March 2018, 185 thyroid nodules from 154 patients who underwent contrast enhanced ultrasound (CEUS) and fine-needle aspiration or thyroidectomy in Shanghai General Hospital were included. The χ2 test was used to compare the CEUS characteristics of benign and malignant thyroid nodules, and the CEUS features of malignant nodules assigned scores. The total score of the CEUS features and the scores of the above nodules were evaluated according to the latest 2017 version of the Thyroid Imaging Reporting and Data System (TI-RADS). The diagnostic performance of the two were compared based on the receiver operating characteristic curves generated for benign and malignant thyroid nodules. RESULTS: The degree, enhancement patterns, boundary, shape, and homogeneity of enhancement in thyroid small solid nodules were significantly different (p＜0.05). No significant differences were seen between benign and malignant thyroid nodules regarding completeness of enhancement and size of enhanced lesions (p＞0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the TI-RADS classification TR5 in diagnosis of malignant nodules were 90.10%, 55.95%, 74.59%, 72.22%, and 82.46%, respectively (area under the curve [AUC]=0.738; 95% confidence interval[CI], 0.663-0.813). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the total score of CEUS qualitative analysis indicators were 86.13%, 89.29%, 87.57%, 90.63%, and 84.27% respectively (AUC = 0.916; 95% CI, 0.871-0.961). CONCLUSION: CEUS qualitative analysis is superior to TI-RADS in evaluating the diagnostic performance of small, solid thyroid nodules. Qualitative analysis of CEUS has a significantly higher specificity for diagnosis of malignant thyroid nodules than TI-RADS. ADVANCES IN KNOWLEDGE: The 2017 version of TI-RADS has recently suggested the malignant stratification of thyroid nodules by ultrasound. In this paper we applied this system and CEUS to evaluate 185 nodules and compare the results with pathological findings to access the diagnostic performance.

Detection of thyroiditis on PET/CT imaging: a systematic review.

PURPOSE: The incidence and clinical significance of thyroiditis detected by molecular imaging methods is a clinical challenge that is not widely investigated in the literature. The aim of this systematic review was to analyze published data about the detection of thyroiditis on PET or PET/CT using different tracers. METHODS: A comprehensive computer literature search of the Scopus, PubMed/MEDLINE, Embase, and Cochrane library databases was conducted up to November 2019 to find relevant papers on the detection of thyroiditis by PET/CT, the metabolic appearance, and the clinical significance. RESULTS: Twenty-six articles were selected and retrieved in full-text version. From the analyses of these studies, the following main findings have been found. Diffuse thyroid uptake of PET tracers is a relatively frequent event, ranging from 0.4 to 46.2%, and it is commonly related to benign disease. Thyroiditis is the most frequent reason for diffuse increased thyroid 18F-FDG uptake. Cases of malignant disease with a pattern of diffuse 18F-FDG thyroid uptake are less frequent. Preliminary studies show a possible role of thyroiditis detected by 18F-FDG PET/CT in evaluating treatment response and as a prognostic marker in oncological patients treated with immunotherapy. However, further studies are needed. CONCLUSIONS: Diffuse 18F-FDG thyroid uptake is a relatively rare event commonly due to benign diseases, among which thyroiditis is the most common. The rate of neoplastic disease with diffuse 18F-FDG thyroid uptake is very low. Diffuse 18F-FDG thyroid uptake requires further investigation and clinical evaluation for the correct diagnosis. Currently, cases of diffuse thyroid uptake with non-18F-FDG radiotracer are only anecdotal.

Immune-related adverse events as predictors of response in cancer patients undergoing immunotherapy. / Reacciones adversas inmunomediadas como predictoras de respuesta en pacientes oncológicos en tratamiento con inmunoterapia.

OBJECTIVE: To determine the incidence of immune-mediated adverse reactions with and without radiologic manifestations and to correlate them with the response to immunotherapy. MATERIAL AND METHODS: We retrospectively included 79 patients with stage IV lung carcinomas (n=24), renal carcinomas (n=11), or melanoma (n=44) treated with immunotherapy. We evaluated the occurrence of immune-mediated adverse reactions, their radiologic manifestations, and the response pattern according to the immune-related response criteria (irRC). We correlated the presence of immune-mediated adverse reactions with the response pattern. RESULTS: Immune-mediated adverse reactions occurred in 27.8%, being most common in patients with melanoma (40.9%). In 59.1% of patients with adverse reactions, there were radiologic manifestations such as pneumonitis, colitis, hypophysitis, thyroiditis, or myocarditis. Pneumonitis was the most common radiologic manifestation of immune-mediated adverse reactions, even in asymptomatic patients. The rate of response to immunotherapy was higher among patients who developed immune-mediated adverse reactions than in those who did not (68.2% vs. 38.6%, respectively, χ2 5.58; p=0.018). The rate of favorable responses was higher in patients with radiologic manifestations of immune-mediated adverse reactions than in those without radiologic manifestations (84.6% vs. 44.4%, respectively; p=0.023). CONCLUSIONS: The presence of immune-mediated adverse reactions is associated with a better response to immunotherapy. The association with a favorable response is even stronger in patients with radiologic manifestations of the immune-mediated adverse reactions.

Pitfalls in Thyroid Cytopathology.

Fine-needle aspiration (FNA) is among the first diagnostic tools used in the evaluation of thyroid nodules. It has the ability to triage patients with benign and malignant lesions, thus defining the optimum clinical and/or surgical management. The Bethesda System for Reporting Thyroid Cytopathology has found worldwide acceptance. Thyroid FNA offers high positive predictive value (97%-99%), with sensitivities and specificities of 65% to 99% and 72% to 100%, respectively. Nonetheless, many potential diagnostic pitfalls exist that can lead to false-positive and/or false-negative results. This article discusses several of the potential pitfalls in the cytologic evaluation of thyroid lesions.

Comparison between peak systolic velocity of the inferior thyroid artery and technetium-99m pertechnetate thyroid uptake in differentiating Graves' disease from thyroiditis

ABSTRACT Objectives The differentiation between the various etiologies of thyrotoxicosis, including those with hyperthyroidism (especially Graves' disease [GD], the most common cause of hyperthyroidism) and without hyperthyroidism (like thyroiditis), is an important step in planning specific therapy. Technetium-99m (99mTc) pertechnetate thyroid scanning is the gold standard in differentiating GD from thyroiditis. However, this technique has limited availability, is contraindicated in pregnancy and lactation, and is not helpful in cases with history of recent exposure to excess iodine. The aim of this study was to identify the diagnostic value of the peak systolic velocity of the inferior thyroid artery (PSV-ITA) assessed by color-flow Doppler ultrasound (CFDU) and compare the sensitivity and specificity of this method versus 99mTc pertechnetate thyroid uptake. Subjects and methods We prospectively analyzed 65 patients (46 with GD and 19 with thyroiditis). All patients were evaluated with clinical history and physical examination and underwent 99mTc pertechnetate scanning and measurement of TRAb levels and PSV-ITA values by CFDU. The diagnosis was based on findings from signs and symptoms, physical examination, and 99mTc pertechnetate uptake. Results Patients with GD had significantly higher mean PSV-ITA values than those with thyroiditis. At a mean PSV-ITA cutoff value of 30 cm/sec, PSV-ITA discriminated GD from thyroiditis with a sensitivity of 91% and specificity of 89%. Conclusion Measurement of PSV-ITA by CFDU is a good diagnostic approach to discriminate between GD and thyroiditis, with sensitivity and specificity values comparable to those of 99mTc pertechnetate thyroid uptake.

Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab.

BACKGROUND: Blocking the PD-1 pathway induces immune-related adverse events (irAEs) which often involve the thyroid gland (thyroid irAEs). Clinical features of a thyroid irAE including its predictability and relationship to prognosis remain to be elucidated. METHODS: Two hundred consecutive patients treated with nivolumab at Kyoto University Hospital between September 1, 2014 and August 31, 2017 were included in a retrospective cohort study. We systematically determined and classified subclinical and overt thyroid irAEs based on data collected of serum free T4 and TSH levels. Baseline characteristics and detailed clinical data were analyzed, and analyses of overall survival (OS) excluded patients censored within 1 month from the first administration of nivolumab. RESULTS: Sixty-seven patients (33.5%) developed thyroid irAEs and these were divided into a subclinical thyroid irAE group (n = 40, 20.0%) and an overt thyroid irAE group (n = 27, 13.5%). Patients with thyroid uptake of FDG-PET before treatment showed high incidences of overt thyroid irAE (adjusted odds ratio 14.48; 95% confidence interval [CI] 3.12-67.19), while the same relationship was not seen with subclinical thyroid irAE. Regarding the total cohort, the thyroid irAE (+) group had a significantly longer median OS than the thyroid irAE (-) group (16.1 versus 13.6 months, hazard ratio [HR] 0.61; 95% CI 0.39-0.93). In 112 non-excluded patients with lung cancer, the thyroid irAE (+) group similarly had a longer median OS than the thyroid irAE (-) group (not reached versus 14.2 months, HR 0.51; 95% CI 0.27-0.92). However, this observation was not seen in 41 non-excluded patients with malignant melanoma (12.0 versus 18.3 months, HR 1.54; 95% CI 0.67-3.43). CONCLUSIONS: By thyroid uptake of FDG-PET, overt thyroid irAEs could be predicted before nivolumab therapy. Thyroid irAEs related to good prognosis in lung cancer but might be inconclusive in malignant melanoma.

Pembrolizumab-Induced Thyroiditis.

Immune checkpoint inhibitors act to restore T cell-mediated antitumor immunity. By this nature, these cancer immunotherapy drugs are associated with various immune-related adverse events such as thyroid dysfunction. We describe a case of thyrotoxicosis secondary to a programmed cell death 1 (PD-1) immune checkpoint inhibitor, pembrolizumab. A 30-year-old female was started on pembrolizumab immunotherapy for stage III small cell carcinoma of the ovary, hypercalcemic type. Thirteen days after her second cycle of therapy, she presented with symptoms consistent with thyrotoxicosis. A thyroiditis was diagnosed by thyroid function tests and ultrasonography. She was originally treated with prednisone and metoprolol for possible Grave's disease. Pertechnetate thyroid scan was more consistent with thyroiditis secondary to pembrolizumab. She underwent a total thyroidectomy 10 days after initial presentation for refractory thyrotoxicosis despite maximal medical therapy. Her symptoms resolved and thyroid function tests significantly improved. Pathology was consistent with severe thyroiditis. Immune microenvironment may play a role in the expression of programmed cell death protein 1 ligand 1 (PD-L1). Chronic inflammation surrounding tumor upregulates PD-L1 expression on tumor cells by the release of cytokines, which acts to inhibit tumor destruction. We suggest that our patient had an undetected chronic inflammation of the thyroid, specifically Hashimoto's thyroidits, which predisposed her to thyroid destruction when taking pembrolizumab. Understanding that an inflammatory environment impacts thyroid toxicity to PD-1 inhibitor therapy is novel and should be further studied.

Thyroiditis and immune check point inhibitors: the post-marketing experience using the French National Pharmacovigilance database.

Immunotherapy with immune checkpoint inhibitors (ICIs) for cancer has become increasingly prescribed in recent years. Indeed, it is used to treat both solid and hematological malignancies due to their considerable potential in treating melanoma, non-small cell lung and other cancers. Immune-mediated related adverse endocrine toxicity, and especially thyroiditis, is seen as a growing problem needing specific screening and management. This study aims at describing thyroid dysfunctions induced by the ICIs marketed in France, which are registered in the French Pharmacovigilance database. This database was queried for nivolumab, pembrolizumab, and ipilimumab-induced adverse drug reactions reported before April 30, 2017. Both a pharmacologist and an endocrinologist have reviewed each case to select only those of peripheral thyroiditis (thyrotoxicosis and hypothyroidism). During this period, 110 thyroiditis following ICI therapy were reported. Sex/ratio was around one. Most of the cases (47.2%) were asymptomatic. Although some thyrotoxicosis cases were severe, no orbitopathy was reported. Hypothyroidism and thyrotoxicosis were equally described. Antithyroid antibodies were positive in only 16% patients. The ultrasonography was informative in 19% patients. Levothyroxine supplementation was necessary in 57% patients, leading to 19% recovery. With a dedicated optimized management, most of the cases did not require immunotherapy discontinuation. Finally, immune-mediated related thyroiditis is increasing due to a wider prescription of ICI therapy in various cancer conditions and systematic screening. Often asymptomatic, they lead to a local activation accompanied by hormonal deficiency in the long run. It is necessary to carry out an early and sustained multidisciplinary screening to allow immunotherapy continuation.

Difficulties in diagnosis of Riedel's thyroiditis on aspiration cytology: A case report and brief review of the literature.

Riedel's thyroiditis (RT) is a rare disorder characterized by extensive fibrosis extending to the extrathyroidal tissues. An elderly male presented with diffuse moderate thyromegaly and hoarseness of voice for two years. Radiology showed extrathyroidal extension around trachea with compression and deviation suggestive of malignancy. Thyroid was hard and non tender. Ultrasound guided Fine Needle Aspiration (FNA) from multiple foci on both sides using thinner needle yielded moderately cellularity showing follicular cells, lymphoplasmacytic infiltrate, scant colloid and fibrous tissue fragments. Hurthle cells were absent. Adiagnosis of chronic thyroiditis was given with possibility of RT in view of clinical and radiological findings. A core biopsy showed similar picture as cytology. Guided FNA from multiple foci using thinner needle helped to obtain adequate material allowing a confident diagnosis. This case adds to the meagre literature available on the cytologic diagnosis of RT and highlights the diagnostic challenge due to suspicious radiology findings.

Progression of Focal to Diffuse Thyroid Uptake Detected by 18F-FDG PET/CT: Malignant Metastatic Disease or Benign Thyroiditis?

A 49-year-old man was referred to our department for an assessment of a cerebral metastasis of unknown primary with F-FDG PET/CT. This imaging led to detection of a suspected pulmonary primary carcinoma, as well as an incidental left focal thyroid uptake. An ultrasonography, performed a month later, revealed a thyroiditis aspect. An anti-PD1 immunotherapy was also proposed 2 months later after confirmation of a lung adenocarcinoma. A second baseline FDG PET/CT surprisingly showed a diffuse thyroid uptake. A fine-needle aspiration biopsy of thyroid parenchyma finally revealed a diffuse involvement from lung adenocarcinoma (ie, primary lung metastasis to the thyroid gland).

18F-FDG PET/CT Can Predict Development of Thyroiditis Due to Immunotherapy for Lung Cancer.

Our primary purpose was to determine whether increased 18F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism in patients undergoing immunotherapy with nivolumab for lung cancer. Secondarily, we determined whether 18F-FDG uptake in the thyroid gland correlates with number of administered cycles of nivolumab. Methods: Retrospective chart review over 2 y found 18 lung cancer patients treated with nivolumab who underwent 18F-FDG PET/CT before and during therapy. SUVmean, SUVmax, and total lesion glycolysis of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver, and spleen. Patients underwent monthly thyroid testing. PET/CT parameters were analyzed by unpaired t testing for differences between 2 groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab was also tested. Results: Six of 18 patients developed hypothyroidism. The t test comparing the 2 groups demonstrated significant differences in SUVmean (P = 0.04), SUVmax (P = 0.04), and total lesion glycolysis (P = 0.02) of the thyroid gland. Two of 4 patients who developed thyroiditis and had increased 18F-FDG uptake in the thyroid gland had a normal TSH level at the time of follow-up 18F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) than patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver, or spleen. Conclusion:18F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy.

Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms.

Context: Thyroid immune-related adverse events (irAEs) in patients treated with programmed death receptor-1 (PD-1) blockade are increasingly recognized as one of the most common adverse effects. Our aim was to determine the incidence and examine the potential mechanisms of anti-PD-1-induced thyroid irAEs. Design: Single-center, retrospective cohort study. Patients and Measurements: We studied 93 patients with advanced cancer (ages 24 to 82 years; 60% males) who received at least one infusion of pembrolizumab. Thyroid test results and thyroid imaging modalities were reviewed. Comprehensive 10-color flow cytometry of peripheral blood was performed. Results: Thirteen (14%) thyroid irAEs were observed. Thyroiditis occurred in seven patients (54%), from which four recovered. New onset of hypothyroidism overt/subclinical developed in three patients. Levothyroxine dosing required doubling in three patients with a known history of hypothyroidism. Thyroperoxidase antibodies were positive in the minority of the patients [4/13 (31%)] and diffuse increased 18fludeoxyglucose uptake of the thyroid gland was observed in the majority [7/11 (64%)] of patients. We observed more circulating CD56+CD16+ natural killer (NK) cells and an elevated HLA-DR surface expression in the inflammatory intermediate CD14+CD16+ monocytes in anti-PD-1-treated patients. Conclusions: Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.