scholarly journals Management of thyrotoxicosis induced by PD1 or PD-L1 blockade

Author(s):  
Alessandro Brancatella ◽  
Isabella Lupi ◽  
Lucia Montanelli ◽  
Debora Ricci ◽  
Nicola Viola ◽  
...  

Abstract Background Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is lacking, as are data on response to treatment and follow-up. Aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment. Methods We conducted a retrospective study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mTechnecium scintiscan and longitudinal thyroid function tests. Results Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusion Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or euthyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis.

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A841-A841
Author(s):  
Alessandro Brancatella ◽  
Isabella Lupi ◽  
Lucia Montanelli ◽  
Debora Ricci ◽  
Nicola Viola ◽  
...  

Abstract Context: Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 checkpoint inhibitors. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is missing, as are data on response to treatment and follow-up. Objectives: To better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and informing management. Methods: We conducted a prospective cohort study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, scintigraphy, and longitudinal thyroid function tests. Results: Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusions: Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or eu-thyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis


2008 ◽  
Vol 21 (2) ◽  
pp. 179-182
Author(s):  
Carol F. Adair ◽  
John T. Preskitt ◽  
Kristin L. Joyner ◽  
Robin W. Dobson

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A870-A870
Author(s):  
Bay Quang Nguyen

Abstract Background: Incidental thyroid nodules has become more prevalent in recent years due to applying diagnostic imaging tests. Many studies show that the rate of thyroid cancer in this group of patients is relatively high. Objective: To assess patients with incidentally detected thyroid nodules, including those who were diagnosed with thyroid cancer. Materials and Methods: A cross-sectional study, which involved 208 patients with 389 thyroid nodules detected by thyroid ultrasound. All patients have thyroid function tests. 272 nodules were performed fine-needle aspiration. Patients with thyroid cancer were assessed histopathology after removal. Results: The participants’ mean age was 47.22 ± 12.02. The female / male ratio is 6.7/1. No patients had history of head and neck irradiation or living in epidemiological areas with high prevalence of goiter. TSH level: 96.2% normal, 2.4% low, 1.4% high. In thyroid cancer group: 100% of patients had normal thyroid function. Nodule characteristics on ultrasound: Majority of thyroid nodules had diameters less than 1.5 cm (85.6%), multi-nodularity(52.9%). The largest carcinoma nodule was 2.35 cm, 22.2% of patients with thyroid cancer had ≥ 3 nodules. The malignancy rate of TIRADS 5 was 70.6%. FNA results of 272 thyroid nodules: the majority were Bethesda II (74,2%); the incidence of carcinoma (Bethesda V, VI) is 17.4%. 36 patients account for 17,3%, with 42 nodules were performed surgery, the results of histopathology were 100% of papillary thyroid carcinoma, which was consistent with cytological results. Conclusion: Thyroid nodules are common in women patients at the age of 31-60 with normal thyroid function. Most of them are <1.5 cm in size. There are 17.3% of patients were thyroid carcinoma.


2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Dou ◽  
Yingji Chen ◽  
Daixing Hu ◽  
Xinliang Su

PurposeManagement strategies after lobectomy for low-risk papillary thyroid carcinoma (PTC) are controversial. This study aimed to identify the proportion of patients among low-risk PTC patients who do not require hormone replacement therapy and to evaluate the risk factors for postoperative hypothyroidism after lobectomy.Patients and MethodsThe records of 190 PTC patients who underwent thyroid lobectomy from January 2017 to December 2018 were retrospectively reviewed. Clinicopathological characteristics and follow-up data were collected. Univariate and multivariate analyses were performed to identify the risk factors associated with postoperative hypothyroidism and the recovery of thyroid function.ResultsIn summary, 74.21% of patients (141/190) had normal thyroid function without levothyroxine supplementation, while 40.53% (77/190) developed temporary or permanent hypothyroidism. Multivariate analysis indicated that higher preoperative thyroid-stimulating hormone (TSH) levels (>2.62 mIU/L), Hashimoto’s thyroiditis (HT), and right lobectomy were associated with hypothyroidism (all P<0.05). The Area Under Curve (AUC) by logistic analysis was 0.829. Twenty-eight (28/77, 36.4%) patients recovered to the euthyroid state in the first year after surgery, and this recovery was significantly associated with preoperative TSH level. Forty-nine (49/77, 63.6%) patients developed persistent hypothyroidism. The thyroid function of most patients (11/28, 39.3%) recovered in the third month after surgery.ConclusionPatients with a lower level of preoperative TSH, with left lobectomy and without Hashimoto’s thyroiditis had a higher chance of normal thyroid function within the first year after lobectomy. The recovery of thyroid function was associated with the level of preoperative TSH.


2020 ◽  
Vol 183 (4) ◽  
pp. 381-387 ◽  
Author(s):  
Andrea Lania ◽  
Maria Teresa Sandri ◽  
Miriam Cellini ◽  
Marco Mirani ◽  
Elisabetta Lavezzi ◽  
...  

Objective: This study assessed thyroid function in patients affected by the coronavirus disease-19 (COVID-19), based on the hypothesis that the cytokine storm associated with COVID-19 may influence thyroid function and/or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may directly act on thyroid cells, such as previously demonstrated for SARS-CoV-1 infection. Design and methods: This single-center study was retrospective and consisted in evaluating thyroid function tests and serum interleukin-6 (IL-6) values in 287 consecutive patients (193 males, median age: 66 years, range: 27–92) hospitalized for COVID-19 in non-intensive care units. Results: Fifty-eight patients (20.2%) were found with thyrotoxicosis (overt in 31 cases), 15 (5.2%) with hypothyroidism (overt in only 2 cases), and 214 (74.6%) with normal thyroid function. Serum thyrotropin (TSH) values were inversely correlated with age of patients (rho −0.27; P < 0.001) and IL-6 (rho −0.41; P < 0.001). In the multivariate analysis, thyrotoxicosis resulted to be significantly associated with higher IL-6 (odds ratio: 3.25, 95% confidence interval: 1.97–5.36; P < 0.001), whereas the association with age of patients was lost (P = 0.09). Conclusions: This study provides first evidence that COVID-19 may be associated with high risk of thyrotoxicosis in relationship with systemic immune activation induced by the SARS-CoV-2 infection.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17025-e17025
Author(s):  
Z. Akgun ◽  
B. Atasoy ◽  
Z. Ozen ◽  
B. Gulluoglu ◽  
M. U. Abacioglu

e17025 Background: In our study, we aimed to evaluate the possible predictors of thyroid disorders after radiotherapy to the neck, focusing on radiation dose-volume factors. Methods: Thyroid function was measured in 65 patients treated with radiation ports including the thyroid, between 2005 and 2008. All of the radiation-induced thyroid dysfunction was determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4), thyroglobulin antibodies (ATG), thyroid peroxidase antibodies (TPA), thyroid binding globulin (TBG) levels. In 65 patients, radiation dose-volume parameters were calculated; e.g. total volume of the thyroid, mean radiation dose to the thyroid, and percentage of the thyroid volume which received radiation doses of no less than 10–50 Gy (V10-V50). The evaluated risk factors for thyroid dysfunction included these dose-volume parameters, sex, age, treatment modality and primary disease. Results: Most patients (72.3%) had a normal thyroid function, 17 (26.2%) hypothyroidism, 1 (1.5%) hyperthyroidism, and 12 (18.4%) thyroiditis with normal thyroid function. Four of 17 patients with hypothyroidism had overt hypothyroidism. In our analysis, DVHs (dose volume histograms) were calculated and no associations were found between the V10, V20, V40, and V50 percentages and thyroid disorders. V30 and minimum absorbed thyroid dose (Dmin) more than 25 Gy appeared to be correlated with high TSH values (p = 0.01 and p = 0.04, respectively). The patients with hypothyroidism were between 40–60 years. Female gender was associated with a higher incidence of TBG abnormality. Baseline TSH values were available in 16 patients, and hypothyroidism was diagnosed in 4 (25%) of them. No correlation was found between tumor-related variables and incidence of thyroid disorders. Conclusions: Thyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. Further prospective well designed studies on dose-effect relationship for radiotherapy-induced thyroid toxicity are therefore needed, and thyroid should be considered as an organ at risk in all patients treated for head and neck tumors. No significant financial relationships to disclose.


Immunotherapy ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 625-628 ◽  
Author(s):  
Kamelah Abushalha ◽  
Sawsan Abulaimoun ◽  
Peter T Silberstein

Background: Immunotherapy has revolutionized the treatment of cancer, but this has not come without a cost. Although immune checkpoint inhibitors are less toxic than conventional chemotherapy, they are associated with more frequent autoimmune side effects. Case presentation: We report a case of a patient with metastatic renal cell carcinoma who was treated with nivolumab and subsequently developed treatment related hypothyroidism with consequent rhabdomyolysis. Treatment with thyroxine resulted in resolution of the symptoms. Because of normal thyroid function tests before initiating nivolumab therapy and the absence of any other causes of hypothyroidism, it was safe to extrapolate a causal relationship between nivolumab and hypothyroidism. To date, this is the first reported case of a programmed cell death-1 inhibitor causing hypothyroidism, severe enough to induce rhabdomyolysis. Conclusion: Patients on nivolumab and other PD-1 inhibitors should be monitored and screened regularly for immune-related adverse events.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
F. Brucker-Davis ◽  
P. Ferrari ◽  
J. Gal ◽  
F. Berthier ◽  
P. Fenichel ◽  
...  

Aim. To assess the impact of iodine status in early pregnancy on thyroid function.Methods. Women >18 years old seen at their first prenatal consult before 12 weeks of amenorrhea and without personal thyroid history were proposed thyroid screening and were eligible if they had strictly normal thyroid tests (fT4 > 10th percentile, TSH < 2.5 mUI/L, negative anti-TPO antibodies). Evaluation included thyroid ultrasound, extensive thyroid tests, and ioduria (UIE).Results. 110 women (27.5 y, 8 weeks of amenorrhea, smoking status: 28% current smokers) were enrolled. Results are expressed as medians. UIE was 116 μg/L. 66.3% of women had iodine deficiency (ID) defined as UIE < 150. FT4 was 14.35 pmol/L; TSH 1.18 mUI/L; fT3 5 pmol/L; thyroglobulin 17.4 ng/mL; rT3 0.27 ng/mL; thyroid volume: 9.4 ml. UIE did not correlate with any thyroid tests, but correlated negatively with thyroid volume. UIE and all thyroid tests, except fT3, correlated strongly withβhCG. Smoking correlated with higher thyroid volume and thyroglobulin and with lower rT3.Conclusions. In pregnant women selected for normal thyroid function, mild ID is present in 66% during the 1st trimester. The absence of correlation between UIE and thyroid tests at that stage contrasts with the impact ofβhCG and, to a lesser degree, maternal smoking.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A840-A841
Author(s):  
David T W Lui ◽  
Chi Ho Lee ◽  
Wing Sun Chow ◽  
Alan C H Lee ◽  
Anthony Raymond Tam ◽  
...  

Abstract Objective: Occurrence of Graves’ disease and Hashimoto’s thyroiditis after coronavirus disease 2019 (COVID-19) raised the concern about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggering thyroid autoimmunity. Uncertainties remain regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. We carried out a prospective study to characterize the evolution of thyroid function and autoimmunity among COVID-19 survivors. Method: Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for confirmed COVID-19 from 21 July to 21 September 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission and at 3 months. Positive anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) was defined by &gt;100 units. Results: Among 200 COVID-19 survivors, 122 had reassessment thyroid function tests (TFTs) (median age: 57.5 years; 49.2% men). Baseline characteristics of patients who did and did not have reassessment were comparable. Among the 20 patients with baseline abnormal TFTs on admission, mostly low fT3, 15 recovered. Of the 102 patients with normal TFTs on admission, two (2.0%) had new onset abnormal TFTs, which may represent TFTs in different phases of thyroiditis (one had mildly elevated TSH 5.8 mIU/L, with normal fT4 [16 pmol/L] and fT3 [4.3 pmol/L], the other had mildly raised fT4 25 pmol/L with normal TSH [1.1 mIU/L] and fT3 [4.7 pmol/L]). Among 104 patients with anti-thyroid antibody titers reassessed, we observed increases in anti-TPO (baseline: 28.3 units [IQR 14.0-67.4] vs reassessment: 35.0 units [IQR: 18.8-99.0]; p&lt;0.001) and anti-Tg titers (baseline: 6.6 units [IQR 4.9-15.6] vs reassessment: 8.7 units [IQR: 6.6-15.4]; p&lt;0.001), but no change in anti-TSHR titer (baseline: 1.0 IU/L [IQR: 0.8-1.2] vs reassessment: 1.0 IU/L [IQR: 0.8-1.3]; p=0.486). Of the 82 patients with negative anti-TPO at baseline, 16 had significant interval increase in anti-TPO titer by &gt;12 units (2×6 [precision of the anti-TPO assay in normal range being 6 units per SD]), of these, four became anti-TPO positive. Factors associated a significant increase in anti-TPO titer included worse baseline clinical severity (p=0.018), elevated C-reactive protein during hospitalization (p=0.033), and higher baseline anti-TPO titer (p=0.005). Conclusion: Majority of thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis could occur during convalescence, though uncommon. Importantly, we provided the novel observation of an increase in anti-thyroid antibody titers post-COVID-19, suggesting the potential of SARS-CoV-2 in triggering thyroid autoimmunity, which warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.


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