scholarly journals OR28-07 Increased BMI Is Associated With Anti PD-1/PD-L1-Induced Thyroid Immune-Related Adverse Events

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Rena Pollack ◽  
Amit Ashash ◽  
Avivit Cahn ◽  
Rivka Dresner-Pollak
Keyword(s):  
Adverse Events ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Overt Hypothyroidism ◽  
Thyroid Function Tests ◽  
Normal Thyroid Function ◽  
Baseline Bmi ◽  
Insight Into ◽  
Overt Hyperthyroidism

Abstract Background: Immune checkpoint inhibitors have revolutionized cancer therapy, however, are associated with immune related adverse events (irAEs). Obesity is a pro-inflammatory metabolic state that may play a role in the development of irAEs. Hypothesis: We hypothesized that likelihood of developing thyroid irAEs following anti-PD-1/L1 therapy increases with increasing body mass index (BMI). Methods: We retrospectively analyzed data of 187 cancer patients who initiated anti-PD-1/L1 at our institution between 01/2014-12/2018, had normal thyroid function tests at baseline and had baseline BMI data available. Results: Overall, 97 (52.2%) patients were with low-normal BMI (<25 kg/m2), 52 (28.0%) overweight (≥25-30 kg/m2) and 37 (19.9%) obese (≥30 kg/m2). Thyroid dysfunction (hyper or hypo, overt or subclinical) developed in 72/187 (38.7%) patients, of whom 29/97 (29.9%) had low-normal BMI, 22/52 (42.3%) were overweight and 21/37 (56.8%) obese (p=0.14). With every 1 kg/m2 increase in BMI, the likelihood of thyroid dysfunction increased by 8.8% (p=0.004). Overt hyperthyroidism occurred in 32/186 (9.1%) of the patients - in 4.1% of patients with low-normal BMI, 11.5% of overweight patients and 18.9% of obese (p=0.006). Overt hypothyroidism occurred in 32/186 (17.2%) of the patients and was not significantly associated with BMI. Hyperthyroidism followed by overt hypothyroidism, consistent with thyroiditis, occurred in 13/186 (7.0%) of patients and was significantly associated with increasing BMI category (p=0.03). Conclusions: Increased BMI was associated with increased thyroid irAEs in patients treated with PD-1/L1 inhibitors. Further exploration of the interaction between obesity and immunotherapy may provide insight into the role of inflammation in mediating immune response.

scholarly journals COGNITIVE FUNCTION IN WORKING POPULATION WITH ABNORMAL THYROID FUNCTION TEST

2020 ◽  
pp. 1-3
Author(s):  
Nilanjana Debnath ◽  
Keshao B. Nagpure ◽  
Preetam N. Wasnik
Keyword(s):  
Cognitive Function ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Mmse Score ◽  
Overt Hypothyroidism ◽  
Thyroid Function Tests ◽  
Working Population ◽  
Function Tests ◽  
The Mean ◽  
Overt Hyperthyroidism

Context: Cognitive impairment is linked to thyroid dysfunction in various studies; however, the evidence is mixed. Aims: To determine cognitive function in the working population with abnormal thyroid function tests. Settings: Outpatient department of Medicine in a tertiary care hospital located in Central India. Design: Hospital-based, cross-sectional study. Methods and Material:100 patients between 15-64 years of age with different patterns of thyroid dysfunction were subjected to cognitive function testing via the Mini-Mental Status Examination (MMSE) questionnaire. Statistical analysis used: The data obtained was coded in a Microsoft Excel Worksheet and analyzed by SPSS software version 21. Results: 100 patients (11 % men and 89 % women) were included in the present study. The mean age of the study population was 37.11±8.76 years. 87 % had overt hypothyroidism, 6 % had subclinical hypothyroidism, 6 % had overt hyperthyroidism. The mean MMSE score of patients with abnormal thyroid function tests was 27.62 ±2.04 (Range 23-30). The mean MMSE score in patients with overt hypothyroidism was 27.54 ± 2.07, that of overt hyperthyroidism 28.33 ±1.03, and that of subclinical hypothyroidism was 27.67 ± 2.50. MMSE scores among different patterns of thyroid dysfunction were not found to be statistically significant. The MMSE scores between newly and previously diagnosed patients with thyroid dysfunction were not statistically significant. (28.3 ± 1.06 vs 27.54 ± 2.12). Conclusions: The results suggest no association between cognitive function and abnormal thyroid function tests in the working population.

scholarly journals Phenotypic Differences in Thyroid Immune Related Adverse Events Following Treatment With Immune Checkpoint Inhibitors

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A876-A877
Author(s):  
Christopher Alan Muir ◽  
Alexander M Menzies ◽  
Roderick John Clifton-Bligh ◽  
Georgina V Long ◽  
Richard A Scolyer ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Thyroid Dysfunction ◽  
Cancer Survival ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Organ Systems ◽  
Euthyroid Hyperthyroxinemia ◽  
Overt Hyperthyroidism

Abstract Background: Thyroid toxicity is common following immune checkpoint inhibitor (ICI) treatment. Published studies estimate the incidence at 10-20%, although rates vary widely between different ICIs. The etiology of ICI-associated thyroid immune related adverse events (irAEs) is unknown & not all patients develop a classic thyroiditis-like presentation of transient hyperthyroidism followed by a hypothyroid phase. Only small observational cohorts have been reported & the clinical & biochemical features of thyroid irAEs have not been well characterized. The current study aimed to describe thyroid irAEs in a large cohort of patients with melanoma. Methods: We reviewed outcomes in a prospective cohort of adult patients undergoing ICI treatment for advanced melanoma. Thyroid function was measured at baseline & at regular intervals during treatment. Thyroid irAEs were defined as new biochemical thyroid dysfunction developing over the course of routine follow-up. Results: Thyroid irAEs occurred in 518 of 1246 (42%) patients. Median follow-up was 11.3 months. Multiple patterns of thyroid-irAEs were observed, such as hyperthyroidism (subclinical or overt) in 31%, hypothyroidism in 8%, & euthyroid hyperthyroxinemia, hypothyroxinemia & isolated low FT3 syndrome each in 1% of participants. Thyroid irAEs were more frequent following combination (CTLA-4 + PD-1) ICI treatment (56%) than following PD-1 (38%) or CTLA-4 (25%) based monotherapies (p=0.001). The severity of thyroid irAEs differed by ICI, with higher rates of overt (vs. subclinical) thyroid dysfunction following combination ICI treatment (47%) relative to PD-1 (37%) & CTLA-4 (19%) monotherapies (p=0.001). Younger age (OR 0.88 per 10-yrs; 95% CI 0.81-0.96), female sex (OR 1.62; 95% CI 1.27-2.08) & combination ICI-treatment (vs. CTLA-4, OR 3.76, 95% CI 2.49-5.75; vs. PD-1, OR 1.90, 95% CI 1.45-2.49) were associated with higher odds of thyroid irAE. Time to onset of thyroid dysfunction was shorter in patients with overt hyperthyroidism relative to other types of thyroid irAE (log rank p=0.001). Overt hyperthyroidism was associated with increased irAEs in other organ systems (colitis, hepatitis, etc), increased irAE severity & increased multi-system irAEs than euthyroid patients or patients with other subtypes of thyroid irAE (p=0.003). Overt hyperthyroidism was also associated with improved progression free survival (HR 0.57; 95% CI 0.39-0.84; p=0.005) & overall survival (HR 0.68; 95% CI 0.49-0.94; p=0.02). No benefit to cancer survival was observed with other thyroid irAE subtypes. Conclusions: Thyroid irAEs were common. Combination ICI treatment resulted in more frequent, more severe, & earlier onset thyroid irAEs. Of thyroid irAE subtypes, overt hyperthyroidism was uniquely associated with increased immune responsiveness, as evidenced by higher incidence of extra-thyroidal irAEs & improvements in cancer survival.

scholarly journals SAT-463 Thyrotoxicosis from Nivolumab in a Patient with Preexisting Graves’ Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Preethi Polavarapu ◽  
Padmaja Akkireddy
Keyword(s):  
Adverse Events ◽  
Thyroid Function ◽  
Autoimmune Thyroiditis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Thyroid Dysfunction ◽  
Checkpoint Inhibitors ◽  
Graves Disease ◽  
Thyroid Function Tests ◽  
Free T4

Abstract Introduction Thyroid dysfunction is one of the common immune-related adverse events associated with immune checkpoint inhibitors like Nivolumab. Thyroiditis or primary hypothyroidism is the most commonly reported presentation. Graves’ disease is less frequently reported. We report a case of preexisting Graves’ disease patient, on antithyroid meds who developed thyrotoxicosis followed by hypothyroidism after receiving Nivolumab therapy. Case 66 y/o female patient with newly diagnosed metastatic melanoma presented to us for evaluation of abnormal thyroid test after her second cycle of Nivolumab. She has a long-standing history of Graves’ disease and has been on methimazole since her diagnosis. Her baseline thyroid labs before the start of Nivolumab were within normal limits (on methimazole 2.5 mg daily). She presented with weight loss, palpitations, and tremors four weeks after the start of Nivolumab. On exam, she was tachycardic with tremors noted to outstretched hands and had diffusely enlarged thyroid. Repeat lab work done before her second cycle revealed suppressed TSH 0.02 (0.4-4.5 uIU/ml) with elevated free T4 and T3. Her TSI titers were elevated. Methimazole dose was increased to 10 mg daily, and follow up labs done in a month revealed TSH of 89 uIU/ml, Free T4 0.16 (0.76-1.8 ng/dl). Methimazole was completely stopped at this time. She continued to have elevated TSH despite being off of methimazole for more than a month, concerning for the development of hypothyroidism. She was started on levothyroxine, after which labs returned to normal. The patient continued on immunotherapy during this period. Discussion Immune checkpoint inhibitors have been increasingly used for cancer therapy. Endocrinopathies are the most common immune-related adverse events associated with the use of these agents, with thyroid dysfunction being more common. Our patient had well-controlled Graves’ disease and was on a stable dose of methimazole for years. She developed autoimmune thyroiditis four weeks after receiving immunotherapy and subsequently developed hypothyroidism. The literature search did not reveal cases of autoimmune thyroiditis in a patient with preexisting Graves’ disease. One study reported that the timeline for developing the thyrotoxic phase is five weeks, which is followed by the rapid development of either euthyroid or hypothyroid phase. Management during the thyrotoxic phase is usually beta-blockers. Current guidelines recommend checking thyroid function test before initiation of therapy and every two weeks after the diagnosis of thyrotoxicosis until they become euthyroid or hypothyroid. Our case illustrates that patients with preexisting Graves’ disease can develop thyroiditis after receiving immune checkpoint inhibitors, and hence, frequent monitoring with thyroid function tests is needed.

scholarly journals Prevalence of thyroid dysfunction and its effects on fetomaternal outcome in pregnant women of Eastern Uttar Pradesh, India

2018 ◽  
Vol 7 (11) ◽  
pp. 4379
Author(s):  
Ankita Kumari ◽  
Reena Srivastav ◽  
Shaila Mitra
Keyword(s):  
Thyroid Dysfunction ◽  
Uttar Pradesh ◽  
Overt Hypothyroidism ◽  
Thyroid Function Tests ◽  
Thyroid Disorder ◽  
Medical College ◽  
Thyroid Screening ◽  
Fetal Complications ◽  
Adverse Pregnancy ◽  
Eastern Uttar Pradesh

Background: The aim of the study is to determine the prevalence of thyroid dysfunction in pregnancy and its impact on obstetrical outcome in Eastern Uttar Pradesh.Methods: This was a prospective observational study undertaken at antenatal clinics and indoor of BRD Medical College, Gorakhpur. Total 720 antenatal women, ≤20 weeks of gestation were recruited for the study. In all patients’ routine obstetrical investigations and thyroid function tests were done. All patients were followed up to delivery. Maternal and perinatal outcome were ascertained.Results: Prevalence of thyroid dysfunction among pregnant was found to be 21.1% and subclinical hypothyroidism (15.9%) was the commonest thyroid disorder. Most common complication observed in subclinical and overt hypothyroidism was preeclampsia (9.56 % versus 20%) followed by preterm labour (7.82% versus 10%). Major fetal complications in hypothyroid mothers included intrauterine growth restriction, low birth weight and stillbirth.Conclusions: Prevalence of hypothyroidism was found to be high in our study and was associated with adverse pregnancy outcomes; hence, thyroid screening should be included in routine antenatal investigations.

scholarly journals Association between ultrasonography echogenicity and heterogeneity and thyroid function in autoimmune diffuse thyroid diseases in children and adolescents 

2021 ◽  
Author(s):  
Ji Eun Park ◽  
Sook Min Hwang ◽  
Ji-Young Hwang ◽  
Jin Hee Moon ◽  
Ik Yang ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Diseases ◽  
Overt Hypothyroidism ◽  
Thyroid Ultrasound ◽  
Thyroid Status ◽  
Children And Adolescent ◽  
Overt Hyperthyroidism

Abstract Purpose: To evaluate the association between thyroid echogenicity and heterogeneity seen on ultrasonography (US) and thyroid function in pediatric and adolescent populations with autoimmune diffuse thyroid diseases (AITD).Methods: From 2000 to 2020, we reviewed thyroid ultrasound (US) images and thyroid function statuses in 133 children and adolescent AITD patients. Our review of the images focused on decreased echogenicity and heterogeneity, which were classified into four grades.Results: Among patients with overt hypothyroidism or overt hyperthyroidism, 94.2% (65/69) showed a US grade of 3 or 4. In patients with subclinical hyper/hypothyroidism or euthyroidism, 45.3% (29/64) showed grades 1 or 2. There were no overt hyper/hypothyroidism patients with US grade 1. When we compared US grades according to thyroid status, more severe thyroid dysfunction was significantly associated with higher US grade (p=0.047). Thyroid stimulating hormone (TSH) level differed significantly according to US grades when we evaluated hyperthyroid (p=0.035) and hypothyroid (p=0.027) states independently. 11 patients showed both US grade and thyroid function status changes on follow-up US.Conclusions: In children and adolescent AITD patients, there was an association between decreased echogenicity and heterogeneity on US and thyroid dysfunction.

scholarly journals Thyroid dysfunction in preeclampsia and related fetomaternal outcomes

2019 ◽  
Vol 8 (5) ◽  
pp. 1928
Author(s):  
Puja Banik ◽  
R. K. Praneshwari Devi ◽  
Aheibam Bidya ◽  
Akoijam Tamphasana ◽  
M. Agalya ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Birth Asphyxia ◽  
Normal Pregnancy ◽  
Thyroid Stimulating Hormone ◽  
Severe Preeclampsia ◽  
Intrauterine Fetal Death ◽  
Overt Hypothyroidism ◽  
Thyroid Function Tests ◽  
Cross Sectional

Background: Changes in thyroid function in normal pregnancy are well-documented but in complicated pregnancy like preeclampsia, very little is known. Studies have shown evidences of hypothyroidism in preeclampsia necessitating thyroid function tests to be done in preeclampsia. The study was done to analyze the fetomaternal outcome of preeclampsia with coexisting thyroid dysfunction.Methods: A cross-sectional analytical study was done over 18 months on 95 preeclamptic patients admitted at the antenatal ward and fetomaternal outcomes were analyzed according to thyroid status.Results: Out of 95 patients with preeclampsia, 42 (44.2%) had thyroid dysfunction. Among these 42 patients, 37 (38.9%) patients had subclinical hypothyroidism, 4 (4.2%) had overt hypothyroidism and 1 (1%) had hyperthyroidism. Severe preeclampsia was seen in 64.3% of the patients with thyroid dysfunction compared with 39.6% in euthyroid patients. The mean thyroid stimulating hormone (TSH) level was significantly higher and means free thyroxine (fT4) level was significantly lower in severe preeclampsia compared with non-severe preeclampsia. Complications like abruption, intrauterine fetal death (IUD), intrauterine growth restriction (IUGR), oligohydramnios, preterm deliveries, postpartum hemorrhage (PPH), low birth weight babies, birth asphyxia in babies and subsequent neonatal intensive care unit (NICU) admissions were significantly higher (p <0.05) in the preeclampsia patients with thyroid dysfunction in comparison with euthyroid ones.Conclusions: Hypothyroidism may be a modifiable risk factor for preeclampsia. Thyroid screening early in pregnancy may be helpful in predicting the occurrence of preeclampsia and timely thyroid hormone administration can reduce the maternal and perinatal morbidity and mortality associated with preeclampsia.

scholarly journals Overt Hypothyroidism Induced by Prolonged Therapy With Imatinib

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A945-A946
Author(s):  
Ally W Wang ◽  
Emily V Nosova
Keyword(s):  
Tyrosine Kinase ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Case Reports ◽  
Myelogenous Leukemia ◽  
Prolonged Treatment ◽  
Overt Hypothyroidism ◽  
Imatinib Treatment ◽  
Thyroid Function Tests ◽  
History Of

Abstract Background: Imatinib, a tyrosine kinase inhibitor (TKI), is commonly used to treat chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors. TKI-induced thyroid dysfunction is recognized as an adverse class effect with most cases occurring between six to twelve months after treatment initiation. Clinical Case: 76-year-old man with hypertension and CML on Imatinib that had been started twenty months prior was admitted for confusion. The patient also reported constipation, cold intolerance, and weight gain despite no change in diet, appetite, or physical activity. On evaluation, his responses to questioning were noticeably delayed, however he was not lethargic. His vital signs were normal and he was otherwise euthyroid on physical exam. He had no known history of thyroid dysfunction. Labs showed a TSH of 94.7 (0.4 - 4.2 uIU/mL), Free T4 0.4 (0.8 - 1.5 ng/dL), and Total T3 30 (87 - 178 ng/dL). Thyroglobulin antibody was 1016 (0.0 - 4.1 U/mL) and TPO antibody was &gt;2000 (0.0 - 5.6 IU/mL). A TSH checked two months before admission was 1.1. Antibody levels had not been checked previously. Thyroid ultrasound demonstrated a hyperemic and heterogeneous thyroid, consistent with thyroiditis. Levothyroxine at a dose of 50 mcg daily was advised, due to patient’s advanced age as well as history of arrhythmia. The patient’s confusion resolved on hospital day three. Repeat thyroid function tests will be checked four to six weeks after Levothyroxine initiation. Discussion: As a class, tyrosine kinase inhibitors are known to cause thyroid dysfunction with the most common medication being Sunitinib. Data related to the effects of thyroid function during Imatinib treatment are limited. Previous cases of Imatinib-induced thyroid dysfunction report only hypothyroidism in thyroidectomized patients and no clinically significant change in thyroid function among patients who were euthyroid prior to therapy initiation. Our case reports a patient with no prior thyroidectomy who developed overt hypothyroidism while on Imatinib for nearly two years. The mechanism for TKI-induced thyroid dysfunction has not been elucidated. Due to relatively acute onset and markedly positive TPO and thyroglobulin antibodies, we suspect that TKI may alter HLA recognition on thyroid follicular cells, thereby inducing autoimmunity. Our case showcases the need to maintain awareness and continuous surveillance for thyroid dysfunction when patients are on long term TKI as overt hypothyroidism may be induced by prolonged treatment.

scholarly journals Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A841-A841
Author(s):  
Alessandro Brancatella ◽  
Isabella Lupi ◽  
Lucia Montanelli ◽  
Debora Ricci ◽  
Nicola Viola ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Checkpoint Inhibitors ◽  
Thyroid Volume ◽  
Clinical Severity ◽  
Response To Treatment ◽  
Thyroid Function Tests ◽  
Thyroid Ultrasound ◽  
Normal Thyroid ◽  
Normal Thyroid Function

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&lt;0.05). Methimazole (MMI) was effective only in Sci+ subjects (P&lt;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

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