Onset Of Hypothyroidism Research Articles

Longitudinal assessment of thyroid function in dogs with hypoadrenocorticism: Clinical outcomes and prevalence of autoantibodies.

Knowledge about primary hypoadrenocorticism coexisting with immune-mediated thyroiditis (Schmidt's syndrome) in dogs is limited. To evaluate thyroid function in dogs with naturally occurring hypoadrenocorticism before and during treatment. Sixty-six client-owned dogs. Measurement of canine thyroid stimulating hormone (cTSH), total thyroxine (T4), free thyroxine, and autoantibodies against thyroglobulin, T4, and total triiodothyronine. Thirty-eight dogs were assessed before and 28 during treatment. Follow-up data were available for 24/38 and 17/28 dogs, with median follow-up duration of 3.8 years (range, <1.0-8.8 years) and 4 years (range, 1.1 weeks to 10.5 years), respectively. Canine thyroid stimulating hormone was above the reference range at the time of diagnosis of hypoadrenocorticism in 10 of 38 dogs but decreased into the reference range in 7 for which follow-up data was available. Hypothyroidism was confirmed in 5 dogs at a median age of 11 years (range, 7-15 years). In 4 dogs, the condition was diagnosed after a median treatment duration of 5.75 years (range, 2.6-10 years), while in 1 dog, the diagnosis was made concurrently. One dog had detectable thyroid autoantibodies. Hypothyroidism occurs as a rare concurrent condition in dogs with hypoadrenocorticism, potentially at any phase of treatment. Close monitoring of cTSH levels in these dogs could be beneficial, as early changes might indicate the onset of hypothyroidism. The low prevalence of detectable thyroid autoantibodies suggests that nonimmune mechanisms might contribute to thyroid dysfunction.

6781 A Rare Case of Diffuse Large B Cell Lymphoma of the Thyroid

Abstract Disclosure: D. Deyar: None. M. Herrera: None. M. Ahmad: None. P. Ucciferro: None. Introduction: Primary thyroid lymphoma (PTL) is rare, comprising less than 5% of thyroid cancers. It is frequently seen in middle-aged women and 1.5% of patients with Hashimoto’s thyroiditis. PTL may present with rapidly growing mass, dysphagia, stridor, or hoarseness. We describe a case of a female patient presenting with a neck mass and new onset hypothyroidism who was found to have DLBCL of the thyroid. We aim to raise clinical awareness regarding PTL and elucidate its association with Hashimoto’s disease and discuss treatment strategies. Case presentation: The patient was a 62-year-old female with a past medical history of type 2 diabetes, hypertension, and hyperlipidemia, presenting for worsening neck swelling for the past four weeks. She reported tenderness around the mass along with voice hoarseness and difficulty swallowing. She also reported increased shortness of breath associated with the mass while lying flat and denied any heat intolerance, cold intolerance, weight changes or bowel habit changes. The patient’s vitals were as follows: blood pressure: 146/104 mmHg, heart rate: 58 beats per minute, temperature: 36.3 C, respiratory rate: 20 breaths per minute. Initial blood work demonstrated the following: sodium: 137 mmol/L, potassium: 4.2 mmol/L, 9.4 mg/dL, white blood cell count: 12.1 × 109/L, hemoglobin: 14.5 g/dL, platelets: 330 × 109/L, thyroid stimulating hormone: 17.1 uIU/mL, free T4: 0.4 ng/dL, and TPO antibodies: 300 IU/mL. A CT scan of her neck demonstrated a left sided mass measuring 6.6 cm, by 5.6 cm, by 11 cm. The patient was started on 50 mcg of levothyroxine and was assessed by otorhinolaryngology and underwent fine needle aspiration biopsy. The patient’s biopsy demonstrated diffuse large B cell lymphoma of the thyroid gland. The patient was started on R-CHOP chemotherapy for her lymphoma as an outpatient and had a significant decrease in the size of her neck mass and improvement in her compressive symptoms. She is scheduled for six cycles of R-CHOP therapy and continues to follow with oncology. Discussion: Diffuse Large B Cell Lymphoma (DLBCL) of the thyroid is rare and necessitates distinct therapeutic considerations. Patients with Hashimoto's thyroiditis have been found to be 60-fold times more likely to develop primary thyroid lymphoma as compared to those without thyroiditis. The pathophysiology regarding this association remains unclear, however some suggest it may be due to chronic lymphocytic inflammation of the thyroid gland leading to monoclonal lymphocyte growth. Treatment of DLBCL of the thyroid requires immunotherapy, most commonly with the R-CHOP therapy which distinguishes it from the conventional management of thyroid carcinomas. Physicians should be vigilant in considering these treatment differences and to consider PTL as an etiology of growing thyroid mass in patients with Hashimoto’s thyroiditis. Presentation: 6/2/2024

Stage IV renal cell carcinoma achieves pathologic complete response after two ipilimumab plus nivolumab courses despite severe immune-related adverse events: a case report

BackgroundIpilimumab (Ipi) plus nivolumab (Nivo) is the recommended first-line treatment for renal cell carcinoma (RCC). This report describes a case where pancreatic metastases disappeared after only two courses of Ipi + Nivo therapy. The primary tumor was cured by surgery, and a pathological Complete Response (pCR) was observed despite multiple serious immune-related Adverse Events (irAEs).Case presentationA 54-year-old woman with RCC and pancreatic metastasis at stage IV, diagnosed with intermediate risk according to the International Metastatic RCC Database Consortium classification, underwent initiation of Ipi + Nivo therapy. On day 26, she developed hyperthyroidism accompanied by tachycardia, leading to the commencement of metoprolol tartrate treatment. Following the resolution of tachycardia, a second course of Ipi + Nivo therapy was administered on day 50. By day 70, the patient exhibited Grade 3 hepatic dysfunction, followed by the onset of hypothyroidism on day 75, necessitating treatment with steroids and levothyroxine. After positive treatment, a Grade 3 skin disorder emerged on day 87 while tapering steroids, prompting treatment with methylprednisolone (mPSL) pulse therapy. The skin disorder responded to steroids, allowing for tapering. However, on day 113, a recurrence of Grade 3 skin disorder occurred, necessitating another mPSL pulse. The patient responded well to treatment, exhibiting improvement in her condition. On day 131, she presented at the hospital with complaints of respiratory distress, prompting a Computed Tomography (CT) scan that revealed interstitial pneumonia. By day 272, subsequent CT imaging showed the disappearance of pancreatic metastasis and shrinkage of the primary tumor. On day 294, she underwent a laparoscopic left nephrectomy. Pathological analysis confirmed a pCR in the primary tumor, indicating successful eradication of RCC through surgical intervention.ConclusionsThis case report presents a scenario where multiple severe irAEs appeared in a patient, yet metastases disappeared after only two courses of Ipi + Nivo therapy. The patient was ultimately cured by surgery and achieved a pCR. This case highlights that despite the occurrence of severe irAEs during RCC treatment with Ipi + Nivo therapy, they can be managed appropriately to maximize the therapeutic effects of checkpoint inhibitors.

Patterns and outcomes of late onset thyroid disturbances after COVID-19 vaccination: A report of 75 cases.

Isolated cases of subacute thyroiditis exist in the early period of COVID-19 vaccination, largely after mRNA vaccines. Here we report late onset thyroid disturbances and persistent health issues in patients of thyroid disorders after COVID-19 vaccination. Seventy-five patients with post COVID-19 vaccination thyroid disturbances were identified. Among these, 41 had flare of underlying thyroid illness, majority occurring at a median time lag of 28.4 weeks since 2nd dose. Thirty-one cases of new onset hypothyroidism and three of new onset hyperthyroidism were reported, with a median time lag respectively of 17.2 and 22.6 weeks since 2nd dose. Most cases occurred after ChAdOx1-nCoV-19, which was the commonest vaccine employed in mass roll out in India. Significant improvement was observed in majority, after a median follow up of 22-26 weeks. New onset health issues persisting for ≥4 weeks were reported in 37.3% and were common in individuals with history of COVID-19 before vaccine. New onset metabolic, musculoskeletal, and reproductive disorders were the common health complaints. Active monitoring is warranted for late onset adverse events after COVID-19 vaccines of all types. Larger studies with involvement of unvaccinated individuals are required to understand the incidence and causality of late onset thyroid disturbances after COVID-19 vaccines.

Complex relationship between gut microbiota and thyroid dysfunction: a bidirectional two-sample Mendelian randomization study.

Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes in gut microbiota after the onset of thyroid dysfunction are not clear. A two-sample Mendelian randomization (MR) study was used to explore the complex relationship between gut microbiota and thyroid dysfunction. Data on 211 bacterial taxa were obtained from the MiBioGen consortium, and data on thyroid dysfunction, including hypothyroidism, thyroid-stimulating hormone alteration, thyroxine deficiency, and thyroid peroxidase antibodies positivity, were derived from several databases. Inverse variance weighting (IVW), weighted median, MR-Egger, weighted mode, and simple mode were applied to assess the causal effects of gut microbiota on thyroid dysfunction. Comprehensive sensitivity analyses were followed to validate the robustness of the results. Finally, a reverse MR study was conducted to explore the alteration of gut microbiota after hypothyroidism onset. Our bidirectional two-sample MR study revealed that the genera Intestinimonas, Eubacterium brachy group, Ruminiclostridium5, and Ruminococcaceae UCG004 were the risk factors for decreased thyroid function, whereas the genera Bifidobacterium and Lachnospiraceae UCG008 and phyla Actinobacteria and Verrucomicrobia were protective. The abundance of eight bacterial taxa varied after the onset of hypothyroidism. Sensitivity analysis showed that no heterogeneity or pleiotropy existed in the results of this study. This novel MR study systematically demonstrated the complex relationship between gut microbiota and thyroid dysfunction, which supports the selection of more targeted probiotics to maintain thyroid-gut axis homeostasis and thus to prevent, control, and reverse the development of thyroid dysfunction.

Development of a predictive score for post-hemithyroidectomy hypothyroidism using skeletal muscle index, remnant thyroid index, and thyroid-stimulating hormone levels: a retrospective cohort study.

Hypothyroidism is a major complication of hemithyroidectomy. Low remnant thyroid volume and high serum thyroid-stimulating hormone (TSH) levels are suggested as risk factors for post-hemithyroidectomy hypothyroidism. Reduced skeletal muscle mass is associated with a variety of postoperative complications. However, its impact on post-hemithyroidectomy hypothyroidism has not yet been studied. This study aimed to evaluate the association between skeletal muscle mass and the onset of post-hemithyroidectomy hypothyroidism and develop a predictive score using skeletal muscle mass in combination with previously reported risk factors. This study retrospectively analyzed 226 consecutive patients who underwent hemithyroidectomy at Shinshu University Hospital between January 2011 and December 2020. The skeletal muscle area at the fourth thoracic vertebral level and maximal remnant thyroid area were quantified using preoperative computed tomography and standardized by dividing them by the square of the patient's height, designated as the skeletal muscle index (SMI) and remnant thyroid volume index (RTI). Subclinical hypothyroidism was defined as a postoperative elevated serum TSH level (>5 µU/mL) with a normal free thyroxine (FT4) level (≥0.9 ng/dL), overt hypothyroidism as a postoperative increase in serum TSH level (>5 µU/mL) and a decrease in serum FT4 level (<0.9 ng/dL), and symptomatic hypothyroidism as an elevated serum TSH level (>5 µU/mL) with hypothyroidism-related symptoms. Logistic regression analysis was used to determine the factors associated with the onset of hypothyroidism. Patients with euthyroid status had significantly higher SMI and RTI than those who developed post-hemithyroidectomy hypothyroidism (SMI, euthyroid: 12.0±2.4 vs. subclinical hypothyroid: 10.2±1.7, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 10.1±1.7, P<0.001, RTI, euthyroid: 1.19±0.41 vs. subclinical hypothyroid: 0.92±0.35, P<0.001, euthyroid vs. overt or symptomatic hypothyroid: 0.84±0.30, P<0.001). Multivariable analysis demonstrated that low SMI, low RTI [hazard ratio (HR): 3.35, P<0.001], and preoperative high serum TSH levels (HR: 2.54, P=0.003) were independent predictive factors for hypothyroidism. Patients who had low SMI, low RTI, and preoperative high serum TSH levels were more likely to develop hypothyroidism (68.8%) than those with either one (25.3%), two (47.8%), or none (15.2%) of these three factors. Preoperative evaluation of the SMI, RTI, and serum TSH levels may be useful in predicting the development of post-hemithyroidectomy hypothyroidism.

Hypothyroidism.

Hypothyroidism is the common clinical condition of thyroid hormone deficiency and, if left untreated, can lead to serious adverse health effects on multiple organ systems, with the cardiovascular system as the most robustly studied target. Overt primary hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) concentration in combination with free thyroxine (fT4) concentration below the reference range. Subclinical hypothyroidism, commonly considered an early sign of thyroid failure, is defined by elevated TSH concentrations but fT4 concentrations within the reference range. Hypothyroidism is classified as primary, central or peripheral based on pathology in the thyroid, the pituitary or hypothalamus, or peripheral tissue, respectively. Acquired primary hypothyroidism is the most prevalent form and can be caused by severe iodine deficiency but is more frequently caused by chronic autoimmune thyroiditis in iodine-replete areas. The onset of hypothyroidism is insidious in most cases and symptoms may present relatively late in the disease process. There is a large variation in clinical presentation and the presence of hypothyroid symptoms, especially in pregnancy and in children. Levothyroxine (LT4) is the mainstay of treatment and is one of the most commonly prescribed drugs worldwide. After normalization of TSH and fT4 concentrations, a considerable proportion of patients treated with LT4 continue to have persistent complaints, compromising quality of life. Further research is needed regarding the appropriateness of currently applied reference ranges and treatment thresholds, particularly in pregnancy, and the potential benefit of LT4/liothyronine combination therapy for thyroid-related symptom relief, patient satisfaction and long-term adverse effects.

Primary hypothyroidism and quality of life.

In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic L form of tetraiodothyronine. Since then, no major innovation has emerged for the treatment of hypothyroidism. The biochemical definition of subclinical hypothyroidism is a matter of debate. Indiscriminate screening for hypothyroidism has led to overdiagnosis and treatment initiation at lower serum levels of thyroid-stimulating hormone (TSH) than previously. Adverse health effects have been documented in individuals with hypothyroidism or hyperthyroidism, and these adverse effects can affect health-related quality of life (QOL). Levothyroxine substitution improves, but does not always normalize, QOL, especially for individuals with mild hypothyroidism. However, neither studies combining levothyroxine and liothyronine (the synthetic form of tri-iodothyronine) nor the use of desiccated thyroid extract have shown robust improvements in patient satisfaction. Future studies should focus not only on a better understanding of an individual's TSH set point (the innate narrow physiological range of serum concentration of TSH in an individual, before the onset of hypothyroidism) and alternative thyroid hormone combinations and formulations, but also on autoimmunity and comorbidities unrelated to hypothyroidism as drivers of patient dissatisfaction. Attention to the long-term health consequences of hypothyroidism, beyond QOL, and the risks of overtreatment is imperative.

Association between valproate treatment for acute phase schizophrenia and risk of new onset hypothyroidism

AimTo assess the association between acute phase treatment by valproate as an adjunctive drug and risk of new onset hypothyroidism in a large cohort of patients affected by schizophrenia. MethodsWe conducted a retrospective cohort study in a psychiatric hospital in China between January 2016 and December 2018. We obtained approval from the Ethics Committee of the study hospital prior to the commencement of the study. Patients who were diagnosed with schizophrenia and admitted to the study hospital during the study period with thyroid function tests at admission and during hospitalization were included. Patients with abnormal thyroid function at admission were excluded. Hypothyroidism, defined as TSH>4.2 mU/L or on L-thyroxine treatment, was the primary outcome. The primary exposure was adjunctive valproate plus atypical antipsychotics (AAPD), the secondary exposure was lithium plus AAPD and the comparison group was AAPD only. Adjusted relative risk (RR) and 95% confidence interval (CI) were estimated by log-binomial model to assess the independent association between valproate treatment and risk of hypothyroidism. ResultsA total of 1622 eligible patients were included the final analysis. Rate of new onset hypothyroidism was 10.7% and 20.9% in AAPD only and valproate plus AAPD groups, respectively. Adjusted RR (95% CI) for valproate plus AAPD was 1.85 (1.44–2.38), with AAPD only group as reference. Similarly, adjusted RR (95% CI) for lithium plus AAPD was 1.93 (1.32–2.69). ConclusionSimilar with lithium, valproate as adjunctive drug is associated with increased risk of new onset hypothyroidism during acute phase treatment for schizophrenia.

Canine Adult-Onset Hypothyroidism: Prevalence, Clinical and Laboratory Findings with Special Reference to Therapeutic Approach

Hypothyroidism is one of the most common endocrinopathies in dogs, it is defined as a decrease in production of thyroid hormones. Hypothyroidism results in vague clinical of signs but metabolic and dermatological signs are the most reported manifestations. This investigation aimed to study canine hypothyroidism in terms of clinical, haemato- biochemical, and thyroid panel alterations and evaluate response to treatment in adult onset hypothyroidism in dogs’ cosmopolitan in Cairo and Giza governorates. To crude determination of disease in dog cosmopolitan in Cairo and Giza governorates, multicenter study was conducted. In the period from December-2019 to May-2020, 220 dogs with various dermatologic signs represented to different clinics, after ruling out other causes, 40 with signs consistent with hypothyroidism were subjected to initial screening for hypothyroidism using TT4. Only 15 dogs showed decrease in TT4 and these dogs were further investigated, additional 8 clinically healthy dogs enrolled as control group. Blood sample was taken from both hypothyroid dogs [N=15] and control dogs [N=8] for hematology analysis, TT4, fT4, TSH. Cholesterol, ALT and ALP. Diseased group [15 dogs] were treated with levothyroxine and re-evaluated after 1-month period. Overall prevalence of hypothyroidism in this investigation was 7.5 percent. Significant decrease in RBCs, PCV, TT4 and fT4 along with non-significant increase in TSH and cholesterol were recorded in hypothyroid patients compared to control group. Treatment with levothyroxine caused thyroid hormones to be within normal reference range. The Prevalence of hypothyroidism in studied cases in this investigation was 7.5 % and is similar to the reported prevalence; diagnosis of hypothyroidism should be relying on combination of clinical and laboratory data. Usage of human levothyroxine can successfully manage caninehypothyroidism.

Thyroid hormones modulate irisin concentrations in patients with recently onset hypothyroidism following total thyroidectomy

PurposeIrisin is a newly discovered adipo-myokine known for having significant effects on body metabolism. Currently, there is a discussion regarding the relation between thyroid function and irisin concentration. This study was designed to evaluate the influential role of levothyroxine replacement therapy on circulating levels of irisin in patients with recently onset hypothyroidism following total thyroidectomy.MethodsCirculating levels of thyroid hormones, irisin and other metabolic parameters, were assessed in 40 recently thyroidectomized patients (34 females, mean age 50.1 ± 15.2 years) at baseline (5–7 day after surgery) and after 2 months under replacement therapy with levothyroxine.ResultsAt baseline, circulating levels of thyroid hormones were indicative of hypothyroidism (TSH 12.7 ± 5.0 μU/mL, FT3 1.9 ± 0.7 pg/mL, FT4 8.7 ± 3.6 pg/mL). Mean serum irisin concentrations significantly increased after 2 months under replacement therapy with levothyroxine (from 2.2 ± 0.6 to 2.9 ± 0.6 μg/mL, p < 0.0001). Variations of circulating levels of irisin under levothyroxine replacement therapy were directly correlated with those of FT3 (Rho = 0.454, p = 0.0033) and FT4 (Rho = 0.451, p = 0.0035). Multivariate regression analysis revealed that changes in thyroid hormones concentrations explained up to 10% of the variations of serum irisin levels under levothyroxine replacement therapy (FT3 R2 = 0.098, FT4 R2 = 0.103).ConclusionOur study suggests that levothyroxine replacement therapy mildly influences irisin metabolism in patients with recently onset hypothyroidism following total thyroidectomy.

Acquired Hypothyroidism in Patients with Metastatic Renal Cell Carcinoma Treated with Tyrosine Kinase Inhibitors.

PurposeWe analyze a number of studies that describe the relationship between the onset of hypothyroidism and the prognosis of patients with metastatic renal cell carcinoma (mRCC) treated with TKIs.Patients and MethodsTargeted therapies are currently considered as the first-line treatment for patients with mRCC. The occurrence of hypothyroidism in the treatment of mRCC with TKIs is a major side effect. A comprehensive search was performed in Pubmed, Cochrane Library, Institute for Scientific Information, and CKNI. The following keywords and descriptors were used during the search and were combined in a number of sequences in English and Chinese languages: protein kinase inhibitors (including sunitinib, pazopanib, tivozanib, cabozantinib, axitinib, sorafenib), hypothyroidism and renal cell carcinoma.ResultsScholars have studied the clinical relationship between hypothyroidism and TKI treatment and its molecular biology mechanism. Most studies hold that hypothyroidism occurring during TKI therapy may serve as potential biomarkers of response and efficacy of treatment, but there is no consensus on this point.ConclusionThe mechanism of hypothyroidism occurring is still unclear. Therefore, more studies are needed to clarify whether better outcomes are associated with TKI-induced hypothyroidism in mRCC patients, helping to maximize the treatment outcome of mRCC patients.

SAT-158 New Data on High Prevalence and Time of Occurrence of New Onset Hypothyroidism Associated with Mitotane Therapy in a Cohort of Adrenocortical Cancer

Context. Mitotane is a steroidogenesis inhibitor and an adrenocorticolytic drug used to treat adrenocortical cancer (ACC). Central hypothyroidism is recognized in mitotane-treated patients and recent data suggested that mitotane could have an inhibitory effect on TSH-secreting cells in the pituitary gland. Moreover, mitotane may lead to induction of thyroid hormone metabolism. Clinical data on hypothyroidism related to mitotane such as prevalence and time of occurrence was described in a limited number of patients. Objective. To better characterize clinically secondary hypothyroidism in patients with ACC treated with mitotane therapy. Methods. We reviewed retrospectively paper charts and electronic records from patients with histologically confirmed diagnosis of ACC evaluated at our center from 1995-2019. We analysed the pattern of TSH and thyroid function, but also mitotane timing and levels at baseline and during treatment of patients under mitotane therapy. Thyroid hormone assessment including TSH, FT4 and FT3 was performed at least every 3 months during follow-up. Results. Our cohort of 104 patients with ACC includes 84 patients that received mitotane therapy. Among them, thyroid function data was incomplete for 39 cases. Complete data was retrieved from 45 patients. Ten out of 45 (22.2%) patients were already known for primary hypothyroidism and were receiving L-T4 replacement before the initiation of mitotane. Two of 45 (4.4%) patients maintained a normal thyroid function during complete follow up (4.5 years) and 33/45 (73.3%) had new onset hypothyroidism requiring levothyroxine treatment. Of these 33 patients, 22 were females and 11 were males, ranging from 22-74 yo with a median of 46 yo. The number of patients with ENSAT stage I, II, III and IV of disease were 1, 8, 11 and 13 respectively. Thyroid profiles were compatible with central hypothyroidism (low T4 with low or inappropriately normal TSH) in 22/33 patients (66.7%). Interestingly, 6/33 patients (18.2%) developed a TSH elevation with a normal lower-limit or low T4 level. The timeline distribution of the occurrence of hypothyroidism was 21.2% (n:7) at <3 months, 15.2% (n:5) between 3-6 months, 21.2% (n:7) between 6-9 months and 15.2% (n:5) between 9-12 months. 9.1% (n:3) occurred within the second year of treatment (between 12-24 months). However, in 5/33 (15.2%) cases, the exact time of new hypothyroidism onset was undetermined. Conclusion. Mitotane therapy is frequently associated with new onset hypothyroidism with a prevalence of 73% in our cohort of exposed patients and is most likely of central etiology. 72.7% of cases occur in the first year of treatment while 9.1% occur in the second year. This study supports the importance of monitoring thyroid function (including a free T4 level) during the complete course of mitotane therapy.

SUN-414 Tyrosine Kinase Inhibitors Induced Thyroid Dysfunction: An Experience from a Tertiary Care Hospital

Tyrosine kinase inhibitors (TKI) belong to a new class of molecular multi-targeted anticancer therapy which targets different growth factor receptors and hence attenuates cancer cell survival and growth. TKI-induced thyroid dysfunction is recognized as a common adverse effect of treatment., but the onset of thyroid dysfunction is variable. This study analysed correlation between initiation of TKIs and the onset of thyroid dysfunction in non-thyroid cancers patients without any background thyroid dysfunction.METHODS:This was a retrospective cohort study to evaluate thyroid dysfunction in adult patients (n=227, M:F=153:74) with non-thyroidal cancers treated with TKIs. Patients having pre-existing thyroid disease including euthyroid goitres were excluded. Demographic, clinical, and cancer treatment data were collected. Thyroid function tests (TFTs) were done prior to initiation, at 2 months, 6 months and at 1 year. TFTs were classified as euthyroid (thyrotropin [TSH] normal), subclinical (SCH; TSH 5-10 mIU/L, or higher TSH if free thyroxine normal), or overt hypothyroidism (OH; TSH >10 mIU/L, low free thyroxine, or requiring replacement).RESULTS:Of the 227 patients in the study, OH occurred in 57 patients (25.1%)(M:F = 19:38) and SCH occurred in 89 patients (39.2%) (M:F=39:50) with TKI therapy at the end of 12 months. 37 patients (M:F=13:24) developed OH in first 6 months after initiation of TKIs. Female patients were more likely to have OH in the first 6-month period following TKIs irrespective of type of TKI or the cancers. SCH was also more common after 2 months in female patients (n=23) (M:F=6:17) but the conversion of SCH to OH was more common in male patients at the end of 12 months. The symptoms were variable and most the patients did have any thyroid specific symptoms. After adjustment for age, sex, cancer type, cancer stage, performance status, and type of TKI, OH remained significantly associated with survival at 1-year (hazard ratio=0.461; p<0.0001), whereas SCH did not (hazard ratio=0.591; p=0.165). Analysis of hypothyroid patients (SCH and OH) with TSH >5 and <10 mIU/L stratified by hormone replacement status showed improved survival associated with hormone replacement, although 1 year follow-up is too short to comment on overall survival rates.CONCLUSIONS:New onset hypothyroidism, both OH and SCH is common in non-thyroidal cancer patients treated with TKI. SCH is more common after 2 months and OH after 6 months following TKI initiation. Female sex is more predisposed to develop thyroid dysfunction irrespective of underlying cancer or type of TKI used but male patients progressed to OH at the end of 12 months.

PD-L1 Inhibitor-Induced Thyroiditis Is Associated with Better Overall Survival in Cancer Patients.

Background: Thyroid immune-related adverse events (IRAEs) have been reported more frequently with programmed cell death protein-1 (PD-1) inhibitors than cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, but there is limited data describing endocrinopathies from programmed cell death protein-ligand 1 (PD-L1) inhibitors. This study characterizes thyroid IRAEs in cancer patients treated with PD-L1 inhibitors and examines the impact on overall survival. Methods: This is a retrospective cohort study of cancer patients treated with atezolizumab and avelumab at the Mayo Clinic, Rochester, Minnesota, from June 1, 2016 to January 30, 2018, and followed for a median of 10.1 months. Thyroid IRAEs were characterized as new onset hypothyroidism, thyrotoxicosis, and worsening of pre-existing hypothyroidism. Results: Of 91 patients treated with a PD-L1 inhibitor, 19 (21%) developed new onset thyroid dysfunction, of whom 14 presented with hypothyroidism and 5 with thyrotoxicosis (3 progressed to hypothyroidism and 2 returned to euthyroidism), and 4 (4%) had worsening of pre-existing hypothyroidism. Thyroid IRAEs occurred after a median of two doses (6 weeks), 48% required thyroid hormone replacement, and none required steroids or discontinuation of immunotherapy. Two out of four patients with thyroid peroxidase (TPO) antibody >9 IU/mL at baseline developed thyroid IRAEs. Median TPO antibody titer was not different between those with and without thyroid IRAEs but was higher in those with overt than those with subclinical hypothyroidism (5 vs. 0.3 IU/mL, p = 0.003) and those prescribed thyroid hormone replacement as compared with observation (5.5 vs. 0.3, p = 0.008). Diffusely increased thyroid 18-fluorodeoxyglucose (18FDG) uptake on positron emission tomography (PET) scan occurred in 71% with thyroid IRAE as compared with 6% without thyroid IRAEs (p = 0.001). Patients who developed thyroid IRAEs had longer overall survival (p = 0.027) and lower mortality (hazard ratio 0.49 [95% CI 0.25-0.99], p = 0.034) after adjusting for potential confounders. Conclusions: PD-L1 inhibitors lead to immune-mediated thyroiditis, the most frequent endocrine IRAE. In most cases, management is supportive without requiring steroids or discontinuation of immunotherapy. Diffusely increased thyroid 18FDG uptake on PET scan may predict the occurrence of thyroiditis, whereas TPO antibodies may help identify its severity. Thyroiditis may be a biomarker for antitumor immune response, highlighting the need to further characterize its underlying mechanism.

Onset of hypothyroidism after total laryngectomy: Effects of thyroid gland surgery and preoperative and postoperative radiotherapy.

BackgroundTo determine time of onset and risk of hypothyroidism after total laryngectomy (TL) with and without (hemi)thyroidectomy in relation to treatment regimen, that is, preoperative radiotherapy (RT‐TL), postoperative radiotherapy (TL‐RT), and postoperative re‐irradiation (RT‐TL‐RT).MethodsRetrospective review of 128 patients treated by RT‐TL (51 patients), TL‐RT (55 patients), and RT‐TL‐RT (22 patients). Risk of hypothyroidism was determined by multivariable Cox regression analysis and euthyroid survival was calculated using Kaplan‐Meier method.ResultsHypothyroidism developed in 69 (54%) patients. The median onset of hypothyroidism was later (P < .01) and the risk of hypothyroidism was lower (hazard ratio 0.49; P = .014) in the TL‐RT group compared to both other treatment regimens. Euthyroid survival did not differ between the treatment regimens. Two years euthyroid survival was 24% with and 61% without (hemi)thyroidectomy (P < .001).ConclusionsPatients treated with TL‐RT have later onset of hypothyroidism. Higher risk for hypothyroidism is associated with salvage TL after radiotherapy and (hemi)thyroidectomy.

Wolcott-Rallison Syndrome-Endocrinopathy with Recurrent Acute Liver Failure

A 2-yr-old child with early onset diabetes and hypothyroidism, and diagnosed as Wolcott-Rallison Syndrome, developed two episodes of acute liver failure and recovered, but he remains at high risk of developing another episode of acute liver failure. Autoimmune, metabolic or genetic disorders should be evaluated in children with recurrent acute liver failure and genetic tests needs to be considered.

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma

Background: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. Objective: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). Methods: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. Results: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. Conclusion: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.

Levothyroxine Dosing after Delivery in Women Diagnosed with Hypothyroidism During Pregnancy-A Retrospective, Observational Study.

Background:Pregnancy leads to profound alteration in thyroid function and dysthyroidism contributes to adverse pregnancy outcomes. Though the management of hypothyroidism during pregnancy is highlighted, the same is often neglected during postpartum. We have evaluated the postpartum levothyroxine (LT4) dose change in patients with new onset hypothyroidism.Methods:We conducted this retrospective, observational study between 2014 and 2016 using the medical records of patients with new onset hypothyroidism during pregnancy. We included patients who continued with LT4 after delivery (as per predetermined protocol) and the availability of 2-year follow up record. We excluded patients who stopped LT4 and use of other drugs that affect the thyroid function tests (TFT) after delivery. The patients were divided into 2 groups for comparison [Group 1-Overt hypothyroidism (OH) and Group 2-Subclinical hypothyroidism (SCH)] based on the initial TFT reports. The data were analyzed using appropriate statistical methods and a P value of less than 0.05 was considered significant.Results:A total of 159 women continued using LT4 after delivery and the final follow up data were available for 130 patients only. LT4 dose up titration was observed more in group 1 than in group 2 (P = 0.0336). In both the groups, the presence of goitre, thyroid autoimmunity and a repeat pregnancy are associated with increasing LT4 requirement.Conclusion:Majority of patients with OH during pregnancy require more than half of the final dose after delivery. Goitre and autoimmunity are associated with higher LT4 dose after delivery.

Micro-lithography on paper, surface process modifications for biomedical performance enhancement

We have enhanced the performance of lithographically patterned microchannels on paper and tailored it to a do it yourself method by examining the impact of each microfabrication step on surface properties. Modification of photoresist spreading, baking, exposure and developing steps improved paper and channels quality and decreased fabrication costs and time. The proper concentration of SU-8 in cyclopentene was found 1/8 (volumetric), to enable coating on paper by soaking, faster baking (10 min-65 ℃), and improved paper hydrophilicity. The UV-exposure time and energy were modified to enhance the channel quality. Then, the patterned paper was washed in cyclopentene for 15 min, and baked for 1 min at 95 ℃. The modified process leaves 100 μm uniform channels on paper in around 26 min, from design to completion. Each step modification was assessed by analyte flow testing. The tuned process also improved the uniformity of channels, and eliminated the need for a spinner or hotplate. Exposure refinement alleviated the necessity for a mask aligner machine, and sunlight may also be used instead of UV. Channels were finally treated with BSA to improve partitioning and analyte flow, and reduce longitudinal binding, verified by IR absorption spectrum. The resulting μ PAD was used for detection of TSH on the onset of hypothyroidism at 4 mU/L in four minutes, using an ELISA protocol.