High Incidence Of Hypothyroidism Research Articles

Lenvatinib Plus Pembrolizumab versus Doxorubicin for Advanced or Recurrent Endometrial Cancer with Short Treatment-Free Intervals Following First-Line Carboplatin Plus Paclitaxel

Background: The treatment-free interval is a significant predictor of worse prognosis and poor response rates of the second-line treatment in patients with carboplatin and paclitaxel (PT)-pretreated, advanced, or recurrent endometrial cancer (EC). Whether lenvatinib plus pembrolizumab still confers a survival benefit compared with doxorubicin in patients with platinum-free intervals of <6 months remains unclear. Methods: This multi-institutional retrospective analysis was performed using de-identified electronic health records from the TriNetX Research Network. Patients with advanced or recurrent ECs who received lenvatinib plus pembrolizumab or doxorubicin within six months of first-line PT were identified. A 1:1 propensity score matching (PSM) was conducted to control for potential confounding variables. Overall survival (OS) and adverse event profile were the primary and secondary outcomes. Results: Between January 2018 and February 2024, 130 patients with PT-treated, advanced, or recurrent ECs who received lenvatinib plus pembrolizumab and 122 patients who received doxorubicin at a platinum-free interval of <6 months were identified across 31 healthcare organizations. In the balanced cohort following PSM with 117 patients in each group, treatment with lenvatinib plus pembrolizumab was associated with improved OS compared with treatment with doxorubicin (12.8 vs. 8.2 months, p = 0.012, hazard ratio: 0.65, 95% confidence interval: 0.46–0.91). Regarding adverse event analysis, a higher incidence of hypothyroidism and proteinuria was observed with lenvatinib plus pembrolizumab, and more hematological toxicities were observed with doxorubicin. Conclusions: in patients with treatment-free intervals of <6 months, lenvatinib plus pembrolizumab still confers improved survival compared with doxorubicin in PT-treated, advanced, or recurrent ECs.

A Rare association of Mauriac syndrome and Van-Wyk Grumbach syndrome found in a young Saudi girl with poorly controlled type 1 Diabetes and Hypothyroidism: A Case Report and Brief literature review

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insufficient insulin production of the pancreatic beta-cells. Patients with T1DM will have a higher risk of other autoimmune disorders like celiac and thyroid diseases. Hypothyroidism is the failure of the thyroid gland to secrete an adequate amount of thyroxine, which is required for physical growth, brain development, and cellular metabolism. Most studies reported that children with T1DM have a higher incidence of hypothyroidism than normal children, with 9.6% having hypothyroidism and 19% having positive anti-TPO antibodies. Hypothyroidism will aggravate the condition in a child with T1DM and vice versa. Uncontrolled diabetes for a long time might increase insulin resistance due to complete depression of the hypothalamus-pituitary thyroid axis. A rare complication of poorly controlled T1DM is Mauriac syndrome, characterized by elevated liver enzymes, hyperlipidemia, cushingoid features, growth retardation, and hepatomegaly due to glycogenic hepatopathy. Van Wyk–Grumbach syndrome is also a rare complication of long-standing, untreated hypothyroidism, manifested by breast development, multicystic ovary, uterine bleeding associated with lack of pubic and axillary hair growth, and delayed bone age. Here, we report a case with two rare complications of Mauriac syndrome and Van Wyk–Grumbach syndrome in a child with hypothyroidism and poorly controlled T1DM.

Factors predictive of the development of hypothyroidism after intensity-modulated radiation therapy for pharyngeal cancer

Background Hypothyroidism is a common adverse event after radiotherapy for head and neck tumors and the incidence need to be re-evaluated because of using intensity-modulated radiotherapy (IMRT). Aims/Objectives Confirm the dose-volume effect of IMRT for pharyngeal cancer on hypothyroidism. Materials and methods This was a retrospective analysis of patients underwent IMRT for pharyngeal cancer from June 2011 to May 2018. Patients were classified into group A (thyroid stimulating hormone (TSH) <5μU/ml), group B (5< =TSH < 10), and group C (10< =TSH) based on TSH over 36 months post-radiation. Radiation dose, thyroid volume, and the proportion of the thyroid that received X Gy or greater (Vx) were measured. Results Fifty-two patients were included in this work. Hypothyroidism developed in 33/52 (63%) patients, 13 in group B and 20 in group C. The mean radiation dose to the thyroid was 49.4 Gy and the median time until hypothyroidism was 39 months after irradiation. Hypothyroidism was significantly related to neck dissection (ND) and radiation dose to the thyroid. Patients whose thyroid received 45 Gy or more (V45) >67% had a significantly higher incidence of hypothyroidism. Conclusions and significance Patients with pharyngeal cancer who had ND and V45 to the thyroid >67% are at risk of hypothyroidism.

High Incidence of Hypothyroidism Within a Month in Neonates with Down Syndrome Who Are Euthyroid at Birth: Results of A Prospective Study

The objective was to test for hypothyroidism (HYT) in infants with Down Syndrome (DS) who tested euthyroid on state newborn screening for congenital HYT. In 39 infants with DS who were euthyroid at birth, serum TSH, total T4 (TT4) and free T4 (FT4) levels were measured during 15 to 120 days of age. TSH, TT4 and FT4 were measured by standard techniques. Depending up on age specific TSH and thyroid hormone (TH) levels, babies were classified as: Euthyroid (normal TSH and normal TH), Primary HYT (high TSH and low TH), compensated HYT (high TSH and normal TH) and sick thyroid (low TSH and low TH). Comparisons among different groups were performed using two-sample t-tests. Twenty-nine babies (72%) remained euthyroid (TSH 6.1 ± 2.6 mIU/ml, TT4 10.8 ± 1.8 µg/ dl and FT4 1.57 ± 0.4 ng/dl). Six (18%) babies developed primary HYT (TSH 23.5 ± 10, TT4 5.1 ± 1.2, FT4 1.17 ± 0.2) within a month of life needing T4 therapy. While 4 (10%) babies developed compensated HYT (TSH 29.3 ± 10, TT4 10.6 ± 3.6 and FT4 1.83 ± 0.3), one (2.5%) had sick thyroid syndrome (TSH 4.6, TT4 4.6 and FT4 1.1). All four babies with compensated HYT were euthyroid by four months of age. Despite normal newborn screening at birth, the incidence of any HYT was much higher (28 %) than the normal neonatal population (1/2000-4000). More importantly, HYT developed within a month of age. Recommendations by the AAP about retesting TH function in infants with DS should be revised.

Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials.

A potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

The Impact of Advanced Age on Major Cardiovascular Events and Mortality in Patients with ST-Elevation Myocardial Infarction Undergoing a Pharmaco-Invasive Strategy.

BackgroundThere is little research in the efficacy and safety of a pharmaco-invasive strategy (PIS) in patients ≥75 years versus <75 years of age. We aimed to evaluate and compare the influence of advanced age on the risk of death and major adverse cardiac events (MACE) in patients undergoing PIS.MethodsBetween January 2010 and November 2016, 14 municipal emergency rooms in São Paulo, Brazil, used full-dose tenecteplase to treat patients with STEMI as part of a pharmaco-invasive strategy for a local network implementation.ResultsA total of 1852 patients undergoing PIS were evaluated, of which 160 (9%) were ≥75 years of age. Compared to patients <75 years, those ≥75 years were more often female, had lower body mass index, higher rates of hypertension; higher incidence of hypothyroidism, chronic renal failure, prior stroke, and diabetes. Compared to patients <75 years of age, in-hospital MACE and mortality were higher in patients with ≥75 years (6.5% versus 19.4%; p<0.001; and 4.0% versus 18.2%; p<0.001, respectively). Patients ≥75 years had higher rates of in-hospital major bleeding (2.7% versus 5.6%; p=0.04) and higher incidence of cardiogenic shock (7.0% versus 19.6%; p<0.001). By multivariable analysis, age ≥75 years was independent predictor of MACE (OR 3.57, 95% CI 1.72 to 7.42, p=0.001) and death (OR 2.07, 95% CI 1.12–3.82, p=0.020).ConclusionIn patients with ST-segment elevation myocardial infarction undergoing PIS, age ≥75 years was an independent factor that entailed a 3.5-fold higher MACE and 2-fold higher mortality rate compared to patients <75 years of age.

NATIONAL OBSERVATIONS OF ISCHEMIC AND HEMORRHAGIC CEREBROVASCULAR ACCIDENTS (CVA) IN TAKOTSUBO CARDIOMYOPATHY

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Takotsubo Cardiomyopathy (TTC) or stress-induced cardiomyopathy has been speculated to increase the risk of stroke with literature suggesting an incidence ranging up to 7.7% in this population. TTC can occur as a cause or a complication of stroke (CVA) and the temporal relationship between the two events is often unclear. We sought to evaluate the incidence of ischemic vs hemorrhagic CVA in patients diagnosed with TTC. We also sought to assess the comorbidities serving as predictors, the demographics and health care utilization in these groups. METHODS: We queried the National Inpatient Sample (NIS) dataset from 2007 to 2014 to identify a diagnosis of TTC with the International Classification of Disease (ICD) Code 429.83. We then identified the two groups: patients without CVA and those with CVA which was further divided into ischemic CVA with ICD codes 433.01, 433.11, 433.21, 433.31, 433.81, 433.91, 434x, 436x and hemorrhagic CVA with ICD codes 430.x, 431x, 432x. Multivariate and Chi-square analysis were done by using the statistical software, SAS. RESULTS: A total of 154,880 cases of TTC were diagnosed from the year 2007 to 2014 in the United States, with a 4.3% incidence of CVA with ischemic being 64% of total CVA. Mortality was higher in hemorrhagic CVA patients than ischemic (23.5% vs 16.1%, p < 0.05). Patients with ischemic CVA were more likely to have hypertension (65.3% vs 56.8% p<0.05), renal failure (10.6% vs 6.8% p<0.05) and diabetes (20.3% vs 11.5% p<0.05) than hemorrhagic CVA. There was almost a two-fold rise in patients with Valvular disease in those with both ischemic and hemorrhagic CVA than no stroke (10% vs 9.4% vs 4.6% p<0.05). Interestingly, a higher incidence of hypothyroidism was seen in patients without CVA than those with ischemic and hemorrhagic CVA respectively (17.7% vs 12.7% vs 9.48% p<0.05). Coagulopathy was more associated with hemorrhagic CVA than without CVA (23.6% vs 4.08% p<0.05). Length of stay and cost were higher in both types of CVA. There was an increased proportion of males developing ischemic and hemorrhagic CVA than those without CVA (17.4% and 19.7% vs 12.9% p<0.05). CONCLUSIONS: TTC was associated with a higher incidence of ischemic CVA than hemorrhagic. Preexisting cardiac risk factors were more associated with development of stroke. This included hypertension, diabetes and renal failure. Although females were more likely to have TTC, the proportion that developed CVA dropped in comparison. Outcome measures were worse in hemorrhagic stroke, likely attributed to the disease process itself. CLINICAL IMPLICATIONS: It is prudent to believe an increased risk of stroke in TTC, calling for further prospective trials to evaluate the predictors. By identifying at-risk populations, targeted interventions such as anti-platelet therapy, tighter glycemic control, may be used. DISCLOSURES: No relevant relationships by Ayesha Azmeen, source=Web Response No relevant relationships by ayesha shaik, source=Web Response No relevant relationships by Varun Tandon, source=Web Response

A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors.

Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4), programed cell death 1 (PD-1), or its ligand (PD-L1) have become the mainstay for advanced malignancies. The incidence of endocrine adverse events provoked by these immune checkpoint inhibitors (ICI) is based on data from randomized controlled trials, which have their drawbacks. PubMed was searched through August 22nd, 2017, by 2 reviewers independently (J.d.F. and C.E.A.). Early phase I/II, phase III experimental trials, prospective and retrospective observational studies were included. The weighted incidence and risk ratio were estimated for hypophysitis, primary thyroid disease, primary adrenal insufficiency, and diabetes mellitus. Their management is discussed in a systematic review. A total of 101 studies involving 19 922 patients were included. Ipilimumab-treated patients experienced hypophysitis in 5.6% (95% CI, 3.9-8.1), which was higher than nivolumab (0.5%; 95% CI, 0.2-1.2) and pembrolizumab (1.1%; 95% CI, 0.5-2.6). PD-1/PD-L1 inhibitors had a higher incidence of thyroid dysfunction - particularly hypothyroidism (nivolumab, 8.0%; 95% CI, 6.4-9.8; pembrolizumab, 8.5%; 95% CI, 7.5-9.7; PD-L1, 5.5%; 95% CI, 4.4-6.8; ipilimumab, 3.8%; 95% CI, 2.6-5.5). Combination therapy was associated with a high incidence of hypothyroidism (10.2-16.4%), hyperthyroidism (9.4-10.4%), hypophysitis (8.8-10.5%), and primary adrenal insufficiency (5.2-7.6%). Diabetes mellitus and primary adrenal insufficiency were less frequent findings on monotherapy. Our meta-analysis shows a high incidence of endocrine adverse events provoked by single agent checkpoint blockade, further reinforced by combined treatment.

KADAR IODIUM DALAM GARAM PADA DAERAH DENGAN KASUS HIPOTIROID DAN HIPERTIROID TINGGI

Background. Iodized salt is universal effort to eliminate iodine deficiency disorders (IDD). Iodine consentration in iodized salt needs to be evaluated due to many cases of hypothyroid and hyperthyroidism. Objective. The purpose of this study was to describe whether iodized salt consumed by peoples contributes to hypothyroidism and hyperthyroidism cases. Method. This was a descriptive study in area with the highest cases of hypothyroidism and hyperthyroidism based on data from Klinik Litbang GAKI Magelang 2005-2012. Samples were taken using purposive sampling with a sample size of 90 households per area. Area with the highest case of hyperthyroidism is Mertoyudan Sub District while area with the highest case of hypothyroidism is Salaman Sub Districts, both in Magelang District. Iodine content in salt was by taking sample of salt from households which used for daily consumption. Statistic analysed used were independent sample t test and Chi Square. Result. The results showed that salt consumed in both areas already contains iodine. Salt iodine content level in area with the highest hyperthyroidism (55.1±23.84 ppm) was higher than in the area with the highest hypothyroidism (49.79±39.28 ppm). According to the category of iodine content in salt, iodine content below standards ( 80 ppm) is higher in area with the highest hyperthyroidism (13.2 percent). However iodine content in both areas showed no significant difference (p=0.27). Conclusion. Iodized salt consumption does not contribute to the high case of hypothyroidism or hyperthyroidism. Salt consumed in area with the highest cases of hypothyroidism and hyperthyroidism already contains iodine as standard. It is possible that there are other factors that cause high incidence of hypothyroidism and hyperthyroidism in those areas that needs further research. Keywords: hyperthyroidism, hypothyroidism, iodine, salt

Abstract TP95: Hypothyroidism is Associated With Cerebral Aneurysms in Women

Background: Endocrine dysfunction, including thyroid function, has been known to affect cerebral vascular dysfunction. Hypothyroidism has been shown to cause mucopolysaccharide deposition which has been associated with the weakening of blood vessel walls and aneurysm formation in some case reports. However, the connection between hypothyroidism and cerebral aneurysm has not been well studied. We hypothesized that hypothyroidism maybe associated with occurrence of cerebral aneurysms. Methods: We performed a retrospective case-control study of consecutive patients receiving cerebral angiography at our tertiary-care academic medical center. Inclusion criteria included undergoing 3-vessel angiography. Exclusion criteria included any ruptured aneurysm or previous intracranial hemorrhage. Medical history of hypothyroidism was noted along with all other risk factors. The control group of patients did not have any intra-cranial abnormality on angiography. Patients with cerebral aneurysm were matched with controls for known risk factors of cerebral aneurysm, including: age, hypertension, and smoking history. Cases were further subdivided base on gender given females are known to have higher incidence of hypothyroidism. Results: From 2008 through 2013, 82 female and 59 male patients with aneurysms were identified for this study and were matched with equal numbers of controls. Among women, hypothyroidism was present in 20.7% (17/82) among patients with cerebral aneurysms vs. in only 6.1% (5/82) among matched controls: odds ratio (OR) 4.03 (95% CI 1.41-11.51, p=0.01). Among men, 8.5% (5/59) cases and 0/59 controls had hypothyroidism, showing no significant association, with an odds ratio of 12.01 (95% CI 0.65-222.3, p=0.095). Conclusion: We found a significant association of history of hypothyroidism with cerebral aneurysm in women in our patient cohort. Given the potential pathophysiologic connection between hypothyroidism and vascular wall dysfunction, this should be explored further.

Pemphigus and associated comorbidities: a cross-sectional study.

Pemphigus is a rare autoimmune blistering disease, reported to be associated with other coexisting and autoimmune diseases, including thyroid diseases, rheumatoid arthritis, alopecia areata, vitiligo, systemic lupus erythematosus, scleroderma and rare entities such as myasthenia gravis. To identify and describe patients with pemphigus with a diagnosed comorbidity, and to quantify the risk of additional comorbidities. This was a cross-sectional study of patients with pemphigus treated at a tertiary referral centre. Prevalence rates of 15 comorbid diseases were calculated. Age-standardized prevalence ratio (SPR) and 95% CI were calculated in comparison with prevalence rates in the general Canadian population using data from the Canadian Community Health Survey. Data were analysed using SAS software. In total, 295 patients were identified. An increased risk of hypothyroidism (n=38, SPR=1.53, 95% CI 1.08-2.10) and inflammatory bowel disease (IBD) (SPR=1.48, 95% CI 0.40-3.80), and a two-fold increased risk of diabetes (SPR=2.20, 95% CI 1.64-2.87) were observed. Patients with pemphigus have a higher incidence of hypothyroidism, IBD and diabetes compared with the general population. As part of pemphigus investigations and surveillance, investigating for these conditions may be considered.

Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver.

BackgroundThyroid hormones (THs) are potent hormones modulating liver lipid homeostasis. The perturbation of lipid homeostasis is a hallmark of non-alcoholic fatty liver disease (NAFLD), a very common liver disorder. It was reported that NAFLD patients were associated with higher incidence of hypothyroidism. However, whether abnormal thyroid function contributes to the pathogenesis of NAFLD remains unclear.ResultsWe used in vivo models to investigate the influence of hypothyroidism and TH on hepatic lipid homeostasis. We did not observe hepatic triglyceride accumulation in the liver of hypothyroid mice, although the liver was enlarged. We then characterized the hepatic fatty acid composition with gas chromatography–mass spectrometry in mice under different thyroid states. We found that hypothyroidism decreased saturated fatty acid (SFA) content while TH treatment restored the level of SFA. In agreement with this finding, we observed that the expression of acetyl-CoA carboxylase 1 and fatty acid synthase, the rate-limit enzymes for de novo lipogenesis (DNL), decreased in hypothyroid mice while increased after TH treatment. We also found that the ratio of C18:1n-9/C18:0 and C16:1n-7/C16:0 was decreased by TH treatment, suggesting the activity of stearoyl-CoA desaturase-1 was suppressed. This finding indicated that TH is able to suppress triglyceride accumulation by reducing fatty acid desaturation. Additionally, we found that hepatic glycogen content was substantially influenced by TH status, which was associated with glycogen synthase expression. The increased glycogen storage might explain the enlarged liver we observed in hypothyroid mice.ConclusionsTaken together, our study here suggested that hypothyroidism in mice might not lead to the development of NAFLD although the liver became enlarged. However, disturbed TH levels led to altered hepatic fatty acid composition and glycogen accumulation.

English

In order to study the incidence of hypothyroidism in women of reproductive age in Raichur, the data of women who were referred to Tunge Diagnostic Centre in Raichur was collected and the levels of T4 and TSH hormones recorded. The incidence in non pregnant women is 9.29% and in the case of pregnant women, the incidence is reported as 7.89%. Overall, an incidence of 11.97% has been found, indicating the high incidence of hypothyroidism in women of this region. INTRODUCTION: Thyroid disorders are one of the most commonly encountered endocrine disorders in India, and the effect it has on the women of reproductive age is noteworthy. One of the most common thyroid disorders in women of that age group is hypothyroidism, which leads to the clinical manifestations such as delay in sexual maturation and onset of puberty, reduced fertility 5

Fibromyalgia, Thyroid Dysfunction and Treatment Modalities

Fibromyalgia is a debilitating condition presenting with symptoms of chronic muscular pain, fatigue, insomnia and cognitive dysfunction among other symptoms, which lead to a diminished quality of life. Although the exact pathogenesis and underlying mechanisms which lead to clinical manifestation are unknown, there is a growing line of evidence suggesting an association between fibromyalgia and thyroid dysfunction. Numerous studies have reported that patients with fibromyalgia have a high incidence of hypothyroidism. Further, thyroid autoimmunity has also been associated with fibromyalgia symptom severity. Circulating thyroid hormones do not provide an accurate status of thyroid function in patients with fibromyalgia, rather intracellular thyroid hormone levels are more relevant. Low levels of intracellular hormones may result from mitochondrial dysfunction as active transport of hormones across cellular membranes is required. It is well known that mitochondrial dysfunction is associated with fibromyalgia. In order to correct thyroid dysfunction and manage symptoms presenting in fibromyalgia patients, a multi-disciplinary approach should be taken incorporating dietary supplements, nutraceuticals, dietary changes and complementary alternative therapies.

Increased risk of hypothyroidism and hyperthyroidism in patients with major depressive disorder: A population-based study

ObjectiveTo determine the prevalence and incidence of hypothyroidism, hyperthyroidism, and risk factors in patients with major depressive disorder (MDD). MethodsThe National Health Research Institute provided a database of 1,000,000 random subjects for health service studies. We identified subjects aged ≥18years who had at least 1 service claim during 2005 with a primary diagnosis of MDD or with a primary or secondary diagnosis of hypothyroidism or hyperthyroidism. We also compared the incidence of hypothyroidism and hyperthyroidism among patients with MDD and the general population from 2006 through 2010. ResultsThe prevalence of hypothyroidism in patients with MDD was higher than that in the general population (1.20% vs. 0.30%; odds ratio, 3.08; 95% confidence interval, 2.35–4.03) in 2005. The prevalence of hyperthyroidism was also higher in patients with MDD than in the general population (2.46% vs. 0.79%; odds ratio, 2.77; 95% confidence interval, 2.29–3.35) in 2005. The annual incidence of hypothyroidism was higher in patients with MDD than that in the general population (0.40% vs. 0.13%; risk ratio, 2.47; 95% confidence interval, 2.00–3.06). The annual incidence of hyperthyroidism was also higher in patients with MDD than that in the general population (0.72% vs. 0.32%; risk ratio, 2.06; 95% confidence interval, 1.75–2.43). ConclusionsPatients with MDD had a higher prevalence and a higher incidence of hypothyroidism or hyperthyroidism than the general population. Female sex was a risk factor for hypothyroidism and hyperthyroidism in MDD.

Thyroid Dysfunction in Patients Treated With Sunitinib or Sorafenib

IntroductionSunitinib and sorafenib are tyrosine kinase inhibitors used in metastatic renal cell carcinoma and are known to cause hypothyroidism in a subset of patients. The goal of this study was to better characterize the development of hypothyroidism in patients and to examine its relationship to progression-free survival. Patients and MethodsA retrospective chart review was performed on patients treated with sunitinib or sorafenib from January 1, 2005, to January 1, 2011. Data pertaining to the treatment course and development of hypothyroidism were extracted. Patients with hypothyroidism at the beginning of treatment were analyzed separately. ResultsA total of 73 treatment periods had sufficient data to analyze. Among patients with normal baseline thyroid function, 15 (44%) of 34 patients treated with sunitinib and 6 (27%) of 22 patients treated with sorafenib developed hypothyroidism. The hazard ratio for the development of hypothyroidism with sorafenib vs. sunitinib treatment was significant, at 0.38 (95% CI, 0.14-0.97). There was a statistically significant difference in the progression-free survival between patients who developed hypothyroidism while receiving treatment compared with those who did not, 18.2 vs. 10.1 months (P = .01). ConclusionsThis study demonstrated a significant difference in the incidence of hypothyroidism during treatment with sunitinib and sorafenib, with a higher incidence of hypothyroidism in patients treated with sunitinib. The development of hypothyroidism was associated with a longer progression-free survival.

Nilotinib-induced hypothyroidism in a patient with chronic myeloid leukemia

Peripheral edema often occurs in patients with chronic myeloid leukemia (CML) treated with kinase inhibitors (TKIs). However, there are few reports indicating that the edema is caused by TKIs-induced hypothyroidism. We present the case of a 76-year-old man with chronic-phase CML who suffered from severe systemic edema after introduction of nilotinib. Laboratory tests revealed hypothyroidism; the patient was euthyroid prior to introduction of nilotinib. After further examination, we attributed this hypothyroidism to nilotinib. His edema regressed dramatically after thyroid hormone replacement therapy, with continued treatment with nilotinib. Laboratory examination of thyroid function also improved markedly. Although sunitinib, a multi-targeted TKI, is associated with a high incidence of hypothyroidism, TKIs targeting Bcr-Abl have rarely been reported to cause hypothyroidism. We report nilotinib-induced hypothyroidism, and suggest that hypothyroidism should be considered as a possible etiology when patients receivingTKIs suffer from edema.

The impact of sunitinib-induced hypothyroidism on progression-free survival of metastatic renal cancer patients: A prospective single-center study

BackgroundSeveral studies have reported unexpected rates of hypothyroidism in patients treated with sunitinib. The biochemical basis of this impairment is unknown. A relationship between hypothyroidism and improved outcome has been suggested in some cancer patients. Here we describe the incidence of newly onset hypothyroidism and its relationship with progression-free survival in metastatic renal cell carcinoma patients undergoing sunitinib treatment at our institution. Patients and methodsBetween July 2007 and June 2009, 22 patients received a first line sunitinib for metastatic renal cell carcinoma. Thyroid function tests were prospectively evaluated as routine laboratory assessment in every patient, at baseline and on the first and last day of every ON and OFF sunitinib period. ResultsThe median duration of treatment was 39.5 weeks. During sunitinib therapy, 13 patients (59.1%) showed at least one elevated TSH level. No reductions of TSH below normal ranges were observed. L-thyroxine replacement therapy was required in 2 patients. Based on thyroid function, median progression-free survival was 8.55 months for hypothyroid compared with 7.03 months for euthyroid patients (P < 0.05). ConclusionPatients administered sunitinib have an high incidence of hypothyroidism. The improved outcome of hypothyroid patients suggests an important relationship between sunitinib and this uncommon side effect.

Thyroid Gland in Patients with Rheumatoid Arthritis

The purpose of our study was to investigate the main parameters of thyroid status in patients with rheumatoid arthritis (RA), as well as particularities of course of this disease depending on of thyroid gland function disorder. Materials and methods. 52 women with RA were examined. The first group consisted of 11 women with subclinical and manifestive hypothyroidism the second one 41 women without thyroid gland function disorder. The group comparison was conducted on main indexes of thyroid gland condition the hormon level, AT-TPO, ultrasonic data, as well as clinical and laboratory RA data. Results. In women with hypothyroidism the systemic manifestations of RA were more often truely diagnosed; DAS28 indexes, ESR, the number ot swollen joints were higher. The high level ot AT-TPO was diagnosed in 54,55% – I group and in 31,7% – II group TTG level was really less in patients receiving synthetic glycocorticoids. Small thyroid gland volume was diagnosed in 23,07% of examined patients. The thyroid gland status indexes in them did not differ from patients with normal thyroid gland volume. Reliable increasing of the peripheral resistance index was revealed in lower thyroid artery according to the ultrasonic study data under the reduced thyroid gland size. Conclusions. High incidence of hypothyroidism and AT-TPO carriage in RA was revealed. Hypothyroidism development is accompanied by high clinic-laboratory RA activity. The reduction of the thyroid gland volumes in RA is possibly stipulated not only by autoimmunal pathology, but also chronic ischemia of the organ in the conditions of immune-complex vasculitis and early atherosclerosis. The TTG level in patients with RA is defined not only by pathology of the thyroid gland, but glycocorticoid therapy as well.

Survival and long-term toxicities of biochemotherapy for metastatic melanoma

8553 Purpose: Because long-term survival after therapy for advanced stage IV melanoma is rare, we thought it would be useful to examine our series of survivors treated with biochemotherapy for melanoma to analyze the characteristics of survivors and their chronic toxicities. Patients and Methods: We reviewed our previously reported (J Clin Oncol. 2005:23:16s suppl, abstract 7547) consecutive series of 38 patients treated between 9/02 and 7/04. They received 6 cycles of inpatient temozolomide, cisplatin, vinblastine, decrescendo high- dose iv IL-2 , and interferon followed by maintenance immunotherapy using IL-2 and sargramostim using the O’Day regimen (Clinical Cancer Res. 2002:8:2775).Two of the ten long-term survivors received surgery for resection of residual disease after achieving a partial response with biochemotherapy. Maintenance immunotherapy was given for 6 to 24 months after biochemotherapy. Results: The median progression- free survival was 7.3 months. No patient developed progression later than 17 months after the start of therapy with the progression-free survival curve level at 24%. Median overall survival was 16.2 months. 10 of the 38 patients are alive and disease-free off therapy after an average of 3.3 years follow-up. Durable complete responses were seen in visceral sites including lung, bone, and pericardium, with 8 of 10 long- term survivors having M1B or M1C disease. 3 patients have significant lymphedema related to prior surgery, radiation therapy, or both. 2 patients, one with pre-existing diabetes, have significant persisting neuropathy. 5 of the 10 patients are hypothyroid. Menstrual function returned in the three women under age 45 in this study. Conclusion: This series supports the findings from other series that biochemotherapy, like high-dose IL-2, can give prolonged disease-free survival. Survivors have a high incidence of hypothyroidism but neuropathy and lymphedema, which affected a minority of patients, were the most bothersome long-term toxicities. No significant financial relationships to disclose.