Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy.

PURPOSE: Immunotherapy against immune checkpoints has significantly improved survival both in metastatic and adjuvant setting in several types of cancers. Thyroid dysfunction is the most common endocrine adverse event reported. Patients who are at risk of developing thyroid dysfunction remain to be defined. We aimed to identify predictive factors for the development of thyroid dysfunction during immunotherapy. METHODS: This is a retrospective study including a total of 68 patients who were treated with immune checkpoint inhibitors (ICIs) for metastatic or unresectable advanced cancers. The majority of patients were treated with anti-PD1 drugs in monotherapy or in combination with anti-CTLA4 inhibitors. Thyroid function and anti-thyroid antibodies, before starting immunotherapy and during treatment, were evaluated. Thyroid ultrasound was also performed in a subgroup of patients at the time of enrolment in the study. RESULTS: Eleven out of 68 patients (16.1%) developed immune-related overt thyroid dysfunction. By ROC curve analysis, we found that a serum TSH cut-off of 1.72 mUI/l, at baseline, had a good diagnostic accuracy in identifying patients without overt thyroid dysfunction (NPV = 100%, p = 0.0029). At multivariate analysis, both TSH and positive anti-thyroid antibodies (ATAbs) levels, before ICIs treatment, were independently associated with the development of overt thyroid dysfunction during immunotherapy (p = 0.0001 and p = 0.009, respectively). CONCLUSIONS: Pre-treatment serum TSH and ATAbs levels may help to identify patients at high risk for primary thyroid dysfunction. Our study suggests guidance for an appropriate timely screening and for a tailored management of thyroid dysfunctions in patients treated with ICIs.

Reference Values of Thyroid Hormones During the First Trimester of Pregnancy in Valencian Community (Spain) and Their Relationship with Iodine Intake.

Thyroid hormones require special monitoring during the first trimester of gestation. Local reference values should be applied if available, especially in iodine-deficient areas, as generalized iodine supplementation is controversial. The aim of the present study was to establish thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference values in the first trimester of gestation in the Valencian community (Spain) and relate them to iodine intake. A total of 261 healthy pregnant women participated in the study. The calculated reference values were 0.128-4.455 mIU/L for TSH and 0.9-1.592 ng/dL for FT4. The upper TSH reference value for pregnant women in the first trimester in our environment was similar to the latest American Thyroid Association (ATA) recommendation (4 mIU/L). The mean TSH value was significantly lower in smokers, and there were no significant differences when analyzing the influence of iodine supplementation, although the low duration of supplement intake needs to be taken into consideration. Ioduria levels (median 57 µg/L) confirmed iodine deficiency. We found statistically significant differences in ioduria levels among patients who consumed iodized salt and iodine supplements and those who did not. It is essential to focus on recommending adequate consumption of iodized salt and iodine supplements prior to gestation and at least during the first trimester to avoid possible maternal thyroid dysfunction and perinatal complications.

Reducing waste: a guidelines-based approach to reducing inappropriate vitamin D and TSH testing in the inpatient rehabilitation setting.

Background: Laboratory overutilisation increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Discipline-specific guidelines do not support routine testing for Vitamin D and thyroid-stimulating hormone (TSH) in the inpatient rehabilitation setting, yet 94% of patients had Vitamin D and TSH tests on admission to inpatient rehabilitation at our institution. Our objective was to reduce Vitamin D and TSH testing by 25% on admission to inpatient Stroke, Spinal Cord Injury, Acquired Brain Injury and Amputee Rehabilitation units. Methods: A fishbone framework for root cause analysis revealed potential causes underlying overutilisation of Vitamin D and TSH testing. A series of Plan-Do-Study-Act (PDSA) cycles were introduced to target remediable factors, starting with an academic detailing intervention with key stakeholders that reviewed applicable clinical guidelines for each patient care discipline and the rationale for reducing admission testing. Simultaneously, computerised clinical decision support (CCDS) limited Vitamin D testing to specific criteria. Audit and feedback were used in a subsequent PDSA cycle. Frequency of Vitamin D and TSH testing on admission was the primary outcome measure. The number of electronic admission order caresets containing automatic Vitamin D and/or TSH orders before and after the interventions was the process measure. Rate of Vitamin D supplementation and changes in thyroid-related medication were the balancing measures. Results: After implementation, 2.9% of patients had admission Vitamin D testing (97% relative reduction) and 53% of patients had admission TSH testing (43% relative reduction). Admission order caresets with prepopulated Vitamin D and TSH orders decreased from 100% (n=6) to 0%. The interventions were successful; similar to previous literature, CCDS was more effective than education and audit and feedback interventions alone. The interventions represent >$9000 annualised savings.

Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters.

Thyroid hormones and thyroid autoantibodies, along with serum concentrations of two phytoestrogens of the isoflavone series, daidzein and genistein, were measured in 268 children without overt thyroid diseases, screened for iodine deficiency in one region of the Czech Republic. Since both phytoestrogens have been reported to inhibit thyroid hormone biosynthesis and in high concentrations to exert goitrogenic effects, we investigated whether their presence in the circulation could influence thyroid hormone function in a population where soy consumption is not common. Correlation analysis revealed a significant positive association of genistein with thyroglobulin autoantibodies and a negative correlation with thyroid volume. Multiple regression analysis of the relationships between actual phytoestrogen levels and measured thyroid parameters revealed only a weak but significant association between genistein and thyroid variables. Higher levels of free thyroxine were found in a subgroup of 36 children who ate soy food in the previous 24 h. In conclusion, only modest association was found between actual phytoestrogen levels and parameters of thyroid function. On the other hand, even small differences in soy phytoestrogen intake may influence thyroid function, which could be important when iodine intake is insufficient.

Goiter prevalence, serum selenium, and urine iodine status in a previously iodine-deficient area in Turkey.

This study was planned to investigate goiter prevalence and serum selenium and urine iodine status among school-age children in the Ankara region of Turkey. Nine hundred five (905) children were investigated; 847 of them were included in the study. Thyroid ultrasound was performed on children who were suspected of being goitrous at physical examination. Serum TSH, thyroxine, triiodotyronine, thyroid antibody, and urine iodine concentrations (UIC) are also measured. Ultrasound measurements revealed a goiter in 107 (12.6%) of the 847 children. Goiter prevalence was significantly lower among iodized-salt users compared to the noniodized salt using group. UIC and serum selenium levels in the goitrous group were significantly lower compared to the nongoitrous group. Despite legally enforced table salt iodization, the region shows the characteristics of mild iodine deficiency. In addition to lower UIC, goitrous children have lower serum selenium levels compared to the nongoitrous ones. Thus, selenium deficiency plays an important role in goiter endemics in Turkey. It can be postulated that table salt iodization might not be enough for the preventive measures of goiter, but informing people about the correct ways of iodized salt consumption, enforcing the iodization of industrial salts, and, as important as these measures, taking selenium deficiency into consideration are essential for preventing goiters in endemic areas.

The role of thyroid tests in handling of patients in general practice. A phenomenologic study.

During a period of 2 months thyroid function tests, performed on out-patients referred to the laboratory from general practitioners, were studied. The relative informative value of the tests was estimated in relation to the reasons given for requesting the tests. In 86% of the samples from patients with no history of earlier thyroid disease the conventional thyroid tests were found within the reference intervals. 3% showed a definite abnormal pattern of values. In 11% the results were in some way abnormal. In the group of patients with earlier history of thyroid disease 50% of the tests were abnormal. The relative merits of adding a sensitive TSH assay test were analyzed, and it was estimated whether using the sensitive TSH as a first-line discrimination test would add or subtract information compared to the conventional thyroid function tests. It was concluded that in the situation where the general practitioner wants laboratory information of thyroid parameters on patients in order to make decisions on the further handling of the patient, the sensitive TSH test is of limited value as a first-line discrimination test and should be supplemented by other tests.