Variation in the reference range limits of thyroid function tests and association with the prevalence of levothyroxine treatment.

Many individuals with marginally abnormal thyroid function test (TFT) results may be treated and it is unknown if the limits of the thyrotropin (TSH) and free thyroxine (FT4) reference intervals reported alongside the laboratory results are associated with the prevalence of levothyroxine treatment. We obtained information regarding reported TFT reference intervals from UK National Health Service (NHS) laboratories and evaluated its relationship with the prevalence of levothyroxine treatment for corresponding health areas for 2014. The upper limit of serum TSH was significantly, linearly, independently, and negatively associated with prevalent levothyroxine treatment: -0.54% (95% CI, -0.68% to -0.40%). The lower limit of serum FT4 was significantly and independently associated with the prevalence of levothyroxine treatment in a non-linear (J-shaped) manner with an increase being noted from a FT4 level of ≈9.5 pmol/L onwards. We conclude that minor changes in the reference range limits for serum TSH and FT4 are associated with levothyroxine treatment.

Treatment of subclinical hypothyroidism: assessing when treatment is likely to be beneficial.

Introduction: Subclinical hypothyroidism (SCH) is a common condition diagnosed in up to 16% of the population. SCH is diagnosed when serum TSH is high and circulating thyroid hormones are within the reference range. SCH is considered to be a mild form of thyroid failure by some due to the log-linear relationship between TSH and thyroid hormones. Nevertheless, it is unclear whether the treatment of SCH with thyroid hormones is beneficial, and hence, it is not surprising that expert opinions and recommendations from societies differ in their opinions on how best to manage SCH.Areas covered: This article reviews the currently available evidence pertaining to SCH and provides recommendations as to when treatment of SCH should be considered. An electronic search of PubMed from 1970 to 2019 was performed and systematically reviewed studies assessing the effects of treatment in SCH. The main areas that are considered are the effects of treatment on symptoms and quality of life, and important clinical consequences including psychocognitive outcomes and cardiovascular events.Expert opinion: Treatment of SCH with thyroid hormones is debated and the current literature in this area lacks clarity. We provide an evidence-based recommendation for when treatment of SCH with thyroid hormones should be considered.

Sample Timing, Diagnosis of Subclinical Thyroid Dysfunction and Mortality in Acute Myocardial Infarction: ThyrAMI1 Study.

OBJECTIVE: The objective of this study was to determine the impact of blood sample timing on the diagnosis of subclinical thyroid dysfunction (SCTD) and mortality in patients with acute myocardial infarction (AMI). PATIENTS, DESIGN, AND MAIN OUTCOME MEASURES: Patients with AMI had thyroid function evaluated on admission between December 2014 and December 2016 and those with abnormal serum thyrotropin (TSH) had repeat thyroid function assessed at least a week later. The association between sample timing and SCTD was evaluated by logistic regression analysis. Secondary outcomes were confirmation of SCTD on repeat testing and all-cause mortality up to June 2018. RESULTS: Of the 1806 patients [29.2% women, mean (± standard deviation) age of 64.2 (±12.1) years] analyzed, the prevalence of subclinical hypothyroidism (SCH) was 17.2% (n = 311) and subclinical hyperthyroidism (SHyper) was 1.2% (n = 22) using a uniform TSH reference interval. The risk of being diagnosed with SCTD varied by sample timing in fully-adjusted models. The risk of SCH was highest between 00.01 and 06.00 hours and lowest between 12.01 and 18.00 hours, P for trend <.001, and risk of SHyper was highest between 12.01 hours and 18.00 hours and lowest between 00.01 hours and 06.00 hours. Furthermore, time of the initial sample was associated with the risk of remaining in a SCH state subsequently. Mortality in SCH patients was not elevated when a uniform TSH reference interval was utilized. However, when time period-specific TSH reference ranges were utilized, the mortality risk was significantly higher in SCH patients with HR (95% CI) of 2.26 (1.01-5.19), P = .04. CONCLUSIONS: Sample timing impacts on the diagnosis and prognosis of SCH in AMI patients. If sample timing is not accounted for, SCH is systemically misclassified, and its measurable influence on mortality is lost.

Hypothyroidism in the older population.

BACKGROUND: Both overt hypothyroidism as well as minor elevations of serum thyrotropin (TSH) levels associated with thyroid hormones within their respective reference ranges (termed subclinical hypothyroidism) are relatively common in older individuals. There is growing evidence that treatment of subclinical hypothyroidism may not be beneficial, particularly in an older person. These findings are relevant at a time when treatment with thyroid hormones is increasing and more than 10-15% of people aged over 80 years are prescribed levothyroxine replacement therapy. MAIN BODY: The prevalence of hypothyroidism increases with age. However, the reference range for TSH also rises with age, as the population distribution of TSH concentration progressively rises with age. Furthermore, there is evidence to suggest that minor TSH elevations are not associated with important outcomes such as impaired quality of life, symptoms, cognition, cardiovascular events and mortality in older individuals. There is also evidence that treatment of mild subclinical hypothyroidism may not benefit quality of life and/or symptoms in older people. It is unknown whether treatment targets should be reset depending on the age of the patient. It is likely that some older patients with non-specific symptoms and incidental mild subclinical hypothyroidism may be treated with thyroid hormones and could potentially be harmed as a result. This article reviews the current literature pertaining to hypothyroidism with a special emphasis on the older individual and assesses the risk/benefit impact of contemporary management on outcomes in this age group. CONCLUSIONS: Current evidence suggests that threshold for treating mild subclinical hypothyroidism in older people should be high. It is reasonable to aim for a higher TSH target in treated older hypothyroid patients as their thyroid hormone requirements may be lower. In addition, age-appropriate TSH reference ranges should be considered in the diagnostic pathway of identifying individuals at risk of developing hypothyroidism. Appropriately designed and powered randomised controlled trials are required to confirm risk/benefit of treatment of subclinical hypothyroidism in older people. Until the results of such RCTs are available to guide clinical management international guidelines should be followed that advocate a conservative policy in the management of mild subclinical hypothyroidism in older individuals.

REMISSION OF LONGSTANDING INSULIN-TREATED DIABETES MELLITUS FOLLOWING SURGICAL RESECTION OF PHEOCHROMOCYTOMA.

OBJECTIVE: To describe the case of a woman with a longstanding misdiagnosis of type 1 diabetes mellitus (T1DM), in whom diabetes remission was achieved following surgical resection of adrenal pheochromocytoma. METHODS: We present a case report with accompanying biochemical, histologic, and genetic investigation results. RESULTS: We report the case of a 57-year-old woman with a 13-year history of apparent T1DM, and her presentation with intermittent exertional nausea. An abdominal ultrasound scan identified a rounded heterogeneous mass measuring 120 × 110 × 104 mm superior to her left kidney. Plasma metanephrine levels were markedly elevated with normetaneprhine at 17,856 pmol/L (reference range is 120 to 1,180 pmol/L), metanephrine >25,000 pmol/L (reference range is 80 to 510 pmol/L), 3-methoxytyramine at 1,393 pmol/L (reference range is 0 to 180 pmol/L). The mass demonstrated marked uptake on an iodine-123-meta-iodobenzylguanidine scan. The patient's hypertension was managed with phenoxybenzamine, and she underwent adrenalectomy. Following surgery, she was able to discontinue all diabetes medications and has maintained a hemoglobin A1c value <48 mmol/mol for over 12 months. CONCLUSION: The case illustrates that remission of T1DM is possible even after prolonged insulin treatment upon surgical resection of pheochromocytoma. It highlights the potential benefits of reevaluating the diagnostic classification of T1DM in the light of new clinical information.

Effect of In Situ High-Fidelity Simulation Training on the Emergency management of Pneumonia (INSTEP): a mixed-methods study.

Background: The patient safety agenda has propelled the rise of simulation education, but relatively few evaluations of simulation-based educational interventions have focused on patient outcomes. Objective: To evaluate the impact of an in situ, high-fidelity simulation teaching intervention on the management of community-acquired pneumonia in the ambulatory care unit of a district general hospital. Methods: This study used a mixed-methods approach to evaluate the impact of a programme of 10 in situ high-fidelity simulation education sessions delivered to a total of 10 junior doctors, nine nurses and seven healthcare assistants. Participants were tasked with managing a manikin simulating a patient with pneumonia in real time in a working clinical area. Subsequent structured debrief emphasised key themes from the national guidelines on pneumonia management. The intervention was evaluated through an immediate feedback form, follow-up semistructured interviews by independent qualitative researchers that underwent content analysis and triangulation with audit data on compliance with national pneumonia guidelines before and after the simulation intervention. Results: The in situ simulation intervention was valued by participants both in immediate written feedback and in follow-up semistructured interviews. In these interviews, 17 of 18 participants were able to identify a self-reported change in practice following the simulation intervention. Furthermore, most participants reported observing a change in the clinical practice of their colleagues following the training. Collected audit data did not show a statistically significant change in compliance with the guidelines for the management of pneumonia. Conclusion: This study found evidence of a change in both self-reported and observed clinical practice following a simulation intervention, supporting expert opinion that simulation education can impact clinician behaviours and patient outcomes in complex clinical scenarios. Furthermore, this feasibility study provides a transferrable method to evaluate the real-world impact of simulation education that merits further investigation through an appropriately powered study.