Thyroid testing in acutely ill patients may be an expensive distraction

In health, an efficient negative feedback mechanism maintains serum thyroid hormone concentrations within an exquisitely controlled narrow range. Therefore any change that occurs to thyroid hormones in intrinsic thyroid disease is concordant and easy to interpret. Optimal functioning of the many tissues they influence is thereby facilitated. The situation in acute illnesses is different. Mechanisms that operate in these circumstances influence the hypothalamic-pituitary-thyroid axis and its components producing thyroid test results, which are discordant, do not fit recognizable patterns and are difficult to interpret. The yield of abnormalities is also low (about 7%). As many studies indicate, thyroid tests are expensive and consume large amounts of the hospital budget and resources of hospital laboratories. Other studies have shown that when abnormalities are detected, clinicians do not intervene or follow up these subjects. Therefore the clinical utility of thyroid testing in acutely ill patients is debatable. Interventions to change requestor behaviour with regard to thyroid testing in acutely ill subjects and the success of some audit and educational interventions are worthy of note. Thyroid testing in acutely ill patients is often an expensive distraction and is of limited clinical value. Targeted thyroid testing should be offered in this group only to those with: (a) symptoms or signs of thyroid disease e.g. goiter or orbitopathy; (b) risk factors for thyroid disease, previous or family history of thyroid disease; (c) taking drugs which potentially affect thyroid function e.g. thyroxine replacement therapy, amiodarone, lithium, mechanistic target of rapamycin (mTOR) inhibitors, interferon, alemtuzumab etc; (d) unexplained tachydysrhythmias

Trends in costs and prescribing for liothyronine and levothyroxine in England and wales 2011–2020

From Wiley via Jisc Publications RouterHistory: received 2020-11-08, rev-recd 2020-12-14, accepted 2020-12-21, pub-electronic 2021-03-21, pub-print 2021-06Article version: VoRPublication status: PublishedAbstract: Introduction: Recent prescribing policies in England and Wales have imposed significant restrictions on liothyronine prescribing in general practice driven by the prohibitive costs and uncertain benefits of liothyronine in the management of hypothyroidism. However, the impact of these policies on liothyronine usage and costs is still unclear. Methods: Data were downloaded from the NHS monthly General Practice Prescribing Data in England and from the Comparative Analysis System for Prescribing Audit (CASPA) in Wales for 2011–2020. Trends over the period in amount and costs of levothyroxine and liothyronine prescribing were analysed. Results: The total medication costs per year for England Wales for hypothyroidism rose from £60.8 million to £129.8 million in 2015–16 and have since reduced to £88.4 million. Levothyroxine prescriptions have been growing above the population growth rate at 0.7%/annum in England and 1.1% in Wales. The costs/patient/year for liothyronine rose from £550 to £3000 in 2015–16 and has since fallen to £2500. Use of liothyronine as a percentage of levothyroxine started to fall in 2015–16 at 7%/annum in England and 3% in Wales. Nevertheless, 0.5% of levothyroxine‐treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019–20. Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice, a significant number of patients continue to receive this therapy. The price differential of liothyronine vs levothyroxine should be examined again in light of the continuing use of liothyronine

Natural desiccated thyroid for the treatment of hypothyroidism?

Primary hypothyroidism affects about 3% of the general population in Europe. Early treatments in the late 19th Century involved subcutaneous as well as oral administration of thyroid extract. Until the early 1970s, the majority of people across the world with hypothyroidism were treated with natural desiccated thyroid (NDT) (derived from pig thyroid glands) in various formulations, with the majority of people since then being treated with levothyroxine (L-thyroxine). There is emerging evidence that may account for the efficacy of liothyronine (NDT contains a mixture of levothyroxine and liothyronine) in people who are symptomatically unresponsive to levothyroxine. While this is a highly selected group of people, the severity and chronicity of their symptoms and the fact that many patients have found their symptoms to be alleviated, can be viewed as valid evidence for the potential benefit of NDT when given after careful consideration of other differential diagnoses and other treatment options

Liothyronine and levothyroxine prescribing in England: A comprehensive survey and evaluation

Introduction The approach to thyroid hormone replacement varies across centres, but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors. Methods Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011-2020. Results The study covered a population of 19.4 million women over 30 years of age, attending 6,660 GP practices and being provided with 33.7 million prescriptions of LT4 and LT3 at a total cost of £90million/year. Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019-2020. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. Whereas factors that were associated with increased levels of liothyronine prescribing (model accounted for 17% of variance), were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58 mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates. Conclusion In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG-related factors influencing prescribing of both levothyroxine and liothyronine across England

Liothyronine and levothyroxine prescribing in England: A comprehensive survey and evaluation

From Wiley via Jisc Publications RouterHistory: received 2021-01-06, rev-recd 2021-03-28, accepted 2021-04-12, pub-electronic 2021-07-06Article version: VoRPublication status: PublishedAbstract: Introduction: The approach to thyroid hormone replacement varies across centres, but the extent and determinants of variation is unclear. We evaluated geographical variation in levothyroxine (LT4) and liothyronine (LT3) prescribing across General Practices in England and analysed the relationship of prescribing patterns to clinical and socioeconomic factors. Methods: Data was downloaded from the NHS monthly General Practice Prescribing Data in England for the period 2011‐2020. Results: The study covered a population of 19.4 million women over 30 years of age, attending 6,660 GP practices and being provided with 33.7 million prescriptions of LT4 and LT3 at a total cost of £90million/year. Overall, 0.5% of levothyroxine treated patients continue to receive liothyronine. All Clinical Commission Groups (CCGs) in England continue to have at least one liothyronine prescribing practice and 48.5% of English general practices prescribed liothyronine in 2019‐2020. Factors strongly influencing more levothyroxine prescribing (model accounted for 62% of variance) were the CCG to which the practice belonged and the proportion of people with diabetes registered on the practice list plus antidepressant prescribing, with socioeconomic disadvantage associated with less levothyroxine prescribing. Whereas factors that were associated with increased levels of liothyronine prescribing (model accounted for 17% of variance), were antidepressant prescribing and % of type 2 diabetes mellitus individuals achieving HbA1c control of 58 mmol/mol or less. Factors that were associated with reduced levels of liothyronine prescribing included smoking and higher obesity rates. Conclusion: In spite of strenuous attempts to limit prescribing of liothyronine in general practice a significant number of patients continue to receive this therapy, although there is significant geographical variation in the prescribing of this as for levothyroxine, with specific general practice and CCG‐related factors influencing prescribing of both levothyroxine and liothyronine across England

Antithyroid drug therapy in pregnancy and risk of congenital anomalies: Systematic review and meta-analysis

Objectives The risk of congenital anomalies following in utero exposure to thionamide antithyroid drugs (ATDs) is unresolved. Observational studies are contradictory and existing meta-analyses predate and preclude more recent studies. We undertook an updated meta-analysis of congenital anomaly risk in women exposed to carbimazole or methimazole (CMZ/MMI), propylthiouracil (PTU), or untreated hyperthyroidism in pregnancy. Methods We searched Medline, Embase, and the Cochrane database for articles published up till August 2021. We pooled separate crude and adjusted risk estimates using random effects models and subgroup analyses to address heterogeneity. Results We identified 16 cohort studies comprising 5957, 15,785, and 15,666 exposures to CMZ/MMI, PTU, and untreated hyperthyroidism, respectively. Compared to nondisease controls, adjusted risk ratio (RR) and 95% confidence intervals (95% CIs) for congenital anomalies was increased for CMZ/MMI (RR, 1.28; 95% CI, 1.06–1.54) and PTU (RR, 1.16; 95% CI, 1.08–1.25). Crude risk for CMZ/MMI was increased relative to PTU (RR, 1.20; 95% CI, 1.01–1.43). Increased risk was also seen with exposure to both CMZ/MMI and PTU, that is, women who switched ATDs in pregnancy (RR, 1.51; 95% CI, 1.14–1.99). However, the timing of ATD switch was highly variable and included prepregnancy switches in some studies. The excess number of anomalies per 1000 live births was 17.2 for patients exposed to CMZ/MMI, 9.8, for PTU exposure, and 31.4 for exposure to both CMZ/MMI and PTU. Risk in the untreated group did not differ from control or ATD groups. The untreated group was however highly heterogeneous in terms of thyroid status. Subgroup analysis showed more positive associations in studies with >500 exposures and up to 1-year follow-up. Conclusions ATD therapy carries a small risk of congenital anomalies which is higher for CMZ/MMI than for PTU and does not appear to be reduced by switching ATDs in pregnancy. Due to key limitations in the available data, further studies will be required to clarify the risks associated with untreated hyperthyroidism and with switching ATDs in pregnancy

Acute postprandial gut hormone, leptin, glucose and insulin responses to resistant starch in obese children: a single blind crossover study

Introduction: Resistant starch (RS) has beneficial effects on postprandial glucose metabolism in both animals and adults. Hitherto, there have been no studies in children of the acute metabolic and hormonal effects of RS-containing meals. Objectives: We aimed to compare serial plasma glucose, insulin, gut hormone, leptin profiles and satiety scores in obese children after meals containing variable amounts of RS. Methods: This was a single blind, non-randomised, crossover study of 20 obese children aged 10–14 years old without comorbidities. Three test meals containing rice (M1), rice cooked with coconut oil (M2), rice cooked in coconut oil with lentils (M3) were given in sequence after a 12-hour fast . Blood samples were analysed for glucose (PG), insulin, leptin, glucagon-like polypeptide (GLP) 1, ghrelin and peptide YY (PYY) at appropriate times between 0 and 180 min. Results: Meal M2 resulted in significantly lower postprandial glucose values compared with meal M1 (maximal incremental glucose, ∆Cmax, p<0.05; area under the curve, ∆AUC0–3, p<0.01) and meal M3 (maximal concentration, Cmax, p<0.01; ∆Cmax, p<0.001, and ∆AUC0–3p<0.01). M2 also produced lower insulin values compared with M1 (p<0.05). Postprandial ghrelin was significantly higher after M1 compared with M3 (p<0.05). PYY, GLP1 and median satiety scores were not significantly different between the three meals. Conclusion: This study shows that M2, the meal containing RS alone, induced beneficial effects on acute postprandial glucose, insulin and ghrelin concentrations in obese children without diabetes. Acute postprandial satiety scores were not significantly affected by the three meals. Trial registration number: SLCTR/2020/007

The prevalence of diabetes and thyroid related autoantibodies in Sri Lankan children with type 1 diabetes and their unaffected siblings – The utility of a new screening assay

BackgroundThere is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka.ObjectivesTo assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA).MethodsWe selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo.ResultsThe median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up.ConclusionsThe 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity

Is there a role for natural desiccated thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a consecutive case series

From Wiley via Jisc Publications RouterHistory: received 2021-08-10, rev-recd 2021-09-19, accepted 2021-10-06, pub-electronic 2021-11-20Article version: VoRPublication status: PublishedAbstract: Introduction: Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a natural desiccated thyroid (NDT) preparation such as Armour Thyroid ® or ERFA Thyroid ® . These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods: The ThyPRO39 (thyroid symptomatology) and EQ‐5D‐5L‐related QoL/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results: There were 28 women and 3 men. The dose range of NDT was 60‐180 mg daily. Age range was 26‐77 years with length of time since diagnosis with hypothyroidism ranging from 2 to 40 years. One person discontinued the NDT because of lack of response; two because of cardiac symptoms. EQ‐5D‐5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241‐0.542), t = 6.82, P < .001. EQ‐VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95% CI 25.2‐50.2), t = −4.9, P < .001. ThyPRO scores showed consistent fall across all domains with the composite QoL‐impact Score improving from 68.3 (95% CI 60.9‐75.7) to 25.2 (95% CI 18.7‐31.7), a difference of 43.1 (95% CI 33‐53.2) (t = 5.6, P < .001). Conclusion: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT, suggesting the need for further evaluation of NDT in this context