Subclinical hypothyroidism in Wales from 2000 to 2021: A descriptive cohort study based on electronic health records.

BACKGROUND: Subclinical hypothyroidism (SCH) is a biochemical thyroid disorder characterised by elevated levels of Thyroid Stimulating Hormone (TSH) together with normal levels of thyroid hormones. Evidence on the benefits of treatment is limited, resulting in persistent controversies relating to its clinical management. AIM: This study describes the demographic and clinical characteristics of patients identified as having subclinical hypothyroidism in Wales between 2000 and 2021, the annual cumulative incidence during this period and the testing and treatment patterns associated with this disorder. METHODS: We used linked electronic health records from SAIL Databank. Eligible patients were identified using a combination of diagnostic codes and Thyroid Function Test results. Descriptive analyses were then performed. RESULTS: 199,520 individuals (63.8% female) were identified as having SCH, 23.6% (n = 47,104) of whom received levothyroxine for treatment over the study period. The median study follow-up time was 5.75 person-years (IQR 2.65-9.65). Annual cumulative incidence was highest in 2012 at 502 cases per 100,000 people. 92.5% (n = 184,484) of the study population had TSH levels between the upper limit of normal and 10mIU/L on their first test. 61.9% (n = 5,071) of patients identified using Read v2 codes were in the treated group. 41.9% (n = 19,716) of treated patients had a history of a single abnormal test result before their first prescription. CONCLUSION: In Wales, the number of incident cases of SCH has risen unevenly between 2000 and 2021. Most of the study population had mild SCH on their index test, but more than a third of the identified patients received levothyroxine after a single abnormal test result. Patients with clinically recorded diagnoses were more likely to be treated. Given the expectation of steadily increasing patient numbers, more evidence is required to support the clinical management of subclinical hypothyroidism.

The impact of the management strategies for patients with subclinical hypothyroidism on long-term clinical outcomes: An umbrella review.

AIM: This umbrella review summarises and compares synthesised evidence on the impact of subclinical hypothyroidism and its management on long-term clinical outcomes. METHODS: We conducted comprehensive searches on MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis, the PROSPERO register, Epistemonikos Database and PDQ Evidence from inception to February and July 2021 using keywords on subclinical hypothyroidism, treatment with levothyroxine, monitoring and primary outcomes (all-cause mortality, cardiovascular events, stroke, frailty fractures and quality of life). Only systematic reviews and meta-analyses on adult patient populations were considered. Study selection, data extraction and quality appraisal using AMSTAR-2 were done independently by two reviewers and discrepancies were resolved through discussion. Overlap across the selected reviews was also assessed, followed by a narrative synthesis of findings. RESULTS: A total of 763 studies were identified from literature searches; 20 reviews met inclusion criteria. Methodological quality ratings were high (n = 8), moderate (n = 7), and low (n = 5), but no reviews were excluded on this basis. Though there was slight overlap across all reviews, some pairwise comparisons had high corrected covered area scores. Compared to euthyroidism, untreated subclinical hypothyroidism was associated with a higher risk of cardiovascular events or death if Thyroid Stimulating Hormone was above 10mIU/L at baseline. Treatment was associated with a lower risk of death from all causes for patients younger than 70 years and possibly better cognitive and quality of life scores than untreated individuals. Evidence on the risk of strokes and fractures was inconclusive. CONCLUSION: In the long term, treatment of subclinical hypothyroidism may be beneficial for some patient groups. However, the findings of this review are negatively impacted by the relative sparseness and poor quality of available evidence. Additional large and adequately powered studies are needed to investigate this topic further. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (CRD42021235172).

Management strategies for patients with subclinical hypothyroidism: a protocol for an umbrella review.

BACKGROUND: Subclinical hypothyroidism is a thyroid disorder diagnosed from the laboratory blood test results of otherwise asymptomatic patients. It has been associated with poor cardiovascular outcomes, mortality and progression to overt thyroid hormone deficiency. Current guidelines on the management of subclinical hypothyroidism differ because of conflicting evidence on long-term treatment benefits. Even though there are several existing systematic reviews on its clinical outcomes, no definitive conclusion has been reached yet. As such, a new synthesis could help provide more insight and consensus on this topic. To this purpose, this umbrella review will evaluate and synthesise current evidence on the long-term clinical outcomes of the different management strategies for subclinical hypothyroidism. METHODS: This is a protocol for an umbrella review on the management strategies for subclinical hypothyroidism. We will conduct literature searches in multiple electronic databases (from inception onwards), namely MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis, Epistemonikos database, PDQ Evidence and the PROSPERO register. There will be no restriction on the date or language of publication. Additional material will be identified through grey literature searches and citation chaining. Review inclusion criteria will be patients with subclinical hypothyroidism, receiving treatment or monitoring, no restrictions on the comparators used and with cardiovascular events, frailty fractures, quality of life and all-cause mortality as primary outcomes of interest. Two reviewers will independently screen all citations, full-text articles and abstract data on a pre-piloted form in duplicate. Methodological quality (or bias) of included studies will be appraised using AMSTAR-2. Any conflicts that arise will be resolved through discussion or involving a third reviewer. A narrative synthesis will be provided with information presented in the main text and tables to summarise and explain the characteristics and findings of the included reviews. Even so, it is not expected that a meta-analysis will be performed due to review variability. Study limitations and methodological quality assessments will also be reported to provide context for the overall summary of evidence. DISCUSSION: This review will provide a comprehensive summary of the effects of the pharmacological and non-pharmacological management of subclinical hypothyroidism on specific long-term clinical outcomes. It is anticipated that the findings of this umbrella review will aid in the development of consensus-based clinical recommendations for subclinical hypothyroidism, as well as highlight areas for future research. Review findings will be disseminated primarily through peer-reviewed publications. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021235172.