European Journal of Endocrinology www.eje-online.org © 2017 European Society of Endocrinology Printed in Great Britain Published by Bioscientifica Ltd. DOI: 10.1530/EJE-16-0708 Elevated TSH in adults treated for hypothyroidism is associated with increased mortality Amit Akirov 1,2 , Hannah Gimbel 2 , Alon Grossman 2,3 , Tzipora Shochat 4 and Ilan Shimon 1,2 1 Institute of Endocrinology, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel, 2 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel, 3 Internal Medicine E, and 4 Statistical Consulting Unit, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel Abstract Context: Numerous studies investigated the link between hypothyroidism and mortality, but a defnite conclusion is hard to reach as these were limited by a number of factors, including age of participants, comorbidities and single measurement of thyroid function. Objective: To evaluate the association between TSH and fT4 levels and mortality in patients with levothyroxine- treated hypothyroidism. Design and setting: Observational data of hospitalized patients (2011–2014). TSH and fT4 levels obtained between at least 30 days after discharge and until death or end of follow-up were collected. Median TSH and fT4 levels were stratifed into categories. Patients: In total, 611 patients with treated hypothyroidism, aged 60–80 years (72% females, mean age 71 ± 6 years) were included in the study. Main outcome measure: All-cause mortality up to 66 months after discharge, by TSH and fT4 categories. Results: During follow-up, the average numbers of TSH and fT4 measurements were 5.5 ± 3.8 and 2.5 ± 4.2 per patient respectively. Mortality rates were 28%, 29% and 54% with median TSH of 0.5–2.5, 2.5–5.0 and 5.0–10.0 IU/L respectively. Adjusted hazard ratios for mortality with median TSH between 5.0 and 10.0 IU/L were 2.3 (95% CI: 1.6–3.4) and 2.2 (95% CI: 1.6–3.2) compared with patients with TSH between 0.5–2.5 IU/L and 2.5–5 IU/L respectively. There was no difference in mortality between patients with median fT4 10–15 or 15–20 pmol/L. Conclusion: In treated hypothyroid adult patients and serial measurements of thyroid function tests, median TSH levels of 5–10 IU/L are associated with increased mortality with no effect of fT4 levels. Treatment should aim at achieving euthyroidism to improve survival. www.eje-online.org © 2017 European Society of Endocrinology 176:1 57–66 A Akirov and others Thyroid function and mortality European Journal of Endocrinology (2017) 176, 57–66 Clinical Study Correspondence should be addressed to A Akirov Email amit.akirov@gmail.com Introduction Thyroid function disorders are common in the general population, and the prevalence of overt hypothyroidism ranges between 1% and 7% (1, 2). Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy are frequently observed in this population (3). Previous studies in elderly patients have suggested an association between thyroid dysfunction and mortality (4, 5). Numerous studies investigated the link between subclinical and overt hypothyroidism and mortality, with conficting results (4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17). Waring et al. reported that a single measurement of thyroid- stimulating hormone (TSH) and free T4 (fT4) did not predict the mortality in older men (7). Iglesias et al. investigated Downloaded from Bioscientifica.com at 12/15/2021 04:15:42PM via free access