Changes in prescription routines for treating hypothyroidism between 2001 and 2015 - an observational study of 929,684 primary care patients in Copenhagen

Background Increased public attention towards health and quality of life issues has led to more intensified screening for various medical conditions including hypothyroidism. A falling serum thyroid stimulating hormone (s-TSH) at initiation of levothyroxine (L-T4) treatment has been reported in the UK between 2001- 2009 indicating a falling TSH threshold which may lead to less benefit from therapy and possibly overtreatment. Objective To investigate changes in s-TSH threshold used by the general practitioners to initiate L-T4 therapy between 2001-2015 in Copenhagen. Methods Retrospective analysis of all s-TSH measurements between 2001 and 2015 performed at the general practitioners' joint laboratory merged with The Danish Register of Medicinal Products Statistics and The Danish National Patient Registry. For each year both the median s-TSH at therapy initiation and the estimated treatment threshold calculated from all s-TSH measurements performed in that year, representing the s-TSH level where the estimated probability of starting L-T4 therapy was 50%. Results 929,684 individuals with 2,975,277 s-TSH measurements were included for the calculations. The size and composition of the study population remained virtually unchanged. During the study period the number of performed s-TSH measurements increased from 110,886 to 292,911 (164%) and the number of patients initiating L-T4 therapy increased from 786 to 1,825 (132%), though comparably unchanged from 2010 to 2015. The median s-TSH at therapy initiation decreased from 10 mU/l (IQR 5·2-29·7) in 2001 to 6·8 mU/l (IQR 5·1-11) in 2015, while the estimated treatment threshold decreased from 28·3 (95% CI 21·0-40·2) mU/l in 2001 to 14·2 (95% CI 12·0-18·0) in 2007. In 2015 25% of patients started L-T4 therapy with s- TSH ≤ 5 mU/l and during the entire period 50 % of patients started therapy with a single s-TSH measurement above 5 mU/l. Conclusions This study performed on a sizeable primary care population demonstrates a considerable fall in the threshold for initiating L-T4 therapy in hypothyroid patients. Hereby increasing the risk of futile treatment as well as overtreatment.