Recommended TSH Norm for Patients on Thyroxine Shows No Ill Effect

By Anne Harding

September 19, 2019

NEW YORK (Reuters Health) - Recommended "normal" thyroid-stimulating hormone (TSH) concentrations for hypothyroid patients receiving thyroxine are not associated with increased risk of cardiovascular disease, fractures, or all-cause mortality, according to new findings.

But higher TSH was associated with an increased risk of ischemic heart disease and heart failure, and the highest and lowest TSH levels were linked to increased mortality, Dr. Krishnarajah Nirantharakumar of the Institute of Applied Health Research at the University of Birmingham, in the U.K., and colleagues found.

Based on the results, online September 3 in The BMJ, clinicians should feel comfortable keeping hypothyroid patients' TSH levels within 0.4-4.0 mIU/L with thyroxine treatment, Dr. Nirantharakumar told Reuters Health in a telephone interview. "It takes away any doubt," he said.

European and U.S. guidelines recommend thyroid-hormone replacement therapy to normalize TSH concentrations, Dr. Nirantharakumar and colleagues note.

"However, no specific optimal target for TSH exists in the context of thyroid hormone replacement," they add. Guidelines recommend a range of TSH between 0.4-4.0 mIU/L, but cite the lack of supporting evidence.

The authors analyzed electronic records for more than 162,000 adult patients with hypothyroidism diagnosed in 1995-2017 from The Health Improvement Network (THIN), a U.K. primary care database. Follow-up lasted a median of six years, and included more than 863,000 TSH measurements.

TSH concentrations within the normal range of 0.4-4.0 mIU/L were not associated with increased risk of ischemic heart disease, heart failure, stroke/transient ischemic attack, atrial fibrillation, fractures, fragility fractures or mortality.

Compared with the reference category of 2-2.5 mIU/L, TSH concentrations above 10 mIU/L were associated with a significantly increased risk of ischemic heart disease (hazard ratio, 1.18) and heart failure (HR, 1.42), while low concentrations appeared protective against heart failure (HR, 0.79 with TSH below 0.1 mIU/L; 0.76 with TSH of 0.1-0.4 mIU/L).

Mortality risk was significantly higher for the lowest and highest TSH concentrations, with HRs of 1.18 for TSH levels under 0.1 mIU/L, 1.29 for 4-10 mIU/L and 2.21 for TSH above 10 mIU/L.

The highest TSH levels were also associated with a significantly increased risk of fragility fractures (HR, 1.15), particularly in women and people over 65.

"In clinical terms, these findings corroborate the current recommendations for management of hypothyroid patients. However, by showing effects on all-cause mortality when hypothyroidism is suboptimally treated, our findings challenge the notion of a 'benign' disease and underline the need for diligent monitoring, which is sometimes overlooked during the long course of the disease in real life scenarios," the authors conclude.

SOURCE: https://bit.ly/2mhboMI

BMJ 2019.

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