Undertreated Hypothyroidism May Worsen Hospital Outcomes

Suboptimal treatment of primary hypothyroidism may increase the risk of worse hospital outcomes, new research suggests.

The risks, including longer length of stay (LOS) and higher readmission rates, were no longer present in patients with adequately treated hypothyroidism, and in fact, appeared better than among those without hypothyroidism.

"Unfortunately, suboptimal treatment is common amongst the patient population with hypothyroidism," write Matthew D. Ettleson, MD, of the Section of Endocrinology, Diabetes, and Metabolism at the University of Chicago, Illinois, and colleagues.

"It is important for both patients and physicians to know that maintaining optimal thyroid hormone replacement is important to minimize length of hospital stays and hospital readmission. It is particularly important for planned admissions where thyroid hormone replacement can be adjusted if needed prior to admission," said Ettleson in a press release from the Endocrine Society.

More Evidence of Adverse Effects of Suboptimal Treatment

The findings, from a large US claims database, "add to the growing body of evidence demonstrating the serious adverse short- and long-term health effects associated with suboptimal treatment of hypothyroidism," the authors write in their article, published online April 26 in the Journal of Clinical Endocrinology and Metabolism. Ettleson will also present the data on June 11 at the ENDO 2022 meeting.

Thyroid hormone replacement therapy — generally levothyroxine — is given for primary hypothyroidism with the aim of maintaining serum thyroid-stimulating hormone (TSH) within the normal reference range.

TSH is inversely related to the level of circulating thyroid hormone, so low levels of TSH indicate overtreatment of thyroid disease and high levels indicate undertreatment.

Worse Hospital Outcomes Associated With High TSH

In their study, Ettleson and colleagues retrospectively examined IBM MarketScan claims for 43,478 privately insured patients younger than age 65 years and hospitalized for medical or surgical reasons in 2008-2015.

Of those, 8873 met the criteria for primary hypothyroidism based on a pre-admission prescription claim for levothyroxine, TSH > 10.00 mIU/L, confirmed diagnosis of hypothyroidism during hospitalization, or chronic lymphocytic thyroiditis. Of those, 4770 (53.8%) had a prescription claim for levothyroxine.

Patients who met the clinical criteria for hypothyroidism were divided into four subgroups based on prehospitalization TSH level: low (< 0.40 mIU/L), normal (0.40-4.50 mIU/L), intermediate (4.51-10.00 mIU/L), and high (> 10.00 mIU/L).

The median length of time between TSH collection and hospital admission was 56 days in the hypothyroidism group and 63 days in the control group.

There were no differences in hospital outcomes between those with and without hypothyroidism among those who had low or intermediate TSH levels, in a multivariate analysis that used propensity-score matching.

In those with normal TSH levels, those with hypothyroidism actually had a lower risk of in-hospital death (risk ratio [RR], 0.46; P = .004) and 90-day readmission rate (RR, 0.92; P = .02) than controls.

And those in the high TSH level subgroup had longer length of stay (+1.2 days; P = .003) and higher risk of 30-day readmission (RR, 1.49; P < .001) and 90-day readmission (RR, 1.43; P < .001) compared with balanced controls.

Public Health Effort Needed to Improve Quality of Care

There are multiple reasons why those with undertreated or undiagnosed hypothyroidism might have worse hospital outcomes, the authors say.

A bit more puzzling is why those with well-controlled hypothyroidism appeared to do better than those without hypothyroidism, given that thyroid hormone replacement isn't likely to provide an advantage over normal, endogenous thyroid hormone production.

Ettleson and colleagues speculate that in-range TSH values may be a surrogate for regular healthcare and adherence to medical therapy, which likely leads to better hospital outcomes.

"The long- and short-term adverse health effects associated with off-target treatment of hypothyroidism, coupled with the high frequency of off-target treatment amongst the millions of patients in the US on thyroid hormone, suggest that a public health effort to improve the quality of care of hypothyroidism is necessary," Ettleson and colleagues write.

However, they note that there is currently no quality measure regarding appropriate treatment of hypothyroidism within the Merit-Based Incentive Payment System of the Centers for Medicare & Medicaid Services.

"The presence of guidelines alone may not be sufficient, as demonstrated by the inadequate application of guidelines for the use of levothyroxine in the treatment of thyroid cancer, a serious but much less common disease than clinical hypothyroidism," the authors add.

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Ettleson has reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online April 26, 2022. Abstract

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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