June 11, 2008 — Many patients with chronic kidney disease have mild reductions in thyroid function, or subclinical hypothyroidism, which becomes more common as kidney function declines, according to the results of a study reported in the June 11 Online First issue of the Clinical Journal of the American Society of Nephrology.

"Subclinical primary hypothyroidism is highly prevalent in the general population, especially in the elderly," write Michel Chonchol, MD, from the University of Colorado Health Sciences Center in Denver, and colleagues. "However, the prevalence of subclinical primary hypothyroidism in persons with chronic kidney disease (CKD) not requiring chronic dialysis is not well defined."

The investigators analyzed cross-sectional data from 3089 adult outpatients consecutively referred by general practitioners for routine blood testing during the last 2 years. The abbreviated Modification of Diet in Renal Disease equation was used to estimate glomerular filtration rate (GFR), and multivariable logistic regression was used to characterize the independent association between prevalent subclinical primary hypothyroidism and estimated GFR.

Of 3089 adult participants, 293 (9.5%) had subclinical primary hypothyroidism, and 277 (9%) had an estimated GFR of less than 60 mL/minute per 1.73 m². Subclinical primary hypothyroidism became more prevalent as GFR decreased, with a prevalence of 7% at an estimated GFR of more than 90 mL/minute per 1.73 m², and 17.9% at an estimated GFR of less than 60 mL/minute per 1.73 m² (P < .0001 for trend).

After adjustment for age; sex; and fasting plasma glucose, total cholesterol, and triglyceride concentrations, the odds of subclinical primary hypothyroidism were increased in participants with an estimated GFR of less than 60 mL/minute per 1.73 m² vs participants with an estimated GFR of more than 60 mL/minute per 1.73 m².

"These findings suggest that subclinical primary hypothyroidism is a relatively common condition (~18%) among persons with CKD not requiring chronic dialysis, and it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults," the study authors write. "Future clinical and experimental studies should explore potential causal mechanisms linking subclinical primary hypothyroidism and CKD."

Limitations of this study include cross-sectional design, precluding determination of causal or temporal relationships between subclinical primary hypothyroidism and kidney disease; definition of kidney function based on estimated GFR vs more precise markers such as iothalamate clearance; inability to identify nonthyroidal and thyroidal causes of subclinical hypothyroidism; possible misclassification resulting from use of automated databases; and lack of data on comorbid medical conditions and current use of thyroid medications.

"The possible adverse effects of subclinical hypothyroidism on cardiovascular risk associated with CKD are presently unknown," the study authors conclude. "Whether adult patients with CKD should be routinely screened for subclinical primary hypothyroidism requires further investigation."

The study authors have disclosed no relevant financial relationships.

Clin J Am Soc Nephrol. Published online June 11, 2008.

Clinical Context

Study Highlights

• This study used results of serum creatinine, glucose, lipids, and thyroid function tests in a large database from the Clinical Chemistry Laboratory at the Verona University Hospital in Italy.
• From December 2005 to December 2007, a total of 3233 outpatient adults 18 years and older were consecutively referred by general practitioners for routine blood testing.
• All patients with low or high normal free thyroxine levels (n = 144) were excluded, leaving 3089 adult participants included in the final analysis.
• Mean age was 54.9 ± 16.2 years (range, 18 - 94 years); 78.4% were women.
• GFR was estimated from the abbreviated Modification of Diet in Renal Disease equation.
• The independent association between prevalent subclinical primary hypothyroidism and estimated GFR was determined with multivariable logistic regression.
• Subclinical primary hypothyroidism occurred in 293 (9.5%) of 3089 adult participants.
• Participants with subclinical primary hypothyroidism were likely to be older and had higher values of fasting plasma glucose, total cholesterol, and triglycerides, and lower estimated GFR levels vs those with no subclinical hypothyroidism.
• Estimated GFR was less than 60 mL/minute per 1.73 m² in 277 (9%) participants.
• Subclinical primary hypothyroidism became more prevalent with decreasing GFR.
• The prevalence of subclinical primary hypothyroidism was 7% at an estimated GFR of more than 90 mL/minute per 1.73 m² and 17.9% at an estimated GFR of less than 60 mL/minute per 1.73 m² (P < .0001 for trend).
• Odds of subclinical primary hypothyroidism were increased in participants with an estimated GFR of less than 60 mL/minute per 1.73 m² vs those with an estimated GFR of more than 60 mL/minute per 1.73 m² after adjustment for age; sex; and fasting plasma glucose, total cholesterol, and triglyceride concentrations.
• Throughout the normal and high TSH ranges, there was a significant inverse association between estimated GFR and TSH levels.
• Older age was also independently associated with prevalent subclinical hypothyroidism, but sex, fasting plasma glucose levels, and lipid levels were not.
• The investigators concluded that subclinical primary hypothyroidism is relatively prevalent (approximately 18%) among persons with CKD not requiring long-term dialysis and that it is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults.
• Limitations of the study include cross-sectional design, precluding determination of causal or temporal relationships; definition of kidney function based on estimated GFR; inability to identify nonthyroidal and thyroidal causes of subclinical hypothyroidism; possible misclassification resulting from use of automated databases; and lack of data on comorbid conditions and use of thyroid medications.

Pearls for Practice

• Subclinical primary hypothyroidism is relatively prevalent (approximately18%) among adults with CKD not requiring long-term dialysis.
• Subclinical primary hypothyroidism is independently associated with progressively lower estimated GFR in a large cohort of unselected outpatient adults. Throughout the normal and high TSH ranges, there was a significant inverse association between estimated GFR and TSH levels.

CME Test