People with long-standing type 2 diabetes may benefit from regular monitoring of their thyroid function because persistent subclinical hypothyroidism is linked with rising albuminuria, Australian endocrinologists say.
Professor Tim Davis
Researchers from the University of Western Australia and Fremantle Hospital investigated whether mild thyroid dysfunction, often regarded as clinically insignificant, contributed to renal risk in people with established diabetes.
Led by Fremantle Hospital diabetologist Professor Tim Davis, the investigators noted subclinical hypothyroidism remained controversial in both screening and treatment, with most guidelines advising against routine testing in asymptomatic individuals, investigators note.
But they argue that growing evidence has made the question increasingly important in people with long-standing diabetes, where even subtle contributors to kidney damage can have meaningful clinical consequences.
“Whether SCH contributes independently to progressive renal dysfunction and/or albuminuria is an important question, as the role of thyroid replacement therapy for SCH remains controversial and guidelines recommend against thyroid function testing solely because a patient has type 2 diabetes,” they wrote in the study published in the Journal of Clinical Endocrinology and Metabolism [link here].
“If SCH has significant clinical implications, there may be an argument for enhanced screening and more intensive management,” they added.
The findings come from the Fremantle Diabetes Study Phase II, which followed 725 adults with type 2 diabetes and no known thyroid disease at baseline for a mean of 4.3 years, tracking changes in kidney filtration and urinary albumin excretion across thyroid-status groups.
Most participants remained euthyroid (n = 683), while 18 developed transient subclinical or mild overt hypothyroidism and 24 had persistent abnormalities.
Across all three groups, estimated glomerular filtration rate (eGFR) remained broadly stable, with no significant difference in average change or in the proportion experiencing a clinically important decline of more than 30%.
Albuminuria worsened in persistent thyroid dysfunction
A different picture emerged when researchers examined albuminuria.
Participants with persistent subclinical or mild overt hypothyroidism recorded a mean rise in albumin-to-creatinine ratio (ACR) of 22.0 mg/mmol, compared with just 0.4 mg/mmol in euthyroid participants and a slight decrease (-0.3 mg/mmol) in those whose thyroid dysfunction was transient – a between-group difference that reached statistical significance (P = 0.027).
The association persisted even when individuals with established macroalbuminuria at baseline were excluded.
The effect was most pronounced among participants who began the study with normal urinary albumin levels, where worsening ACR and a rising trend toward new-onset macroalbuminuria were seen across thyroid-status categories.
In contrast, no meaningful differences in albumin changes were observed among those who already had microalbuminuria at baseline.
The investigators said the findings point to sustained thyroid dysfunction as the driver of worsening kidney damage.
“Our data suggest that more prolonged mild hypothyroidism, whether SCH or overt, may be a risk factor for clinically significant increases in ACR and the incidence of macroalbuminuria in people with type 2 diabetes, especially in those with normal ACR at baseline.”
Exploring possible mechanisms
Because subclinical hypothyroidism has been linked in prior research to both insulin resistance and hypertension – known contributors to kidney damage – investigators examined whether either pathway explained the rise in albuminuria.
“Given that SCH can be associated with insulin resistance and hypertension, the benefits of treatment of SCH for albuminuria may be through these risk factors rather than through a direct effect on CKD pathophysiology in type 2 diabetes,” investigators said.
However, the current study found no association between persistent thyroid dysfunction and changes in blood pressure or insulin resistance, suggesting these factors did not mediate the observed kidney injury.
The authors noted that alternative biological mechanisms, including endothelial dysfunction and direct effects of low thyroid hormone levels on kidney filtration cells, may contribute.
While cautioning that relatively few participants had persistent thyroid dysfunction – limiting statistical power – and that reverse causality cannot be excluded, the investigators said the findings raise important questions about current screening practice.
If subclinical hypothyroidism is shown to carry meaningful clinical consequences, they added, there may be justification for enhanced monitoring and management beyond existing guideline recommendations.
“Persistent SCH/overt hypothyroidism was associated with incident increased albuminuria not observed in euthyroid participants. Assessment of thyroid function in all patients with T2DM may be indicated, as some previous studies provide evidence that thyroxine replacement may ameliorate albuminuria,” they concluded.