Improving health equity in endocrinology

Vitamin D testing in certain patient groups is highly variable — but new diagnostic technologies can create equity

Blood tests shouldn’t discriminate. Everyone should be able to access accurate results — regardless of clinical population. But in endocrinology in the Asia-Pacific region, that isn’t the case. Hormone results including Vitamin D, a key biomarker, can vary widely across testing methods and laboratories^{(1,2 )}.

Vitamin D supports almost every organ system in the human body, particularly bone health. Deficiency is associated with a number of debilitating diseases: bone metabolic disorders, tumors, cardiovascular diseases and diabetes⁽³⁾. Vitamin D deficiency is widespread across our region and the world, affecting an estimated 22% of South East Asia’s population and 10% of the Western Pacific population⁽⁴⁾.

The immunoassay challenge

Cross-reactivity

Early detection of vitamin D deficiency allows time for intervention. Unfortunately, standard testing methods — immunoassays — come with major limitations. Cross-reactive metabolites (similar molecules) often lead to inaccurate measurements.

Many immunoassays aim to measure both forms of Vitamin D: D2 and D3. But immunoassays often lack specificity for the D2 form, with an ‘overaffinity’ for D3 — and fail to detect the D2. This leads to an underestimation of total Vitamin D levels in some patients^(5,6).

Epimers

C3-epimers are a natural variant of Vitamin D, formed in the liver with a near-identical structure. C3-epimers are highest in infants but also exist in adults. Most routine immunoassays cannot distinguish between them and will count the epimer as part of the total Vitamin D measurement, leading to inaccurately high results^(7,8,9). 

Certain patient groups are disproportionately affected

This variability in results creates health inequity. A systematic review of 21 studies across Thailand, Vietnam, Malaysia, Cambodia and Indonesia found that 52-90% of infants lack sufficient Vitamin D, but the presence of C3-epimers can lead to false positives — masking genuine deficiency⁽¹⁰⁾.

In pregnancy, Vitamin D plays a vital role. Deficiency is associated with multiple adverse outcomes. ‘Free’ Vitamin D — the active molecule — is bound to vitamin D binding protein (VDBP) in blood and is carried to the liver, kidneys and other target tissues. Accurate Vitamin D measurement depends on complete removal from the binding protein, but VDBP concentrations increase in maternal serum during pregnancy, obfuscating the results⁽¹¹⁾.

Chronically ill patients, too — particularly people living with liver failure and kidney disease (CKD) — are more likely to receive inaccurate test results⁽¹²⁾. VDBP is produced in the liver, but liver disease inhibits this process, meaning total Vitamin D levels are reduced and standard immunoassays flag a deficiency when free Vitamin D levels may be normal.

This variability is higher in people living with cirrhosis compared to healthy individuals and stable outpatients with other chronic conditions. CKD patients face similar challenges; as renal function declines, the metabolism of Vitamin D is disrupted and protein levels fluctuate, often rendering standard immunoassay results unreliable precisely when accurate monitoring is most critical for bone and cardiovascular health⁽¹³⁾.

Mass spectrometry testing reduces variability and improves health equity

Mass spectrometry solves this problem. Considered the ‘gold standard’ for Vitamin D testing, mass spectrometry can precisely distinguish between different types of vitamin D. It can identify functional vitamin D deficiency and allows for personalised assessment of vitamin D status.

For pregnant women, newborns, kidney patients or those in critical care, mass spectrometry holds the key to personalising treatment and addressing a wide range of health conditions.

Historically, adopting mass spectrometry at scale was difficult. Laboratories faced complex hurdles: numerous instrument configurations, varying pre-analytic methods, and inconsistent data acquisition conditions.

The next generation of automated mass spectrometry solutions, however, is overcoming these barriers. By standardising test menus to be traceable to international reference methods, modern systems ensure that a test result is valid and comparable no matter where the analysis is performed.

It brings high-quality precision into routine clinical practice. It ensures a patient in a remote community receives the same diagnostic insights as a patient in a specialised academic hospital.

This is how we can improve health equity in endocrinology — ensuring that every patient, regardless of their condition or location, receives the quality of care they deserve.