Hypothyroidism Screening Needed for Patients with Alkaptonuria

Shirisha Avadhanula, MD

Screening for hypothyroidism should be considered for patients with alkaptonuria, according to recent study findings.

Shirisha Avadhanula, MD, and colleagues aimed to assess thyroid structure and function in adults with alkaptonuria. The team found a high prevalence of primary hypothyroidism noted in such patients.

Avadhanula, from the National Institute of Diabetes and Digestive and Kidney Diseases at the National Institutes of Health (NIH), and the investigative team included 125 adults with alkaptonuria who were enrolled at the NIH from February 2000-December 2018. The investigators included patients who had thyroid function tests repeated >2 times per week and had information on the medical management of their thyroid disorder.

The team measured serum thyrotropin and free thyroxine levels by immunoassay and were repeated in each patients a median of 3 times. The results were verified by liquid chromatography with tandem mass spectrometry >1 time during follow-up.

The primary outcome was to analyze the prevalence of thyroid dysfunction in patients with alkaptonuria to compare with the standard US adult population (control group). Additional measures included the association of thyroid dysfunction with age, sex, and thyroid peroxidase antibodies.

The study cohort included 53 women (42.4%) with a median age at first thyrotropin measurement of 45 years old, who were followed up for a median of 93 months.

The prevalence of hyperthyroidism was .8%, which was similar to that of the general population, .5% (difference, .003; 95% CI, -.001 to .04; P=.88). Primary hypothyroidism prevalence was 16% (20 of 125 patients), which was significantly higher than the 3.7% reported among patients in the general population (difference, .12; 95% CI, .1-.24; P <.001).

Women were more likely to have primary hypothyroidism than men (OR, 10.99; 95% CI, 3.13-38.66; P <.001). Those who had thyroid peroxidase antibodies also had higher rates of primary hypothyroidism than those without (OR, 7.36; 95% CI, 1.89-28.62; P=.004).

The investigators did not find a significant difference in the prevalence of thyroid nodules between patients in the study (59.2%) compared to the general population (68%) (difference, .088; 95% CI, -.44 to .73; P=.2) or of cancer (7% vs 5%; difference, .01; 95% CI, -.01 to .17; P=.86).

A majority of the patients presented with overt hypothyroidism and were treated with a median levothyroxine dose of 1.4 μg/kg of body weight.

The findings were consistent to prior research which found that both female sex and presence of thyroid peroxidase antibodies were associated with a higher likelihood of primary hypothyroidism compared with male sex and thyroid peroxidase antibody-negative status in patients with alkaptonuria.

The high prevalence of primary hypothyroidism suggested that screening for the condition in patients with alkaptonuria should be considered, the investigators wrote. The initial screening should occur at the diagnosis of alkaptonuria and should be repeated regularly (every 1-2 years) afterwards.

Additional research could be conducted based on the findings to learn the functional role of homogentisic acid deposition in the thyroid gland.

The study, “Assessment of Thyroid Function in Patients With Alkaptonuria,” was published online in JAMA Network Open.