National Taiwan University Hospital (NTUH) yesterday announced the discovery of a potentially deadly side effect of antithyroid medications called agranulocytosis, which can lead to sepsis and even death.
Agranulocytosis is a condition characterized by a severe reduction in the number of granulocytes, a type of white blood cells that help the body fight bacterial infection.
Specialists from the NTUH and the Academia Sinica formed the research team that has established a link between two human leukocyte antigen (HLA) genes (HLA-B38:02 and HLA-DRB1 08:03) with an increased risk of life-threatening agranulocytosis. The breakthrough has come after 15 years of research.
The study found that patients carrying HLA-B38:02 or HLA-DRB108:03 are respectively 21.48 times and 6.13 times more susceptible to developing agranulocytosis than those without these genes.
Those carrying both genes face an even greater chance of having the potentially fatal condition, up to 48.41 times, the research indicated.
“Overactive thyroid, also known as hyperthyroidism, is a rather common condition, affecting three out of every 1,000 in the population,” NTUH’s Department of Internal Medicine director Chang Tien-chun (張天鈞) told a press conference in Taipei yesterday afternoon.
Chang, a leading figure in Taiwan’s endocrinology studies and one of the corresponding authors for the study, said women are more prone to developing the condition, with the male-female ratio for the disease at about 1:5.
While medication has been the first-line treatment for the condition, Chang said about 10 percent of patients would experience side effects and that some even develop agranulocytosis.
“In the past, doctors had no way of knowing whether and when a hyperthyroidism patient on anti-thyroid drugs would experience agranulocytosis. We could only ask patients to watch for symptoms such as fever and a sore throat, and hope the condition was detected in time,” Chang said.
Chang said the discovery is likely to help physicians determine each patient’s risk of developing agranulocytosis and offer them other choices of treatment.
However, given that HLA allele and haplotype frequencies vary among ethnic groups, the results apply only to those of Asian ethnicity, Chang added.
The study was published in the scientific journal Nature on Tuesday.
NTUH Department of Medical Genetics attending physician Chen Pei-lung (陳沛隆) said it is estimated that about 10 percent of Taiwanese carry the HLA-DRB108:03 gene and about 6 percent carry HLA-B38:02.
“Generally, a healthy person has 2,000 to 6,000 granulocytes per 3mm of blood, but a patient with agranulocytosis could have less than 500 per 3mm of blood. The number can drop to zero without timely medical intervention,” Chen said.
Academia Sinica’s Institute of Biomedical Sciences researcher Cathy Fann (范盛娟) said the research means overactive thyroid patients can be screened for the two genes before antithyroid medication is prescribed.
It could protect patients from potentially fatal side-effects and save the National Health Insurance program a large sum of money that would otherwise be spent on their treatment should they develop agranulocytosis,” Fann said.
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