Gene heterogeneity may affect thyroid hormone resistance outcomes
Japanese researchers have reported the case of a 28-year old woman with resistance to thyroid hormone (RTH) and chronic thyroiditis.
Writing in an advance online publication by the Endocrinology Journal, the team explains that RTH is commonly characterized by decreased tissue responsiveness to thyroid hormone, due mainly to mutation of the thyroid hormone receptor (TR)-β gene.
Furthermore, they add: "It has been reported that serum of patients with RTH lack autoantibodies against thyroglobulin (Tg) and thyroid peroxidase (TPO), except in rare cases where there is a co-occurrence of coincidental autoimmune thyroiditis."
To investigate this issue, the researchers studied the levels of these factors as well as thyroid hormone levels in a 28-year old woman with RTH and chronic thyroiditis and her father who also had these two conditions.
Results of thyroid function tests showed that she had raised levels of free triiodothyronine (fT3) and free thyroxine (fT4), but that her thyroid stimulating hormone (TSH) levels were within the normal range.
Her anti-Tg antibody levels, at 14.6 IU/ml, and her anti-TPO antibody levels, at 0.5 IU/ml, were slightly elevated, suggesting mild chronic thryoiditis.
Similarly, the patient's father also demonstrated elevated levels of TSH, fT3 and fT4, and was positive for both anti-Tg and anti-TPO antibodies.
Genotyping analyses revealed that both the patient and her father had a codon 453 mutation of the TR-β gene.
Haruhiro Sato and Hideto Sakai, from Tokai University School of Medicine in Boseidai, say that the patient's condition was stable until 2003 when she developed severe palpitations, emotional disturbance, anxiety, appetite loss and nervousness. She was prescribed the anti-anxiety drug lorazepam and her condition improved.
They note that, in addition, the patients' cardiac symptoms and emotional status differed from those of her relatives, who had different polymorphisms of the TR-β gene.
"Thus, the most likely explanation for the variable clinical manifestations of this condition is the genetic heterogeneity of the many co-factors that modulate the receptor-dependent action of thyroid hormone," Sato and Sakai conclude.