Endocrine Abstracts

Objective: Hypothyroidism is one of the most common disturbances of thyroid function caused by a thyroid hormone deficiency, found predominantly in young women. The general slowdown of metabolic processes and low-grade chronic inflammatory state occurs in the broad spectra of clinical hypothyroidism manifestations. Although several risk factors of hypothyroidism have been identified, the exact pathogenic mechanisms remain unexplained. The conventional treatment of hypothyroidism is hormone replacement therapy with levothyroxine, one of the main prescribed drugs worldwide. The metabolism of tryptophan (TRP) via the kynurenine pathway (KP), affecting the immune system, contributes to numerous fundamental biological processes. Since the role of the above-mentioned metabolic pathway in hypothyroidism is unknown, the current study aimed to determine KP activity in young women with diagnosed hypothyroidism.

Methods: The study population consisted of 50 women with hypothyroidism treated with thyroid hormone replacement therapy (mean levothyroxine dosage of 1.09±0.36 µg per kilogram of body weight per day, mean age 32.22±9.68) and 33 healthy, age-matched women (CON). Serum levels of TRP, kynurenine (KYN), and its further metabolites: 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA), anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-HAA) were determined by HPLC (Agilent Technologies 1260 series LC system), with DAD and FLD detection. Statistical evaluation of the results was performed using STATISTICA, version 13.3.

Results: TRP concentrations in both groups were similar, while KYN and 3-HKYN levels were significantly elevated in the patients’ group compared to CON (P < 0.001). The KYN/TRP ratio, which reflects the activity of the indole 2,3-dehydrogenase enzyme (IDO-1) involved in the conversion of TRP to KYN, was elevated in hypothyroidism compared to CON (P < 0.05). KYNA concentrations were decreased (P < 0.05), and KYNA/KYN ratio, which reflected kynurenine aminotransferase-1 (KAT-1) activity, was significantly lower in women with hypothyroidism compared to CON (P < 0.01). In contrast, AA levels were significantly higher in the patients compared to CON (P < 0.0001), whereas 3-HAA levels were comparable between both groups. In addition, the 3-HAA/AA ratio, indicating the transformation of AA to 3-HAA was significantly reduced in HT patients compared to healthy subjects (P < 0.001).

Conclusions: Young women with hypothyroidism manifest alteration of TRP metabolism through the kynurenine pathway. The accumulation of KYN, 3-HKYN, and particularly AA occurred, with simultaneously limited KYNA production. Disturbances in the balance between KYNA and AA formation may potentially impact the development of the indicated thyroid function disturbance, which requires further research.

Founding: The above study was funded by the Medical University of Bialystok, Poland; grant no B.SUB.23.182