Accurate interpretation of thyroid dysfunction during pregnancy: should we continue to use published guidelines instead of population-based gestation-specific reference intervals for the thyroid-stimulating hormone (TSH)?

BACKGROUND: Considering the changes in thyroid physiology associated with pregnancy and poor outcomes related to abnormal maternal thyroid function, international guidelines recommend using population-based trimester-specific reference intervals (RIs) for thyroid testing. If these RIs are not available in the laboratory, implementing recommended fixed cut-off values globally is still controversial. To address this issue, we aimed to establish appropriate RI of thyroid-stimulating hormone (TSH) in pregnant Turkish women for our laboratory and compare the prevalence of thyroid dysfunction based on the established and recommended criteria. METHODS: Of 2638 pregnant women, 1777 women followed in the obstetric outpatient were enrolled in the reference interval study after applying exclusion criteria related to medical and prenatal history. A retrospective study was conducted by collecting data from July 2016 to March 2019. Serum TSH was measured by UniCel DxI 800 Immunoassay System (Beckman Coulter Inc., Brea, CA, USA). The study design relied on two approaches in order to classify pregnant women: trimester-specific and subgroup-specific; the latter involved dividing each trimester into two subgroups: T1a, T1b, T2a, T2b, T3a, T3b. The lower and upper limits of the RIs were derived by the parametric method after normalizing the data distribution using the modified Box-Cox power transformation method. RESULTS: The lowest TSH value was detected at 8-12 weeks in early pregnancy, and the median value of TSH in the T1b subgroup was significantly lower than the T1a subgroup (P < 0.05). TSH levels showed a gradual trend of increase along with the pregnancy and increased significantly in the T2a, T2b, and T3b subgroups compared to the preceding subgroups (P < 0.05). Compared to the diagnostic criteria recommended by American Thyroid Association (ATA), the prevalence of thyroid dysfunction was significantly different from the established trimester- and subgroup-specific RIs throughout the pregnancy (P < 0.001). CONCLUSIONS: We conclude that establishing gestation- and laboratory-specific RIs, especially for TSH, is essential for diagnosing thyroid disorders in pregnancy, and the recommended universal cut-off values, which may contribute to the risk of a misdiagnosis or a missed diagnosis, should be taken with caution in the clinical setting. However, regarding the fluctuation of thyroid function tests throughout pregnancy, trimester-specific RIs are insufficient, and implementing split phases is required.

The association of free testosterone levels with coronavirus disease 2019.

BACKGROUND: Angiotensin-converting enzyme 2 and transmembrane protease serine 2 are critical factors of virus transmission. Expression of angiotensin-converting enzyme 2 is highest in testes, and testicular function and testosterone levels were affected by coronavirus disease 2019. Low testosterone levels are related to infections, especially respiratory tract infections, and could worsen clinical conditions by exacerbating cytokine storms and increasing pro-inflammatory cytokines. OBJECTIVES: We aimed to evaluate the acute and chronic effects of coronavirus disease 2019 on gonadal functions. Our second aim was to detect the relationship between free testosterone levels and disease prognosis and determine the impact of low-free testosterone on admission to the intensive care unit. METHODS: Eighty-one patients with reverse-transcription polymerase chain reaction-confirmed coronavirus disease 2019 were enrolled. Twenty-nine patients were assessed again for 6 months post-coronavirus disease 2019 follow-up, and seven of them had a semen analysis. Serum follicle-stimulating hormone, luteinizing hormone, sex hormone-binding globulin, and total testosterone levels were measured. RESULTS: In this observational study, 71.6% (n = 58) of patients had low free testosterone levels at baseline, in which 69% were considered secondary hypogonadism. A longer length of hospitalization and increased inflammatory markers (d-dimer, high-sensitive C-reactive protein, and procalcitonin) were detected in the low-free testosterone group. Follicle-stimulating hormone, total, free, and bioavailable testosterone levels were lower in patients who required admission to the intensive care unit. Free testosterone levels were inversely correlated with the length of hospitalization and prognostic disease factors. Oligozoospermia and impaired progressive motility were present in 42.8% (3/7) of the patients. In 6 months post-coronavirus disease 2019 follow-up, out of 29 patients, 48.2% still had low testosterone levels. CONCLUSION: A high rate of hypogonadism (71.6%) was found, especially secondary hypogonadism, and about half of the patients had hypogonadism in the sixth months' follow-up. Low free testosterone levels were correlated with inflammatory parameters, and it is related to the intensive care unit admission. Studies with long-term follow-up data in larger groups are needed to determine persistent hypogonadism and impaired spermatogenesis.