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.

Appropriate care of pregnant women with coexisting thyroid dysfunction is still a subject of much controversy. In recent years, there has been a dynamic increase in the number of scientific reports on the diagnosis and treatment of thyroid diseases in women planning pregnancy, pregnant women, and women in the postpartum period. These mainly concern the management of hypothyroidism, autoimmune thyroid diseases, and fertility disorders. Therefore, the Polish Society of Endocrinology deemed it necessary to update the guidelines on principles of diagnostic and therapeutic management in this group of patients, previously published in 2011. The recommendations were prepared by Polish experts according to evidence based medicine principles, if such data were available.

Immune checkpoint inhibitors (ICIs) have become a promising treatment for advanced malignancies. However, these drugs can induce immune-related adverse events (irAEs) in several organs, including skin, gastrointestinal tract, liver, muscle, nerve, and endocrine organs. Endocrine irAEs comprise hypopituitarism, primary adrenal insufficiency, thyroid dysfunction, hypoparathyroidism, and type 1 diabetes mellitus. These conditions have the potential to lead to life-threatening consequences, such as adrenal crisis, thyroid storm, severe hypocalcemia, and diabetic ketoacidosis. It is therefore important that both endocrinologists and oncologists understand the clinical features of each endocrine irAE to manage them appropriately. This opinion paper provides the guidelines of the Japan Endocrine Society and in part the Japan Diabetes Society for the management of endocrine irAEs induced by ICIs.