Predictive factors for delayed hyponatremia after transsphenoidal surgery in patients with pituitary adenomas

Objective: To evaluate the incidence and duration of delayed hyponatremia and to assess the factors influencing the development of delayed hyponatremia after transsphenoidal surgery (TSS) in pituitary adenomas. Methods: We retrospectively analyzed the clinical data of patients with pituitary adenoma who underwent TSS. Univariable and multivariable statistics were carried out to identify factors independently associated with the occurrence of delayed hyponatremia. Results: Of the 285 patients with pituitary adenoma who underwent microscopic TSS, 44 (15.4%) developed postoperative delayed hyponatremia and 241 (84.6%) did not. The onset of delayed hyponatremia occurred an average of 5.84 days post-surgery and persisted for an average of 5.36 days. Logistic regression analysis showed the highest risk of delayed hyponatremia in patients with significant change in tumor cavity height (odds ratio [OR], 1.158; 95% confidence interval [CI], 1.062, 1.262; P = 0.001), preoperative hypothalamus-pituitary-thyroid axis hypofunction(OR, 3.112; 95% CI, 1.481, 6.539; P = 0.003), and significant difference in blood sodium levels before and 2 days after TSS(OR, 1.101; 95% CI, 1.005, 1.206; P = 0.039). Conclusions: Preoperative hypothyroidism, difference in blood sodium levels before and 2 days after TSS, and the change in tumor cavity height after TSS played important roles in predicting postoperative delayed hyponatremia onset in patients with pituitary adenomas.

Persisting neuroendocrine abnormalities and their association with physical impairment 5 years after critical illness

Background Critical illness is hallmarked by neuroendocrine alterations throughout ICU stay. We investigated whether the neuroendocrine axes recover after ICU discharge and whether any residual abnormalities associate with physical functional impairments assessed 5 years after critical illness. Methods In this preplanned secondary analysis of the EPaNIC randomized controlled trial, we compared serum concentrations of hormones and binding proteins of the thyroid axis, the somatotropic axis and the adrenal axis in 436 adult patients who participated in the prospective 5-year clinical follow-up and who provided a blood sample with those in 50 demographically matched controls. We investigated independent associations between any long-term hormonal abnormalities and physical functional impairments (handgrip strength, 6-min walk distance, and physical health-related quality-of-life) with use of multivariable linear regression analyses. Results At 5-year follow-up, patients and controls had comparable serum concentrations of thyroid-stimulating hormone, thyroxine (T4), triiodothyronine (T3) and thyroxine-binding globulin, whereas patients had higher reverse T3 (rT3, p = 0.0002) and lower T3/rT3 (p = 0.0012) than controls. Patients had comparable concentrations of growth hormone, insulin-like growth factor-I (IGF-I) and IGF-binding protein 1 (IGFBP1), but higher IGFBP3 (p = 0.030) than controls. Total and free cortisol, cortisol-binding globulin and albumin concentrations were comparable for patients and controls. A lower T3/rT3 was independently associated with lower handgrip strength and shorter 6-min walk distance (p ≤ 0.036), and a higher IGFBP3 was independently associated with higher handgrip strength (p = 0.031). Conclusions Five years after ICU admission, most hormones and binding proteins of the thyroid, somatotropic and adrenal axes had recovered. The residual long-term abnormality within the thyroid axis was identified as risk factor for long-term physical impairment, whereas that within the somatotropic axis may be a compensatory protective response. Whether targeting of the residual abnormality in the thyroid axis may improve long-term physical outcome of the patients remains to be investigated. Trial registration ClinicalTrials.gov: NCT00512122, registered on July 31, 2007 (https://www.clinicaltrials.gov/ct2/show/NCT00512122). Graphical Abstract

The Many Faces of Elevated TSH: When to Avoid Thyroid Hormone Therapy in Older Adults

We have previously demonstrated that hypothalamic-pituitary-thyroid axis aging is characterized by several distinct patterns. An elevated thyrotropin (TSH) level (mean 5.6mIU/L) with normal free thyroxine (FT4) was present in 75 BLSA participants with at least 3 visits. Twenty-one percent had an historical pattern consistent with primary gland failure, while 13% had a pattern consistent with an HPT response to stressors (aging-adaptation). The remainder had intermediate patterns of change. FT4 >0.92pg/ml identified those in whom TSH elevations occurred with aging-adaptation with a 90.0% sensitivity and 93.8% specificity, indicating no need for therapy. In addition, among 597 participants with stable TSH levels in the reference range, being on thyroid hormone therapy increased mortality risk (IRR=1.8; 95% CI 0.9-2.1). Thus, including FT4 in the diagnostic criteria for hypothyroidism in older adults could target therapy to avoid the potential harm of reversing the aging adaptations in those who do not have true early hypothyroidism.

Homocysteine, pituitary and thyroid hormones in children with different physical development levels after forest fires in the Chornobyl exclusion zone

Objective We performed a comparative assessment of the blood levels of homocysteine, pituitary and thyroid hormones in children with different levels of physical development before and after forest fires in the Chornobyl exclusion zone (ChEZ) in 2015. Methods: We used immunochemical, instrumental, mathematical and statistical methods. Results: The analysis of variable dynamics was performed in 336 adolescents of the Polisskyi and the Ivankivskyi districts of Kyiv region. An association was found between homocysteine (Нсу), hormones of the pituitary-thyroid axis and physical development of children. A statistically significantly higher level of Нсу was observed in the adolescents from the Ivankivskyi district in comparison with the children from the Polisskyi district. Forest fires in the spring and summer of 2015 in the ChEZ should be considered the main cause for the increase in Нсу in the blood of the adolescents. The increased level of Т3 in the peripheral tissues induced by Нсy and TSH contributed to a decrease in the physical development index values. Due to a decrease in the intensity of the Т4 deiodination process, the insufficient formation of Т3 in the peripheral tissues was recorded in the group of children with a disharmonious high physical development.

Phenotypic Variation Through Ontogeny: Thyroid Axis Disruption During Larval Development in the Frog Pleurodema borellii

Studies of the effects of thyroid hormones on larval development in the frog Xenopus spp. have provided baseline information to identify developmental constraints and elucidate genetic and hormonal mechanisms driving development, growth, and life history transitions. However, this knowledge requires data based on other anurans to complete a comprehensive approach to the understanding of larval developmental diversity and phenotypic variation through ontogeny. Mesocosm experiments provide realistic data about environmental conditions and timing; this information is useful to describe anuran larval development and/or analyze endocrine disruption. In this study, mesocosm experiments of the larval development of the frog Pleurodema borellii were conducted to explore the consequences of thyroid axis disruption; the sensitivity of tadpoles to the methimazole (2.66 mg/l) and thyroxine (T4) (1.66 μg/l) was compared. These concentrations were selected based on previous studies in Pleurodema borellii. We test the effects of methimazole and thyroxine on development in early exposure (from beginning of larval development) and late exposure, 18 days after hatching, with doses administered every 48 h. Tadpoles were evaluated 31 days after hatching. Methimazole caused moderate hypertrophy of the thyroid gland, alteration in the growth rates, differentiation without inhibition of development, and an increase of developmental variability. Thyroxine produced slight atrophy of the thyroid gland, accelerated growth rates and differentiation, and minor developmental variability. In tadpoles at stages previous to metamorphose, skull development (differentiation of olfactory capsules, appearance of dermal bones, and cartilage remodeling) seemed to be unaltered by the disruptors. Moreover, similar abnormal morphogenesis converged in specimens under methimazole and thyroxine exposures. Abnormalities occurred in pelvic and pectoral girdles, and vent tube, and could have been originated at the time of differentiation of musculoskeletal tissues of girdles. Our results indicate that premetamorphic stages (Gosner Stages 25–35) are sensitive to minimal thyroid axis disruption, which produces changes in developmental rates; these stages would also be critical for appendicular musculoskeletal morphogenesis to achieve the optimal condition to start metamorphosis.