HPT‐ Axis Activation During Cold Head Out Water Immersion is Not Modified by Moderate Hypoxia
Authors: Greenshields Joel T. , Goss Curtis S. , Keeler Jasosn M. , Baker Tyler B. , Logan Richara T. , Chapman Robert F. , Johnson Blair D. , Schlader Zachary J. 
Published: May 2022

Purpose

The Bajau, an indigenous population renowned for breath‐hold diving, have comparatively large spleen volumes. This adaptation is purportedly indicative of a greater capacity to store red blood cells, which may aid operations in the aquatic environment. Spleen size in the Bajau is associated with the PDE10A genotype that encodes an enzyme that catalyzes the release of thyroxine (T4) from the thyroid gland. T4 is readily released during cold stress as the terminus to activation of the hypothalamus‐pituitary‐thyroid (HPT) ‐axis to increase metabolic rate. T4, and downstream counterpart triiodothyronine (T3), can also stimulate erythropoiesis by increasing erythropoietin production, which can be further promoted with hypoxia. Thus, exposure to cold water may augment erythropoiesis as hypoxia develops during breath‐hold diving via activation of the HPT‐axis. However, interactions between cold exposure and hypoxia on HPT‐axis activation have not been directly explored. Mountaineering expedition studies indirectly suggest that T4 release is elevated by hypoxia. Thus, this study tested the hypothesis that during cold head out water immersion (HOWI) acute hypoxia augments circulating thyroid hormone concentrations compared to normoxia.

Methods

In a randomized crossover single blind design, 12 healthy adults (27 ± 2 y, 2 women) completed one hour of cold (22.0 ± 0.1⁰C) HOWI breathing either normobaric normoxia (FiO2 = 0.21 ± 00, NORM) or normobaric hypoxia (FiO2 = 0.13 ± 00, HYP). Free (f) and total (t) T3 and T4, and thyroid stimulating hormone (TSH) were measured in venous blood samples obtained before (baseline), during (15‐, 30‐, and 60‐min), and 15 min following immersion (post‐). Arterial oxyhemoglobin saturation (SpO2) and rectal temperature were measured continuously. Data are presented as mean ± SD.

Results

SpO2 was lower in HYP (90 ± 3%) compared to NORM (98 ± 1%, p <.001). Rectal temperature did not differ between HYP and NORM (p > .711) but decreased over time in both trials (HYP ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.4 ± 0.5⁰C, p<.001, NORM ‐ baseline: 37.2 ± 0.4⁰C, post‐: 36.3 ± 0.5⁰C, p <.001). From baseline to post‐HOWI, fT3 (HYP: +0.3 ± 0.4 pg/mL, NORM: +0.4 ± 0.6 pg/mL, p <.001), fT4 (HYP: +1.6 ± 1.7 pg/mL, NORM: +0.7 ± 1.3 pg/mL, p <.001), tT3 (HYP: +0.3 ± 0.5 ng/mL, NORM: +0.2 ± 0.4 ng/mL, p= .053), and tT4 (HYP: +0.6 ± 0.4 µg%, NORM: +0.4 ± 0.5 µg%, p < .001) increased, but the magnitude did not differ between inspirates (p > .165). Relative to baseline, tT4 at 15 min (HYP: ‐0.2 ± 0.3 µg%, NORM: ‐0.3 ± 0.3 µg%, p = .025), and TSH at 30 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.2 ± 0.3 µIU/mL, p = .029) and 60 min (HYP: ‐0.2 ± 0.2 µIU/mL, NORM: ‐0.3 ± 0.4 µIU/mL, p = .008) of HOWI were lower, but did not differ between inspirates (p = .921).

Conclusions

Increases in circulating thyroid hormone concentrations during one hour of cold HOWI are not modified by normobaric hypoxia. Thus, moderate hypoxia does not likely affect activation of the HPT‐axis during short duration cold exposure. Further investigation is warranted to determine the possibility of circulating thyroid hormones to augment the erythropoietic response to acute hypoxia during cold exposure.