Thyroid and pituitary-adrenal activity in patients with asthma and endemic subclinical hypothyroidism in response of respiratory tract to a cold stimulus

Introduction. In patients with uncontrolled asthma, the stress-induced production of glucocorticosteroids in response to a cold bronchoprovocation test is increased, which is associated with an increase in the level of thyroidstimulating hormone (TSH), characteristic of the syndrome of subclinical hypothyroidism (SH). The peculiarities of thyroid hormone metabolism and changes in pituitary-adrenal homeostasis that develop in asthma in a goiter-endemic region under the influence of cold stress factors on the respiratory system are poorly studied.

Aim. To assess the activity of the pituitary-thyroid and pituitary-adrenal systems in response to bronchoprovocation with cold air in asthma patients with cold airway hyperresponsiveness (CAHR) and SH living in conditions of goiter endemic in the Amur Region.

Materials and methods. In 34 asthma patients with CAHR, without symptoms of thyroid diseases, the level of disease control was assessed using the Asthma Control Test (ACT) questionnaire. Lung function and airway reaction to a cold stimulus (ΔFEV_1IHCA) during 3-minute isocapnic hyperventilation with cold (-20ºC) air (IHCA) were measured. Methods of immunological diagnostics in the blood of patients before and after the IHCA test were used to measure the concentrations of thyroid-stimulating (TSH) and adrenocorticotropic (ACTH) hormones, common and active forms of thyroxine (T4) and triiodothyronine (T3), thyroglobulin (TG), autoantibodies to thyroperoxidase (AB-TPO), cortisol. The content of cyclic adenosine monophosphate (cAMP) was determined in leukocytes.

Results. The patients were divided into two groups: group 1 included 25 patients with an initially low (<4.0) TSH level (2.39±0.18 mU/L), group 2 included 9 patients with an initially high (>4, 0) TSH level (4.80±0.46 mU/L, p<0.0001). The ACT control level in groups 1 and 2 was 16.6±1.0 and 15.3±1.5 points (p>0.05), base FEV1 was 95.8±3.3 and 81.0±5.4% (p=0.026), ΔFEV_1IHCA -11.9±0.96 and -13.5±2.7 (p>0.05), respectively. In group 1, in response to IHCA, the level of free T4 increased from 14.2±0.70 to 15.2±0.71 pmol/L (p<0.05), free T3 from 3.73±0.24 to 4.15±0.21 nmol/L (p<0.05). In group 2, a lower level of free T4 was recorded, both before (12.2±1.52 pmol/L) and after IHCA (11.6±1.60 pmol/L, p=0.041). In addition, in group 2 patients, the cortisol concentration at baseline and after IHCA (516.6±31.6 and 397.4±40.4 nmol/L, p<0.05) was significantly lower than in group 1 (628.3±27.5 and 608.3±34.1 nmol/L, p=0.042; p=0.002, respectively). A close correlation was found between ΔFEV₁ and the T4 level before (r=0.54; p<0.01) and after the test (r=0.41; p<0.05), with the amount of cAMP up to (r=0.58; p=0.008) and after the test (r=0.47; p=0.009), as well as the correlation between ΔМEF₅₀ and the initial level of cortisol in the blood serum (r=0.50; p=0.002).

Conclusion. In asthma patients with CAHR living in the region of cold climate and goiter endemic, the presence of SH can be considered as a prognostic sign of the development of dysadaptation of the respiratory system to cold exposure.

1. Zakharenko R.V., Sirotin B.Z. On the history of the study of goiter in the Far East. Problems of Endocrinology 2004; 50(2):54−55 (in Russian). https://doi.org/10.14341/probl11396

2. Balabolkin M.I. Developed and unsolved issues of endemic goiter and iodhythic states (lecture). Problems of Endocrinology 2005; 51(4):31−37 (in Russian). https://doi.org/10.14341/probl200551431-37

3. Prikhodko A.G., Perelman J.M., Kolosov V.P. Airway hyperresponsiveness. Vladivostok: Dal'nauka; 2011 (in Russian).

4. Landyshev Yu.S. Bronchial asthma (neuroendocrine system, immunity, clinic, diagnosis, treatment). Blagoveshchensk: AGMA, 2006 (in Russian).

5. Mal'tseva T.A., Kolosov V.P., Pirogov A.B. The influence of steroid hormones of adrenal gland cortex on the functional state of hypophisial-thyroidal system of patients with bronchial asthma. Bûlleten' fiziologii i patologii dyhaniâ = Bulletin Physiology and Pathology of Respiration 2012; (44):41−45 (in Russian).

6. UK Guidelines for the Use of Thyroid Function Tests. London: Association of Clinical Biochemistry, British Thyroid Association, and British Thyroid Foundation; 2006. Available at: https://www.british-thyroid-association.org/sandbox/bta2016/uk_guidelines_for_the_use_of_thyroid_function_tests.pdf

7. Hollowell J.G., Staehling N.W., Flanders W. D., Hannon W.H., Gunter E.W., Spencer C.A., Braverman L.E. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J. Clin. Endocrinol. Metab. 2002; 87(2):489−499. https://doi.org/10.1210/jcem.87.2.8182

8. Podzolkov A.V., Fadeyev V.V. Hypothyroidism, Subclinical Hypothyroidism, High-normal TSH-level. Clinical and experimental thyroidology 2009; 5(2):4−16 (in Russian). https://doi.org/10.14341/ket2009524-16

9. Col N.F., Surks M.I., Daniels G.H. Subclinical thyroid disease: clinical applications. JAMA 2004; 291(2):239−243. https://doi.org/10.1001/jama.291.2.239

10. Surks M.I., Ortiz E., Daniels G.H., Sawin C.T., Col N.F., Cobin R.H., Franklyn J.A., Hershman J.M., Burman K.D., Denke M.A., Gorman C., Cooper R.S., Weissman N.J. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291(2):228−238. https://doi.org/10.1001/jama.291.2.228

11. Levchenko I.A., Fadeev V.V. Subclinical hypothyrosis. Problems of Endocrinology 2002; 48(2):13−22 (in Russian). https://doi.org/10.14341/probl11502

12. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (2018 update). Available at: www.ginasthma.com

13. Pellegrino R., Viegi G., Brusasco V., Crapo R.O., Burgos F., Casaburi R., Coates A., Van der Grinten C.P.M., Gustafsson P., Hankinson J., Jensen R., Johnson D.C., MacIntyre N., McKay R., Miller M.R., Navajas D., Pedersen O.F., Wanger J. Interpretative strategies for lung function tests. Eur. Respir. J. 2005; 26:948−968. https://doi.org/10.1183/09031936.05.00035205

14. Panin L.B. Biochemical stress mechanisms. Novosibirsk: Nauka; 1983 (in Russian).