The role of visceral hypersensitivity and cortisol levels in the development of intestinal dysfunction in coexisting hypothyroidism

Authors

DOI:

https://doi.org/10.14739/2310-1210.2025.1.313844

Keywords:

hypothyroidism, irritable bowel syndrome, visceral hypersensitivity, cortisol, calprotectin

Abstract

The increasing dysfunction of the thyroid gland, particularly hypothyroidism, and its multifaceted effects on the gastrointestinal tract, such as potential changes in hormonal receptor sensitivity, neuromuscular disorders, and myopathy caused by infiltration of the colonic wall, lead to impaired bowel function. Although constipation remains the most common gastrointestinal complaint in hypothyroidism, hypomotility may contribute to excessive bacterial growth in the small intestine and the development of diarrhea.

The aim is to study the role of visceral hypersensitivity and cortisol levels in patients with intestinal dysfunction in coexisting hypothyroidism and in those with constipation or diarrhea without thyroid dysfunction.

Materials and methods. A total of 41 patients with hypothyroidism were examined, of whom 24 were diagnosed with persistent constipation and 17 with diarrhea, along with 36 patients with irritable bowel syndrome (IBS) (control group), of whom 22 had constipation and 14 had diarrhea. In all the patients, visceral hypersensitivity was assessed using the Visceral Sensitivity Index (VSI), and serum cortisol levels were measured by enzyme-linked immunosorbent assay (ELISA) using commercial kits from Sanguin (USA). Fecal calprotectin levels were assessed with the Human CALPE (Calprotectin) ELISA KIT by Elabscienсe (USA).

Results. VSI was higher in patients with hypothyroidism and diarrhea and scored 66.0 (61.0; 68.0) points. In individuals with IBS and diarrhea without thyroid dysfunction, VSI was 58.0 (54.0; 62.0) points. Meanwhile, VSI was 65.0 (60.0; 69.0) points in patients with constipation due to hypothyroidism, whereas in IBS patients without thyroid dysfunction, it was significantly lower – 24.0 (22.0; 26.0) points (p < 0.05). In the control group without bowel and thyroid pathology, VSI scored 15.0 (12.0; 18.0) points. The serum cortisol level in patients with hypothyroidism and diarrhea was 305.41 (270.24; 309.3) nmol/L, while in patients with IBS and diarrhea without thyroid dysfunction, it was 211.0 (205.0; 222.5) nmol/L. In patients with constipation due to hypothyroidism, the serum cortisol level was 310.625 (308.440; 337.285) nmol/L, whereas in IBS patients with constipation, it was 178.0 (172.0; 187.5) nmol/L. For healthy individuals, the cortisol level was 158.0 (152.0; 167.5) nmol/L. A direct correlation has been found between a high degree of visceral sensitivity and cortisol levels in patients with hypothyroidism and constipation, as well as an inverse correlation in patients with hypothyroidism and diarrhea. The obtained data may indicate a shift towards hypersensitivity and the development of symptoms characteristic of IBS.

Conclusions. Visceral hypersensitivity is observed both in cases of diarrhea developing against the background of hypothyroidism and in irritable bowel syndrome with a similar clinical presentation. At the same time, in cases of constipation associated with hypothyroidism, hypersensitivity is also present but tends to be less pronounced in IBS with constipation. Patients with hypothyroidism, regardless of the presence of constipation or diarrhoea, have an increase in blood cortisol levels, while in some variants of IBS, they do not differ significantly from those of healthy individuals. A direct correlation was found between a high degree of visceral hypersensitivity and cortisol levels in hypothyroid patients with constipation and the opposite in hypothyroid patients with diarrhoea.

Author Biographies

V. H. Mishchuk, Ivano-Frankivsk National Medical University

MD, PhD, DSc, Professor, Head of the Department of General Practice – Family Medicine and Rehabilitation

H. V. Kozinchuk, Ivano-Frankivsk National Medical University

MD, Assistant of the Department of General Practice – Family Medicine and Rehabilitation

O. Z. Venhrovych, Ivano-Frankivsk National Medical University

MD, PhD, Associate Professor of the Department of General Practice – Family Medicine and Rehabilitation

U. P. Shalamai, Ivano-Frankivsk National Medical University

MD, PhD, Associate Professor of the Department of General Practice – Family Medicine and Rehabilitation

References

  1. Drossman DA, Hasler WL. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150(6):1257-61. doi: https://doi.org/10.1053/j.gastro.2016.03.035
  2. de Vries EM, Fliers E, Boelen A. The molecular basis of the non-thyroidal illness syndrome. J Endocrinol. 2015;225(3). doi: https://doi.org/10.1530/JOE-15-0133
  3. Ciobanu L, Dumitrascu DL. Gastrointestinal motility disorders in endocrine diseases. Pol Arch Med Wewn. 2011;121(4):129-36.
  4. Fenneman AC, Bruinstroop E, Nieuwdorp M, van der Spek AH, Boelen A. A Comprehensive Review of Thyroid Hormone Metabolism in the Gut and Its Clinical Implications. Thyroid. 2023;33(1):32-44. doi: https://doi.org/10.1089/thy.2022.0491
  5. Giorda CB, Carnà P, Romeo F, Costa G, Tartaglino B, Gnavi R. Prevalence, incidence and associated comorbidities of treated hypothyroidism: an update from a European population. Eur J Endocrinol. 2017;176(5):533-42. doi: https://doi.org/10.1530/EJE-16-0559
  6. Alves C, Silverio N, Batel Marques F. Prevalence of Undiagnosed Hypothyroidism in Europe: A Systematic Review and Meta-Analysis. Eur Thyroid J. 2019;8(3):130-43. doi: https://doi.org/10.1159/000499751
  7. Garmendia Madariaga A, Santos Palacios S, Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014;99(3):923-31. doi: https://doi.org/10.1210/jc.2013-2409
  8. Ríos-Prego M, Anibarro L, Sánchez-Sobrino P. Relationship between thyroid dysfunction and body weight: a not so evident paradigm. Int J Gen Med. 2019;12:299-304. doi: https://doi.org/10.2147/IJGM.S206983
  9. Patil AD. Link between hypothyroidism and small intestinal bacterial overgrowth. Indian J Endocrinol Metab. 2014;18(3):307-9. doi: https://doi.org/10.4103/2230-8210.131155
  10. Almandoz JP, Gharib H. Hypothyroidism: etiology, diagnosis, and management. Med Clin North Am. 2012;96(2):203-21. doi: https://doi.org/10.1016/j.mcna.2012.01.005
  11. Bargiel P, Szczuko M, Stachowska L, Prowans P, Czapla N, Markowska M, et al. Microbiome metabolites and thyroid dysfunction. J Clin Med. 2021;10(16):3609. doi: https://doi.org/10.3390/jcm10163609
  12. Patyra K, Jaeschke H, Löf C, Jännäri M, Ruohonen ST, Undeutsch H, et al. Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice. FASEB J. 2018 May 25. doi: https://doi.org/10.1096/fj.201800211R
  13. Yao Z, Zhao M, Gong Y, Chen W, Wang Q, Fu Y, et al. Relation of gut microbes and L-thyroxine through altered thyroxine metabolism in subclinical hypothyroidism subjects. Front Cell Infect Microbiol. 2020;10:495. doi: https://doi.org/10.3389/fcimb.2020.00495
  14. Jiang W, Yu X, Kosik RO, Song Y, Qiao T, Tong J, et al. Gut microbiota may play a significant role in the pathogenesis of Graves’ disease. Thyroid. 2021;31(5):810-20. doi: https://doi.org/10.1089/thy.2020.0193
  15. Khadka M, Kafle B, Sharma S. Prevalence of thyroid dysfunction in irritable bowel syndrome. J Universal Coll Med Sci. 2018;4(2):1. doi: https://doi.org/10.3126/jucms.v4i2.19082
  16. Yeşilova A, Bilge M, Gökden Y, Adaş M. Irritable bowel syndrome in women with euthyroid Hashimoto’s thyroiditis: is there any relationship between thyroid autoimmunity and irritable bowel syndrome? Cerrahpasa Med J. 2023;47:123-8. doi: https://doi.org/10.5152/cjm.2022.22054
  17. Ford AC, Talley NJ, Walker MM, Jones MP. Increased prevalence of autoimmune diseases in functional gastrointestinal disorders: case-control study of 23,471 primary care patients. Aliment Pharmacol Ther. 2014;40(7):827-34. doi: https://doi.org/10.1111/apt.12903
  18. Ruscio M, Guard G, Piedrahita G, D’Adamo CR. The relationship between gastrointestinal health, micronutrient concentrations, and autoimmunity: a focus on the thyroid. Nutrients. 2022;14(17):3572. doi: https://doi.org/10.3390/nu14173572
  19. Yanping W, Gao X, Cheng Y, Liu M, Liao S, Zhou J, et al. The interaction between obesity and visceral hypersensitivity. J Gastroenterol Hepatol. 2023;38:370-7. doi: https://doi.org/10.1111/jgh.16083
  20. Benson S, Siebert C, Koenen LR, Engler H, Kleine-Borgmann J, Bingel U, et al. Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women. Pain. 2019;160(8):1719-28. doi: https://doi.org/10.1097/j.pain.0000000000001579
  21. Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396(10263):1664-74. doi: https://doi.org/10.1016/S0140-6736(20)32115-2
  22. Labus JS, Bolus R, Chang L, Wiklund I, Naesdal J, Mayer EA, et al. The Visceral Sensitivity Index: development and validation of a gastrointestinal symptom-specific anxiety scale. Aliment Pharmacol Ther. 2004;20:89-97. doi: https://doi.org/10.1111/j.1365-2036.2004.02007.x
  23. Saigo T, Tayama J, Hamaguchi T, Nakaya N, Tomiie T, Bernick PJ, et al. Gastrointestinal specific anxiety in irritable bowel syndrome: validation of the Japanese version of the visceral sensitivity index for university students. Biopsychosoc Med. 2014;8(1):10. doi: https://doi.org/10.1186/1751-0759-8-10
  24. Neverovskyi A, Shypulin V, Mikhnova N. Translation and validation of the Ukrainian version of the visceral sensitivity index for patients with irritable bowel syndrome. Prz Gastroenterol. 2023;18(3):313-9. doi: https://doi.org/10.5114/pg.2023.131391
  25. Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta. 2013;1830(7):3987-4003. doi: https://doi.org/10.1016/j.bbagen.2012.08.005
  26. Nakazawa N, Sohda M, Ogata K, Sano A, Sakai M, Ogawa H, et al. Impact of neutrophil-lymphocyte ratio, Glasgow Prognostic Score, and postoperative decrease in psoas muscle index on recurrence after curative gastrectomy. J Med Invest. 2021;68(1.2):119-24. doi: https://doi.org/10.2152/jmi.68.119
  27. Jiang W, Lu G, Gao D, Lv Z, Li D. The relationships between the gut microbiota and its metabolites with thyroid diseases. Front Endocrinol (Lausanne). 2022;13:943408. doi: https://doi.org/10.3389/fendo.2022.943408
  28. David LE, Surdea-Blaga T, Dumitrascu DL. Semiquantitative fecal calprotectin test in postinfectious and non-postinfectious irritable bowel syndrome: cross-sectional study. Sao Paulo Med J. 2015;133(4):343-9. doi: https://doi.org/10.1590/1516-3180.2014.8000815
  29. Chosakai UC, Sachdeva S, Pratap N, Karyampudi A, Abraham UM, Bhatt CB, et al. Indian consensus statements on irritable bowel syndrome in adults: a guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology. Indian J Gastroenterol. 2023;42(2):243-73. doi: https://doi.org/10.1007/s12664-022-01333-5
  30. Zhang Y, Wu XX, Li S, Wu JF, Han S, Lin ZJ, et al. Peroxiredoxin 1 as an inflammatory marker in diarrhea-predominant and postinfectious irritable bowel syndrome. Neurogastroenterol Motil. 2020;32(2):e13741. doi: https://doi.org/10.1111/nmo.13741
  31. Savarino E, Zingone F, Barberio B, Marasco G, Akyuz F, Akpinar H, et al. Functional bowel disorders with diarrhoea: Clinical guidelines of the United European Gastroenterology and European Society for Neurogastroenterology and Motility. United European Gastroenterol J. 2022;10(6):556-84. doi: https://doi.org/10.1002/ueg2.12259
  32. Dajti E, Frazzoni L, Iascone V, Secco M, Vestito A, Fuccio L, et al. Systematic review with meta-analysis: diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults. Aliment Pharmacol Ther. 2023;58(11-12):1120-31. doi: https://doi.org/10.1111/apt.17754
  33. Skrobisz K, Piotrowicz G, Drozdowska A, Markiet K, Sabisz A, Naumczyk P, et al. Use of functional magnetic resonance imaging in patients with irritable bowel syndrome and functional dyspepsia. Gastroenterology Review. 2019;14(3):163-7. doi: https://doi.org/10.5114/pg.2019.88163
  34. Ustianowska K, Ustianowski L, Machaj F, Goracy A, Rosik J, Szostak B, et al. The role of the human microbiome in the pathogenesis of pain. Int J Mol Sci. 2022;23(21):13267. doi: https://doi.org/10.3390/ijms232113267
  35. Takeda T, Asaoka D, Nojiri S, Yanagisawa N, Nishizaki Y, Osada T, et al. Usefulness of Bifidobacterium longum BB536 in elderly individuals with chronic constipation: A randomized controlled trial. Am J Gastroenterol. 2023;118(3):561-8. doi: https://doi.org/10.14309/ajg.0000000000002028
  36. Bokic T, Storr M, Schicho R. Potential causes and present pharmacotherapy of irritable bowel syndrome: an overview. Pharmacology. 2015;96(1-2):76-85. doi: https://doi.org/10.1159/000435816
  37. Sinha RS, Prakash P, Keshari JR, Kumari R, Prakash V. Assessment of serum cortisol levels in hypothyroidism patients: a cross-sectional study. Cureus. 2023;15(12):e50199. doi: https://doi.org/10.7759/cureus.50199
  38. Fox TJ, Anastasopoulou C. Pituitary hyperplasia in primary hypothyroidism. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. Updated 2023 Aug 28. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562316/

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2025-02-17

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1.
Mishchuk VH, Kozinchuk HV, Venhrovych OZ, Shalamai UP. The role of visceral hypersensitivity and cortisol levels in the development of intestinal dysfunction in coexisting hypothyroidism. Zaporozhye Medical Journal [Internet]. 2025Feb.17 [cited 2026May6];27(1):44-50. Available from: https://zmj.zsmu.edu.ua/article/view/313844

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Vol. 27 No. 1 (2025)

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Original research

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