Background: The thyroid gland secretes hormones crucial for growth, differentiation, regulation of metabolic processes, and homeostasis. In response to underactivity of this gland, the pituitary secretes thyrotropin, also known as the thyroid-stimulating hormone (TSH). Medication for thyroid hypofunction is usually started when TSH levels exceed 10 mIU/L. However, we hypothesize that TSH levels much below this therapeutic threshold level may herald significant renal and hepatic dysfunction. The present study was thus conducted to assess liver and kidney function parameters in cases having TSH in the subclinical range with particular focus on the therapeutically neglected (6.5–8 mIU/L) range.

Methods: Hospital laboratory archives of 297 adults with laboratory evidence of hypothyroidism, that is, TSH > 6.5 mIU/L, were retrieved and compared with data obtained from 430 euthyroid hospital controls, that is, TSH < 2.5 mIU/L, also from the same period. The thyroid profile and clinical chemistry analyses were performed on Beckman Coulter’s UniCel DxI 800 and AU 5800, respectively. SPSS version 20 was used to analyze the results.

Results: Significant differences in triiodothyronine (T3), thyroxine (T4), TSH, urea, creatinine, total bilirubin, total protein (TP), and liver enzymes were observed between cases with TSH > 6.5 mIU/L and controls (P < 0.05). There was also a significant difference in T4, TSH, urea, creatinine, total bilirubin, albumin and aspartate aminotransferase (AST) among cases with TSH in the range of 6.5–8 mIU/L when compared with controls (P < 0.05). A correlation of T3 with TSH, urea, and creatinine was seen (P < 0.05). No correlations between TSH and other clinical chemistry parameters could be observed. However, in the 6.5–8 mIU/L subgroup, correlation of TSH was seen with TP and albumin only.

Conclusion: Authors found that, as a rule, subtle renal and hepatic dysfunction were established in cases with TSH levels <8 mIU/L, which was below the typical “therapeutic cut-off” of 10 mIU/L. Accordingly, we advocate against incautiousness and suggest regular monitoring, especially in the 6.5–8 mIU/L range.

subclinical hypothyroidism, liver function test, kidney function test, thyroidstimulating hormone

[1] Brix, K., Szumska, J., Weber, J., et al. (2020). Auto-regulation of the thyroid gland beyond classical pathways. Experimental and Clinical Endocrinology & Diabetes, vol. 128, no. 6–7, pp, 437–445.

[2] Damiano, F., Rochira, A., Gnoni, A., et al. (2017). Action of thyroid hormones, T3 and T2, on hepatic fatty acids: Differences in metabolic effects and molecular mechanisms. International Journal of Molecular Sciences, vol. 18, no. 744, pp. 1– 19.

[3] Iglesias, P., Bajo, M. A., Selgas, R., et al. (2017). Thyroid dysfunction and kidney disease: An update. Reviews in Endocrine and Metabolic Disorders, vol. 18, p. 131– 144.

[4] Liu, L., Li, P., Mi, Y., et al. (2019). Thyroid-stimulating hormone is associated with nonalcoholic steatohepatitis in patients with chronic hepatitis B. Medicine, vol. 98, no. 46, pp. 1–5.

[5] Fuhrer, D., Brix, K., and Bibermann, H. (2015). Understanding the healthy thyroid state in 2015. European Thyroid Journal, vol. 4, no. 1, pp. 1–8.

[6] Unnikrishnan, A. G. (2020). Thyroid disorders: A South Asian perspective. In S. Melmed, R. J. Auchus, A. B. Goldfine, R. J. Koenig, C. J. Rosen (Eds.), Williams textbook of endocrinology (pp. 1731–1733). New Delhi, India: Elsevier Inc.

[7] Melville, N. A. (2021, June 24). Levothyroxine overprescribing is common, consistent over time. Medscape. Retrieved from: https://www.medscape.com/viewarticle/953652

[8] Surks, M. I., Ortiz, E., Daniels, G. H., et al. (2004). Subclinical thyroid disease: Scientific review and guidelines for diagnosis and management. JAMA, vol. 291, no. 2, pp. 228–238.

[9] Almandoz, J. P. and Gharib, H. (2012). Hypothyroidism: etiology, diagnosis, and management. Medical Clinics of North America, vol. 96, pp. 203–221.

[10] Calissendorff, J. and Falhammar, H. (2020). To treat or not to treat subclinical hypothyroidism. What is the evidence? Medicina, vol. 56, no. 40, pp. 1–11.

[11] Cohen, B. M., Sommer, B. R., and Vuckovic, A. (2018). Antidepressant-resistant depression in patients with comorbid subclinical hypothyroidism or high-normal TSH levels. The American Journal of Psychiatry, vol. 175, no. 7, pp. 598–604.

[12] Jokar, T. O., Fourman, L. T., Lee, H., et al. (2018). Higher TSH Levels within the normal range are associated with unexplained infertility. The Journal of Clinical Endocrinology and Metabolism, vol. 103, no. 2, pp. 632–639.

[13] Chang, Y., Hua, S., Chang, C., et al. (2019). High TSH level within normal range is associated with obesity, dyslipidemia, hypertension, inflammation, hypercoagulability, and the metabolic syndrome: A novel cardiometabolic marker. Journal of Clinical Medicine, vol. 8, no. 817, pp. 1–15.

[14] Bulur, O., Dal, K., Ertugrul, D. T., et al. (2017). Renal function improves with the treatment of hypothyroidism. Endocrine Research, vol. 42, no. 3, pp. 246–251.

[15] Gomez, I. R., Banegas, I., Wangensteen, R., et al. (2013). Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats. Journal of Endocrinology, vol. 216, no. 1, pp. 43–51.

[16] Ichihara, A., Kobori, H., Miyashita, Y., et al. (1998). Differential effects of thyroid hormone on renin secretion, content, and mRNA in juxtaglomerular cells. American Journal of Physiology, vol. 274, no. 2, pp. E224–E231.

[17] Saini, V., Yadav, A., Arora, M. K., et al. (2012). Correlation of creatinine with TSH levels in overt hypothyroidism — A requirement for monitoring of renal function in hypothyroid patients ? Clinical Biochemistry, vol. 45, no. 3, pp. 212–214.

[18] Belasco, I. J. (1941). The effect of thyroxin and thyrotropic hormone on liver and kidney tissue respiration of rats of various ages. Endocrinology, vol. 28, no. 2, pp. 153–160.

[19] Lamberg, B. and Grasbeck, R. (1955). The serum protein pattern in disorders of thyroid function. European Journal of Endocrinology, vol. 19, no. 1, pp. 91–100.

[20] Finamore, F. J. and Frieden, E. (1960). Nucleic acids and induced amphibian metamorphosis. Journal of Biological Chemistry, vol. 235, no. 6, pp. 1751–1755.

[21] Tata, J. R. (1966). In vivo synthesis of nuclear protein during growth of the liver induced by hormones. Nature, vol. 212, no. 5068, pp. 1312–1314.

[22] Menahan, L. A. and Wieland, O. (1969). The role of thyroid function in the metabolism of perfused rat liver with particular reference to gluconeogenesis. European Journal of Biochemistry, vol. 10, no. 1, pp. 188–194.

[23] Oppenheimer, J. H., Koerner, D., Schwartz, H. L., et al. (1972). Specific-nuclear Triiodothyronine binding sites in rat liver and kidney. The Journal of Clinical Endocrinology and Metabolism, vol. 35, no. 2, pp. 330–333.

[24] Oppenheimer, J. H. (1979). Thyroid hormone action at the cellular level. Science, vol. 203, no. 4384, pp. 971–979.

[25] Malik, R. and Hodgson, H. (2002). The relationship between the thyroid gland and the liver. QJM, vol. 95, no. 9, pp. 559–569.

[26] Arora, S., Chawla, R., Tayal, D., et al. (2009). Biochemical markers of liver and kidney function are influenced by thyroid function-a case-controlled follow up study in Indian hypothyroid subjects. Indian Journal of Clinical Biochemistry, vol. 24, no. 4, pp. 370– 374.

[27] Yadav, A., Arora, S., Saini, V., et al. (2013). Influence of thyroid hormones on biochemical parameters of liver function : A case-control study in North Indian population. Internet Journal of Medical Update, vol. 8, no. 1, pp. 4–8.

[28] Kim, H. J. (2020). Importance of thyroid-stimulating hormone levels in liver disease. Journal of Pediatric Endocrinology and Metabolism, vol. 33, no. 9, pp. 1133–1137.

[29] Schairer, B., Jungrethmayr, V., Schuster, M., et al. (2020). Effect of thyroid hormones on kidney function in patients after kidney transplantation. Scientific Reports, vol. 10, no. 2156, pp. 1–7.

[30] Shin, D. H., Lee, M. J., Lee, H. S., et al. (2013). Thyroid hormone replacement therapy attenuates the decline of renal function in chronic kidney disease patients with subclinical hypothyroidism. Thyroid, vol. 23, no. 6, pp. 654–661.

[31] Tsuda, A., Inaba, M., Ichii, M., et al. (2013). Relationship between serum TSH levels and intrarenal hemodynamic parameters in euthyroid subjects. European Journal of Endocrinology, vol. 169, no. 1, pp. 45–50.

[32] Kim, D., Kim, W., Joo, S. K., et al. (2018). Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis. Clinical Gastroenterology and Hepatology, vol. 16, no. 1, pp. 123–131.

[33] Duong, N., Lee, A., and Lewis, J. (2018). Case of acute mixed liver injury due to hypothyroidism. BMJ Case Reports, vol. 2018, bcr2017222373.

[34] Walsh, J. P. (2011). Setpoints and susceptibility: Do small differences in thyroid function really matter? Clinical Endocrinology, vol. 75, no. 2, pp. 158–159.