Key findings:

Key findings from the study on the correlation between hematological parameters and thyroid hormones in anemic hemodialysis patients include: significant positive correlations between hemoglobin, red blood cell count, hematocrit, and FT3; significantly decreased levels of FT4 and FT3 in anemic patients compared to healthy controls; and no significant effect on TSH levels.

What is known and what is new?

The known aspect in this abstract is the association between anemia and thyroid dysfunction in renal failure patients. The new contribution is the investigation of specific correlations among hematological parameters and thyroid hormone concentrations in anemic patients undergoing hemodialysis, shedding light on the potential impact of anemia on thyroid gland hormone status in this population.

What is the implication, and what should change now?

The implication of this study on anemia and thyroid dysfunction in hemodialysis patients suggests the need for routine monitoring of thyroid hormones in this population. Changes needed include incorporating thyroid function tests in the management of anemia in hemodialysis patients to identify and address potential thyroid dysfunction, which may impact overall health outcomes.

Anemia commonly complicates renal failure, especially chronic one, when their glomerular filtration rate (GFR) drops below 60 ml/min. [1,2]. 

The primary cause of anemia is the reduced erythropoietin (EPO) insufficiency, which reflects decreased number of cells responsible for EPO-production. In CRF patients, EPO levels remain low despite anemia, unlike in patients with normal GFR [3]. Recent findings highlight iron deficiency as a significant contributor to persistent anemia in patients on maintenance dialysis and in those unresponsive to EPO treatment. Consequently, recent guidelines have emphasized the importance of iron management in anemic patients [4,5].

Most patients with chronic renal failure (CRF) also experience iron deficiency due to chronic loss of blood caused which may be due to many factors, including platelet dysfunction, coagulation systems abnormalities, gastrointestinal bleeding from uremic gastroenteritis, and frequent sampling  withdrawals for tests [6]. Patients with disturbed renal function often suffer from anorexia and malnutrition, and their ability for iron absorption may be further compromised by disturbances of   gastric pH from frequent use of H2 antagonist, exacerbating reduction of iron [6]. Additionally, deficiencies in other factors like folate and vitamin B12 can worsen the condition [7].

Iron has an important role for the first steps in thyroid hormone synthesis, which requires the incorporation of iodine into the tyrosine part of thyroglobulin, a process aided by iron-containing thyroperoxidase. On the other hand, other iron-dependent enzymes, such as cytochrome C, myeloperoxidase, and succinate dehydrogenase, are also severely sensitive to reduction in iron. So Severe iron deficiency can thus disturb thyroid hormone synthesis [8]. Tomoda et al. found that treating anemia patient undergoing hemodialysis with recombinant human erythropoietin (Rh EPO) improved the function of the hypothalamic-pituitary-thyroid endocrine axis and serum thyroid hormone levels [9]. The aim of this study was to investigate the correlation among various hematological parameters with thyroid hormone concentration in anemic patients undergoing hemodialysis.

This study included 40 control individuals and 40 patients with end-stage renal disease (24 males and 16 females) undergoing regular hemodialysis at Baqubah Teaching Hospital. The participants ranged in age from 20 to 70 years. A comprehensive clinical evaluation, including medical history and physical examinations, was conducted for all patients, and those with no previous history of thyroid disorders were included in the study. 

Venous sampling were taken pre heparin administration and hemodialysis and forty individual healthy control group .Red Blood Cells, Hemoglobin, Hematocrit Were measured using an automated cell hematology counter (ABX-HORIBA) , ft3, fT4, and TSH  were assessed using radioimmunoassay techniques with a VIDAS instrument and hormone kits provided by BIOMERIEUX.

Statistics 

Data were collected for samples study and statistically analyzed using system (SPSS 14) system of Windows (SPSS, Chicago, Illinois and USA) as linked some variables with each in the form of correlation coefficient linear (Linear correlation coefficient) was measured bond strength through coefficient Pearson Alazumito link to (Person's moment correlation) and also confirmed the availability of linear correlation between two variables been linked since the presence of the link between any two variables does not mean that a two variables cause in the presence of other variable so it was a test (significance correlation coefficient significance of correlation coefficient level of significance P <0.05). 

The results of the current study , based on an analysis of 40 patients with end-stage renal failure (24 males, 16 females), which showed  reduction in the serum levels of fT3 and fT4 in patients compared to the control group  and this reduction were statistically significant (P < 0.001). Another hand the mean serum TSH levels in patients were slightly higher than in the control group, the difference was statistically not significant as shown in table 1 below.

              Table ( 1 ), fT4, fT3 and TSH in patients and control group

*P < 0.05 ,**P < 0.01 ,*** P < 0.001       

Regarding hematological parameters, The mean of these parameters in hemodialysis patients showed a decrease in the mean value of Hb (8.735 g/ dl), HCT (27.850 %), RBC (3.033 10⁶/ml) in comparison with control individuals. as shown in table 2 below.

Table (2).  Hematological parameters in patients and control group 

Using the Pearson Correlation between hematological parameters and thyroid hormones, There were a significant association between serum free T3 with Hb and RBC (r=0.594 p<0.000),       (r= 0.466 p<0.002), (r= 0.395 p<0.01),    (r=0.322 p<0.04) respectively .

 as shown in table 3 below. 

Table (3) Pearson Correlation among hematological parameters and thyroid hormones of hemodialysis patients. 

Normal thyroid function depends on various trace components necessary for the production and metabolism of thyroid gland hormones, iodine being the most crucial as it is an element of thyroxine (T4) and triiodothyronine (T3). 

In this study, free thyroid hormone concentrations are found to decrease in patients with impaired renal function, and this result was consistent with results of previous research findings.  

The low levels of free T4 (fT4) in these patients may be due to impaired T4 binding to carrier proteins. Various inhibitors of T4 binding present in patients with chronic renal failure contribute to these decreased levels [17,18.19]. The current study also found a significant reduction in serum free T3 (fT3) concentration in CRF patients group in comparison to the healthy group (p<0.001), corroborating previous studies   . Decrease in total T3 levels may result from increased urinary excretion of bound and free T4 or a disturb in the peripheral conversion of T4 to T3 [20.21.22].

Additionally, my study found significant correlations between hemoglobin (Hb) and fT3 (r= 0.466, p<0.002), red blood cells (RBC) and fT3 (r=0.322, p<0.04), and hematocrit (HCT) and fT3 (r=0.344, p<0.03).  Significant reduction in iron may affect thyroid peroxidase activity, thereby interfering with thyroid hormone synthesis.  Which Begins with two steps catalyzed by heme-containing thyroid peroxidase. Hess et al. found that iron deficiency anemia significantly reduces thyroid peroxidase activity, which impairs conversion of T4 to T3 and affects the TSH response to thyroid releasing hormone (TRH) [22,23]  .

Tomoda et al. study the impact of anemia on thyroid function in patient undergoing  chronic hemodialysis (HD) due to chronic renal failure , showing that treatment with recombinant human erythropoietin (rhEPO) significantly increased thyroid hormone levels in patients whose hematocrit increased by more than 5%. No significant hormone increase was observed in patients with less than a 5% hematocrit increase, but a significant correlation between hematocrit and fT3 was found in all subjects [9]. According to Dabaganesha et al.  Patients suffering from iron deficiency had higher TSH level and lower fT4 levels in comparison to those with normal serum ferritin [15].

1. Tong, Eric M., and Allen R. Nissenson. "Erythropoietin and anemia." Seminars in nephrology. Vol. 21. No. 2. Elsevier, 2001. https://doi.org/10.1053/snep.2001.20939 
2. Yamanouchi, Masayuki, et al. "Serum hemoglobin concentration and risk of renal function decline in early stages of diabetic kidney disease: a nationwide, biopsy-based cohort study." Nephrology Dialysis Transplantation 37.3 (2022): 489-497. https://doi.org/10.1093/ndt/gfab185 
3. Miyauchi, Kenichiro, et al. "Renal interstitial fibroblasts coproduce erythropoietin and renin under anaemic conditions." EBioMedicine 64 (2021). https://doi.org/10.1016/j.ebiom.2021.103209 
4. NKF-DOQI Clinical practice guidelines for anemia of chronic kidney disease. Update 2000. Am J Kidney Dis (2001);37(Suppl 1): S182-238.
5. Alzoubi, Beyann, et al. "Post-transplant erythrocytosis after kidney transplantation: A review." World Journal of Transplantation 11.6 (2021): 220. https://doi.org/10.5500%2Fwjt.v11.i6.220 
6. Tarif, N., Mitwalli, A. H., Alwakeel, J. S., et al. "Intravenous Bolus Ferrous Saccharate Administration in Hemodialysis Patients." JASN, (2001), Abstract.
7. Weir, Matthew R. "Managing anemia across the stages of kidney disease in those hyporesponsive to erythropoiesis-stimulating agents." American Journal of Nephrology 52.6 (2021): 450-466. https://doi.org/10.1159/000516901 
8. van der Reijden, Olivia L., et al. "Iodine bioavailability from cow milk: a randomized, crossover balance study in healthy iodine-replete adults." The American journal of clinical nutrition 110.1 (2019): 102-110. https://doi.org/10.1093/ajcn/nqz092 
9. Tomoda, Fumihiro, et al. "Effects of erythropoietin treatment on thyroid dysfunction in hemodialysis patients with renal anemia." Nephron 66.3 (1994): 307-311. https://doi.org/10.1159/000187828 
10. Galton, Valerie Anne, and Arturo Hernandez. "Thyroid hormone metabolism: a historical perspective." Thyroid 33.1 (2023): 24-31. https://doi.org/10.1089/thy.2022.0161 

11. Mohammed, Abdullah Watman, and Zrar Saleem Kareem. "Diagnosis and Differentiation of Hypochromic Microcytic Anemia among Elementary School Children in Ranya District." Journal of Advanced Laboratory Research in Biology (2021)

    . https://www.academia.edu/download/84451950/diagnosis_and_differentiation_of_hypochromic_microcytic_anemia_among_primary_school_pupils_in_ranya_district.pdf 

12. Sari, Puspa, et al. "Iron Deficiency anemia and associated factors among adolescent girls and women in a rural area of Jatinangor, Indonesia." International Journal of Women's Health (2022): 1137-1147. https://www.tandfonline.com/doi/abs/10.2147/IJWH.S376023 
13. Hess, Sonja Y., et al. "Iron deficiency anemia reduces thyroid peroxidase activity in rats." The Journal of nutrition 132.7 (2002): 1951-1955. https://doi.org/10.1093/jn/132.7.1951 
14. Tang, F., T. M. Wong, and T. T. Loh. "Effects of cold exposure or TRH on the serum TSH levels in the iron-deficient rat." Hormone and Metabolic Research 20.10 (1988): 616-619. DOI: 10.1055/s-2007-1010899 
15. DABAGHMANESH, MH, et al. "The role of iron deficiency in persistent goiter." (2008): 157-161. https://www.sid.ir/EN/VEWSSID/J_pdf/86920080205.pdf 
16. Palmer, Biff F. "Metabolic disturbances in chronic renal failure." Saudi Journal of Kidney Diseases and Transplantation 13.3 (2002): 273-280. https://journals.lww.com/sjkd/fulltext/2002/13030/metabolic_disturbances_in_chronic_renal_failure.5.aspx 
17. Luongo, C., et al. "Higher baseline TSH levels predict early hypothyroidism during cancer immunotherapy." Journal of Endocrinological Investigation 44 (2021): 1927-1933. https://link.springer.com/article/10.1007/s40618-021-01508-5 
18. Sen, Saniye, Gülay Durmuş Altun, Şükran Çiftçi, Funda Üstün, and Şakir Berkarda. "Alteration of Thyroid Functional and Morphology in Patients Undergoing Regular Hemodialysis and Continuous Ambulatory Peritoneal Dialysis." Turk Nefroloji Diyaliz ve Transplantasyon Dergisi: Official Journal of the Turkish Nephrology Association, vol. 3, (2000).
19. Malyszko, Jolanta, et al. "Adiponectin, leptin and thyroid hormones in patients with chronic renal failure and on renal replacement therapy: are they related?." Nephrology Dialysis Transplantation 21.1 (2006): 145-152. https://doi.org/10.1093/ndt/gfi081 
20. Ali, Layla K. "The Effect of Chronic Renal Failure on Thyroid Hormones." Iraqi Journal of Pharmaceutical Sciences (P-ISSN 1683-3597 E-ISSN 2521-3512) 19.1 (2010): 65-68. https://doi.org/10.31351/vol19iss1pp65-68 
21. Rotondi, Mario, et al. "Pretransplant serum FT3 levels in kidney graft recipients are useful for identifying patients with higher risk for graft failure." Clinical Endocrinology 68.2 (2008): 220-225. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2265.2007.03022.x 

22. Jusufovic, Selma, Emir Hodzic, and Alma Halilcevic. "Role of renal anemia in the functional, morphological and autoimmune thyroid disorders in patients on chronic hemodialysis." Medical Archives 65.4 (2011): 228. https://www.researchgate.net/profile/Alma-Halilcevic/publication/51676358_Role_of_Renal_Anemia_in_the_Functional_

    Morphological_and_Autoimmune_Thyroid_Disorders_in_patients_on_Chronic_Hemodialysis/links/5def66ca299bf10bc34ecf25/Role-of-Renal-Anemia-in-the-Functional-Morphological-and-Autoimmune-Thyroid-Disorders-in-patients-on-Chronic-Hemodialysis.pdf 

23. AL-Mahdawi, Fatimah Kadhim Ibrahim, Noor Nayyef Oudah, and Mazin Razooqi Mohammed. "Common hemoglobinopathies for couples premarital individual and its influence on hemostasis and immune state." Medico-legal Update 21.2 (2021): 529. https://www.researchgate.net/profile/Noor-No/publication/350373648_Common_Hemoglobinopathies_for_Couples_Premarital_Individual_and_its_Influence

    _on_Hemostasis_and_Immune_State/links/605c4f2ba6fdccbfea04b81f/Common-Hemoglobinopathies-for-Couples-Premarital-Individual-and-its-Influence-on-Hemostasis-and-Immune-State.pdf