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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Material and method
 ::  Results
 ::  Discussion
 ::  References

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Year : 1991  |  Volume : 37  |  Issue : 2  |  Page : 79-83

Total and free thyroid hormone levels in chronic renal failure.

Department of Nephrology, K. E. M. Hospital, Bombay, Maharashtra.

Correspondence Address:
Department of Nephrology, K. E. M. Hospital, Bombay, Maharashtra.

  ::  Abstract

The levels of serum total thyroxine (TT4), triiodothyronine (TT3), free T3, (FT3) free T4 (FT4) and thyrotropin (TSH) were measured in 127 clinically euthyroid patients with varying grades of chronic renal failure (CRF); and 97 healthy individuals. They were grouped as: Group I containing 93 patients on conservative management; Group II containing 34 patients on regular dialysis therapy; and Group III (normals). Group I patients showed significant decrease in TT3, TT4 and FT3 levels (p less than 0.001) as compared to Group III, whereas FT4 and TSH values in group I were not significantly altered. TT3, TT4 and FT3 levels reduced as the severity of renal damage increased. Variations in TT3, TT4, FT3, FT4 and TSH levels in Group II patients were similar to those in Group I, except for a decrease in TSH levels (p less than 0.05) as compared to normals. Several thyroid function tests are abnormal in CRF patients, however, finding of normal FT4 and TSH levels would indicate functional euthyroid status.

How to cite this article:
Mehta H J, Joseph L J, Desai K B, Mehta M N, Samuel A M, Almeida A F, Acharya V N. Total and free thyroid hormone levels in chronic renal failure. J Postgrad Med 1991;37:79-83

How to cite this URL:
Mehta H J, Joseph L J, Desai K B, Mehta M N, Samuel A M, Almeida A F, Acharya V N. Total and free thyroid hormone levels in chronic renal failure. J Postgrad Med [serial online] 1991 [cited 2023 May 31];37:79-83. Available from:

  ::   Introduction Top

Patients with end stage renal disease display a variety of endocrine disturbances. However, the evidence of endocrine dysfunction commonly consists only of laboratory abnormalities, many of which are not associated with apparent disease[7].
Thyroid function has been extensively evaluated in patients with chronic renal failure (CRF); however the results are variable. A major contribution in this field is by Ramirez and associates, who reported upto 58% prevalence of goitre in their patients on chronic haemodialysis as compared to 8% in control cases from the same geographic area[15]. Recently, Quion-Verde et al have also reported a higher prevalence (5%) of hypothyroidism in patients with terminal renal failure in comparison with that in hospitalised patients with normal renal function (0.6%)[12].
A few reports have appeared from India, where various parameters of thyroid function were measured in patients with CRF[3],[6],[10]. In order to gain further insight, this study included measuring the free thyroid hormone levels, not assayed in previous Indian studies.

  ::   Material and method Top

One hundred and twenty seven patients with no previous history of thyroid dysfunction, and with varying grades of CRF were included in this study. Ninety-three patients were on conservative treatment (Group I) and were subdivided according to the severity of renal dysfunction[1]: Group I (a): Mild (serum creatinine value 13-2.9 mg/dl) (n = 34); Group I (b): Moderate (serum creatinine value 3.0-4.9 mg/dl) (n = 36); and Group 1(c): Severe (serum creatinine value ? 5 mg/dl) (n = 23). Remaining 34 patients who also had severe renal failure were on regular haemodialysis treatment (RDT) while awaiting a live related donor renal transplantation (Group II).
The treatment included iron salts, vitamins, aluminium hydroxide (as phosphate binder) and furesamide (40-160 mg/day) when indicated; and anti-hypertensive agents as required viz. alphamethyl dopa, calcium channel blockers, hydrallazine, clonidine and atenolol. Patients were not given any medications except for furesamide given in small doses, which are known to influence the thyroid functions.
Patients underwent haemodialysis (HD) each of 4 hours duration; thrice a week, on a disposable capillary hollow fibre dialyzer, with heparin as anticoagulant during HD. Estimations of serum total triiodothyronine (TT3), total thyroxine (TT4): and thyrotropin (TSH) were performed by RIA (kits from BARC, Mumbai). Free triidodthyronine (FT3) and free thyroxine (FT4) concentrations in the serum were measured by the method of Romelli et al[16], as modified by Rajan and Samuel [13]. Results obtained in patients with CRF were compared with those in 97 normal cuthyroid individuals (Group III). Statistical analysis was done using student's unpaired 't' test, p value < 0.05 was taken as significant.

  ::   Results Top

The results are shown in [Table - 1]. All patients were clinically euthyroid and non goiterous. Ninety-three patients on conservative treatment showed significant reduction in their TT3, TT4 and FT3 levels in comparison with those in normal subjects. However, TSH and FT4 levels did not show significant alterations. Mean TT3, TT4 and FT3 levels reduced as the severity of renal damage increased, showing significant difference between Group I (b) and Group I (c). Though TSH levels were lower in Group I as compared to normal, significant difference was observed between Group I (a) and I (b).
Though TT3 and FT3 levels were found to be reducing as the severity of renal damage progressed (Groups Ia, b, c), when individual values of TT3 and FT3 were plotted against their respective serum creatinine levels, no linear co-relationship was observed between these parameters.
Variations in TT3, FT3, TT4, FT4 and TSH levels in Group II patients were more or less similar to those in Group I, except for TSH levels which were slightly but significantly altered as compared to normal subjects (p).

  ::   Discussion Top

Two individual observations encouraged us to measure various parameters of thyroid function in our patient population with CRE One was by Ramirez and associates [14] (vide supra) and the other was by Ganatra et al[4], who conducted a goitre survey in school going children of Mumbai, thereby revealing mild dietary iodine deficiency and prevalence of goitre of varying grades[4].
Our previous investigations[3] in these regards had revealed that goitre was rare in CRF patients and all of them were clinically euthyroid. It also showed that TT3 and TT4 levels were lower than normal at all grades of CRF and a progressive reduction in values of TT3 and TT4 were noticed as the severity of renal failure increased. TSH levels were however, within normal limits. Since abnormalities were noted in various parameters of thyroid function in association with euthyroid state of these patients, the present study was designed for confirming our previous conclusions and for studying the FT3 and FT4 levels at the same time.
Several investigators have studied thyroid hormone levels in CRF and obtained variable results. Low TT3[2],[8],[14],[17] normal TT3[14] low FT3[2],[17] normal FT3 in patients on HD [11], low TT4 (low T4 syndrome),11 normal TT4[8],[14],[15] and low normal or lower IFT48,11 levels have been reported. Basal concentrations of circulating TSH have been found at different levels in different studies. Normal levels or TSH were reported from previous Indian studies[3],[6],[10]. Thus a multitude of defects at all levels of hypothalamic-pituitary-thyroidaloeripheral axis does seem to exist in uremia[9].
In the majority of studies, including the present one, TT4 concentrations were found to be low or low normal. However, FT4 levels were within normal limits. This is attributed to lowering of thyroxine binding globulin concentration as well as presence of inhibitors of thyroid hormone bindings to the thyroid binding proteins[19]. Levels of TT3 and FT3 suffer further reductions in CRF, which is thought to be due to impairment in deiodination of T4, a principal process by which T3 is produced at peripheral levels.
Several factors are responsible for obtaining controversial results of thyroid hormone levels in CRE. The important amongst them are heterogenity of patient groups studied, methodological variations and varying treatment[9]. There have been speculations on the nature of the presumptive inhibitors in uremia patients, and drugs have been accounted for low T3 and T4 levels[5]. In the present study, the drugs which could have influenced the thyroid hormone levels were furesamide and heparin. Other commonly used drugs known to supress thyroid hormones like propranolol, glucocorticoids, sulphonylurea, dilantin and phenobarbitones were not given to any of the patients.
As heparin is known to acutely raise both total and free thyroxine levels in the blood, the samples for thyroid hormones estimation were drawn immediately before heparin administration[11]. Furesamide inhibits T4 and T3 binding to serum proteins at high levels and by a concentration dependent process resulting in artifactually low, percent FT4 and estimated FT4 concentrations. 18 However, the dose of furesamide administered in this study was insufficient to influence FT4 levels.
In conclusion, our results indicated low TT3, FT3 and TT4 values in clinically euthyroid CRF patients.
However, finding of normal FT4 values (which is metabolically active fraction) and TSH would indicate functional euthyroid status. It can be presumed that FT4 values would fall, if these patients develop hypothyroidism, and TSH values would rise simultaneously. Thus, FT4 and TSH levels combined can be used for the diagnosis of hypothyroidism in presence of CRE

  ::   References Top

1. Anderson RJ, Schrier RW. Clinical spectrum of oliguric and non-oliguric acute renal failure. In: "Acute renal failure" (Contemporary issues in Nephrology. Vol. 67). Brenner BM, Stein JH, editors. New York: Churchill Livingstone; 1980.  Back to cited text no. 1    
2.Chopra IJ, Chopra U, Smith, SR, Reza M, Solomen DH. Reciprocal changes in serum concentrations of 3, 3, 5 triiodothyronine (reverse T3) and 3, 3, 5 triiodothyronine (T3) in systemic illnesses. J Clin Endocrinol Met 1975; 41:1043-1049.  Back to cited text no. 2    
3.Dudani RA, Desai KB, Mehta MN, Mani LS, Acharya VN. Thyroid dysfunction in uremia. J Assoc Phys India 1981; 29: 1038-1040.  Back to cited text no. 3    
4.Ganatra RD, Sharma SM, DaCosta H, Samuel AM, Atmaram SH, Mehta MN, Patel MC, Bagwe BA, Mani LS, Mandlik MY, Shah DH, et al. Goitre Survey in the school children of Mumbai Proc. 4th Annual Conference of Society of Nuclear Medicine.India, Abstract 1972, pp 27.  Back to cited text no. 4    
5.Kaplan MM: Clinical and laboratory assessment of thyroid abnormality. Med Clin N Amer 1985; 69: 863-880.  Back to cited text no. 5    
6.Karunanidhi A, Kanagasabapathy AS, Shastry JCM, Koshi TS. Thyroid function in patients with chronic renal failure. Ind J Med Res 1979; 69:792-797.  Back to cited text no. 6    
7.Knochell JP. Endocrine changes in patients on chronic dialysis. In: "Replacement of function by dialysis". W Drukker, FM Parsons, JF Maher, editors. 2nd Edition. Boston: Martinus Nijhoff Publishers; 1983, pp 712-723.  Back to cited text no. 7    
8.Lim VS, Fang VS, Katz AI, Refetoff S. Thyroid dysfunction in chronic renal failure. A study of the pituitary thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine. J Clin Invest 1977; 60:522-534.  Back to cited text no. 8    
9.Mujais SK, Sanitini S, Kurtzman NA. Pathophysiology of uremic syndrome. In: "The Kidney", BM Brenner, FC Rector, editors. 3rd Edition. Philadelphia: WB Saunders Company; 1986, pp 1587-1630.  Back to cited text no. 9    
10.Neela P, Karunanidhi A, Kanagasabapathy AS, John L, Shastry JCM. Raised reverse thiodothyronine in patients with chronic renal failure. Indian J Med Res 1981; 73:240- 245.  Back to cited text no. 10    
11.Pagliacci MC, Pelicei G, Grigani, F, Giammartino C, Fedeli L, Carobi C, Buoncristiani U, Nicoletti I, et al. Thyroid function tests in patients undergoing maintenance dialysis: Characterisation of 'Low T4 Syndrome' in subjects on regular haemodialysis and continuous ambulatory peritoneal dialysis. Nephron 1987; 46:225-230.  Back to cited text no. 11    
12.Quion-Verde H, Kaptein EM, Chooljian CJ, Rodriquez HJ, Massary SG. Prevalence of thyroid disease in chronic renal failure (CRF) and dialysis patients. Los Angeles: IXth Int Congr of Nephrol; Abstract No: 120, 1984.  Back to cited text no. 12    
13.Rajan MGR, Samuel AM. Adopting the total triiodothyronine (T3) radioimmunoassay kit to measure serum free T3: Indian J Med Res 1988; 87:179-185, .  Back to cited text no. 13    
14.Ramirez G, Jubiz W, Gutch C, Bloomer HA, Segler R, Kolft WJ. Thyroid abnormalities in renal failure: A study of 53 patients on chronic hemodialysis. Annals of Int Med 1973; 19:500.  Back to cited text no. 14    
15.Ramirez G, O'Neill W, Jubiz W, Bloomer HA. Thyroid dysfunction in uremia: Evidence for thyroid and hypophyseal abnormalities. Ann Intern Med 1976; 84:672-676.  Back to cited text no. 15    
16.Romelli PB, Pennisi F, Vancheri L. Measurement of free thyroid hormones in serum by column adsorption chromatography and radioimmunoassay. J Endocrinol Invest 1979; 2:25-40.  Back to cited text no. 16    
17.Savdie E, Stewart JH, Mahony JF, Hayes JM, Lazarus L, Simons LA, et al. Circulating thyroid hormone levels and adequacy of dialysis. Clin Nephrol 1978; 9:68-72.  Back to cited text no. 17    
18.Stockigt JR, Lim FF, Barlow JW, Stevens V, Topliss DJ, Wynne KN, et al. High concentrations of furesamide inhibit serum binding of thyroxine. J Clin Endocrinol Metab 1984; 59:62-66.  Back to cited text no. 18    
19.Tibaldi JM, Surks MI. Effects of non-thyroidal illness on thyroid function. Med Clin N Amer 1985; 69:899-911.   Back to cited text no. 19    

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