This article is mentioned in:

Introduction

Thyroid-stimulating hormone (TSH), produced by the anterior pituitary gland, plays a crucial role in regulating the thyroid hormones generated by the thyroid gland (1). On the other hand, creatinine is a waste product generated during muscle metabolism (2) and serves as a commonly used indicator of kidney function (3,4).

Hypothyroidism is often accompanied by a decrease in the glomerular filtration rate, resulting in the reduced clearance of creatinine from the bloodstream (5). This leads to significantly higher levels of creatinine due to decreased renal filtration and increased production from muscle breakdown.

Thyroid dysfunction, whether in the form of subclinical or overt thyroid disease, is recognized as a risk factor for chronic kidney disease due to its association with significant alterations in creatinine levels (6). Several studies have consistently demonstrated an association between serum TSH levels, the risk of developing hypothyroidism and renal function (7-9). TSH exerts a direct influence on the thyroid gland and has been found to affect kidney function, particularly concerning the creatinine levels. Studies have established an association between TSH and glycated albumin (10), as well as between TSH and serum creatinine levels (11), particularly among individuals diagnosed with hypothyroidism. In individuals with overt hypothyroidism and TSH levels ≥10.0 µIU/l, there is a marked increase in the serum levels of urea, creatinine and uric acid. Similarly, patients with subclinical hypothyroidism exhibit significantly higher serum levels of urea and creatinine (12). TSH demonstrates a significant association with serum creatinine levels in both overt and subclinical hypothyroidism cases (13).

Although there are a limited number of studies available on the impact of hypothyroidism on renal function, particularly as regards creatinine, a reversible elevation of serum creatinine has been observed following hormone substitution therapy in patients with hypothyroidism (14-17).

The aim of the present study was to examine and evaluate the association between serum TSH levels and alterations in the biochemical markers of renal function, specifically creatinine levels, among patients with hypothyroidism.

Patients and methods

Study design

The present study was a descriptive cross-sectional study conducted among a convenience sample of volunteers located in Tripoli, Libya.

Study setting

The present study was carried out by distributing questionnaires through personal interviews to facilitate completion by the patients. The cases were randomly selected from subjects attending the following outpatient clinics: Tripoli University Hospital, the Tripoli Center for Kidney Services, Al-Firdous Clinic in Tripoli, and Yashfin Specialized Clinic (all in Tripoli, Libya).

Ethical considerations

Ethical approval for conducting the study was obtained from the Higher Institute of Medical Sciences and Technology, Tripoli, Libya. Informed consent was obtained from individuals or legal guardians through an official document after submitting the study proposal, ensuring that participation was voluntary. Volunteers were also informed that their responses would be anonymous and confidential.

Sample size

The number of volunteers participating in the study was 120, representing the total number of individuals enrolled from November 7, 2022 to January 18, 2023.

Criteria of study groups

Patients with hypothyroidism, in the age group of 13-84 years of both sexes were included.

Study groups

The patients with hypothyroidism with biochemical measurements were divided into four groups according to their serum TSH level, as follows: Group 1, patients with a TSH level >4.00 µIU/l; group 2, patients with a TSH level <0.46 µIU/l; group 3, patients with a TSH level ranging from 0.60 to 2.8 µIU/l; and group 4, patients with a TSH level ranging from 2.94 to 3.60 µIU/l. The cases comprising the control group were randomly selected, and they did not have thyroid disorders or kidney disorders. The control group consisted of 30 participants who had normal levels of blood TSH (0.4-4.0 µIU/l) and creatinine (0.6-1.4 mg/dl).

Statistical analysis

Statistical analysis was conducted using IBM SPSS version 21 software (IBM Corp.). Descriptive procedures, including frequency, percentages, mean, and standard deviation (SD), were employed. Statistical tests such as the independent samples (unpaired) Student's t-test, and one-way ANOVA with Tukey's HSD post hoc test were utilized. Pearson's correlation coefficient was applied to examine the correlation between serum creatinine levels and the severity of hypothyroidism. A P-value <0.05 was considered to indicate a statistically significant difference, while a P-value <0.001 was considered to indicate a highly statistically significant difference.

Results

Selection of patients with hypothyroidism for analysis

Among the 90 patients diagnosed with hypothyroidism in the medical clinic, 74 patients were included in the biochemical parameters of the present study. These patients had serum TSH levels ranging from <0.4 to >4.0 µIU/l and serum creatinine levels from 0.6 to >1.4 mg/dl. The remaining 16 patients were undergoing hemodialysis and were excluded from the study.

Patient demographics

The present study found that, among the 74 participating patients with hypothyroidism, 28 patients were male and 46 patients were female. The male patients had a mean age of 46 years, while the female patients had a slightly older mean age of 49 years, indicating that hypothyroidism affects different age groups similarly across the sexes. There was no statistically significant difference in age between the two sex groups (P=0.322), indicating that hypothyroidism affects different age groups similarly across sexes (Table I).

Table I Demographic and baseline characteristics of the study participants.

Table I

Demographic and baseline characteristics of the study participants.

A, Differences in age, TSH and creatinine levels as regards sex
Parameter	Sex	No. of patients	Min	Max	Mean	SD	P-valuea
Age (years) of patients	Male	28	13.00	84.00	46.18	13.89	0.322
with hypothyroidism	Female	46	26.00	76.00	49.20	11.78
TSH (µIU/l) of patients	Male	28	0.39	8.46	3.10	1.93	0.566
with hypothyroidism	Female	46	0.02	8.50	2.81	2.19
Creatinine (mg/dl) of	Male	28	0.20	1.20	0.67	0.28	0.249
patients with hypothyroidism	Female	46	0.10	9.50	1.05	1.69
Sex	Males: 28 (37.84%)		Females: 46 (62.16%)			Ratio: 1:1.64
B, TSH levels as regards sex in each group
			TSH (µIU/l)
Group	Sex	No. of participants	%	Min	Max	Mean	SD
CG	Male	12	40.00	0.60	3.74	1.99	1.04
	Female	18	60.00	0.45	4.00	1.99	1.17
G1	Male	9	42.90	4.20	8.46	5.35	1.21
	Female	12	57.10	4.25	8.50	5.91	1.23
G2	Male	1	11.10	0.39	0.39	0.39	-
	Female	8	88.90	0.02	0.45	0.27	0.15
G3	Male	15	46.90	0.63	2.85	1.62	0.73
	Female	17	53.10	0.74	2.87	1.77	0.70
G4	Male	4	33.30	3.45	3.78	3.64	0.15
	Female	8	66.70	2.94	3.78	3.24	0.29
C, Creatinine levels as regards sex in each group
			Creatinine (mg/dl)
Group	Sex	No. of participants	%	Min	Max	Mean	SD
CG	Male	12	40.00	0.54	1.40	0.81	0.21
	Female	18	60.00	0.60	1.00	0.75	0.16
G1	Male	9	42.90	0.20	0.90	0.58	0.24
	Female	12	57.10	0.30	1.10	0.70	0.21
G2	Male	1	11.10	0.40	0.40	0.40	-
	Female	8	88.90	0.30	9.50	2.77	3.73
G3	Male	15	46.90	0.40	1.20	0.70	0.32
	Female	17	53.10	0.10	1.50	0.70	0.33
G4	Male	4	33.30	0.70	0.90	0.85	0.10
	Female	8	66.70	0.40	1.00	0.70	0.20
D, Age demographics of the participants in all groups
Age
Group	≤20 years	21-30 years	31-40 years	41-50 years	51-60 years	61-70 years	≥71 years
CG	0 (0%)	2 (6.70%)	10 (33.30%)	17 (56.70%)	1 (3.30%)	0 (0%)	0 (0%)
All patients with hypothyroidism	1 (1.35%)	3 (4.05%)	14 (18.92%)	28 (37.84)	20 (27.03)	4 (5.41%)	4 (5.41%)
G1	1 (4.80%)	0 (0%)	6 (28.60%)	9 (42.90%)	4 (19.00%)	1 (4.80%)	0 (0%)
G2	0 (0%)	1 (11.10%)	0 (0%)	1 (11.10%)	6 (66.70%)	0 (0%)	1 (11.10%)
G3	0 (0%)	2 (6.30%)	7 (21.90%)	12 (37.50%)	8 (25.00%)	2 (6.30%)	1 (3.10%)
G4	0 (0%)	0 (0%)	1 (8.30%)	6 (50.00%)	2 (16.70%)	1	2

[i] ^aComparisons of various parameters among the sex groups with hypothyroidism were performed using an independent samples unpaired Student's t-test to assess differences between the sexes. TSH, thyroid-stimulating hormone, CG, control groups; G1, group 1 (TSH >4.0 µIU/l); G2, group 2 (TSH <0.46 µIU/l); G3, group 3 (TSH 0.47 to 2.8 µIU/l); G4, group 4 (TSH 2.94 to 3.6 µIU/l).

The mean TSH levels for the males were recorded at 3 µIU/l, while the females had a mean TSH level of 2 µIU/l. No significant difference in TSH levels were observed between the sexes (P=0.566), suggesting that the severity of hypothyroidism, as measured using the TSH levels, was comparable across both sexes (Table I).

The male patients had a mean creatinine level of 0.67 mg/dl, while the female patients exhibited a higher mean level of 1.05 mg/dl. Again, there was no significant difference in creatinine levels between the sexes (P=0.249; Table I). This could point to a slight trend of higher kidney function markers in males. As shown in Table I, the findings indicated a slight increase in the mean TSH levels in males compared with females, while the creatinine levels were higher on average in the female than in the male patients.

Age of the participants with hypothyroidism

The study population, comprising individuals with hypothyroidism, was categorized into seven distinct age groups as follows: ≤20 years, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years and ≥71 years. Notably, the age group of 41 to 50 years exhibited a prominent presence among the collected samples. Furthermore, the mean age for the female participants was determined to be 49 years, while for the male participants, it was 46 years (Table I).

Biochemical parameters among the hypothyroidism groups and control group

The investigation revealed that group 1, consisting of individuals with TSH levels >4.0 µIU/l, demonstrated a lower mean creatinine value of 0.65 mg/dl compared with the control group (0.77 mg/dl). Conversely, group 2, comprising individuals with TSH levels <0.46 µIU/l, exhibited a notably higher mean creatinine value of 2.50 mg/dl. Group 3, representing individuals with TSH levels ranging from 0.47 to 2.8 µIU/l, displayed a mean creatinine value of 0.70 mg/dl, which was similar to that of the control group. Similarly, group 4, including individuals with TSH levels ranging from 2.94 to 3.6 µIU/l, exhibited a mean creatinine value of 0.75 mg/dl, which was close to that of the control group (Table II).

Table II Mean values of different parameters among patients with hypothyroidism and the controls.

Table II

Mean values of different parameters among patients with hypothyroidism and the controls.

Biochemical parameters	Group	No. of participants	Mean	SD	Comparison vs. group	P-value
TSH (µIU/l)	CG	30	1.98	1.10	G1	0.001a
					G2	0.001a
					G3	0.7286
					G4	0.001a
	G1	21	5.67	1.22	CG	0.001a
					G2	0.001a
					G3	0.001a
					G4	0.001a
	G2	9	0.28	0.15	CG	0.001a
					G1	0.001a
					G3	0.001a
					G4	0.001a
	G3	32	1.70	0.71	CG	0.7286
					G1	0.001a
					G2	0.001a
					G4	0.001a
	G4	12	3.37	0.31	CG	0.001a
					G1	0.001a
					G2	0.001a
					G3	0.001a
Creatinine (mg/dl)	CG	30	0.77	0.18	G1	0.9932
					G2	0.001a
					G3	0.9985
					G4	0.9998
	G1	21	0.65	0.22	CG	0.9932
					G2	0.001a
					G3	0.9998
					G4	0.9985
	G2	9	2.50	3.57	CG	0.001a
					G1	0.001a
					G3	0.001a
					G4	0.002b
	G3	32	0.70	0.32	CG	0.9985
					G1	0.9998
					G2	0.001a
					G4	0.9998
	G4	12	0.75	0.18	CG	0.9998
					G1	0.9985
					G2	0.002b
					G3	0.9998

[i] TSH, thyroid-stimulating hormone. CG: Control Groups, G1: Group 1 (TSH >4.0 µIU/l), G2: Group 2 (TSH <0.46 µIU/l), G3: Group 3 (TSH 0.47 to 2.8 µIU/l), G4: Group 4 (TSH 2.94 to 3.6 µIU/l). Comparisons of the various parameters among the groups were performed using one-way ANOVA (with Tukey's HSD test) (

[ii] ^aP<0.001, indicating a very highly significant difference,

[iii] ^bP<0.01, indicating a highly significant difference).

Correlation of the serum TSH and creatinine levels in the various groups

The present study examined the correlation between creatinine levels and TSH in individuals with hypothyroidism. The results presented in Table III provide comprehensive correlation coefficients (r) and corresponding P-values, illustrating the correlation between TSH and creatinine across the different groups. A rigorous Pearson's correlation analysis was performed to investigate the correlation between serum TSH and serum creatinine levels. The findings consistently revealed a statistically significant correlation (P<0.05) between these parameters in all groups, as described below:

Table III Correlation of TSH with creatinine levels in all groups.

Table III

Correlation of TSH with creatinine levels in all groups.

Groups	No. of participants	Creatinine (r)	P-value
Control groups	30	-0.367	0.046a
Group 1 (TSH > 4.0 µIU/l)	21	0.446	0.043a
Group 2 (TSH < 0.46 µIU/l)	9	-0.892	0.001c
Group 3 (TSH 0.47 to 2.8 µIU/l)	32	0.541	0.001c
Group 4 (TSH 2.94 to 3.7 µIU/l)	12	0.748	0.005b

[i] TSH, thyroid-stimulating hormone.

[ii] ^aIndicates significant correlation (P<0.05);

[iii] ^bindicates highly significant correlation (P<0.01).

[iv] ^cindicates very highly significant correlation (P<0.001).

Correlation between serum TSH and creatinine levels in the control group. In the present study, a negative correlation was observed between the serum TSH and creatinine levels in the control group, which included 30 participants without hypothyroidism (r=-0.367, P=0.046) (Table III).

Correlation between serum TSH and creatinine levels in patients with hypothyroidism in group 1. Group 1 consisted of 21 cases of hypothyroidism, including 12 females and 9 males, with TSH levels >4.0 µIU/l. Notably, the results revealed a positive correlation between the serum TSH and creatinine levels in this group (r=0.446, P=0.043) (Table III).

Correlation between serum TSH and creatinine levels in patients with hypothyroidism in group 2. The second group consisted of 9 cases of hypothyroidism, comprising 8 females and 1 male, with TSH levels <0.46 µIU/l. The analysis of creatinine levels in this patient cohort revealed a wide range, from 0.30 to 9.50 mg/dl. Of note, a significant negative correlation was observed between TSH levels and creatinine in this group (r=-0.892, P=0.001) (Table III).

Correlation between serum TSH and creatinine levels in patients with hypothyroidism in group 3. In group 3, which comprised 32 hypothyroidism patients (17 females and 15 males) with TSH levels ranging from 0.47 to 2.8 µIU/l and who were not undergoing hemodialysis, the analysis of creatinine levels revealed a range from 0.10 to 1.50 mg/dl. Of note, a positive correlation was observed between the TSH and creatinine levels, with a correlation coefficient of 0.541 (P=0.001) (Table III).

Correlation between serum TSH and creatinine levels in patients with hypothyroidism in group 4. In group 4, which included 12 individuals diagnosed with hypothyroidism (8 females and 4 males), TSH levels ranged from 2.94 to 3.78 µIU/l. The assessment of creatinine levels in this group revealed values spanning from 0.40 to 1.00 mg/dl. Notably, a significant positive correlation was observed between serum TSH levels and creatinine in this group (r=0.748, P=0.005) (Table III).

Discussion

The present study investigated the association between TSH levels and kidney function parameters in individuals with hypothyroidism and those without hypothyroidism or kidney disease. In terms of TSH levels, males exhibited higher mean values (3.10 µIU/l) compared to females (2.81 µIU/l), though this difference was not statistically significant. This finding is consistent with previous studies that reported higher mean TSH levels in males with hypothyroidism compared to females (18,19). Conversely, mean creatinine levels were lower in males (0.67 mg/dl) compared to females (1.05 mg/dl).

The prevalence of hypothyroidism in the present study was higher in females (62.16%) compared with males (37.84%), resulting in a male-to-female ratio of 1:1.64 as presented in Table IA. This ratio is lower than the previously reported ratio of 1:4.68(18).

The mean age of all the patients diagnosed with hypothyroidism in the present study was 48.05±12.62 years, closely aligning with the previously reported average age of 47±14.48 years (19). The highest incidence of hypothyroidism was observed in the age group of 41-50 years (37.84%), followed by the 51-60 years group (27.03%). By contrast, the <20 and 21-30 years age groups accounted for a smaller proportion of patients, of 1.35 and 4.05%, respectively. An alternate study reported a higher prevalence of hypothyroidism among individuals aged 21-30 (33.53%) and the 31-40 age group (24.96%) (18).

Several studies have explored the association between the serum TSH and creatinine levels in individuals with hypothyroidism (9,14,20-22). Table II presents the mean creatinine values in both the patients with hypothyroidism and the controls, highlighting the potential impact of hypothyroidism on renal function. The present study demonstrated a significant increase in mean serum creatinine levels in the patients with hypothyroidism in group 2 compared with the other groups. A statistically significant association between TSH and creatinine levels was observed (P<0.05), which is consistent with the findings from other studies (23-26).

In group 1, the lower mean creatinine levels with higher mean TSH levels suggest a potential association between severe hypothyroidism and decreased creatinine levels. By contrast, group 2, with significantly lower mean TSH levels and significantly higher mean creatinine levels, may indicate a potential kidney disorder. In group 3, where the TSH levels were within the normal range, no significant effect on creatinine levels was observed. For group 4, mild elevations were observed in mean TSH levels that may not substantially affect the mean creatinine levels. These findings are consistent with previous research (11,14,15,24,27-29).

Correlation analysis revealed that in the control group, increasing TSH levels within the normal range were associated with a decrease in creatinine levels. In Group 1, a positive correlation between TSH and creatinine levels was observed, indicating that higher TSH levels in cases of severe hypothyroidism are associated with elevated creatinine levels. This is consistent with previous studies (12,13,23,26).

Conversely, group 2 exhibited a strong negative correlation between TSH and creatinine levels, suggesting that lower TSH levels are linked to higher creatinine levels, indicating potential renal dysfunction, in accordance with previous studies (30,31). In group 3, a positive correlation between TSH and creatinine levels was observed, suggesting that TSH levels within the normal range may be associated with increased creatinine levels, in accordance with previous findings (32). Group 4 also demonstrated a positive correlation between TSH and creatinine levels, in accordance with previous findings (33), indicating that even slight elevations in TSH levels may be related to creatinine levels.

The present study highlights the significant impact of hypothyroidism on creatinine levels compared to healthy controls. These findings are consistent with those of previous studies that have reported significantly elevated serum creatinine levels in patients with hypothyroidism, indicating possible renal impairment (30-34). Previous research has also reported significantly elevated serum creatinine levels in cases with subclinical hypothyroidism, emphasizing its potential as an early biomarker for detecting hypothyroidism (25). Furthermore, another study reported a substantial increase in serum creatinine levels in patients with hypothyroidism, along with alterations in thyroid hormone levels and other renal function parameters (35). Additionally, a previous study confirmed elevated serum creatinine levels in cases with both subclinical and overt hypothyroidism, further supporting the association between hypothyroidism and increased creatinine levels (36).

The present study has several limitations, which should be mentioned. These include a small sample size, an imbalanced sex distribution among participants, and limited representation from both public and private hospitals. Additionally, the lack of family physician visits presented a significant challenge in evaluating creatinine levels among hypothyroid patients. Despite these limitations, the outcomes of the present were considered satisfactory for achieving the research objectives.

In conclusion, the present cross-sectional study examined and analyzed the serum levels of TSH and creatinine in various groups of individuals with hypothyroidism. By evaluating these biomarkers, the study identified significant associations and differences related to hypothyroidism, contributing valuable insight into the interplay between TSH and creatinine levels within the study population.

Based on the findings of the present study, it is crucial to provide appropriate treatment strategies for patients with hypothyroidism, recognizing it as a risk factor for the development of renal failure, in order to achieve optimal treatment outcomes. Understanding this association can lead to the avoidance of unnecessary investigations, the reduction of treatment costs, and the alleviation of the anxiety of patients, particularly when creatinine levels are elevated in the presence of hypothyroidism.

On the whole, although the present study had certain limitations due to its small sample size, it underscores the need for further research with a larger number of participants to yield more reliable results. Additionally, it is important to note that the findings presented herein were exploratory and specific to the Tripoli region in Libya. Therefore, conducting a comprehensive survey across Libya is necessary to gain a more thorough understanding. Support from the Libyan Authority for Scientific Research for further research in this field would be required, and additional studies are required to explore the mechanisms through which various biochemical parameters relate to thyroid dysfunction. Health officials need to allocate funds for diagnosis and invest in public education on the importance of early detection and treatment of hypothyroidism. This approach could lead to improved strategies for maintaining renal function. Creatinine levels in patients with hypothyroidism should be closely monitored, and any changes should be discussed with their healthcare provider. Thus, the present study serves as a valuable resource for doctors, highlighting the importance of evaluating renal function in each patient with hypothyroidism to identify potential issues early and implement appropriate safeguard measures.

Acknowledgements

Not applicable.

Funding

Funding: No funding was received.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors' contributions

All authors (SAH, NAS, MMF, GMS, AMA, SOA, RFA and ZAA) made significant contributions to the acquisition, analysis and interpretation of the data. SAH and SOA collected samples from the center for analysis and presented accurate research results. All authors have reviewed, and have read and approved the final version of the manuscript. SAH and SOA confirm the authenticity of all the raw data.

Ethics approval and consent to participate

Ethical approval for conducting the study was obtained from the Higher Institute of Medical Sciences and Technology, Tripoli, Libya. Informed consent was obtained from individuals or legal guardians through an official document after submitting the study proposal, ensuring that participation was voluntary. Volunteers were also informed that their responses would be anonymous and confidential.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

References