The Impact of Iodinated Contrast Media Used in Epidural Steroid Injections on Thyroid Function Tests

doi:10.21203/rs.3.rs-3401473/v1

Objective

The use of iodinated contrast media (ICM) inevitably increases in conjunction with the growing number of epidural steroid injections (ESI) administrations. The purpose of this study was to investigate the relationship between thyroid functions and ICM exposure through ESI procedures.

Design:

Prospective, observational study.

Setting:

A university hospital pain management center.

Methods

This study was conducted between June 2022 and February 2023. Participants between the ages of 18 and 65 who had received an epidural steroid injection at our outpatient pain clinic comprised the study's population. Thyroid function tests (fT3, fT4, and TSH) were measured before and 3 weeks after the procedure.

Results

A total of 124 participants (80 women and 44 men) were analysed. The average amount of contrast media administered was 1.34 ml. A significant increase was observed only in the fT4 value compared to pre-procedure (p = 0.017), and thyroid disorders developed in 19.5% of the participants (subclinical hyperthyroidism = 19, subclinical hypothyroidism = 3, overt hyperthyroidism = 1).

Conclusion

The current analysis provides an overview of the relationship between ICM volume and a higher risk of thyroid disorders and dysfunction.

contrast media

epidural injection

iodine

thyroid functions

Spinal pain management has become a major health issue as a result of longer life expectancies and an increase in the frequency of age-related spinal disorders. The current clinical treatment of spinal conditions is composed of NSAIDs, physical therapy, therapeutic injections, and surgery.

Epidural steroid injections (ESIs) are one of the most often used procedures for managing spinal pain among the various treatment modalities that are available [1]. There have been reports of substantial increases in ESI utilization among the US Medicare population, reflecting a 24% annual growth rate [2]. ESI can be implemented precisely and securely with the use of computed tomography (CT) or fluoroscopy. Even so, in order to confirm the exact needle tip position and avoid inadvertent non-epidural injections (intravascular, subdural, subarachnoid, etc.), the use of iodinated contrast media (ICM) is crucial and imperative [3].

The amount of contrast used in ESIs varies depending on factors such as procedure type, number of procedures, practitioner experience, and anatomical structures. Since many factors are involved in the procedures, even though a small dosage of contrast media is generally adequate, these doses may be raised, which might also elevate the risk of the contrast media’s adverse effects.

The amount of iodine in ICM is considerable. The amount of iodine that the patient may receive during a single computed tomography scan might range from 100 to thousands of times the normal limit [4, 5]. Free iodine in the serum is utilized by the thyroid gland to synthesize thyroid hormone for metabolic processes. The normal thyroid gland is capable of adapting to an increase in iodine. When rapid overload iodine doses are administered suddenly, the regulation of thyroid hormone is disrupted, which can lead to either hyperthyroidism (the Wolff-Chaikoff effect) or hypothyroidism (the jod basedow) [6–8].

The impact of ICM on nephrotoxicity has been widely explored; however, several studies have addressed ICM's effects on the normal thyroid gland in clinical practice, and most of those studies were related to the use of CT scans [9, 10]. To the best of our knowledge, there have been no reports examining the association between ICM exposure via ESI procedures applied with fluoroscopy guidance and subsequent thyroid functionality. We hypothesize that ICM used in ESIs may compromise thyroid gland functions, and the dysfunction of thyroid hormones may be correlated with ICM’s dose.

Hence, the aim of this prospective research is to determine whether exposure to ICM is linked to thyroid dysfunction in the ESI population.

This prospective observational study was carried out at our outpatient pain clinic from June 2022 to February 2023 (clinical trial registration number: NCT05404412). The population of the study consisted of patients between the ages of 18–65, who had undergone any type of epidural steroid injection, including lumbar, cervical, and caudal epidural steroid injections, for any reason in our outpatient clinic. Exclusion criteria were; (A) suffering or had suffered thyroid or metabolic diseases, thyroid dysfunction, or thyroid surgery; (B) suffering or had suffered hypothalamic or pituitary diseases; (C) a current prescription for levothyroxine, antithyroid drugs, amiodarone, or lithium; (D) systemic and/or local infections, malignancy, or bleeding diathesis; (E) a known allergy to contrast material and/or local anesthetic substances; (F) a known history of any psychiatric disorder; and (G) a history of pregnancy. Verbal and written informed consent was obtained from all patients participating in the study.

The flowchart for determining the study population was displayed in Fig. 1.

In conjunction with the recording of the demographic data of the patients participating in this study (age, sex, body mass index, contrast medium doses, etc.), the values of TFTs (thyroid function test) including free T3, free T4, and thyroid-stimulating hormone (TSH) were analyzed before the procedure and the 3rd week after the procedure. The Immuno-Serology Laboratory measured serum TSH, free triiodothyronine (FT3), and free thyroxine (FT4). Blood samples were taken when the participants were fasting.

TSH, fT4 and fT3 were measured using Electrochemiluminescence immunoassay (Cobas Integra 8000, Roche, Diagnostics, Germany). The reference ranges for TSH, FT3, and FT4 were; 0.48–4.81 mIU/L, 2.02–4.42 ng/L, and 0.78–1.51 ng/dL, respectively.

The laboratory analyses have been authorized for use in clinical settings. Epidural steroid injections were performed by a 10-years experienced interventional pain specialist (SS) under sterile conditions with the C-arm fluoroscopy guidance. Throughout the process, details on the procedure that can affect the outcomes were recorded, including the type of ESI, the number of interventions, the frequency of inadvertent injections, the volume of the contrast, and the route of the contrast administration.

The total contrast volume was measured manually after the procedure. The same injector type was used throughout all procedures. All patients were given the low osmolar, nonionic contrast medium Iohexol (Omnipaque, 300 mg iodine/mL; GE Healthcare, Chicago, IL, USA) for ESIs.

Statistical analysis

Statistical analyses were performed using SPSS version 22.0 software (IBM Corp., Armonk, NY). Continuous variables were expressed in mean (standard deviation) and median (interquartile range), while categorical variables were expressed in number and frequency. The Kolmogorov-Smirnov test was used to analyse the distribution of quantitative data. The Wilcoxon test was performed for the comparison of non-normally distributed data, while the paired t-test was used to compare normally distributed data. The Pearson correlation test was applied to the normally distributed parameters in the correlation, and the the Spearman correlation test was applied to the non-normally distributed parameters. A p-value < 0.05 was considered statistically significant.

A total of 124 participants who had received an epidural steroid injection were analyzed. 35.5% of the patients were male, and 64.5% were female. While the mean age of the patients was 49.32 ± 9.70 , the BMI was found 28.38 ± 4.46. Of the 124 procedures performed, 99 (79.8%) were lumbar, 21 (16.9%) were cervical, and 4 (3.2%) were caudal epidural steroid injections. After contrast agent administration; subclinical hyperthyroidism developed in 19 (15.3%), subclinical hypothyroidism in 3 (2.4%) and overt hypothyroidism in 1 (0.8%) of the patients (Table 1).

There was a significant increase in serum fT4 following administration of contrast media (p:0.017). In contrast, no significant changes were detected in serum TSH (p = 0.810) and serum fT3 (p = 0.972) (Table 2) .No major adverse events were observed during the procedures. As a result of the correlation analysis performed between the contrast agent doses and thyroid function tests, no strong correlation was found (Table 3,4).

This prospective observational study was carried out to evaluate the impact of contrast media on thyroid function in patients who received ESI. First, we revealed that the serum level of FT4 was significantly elevated following ESI. Second, nearly 20% of our patients with euthyroidism developed a thyroid disorder. Third, we discovered that these conditions were unrelated to the ICM dosage.

ICM is routinely and necessarily employed in ESI procedures. An average 1,5 − 2 ml dosage of ICM with a 35µg/ml concentration is used in the procedure, providing 70µg of free iodide, which is much lower than CT or angiography ranges [11, 12]. Some research indicates that repeated ICM exposure and large ICM volumes are more likely to elevate the risk of thyroid disorders [13, 14]. Contrary to these studies, we found no correlation between contrast volume and thyroid hormone dysregulation. This might be due to the low amount of contrast media and the short follow-up period.

The iodine or iodide load provided by ICM likely explains the observed connection between ICM exposure and hyperthyroidism. Once the iodine has entered the thyroid follicles, it is used to produce the thyroid hormones T4 and T3 [15]. After an iodine dose, defective autoregulation is the mechanism behind ICM-induced hyperthyroidism, and a high consumption of iodine will lead to either temporary or permanent hyperthyroidism [16, 17, 18]. This mechanism may shed light on the link between ICM-exposure in our study. Similar to the findings of Chen Y et al., we discovered a slight difference in T3 and TSH levels but a significant change in T4 levels compared to pre-treatment. However, when compared, the amount of contrast material used differs [10]. We postulated that this may be due to non-dose-dependent personal and other variables, including living in an iodine-deficiency region and having an underlying autoimmune disease or thyroid issues (euthyroid goiter, euthyroid sick syndrome, etc.).

One-fifth of the participants in our research experienced subclinical hyperthyroidism after ICM exposure. A prospective observational cohort research examined the long-term consequences on thyroid function in euthyroid individuals employing ICM for coronary angiography. After eight weeks, they discovered that ICM may give rise to subclinical hyperthyroidism [21]. It has been proposed that the association between ICM exposure and developing thyroid dysfunction may be more widespread than previously anticipated [22]. A nested case-control study between 1990–2010 consisting of 3678 individuals was conducted in the euthyroid population by Rhee, C. M., et al. [6]. They showed that overt hypothyroidism and hyperthyroidism were significantly associated with ICM exposure. Over the course of a year, 1 million patients in the general population of Taiwan showed a considerably greater incidence of ICM-induced thyroid dysfunction after 6 years of observation [5]. Using Taiwan's National Health Insurance Research Data- Base, a later investigation discovered that individuals with euthyroid nodular goiter had a nearly 5-fold greater incidence of ICM-induced thyroid dysfunction than those without thyroid nodules [19]. Yet, in certain studies, ICM exposure caused thyroid dysfunction, particularly in patients with a history of thyroid illness or renal insufficiency [14, 19, 20]. However, since we were unable to recruit adequate patients with thyroid dysfunction, our investigation focused on participants with normal thyroid function. In our subsequent investigation, we intend to include individuals with thyroid disorders.

Despite convincing retrospective research, the outcomes of prospective observational studies in various regions assessing changes in thyroid hormone levels after a single exposure to ICM are highly diverse [23, 24, 25]. In accordance with a recent systematic review and meta-analysis, during radiographic processes, the frequency of thyroid dysfunction following ICM injection is remarkably low [23]. These differences may be caused by the selection of participants (based on thyroid functions), the amount and type of contrast agent used, and the follow-up period, which cause substantial heterogeneity among studies [26].

Our study has several limitations. First, our study has a short follow-up period. On the other hand, the relationship between ICM volume and the long-term risk of thyroid illness, as well as the requirement of thyroid function monitoring, remains obscure. Second, due to the nature of the technique, we carried out ESI utilizing low-dose contrast volumes. Third, participants in our study were not strictly selected from an iodine-sufficient region. Finally, due to the difficulties in diagnosing asymptomatic autoimmune diseases and goiter, this population may be mistakenly included. It might affect our clinical results.

We also have strengths in our study. It is the first study to address the change in thyroid function tests due to ICM exposure in ESIs. Moreover, we demonstrated that those procedures could deteriorate thyroid function values and lead to a thyroid disorder in euthyroid individuals. Given the growing prevalence of ESI implementations in clinical practice, the results obtained are of importance in the daily routine practice of ESI.

The current study provides an overview of the association between ICM and an elevated risk of thyroid dysfunction and thyroid disorder in the ESI population. Given the widespread use of contrast media in interventional pain management such as ESI, routine thyroid examinations prior to and after ESI are required, particularly for patients who are inclined to thyroid dysfunction. Consequently, physicians and patients should be acquainted with the possible thyroid issues related to ICM, and in order to clarify this issue, further studies with various contrast media volumes and longer follow-up periods are needed.

Acknowledgment

We appreciate Sahin Azizov, MD works at Ege Hospital/Baku for his contribution to data collection.

Compliance with Ethical Standards

Conflict of Interest: The authors declare that they have no conflict of interest.

Ethical Approval: Ethical approval was obtained.

Informed Consent: Verbal and written informed consent was obtained from all patients participating in the study.

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Table 1. Demographic data, procedure types, post-procedure thyroid function

Variable values	Mean (SD) or %
Age (years)	49.32 ± 9.70
BMI (kg/m2 )	28.38 ± 4.46
Gender (n / %) Male Female	44 (35.5) 80 (64.5)
Procedure (n / %) Lumbar ESI Cervical ESI Caudal ESI	99 (79.8) 21 (16.9) 4 (3.2)
Post-procedure thyroid function (n / %) Euthyroidism Subclinical hyperthyroidism Subclinical hypothyroidism Overt hypothyroidism	101 (81.5) 19 (15.3) 3 (2.4) 1 (0.8)
The amount of contrast media (ml)	1.34 ± 0.63

The descriptive data was provided as n (%), mean ± SD (min-max), and median (min-max) values. ESI, epidural steroid injection; BMI, body mass index

Table 2. Comparison of thyroid function test values before and after contrast administration

	Preprocedure	Postprocedure	p value

T3	2.98 ± 0.44	2.98 ± 0.53	0.972
T4	1.21 ± 0.24	1.25 ± 0.24	0.017
TSH	1.59 (0.13-4.72)	1.54 (0.10-9.83)	0.810

Statistical analyses were conducted using the Paired-T test for T3 and T4, the Wilcoxon test for TSH. TSH, thyroid stimulating hormone

Table 3. Correlation between contrast media and T3-T4 values

		Contrast Media	preT3	preT4	postT3	postT4
Contrast Media	r	1	0.194^*	0.002	0.025	-0.149
Contrast Media	p		0.038	0.982	0.785	0.099
preT3	r		1	-0.090	0.441^*	-0.109
preT3	p			0.341	<0.001	0.247
preT4	r			1	-0.066	0.724^*
preT4	p				0.481	<0.001
postT3	r				1	0.090
postT3	p					0.331
postT4	r					1
* Correlation is significant at the 0.05 level.

Table 4. Correlation between contrast media and TSH values

		Contrast Media	preTSH	postTSH
Contrast Media	rho	1	0.135	0.059
Contrast Media	p		0.136	0.518
preTSH	rho		1	0.667^*
preTSH	p			<0.001
preTSH	rho			1
*. Correlation is significant at the 0.05 level.

The Impact of Iodinated Contrast Media Used in Epidural Steroid Injections on Thyroid Function Tests

Status:

Version 1

Abstract

Objective

Design:

Setting:

Methods

Results

Conclusion

Figures

Introduction

Materials And Methods

Statistical analysis

Results

Discussion

Conclusion

Declarations

References

Tables

Status:

Version 1