Change in insulin-like growth factor type 1 concentration after radioactive iodine treatment in cats with hyperthyroidism

Abstract

Objectives

This study aimed to evaluate changes in serum insulin-like growth factor type 1 (IGF-1) concentrations in cats with hyperthyroidism before and after radioactive iodine (RAI) treatment, as well as investigate the correlation between thyroid volume and serum IGF-1 concentrations.

Methods

A total of 13 cats with hyperthyroidism and 14 healthy controls were included. Serum total thyroxine (TT4)/thyroid-stimulating hormone (TSH) and IGF-1/insulin-like growth factor binding protein-3 (IGFBP-3) concentrations were measured using chemiluminescence immunoassay and ELISA, respectively, at presentation and 6 months after RAI treatment. The results were compared with thyroid volume measured using scintigraphy. Data are presented as median (interquartile range [IQR]) and analysed using non-parametric tests.

Results

Serum TT4 concentrations significantly decreased from 9.30 µg/dl (IQR 6.49–12.7) to 2.23 µg/dl (IQR 1.34–2.94) after RAI treatment (P <0.001), while TSH levels increased from 0.021 ng/ml (IQR 0.021–0.021) to 0.125 ng/ml (IQR 0.050–0.257) (P = 0.002). IGF-1 levels significantly increased from 329 ng/ml (IQR 240–479) to 572 ng/ml (IQR 402–1038) after RAI treatment (P = 0.011), while IGFBP-3 levels did not differ. Serum creatinine concentrations significantly increased from 1.3 mg/dl (IQR 1.2–1.6) to 2.0 mg/dl (IQR 1.7–2.3) after RAI treatment (P = 0.006). No correlation was observed between IGF-1 and any variable, except IGFBP-3 (r_s = 0.587; P = 0.039) in the pretreatment group. IGF-1 and body weight were significantly positively correlated after RAI treatment (r_s = 0.696; P = 0.011) but not before. In healthy cats, IGF-1 was negatively correlated with serum TT4 (r_s = –0.627; P = 0.019).

Conclusions and relevance

The increased serum IGF-1 concentrations after RAI treatment may reflect the restoration of anabolic status in cats with hyperthyroidism. In this study population, no correlation was found between thyroid volume and serum IGF-1 concentrations.

Plain language summary

IGF-1 may serve as a useful biomarker for metabolic recovery after definitive treatment of hyperthyroidism

Hyperthyroidism is a common endocrine disorder in older cats. Current therapeutic strategies focus on managing the overproduction of thyroid hormones by the adenomatous thyroid gland because the underlying pathogenesis of feline hyperthyroidism remains unclear. Available treatment modalities include the use of iodine-restricted diet, anti-thyroid medications, surgical excision of the affected thyroid tissue and radioiodine therapy. Normal function of thyroid hormones and the growth hormone/insulin-like growth factor type 1 (IGF-1) system is closely connected. Radioactive iodine (RAI) is the definitive treatment of choice, with a single dose proving effective in over 90% of affected cats, regardless of dose or administration route. Therefore, this study aimed to evaluate changes in serum IGF-1 concentrations before and after RAI treatment in cats with hyperthyroidism and investigate the correlation between thyroid volume and serum IGF-1 concentrations. This study demonstrates that serum IGF-1 concentrations tend to increase after RAI treatment in cats with hyperthyroidism. Although a significant positive correlation was observed between body weight and IGF-1 concentration after treatment, no such relationship was evident before treatment. We believe that our study makes a significant contribution to the literature because it suggests that the restoration of euthyroid status through RAI treatment resolves endocrine and metabolic disturbances, thereby unmasking the physiological relationship between IGF-1 and body weight. Consequently, IGF-1 may serve as a useful biomarker for metabolic recovery after definitive treatment of hyperthyroidism.

Keywords

Body weight insulin-like growth factor type 1 insulin-like growth factor binding protein-3 thyroid

Introduction

The normal function of thyroid hormones and the growth hormone (GH)/insulin-like growth factor type 1 (IGF-1) system is closely connected.^1
–3 Somatostatin reduces thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) secretion from the hypothalamus and pituitary gland, respectively.^4
–7 Thyroid cells have IGF-1 receptors that enable IGF-1 to stimulate cell growth and increase thyroglobulin production. Those with hyperplasia can produce IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3).^8,9

Cats with hyperthyroidism exhibit higher serum IGF-1 levels than healthy cats; however, the difference is not statistically significant and varies by assay.¹⁰ Serum IGF-1 levels decrease with increasing hyperthyroidism severity and rise significantly after thiamazole treatment in affected cats.¹¹ Increased serum IGF-1 concentrations after thiamazole treatment are presumably due to suppressed leptin level recovery, which may indirectly stimulate GH secretion. However, this interpretation remains inconclusive since thyroid tissue volume may increase over time despite thiamazole therapy, and serum IGF-1 levels could rise with expanding thyroid tissue.⁸ Radioactive iodine (RAI) is recognised as the definitive treatment of choice,^12,13 with a single administration – regardless of dose or route – proven effective in over 90% of affected cats.^14
–19 This study evaluated serum IGF-1 concentrations before and after RAI treatment in cats with hyperthyroidism and investigated the correlation between thyroid volume and serum IGF-1 levels. We hypothesised that thyroid volume positively correlates with serum IGF-1 levels and RAI reduces IGF-1 concentrations by lowering abnormally hyperplastic thyroid tissue volume compared with thiamazole.

Materials and methods

Animals

Between October 2017 and December 2024, 67 cats were enrolled in this observational study (53 cats with hyperthyroidism and 14 control cats). Forty cats with hyperthyroidism were excluded because they did not return for the 6-month follow-up after RAI treatment. Consequently, a total of 27 cats (13 cats with hyperthyroidism and 14 control cats) were enrolled. Figure 1 shows the flow diagram for case selection and grouping. Hyperthyroidism diagnosis, without histopathological evidence, was based on the following criteria:²⁰ clinical signs of hyperthyroidism and elevated total thyroxine (tT4) levels. Cats with serum tT4 concentrations within the reference interval were classified as euthyroid. In addition, cats were excluded if they had concurrent diseases known to affect serum IGF-1 concentrations, including diabetes mellitus, acromegaly or chronic kidney disease classified as International Renal Interest Society stage 2 or above.^21–23 Those that received corticosteroids within 30 days before enrolment were excluded, as steroids can influence blood parameters, including IGF-1 concentrations.²⁴ The control group comprised cats without clinical signs of hyperthyroidism, with normal serum TT4 concentrations and no concurrent diseases.

Figure 1

Flow diagram for selection, exclusion and grouping for the cats with hyperthyroidism and those with normal thyroid function

Hormone assays

Serum IGF-1 concentrations were measured using ELISA (Mediagnost E20 IGF-1 ELISA; Mediagnost), which were validated in feline samples.²⁵ All assay components were provided with the kit. The standard curve was based on recombinant human IGF-1, calibrated against the World Health Organization International Standard 02/254, with concentrations of 2, 5, 15, 30 and 50 ng/ml. Serum samples were diluted 1:11 to 1:310 with acidic assay buffer containing IGF-2, as recommended. They were added to wells precoated with a primary anti-human IGF-1 antibody, followed by a biotinylated secondary anti-IGF-1 antibody. After a 1-h incubation and washing step, streptavidin–peroxidase conjugate was added and incubated for 30 mins. Colour development was achieved using tetramethylbenzidine substrate; the reaction was stopped with sulfuric acid. Absorbance was measured at 450 nm with a 650 nm reference filter using a Tecan Sunrise Absorbance Reader (Tecan). IGF-1 concentrations were calculated from the standard curve (expressed in ng/ml). Inter- and intra-assay variabilities were in the range of 2.4–5.0%, and the assay sensitivity was 28 ng/ml.²⁵

Serum IGFBP-3 concentrations were measured using a commercial ELISA kit (Nori Feline IGFBP-3 ELISA Kit; Genorise Scientific). Briefly, 100 µl of standards and serum samples were added to each well of a 96-well plate and incubated at room temperature (RT) for 1 h. After washing, 100 µl of the working detection antibody was added to each well and incubated for 1 h at RT. After a wash step, 100 µl of working streptavidin–horseradish peroxidase was added and incubated for 20 mins at RT. After a final wash, 100 µl of substrate solution was added and incubated for 5–30 mins at RT in the dark. The reaction was terminated by adding 50 µl of stop solution. Absorbance was measured immediately at 450 nm using a microplate reader. Concentrations were calculated following a standard curve. Inter- and intra-assay variabilities were 9.0% and 6.0%, respectively, and the assay sensitivity was 25 pg/ml, according to the manufacturer’s instructions.

Serum tT4 and TSH concentrations were measured using a validated chemiluminescent immunoassay analyser (IMMULITE 2000 XPi Immunoassay System; Siemens Healthcare Diagnostics).^26,27 Blood samples were collected via jugular venipuncture. Serum was separated by centrifugation within 30 mins of collection and then stored at –80°C until analysis. All assays were performed in a single batch to minimise inter-assay variability.

Thyroid scintigraphy

Thyroid scintigraphy was performed using a small field-of-view gamma camera (Dilon 6800; Dilon Technologies) equipped with a high-resolution parallel-hole collimator and a sodium iodide scintillation detector (spatial resolution 3.3 mm, energy resolution 13.5%). Cats were intravenously administered 74 or 148 MBq of technetium-99m pertechnetate (99mTcO₄) via the cephalic vein. Thyroid images were acquired at 20, 40 and 60 mins after injection, with the cats positioned in ventral recumbency directly on the collimator. Images were obtained under multiple acquisition conditions and processed using Dilon 6800 software (Dilon Technologies).²⁸

Images were analysed using Dilon 6800 to quantify 99mTcO₄ uptake in the thyroid lobes, zygomatic/molar salivary glands and background (axillary region). A single operator manually delineated regions of interest (ROIs). Thyroid:salivary ratio (TSR) and thyroid:background ratio (TBR) were calculated by dividing the mean thyroid lobe count density by that of the salivary glands and background, respectively. Thyroid volume was calculated using the ellipsoid formula (volume = π/6 × length × width × height) applied to each thyroid lobe, with measurements obtained from manually delineated ROIs on scintigraphic images. The bloom effect was minimised by applying the full dynamic range setting to normalise the image display, and ROIs were subsequently drawn over the affected thyroid lobes using a 30% threshold.^29,30 The total thyroid volume was calculated by summing the values of both lobes.

RAI treatment

The RAI (Thyrokitty; Korea Atomic Energy Research Institute) dose was individualised for each cat based on a scoring system incorporating clinical severity, serum TT4 concentration and palpable thyroid gland size (determined by digital palpation using callipers [length × width]),¹⁵ with a fixed low dose (74 MBq) applied for cats with serum tT4 below 11 µg/dl or total score below 6. If both thyroid lobes were enlarged, the sizes of both lobes were added together to determine the individualised scoring. The range of ¹³¹iodine (I-131) doses administered was 74–167.2 MBq in all cats included in the present study. The calculated RAI dose was administered subcutaneously. Follow-up evaluation was performed 6 months after RAI treatment by measuring serum tT4 and TSH concentrations.

Statistical analyses

The variables analysed included tT4, TSH, IGF-1, IGFBP-3, body weight, blood urea nitrogen (BUN), creatinine, TSR, TBR and thyroid volume. All statistical analyses were performed using Prism 10.0 (GraphPad Software). Normality of continuous variables was assessed using the Shapiro–Wilk test. Subsequent statistical analyses were conducted with non-parametric tests, as many groups did not follow a normal distribution. Continuous data were expressed as medians (interquartile ranges) and compared between the groups using the Mann–Whitney U-test. Pre- and post-treatment groups were compared using the Wilcoxon signed-rank test. Correlations between variables were evaluated using Spearman’s correlation test. Statistical significance was set at P <0.05.

Results

Study population

In total, 13 cats with hyperthyroidism and 14 cats with normal thyroid function (control group) were enrolled, respectively. The cats with hyperthyroidism comprised five domestic shorthairs (DSHs), four Russian Blues, one Siamese, one Persian, one American Shorthair and one Bengal. Among the 13 cats, four (30.7%) were castrated males and nine (69.2%) were spayed females (median age 12 years, interquartile range [IQR] 9–14). The euthyroid cats comprised nine DSHs, two Scottish Folds, one Russian Blue, one Bengal and one British Shorthair, with seven (50%) castrated males and seven (50%) spayed females (median age 5.5 years, IQR 3.8–6.3). Body weight significantly increased after RAI treatment in the 13 cats with paired data, rising from 4.8 kg (IQR 4.0–5.6) before treatment to 5.5 kg (IQR 4.5–6.1) after treatment (P = 0.002). Post-treatment body weight and that of the control group did not differ (5.1 kg, IQR 4.1–6.7).

Comparison of clinical data of the pretreatment, post-treatment and control groups

Serum biochemical parameters were compared among the pretreatment group, post-treatment group at 6 months after RAI and healthy control group (Table 1 and Figure 2).

Table 1

Comparison of clinical data of the pretreatment, post-treatment and control groups

	Pretreatment group (n = 13)	Post-treatment group (n = 13)	Control group (n = 14)	RI
TT4 (ug/dl)	9.30 (6.49–12.7)	2.23 (1.34-2.94)*	2.62 (1.85-3.28)*	0.8–4.7
TSH (ng/ml)	0.021 (0.021–0.021)	0.125 (0.050–0.257)*	0.081 (0.050–0.113)*	0.05–0.42
IGF-1 (ng/ml)	329 (240–479)	572 (402–1038)*	559 (345–742)*	–
IGFBP-3 (pg/ml)	128 (88.4–673)	88.4 (88.4–269)	88.4 (88.4–593)	–
BUN (mg/dl)	25.5 (22.8–26.7)	28.3 (25.1–32.6)	25.2 (20.3–27.3)^†	18–33
Creatinine (mg/dl)	1.3 (1.2–1.6)	2.00 (1.7–2.3)*	1.61 (1.6–1.9)*	0.7–1.8
TSR	2.37 (2.07–8.33)	0.83 (0.76–1.15)*	–	–
TBR	8.00 (6.78–23.7)	2.07 (1.74–3.07)*	–	–

Data are median (interquartile range). Variables were compared between the pre- and post-treatment groups using the Wilcoxon rank-sum test, and between the control and other groups using the Mann–Whitney U-test

Statistically significant difference between these values and the corresponding values in the pretreatment group (P <0.05)

†

Statistically significant difference between this value and the corresponding values in the post-treatment group (P <0.05)

BUN = blood urea nitrogen; IGF-1 = insulin-like growth factor 1; IGFBP-3 = insulin-like growth factor binding protein 3; RI = reference interval; TBR = thyroid:background ratio; TSH = thyroid-stimulating hormone; TSR = thyroid:salivary ratio; TT4 = total thyroxine

Figure 2

Box plots of serum concentrations of (a) total thyroxine (T4) and (b) insulin-like growth factor type 1 (IGF-1) in hyperthyroid cats before (Pre) and after (Post) radioactive iodine treatment (n = 13) and in healthy controls (n = 14). The boxes represent the interquartile range (25th and 75th percentiles). Whiskers represent the 5th and 95th percentiles. The Wilcoxon signed-rank test was used to compare variables between the pre- and post-treatment groups. The Mann–Whitney U-test was used to compare variables between the pre- and post-treatment and control groups, respectively. *P <0.05, ***P <0.001

The pretreatment group (median 9.30 µg/dl, IQR 6.49–12.7) had higher serum TT4 concentrations than the post-treatment (median 2.23 µg/dl, IQR 1.34–2.94) and control (median 2.62 µg/dl, IQR 1.85–3.28) groups (P <0.001) (Figure 2a). TSH concentrations were lower in the pretreatment group (median 0.021 ng/ml, IQR 0.021–0.021) than those in the post-treatment (median 0.125 ng/ml, IQR 0.050–0.257; P = 0.002) and control (median 0.081 ng/ml, IQR 0.050–0.113; P = 0.004) groups. At 6 months after RAI, 2/13 (15%) cats showed normal tT4 concentrations with elevated TSH concentrations and were therefore considered to have subclinical hypothyroidism. None of the cats developed overt hypothyroidism (low T4 with elevated TSH).

Serum IGF-1 concentrations were lower in the pretreatment group (median 329 ng/ml, IQR 240–479) than in the post-treatment (median 572 ng/ml, IQR 402–1038; P = 0.011) and control (median 559 ng/ml, IQR 345–742; P = 0.032) groups (Figure 2b). After excluding two cats with subclinical hypothyroidism, serum IGF-1 concentrations were lower in the pretreatment group (median 304 ng/ml, IQR 239–459) compared with the post-treatment (median 491 ng/ml, IQR 372–625; P = 0.032) and control (median 559 ng/ml, IQR 345–742; P = 0.032) groups. Serum IGF-1 concentrations did not differ between the post-treatment and control groups (with: P = 0.459; without: P = 0.840), including two cats with subclinical hypothyroidism.

Serum IGFBP-3 concentrations in the pretreatment group (median 128 pg/ml, IQR 88.4–673) did not differ from those in the post-treatment (median 88.4 pg/ml, IQR 88.4–269; P = 0.074) and control (median 88.4 pg/ml, IQR 88.4–593; P = 0.198) groups. The statistical results of serum IGFBP-3 were not altered after excluding two cats with subclinical hypothyroidism. Serum IGFBP-3 concentrations did not differ between the post-treatment and control groups (with: P = 0.931; without: P = 0.820), including two cats with subclinical hypothyroidism.

The serum BUN concentrations in the pretreatment group (median 25.5 mg/dl, IQR 22.8–26.7) did not differ from those in the post-treatment (median 28.3 mg/dl, IQR 25.1–32.6; P = 0.057) and control (median 25.2 mg/dl, IQR 20.3–27.3; P = 0.981) groups. However, the serum BUN concentrations were higher in the post-treatment group than in the control group (median 25.2 mg/dl, IQR 20.3–27.3; P = 0.026).

The serum creatinine concentrations of the pretreatment group exhibited markedly lower levels (median 1.3 mg/dl, IQR 1.2–1.6) than the post-treatment (median 2.0 mg/dl, IQR 1.7–2.3; P = 0.001) and control (median 1.6 mg/dl, IQR 1.6–1.9; P = 0.006) groups. However, the serum creatinine concentrations of the post-treatment group did not differ from those of the control group (P = 0.101).

The TSR and TBR results revealed marked reductions after RAI treatment. The pretreatment group had significantly higher TSR (median 2.37, IQR 2.07–8.33) and TBR (median 8.00, IQR 6.78–23.7) than those of the post-treatment group (TSR: median 0.83, IQR 0.76–1.15; TBR: median 2.07, IQR 1.74–3.07) (P <0.001 for both).

Correlation of IGF-1 with thyroidal and metabolic parameters in the pretreatment, post-treatment and control groups

Spearman’s correlation analysis was used to examine the relationship between serum IGF-1 concentrations and various thyroidal and metabolic parameters before and after RAI treatment in cats with hyperthyroidism, as well as in healthy controls. No significant correlation was observed between IGF-1 and any tested variable, including tT4, TSH, BUN, creatinine, TSR, TBR, body weight and thyroid volume, except IGFBP-3 (r_s = 0.587; P = 0.039) in the pretreatment group.

IGF-1 showed a significant positive correlation with body weight in the post-treatment group (r_s = 0.696; P = 0.011) but exhibited no significant correlations with IGFBP-3, tT4, TSH, creatinine, TSR and TBR.

In the control group, a significant negative correlation was identified between IGF-1 and tT4 (r_s = −0.627; P = 0.019), while no significant correlations were observed between IGF-1 and IGFBP-3, TSH, creatinine and body weight.

Scatter plots were generated to illustrate the relationship between IGF-1 and body weight using data from the 13 cats that completed pre- and post-treatment evaluations (Figure 3). No significant correlation was observed between IGF-1 and body weight before treatment (Spearman’s r_s = 0.418; P = 0.157) (Figure 3a). A significant positive correlation between IGF-1 and body weight was detected in the post-treatment group (Spearman’s r_s = 0.696; P = 0.011) (Figure 3b).

Figure 3

Scatter plots showing the correlation between body weight and serum insulin-like growth factor type 1 (IGF-1) concentration (ng/ml) in cats with hyperthyroidism (a) before (Pre) and (b) after (Post) radioactive iodine treatment. Each point represents an individual cat. A simple linear regression line is included in each panel. No significant correlation was observed before treatment (a, Spearman’s r_s = 0.418; P = 0.157 ), whereas a significant positive correlation was found after treatment (b, Spearman’s r_s = 0.696; P = 0.011 ) in cats with hyperthyroidism

Discussion

This study found that serum IGF-1 concentrations were significantly higher in the post-treatment group than those in the pretreatment group. Post-treatment IGF-1 concentrations did not differ from those of healthy controls. No correlation was identified between thyroid volume and serum IGF-1 concentrations in our study population. Furthermore, no significant correlation was observed between tT4 and IGF-1 concentrations before or after treatment. A previous study suggested that IGF-1 concentrations are inversely proportional to hyperthyroidism severity as assessed by tT4 concentration measurement and significantly increase after thiamazole treatment.¹¹ Among the clinical parameters evaluated, serum IGF-1 concentration was correlated with body weight alone in the post-treatment group.

Several mechanisms may underlie the reduced IGF-1 concentrations in cats with hyperthyroidism. One possible explanation is suppressed GH secretion, as thyroid hormones upregulate hypothalamic somatostatin, which inhibits TRH and TSH release, indirectly reducing GH and IGF-1 production.^2,4 Hyperthyroidism is a chronic disease state that can elicit prolonged stress responses. This activates the hypothalamic–pituitary–adrenal axis, leading to increased secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and glucocorticoids, all of which exert suppressive effects on GH release and IGF-1 activity.³¹ Another factor may be reduced leptin levels, previously documented in cats with hyperthyroidism and known to increase after thiamazole therapy.³² Leptin indirectly stimulates GH release by inhibiting somatostatin and neuropeptide Y, while promoting GH-releasing hormone secretion.^4,33 Although the liver is the primary site of IGF-1 production⁴ and hepatic dysfunction lowers its levels in dogs and humans, hepatic enzyme elevation in cats with hyperthyroidism³⁴ does not reflect significant hepatic insufficiency, making liver failure an unlikely cause.³⁵ Finally, excess thyroid hormone in humans reduces peripheral vascular resistance through arteriolar dilation,³⁶ leading to decreased effective circulating volume and the renin–angiotensin–aldosterone system (RAAS) activation as a compensatory mechanism.³⁷ Although the interaction between RAAS and the IGF axis remains incompletely understood, some studies suggest a potential inverse relationship between these systems.

Compared with thiamazole therapy used in a previous study,¹¹ the RAI treatment applied in this study reduces hyperplastic thyroid tissue volume.³⁸ Although the earlier study¹¹ observed serum IGF-1 concentration increase after thiamazole administration, the drug’s inability to reduce thyroid mass limits its capacity to exclude the possibility that IGF-1 is secreted by hyperplastic thyroid cells. Our study revealed a significant serum IGF-1 concentration increase even after successful hyperplastic thyroid tissue ablation via RAI treatment. Furthermore, no significant association was identified between thyroid volume and serum IGF-1 concentrations in our study populations. These suggest that hyperplastic thyroid cells are unlikely to be a major source of circulating IGF-1 in cats with hyperthyroidism. In the present study, serum IGFBP-3 concentrations were not different among the groups; however, there was a positive correlation between serum IGF-1 and IGFBP-3 in the pretreatment group (hyperthyroidism). Therefore, although the roles of IGF-1 and IGFBP-3 on the thyroid gland have not yet been explained, IGFBP-3 may be physiologically related to IGF-1 in cats with hyperthyroidism. In addition, it is difficult to conclude whether IGFBP-3 is related to the function and size of the thyroid gland in cats.

A significant correlation between serum IGF-1 concentration and body weight was not observed in cats with hyperthyroidism before treatment but emerged after RAI treatment, consistent with findings from a previous study using thiamazole treatment.¹¹ During the hyperthyroid state, excessive thyroid hormone secretion induces a pathologically elevated basal metabolic rate and promotes a catabolic state.³⁹ Under such conditions, the physiological association between anabolic hormones, including IGF-1 and body weight is likely disrupted. Elevated thyroid hormone levels increase hypothalamic somatostatin secretion, which suppresses the GH–IGF-1 axis,^2,4 resulting in persistently low IGF-1 concentrations regardless of body weight. After RAI treatment, thyroid hormone level normalisation leads to metabolic balance restoration and recovery of the GH–IGF-1 axis. Consequently, IGF-1 concentrations reflect the animal’s actual anabolic status. This physiological recovery re-establishes the positive correlation between IGF-1 levels and body weight.

Our study revealed a significant negative correlation between serum IGF-1 and tT4 concentrations in the control group alone, suggesting that this physiological inverse relationship is preserved under stable metabolic conditions. No significant correlation was observed in the pre- or post-treatment groups. The absence of pretreatment correlation may be attributed to the disease-induced metabolic disruption, which leads to a loss of normal physiological linkage between the thyroid and somatotropic axes. Although thyroid hormone levels normalised after RAI treatment, the post-treatment group likely remained in an unstable metabolic state, or the sample size may have been insufficient to achieve adequate statistical power. The negative correlation between tT4 and IGF-1 in the control group reflects the suppressive effect of thyroid hormones on the GH–IGF-1 axis. This indicates that metabolic disturbances interfere with the normal inverse relationship, and such correlations are only observed in physiologically stable conditions.

No significant correlation was observed between tT4 and IGF-1 concentrations before or after RAI treatment. The physiological and diagnostic differences between tT4 and free T4 should be considered to interpret this finding. Free T4 represents the biologically active, unbound fraction of circulating thyroid hormone and is a more accurate indicator of thyroid status, especially under conditions influenced by non-thyroidal illness, altered protein levels or concurrent medication use. In addition, tT4 includes free and protein-bound fractions and is more susceptible to T4-binding globulin concentration fluctuations.⁴⁰ A previous study reported a significant negative correlation between free T4 and IGF-1 concentrations before and after anti-thyroid drug treatment.¹¹ The absence of such a correlation in our study may be due to the measurement of tT4 alone, possibly limiting the accurate assessment of physiologically active thyroid hormone levels. Future studies evaluating the relationship between thyroid function and IGF-1 concentrations in cats with hyperthyroidism should include tT4 and free T4 measurements to more accurately reflect thyroid hormone bioactivity.

Interestingly, serum creatinine concentration significantly increased after RAI treatment in hyperthyroid cats. The pretreatment hyperthyroid state is associated with increased renal blood flow and glomerular filtration rate compared with the euthyroid state.³⁷ Consequently, the reduction in renal blood flow after RAI treatment might result in a decrease in the glomerular filtration rate below the reference interval, as reflected by the observed increases in serum creatinine concentration in the present study.

We measured serum IGF-1 concentrations using ELISA rather than the conventional radioimmunoassay method used in previous studies. Although methodological differences may contribute to discrepancies in IGF-1 values, previous validation studies have demonstrated strong agreement between ELISA and radioimmunoassay measurements. High correlations were reported between IGF-1 concentrations measured by ELISA and radioimmunoassay in serum and plasma.⁴¹ ELISA demonstrated high diagnostic accuracy based on receiver operating characteristic curve analysis (area under the curve = 0.99 for serum, 0.93 for plasma), supporting its use as a reliable and practical alternative to radioimmunoassay. ELISA is precise, non-radioactive and more cost-effective, making it well-suited for routine clinical use, including IGF-1 screening in cats with diabetes. Despite methodological differences, the application of ELISA in this study for IGF-1 quantification is considered reliable given its established concordance with radioimmunoassay in previous researches.

The present study has some limitations. First, the relatively small sample size may have limited the statistical power, particularly for some variables, including IGFBP-3, increasing the type II error risk. Second, unavailable long-term follow-up data on IGF-1 concentrations and corresponding weight trajectories limited the assessment of sustained post-treatment changes. Third, the use of a different IGF-1 measurement method compared with previous reports may influence the comparability of results across studies. Lastly, 2/13 (15%) cats demonstrated elevated TSH with normal tT4 values at 6 months after RAI, which we classified as subclinical hypothyroidism. This biochemical pattern may reflect either a persistent mild hypothyroid state or a transitional recovery phase, as pituitary–thyroid axis feedback recovery may lag behind tT4 normalisation. Longer term follow-up would be necessary to distinguish these possibilities. Furthermore, the results of serum IGF-1 and IGFBP-3 were not influenced by the exclusion of two cats with subclinical hypothyroidism.

Conclusions

Serum IGF-1 concentrations tend to increase in cats with hyperthyroidism after RAI treatment. Body weight and IGF-1 concentration were positively correlated after treatment but not before. These findings suggest that euthyroid status restoration through RAI treatment resolves endocrine and metabolic disturbances, thereby unmasking the physiological link between IGF-1 and body weight. Consequently, IGF-1 may serve as a useful biomarker for metabolic recovery after definitive treatment of hyperthyroidism in cats.

Footnotes

Accepted: 23 October 2025

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: this work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry through the Companion Animal Life Cycle Industry Technology Development Program, funded by the Ministry of Agriculture, Food and Rural Affairs (grant number 322095-04).

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers, tissues and samples) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

ORCID iD

Dongheon Shin

Yeon Chae

Taesik Yun

Byeong-Teck Kang

Hakhyun Kim

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