INFLUENCE OF GONADECTOMY ON SERUM FT4 CONCENTRATIONS IN MALE AND FEMALE DOGS

Alicja Krzyżewska-Młodawska¹, Andrzej Max², Bartłomiej J. Bartyzel^3
1 Department of Small Animal Diseases with Clinic, Warsaw University of Life Sciences (SGGW), Poland
² Department of Small Animal Diseases with Clinic, Warsaw University of Life Sciences - SGGW, Poland
³ Department of Morphological Sciences, Warsaw University of Life Sciences - SGGW, Poland

ABSTRACT

The aim of this study was to compare the concentrations of free thyroxine (fT4) in castrated and non-castrated male as well as female dogs. Gonadal resection deprives the body of the primary source of hormones secreted by these organs. It may result in endocrine dysfunctions and among them particularly on thyroid level. Such relationships were reported in rodents, in dogs, however, they are poorly recognized. Dogs (n=124) without clinical signs of  hypothyroidism or dermatological changes were divided into four groups: intact bitches, n=22, spayed bitches,  n=45, intact males, n=26, and castrated males, n=31. The concentration of fT4 was measured by radioimmunoassay using commercial test for the quantitative determination of hormone in human serum. The average values in gonadectomized males and females was lower as compared to intact animals (p<0.05). In addition, in bitches a statistically significant effect of time that has elapsed from castration was observed. The time from castration was longer, the fT4 concentration was lower. In conclusion, the results indicate the enhanced risk of hypothyroidism in castrated dogs of both sexes. Additional studies are needed to recognize the influence of gonadectomy on thyroid gland on morphological, histological and functional levels.

Key words: dog, gonadectomy, ovariectomy, orchiectomy, fT4.

INTRODUCTION

Gonadectomy is the primary treatment of surgical contraception in both females and males. Additionally, castration is a method of surgical treatment of testicular and ovarian diseases, and sometimes other organs. The currency of these treatments on the one hand, and their irreversible effects on the other, tend constantly to reflect on the safety and the harmlessness of the procedure, the more that alternative methods of contraception are implemented [9]. Resection of the gonads is also depriving the body's primary source of hormones secreted by these organs. Experimental studies on changes in thyroid hormone concentrations after gonadectomy were mainly carried out in rats. After ovariectomy a significant reduction in triiodothyronine (T3) concentration was observed, but without any changes in the concentration of thyroid-stimulating hormone (TSH), thus suggesting a direct effect of estradiol on the thyroid gland [12]. Other researchers have noted a decrease in TSH concentration and the amount of TSH receptors in the thyroid gland in castrated males, judging by modulating the action of sex hormones on TSH binding to thyrocytes in rats, but this effect may be different depending on the age and gender [2, 3]. In another study no difference were found in the concentrations of T3 and thyroxine (T4) between neutered males and the control group, and a significant decrease in TSH concentration in castrated rats was noticed. In ovariectomized rats a significant decline in T3 concentration was observed without changes in the level of TSH [14]. It is suggested that gonadal steroids modulate the activity of 5`-deiodinases, the enzymes responsible for the conversion of T4 to T3. Studies in female rats has shown that estrogens stimulate the activity of the pituitary-5'-deiodinase. Ovariectomy reduces this activity and will tend to decrease the enzyme activity in the thyroid gland [13]. In castrated male cats an increase in T3 concentration and in spayed queens a decrease in thyroxine concentration were found [8]. It is suspected that spayed females are more susceptible to hypothyroidism [19, 23]. Extensive epidemiological studies involving more than 3000 dogs diagnosed with hypothyroidism showed a significantly increased risk of the disease in sterilized females, and 30% higher incidence of hypothyroidism in castrated males compared to their intact counterparts [15]. The studies also indicated racial diversity with increased predilection to hypothyroidism in golden retrievers, Doberman pinschers, dachshunds, Shetland sheepdogs, Irish setters, Pomeranians, miniature schnauzers, cocker spaniels, and Airedale terriers, as well as a reduced risk in German shepherds and mongrels. In another publication an increased risk of hypothyroidism in females and castrated dogs was confirmed, although prevalence was only 0.2%. As races of higher risk of hypothyroidism Doberman and golden retriever were listed [19], later studies showed no differences in the concentrations of prolactin, TSH and thyroxine in castrated and non-castrated male beagle dogs [10]. As is apparent from the literature, endocrine interactions still require a lot of research, and the expansion of knowledge in this area is strictly a practical aspect. Free thyroxine (fT4) is an unbound T4 fraction that enters target tissues directly. Therefore, measuring the amount of fT4 in the blood is an effective measure of determining thyroid function. The aim of this study was to compare the concentrations of fT4 in castrated and non-castrated male as well as female dogs.

MATERIALS AND METHODS

The total number of 124 dogs without clinical signs of  hypothyroidism or dermatological changes were included to the study. The animals belonging to different breeds as well as mongrels were divided into four groups: 1) intact bitches, n=22,  2) spayed bitches,  n=45, 3) intact males, n=26, and 4) castrated males, n=31. Peripheral blood samples were collected into dry tubes containing no anticoagulant to obtain serum. Then blood was centrifuged and serum was frozen at the temperature -20°C until the time of testing. The concentration of fT4 was measured by radioimmunoassay using commercial test for the quantitative determination of hormone in human serum RIA-gnost Cisbio Bioassays OCFD03-FT4. Its sensitivity was 0.5 pg/ml (0.65 pmol/L). For statistical calculations the statistical package SPSS 19.0, 2010 was applied. The distribution of analyzed trait - fT4 concentration was checked using the Kolmogorov-Smirnov test. To estimate the effect of castration on hormone concentration the analysis of variance (ANOVA) was carried out. The regression analysis was used for the estimation of the impact of time elapsed from castration and animal’s age on the fT4 concentration. The influence of these two factors was analyzed separately.

RESULTS AND DISCUSSION

The results of fT4 concentrations are shown in Table 1. In the Kolmogorov-Smirnov test the P value for the variable fT4 was 0.768. It indicated a normal distribution of the tested values, which were compared within sexes using one-way analysis of variance. The average concentration value in castrated males and females was lower  as compared to intact animals (p<0.05), what illustrates Figure 1. In addition, in bitches a statistically significant effect of time that has elapsed from castration was observed (Tab. 2). There was namely the lowering of fT4 concentration with increasing time after castration. The regression analysis revealed influence of time on hormone concentration, what is shown in Table 2 and Figure 2. Castration is commonly performed kind of surgical intervention in male and female dogs. Its multiple benefits for the animal health (diseases prevention), for the owners, as well as social are undeniable. One of the lesser known aspects of this treatment is its effect on the structure and function of the thyroid gland. Some authors have noted an increased risk of hypothyroidism in castrated animals [15], while the others did not observe an effect of castration on thyroid function [7, 10]. Therefore, the problem is still neither fully understood, nor the risk estimated. In our study, pre-qualifying patients had to eliminate the accidental effect of systemic diseases on the results of measurements performed. We did not focus on absolute values ​​of fT4 concentration in order to diagnose hyper-, hypo- or euthyroidism. The concentrations of hormone have been compared between animal groups according to sex and carried out (or not) gonadectomy to determine the potential impact of gonadal hormones deficiency on thyroid function. Statistically significant reduction in serum fT4 concentration in both male and female castrated animals has been observed compared to the control group of intact dogs. In the study presented by Günzel-Apel et al. [10] no statistically significant differences in total T4 concentration were found between neutered and intact male dogs. In addition, in castrated females a statistically significant correlation between the time elapsed from castration and hormone level was noted in our study. The time from castration was longer, the fT4 concentration was ​​lower. This result seems logical given that the time is necessary for the appearance of possible structural and/or functional changes in the gland. The changes are more advanced, the more likely it becomes a secretory gland dysfunction. Therefore, given that the reliable indicator of the functional state of the dog’s thyroid gland is the concentration of free fraction of thyroxine [17, 21], it can be concluded that castration may predispose to hypothyroidism in dogs of both sexes. The mechanism of this effect is not recognized and its explanation requires further investigation including sex differences.  In bitches one possibility is the impact of estrogens on blood circulation, which in the case of their deficit as a consequence of performed ovariectomy may result in impaired blood flow through tissues and organs. It is well known, that estrogens affect the flow of blood in the blood vessels of the thyroid gland of women during the menstrual cycle. This leads to an increase in blood flow during the follicular phase. In addition, in girls before puberty and in women during menopause blood flow in the vessels is significantly lower when compared with women of childbearing potential [4, 5]. Similar observations were reported by Polish researchers from the Medical University of Bialystok. In this study, Doppler method for assessing blood flow in the vessels of the thyroid gland in young women was used and increased blood flow with an increase in circulating levels of estrogens was stated [11]. Such relationship can be supposed in other species. On the other hand the ovariectomy resembles the menopause in women. It can therefore hypothesize that estrogen deficiency after castration, by reducing the blood supply to the thyroid gland, has an impact on its functioning and thereby reduced the secretion of hormones and reduced their collection and transport to target tissues and organs. In males, similar role seems to play testosterone  [1, 16, 18, 22, 25]. Tissue blood flow influenced by the action of the hormone consists in extension of blood vessels, including small ones (vasodilatory effect). The long term gonadal hormones deficiency may lead to an atrophic changes of the thyroid gland, increasing the risk of hypothyroidism. Preliminary studies using quantitative scintigraphy with radioactive technetium in dogs suspected of hypothyroidism indicated the possibility of this method application to evaluate the activity of the thyroid gland [6, 20, 24]. This method, however, requires further refinement in order to be considered a standard. Maybe in the future it will allow to track the changes occurring as a result of gonadectomy. In conclusion, the results indicate the enhanced risk of hypothyroidism in castrated dogs of both sexes. Additional studies are needed to recognize the influence of gonadectomy on thyroid gland on morphological, histological and functional levels.

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