All age ranges (Infants, Juvenile, Adolescent, Adult, Middle-aged, Elderly) were included in this study by measuring serological indices such as TT3, TT4, FT3, FT4, TSH, A-TG, ATPO, TG, and ultrasonographic indices such as LAPD, LLD, RAPD, RTD, and RLD in 1027 monkeys. Due to the large sample size, the study was able to establish the most appropriate reference values for each age group. The effect of the interaction of age and sex on these assays was analysed. In addition, the prevalence of thyroid disease in naturally reared rhesus monkeys was assessed.
Due to the most similarity between rhesus monkeys and humans, the rhesus monkeys is widely used in the study of human diseases, which contributed largely to the development of medicine and other disciplines.[12] . There are different populations of rhesus monkeys, usually categorised as Indian rhesus monkeys, Chinese rhesus monkeys and hybrid rhesus monkeys. There is some genetic variability among different populations of monkeys, and therefore some variability in the reference ranges of haematological, physiological and biochemical parameters.[13] Yu et al. collected 1,805 Chinese rhesus monkeys living in southwestern China, measured 24 haematological and 27 biochemical parameters, and determined the most appropriate reference ranges for each age group.[11] Bon-Sang Koo determined 20 haematological and 16 biochemical reference ranges for crab-eating monkeys and monkeys, but the sample sizes were small.[14] The sample size was small. At present, there have been more and more studies on the above basic indexes in Chinese rhesus monkeys, but there is no comprehensive report on thyroid hormones. There are even fewer reports on thyroid ultrasonography in monkeys.
In our study, we found that thyroid hormones (TT4, TT3, FT4, FT3) in monkeys were highest in juvenile age, and the higher hormone levels would be maintained until adolescence; and with age, the hormone levels gradually and slowly declined in youth, and then relatively stabilised in adulthood and middle-age; in old age, the levels of each hormone declined to varying degrees, and the decline in males was more pronounced than that in females. Combined with Paukner A et al.[15] described the growth and development of monkeys as being faster between the ages of 1 and 3 years, Anne H. van der Spek et al.[16] stated that thyroid hormones are essential for the growth and development of the human organism, and similarly, the relatively high levels of thyroid hormones in monkeys during this period can be interpreted as being required for their growth and development. From the age of 4 years, female monkeys begin to have regular menstrual cycles.[17] and male monkeys gradually develop ejaculation[18] This suggests that young monkeys are maturing and becoming fertile, and that their need for thyroid hormones decreases during this period compared to the growth period. During adulthood and middle age, thyroid hormone levels are relatively stable, and this is the period when the rhesus monkeys vital signs are most stable. In old age, thyroid hormone levels decline considerably, especially in male monkeys, and this may be related to the age-related atrophy of the thyroid gland.[19] This may be related to the age-related atrophy of the thyroid gland.
Thyroglobulin and thyroid-associated antibodies (A-TG, A-TPO) do not differ significantly between females and males from infancy to young adulthood, but in adulthood there is a markedly higher prevalence in females than in males, as these tests are associated with autoimmune disorders of the thyroid gland, and, similar to humans, autoimmune thyroiditis is predominantly found in adult females.[20] It is reasonable to assume that there is a similar trend in the distribution of this disease in Chinese rhesus monkeys.
In thyroid ultrasonography, our statistics show that the positive rate of thyroid ultrasonography for structural abnormalities in monkeys is about 14.1%.And the incidence of thyroid nodules is about 1.7%. The positive rate of abnormal thyroid structure is about 55.4-87.5%[21] in Chinese general population, and the diagnostic rate of thyroid nodules by ultrasound is about 20.43%[22, 23]. The detection rates of the two were significantly different, but the female was significantly higher than the male. As we know, the development of thyroid nodules, thyroid cancer and autoimmune thyroiditis is affected by many factors, such as radiation exposure, living environment, mood, diet and heredity.[24] Su YW et al. found that the incidence of thyroid-related diseases was significantly higher in people working in the radiation field and in medical personnel working at high intensity than in the general population, but the incidence of thyroid-related diseases was higher in females than in males.[25] The incidence of thyroid-related diseases in Chinese rhesus monkeys was significantly higher than in the general population. The extremely low positive rate of thyroid ultrasound structural abnormalities in rhesus monkeys may be related to the fact that experimental monkeys are all kept in relatively fixed environments and have diets that meet a variety of nutritional conditions, so the possibility of being affected by environmental influences and dietary influences is drastically reduced, resulting in a markedly lower incidence of thyroid disease. But there is still the appearance of a markedly higher rate of positivity in female than in male rhesus monkeys. This has spawned a justified speculation that if environmental and lifestyle influences were removed, would the incidence of various human thyroid disorders be substantially reduced to a comparable incidence in passerine rhesus monkeys. The ultrasound grid-like changes are one of the most important indicators for the diagnosis of Hashimoto's thyroiditis[26] The rate of positive ultrasound findings in Chinese rhesus monkeys is only 2.3%, making these rhesus monkeys the best animal model for studying Hashimoto's thyroiditis.
Meanwhile, in the statistics of the size of each diameter of the thyroid gland, we found that there were some differences in the size of the longitudinal and transverse diameter of the thyroid gland, which was larger in males than in females, but there was not much difference in the anterior and posterior diameters of the thyroid gland. Combined with the distribution of body weight, male monkeys were significantly heavier than females. This may be related to the larger body size of male rhesus monkeys, for example. We also found that after entering old age, male rhesus monkeys decreased significantly in all diameters, and the magnitude of the decrease was more obvious than that of females. Combined with the fact that the decline in thyroid hormones of male monkeys was more obvious than that of females in old age, which was in line with the study of age-related hypothyroidism in the population by Zhai X et al.[19] The study of age-related hypothyroidism in monkeys was considered to be the result of age-related atrophy of the thyroid gland in rhesus monkeys.
In the correlation analysis of thyroid ultrasonography and thyroid hormones, it was found that in the abnormal ultrasonography group, the age was generally higher and the levels of thyroid hormones (TT4, TT3, FT4, FT3) were increased compared with those of the normal group, but there was no significant difference in thyroglobulin and thyroid-related antibodies (A-TG, A-TPO). It was suggested that the probability of thyroid hormones abnormality in combination with thyroid structure abnormality was significantly higher, which was similar to the population morbidity; however, the reason for the absence of high thyroid-related antibodies was to be analysed.
In summary, our study analysed the differences in thyroid ultrasonography and thyroid hormones in Chinese rhesus monkeys of different sexes in different age groups and established a range of relevant reference values. The prevalence of thyroid ultrasound abnormalities in Chinese rhesus monkeys was initially screened. This study will provide baseline data and theoretical basis for subsequent studies on the thyroid gland in Chinese rhesus monkeys as experimental animals.