| ObjectiveGonadal dysfunction is a clinical symptom complex in endocrinology.Through summarizing hospitalized patients with a gonadal dysfunction during the past 30 years, we introduce the characteristics of the disease distribution and the changes of the disease spectrum.21-hydroxylase deficiency (21-OHD) is a part of the most important disorders in Gonadal dysfunction, as a result of the CYP21 gene mutation.To investigate the relationship between the adrenal CT manifestations and genotype of 21-OHD, we review the patients of 21-OHD with detailed clinical data.Ovotesticular disorders of sex development (DSD) are a disorder of gonadal development was characterised by the presence of both ovarian and testicular tissue in an individual. Through summarizing quantifiable characteristic of TH, we present our experience with evaluation and treatment of 14 patients with this rare form of ambiguous genitalia, focusing on gonadal structure and function before and after gonadal surgery.Methods1. All data of gonadal dysfunction patients admitted to Chinese PLA general hospital between 1985 and 2014 were collected.The sex ratio of patients, visiting ages, final diagnosis, the year of hospitalization and address were retrospectively collected.The etiology and disease spectrum was analyzed built on time and age.2. Among all included cases, we further analyzed those who were diagnosing as 21-hydroxylase deficiency. Patients’clinical characteristics, biochemical examination results, genotype and adrenal imaging features were retrospectively analyzed.3. We retrospectively reviewed the clinical characteristics of 14 patients with histologically confirmed ovotesticular DSD.Results1. ①During the past 30 years,1233 patients, with gonadal dysfunction were admitted to the Chinese PLA General Hospital, of which,790 patients were asked males, and the other 443 patients were raised as females.The overall average age was 20.79±10.42 years old, and the peak age was at puberty, from 13 years old to 18 years old. ②The number of patients was gradually increased year by year.The cause of the disease is complex.Acquired hypogonadotropic hypogonadism(CHH) was the most common disease(34.51%). Idiopathic hypogonadotropic hypogonadism(AHH) was progressively increased year by year(15.20%vs22.24%, P<0.05), as well as the pituitary stalk interruption syndrome(Ovs 12.80%, P<0.05). There is not any significant change in other disorders.③429 patients were diagnosing as disorders of sex development(DSD), of which,298 patients were asked males, and the other 131 patients were raised as females.The average age of patients with DSD was less than none-DSD patients (18.90±7.11 vs 21.65± 11.66years old, P<0.05).The etiology of the disease changed along with the page.DSD includes three broad categories:278 cases of 46, XY DSD (64.80%),86 cases of 46, XX DSD(20.05%) and 65 cases of sex chromosome DSD(15.15%). CHH had the highest proportion in 46, XY DSD(76.26%).21-OHD occupied the greatest proportion in 46, XX DSD (53.49%).⊙The number of patients with DSD was gradually increased year by year.The etiology of the DSD is complex.IHH had the highest proportion in each time period(29.31%,30.69%,33.70%). The hospitalizing rate of the patients from the rural areas increased year by year(24.14%vs27.73%vs37.04%, P<0.05). However, The hospitalizing rate of the patients from the big city was located in decline.2.①The number of patients with 21-OHD was 28, of which,5 male and 23 females. The clinical presentations were divided into the simple visualizing(SV,23 cases) and non-classical(NC,5 cases).The average age was 18.64±12.38 years old.Compared with actual age, the bone age is prior to 5.00±2.52 years old in patients diagnosed with SV. While, bone epiphysis closed in all patients suffered from NC.The reason for hospitalization was modified.All female patients diagnosed with SV had ambiguous genitalia, while, the female patients diagnosed of NC were hospitalized for hirsutism, cutaneous pigmentation and breast dysplasia.Male patients diagnosed of SV were hospitalized for precocious puberty, while male patients diagnosed of NC were hospitalized for adrenal incidentally.Observation of higher basal ACTH and 17-OHP concentrations[46.71 ±33.39pmol/L,35.66 (25.59,60.65) ng/ml], as well as the level of dehydroepiandrosterone and testosterone in female patients. However, the level of serum electrolytes, cortisol, gonadotropin levels was very normal.②In this study,7 kind of mutation was identified in 56 alleles.Most frequent mutations in 28 cases were I172N (39.29%) and i2g (30.36%), followed by P30L (5.36%), R356W (5.36%),exon13de18bp (5.36%),Q318X (3.57%) and Arg484FS (1.79%). ③The adrenal CT features were varied in patients with 21-OHD.The most common manifestation was bilateral adrenal hyperplasia (42.86%), followed by adrenal nodular hyperplasia(14.29%), unilateral adrenal hyperplasia (10.71%), adrenal hyperplasia with unilateral solid cystic lesion (10.71%), adrenal hyperplasia and double side real cystic lesion(3.57%). Moreover,5 patients had normal adrenal CT.Common mutations in different adrenal CT manifestations were varied.④ Group by adrenal CT features, the average age of the group of unilateral adrenal hyperplasia was the lowest. Report to other groups, the level of ACTH and 17-OHP was significantly higher in a group of adrenal nodular hyperplasia.However, the ACTH level was much lower in a group of normal adrenal CT.The multivariate logistic regression analysis showed that severe mutations and the level of ACTH. Cortisol had a sizable effect in adrenal morphology of the patients.3. The number of patients with ovotesticular DSD was 14.8 out of 14 patients was raised as males, and the other six were asked females.All patients had ambiguous genitalia.The most frequent karyotype of ovotesticular DSD was 46, XX, constituting 64.2% of our series. The frequency of searching for the SRY gene in 46, XX cases was 22.2%. Ovotestis was the most frequent finding (42.9%).Exploration of the gonads revealed that bilateral ovotestis in 3 patients, ovotestis plus ovary or testis in 6 patients, ovary on one side and testis on the other side in 5 patients. Observation of lower basal testosterone concentrations and lower basal estradiol levels in 10 patients.All patients received conservative gonadal surgery and 4 patients received hormone replacement therapy.Seven patients were followed for 3 months to 10 years.3 out of 7 patients obtained appropriate pubertal development.No gonadal tumors were noted during followup.Conclusion1. The number of patients with gonadal dysfunction was slightly increased during the past 30 years. The number of DSD was raised, too. The disease spectrum of gonadal dysfunction has been changed. In respect of etiology, CHH topped the list, and then IHH. The hospitalizing rate of the patients from the rural areas increased year by year, while,1. The patients from the big city were located in decline.2. The clinical manifestations of 21-OHD were female masculinization and male precocious puberty, while NC 21-OHD may be asymptomatic. In this study, the most frequent mutation in 28 cases of Chinese 21-OHD was I172N, followed by i2g, and the NC 21-OHD also carried moderate or severe mutations such as i2g, P30L.The adrenal CT features were varied in patients with 21-OHD.The most frequent manifestation was bilateral adrenal hyperplasia. Common mutations in different adrenal CT manifestations were varied.Severe mutations and the level of ACTH, cortisol had a sizable effect in adrenal morphology of the patients.3. Diagnosis of ovotesticular DSD is well defined.It is essential that a thorough examination be made in patients with ambiguous genitalia, cardiomegaly and severe hypospadias.Earlier diagnosis and more appropriate conservative gonadal surgery are very suggestive for the prognosis.The appropriate choice of gender should be made according to the characteristics of external genitals and the prominent gonads.Continued followup is obligatory because of the multiple psychological, gynecological and urological problems encountered postoperatively by these patients. |
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