[Effect of growth hormone supplementation on liver and lung function in patients with hypopituitarism].

To analyze the clinical features of patients with anterior hypopituitarism (HP) complicated with cirrhosis, and to explore the effects of growth hormone supplementation on liver and lung function. A total of 11 patients with HP complicated with cirrhosis admitted to Peking Union Medical College Hospital from January 2016 to December 2022 were included in the study, including 8 males and 3 females, aged [M(Q1, Q3)]31 (20, 37) years. There were 6 patients with pituitary stalk interruption syndrome, 4 patients after craniopharyngioma resection, and 1 patient after germinal cell tumor chemoradiotherapy. Cirrhosis appeared at [M(Q1, Q3)]7 (1, 16) years after the diagnosis of HP. There were 7 cases complicated with hepatopulmonary syndrome (HPS). The liver and lung function of 5 patients were improved significantly after the addition of growth hormone, and the arterial partial pressure of oxygen increased from (47±11) mmHg(1 mmHg=0.133 kPa) to (84±12) mmHg. Timely supplementation of growth hormone can improve the symptoms of fatty liver, cirrhosis and HPS, and postpone or even avoid the transplantation of liver and other organs.

[Clinical discussion on methimazole in the treatment of hyperthyroidism].

Methimazole is the most commonly used medication for hyperthyroidism with good effects and little adverse reactions. However, improper selection of initial dose will affect the efficacy, such as excessive dose is proven to various adverse reactions; insufficient dose can hardly achieve desired efficacy. Based on the literature and personal clinical experience, the author discusses the following clinical issues related to methimazole in the treatment of hyperthyroidism, including the selection of initial dose, dose adjustment and withdrawal of methimazole, drug therapy for patients with liver function injury, and management strategies for methimazole-related adverse reactions.

[Analysis of differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome].

Objective: To analyze the differences in clinical and biochemical characteristics and treatment effects in patients with different genotypes of Prader-Willi syndrome (PWS). Methods: A total of 35 patients with PWS, 20 males and 15 females aged from 0.8 to 10.0 years with an average age of 3.0 years, were retrospectively included in this study. All of them were treated in the Department of Endocrinology of Peking Union Medical College Hospital from May 2017 to December 2018. The clinical material, biochemical data, and peripheral blood samples of the patients were collected. Genomic DNA was extracted from peripheral blood leukocytes of patients, and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was used to detect gene deletion or abnormal methylation. According to the results of detection, 35 patients were divided into two groups: paternal deletion group(n=27) and methylation abnormal group(n=8). The biochemical test results and the effect of growth hormone (GH) treatment of the two groups were analyzed. Results: MS-MLPA showed that 77% (27/35) of the patients were confirmed paternal deletion and 23% (8/35) were abnormal methylation. In terms of biochemical test results, the plasma concentrations of uric acid(UA) in the paternal deletion group were higher than that in the abnormal methylation group [(363±101) µmol/L vs (259±74) µ mol/L, P=0.019 ]. There is a linear relationship between body weight and uric acid level. After adjustment for weight., there was no significant difference in UA level between the two groups (P=0.101). Patients in both groups were treated with GH ((0.14±0.03) U/kg, QD). In paternal deletion group, patients were followed up for (26.0±13.6) months, and their height increased from (99.0±31.5) cm [(-0.3±1.1) SDS] to (107.5±27.0) cm [(0.7±0.9) SDS] (P=0.037). In the abnormal methylation group, patients were followed up for (25.8±11.6) months, and their height increased from (86.4±31.2) cm [(-0.7±1.8) SDS] to (95.6±26.5) cm [(0.0±1.6) SDS] (P=0.557). There was no significant difference in body mass index (BMI) between paternal deletion group and abnormal methylation group before and after treatment [(22.0±7.1) vs (22.4±6.8)] kg/m2, P=0.890;(17.0±3.1) vs (16.4±2.7) kg/m2, P=0.754]. Conclusions: There were no significant differences in biochemical test results between patients with paternal deletion and those with abnormal methylation. Early treatment with GH in PWS patients can effectively improve the increasing height and reduce excessive weight gain.

[Prevalence and related factors of dyslipidemia in patients with 21-hydroxylase deficiency].

Objective: To analyze the prevalence and the related factors of dyslipidemia in 21-hydroxylase deficiency (21-OHD) patients. Methods: A total of 205 patients with 21-OHD were recruited in Peking Union Medical College Hospital from January 2016 to January 2018. The basic information, glucocorticoid replacement therapy, and laboratory examination results of patients were obtained from medical records. The genotypes of CYP21A2 were identified by Sanger sequencing and multiplex ligation dependent probe amplification. The prevalence of dyslipidemia among 21-OHD patients, basic information and related hormone levels of 21-OHD patients with different status of blood lipid were described. Logistic regression model was used to analyze the related factors of dyslipidemia in 21-OHD patients. Results: The age of subjects was 17.0 (8.3, 25.0) years old, including 51 males (24.9%). According to CYP21A2 genotypes, there were 16 cases in Null group, 26 cases in Group A, 105 cases in group B, 27 cases in group C, and 31 cases in group D. The incidence of dyslipidemia was 29.3% (60/205), among which 37.3% (19/51) in male and 26.6% (41/154) in female patients, respectively. The M (Q1, Q3) of total cortisol level (nmol/L) and body mass index (kg/m2) of male 21-OHD patients with dyslipidemia were 0.17 (0.06, 0.35) and 25.76 (17.01, 30.45), respectively, which were higher than those with ortholiposis [0.04 (0.02, 0.21) and 18.83 (16.53, 23.88)] (all P<0.05). The M (Q1, Q3) of progesterone level (nmol/L), body mass index (kg/m2) and age (years) of female 21-OHD patients with dyslipidemia were 74.40 (50.97, 98.52), 23.09 (21.78, 27.78) and 23.00 (16.50, 28.00), respectively, which were higher than those with ortholiposis [52.81 (33.41, 68.85), 21.55 (18.63, 25.71) and 18.00 (9.50, 25.00)] (all P<0.05). The risk of dyslipidemia increased by 5.0% [OR (95%CI): 1.05 (1.01, 1.09)] for every 1 nmol/L increase of progesterone. Conclusion: The incidence of dyslipidemia is high in 21-OHD patients, and progesterone level is positively correlated with dyslipidemia.

[Clinical characteristics of testicular adrenal rest tumor and factors associated with its occurrence in 21-hydroxylase deficiency patients].

Objective: To analyze the occurrence and clinical characteristics of testicular adrenal rest tumor (TART) in 21-hydroxylase deficiency (21-OHD) patients, and further explore the possible factors related to the occurrence of TART. Methods: Twenty-seven male 21-OHD patients who visited Peking Union Medical College Hospital from January to December 2018 were enrolled and their clinical and biochemical data were collected. The CYP21A2 mutations were identified by Sanger sequencing and multiple ligation probe amplification (MLPA). Patients were divided into different subgroups according to the residual activity of 21-hydroxylase: Null (residual enzymatic activity 0, 3 cases), group A (0-<1%, 9 cases), group B (1%-5%, 7 cases), group C (20%-50%, 2 cases) and group D (6 cases). The ultrasound of testis was used to detect whether there was TART and its morphological characteristics. Results: Among 27 patients with 21-OHD [average age (17.4±9.3) years], 55.6% (15/27) had TART lesions, most of them were adolescents, and the youngest was only 4 years old. The lesions were mostly bilateral and hypoechoic. The levels of 17α-hydroxyprogesterone (17-OHP) and progesterone in patients with TART were higher than those in patients without TART [17-OHP: 199.6 (62.1, 232.7) nmol/L vs 7.4 (3.2, 105.0) nmol/L, P=0.003; progesterone: 97.1 (42.0, 126.8) nmol/L vs 5.4 (0.7, 20.0) nmol/L, P=0.004]. There was a correlation between the occurrence of TART and genotype of CYP21A2. Patients with Null and A genotypes were more likely to have TART than those with B and C genotypes (8/12 vs 4/9, P=0.021). Conclusions: TART is common in 21-OHD male patients, which is related to 17-OHP and CYP21A2 genotype. It is of great significance for the early screening of TART in 21-OHD patients.

[Detection of CYP21A2 gene mutations and the differences in the levels of hormones in patients with 21-hydroxylase deficiency].

Objective: To analyze the detection of CYP21A2 gene mutations in 21-hydroxylase deficiency (21-OHD) patients, so as to determine the accuracy of clinical diagnosis. Methods: Totally, 514 patients with 21-OHD who visited Peking Union Medical College Hospital from January 2015 to January 2018 were enrolled and their clinical and biochemical data were collected. DNAs were extracted from peripheral blood leukocytes and CYP21A2 mutations were detected by Sanger sequencing and multiple ligation probe amplification (MLPA) technique. We divided 514 patients into three groups: two mutations of CYP21A2 alleles (group A), one mutation of CYP21A2 (group B), and no mutation of CYP21A2 (group C). Results: Mutation was detected in each allele of CYP21A2 gene in 401 (78.0%) patients, ninety (17.5%) had only one mutant allele and 23 (4.5%) had no mutation. There was no significant difference between the patients with different clinical phenotypes and the number of CYP21A2 gene mutations detected. In male, the cortisol of the patients with simple virilizing 21-OHD in group A [0.04 (0.02, 0.20) nmol/L] was lower than that of group B [0.24 (0.17, 0.28) nmol/L] and the difference was statistically significant (P=0.014). In female, 17-hydroxyprogesterone (17-OHP) of patients with salt wasting 21-OHD in group A [153.7 (90.1, 204.5) nmol/L] was higher than that of group B [38.2 (31.0, 183.3) nmol/L] and C [42.6 (27.8, 48.1) nmol/L] and the differences were statistically significant (both P<0.05). The progesterone of patients with simple virilizing 21-OHD in group C [23.0 (8.6, 33.2) nmol/L] was lower than that of gourp A [57.8 (34.4, 110.2) nmol/L] and B [63.6 (31.4, 110.8) nmol/L] and the difference were statistically significant (both P<0.05). The 17-OHP of patients with non-classical 21-OHD in group C [24.5 (20.4, 54.2) nmol/L] was lower than that of group A [158.7 (59.1, 187.6) nmol/L] and B [147.8 (131.9, 179.3) nmol/L]. The difference were statistically significant (both P<0.05). Conclusions: Mutations of two alleles have not been found in all patients with clinically diagnosed 21-OHD. Other congenital adrenal hyperplasia (CAH) types which can cause similar changes in 17-OHP and other hormones may be misdiagnosed as 21-OHD. Therefore, 21-OHD cannot be diagnosed with help of 17-OHP level only, and gene detection plays a vital role in the differential diagnosis of different CAH types.

[Analysis of copy number variation of CYP21A2 gene and the type of CYP21A1P/CYP21A2 fused gene in patients with 21-hydroxylase deficiency].

Objective: To analyze the copy number variation of CYP21A2 gene in 21-hydroxylase deficiency (21-OHD) patients, and identify the three copy repetition, single copy deletion of CYP21A2 gene and the type and proportion of CYP21A1P/CYP21A2 fused gene in 21-OHD patients. Methods: A total of 424 patients (140 males and 284 females) with 21-OHD who visited Peking Union Medical College Hospital from January 2015 to January 2018 were enrolled and the average age was (17.1±12.4) years. All clinical and biochemical data were collected. DNAs were extracted from peripheral blood leukocytes, and CYP21A2 gene mutation and copy number variation were detected by Sanger sequencing and multiple ligation probe amplification (MLPA). Results: Of 424 21-OHD patients, 287 (67.7%) had two copies of CYP21A2 gene, 137 (32.3%) had copy number variation, of which 1 patients (0.2%) had 3 copies of CYP21A2 gene and 136 (32.1%) were carriers of large deletion/rearrangement mutation of CYP21A2 gene. Three pathogenic mutations including a truncated Q319X protein mutation were detected in the patient with 3 copies of CYP21A2 gene. Of 136 patients with large deletion/rearrangement mutation of CYP21A2 gene, 82 (60.3%) carried fused CYP21A1P/CYP21A2 gene, and the remaining 54 harbored the one allele deletion of CYP21A2. The most common types of fused CYP21A1P/CYP21A2 gene were CH-5, CH-1 and CH-2, with the frequency being 31.7% (26 cases), 26.8% (22 cases) and 19.5% (16 cases), respectively, and followed by CH-4 and CH-7, with the incidence being 8.5% (7 cases) and 4.9% (4 cases), respectively. In addition, two cases of CH-3, CH-6 and CH-8 and one case of CH-9 were detected. Conclusions: This is the first study to detect the occurrence of CYP21A2 gene copy number variation and fused CYP21A1P/CYP21A2 gene in a large cohort of 21-OHD patients. The number of CYP21A2 gene copies in 21-OHD patients includes 2 copies, 1 copy deletion and 3 copies duplication. One copy deletion of CYP21A2 includes one allele deletion of CYP21A2 gene and fused CYP21A1P/CYP21A2 gene. In patients with 3 copies of CYP21A2 gene, pathogenic mutations should be verified in all 3 copies of CYP21A2 gene to make the precise diagnosis. Therefore, the accurate molecular diagnosis of 21-OHD patients should take both genotype and copy number variation of CYP21A2 into account.

[Changes of sex hormones and sex hormone-binding globulin levels in male adults with hyperthyroidism before and after antithyroid drug treatment].

Objective: To observe the changes of sex hormone and sex hormone-binding globulin (SHBG) levels in young male patients with hyperthyroidism before and after antithyroid drug (ATD) treatment. Methods: Between January 2015 and July 2016, forty male patients with hyperthyroidism aged 19-52 years (with an median age of 33.1 years) were enrolled in the Department of Endocrinology of Peking Union Medical College Hospital. Blood samples were taken before treatment and at 1 month, 2 months, 3 months and 5 months after treatment to evaluate thyroid function, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone(T), free testosterone(FT), estradiol(E2), prolactin and SHBG. Results: A total of 40 patients were enrolled but only 35 patients completed the follow-up. The patients had high levels of thyroid function, SHBG and sex hormones before treatment. Before treatment, free thyroxine (FT(4)), free triiodothyronine (FT(3)), SHBG, LH, estradiol, testosterone and free testosterone was (0.30±0.12) pmol/L, (9.68±4.73) pmol/L, (146±111) nmol/L, (8.41±3.61) U/L, (19.9±7.7) pmol/L, (29.9±9.5) nmol/L and (0.24±0.08) nmol/L, respectively. After treatment, the level of triiodothyronine, thyroxine, FT(3) and FT(4) gradually decreased to normal (all P<0.001). Thyroid stimulating hormone (TSH) gradually increased to normal (P<0.001). LH and estradiol levels gradually decreased (all P<0.001). FSH decreased but the difference was not statistically significant. Prolactin did not change significantly. Testosterone and SHBG levels decreased significantly while the levels of free testosterone, free testosterone percentage (FT%), bio-available testosterone (BAT), bio-available testosterone percentage (BAT%), free androgen index (FAI) gradually increased and stabilized (all P<0.001). The difference was not statistically significant between T/LH and E2/LH before and after treatment (all P>0.05). However FT/LH gradually increased and its difference was statistically significant (P<0.001). Conclusion: The levels of LH, estradiol, testosterone and SHBG in male patients with hyperthyroidism significantly increased, while the free testosterone level decreased, but they all gradually returned to normal with the lowering of thyroid hormone levels during ATD treatment.

[Molecular and clinical study on homozygous or heterozygous large deletion of CYP21A2 gene in 21-OHD patients].

Objective: To explore the relationship between homozygous or heterozygous large deletion of CYP21A2 gene and clinical manifestation in 21-hydroxylase deficiency (21-OHD) patients. Methods: The records of 100 patients with 21-OHD were collected between June 2016 and December 2017 in Peking Union Medical College Hospital. Large deletion of CYP21A2 gene was detected by multiplex ligation probe amplification (MLPA). The biochemical results and clinical symptoms of patients with homozygous or heterozygous large deletion were analyzed in order to investigate the influence of complete or single allele deletion of CYP21A2 gene on 21-OHD patients. Results: Large deletion of CYP21A2 gene was detected in 33 patients by MLPA, including 13 males and 20 females, with an median age of 10 (6,16) years. Two of them had simultaneous deletions of two alleles. Among 31 patients with heterozygous deletion, 16 were combined with gene mutations that severely affected 21-hydroxylase enzyme activity (I2G and Q318X), 15 with mutations that retained part enzyme activity (I172N and P30L). Two patients with complete deletion of CYP21A2 gene had no significant difference in biochemical and clinical manifestations compared with those with single allele deletion combined with another gene mutation that severely affected enzyme activity. Both kinds of patients above were manifested as severe salt-wasting type. Patients with a single allele deletion and a mutation retaining part enzyme activity were manifested as mild simple-viralizing type. Conclusion: Large deletion of CYP21A2 gene could appear in 21-OHD patients and the phenotype is similar to that of salt-wasting patients with heterozygous large deletion.

[Diagnostic value of multiplex ligation dependent probe amplification combined with Sanger sequencing in 21-hydroxylase deficiency].

Objective: To study the procedure of CYP21A2 gene mutation detection in 21-hydroxylase deficiency (21-OHD) patients. Methods: The detail clinical and biochemical data of 51 patients with 21-OHD [18 males and 33 females, with an average age of (16.4±9.9) years] were collected between December 2016 and December 2017 at Department of Endocrinology, Peking Union Medical College Hospital. Multiplex ligation dependent probe amplification (MLPA) and Sanger sequencing of the CYP21A2 gene were used to clarify the cause of 21-OHD. The genotype-phenotype correlation was also analyzed. Results: The incidences of large deletion, 8 bp deletion, I2G, I172N and F306+T were 19.6% (20/102), 1.0% (1/102), 30.4% (31/102), 25.5% (26/102) and 1.0%(1/102), respectively, and the detection rate of gene mutation in 51 21-OHD patients was 77.5% (79/102) by MLPA test. Except large and 8 bp deletion, all above mutations contained in MLPA and other 8 mutations, including P31L, Q319X, R361L, R357W, V282L, R484Q, G425S and R342W were detected, and the detection rate was 79.4% (81/102) by Sanger sequencing of CYP21A2. MLPA combined with direct sequencing identified mutations in all patients. Genotype correlated well with clinical phenotype in 21-OHD patients. Conclusions: When MLPA or CYP21A2 gene sequencing were used alone to diagnose the cause of 21-OHD, gene mutations in all patients could not be detected. The combination of the two methods can complement each other and fully clarify the underlying causes of 21-OHD.

[Diagnosis and management of adult-onset idiopathic hypogonadotropic hypogonadism].

Objective: To investigate the clinical features and management of male patients with adult-onset idiopathic hypogonadotropic hypogonadism (AIHH). Methods: Clinical features and treatment of six patients with AIHH between January 2010 and June 2017 were retrospectively reviewed. Results: The patients were all male, with an age of 26 (20-35) years old and they experienced complete pubertal development. The main complaints were decreased libido, erectile dysfunction and gynecomastia. Physical examination found that the testicular size was 15 (12-20) ml and they were fully virilized. The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone was 0.1 (0.1-0.8) U/L, 0.4 (0.1-0.9) U/L and 0.62 (0.10-0.90) nmol/L, respectively. Pituitary MRI and other pituitary hormones were all normal. Testosterone was administrated to three patients and the libido and erectile function returned to normal. Sperm was successfully induced in two patients after combined gonadotropin therapy for 4-6 months. One patient had a reversed hypothalamus-pituitary-testis axis function. Conclusions: The mechanism of male AIHH is unknown. Compared to those with congenital hypogonadotropic hypogonadism, patients with AIHH may achieve better spermatogenesis after gonadotropin therapy. Small portion of patients may have a reversal of hypothalamus-pituitary-testis axis function.

[Effect of recombinant human growth hormone therapy on metabolic parameters in patients with craniopharyngioma].

Objective: To investigate the effects of recombinant human growth hormone (rhGH) on metabolic parameters in patients with craniopharyngioma surgeries. Methods: Totallys 30 patients with craniopharyngioma were included in this retrospective study. They were divided into growth hormone (GH) group and control group according to whether they received rhGH therapy or not. The following parameters, including body mass index (BMI), weight, waist circumstance, transaminase, fasting blood glucose, lipid profile and high-sensitivity C-reactive protein (hsCRP) were compared after rhGH therapy for 4-6 months. Results: In GH group, patients were 18-46 (30.0±8.8) years old. The duration after craniopharyngioma surgery was (12.9±5.4) years. Before rhGH therapy, they had got sufficient thyroid and glucocorticoid hormone replacement. After rhGH therapy, the body weight decreased from (92.3±20.1) to (87.6 ±14.6) kg (P=0.190), with a reduction of BMI from (30.1±5.9) to (28.2±3.7) kg/m(2) (P=0.120). The waist circumference decreased from (104.4±9.4) cm to (98.8±10.6) cm (P=0.002). Alanine aminotransferase (ALT) decreased from (52±34) to (28±19) U/L (P=0.029), with a reduction of aspartate transaminase (AST) from (46±21) to (33±18) U/L (P=0.035) and γ-glutamyl transpeptadase (GGT) from (59±42) to (29±15) U/L (P=0.02). hsCRP decreased from (5.3±4.9) to (2.3±2.8) mg/L (P=0.006) and triglyceride (TG) decreased from (1.8±0.7) to (1.5±0.6) mmol/L (P=0.028). Fasting blood glucose, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and free fat acid (FFA) were not significantly changed(all P>0.05). In the control group, the above mentioned parameters did not changed significantly during 4-6 months of observational period(all P>0.05). Conclusion: rhGH therapy improves metabolic parameters in patients after craniopharyngioma surgery by decreasing body weight, waist circumstance and fat deposit in liver, as well as lowering TG and hsCRP levels.

[Effect of pulsatile GnRH therapy on pituitary-testicular axis function in male patients with pituitary stalk interruption syndrome].

OBJECTIVE: To evaluate the efficacy of pulsatile gonadotropin-releasing hormone (GnRH) therapy in male patients with pituitary stalk interruption syndrome (PSIS). METHODS: Fourteen male PSIS patients, who had received subcutaneous pulsatile GnRH therapy for at least four weeks at Peking Union Medical College Hospital from April 2014 to September 2015, were included in the study. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone level, testicular volume and sperm in ejaculation were measured. After treatment for four weeks, subjects with serum LH≥1.24 U/L were classified as"good response group", and others were classified as"poor response group". RESULTS: All patients were born by breech delivery and presented with absent pubertal development. Laboratory findings showed combined pituitary hormone deficiency in all patients. Pituitary stalk interruption syndrome was diagnosed based on MRI findings. Totally 11 out of 14 patients showed good response to pulsatile GnRH therapy. Their LH level increased from 0.32 (0.15, 0.61) U/L to 4.34(2.52, 7.39)U/L(P<0.001), FSH from 0.84 (0.30, 1.50) U/L to 7.12 (4.53, 10.09) U/L(P<0.001); serum testosterone level from 0 (0, 0.45) nmol/L to 2.46 (0.56, 11.45) nmol/L (P=0.004) and testicular volume from 2.0 (2.0, 4.0) ml to 4.0 (3.0, 6.0) ml (P=0.005). Sperm was detected in seminal samples after treatment for 8 weeks in two patients and for 12 weeks in one patients. Three out of 14 patients showed poor response to pulsatile GnRH therapy. CONCLUSION: Pulsatile GnRH therapy can effectively establish the pituitary-testicular axis function for most patients with pituitary stalk interruption syndrome, indicating enough reserve of gonadotrophs in the pituitary.

[Dysfunction of hypothalamic-pituitary-testicular axis in patients with adrenal hypoplasia congenita due to DAX-1 gene mutation].

OBJECTIVE: To evaluate the hypothalamic-pituitary-testicular axis (HPTA) function and spermatogenesis in male patients with X-linked adrenal hypoplasia congenita (AHC) due to DAX-1 gene mutation. METHODS: Twenty-four adult male patients from Peking Union Medical College Hospital between November 2007 and December 2014 were included.Their DAX-1 gene mutations were confirmed by polymerase chain reaction (PCR) and clinical features, hormone level and semen assay were collected. RESULTS: All patients presented with adrenal deficiency symptom.21 patients (87.5%) showed the symptoms before the age of 10 years old.The average testicular volume was 2.0 (2.0, 3.8) ml at the baseline in 24 patients.Three patients had cryptorchidism.Serum testosterone level increased from 0.1 (0, 0.5) nmol/L to 13.5 (7.6, 15.4) nmol/L (n=16) after human chorionic gonadotropin (HCG) stimulation.23 out of 24 patients were diagnosed as hypogonadotropic hypogonadism (HH) and only one patient was diagnosed as azoospermia with normal gonadotropin and testosterone level.Combined gonadotropin therapy was administered in seven patients and their serum testosterone level reached 15.3(8.4, 25.3) nmol/L, but no obvious testicular enlargement was observed [(4.0±2.9) vs (4.9±3.3) ml , P=0.270] and seminal analysis revealed persistent azoospermia.Another patient showed response to pulsatile GnRH therapy.Luteinizing hormone(LH) level increased from 1.0 U/L to 9.3 U/L, and follicle stimulating hormone(FSH) level increased from 3.0 U/L to 13.5 U/L.Serum testosterone level increased from 0 nmol/L to 10.0 nmol/L, but testicular volume maintained 3 ml after treatment for two months. CONCLUSIONS: Male patients with DAX-1 gene mutations presented with primary defect in spermatogenesis and hypogonadotropic hypogonadism.Their Leydig cell function was almost normal, while Sertoli cell and seminiferous tubule function were seriously damaged.

[Possibility of progesterone as the diagnostic biomarker of 21-hydroxylase deficiency].

Objective: To explore the diagnostic value of progesterone in 21-hydroxylase deficiency (21-OHD). Methods: One hundred and ninety-three patients (female: 127, male: 66) with 21-OHD were recruited at Peking Union Medical College Hospital between January and December 2015. At the same time, 253 patients (female: 162, male: 91) with other disease were included as control, and their sex hormone and 17-OHP were measured simultaneously. The correlation between 17-alpha-hydroxyprogesterone (17-OHP) and progesterone was analyzed and the probability of progesterone as the diagnostic biomarker of 21-OHD was determined. Results: There was obvious positive correlation between progesterone and 17-OHP levels in subjects with different age and gender, and the correlation coefficient was from 0.775 to 0.878 (all P<0.001). Receiver operating characteristic curve (ROC) analysis showed that the area under curve was from 0.930 to 1.000 (all P<0.001) when using progesterone as the diagnostic biomarker. Conclusions: Obvious positive correlation exists between progesterone and 17-OHP in patients with 21-OHD. The measurement of progesterone can be an assistant method for the diagnosis of 21-OHD.

Diabetes insipidus as the first symptom caused by lung cancer metastasis to the pituitary glands: clinical presentations, diagnosis, and management.

BACKGROUND: Central diabetes insipidus (CDI), secondary to pituitary metastatic lesions, is uncommon; however, lung and breast cancer are the commonest malignancies to have metastases to the pituitary. Early management of systemic chemotherapy and pituitary irradiation might improve the prognosis of patients. AIMS: To investigate the clinical features, diagnosis, and management of CDI caused by lung cancer metastasis to the pituitary glands. MATERIALS AND METHODS: We retrospectively reviewed 10 patients who had CDI as their first symptom before their lung cancers were diagnosed. Their clinical presentations, anterior pituitary gland function, sellar magnetic resonance imaging (MRI), management, and prognosis were described. SETTINGS AND DESIGN: This retrospective cross-sectional clinical study was conducted in a medical college hospital. RESULTS: The patient's mean age was 58.6±7.8 years. Diabetes insipidus was the main complaint when they were referred to our hospital. MRI revealed specific dumbbell-shaped masses in the sella turcica in five patients. In seven patients whose hormones were measured, the levels of hormones from adenohypophysis were abnormally low in six patients. The main treatments included surgery, systemic chemotherapy, and sellar irradiation. Although nine patients had poor prognoses, one patient has survived for more than 3 years, suggesting benefit from early diagnosis and treatment. CONCLUSIONS: New-onset CDI might be the only symptom presented by the patients with pituitary metastasis (PM) from lung cancer. Dumbbell-shaped sellar masses in MRI are prone to the diagnosis of PM. A thorough examination for primary cancer should be carried out in these aged and elderly patients.

A comparison of laparoscopic surgery and laparotomy in the treatment of ectopic pregnancy.

OBJECTIVES: To compare the laparoscopic approach with laparotomy in the treatment of ectopic pregnancy. The aim of this study was to evaluate the efficiency of laparoscopic surgery for ectopic pregnancies in China. METHOD: A retrospective analysis involving 142 patients with ectopic pregnancies was done. Seventy-two of the 142 patients were treated laparoscopically. RESULTS: In the laparoscopic group, the operating time and post-hospital stay were significantly shorter but the total cost was higher compared with the laparotomy group. CONCLUSION: Although the laparoscopic surgery for ectopic pregnancies is a new approach and it is not widely practiced in China; it has more advantages than open surgery and it has been well accepted by the surgeons and patients. It is a safe and feasible approach, but the rate of laparoscopic approach for ectopic pregnancy is still low in China when compared with the developed countries.

Molecular cloning and characterization of the rat ovarian 20 alpha-hydroxysteroid dehydrogenase gene.

The rat 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) is an enzyme responsible for the catabolism of progesterone to the inactive 20 alpha-hydroxprogesterone. We have previously shown that the expression of this enzyme is not regulated by post-translational modification, but at the level of transcription. In this study we have established that the 20 alpha-HSD gene contains nine exons and have isolated a 2.5 kb promoter region. The transcription start site was identified and a TATA box was found. 5' deletions of this promoter significantly decreased basal promoter activity. Treatment with forskolin led to a dose dependent inhibition of the 2.5kg-20 alpha-HSD-luciferase construct. Computer analysis identified one CRE, two Nur77 response elements, two putative AP1 sites and one progesterone response element half-site. In summary, we have identified and partially characterized the promoter region of the rat ovarian 20 alpha-HSD and demonstrated that the regulatory elements for 20 alpha-HSD are present within a 2.5 kb 5' flanking region of the gene.