[The relationship between clinical characteristics and pathological features in patients with pheochromocytomas/paragangliomas].

Objective: To explore the correlation between clinical characteristics and pathological features in patients with pheochromocytoma/paraganglioma (PPGLs). Methods: A case series study. A retrospective analysis was conducted on patients with single and primary PPGLs after postoperative pathological diagnosis who were admitted to Peking Union Medical College Hospital between January 2019 and December 2022. The patients were divided into the Ki-67<3% group and the Ki-67≥3% group with Ki-67 proliferation index of 3% as the threshold. The relationship between clinical and pathological characteristics of PPGLs was analyzed. Results: A total of 399 PPGLs patients were included, with 177 males and 222 females, aged [M(Q1, Q3)] 45.0(35.5, 53.0) years. Among them, 226 (56.6%) cases originated from the adrenal gland, while 104 cases (26.1%) from the retroperitoneum. 20.9% (27/129) of the patients were found to harbor germline mutations of susceptibility genes, with SDHB mutations being the most common (10.1%, 13/129). The Ki-67 staining was performed on 302 cases, with a Ki-67 proliferation index [M(Q1, Q3)] of 2.0% (1.0%, 3.0%). There were 194 cases in Ki-67<3% group and 108 cases in Ki-67≥3% group. Compared with the patients in Ki-67<3% group, the age of onset in Ki-67≥3% group was younger (P=0.029). Compared with the patients with paragangliomas without SDHB or Cluster 1A-related gene mutations, positive 131I-meta-iodobenzylguanidine (131I-MIBG) imaging or negative O-6-methylguanine-DNA methyltransferase (MGMT) immunohistochemistry staining, those with SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging or positive MGMT immunohistochemistry staining had a higher Ki-67 index (all P<0.05). Compared with adrenal pheochromocytoma, retroperitoneal paragangliomas had a higher proportion of SDHB mutations and a higher proportion of normetanephrine (NMN) secretory types (all P<0.05). Compared with adrenal pheochromocytoma, the maximum diameter of head and neck paraganglioma tumors was smaller [3.0 (1.9, 3.8) cm vs 4.7 (3.4, 6.4) cm, P<0.001] and the proportion of Ki-67≥3% was higher (61.3% vs 33.8%, P=0.007). Conclusions: PPGLs patients with earlier onset age, SDHB or Cluster 1A-related gene mutations, negative 131I-MIBG imaging, or positive MGMT immunohistochemistry staining tend to have a higher Ki-67 index. Head and neck tumors, though smaller, exhibit a higher proliferation potential.

[Clinical features of patients with metastatic pheochromocytoma/paraganglioma].

Objective: To analyze the clinical features of patients with metastatic pheochromocytoma/paraganglioma (PPGL). Methods: A follow-up study. The clinical data of 250 patients with metastatic PPGL treated at Peking Union Medical College Hospital from January 2018 to August 2023 were retrospectively analyzed, including 124 males and 126 females. The clinical features and treatment status of patients with metastatic PPGL were summarized and analyzed. Kaplan-Meier survival curve was used to evaluate patients' prognosis. Results: The age of onset, age of diagnosis, and age of tumor metastasis in patients with metastatic PPGL were (33.1±14.2) years, (35.4±15.2) years, and (40.7±15.3) years, respectively. Metastasis occurred in 26.4%(66/250) of patients at the time of initial diagnosis. Among patients without metastases at the time of initial diagnosis, the time from primary tumor resection to metastasis[M(Q1, Q3)] was 5.0 (3.0, 9.0) years, among which 20.1%(37/184) of patients had metastases more than 10 years after surgery. Most patients showed increased 24-hour urinary norepinephrine and plasma normetanephrine, accounting for 78.2%(176/225) and 78.7%(85/108), respectively. 42.3%(69/163) of patients had increased neuron specific enolase (NSE)levels. Germline mutations were screened in 201 patients, of which 55.2%(111/201) had germline pathogenic mutations. In patients with gene mutations, 76.5%(85/111) had SDHB mutations. 52.0%(130/250) of metastatic PPGL patients had primary sites outside the adrenal gland, with the Ki-67 index of 5% (3%, 8%). There were 85.6%(214/250) patients had multisystem metastasis, with bone metastasis being the most common site of metastasis, accounting for 60.8%(152/250). In terms of treatment, 32.8%(75/229) of patients underwent two treatment regimens and 8.7%(20/229) of patients underwent three treatment regimens. Most patients had a good prognosis, with a 5-year and 10-year survival rate of 88.0% and 84.0%, respectively. However, some patients had rapid disease progression, and as of August 2023, 30 patients died, and the time from diagnosis to death in deceased patients was 2.0 (1.0, 4.0) years. Conclusions: Patients with metastatic PPGL have a high rate of germline mutations, especially those with SDHB mutations. The metastatic PPGL is usually multisystem metastasis with the characteristics of mostly paraganglioma, large lesion diameter and high Ki-67 index.

[Preliminary study on the ability of 68Ga-Pentixafor PET/CT to differentiate between adrenal aldosterone-producing adenoma and nonfunctional adenoma].

Objective: To evaluate the ability of 68Ga-Pentixafor (nuclide ligand imaging agents for chemokine receptor 4) PET/CT to differentiate between aldosterone-producing adenoma (APA) and adrenal nonfunctional adenoma (NFA), and to assess how well this imaging method correlates with clinical features and postoperative outcomes. Methods: This was a cross-sectional study involving 73 APA and 12 NFA patients who received 68Ga-Pentixafor PET/CT imaging at Peking Union Medical College Hospital from August 2018 to October 2021. The receiver operating characteristic (ROC) curve was used to evaluate the differential value of visual analysis and the maximum standard uptake value (SUVmax) of the focus on APA and NFA. The related factors of SUVmax, and its predictive effect on postoperative outcomes were analyzed using Pearson or Spearman analysis and χ2 text. Results: 68Ga-Pentixafor PET/CT imaging was positive in 64 APA patients (sensitivity=87.7%) and negative in all 12 NFA patients (specificity=100%). The area under the ROC curve with SUVmax differentiating APA and NFA was 0.932 (P<0.001). When the SUVmax cut-off point was 6.23, the sensitivity was 80.8% and the specificity was 100%. The SUVmax correlated positively with lesion size (r=0.598) and aldosterone/renin activity ratio (r=0.313) and correlated negatively with potassium level (r=-0.286), renin activity (r=-0.240) and age of diagnosis (r=-0.273) (all P<0.05). Of the patients who underwent adrenalectomy and received more than 6 months of post-surgical follow-up, the clinical complete remission rate was higher for 68Ga-Pentixafor PET/CT imaging-positive patients than imaging-negative patients (24/39 vs. 0/4, P=0.031). Conclusions: 68Ga-Pentixafor PET/CT is effective at differentiating between APA and NFA. The SUVmax of 68Ga-Pentixafor PET/CT correlates with age at onset, lesion size, and the severity of clinical manifestations, and is able to predict postoperative outcomes.

[Recurrence and metastasis of pheochromocytoma/paraganglioma after tumor resection and clinical characteristics analysis].

Objective: The purpose of this study is to investigate the incidence of recurrence or metastasis of pheochromocytoma/paraganglioma (PPGL) patients after primary tumor resection, and to compare the differences of clinical indicators between patients with or without recurrence or metastasis. Methods: This study is a retrospective study. All 157 patients were followed up after tumor resection in Peking Union Medical College Hospital from 2008 to 2016. We obtained the basic information [age of diagnosis, gender, height, weight and body mass index (BMI)], the onset status of PPGL (age of onset, course of disease, family history, tumor location, whether the tumor is bilateral or multiple, and preoperative blood pressure), clinical and pathological features of PPGL tumor (tumor size, whether it could adhere, invade or infiltrate during operation, whether the tumor capsule is smooth and complete on the postoperative pathological diagnosis, whether there is infiltration growth and cystic necrosis on tumor pathology and Ki-67 index), and laboratory examination results [24 hours urinary norepinephrine (NE), epinephrine (E), dopamine (DA) before operation]. According to the outpatient or telephone follow-up, the postoperative incidences of recurrence and metastasis were explored, and the basic information, status of onset, clinical and pathological characteristics of tumors, and laboratory test results of patients were compared. Results: A total of 157 patients, 69 males and 88 females, were with an average age of (42.4±13.4) years old. There were 103 patients with PCC and 54 with PGL. The average follow-up time was (9.5±2.0) years. Of the 103 patients with PCC, 13 (12.6%) had postoperative recurrence and 9 (8.7%) had distant metastasis. Compared with the patients without recurrence and metastasis, the onset age of the 13 patients with recurrence was younger [(27.3±15.7) years vs (39.3±12.2) years, P=0.003], the course of disease was longer [48.0 (23.0, 141.0) months vs 12.0 (4.0, 60.0) months, P=0.010]. The tumor size of 9 patients with distant metastasis was larger [8.0 (6.1, 12.8) cm vs 5.0 (4.0, 7.0) cm, P=0.027]. Of the 54 patients with PGL, 8 (14.8%) had postoperative recurrence and 5 (9.3%) had distant metastasis. Compared with the patients without recurrence and metastasis, the course of disease of the 8 patients with recurrence was longer [90.0 (36.3, 165.0) months vs 24.0 (8.0, 72.0) months, P=0.009], and the proportion of primary tumors with multiple lesions was higher (4/8 vs 4.4%, P=0.003). The preoperative diastolic blood pressure was higher in 5 patients with distant metastasis [(146.0±32.1) mmHg vs (120.6±25.3) mmHg, P=0.043] (1 mmHg=0.133 kPa), and the proportion of primary tumors with multiple lesions was higher (2/4 vs 4.4%, P=0.029). Conclusion: PPGL patients are prone to have recurrence or metastasis. PPGL patients with postoperative recurrence or distant metastasis had younger onset age, longer course of disease, larger tumor size and higher proportion of multiple lesions.

[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.

[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.

[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.

[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.

[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.

[The application of captopril challenge test in the diagnosis of primary aldosteronism].

Objective: To evaluate the value of captopril challenge test (CCT) in the diagnosis of primary aldosteronism (PA). Methods: A total of 674 patients [(45.0±13.7) years, men 341, women 333] admitted to Peking Union Medical College Hospital from 2000 to 2015 were analyzed. Among them, 222 subjects were with essential hypertension (EH), 28 were with pheochromocytoma (PHEO), 246 were with idiopathic hyperaldosteronism (IHA) and 178 were with aldosterone producing adenoma (APA). All patients received CCT. 24 h urine sodium was measured in partial patients. Plasma renin activity (PRA), aldosterone (ALD) were detected. Results: Compared with EH [PRA: before 0.5(0.2, 0.9) µg·L(-1)·h(-1,) after 0.8(0.4, 1.5) µg·L(-1)·h(-1;) ALD: before (393±122) pmol/L, after (360±97) pmol/L] and PHEO [PRA: before 0.3(0.1, 0.9) µg·L(-1)·h(-1,) after 0.4(0.1, 1.6) µg·L(-1)·h(-1;) ALD: before (396±108) pmol/L, after (374±114) pmol/L], lower levels of PRA and higher levels of ALD before and after CCT were observed in PA patients [PRA: before 0.1 (0.1, 0.2) µg·L(-1)·h(-1,) after 0.1 (0.1, 0.2) µg·L(-1)·h(-1;) ALD: before (468±216) pmol/L; after (457±199) pmol/L]. After CCT, the suppression rate of ALD [2.8% (-8.8%, 15.4%) vs 6.6% (-4.3%, 17.6%)] and increasing rate of PRA [0(0, 50%) vs 50%(0, 200%)] in PA patients were lower than those in EH patients. The ALD/PRA ratio (ARR) were higher in PA than that in EH or PHEO patients. In the EH subjects, ALD levels of seated posture were higher than those of recumbent posture both before and after receiving captopril, but with no changes in ARR after CCT. No significant differences in ALD and ARR (before and after receiving captopril) were observed between seated and recumbent position in the PA group. The ARR after CCT tended to decrease in EH subjects with elevated urine-sodium compared with those with normal urine-sodium. No changes could be viewed in ALD and PRA levels between normal urine-sodium and elevated urine-sodium groups among APA, IHA and EH patients either before or after CCT. Among patients with APA, the ALD levels before CCT and the ARR after CCT were lower in the patients with AngiotensionⅡ(AngⅡ) reactive than those without. A ROC curve analysis suggested that the optimal cutoff value was 46.2 (ALD unit: ng/dl; PRA unit: µg·L(-1)·h(-1)) for ARR after challenge in diagnosing PA, with the sensitivity of 88.7% and specificity of 84.8%. Conclusions: ARR after 25 mg captopril had high sensitivity and specificity in diagnosis of PA with the cutoff of 46.2. Seated CCT could replace recumbent CCT as a more confirmatory test. The PRA increasing rate should be taken into consideration when diagnosis of PA.

[The localization diagnosis of patients with adrenocorticotropic hormone-dependent Cushing's syndrome in adolescence].

Objective: To elucidate the clinical characteristics and localization diagnosis of patients with adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS) in adolescence. Methods: The clinical data, laboratory examination and localization diagnosis from 35 patients aged less than 18 years old with adolescent CS who were treated at Peking Union Medical College Hospital between January 1990 and March 2012 were analyzed. Results: There were 29 cases of Cushing's disease (CD) and 6 cases of ectopic ACTH syndrome (EAS). Compared to patients with EAS, those with CD were older at diagnosis[(15.2±2.7) vs (12.8±4.4) years], and had longer disease course[(1.9±1.5) vs (0.7±0.3) years]and higher serum potassium[(3.8±0.6) vs (2.5±0.7) mmol/L], however the plasma ACTH level[(15.4±14.9) vs (42.5±22.7) pmol/L]was lower (all P<0.05). If the cut-off of the ratio of 24-hour urine free cortisol (24 h UFC) after low-dose dexamethasone suppression test (LDDST) to before LDDST was 0.65, the sensibility to diagnose CD was 70.8%, and the specificity was 100%. If the cut-off of the 24 h UFC ratio after high-dose dexamethasone suppression test (HDDST) to before HDDST was 0.54, the sensibility to diagnose CD was 91.7%, and the specificity was 100%. If the cut-off of the plasma ACTH ratio of inferior petrosal vein[bilateral inferior petrosal sinus sampling (BIPSS)]to peripheral vein was 2, only 6 CD patients (6/8) met it. Conclusion: The study suggested that HDDST was more meaningful in the localization diagnosis of patients with ACTH-dependent CS in adolescence.

[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.