New compound heterozygous mutation causes partial combined 17 alpha-hydroxylase/17,20-lyase deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the CYP17A1 gene mutations in a Chinese 46,XX patient with partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.</p><p><b>METHODS</b>Clinical data were retrospectively analyzed. The genomic DNA of the patient and her parents was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then subclone sequenced. Sequencing results were compared to the established human CYP17A1 sequence.</p><p><b>RESULTS</b>The patient was new compound heterozygous of 5994-5995 delAT/7541 C>T. The mutation 5994-5995 del AT, causing amino acid I259H, 274X, was proposed to result early truncated protein which was lack of the activity center site of P450C17, whereas missense mutation 7541 C>T causing A398V did not lie in the active site of the enzyme according to the computer model of human P450C17. The 46, XX case had irregular menstruation and slightly hypertension and hypokalemia. The ACTH stimulating test as well as the result of the sex hormones suggested that there was partial 17 alpha-hydroxylase/17, 20-lyase enzyme activities in the adrenal and sexual gland. We speculate that A398V might conserve partial of the enzyme's activities. The genotype was coincident with phenotype.</p><p><b>CONCLUSION</b>More study should be done to have better understanding of the function of the mutated P450C17 enzymes.</p>

Study on the genetic mutations of 17 alpha-hydroxylase/17,20-lyase deficiency in Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the CYP17A1 gene mutations in Chinese patients with 17 alpha-hydroxylase/17, 20-lyase deficiency.</p><p><b>METHODS</b>Clinical data were retrospectively analyzed. The CYP17A1 gene mutations were detected in 5 cases with 17 alpha-hydroxylase/17, 20-lyase deficiency and their relatives. The genomic DNA of the patients was isolated from whole blood. Seven pairs of primers were used to amplify eight exons and exon-intron boundaries of the CYP17A1 gene. The amplified PCR products were purified by agarose gel and then directly sequenced. In order to confirm the DNA sequences of different alleles, some fragments were inserted into pMD 18-T vector and then sequenced. Sequencing results were compared to the established human CYP17A1 sequence.</p><p><b>RESULTS</b>Briefly, we found 2 kinds of compound mutations, of which were: (1) 6436-6438(TAC-->AA), causing amino acid Y329K, 418X; (2) 6531-6532(GC-->A), causing amino acid L361F, 418X. Among the five cases, four were homozygous for 6436-6438(TAC-->AA), whereas one was compound heterozygous for 6436-6438(TAC-->AA)/6531-6532(GC-->A). The clinical characteristics of 5 cases were all completely combined defects of 17 alpha-hydroxylase/17, 20-lyase, and they all carried two alleles of CYP17A1 gene mutations that all shifted the reading frame and resulted in truncated protein which lack of the activity center site of P450C17, of which corresponding with their clinical feature.</p><p><b>CONCLUSION</b>Nine alleles have the mutation of 6436-6438(TAC-->AA), accounting for 90% of total alleles (9/10). That suggests this kind of mutation may have racial specificity. More study should be done to have better understanding of the function of the truncated P450C17 enzymes.</p>

The evaluation of the diagnosis and treatment of 32 cases with ectopic ACTH syndrome / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate and discuss the diagnosis and treatment of ectopic ACTH syndrome.</p><p><b>METHODS</b>Clinical data of 32 cases of ectopic ACTH syndrome, recruited from January 1990 to April 2003 in our hospital, was analyzed.</p><p><b>RESULTS</b>All of the 32 cases presented with clinical and biochemical evidences of Cushing's syndrome. Ten cases were definitively diagnosed as ectopic ACTH syndrome by finding ectopic tumors; 4 cases were highly suspected as ectopic ACTH by blood sampling from femoral vein and infra-petrosal vein and 18 cases were suspected as ectopic ACTH by imaging examinations. Fifteen cases (47%), without identified source of ectopic hormone, were treated with bilateral or unilateral total adrenalectomy, with 1-year survival rate of 60%. Seven cases (22%), with possible source of ectopic hormone, underwent no intervention, with 1-year survival rate of 0. Ten cases underwent radical resection of tumor, 6 of which were bronchial carcinoids and 4 of which were thymic carcinoids, with 1-year survival rate of 60%.</p><p><b>CONCLUSION</b>It is very difficult to localize the tumor of ectopic ACTH syndrome patients. Bilateral adrenalectomy followed by hormonal replacement is effective for most of the patients without identifying source of ectopic hormone.</p>

A clinical analysis of 103 cases of adrenal incidentaloma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To improve the diagnosis and treatment of adrenal incidentaloma (AI).</p><p><b>METHODS</b>Retrospective analysis of 103 AI patients in PUMC Hospital from 1994 to 2002.</p><p><b>RESULTS</b>Of the 103 cases (43 men and 60 women), most patients were 40-60 years old. Eighty-five cases (82.5%) were benign masses, of which 36 (35.0%) were non-functional adrenal cortical adenoma, and 12 (11.7%) were pheochromocytoma, 1 (1%) was Cushing's syndrome and 1 for aldosteronomas. Three cases did not show clinical feature and the diagnosis of pheochromocytoma were based on 131I-MIBG. Among 18 (17.5%) malignant tumors, adrenal carcinomas account for the majority (8 cases, 7.8%). Patients with malignant masses were significantly younger than patients with adenomas (P < 0.05), and the adenomas were significantly smaller than malignancy (P < 0.001). A cut-off at 4.0 cm of tumor mass size was set for differentiating benign and malignant tumors.</p><p><b>CONCLUSIONS</b>During the diagnosis of AI, it's essential to evaluate hormonal activity and assess for the risk of malignancy. If the mass size is 4 cm or larger, the risk of malignancy increases. More attention should be paid to subclinical hyperfunctional state.</p>

Incomplete P450 17 alpha enzyme deficiency:report of six cases / 中华妇产科杂志

Objectives To summarize the characteristics,differential diagnosis and management of incomplete 17 alpha-hydroxylase/17,20-1yase deficiency(17 OHD)of Chinese patients.Methods Six cases of incomplete 17 OHD from Peking Union Medical College Hospital were studied retrospectively through analyzing their clinical data,and the molecular pathogenic mechanism was discussed after literature review.Results Four cases of 46,XX incomplete 17 OHD were reported.The clinical characteristics included female phenotype,various degrees of breast development and absent or sparse axillary/pubic hair, oligomenorrhea or secondary amenorrhea,recurrent luteinized ovarian cysts,hypogonadism with persistent hyperprogesteronemia or high serum 17 alpha-hydroxyprogesterone level,with or without hypokalemic hypertension.There were also 2 cases of 46,XY incomplete 17 OHD,in which ambiguous genitalia were present besides hypokalemic hypertension.Conclusions Incomplete 17 OHD is a very rare form of congenital enzymatic deficiencies of steroid synthesis,which should be included in the differential diagnosis when there are menstrual disorders,sexual infantilism,recurrent ovarian cysts or ambiguous genitalia.Under such circumstances,hyperprogesteronemia offers a valuable clue for further investigation.