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OBJECTIVE@#To investigate the efficacy and safety of aromatase inhibitor letrozole in treatment of male children with disorders of sex development (DSD).@*METHODS@#Clinical data of 12 male DSD children with a mean age of 14.6±2.5 years admitted to Peking Union Medical College Hospital from January 2014 to January 2016 were retrospectively analyzed. The patients were treated with letrozole (1.25-2.5 mg, once a day) for 3 months or longer, and followed up for 0.5-2.5 years. Clinical manifestation and laboratory test findings were documented, and the efficacy and safety were evaluated.@*RESULTS@#After half-year treatment, the blood luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone levels of patients increased (all < 0.05), and estrogen levels decreased from baseline ( < 0.05). After 1 year of treatment, the blood testosterone level was significantly higher ( < 0.05); the LH and FSH levels tended to increase and the estrogen level tended to decrease, but there was no significant statistical difference ( >0.05). Semen was routinely detected in 8 patients, and sperms were detected in semen of 3 patients with hypospadias. There were no significant changes in biochemical results after treatment, and no significant adverse event was observed during the treatment.@*CONCLUSIONS@#Letrozole can effectively increase testosterone levels in patients with disorders of sex development and promote spermatogenesis, it has no significant adverse effects in short-term administration.
Subject(s)
Adolescent , Child , Humans , Male , Disorders of Sex Development , Drug Therapy , Follicle Stimulating Hormone , Letrozole , Therapeutic Uses , Luteinizing Hormone , Retrospective Studies , TestosteroneABSTRACT
Mammalian reproduction is closely related to their metabolic status. The hypothalamus-pituitary-gonad axis ( HPG axis) is regulated by various metabolic factors. Glucagon-like peptide-1 ( GLP-1) is one of various metabolic factors that not only affect glycemic and metabolic control, but also with many other effects, including affecting HPA axis. The function of GLP-1 is related to the location of glucagon-like peptide-1 receptor ( GLP-1R) distribution. It has been confirmed that GLP-1R is widely distributed in HPG axis. The effects of GLP-1 and GLP-1R agonists on the HPG axis have also attracted much attention. The positive effects of GLP-1 and GLP-1R agonists on the HPG axis indicated it could be the new target for the new treatment for gonadal diseases. The role of GLP-1 and GLP-1R agonists in the central nervous system is reviewed.
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A retrospective study was conducted on one patient with postmenopausal hyperandrogenism. The postmenopausal female patient was found with significant hyperandrogenism ( total testosterone 6. 4 nmol/ L) and hirsutism, with normal adrenal androgen ( dehydroepiandrosterone-sulfate ) level. Computed tomography and ultrasound did not detect any ovarian and adrenal mass. Positron emission tomography revealed without high metabolic region, either. Ovarian and adrenal vein catheterization did not reveal any positive result. Obviously, ovary-derived hyperandrogenism was highly suspected, but the patient still refused any surgical exploration. After a trial of a single dose of gonadotropin releasing hormone analogue(GnRHa) triptorelin, increased testosterone level returned to normal along with decreasing level of gonadotropin. Multiple doses were needed for maintenance of testosterone at normal level with the intervals of 2 ～ 12 months. This response to the treatment was consistent with that of gonadotropin dependent hyperandrogenism.
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[Summary] Cytochrome P450 oxidoreductase deficiency ( PORD) is a rare disease, which is a subtype of congenital adrenal hyperplasia. The predominant signs include no puberty development, infantile reproductive organs, ear deformities, and bone synostosis in skull or limbs. Here, we analyzed the clinical features of a case with PORD confirmed by gene sequencing. The pathology, genetic features, clinical manifestations, diagnosis and treatment for PORD were reviewed.
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Objective To explore the relationship between SNPs in microRNA binding sites of ABCG5/8 and the glucolipid level during pregnancy.Methods 1 925 pregnant women were recruited at Peking Union Medical College hospital from 2006 to 2011.The clinical data were collected and the total genomic DNA was extracted from whole blood samples.ABCG5/8, which was reported to be related with the glucose and lipid metabolism closely, were selected as the candidate gene and the SNPs in its microRNA binding sites with minor allele frequency >5% in Han Chinese in Beijing were chosen.Then the genotyping was performed and analyzed.Results There was only one SNP matching the criteria, rs2278356, and it is significantly associated with LDL-C and TC level during pregnancy (LDL-C: b=0.104 mmol/L, 95% CI 0.023-0.185 mmol/L, P<0.05;TC: b=0.105 mmol/L, 95% CI 0.080-0.203 mmol/L, P<0.05).Conclusions The association of rs2278356 in 3′UTR of ABCG5/8 with LDL-C and TC level in pregnant Chinese Han women is found, which may provide an individualized treatment strategy for pregnant women with high cholesterol.
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Objective To investigate clinical and pathological characteristics of insulin-induced localized lipoatrophy and treatment.Methods We retrospectively analyzed clinical manifestation, skin biopsy pathology, treatment regimen and follow-up of 6 diabetic patients with insulin-induced localized lipoatrophy in Peking Union Medical College Hospital from January, 2010 to March, 2016, with systemic review of related literatures.Results Among 6 cases with insulin-induced localized lipoatrophy, 5 patients were with insulin allergy.5 patients were with positive insulin-autoimmune antibody, which was similar to the ratio reported in the systematic review (18 out of 19).Insulin-induced lipoatrophy could be caused by various types of preparations of insulin and insulin analogs.Subcutaneous biopsy, performed on the atrophied area, revealed the decrease of the number and volume of adipocytes and tissue fibrosis, probably accompanied with lymphocytes, eosinophils or mast cells infiltration.Lipoatrophy could sometimes be relieved by changing injection sites, types of insulin preparations or drug-delivery way, sometimes by application of systemic/local glucocorticoid or local cromolyn sodium.Conclusions Insulin-induced localized lipoatrophy is a rare adverse reaction of insulin preparations.It might be related to immune response of local tissue and heterogeneous pathological manifestations.The lipoatrophy might be improved by changing injection sites, changing the type of insulin preparations or drug-delivery way, and with possibility to carry out targeted immunosuppressive therapy according to the biopsy pathology in the future.
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The ptrpose of this study was to investigate the effects of long-term estradiol and progesterone combined therapy on bone mineral density (BMD) in patients with Turner syndrome.Eight patients with Turner syndrome received estradiol and progesterone combined therapy for six years were observed and BMD was measured for each of them before hormone replacement therapy (HRT) and at an interval of one to two years after HRT and compared with that in normal age-sex matched women.BMD was significantly lower in patients with Turner syndrome than that in normal controls before HRT.All the patients with Turner syndrome had breast enlargement and irregular vaginal bleeding after HRT.BMD increased slightly in the patients with Turner syndrome after six-year HRT ,but still much lower than that in normal controls.Their BMD of the 2nd to 4th lumbar vertebra increased to (0.84±0.22) g/cm2 after HRT from (0.75±0.12)g/cm2 before it,with Z-score increased to -2.2±0.6 from -3.2±0.9,respectively; and overall BMD of the hip increased to (0.81±0.08) g/cm2 after HRT from (0.68±0.07) g/cm2 before it,with Z-score increased to-1.2 ± 0.3 from-2.2 ± 0.5,respectively.Long-term HRT can improve their BMD for patients with Turner syndrome but can not restore it to normal.
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Objective To analys hyperinsulinemia in Bartter syndrome. Methods Twenty-three cases of Bartter syndrome [age (27 ±9) years;fasting serum potassium(2. 8 ±0. 5)mmol/L], 20 patients of aldosterone-producing adenoma [APA, age (45 ± 11 ) years, fasting serum potassium ( 3.0 ± 0. 4 ) mmol/L], 20 patients of idiopathic hyperaldosteronism [IHA, age (51 ± 11 ) years, fasting serum potassium (3.4 ±0. 2)mmol/L] were diagnosed in Peking Union Medical College Hospital from September 2003 to May 2008. All patients underwent 3-hours oral glucose tolerance test(3hOGTT), postural stimulation test and calculated HOMA-insulin resistance ( HOMA-IR ) and HOMA-insulin sensitivity ( HOMA-IS ) by Homeostasis model.Results The insulin area under curve-(229.0±162.4)mIU·L-1·h] was singnificantly higher than APA group [(227.7±158.6)mIU·-1·h].But HOMA-IR in Bartter group were similar to APA group( 1.96 ± 1.14 vs 1.41 ± 0. 91 ), and HOMA-IR in APA group was lower than IHA group ( 1.96 ± 1.14 vs 2.40 ± 1.60, P ＜ 0. 05 ). There was no deference in HOMA-IS among three groups,but APA group had lower level. In all three groups, the peak of insulin secretion was delayed. Conclusion Bartter syndrome patients commonly present with hyperinsulinemia.
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Objective To clarify the possible gene mutations in luteinizing hormone(LH) receptor gene in a boy with LH independent precocious puberty and probe the mechanism the of diseases caused by LH receptor activating mutations. Methods ( 1 ) Describe the clinical manifestations and laboratory data in a 5-year-old boy with LH independent precocious puberty. (2) Peripheral leukocytes were collected from the proband, his parents and other 20 normal puberty developed males. PCR and direct DNA sequence of 11 exons in LH receptors gene were conducted. Results (1) The proband was diagnosed to have LH independent precocious puberty according to the clinical symptoms and the laboratory tests. (2) A germ-line heterozygous point mutation in the 11 exon of LH receptor gene was found in the proband and his mother:c1193 T→C leading to amino acid change with M398T, which causes consecutively an activation of the LH receptor. (3) Other nucleotide changes in the proband and other normal males include c935 A→ G (N312S) and c1065 T→C(same sense mutation). Conclusions (1) A germ-line heterozygous point mutation in the LH receptor gene with M398T leads to consecutively activation of the LH receptor and LH independent precocious puberty. (2) The same point mutation does not have any influence on the puberty development, menstruation and productive functions of the proband's mother. (3) The LH receptor gene has possible polymorphism in the Han ethnic population.
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Two types of steroid 5?-reductase isozymes were found in human and rats.5?-reductase type 2 deficiency in male lead to male pseudohermaphroditism and other related phenotypes.The content of this review includes:① The progress in the fields of 5?-reductase research;②Biochemical characteristics and physiological effects of 5?-reductase.③ Gene structure and mutation in 5?-reductase genes,clinical and chemical features of 5?-reductase type 2 deficiency syndrome.④Inhibitory agents of 5?-reductase and their mechanism and clinical use.The investigation in 5?-reductase help to illuminate physiological effect and sexual differentiation of androgen.The development of new inhibitory agents for 5?-reductase creats new strategy for diseases caused by imbalance of androgen action.Their mechanism and long effects of clinical use need further investigation and observation.
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Prolactin (PRL) is a multi-functional hormone mainly from pituitary gland. PRL receptors exist ubiquitously in all tissues and organs of immune system and PRL modulates local and systemic immune activities. PRL is involved in many physiological and pathological immune responses. The function of PRL in autoimmune diseases, organ transplantation and tumor occurrence has been explored in recent years. This article is to review the progress of prolactin in the immunology-related field.
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Objective We have summarized the clinical characteristics of inappropriate antidiuresis(SIAD).Methods We adopted retrospective analysis to analyze the clinical and lab data of 40 cases.Results The most common causes of SIAD were malignant tumor,lung disease,and central nervous system disease.The five major abnormal lab data were:hypochloraemia,hypouricemia,hyponitremia,hypocalcemia,and low hematocrit.Conclusion It is important to diagnose SIAD as soon as possible,and patient presented hyponatremia combined with hypouricemia must be suspected to have SIAD.
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Objective To studytherelationshipbetweenhypercortisolismand psychosis. Methods According to pathologic diagnosis, 133 cases of hypercortisolism were dividedinto adrenal lesion group, pituitary adenoma group and ectopic ACTH tumor group, and the relationship between hypercortisolism and psychosis was analyzed. Results (1) There were significant differences between groups regarding cortisol levels and the amplitude of fluctuation. (2) Depression and mania were the main manifestations of psychosis in the patients, and 79.7% of the patients showed symptoms of depression. (3) In ectopic ACTH tumor group, the level and the increased amplitude of 24 h urinary free cortisol were significantly higher than those in the other two groups, all the patients had severe depression, and the rate of suicide tendence (58.3%) was significantly higher than the other two groups. Conclusions (1) Psychosis has a close relationship with hypercortisolism,especially with the marked fluctuation in cortisol level. (2) Sufficient attention should be paid to this relationship, which will improve the diagnosisand treatment of hypercortisolism.
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Objective To analysis the relationship of primary aldosteronism to insulin resistance and abnormal glucose metabolism in patients with primary aldosteronism.Methods One hundred and three patients were diagnosed as aldosterone-producing adenoma(APA),75 cases as idiopathic hyperaldosterenism(IHA),56 patients as metabolic syndrome(MS)in Peking Union Medical College Hospital from September 2003 to December 2005.All patients were accepted 3 h oral glucose tolerance test and calculated HOMA-insulin resistance index (HOMA-IR)by Homeostasis Model.Results The Insulin area under curve[INS_(AUC) 270.8(192.7,370.4)mU?L~(-1)?h~(-1)]、HOMA-IR[3.2(2.4,4.7)]and prevalence of insulin resistance(64.3%)were significantly higher in patients with MS as compared with APA[113.2(81.5,193.6)mU?L~(-1)?h~(-1),1.4(1.0,2.2),16.5%]and IHA[186.9(116.6,243.3)mU?L~(-1)?h~(-1),2.0(1.4,3.1),32.0%]groups (all P＜0.01);The INS_(AUC), HOMA-IR and prevalence of insulin resistance were significantly higher in patients with IHA than those with APA (P＜0.05 or P＜0.01).There was no difference between the prevalence of impaired glucose regulation(41.7%, 34.7%),diabetes mellitus(15.5%,16.0%)in patients with APA,IHA and those with MS(41.1%, 26.8%).Conclusion Insulin resistance is present in primary aldosteronism patients,and the prevalence of insulin resistance is higher in patients with IHA.