Birt-Hogg-Dubé Syndrome Associated with a Renal Tumor / 대한내과학회지

Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant disorder characterized by the formation of hair follicle tumors, kidney tumors, and pulmonary cysts with recurrent spontaneous pneumothorax. A 44-year-old woman visited Wonkwang University Hospital with mild dyspnea. A chest X-ray on admission revealed pneumothorax in both lung fields. Chest computed tomography (CT) revealed both pneumothorax and multiple, irregularly shaped, variable-sized cysts in both lung fields. Upon physical examination, white dome-shaped papules were observed on the face. Histological examination of the skin lesion confirmed fibrofolliculoma, and genetic studies revealed a folliculin gene mutation. Abdominal CT revealed a 1-cm small solid renal mass at the lower pole of the right kidney. We surgically removed the renal tumor, and a histological diagnosis of oncocytoma was made. Here, we report a case of BHD that demonstrated all three clinical manifestations; this is the first case report of its kind in Korea.

Study on the Marker Steroids of New Zealand Deer (Cervus elaphus var. scoticus) Velvet Antler by UPLC-MS/MS and HPLC-PDA Methods

Eleven steroid hormones (SHs: androstene-3,17-dione, estrone, β-estradiol, α-estradiol, testosterone, dehydroepiandrosterone, 17á-hydroxyprogesterone, medroxyprogesterone, megestrol acetate, progesterone, and androsterone) were detected from New Zealand deer (Cervus elaphus var. scoticus) velvet antler (NZA, 鹿茸). A method for the quantification of eleven SHs was established by using ultraperformance liquid chromatography (UPLC)-MS/MS. The linearities (R² > 0.991), limits of quantification (LOQ values, 0.3 ng/mL to 23.1 ng/mL), intraday and interday precisions (relative standard deviation: RSD 0.999), LOQ values (30 ng/mL to 350 ng/mL), intraday and interday precisions (RSD < 1.93%), and recovery rates (97.2% to 103.5%) for the three 7-O-CSs were determined. These quantitative methods are accurate, precise, and reproducible. As a result, it is suggested that the five steroid compounds of androstene-3,17-dione, androsterone, 7-ketocholesterol, 7α-hydroxycholesterol, and 7β-hydroxycholesterol could be marker steroids of NZA. These methods can be applied to quantify or standardize the marker steroids present in NZA.

RNA-Seq De Novo Assembly and Differential Transcriptome Analysis of Korean Medicinal Herb Cirsium japonicum var. spinossimum

Cirsium japonicum belongs to the Asteraceae or Compositae family and is a medicinal plant in Asia that has a variety of effects, including tumour inhibition, improved immunity with flavones, and antidiabetic and hepatoprotective effects. Silymarin is synthesized by 4-coumaroyl-CoA via both the flavonoid and phenylpropanoid pathways to produce the immediate precursors taxifolin and coniferyl alcohol. Then, the oxidative radicalization of taxifolin and coniferyl alcohol produces silymarin. We identified the expression of genes related to the synthesis of silymarin in C. japonicum in three different tissues, namely, flowers, leaves, and roots, through RNA sequencing. We obtained 51,133 unigenes from transcriptome sequencing by de novo assembly using Trinity v2.1.1, TransDecoder v2.0.1, and CD-HIT v4.6 software. The differentially expressed gene analysis revealed that the expression of genes related to the flavonoid pathway was higher in the flowers, whereas the phenylpropanoid pathway was more highly expressed in the roots. In this study, we established a global transcriptome dataset for C. japonicum. The data shall not only be useful to focus more deeply on the genes related to product medicinal metabolite including flavolignan but also to study the functional genomics for genetic engineering of C. japonicum.

Development of Polymorphic Simple Sequence Repeat Markers using High-Throughput Sequencing in Button Mushroom (Agaricus bisporus)

The white button mushroom (Agaricus bisporus) is one of the most widely cultivated species of edible mushroom. Despite its economic importance, relatively little is known about the genetic diversity of this species. Illumina paired-end sequencing produced 43,871,558 clean reads and 69,174 contigs were generated from five offspring. These contigs were subsequently assembled into 57,594 unigenes. The unigenes were annotated with reference genome in which 6,559 unigenes were associated with clusters, indicating orthologous genes. Gene ontology classification assigned many unigenes. Based on genome data of the five offspring, 44 polymorphic simple sequence repeat (SSR) markers were developed. The major allele frequency ranged from 0.42 to 0.92. The number of genotypes and the number of alleles ranged from 1 to 4, and from 2 to 4, respectively. The observed heterozygosity and the expected heterozygosity ranged from 0.00 to 1.00, and from 0.15 to 0.64, respectively. The polymorphic information content value ranged from 0.14 to 0.57. The genetic distances and UPGMA clustering discriminated offspring strains. The SSR markers developed in this study can be applied in polymorphism analyses of button mushroom and for cultivar discrimination.

Distribución de esteroides estrogénicos en plantas de tratamiento de aguas residuales municipales / Distribution of estrogenic steroids in municipal wastewater treatment plants

En la actualidad, existe una preocupación creciente por la presencia de estrógenos en el medio acuático, donde pueden ser introducidos a partir de aguas residuales después de su eliminación incompleta en las plantas de tratamiento. Las aguas residuales sistemáticamente reciben estrógenos naturales y sintéticos, y por lo tanto una comprensión más profunda de la suerte de ellos en el medio ambiente es necesaria. Se evaluaron los niveles de estrógenos en los efluentes de las Plantas de Tratamiento de Aguas Residuales (PTARs) Penha e Ilha do Governador, ambos de tipo convencional de flujo continuo de lodo activado con aireación prolongada. Fue utilizado como el parámetro de determinación de algunos compuestos de interés como estrógenos naturales [estrona (E1), 17β-estradiol (E2), estriol (E3)) y sintéticos (17α-etinilestradiol (EE2)]. Las muestras individuales se recogieron posteriormente al tratamiento de cada PTAR y después de los procedimientos de laboratorio se realizó la determinación de estrógenos basado en la extracción en fase sólida (SPE) y la cromatografía líquida de alta resolución con detector de arreglo de diodos (HPLC-DAD). Las concentraciones fueron de: 0,7 a 5,2 μg/l y de 0,5 a 5,6 de E1; 0,9 a 7,7 y 1,2 a 9,2 μg/l para E2; 2,01 a 6,09 y 1,07 a 4,08 μg/l para EE2 en PTAR Penha y PTAR Ilha do Governador, respectivamente. La capacidad de eliminación de estrógenos fue eficaz, pero denota que la eliminación sistemática de la población es en la actualidad alta. Se recomienda instalar mecanismos para mitigar el consumo exagerado de estas sustancias o implementar una eliminación completa más eficaz.

Currently, there is a growing concern over the presence of estrogens in the aquatic environment, where they can be introduced from wastewater after their incomplete elimination in the treatment plants. Wastewater systematically receives natural and synthetic estrogens, and thus a deeper understanding of the fate of them in the environment is extremely necessary. It was evaluated estrogen levels in the effluent from the Sludge Wastewater Treatment Plants (SWTPs) Penha and Ilha do Governador, both of type conventional continuous-flow activated sludge with extended aeration. The determination of some target compounds as natural estrogens was used as the evaluation parameter [estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic (17α-ethinylestradiol (EE2)]. Individual samples were collected posterior treatment of each SWTP, and after laboratory procedures, the determination of estrogens was performed by a method based on solid phase extraction (SPE) and high performance liquid chromatography-diode array detector (HPLC-DAD). Concentrations ranged from 0.7 to 5.2 μg/l and from 0.5 to 5.6 for E1; 0.9 to 7.7 and 1.2 to 9.2 μg/l for E2; 2.1 to 6.9 and 1.7 to 4.8 μg/l for EE2 at SWTPs Penha and Ilha do Governador, respectively. The removal capacity of estrogens despite its effectiveness denotes that the systematic elimination by the population is high nowadays and urging mechanisms to mitigate the exaggerated consumption or to implement most effective complete removal.

Estrone and Estradiol Levels in Breast Cancer Patients Using Anastrozole Are Not Related to Body Mass Index / Níveis de estrona e estradiol em pacientes com câncer de mama usando anastrozol não estão relacionados ao índice de massa corpórea

ABSTRACT Objective: Obesity is associated with an increased risk for breast cancer. Recent studies have shown that aromatase inhibitors may be less effective in women with a high body mass index (BMI). The aim of this study was to establish the relationship between the BMI and plasma estrone and estradiol levels in postmenopausal women with hormone receptor-positive breast cancer using anastrozole. Methods: In this cohort study, the patients were divided into three groups according to BMI (normal weight, overweight and obese) to compare and correlate plasma hormone levels before starting anastrozole hormone therapy and three months after treatment. Plasma hormone levels were compared for age and use of chemotherapy. Results: A statistically significant reduction in estrone and estradiol levels was observed between baseline and three months after starting the anastrozole treatment (p < 0.05). There was no statistically significant difference in plasma estrone and estradiol levels among the BMI groups (p > 0.05), but a significant reduction in plasma estrone levels was observed after three-months' treatment relative to baseline in all groups, as well as a reduction in estradiol in the obese group (p < 0.05). The use of chemotherapy and age > 65 years had no influence on plasma steroid levels. Conclusion: Changes in estrone and estradiol levels in the studied groups were not associated with BMI, chemotherapy or age.

RESUMO Objetivo: A obesidade está associada com risco aumentado de câncer de mama. Estudos recentes têm mostrado que os inibidores de aromatase podem ser menos eficazes em mulheres com alto índice de massa corporal (IMC). O objetivo deste estudo foi estabelecer a relação entre o IMC e os níveis plasmáticos de estrona e estradiol em mulheres no período pós-menopausa com câncer de mama receptor hormonal positivo, em tratamento com anastrozol. Métodos: Este estudo de coorte acompanhou três grupos de pacientes de acordo com o seu IMC (peso normal, sobrepeso e obesidade), a fim de comparar e correlacionar as dosagens dos hormônios estrona e estradiol antes e após três meses do uso do anastrozol. Os níveis plasmáticos dos hormônios foram também relacionados à idade do paciente e ao uso da quimioterapia. Resultados: Redução estatisticamente significativa de estrona e estradiol foi observada entre os níveis basais e três meses após o início do tratamento com anastrozol (p < 0,05). Não houve diferença estatisticamente significativa entre os níveis plasmáticos de estrona e estradiol em relação ao IMC (p > 0,05), mas houve redução significativa entre os níveis plasmáticos basais de estrona após o tratamento em todos os grupos, e redução de estradiol no grupo de pacientes obesas (p < 0,05). A condução da quimioterapia e da idade acima de 65 anos não interfere com os níveis plasmáticos de esteroides. Conclusão: Os níveis plasmáticos de estrona e estradiol nos grupos estudados não foram alterados em termos de IMC, quimioterapia e idade.

Epithelial folliculin is involved in airway inflammation in workers exposed to toluene diisocyanate

Toluene diisocyanate (TDI) exposure can directly activate and damage airway epithelium. Folliculin (FLCN) is a protein expressed by human airway epithelial cells (HAECs) to maintain airway epithelial integrity and survival. This study investigated the involvement of FLCN in the pathogenesis of TDI-induced occupational asthma (OA). Enzyme-linked immunosorbent assay was used to measure serum levels of FLCN in TDI-exposed subjects (93 TDI-OA patients and 119 asymptomatic exposed controls (AEC)), 200 non-occupational asthma (NOA) patients and 71 unexposed healthy normal controls (NCs). Significantly more subjects in the TDI-OA and AEC groups had high serum levels of FLCN compared to those in the NOA group (P=0.002 and P=0.001, respectively), all of which were higher than the NC group (all P<0.001). The serum level of FLCN was positively correlated with TDI exposure duration (r=0.251, P=0.027), but was negatively correlated with asthma duration of TDI-OA patients (r=−0.329, P=0.029). TDI-exposed subjects with high FLCN levels had higher serum levels of total IgE than those with lower levels. The effects of TDI exposure on FLCN production was investigated by treating HAECs (A549 cells) with TDI-human serum albumin conjugate, which showed increased expression and release of FLCN and interleukin-8 from HAECs. Co-culture with peripheral blood neutrophils also induced FLCN expression and release from HAECs. In conclusion, TDI exposure and TDI-induced neutrophil recruitment into the airways can activate and stimulate HAECs to produce FLCN, which could be involved in airway inflammation in workers exposed to TDI.

Birt-Hogg-Dubé Syndrome Manifesting as Spontaneous Pneumothorax: A Novel Mutation of the Folliculin Gene

Birt-Hogg-Dubé syndrome (BHDS) is a rare disease with autosomal dominant inheritance that manifests through skin tumors, pulmonary cystic lesions, and renal tumors. A mutation of FLCN located on chromosome 17p11.2, which encodes a tumor-suppressor protein (folliculin), is responsible for the development of BHDS. We report the case of a patient presenting with spontaneous pneumothorax, in whom a familial genetic study revealed a novel nonsense mutation: p.(Arg379*) in FLCN.

Birt-Hogg-Dubé Syndrome Manifesting as Spontaneous Pneumothorax: A Novel Mutation of the Folliculin Gene

Birt-Hogg-Dubé syndrome (BHDS) is a rare disease with autosomal dominant inheritance that manifests through skin tumors, pulmonary cystic lesions, and renal tumors. A mutation of FLCN located on chromosome 17p11.2, which encodes a tumor-suppressor protein (folliculin), is responsible for the development of BHDS. We report the case of a patient presenting with spontaneous pneumothorax, in whom a familial genetic study revealed a novel nonsense mutation: p.(Arg379*) in FLCN.

Measurement of serum estrogen and estrogen metabolites in pre- and postmenopausal women with osteoarthritis using high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry

Although 17β-estradiol (E2) deficiency has been linked to the development of osteoarthritis (OA) in middle-aged women, there are few studies relating other estrogens and estrogen metabolites (EMs) to this condition. We developed a high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) method to measure the levels of six EMs (i.e., estrone, E2, estriol, 2-hydroxyestrone, 2-hydroxyestradiol, and 16a-hydroxyestrone) in healthy pre- and postmenopausal women and women with OA. This method had a precision ranging from 1.1 to 3.1% and a detection limit ranging from 10 to 15 pg. Compared to healthy women, serum-free E2 was lower in the luteal and postmenopausal phases in women with OA, and total serum E2 was lower in postmenopausal women with OA. Moreover, compared to healthy women, total serum 2-hydroxyestradiol was higher in postmenopausal women with OA and total serum 2-hydroxyestrone was lower in both the luteal and follicular phases in women with OA. In conclusion, our HPLC-ESI-MS/MS method allowed the measurement of multiple biochemical targets in a single assay, and, given its increased cost-effectiveness, simplicity, and speed relative to previous methods, this method is suitable for clinical studies.

novel mutation causing 17-beta-hydroxysteroid dehydrogenase type 3 deficiency in an Omani child: first case report and review of literature

This is the first case report in Oman and the Gulf region of a 17-beta-hydroxysteroid dehydrogenase type 3 [17-beta-HSD3] deficiency with a novel mutation in the HSD17B3 gene that has not been previously described in the medical literature. An Omani child was diagnosed with 17-beta-HSD3 deficiency and was followed up for 11 years at the Pediatric Endocrinology Clinic, Royal Hospital, Oman. He presented at the age of six weeks with ambiguous genitalia, stretched penile and bilateral undescended testes. Ultrasound showed no evidence of any uterine or ovarian structures with oval shaped solid structures in both inguinal regions that were confirmed by histology to be testicular tissues with immature seminiferous tubules only. The diagnosis was made by demonstrating low serum testosterone and high androstenedione, estrone, and androstenedione:testosterone ratio. Karyotyping confirmed 46,XY and the infant was raised as male. Testosterone injections [25 mg once monthly] were given at two and six months and then three months before his surgeries at five and seven years of age when he underwent multiple operations for orchidopexy and hypospadias correction. At the age of 10 years he developed bilateral gynecomastia [stage 4]. Laboratory investigations showed raised follicle-stimulating hormone, luteinizing hormone, androstenedione, and estrone with low-normal testosterone and low androstendiol glucurunide. Testosterone injections [50 mg once monthly for six months] were given that resulted in significant reduction in his gynecomastia. Molecular analysis revealed a previously unreported homozygous variant in exon eight of the HSD17B3 gene [NM_000197.1:c.576G>A.Trp192*]. This variant creates a premature stop codon, which is very likely to result in a truncated protein or loss of protein production. This is the first report in the medical literature of this novel HSD17B3 gene mutation. A literature review was conducted to identify the previous studies related to this disorder

Birt-Hogg-Dube syndrome incidentally diagnosed during asthma management

Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant hereditary disorder characterized by 3 clinical manifestations, including skin fibrofolliculomas, multiple pulmonary cysts with or without spontaneous pneumothorax, and spontaneous renal tumor. A 60-year-old Korean male who had suffered from bronchial asthma incidentally diagnosed with multiple pulmonary cysts by computed tomography during a regular follow-up. Genetic studies revealed folliculin gene mutation that was a confirmative finding of BHD syndrome. Although this case showed no cutaneous manifestations or renal abnormality, genetic studies of his family and regular follow-up are recommended.

Polymorphisms of SLC22A9 (hOAT7) in Korean Females with Osteoporosis

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and 12.74 microM, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.

Two Cases of Birt-Hogg-Dube Syndrome with Pulmonary Cysts / 대한내과학회지

Birt-Hogg-Dube (BHD) syndrome is a rare autosomal-dominant disease caused by germline folliculin (FLCN) mutations, characterized by fibrofolliculoma or trichodiscoma, renal tumors, and multiple lung cysts with or without spontaneous pneumothorax. Here, we report two cases of BHD syndrome that presented with bilateral pulmonary cysts. One patient was a 39-year-old woman who had a history of pneumothorax, multiple papules on her cheeks, and a family history of the same skin lesions and renal cell carcinoma in her father. BHD syndrome was confirmed by molecular tests that revealed a missense mutation in FLCN gene (exon 4, c.31T > C). The other patient was a 56-year-old man who showed FCLN gene polymorphism and typical radiopathological features of multiple cysts in the lung, but apparently no other manifestation.

Fragmentation pathways of five estrogens using electrospray ionization quadrupole time-of-flight mass spectrometry / 药学学报

The fragmentation pathways of five estrogens (estradiol, estrone, equilin sulfate, 17 a-dihydroequilin sulfate and equilenin sulfate) have been studied with high resolution and high mass accuracy using electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF/MS) in the negative ion mode. Molecular weights were obtained from [M-H](-) ions in the product ion spectra. The results indicate that the five structurally similar estrogens have similar fragmentation pathways. Using their stable isotope forms as internal reference compounds, the accurate mass and composition of the fragment ions were determined. During collision-induced dissociation (CID), cleavage is initiated by loss of oxygen atoms from carbon-17, after which D and C rings cleave sequentially and rearrange to finally form stable conjugate structures with highly abundant characteristic fragment ions at m/z 183 (accompanied by m/z 181), m/z 169 and m/z 145 (accompanied by m/z 143). Understanding these characteristic fragmentation pathways of estrogens will be helpful in identifying the structures of steroid hormones in general.

Single and combined effects of estrone and 17β-estradiol on male goldfish / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To assess the single and combined effects of estrone (E1) and 17β-estradiol (E2) on goldfish (Carassius auratus).</p><p><b>METHODS</b>Batch tests were conducted. Serum levels of vitellogenin (VTG) and E2, gonadosomatic indices (GSI), gonadal DNA damage and liver 7-ethoxyresorufin-O-deethylase (EROD) activity were measured after exposure for 14 days.</p><p><b>RESULTS</b>The VTG level increased significantly in a concentration-dependent manner. The serum E2 level was significantly higher and the GSI level was significantly lower in goldfish after exposed to the 3 drugs. DNA damage occurred in treated samples and EROD activity was significantly suppressed 7 days after exposure. The joint effect of E1 and E2 was additive with regard to VTG induction.</p><p><b>CONCLUSION</b>The results of our study highlight a series of effects of steroidal estrogens on goldfish. Further study is needed to confirm their effect as a whole.</p>

A Case of Birt-Hogg-Dube Syndrome Diagnosed by a Folliculin Gene Mutation / 대한내과학회지

Birt-Hogg-Dube (BHD) syndrome is a rare, autosomal-dominant disorder that is caused by germ-line mutations in the folliculin gene. Clinically, BHD syndrome is characterized by cutaneous follicle tumors, pulmonary cysts, spontaneous pneumothorax, and an increased risk of renal cancer. A 65-year-old woman was admitted to Seoul St. Mary's Hospital to treat pneumonia, and we found that she had experienced recurrent spontaneous pneumothorax and had bilateral multiple pulmonary cysts with no history of smoking. Mutation analysis of the folliculin gene identified a novel mutation in exon 9 (c.997_998delTC; p.Ser333ArgfsX56). Except for the lung manifestation, no other features of BHD syndrome were detected in this case. Here, we report a case of BHD syndrome that manifested only as lung disease with a novel mutation.

A Case of Birt-Hogg-Dube Syndrome Diagnosed by a Folliculin Gene Mutation / 대한내과학회지

Birt-Hogg-Dube (BHD) syndrome is a rare, autosomal-dominant disorder that is caused by germ-line mutations in the folliculin gene. Clinically, BHD syndrome is characterized by cutaneous follicle tumors, pulmonary cysts, spontaneous pneumothorax, and an increased risk of renal cancer. A 65-year-old woman was admitted to Seoul St. Mary's Hospital to treat pneumonia, and we found that she had experienced recurrent spontaneous pneumothorax and had bilateral multiple pulmonary cysts with no history of smoking. Mutation analysis of the folliculin gene identified a novel mutation in exon 9 (c.997_998delTC; p.Ser333ArgfsX56). Except for the lung manifestation, no other features of BHD syndrome were detected in this case. Here, we report a case of BHD syndrome that manifested only as lung disease with a novel mutation.

Serum Concentration of Estradiol and Estrone Following Oral Administration of Low-dose Hormone Therapy in Postmenopausal Korean Women / 대한폐경학회지

OBJECTIVES: To determine the baseline serum concentrations of estradiol and estrone in postmenopausal Korean women and the serum concentrations of estradiol and estrone after 4 and 16 weeks of treatment using 1 mg of estradiol and 2 mg of drospirenone. METHODS: This was a multicenter study. Thirty-six subjects were screened. Serum estradiol, estrone and drospirenone levels were determined by gas chromatography-mass spectrometry and radioimmunoassay. RESULTS: The mean estradiol concentration was 8.37 +/- 12.1 pg/mL at baseline and increased to 53.7 +/- 52.1 and 41.4 +/- 26.1 pg/mL after 4 and 16 weeks of treatment, respectively. The mean estrone concentrations were 28.7 +/- 26.8, 266.1 +/- 182.9, and 256.1 +/- 179.1 pg/mL at baseline, and after 4 and 16 weeks of treatment, respectively. When women were stratified according to the basal estradiol level, the level after 4 weeks of treatment was significantly higher in the women with a detectable level (> or = 5 pg/mL) than in women with an undetectable level (< 5 pg/mL; 65.2 +/- 21.5 vs. 37.4 +/- 25.8 pg/mL, P = 0.008). After 16 weeks of treatment, the estradiol level was still higher in the detectable group (51.6 +/- 28.6 vs. 38.7 +/- 21.7 pg/mL, P = 0.09). CONCLUSION: This study showed that 1 mg of estradiol and 2 mg of drospirenone is an appropriate regimen to achieve the desired serum estradiol level. The difference in serum hormonal levels after 4 weeks of treatment could be caused by different basal levels.

Genetic Study in a Case of Birt-Hogg-Dube Syndrome

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominantly inherited disorder characterized by multiple trichodiscomas, fibrofolliculomas, and acrocordons. There is also an increased risk of developing renal neoplasms and lung cysts/spontaneous pneumothorax. We present a 43-year-old man with multiple, 2~4 mm sized, dome-shaped, and skin-colored papules on his cheek and neck. On the basis of clinical finding and histopathologic examination on the cheek lesion, it was diagnosed as multiple trichodiscomas. Subsequently, molecular analysis revealed a mutation in the folliculin gene. We report a rare case of BHDS with a proved gene mutation.