Severe hyperandrogenemia in postmenopausal woman as a presentation of ovarian hyperthecosis. Case report and mini review of the literature

Ovarian hyperthecosis (OH) is characterized by the presence of abundant luteinized theca cells in ovaries that secret androgen. It typically presents as severe hyperandrogenism and/or virilization in postmenopausal woman. Here we describe a 66-year old woman with presentation of severe hirsutism, alopecia, clitoromegaly and laboratory finding of significantly elevated serum total testosterone concentration and hyperinsulinemia. Performed imaging studies revealed normal sized, homogeneous ovaries, signs of endometrial hypertrophy and normal adrenal glands. Due to severe hyperandrogenemia and signs of endometrial hypertrophy, the total abdominal hysterectomy with bilateral salpingo-oophorectomy has been performed. Pathological examination revealed OH and endometrial hyperplasia. Androgenic activity of ovarian stromal cells has been confirmed using alpha-inhibin histochemical staining. Postmenopausal hyperandrogenemia is a diagnostic and therapeutic challenge and the imaging studies often may be misleading and require careful and critical consideration.     

Serum microRNAs in male subfertility—biomarkers and a potential pathogenetic link to metabolic syndrome

Purpose

The purpose of the study was to identify serum microRNAs providing a link between male subfertility and metabolic syndrome (MetS) and validate their diagnostic potential.

Methods

Sera were analyzed for fertility and MetS-related parameters in subfertile men (n = 79) and controls (n = 38). Literature review identified miR-155-5p, miR-122-5p, miR-200a-3p, and miR-200c-3p which previously were associated with parameters of fertility as well as metabolic disorders. They were measured in the sera using an absolute quantitation method (qPCR). In order to investigate the value of miRNAs in predicting subfertility, receiver operating characteristic analysis was done.

Results

Subfertile men had higher concentrations of miR-155-5p than controls (p = 0.003) and for miR-200c-3p, the difference was borderline statistically significant (p = 0.05). miR-155-5p and miR-200c-3p were also associated with subfertility in men with no metabolic disturbances (p = 0.008, p = 0.004, respectively). This association was abrogated if any component of MetS was present. The combination of miR-155-5p and miR-200c-3p with follicle-stimulating hormone, being a well-established subfertility parameter, resulted in an overall diagnostic power of AUC = 0.87, which was even higher when men without MetS components were analyzed (AUC = 0.93). Regarding MetS components, statistically significant correlations were found between miR-122-5p and fasting triglycerides, and waist circumference, but no association with subfertility was identified.

Conclusions

Among the four miRNAs analyzed, none of them was associated both with male subfertility and MetS components. The ability of miR-155-5p and miR-200c-3p to identify subfertile men was partly overruled by the presence of metabolic disturbances.

     

Melanoma arising in an ovarian cystic teratoma: a systematic review of presentation,treatment, and outcomes

Purpose

To assess the clinical presentation, treatment modalities, and outcome of primary melanomas arising in ovarian cystic teratomas (OCT).

Methods

A systematic review on PubMed/MEDLINE was performed on June 5, 2017, to gather data on patients with primary melanomas arising in OCTs. No systematic reviews were identified. Consequently, only case reports and case series of individuals were analyzed. A total of 37 articles met our inclusion criteria, totaling 41 unique patients.

Results

The average age of diagnosis was 51.5 years. In total, 24% of patients were found to have metastatic disease. In total, 56.7% of patients eventually died of their disease, with an average time from diagnosis to death of 9.3 months. Disease recurrence was common, occurring in 65% of patients. The mainstay of treatment was surgical in 100% of the cases. Adjuvant chemotherapy, immunotherapy, and radiation were also used with varying degrees of efficacy.

Conclusions

Malignant melanoma arising in OCT is a rare disease with poor prognosis. The current mainstay treatment is surgical. Potential benefits of targeted therapy, immunotherapy, and chemotherapy remain to be determined. A limitation of this study is that these melanomas have only been published in case reports.

     

Endometrial adenocarcinoma in situ in complex atypical hyperplasia: correlation with findings in subsequent hysterectomy specimen

Well-differentiated endometrial adenocarcinoma can be difficult to distinguish from complex atypical hyperplasia (CAH) in a curettage or biopsy specimen. When a focus of back-to-back glands or cribriforming smaller than 2.1 mm is seen in a biopsy, we make a diagnosis of adenocarcinoma in situ (AIS). Whether this diagnosis translates into a more frequent diagnosis of carcinoma on the hysterectomy specimen is unknown. The objective of this study was to compare follow-up hysterectomy findings in biopsies showing AIS in CAH with biopsies showing only CAH without AIS. Twelve biopsy/curettage cases diagnosed as endometrial AIS in CAH and 12 biopsy/curettage cases diagnosed as CAH only were reviewed and correlated with corresponding hysterectomy material. A diagnosis of AIS was designated on biopsy/curettings when a focus of back-to-back glands or cribriforming less than 2.1 mm was present. Hysterectomy specimens showed endometrial carcinoma in 6 (50%) of 12 cases of CAH with AIS, and in 2 (17%) of 12 cases diagnosed as CAH only. Endometrial carcinoma with myometrial invasion was identified in 5 (42%) of the cases showing AIS on biopsy, but in none of the 12 cases diagnosed as CAH only on biopsy. Identification of AIS in CAH cases provides useful prognostic information.     

Spatial variations in optical and physiological properties of healthy breast tissue

Near-infrared (NIR) diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) show promise as noninvasive clinical techniques for breast cancer screening and diagnosis. Since NIR methods are based on optical contrast between healthy and diseased tissue, it is essential to characterize the sources of endogenous contrast in normal subjects. We report intra- and inter-subject variation and bilateral asymmetry of the optical and physiological parameters of 31 women using a seven-wavelength NIR frequency-domain photon migration (FDPM) instrument. Wavelength-dependent absorption and reduced scattering parameters (micro(a) and micro(s'), respectively) were measured in four major quadrants and the areolar regions of left and right breasts. These values were used to determine tissue concentrations of oxy-(HbO(2)) and deoxy-(Hb-R) hemoglobin, lipid content, water concentration, and tissue "scatter power." Mean total hemoglobin for premenopausal (PRE) women (20 to 30 microM) is approximately two-fold higher than for postmenopausal (POST) subjects at all positions. POST women have approximately 50% higher lipid content (50 to 60%) than PRE at all positions. Water concentration on average is 1.8-fold higher for PRE subjects (30 to 40%) than POST. These differences are most pronounced when comparing the areolar complex to the other regions of the breast. In premenopausal women, the areolar regions have 40 to 45% increased total hemoglobin concentration (THC), 20 to 25% lower lipid content, and 30 to 60% higher scatter power versus the quadrants. Small-scale (3 cm) changes in optical properties are negligible compared to large-scale variations over all quadrants, where the intrinsic spatial heterogeneity of healthy breast tissue is 20 to 40% for micro(a) and 5 to 12% for micro(s'). Although no consistent right-left differences are observed in the study population, relative differences between symmetric positions ranged from 18 to 30% for THC, 10 to 40% for adipose, 10 to 25% for water, and 4 to 9% for scattering (674 nm) within an individual.     

The variability of clinical presentation of chronic obstructive pulmonary disease in patients with hereditary alpha-1 antitrypsin deficiency

Four patients with alpha-1 antitrypsin (alpha-1 AT) deficiency are presented: one woman with severe (phenotype PiZ) and 3 men with moderate (phenotype PiMZ) deficiency of alpha-1 AT. The variability of clinical presentation of hereditary emphysema is described. In all patients tobacco smoking history, spirometric and 6-minutes walking tests as well as HRCT of the lung were performed and compared. The influence of smoking on the functional status is underlined.     

Steroids and ion channels in evolution: from bacteria to synapses and mind. Evolutionary role of steroid regulation of GABA(A) receptors

Ion channels are vital components of plasma membranes. This article presents an evolutionary view of the biochemical mechanism of controlling activity of ion channels by rigid lipids, such as steroids or biophysically similar molecules, which were instrumental in formation and control of ion channels in cell membranes at the very origin of life. Such regulatory mechanisms exist in all cellular forms of life from ancient bacteria to humans and participate in a diversity of biological functions, from the most basic, such as maintenance of cell shape, homeostasis, feeding, cell fusion, and reproduction to the most intricate, such as the mind. Learning about the regulation of membrane ion channels by steroids and like molecules is important for understanding the evolution of life and various aspects of cell and organism physiology, for unraveling the mysteries of mind, and for practical purposes such as developing new pharmacotherapies.     

VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5(Vcc/null)) completely recapitulate the Pcsk5(Vcc/Vcc) phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development.