Reversible Kallmann syndrome: report of the first case with a KAL1 mutation and literature review

Kallmann syndrome (KS) describes the association of isolated hypogonadotropic hypogonadism with hypo/anosmia. A few KS patients may reverse hypogonadism after testosterone withdrawal, a variant known as reversible KS. Herein, we describe the first mutation in KAL1 in a patient with reversible KS and review the literature. The proband was first seen at 22 years complaining of anosmia and lack of puberty. His brother had puberty at 30 years and a maternal granduncle had anosmia and delayed puberty. On physical examination, he was P(2)G(1), testes were 3 ml and bone age was 14 years. During 20 years of irregular testosterone replacement, he developed secondary sexual characteristics and testicular enlargement. At the age of 41 years, after stopping testosterone replacement for 5 months, his testes were 15 ml, serum testosterone, LH, and FSH responses to GnRH were normal, and his wife was pregnant. The molecular study revealed a cytosine insertion in exon 2 of KAL1, generating a frameshift at codon 75 and a premature stop at codon 85. The expected gene product is a truncated peptide with 85 of the 680 [corrected] amino acids present in the wild-type protein. Fourteen cases of reversible KS have been described but the genotype was only studied in a single case showing a heterozygous fibroblast growth factor receptor type 1 (FGFR1) mutation. Considering the low prevalence of mutations in KAL1 or FGFR1 in KS, it is possible that these genotypes are more prevalent in reversible KS than in other KS patients, but additional studies are necessary to confirm this hypothesis.     

COVID-19 e Injúria Miocárdica em UTI Brasileira: Alta Incidência e Maior Risco de Mortalidade Intra-Hospitalar

BackgroundThe incidence of myocardial injury (MI) in patients with COVID-19 in Brazil and the prognostic impact of MI have not been elucidated.ObjectivesTo describe the incidence of MI in patients with COVID-19 in the intensive care unit (ICU) and to identify variables associated with its occurrence. The secondary objective was to assess high-sensitivity troponin I as a predictor of in-hospital mortality.MethodsRetrospective, observational study conducted between March and April 2020 with cases of confirmed COVID-19 admitted to the ICU. Numerical variables were compared by using Student t test or Mann-Whitney U test. The chi-square test was used for categorical variables. Multivariate analysis was performed with variables associated with MI and p<0.2 to determine predictors of MI. The ROC curve was used to determine the troponin value capable of predicting higher in-hospital mortality. Survival functions were estimated by use of the Kaplan-Meier method from the cut-off point indicated in the ROC curve.ResultsThis study assessed 61 patients (63.9% of the male sex, mean age of 66.1±15.5 years). Myocardial injury was present in 36% of the patients. Systemic arterial hypertension (HAS) [OR 1.198; 95%CI: 2.246-37.665] and body mass index (BMI) [OR 1.143; 95%CI: 1.013-1.289] were independent risk predictors. High-sensitivity troponin I >48.3 ng/mL, which was determined in the ROC curve, predicts higher in-hospital mortality [AUC 0.786; p<0.05]. Survival in the group with high-sensitivity troponin I >48.3 ng/mL was lower than that in the group with values ≤48.3 ng/dL [20.3 x 43.5 days, respectively; p<0.05].ConclusionThere was a high incidence of MI in severe COVID-19 with impact on higher in-hospital mortality. The independent risk predictors of MI were SAH and BMI. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

Evaluation and treatment of hirsutism in premenopausal women: an endocrine society clinical practice guideline

OBJECTIVE: Our objective was to develop clinical practice guidelines for the evaluation and treatment of hirsutism in premenopausal women. PARTICIPANTS: The Task Force was composed of a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, six additional experts, two methodologists, and a medical writer. The Task Force received no corporate funding or remuneration. EVIDENCE: Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) group criteria to describe both the quality of evidence and the strength of recommendations. We used "recommend" for strong recommendations, and "suggest" for weak recommendations. CONSENSUS PROCESS: Consensus was guided by systematic reviews of evidence and discussions during one group meeting, several conference calls, and e-mail communications. The drafts prepared by the Task Force with the help of a medical writer were reviewed successively by The Endocrine Society's CGS, Clinical Affairs Core Committee (CACC), and Council. The version approved by the CGS and CACC was placed on The Endocrine Society's Web site for comments by members. At each stage of review, the Task Force received written comments and incorporated needed changes. CONCLUSIONS: We suggest testing for elevated androgen levels in women with moderate or severe hirsutism or hirsutism of any degree when it is sudden in onset, rapidly progressive, or associated with other abnormalities such as menstrual dysfunction, obesity, or clitoromegaly. For women with patient-important hirsutism despite cosmetic measures, we suggest either pharmacological therapy or direct hair removal methods. For pharmacological therapy, we suggest oral contraceptives for the majority of women, adding an antiandrogen after 6 months if the response is suboptimal. We recommend against antiandrogen monotherapy unless adequate contraception is used. We suggest against using insulin-lowering drugs. For women who choose hair removal therapy, we suggest laser/photoepilation.     

Increasing trends of sleep complaints in the city of Sao Paulo,Brazil

ObjectiveThe aim of this study was to compare the prevalence of sleep habits and complaints and to estimate the secular trends through three population-based surveys carried out in 1987, 1995, and 2007 in the general adult population of the city of Sao Paulo, Brazil.MethodsSurveys were performed using the same three-stage cluster-sampling technique in three consecutive decades to obtain representative samples of the inhabitants of Sao Paulo with respect to gender, age (20–80 years), and socio-economic status. Sample sizes were 1000 volunteers in 1987 and 1995 surveys and 1101 in a 2007 survey. In each survey, the UNIFESP Sleep Questionnaire was administered face-to-face in each household selected.ResultsFor 1987, 1995, and 2007, respectively, difficulty initiating sleep (weighted frequency %; 95% CI) [(13.9; 11.9–16.2), (19.15; 16.8–21.6), and (25.0; 22.5–27.8)], difficulty maintaining sleep [(15.8; 13.7–18.2), (27.6; 24.9–30.4), and (36.5; 33.5–39.5)], and early morning awakening [(10.6; 8.8–12.7), (14.2; 12.2–16.5), and (26.7; 24–29.6)] increased in the general population over time, mostly in women. Habitual snoring was the most commonly reported complaint across decades and was more prevalent in men. There was no statistically significant difference in snoring complaints between 1987 (21.5; 19.1–24.2) and 1995 (19.0; 16.7–21.6), but a significant increase was noted in 2007 (41.7; 38.6–44.8). Nightmares, bruxism, leg cramps, and somnambulism complaints were significantly higher in 2007 compared to 1987 and 1995. All were more frequent in women.ConclusionsThis is the first study comparing sleep complaints in probabilistic population-based samples from the same metropolitan area, using the same methodology across three consecutive decades. Clear trends of increasing sleep complaints were observed, which increased faster between 1995 and 2007 than from 1987 to 1995. These secular trends should be considered a relevant public health issue and support the need for development of health care and educational strategies to supply the population’s increased need for information on sleep disorders and their consequences.     

Impact of the structure of polypropylene meshes in local tissue reaction: in vivo stereological study

Polypropylene slings are monofilament and multifilament meshes. Their features can impact clinical outcomes. We analyzed tissue reaction, inflammation, and the density of collagen fibers elicited by polypropylene meshes in the subcutaneous tissue of female rats. Thirty female Wistar rats underwent the implantation of 8x4-mm polypropylene meshes (two monofilamentar and two multifilamentar). The rats were killed at 7, 60, and 120 days after implant. Stereology was used to analyze the collagen fiber density. Acute inflammation was more intense in the early post-implant period (p=0.006), except for intravaginal slingplasty (p=0.342). Lymphoplasmocytic reaction was more intense in multifilament samples, even after 60 days (p<0.001) and 120 days (p=0.001). The stereological analysis showed significant differences between mono- and multifilament meshes, considering that monofilament meshes induced more collagen deposition and a greater density of collagen fibers (p<0.001). Multifilament meshes produced a more granulomatous reaction. The collagen fiber density was greater in monofilament meshes, which induced more favorable biocompatibility assessed objectively.     

Massive prolapse of the urethral mucosa following periurethral injection of calcium hydroxylapatite for stress urinary incontinence

The injection of bulking agents into the urethral submucosa is designed to create artificial urethral cushions that can improve urethral coaptation and hence restore continence. Ideally, a urethral bulking agent should be non-immunogenic and biocompatible, leading to minimal inflammatory and fibrotic response. The authors present a case report of a granulomatous reaction leading to urethral prolapse, 3 months after the transurethral injection of calcium hydroxylapatite. To our knowledge, this is the first granulomatous reaction described after calcium hydroxylapatite injection.     

Paraurethral leiomyoma in a female causing urinary obstruction

We report a case of paraurethral leiomyoma in a female patient, in which the first symptoms were dysuria and sensation of incomplete voiding. The physical examination revealed a mass in the anterior vaginal wall. The diagnosis was made through ultrasonography and pelvic MRI and confirmed by transvaginal ultrasound-guided needle biopsy. The surgical excision was accomplished without opening the urinary tract. A review of the relevant published studies and a suggestion for the appropriate management of these cases are included.     

Rosuvastatin prevents proteinuria and renal inflammation in nitric oxide-deficient rats

OBJECTIVE:

The aim of the present study was to assess the effects of rosuvastatin on renal injury and inflammation in a model of nitric oxide deficiency.

METHODS:

Male Wistar rats were randomly divided into four groups (n = 10/group) and treated for 28 days with saline (CTRL); 30 mg/kg/day L-NAME (L-name); L-NAME and 20 mg/kg/day rosuvastatin (L-name+ROS-20); or L-NAME and 2 mg/kg/day rosuvastatin (L-name+ROS-2). Systolic blood pressure was measured by plethysmography in the central artery of the tail. The serum total cholesterol, triglycerides, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatinine, nitric oxide, interleukin-6, and tumor necrosis factor alpha levels were analyzed. Urine samples were taken to measure the albumin∶urinary creatinine ratio. Kidneys were sectioned and stained with hematoxylin/eosin and Masson''s trichrome. Immunohistochemical analysis of the renal tissue was performed to detect macrophage infiltration of the glomeruli.

RESULTS:

The systolic blood pressure was elevated in the L-name but not the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups. The L-name group had a significantly reduced nitric oxide level and an increased interleukin-6 and tumor necrosis factor alpha level, albumin∶urinary creatinine ratio and number of macrophages in the renal glomeruli. Rosuvastatin increased the nitric oxide level in the L-name+rosuvastatin-2 group and reduced the interleukin-6 and tumor necrosis factor alpha levels, glomerular macrophage number and albumin∶urinary creatinine ratio in the L-name+rosuvastatin-20 and L-name+rosuvastatin-2 groups.

CONCLUSION:

Rosuvastatin treatment reduced glomerular damage due to improvement in the inflammatory pattern independent of the systolic blood pressure and serum lipid level. These effects may lead to improvements in the treatment of kidney disease.