Anti-Müllerian hormone, testicular descent and cryptorchidism

Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes

Clinical Presentation of Klinefelter's Syndrome: Differences According to Age

The aim of the study was to establish the characteristics of presentation of 94 patients with Kinelfelter's syndrome (KS) referred to the endocrinologist at different ages. The diagnosis of KS was more frequent in the age group between 11 and 20 years (46.8%). Most of the patients (83.7%) showed the classic 47,XXY karyotype and 7.1% showed a 47,XXY/46,XY mosaicism. Half of the patients younger than 18 years presented mild neurodevelopmental disorders. The most frequent clinical findings were cryptorchidism in prepubertal patients, and small testes, cryptorchidism, and gynecomastia in pubertal patients. FSH, LH, AMH, and inhibin B levels were normal in prepubertal patients and became abnormal from midpuberty. Most adults were referred for small testes, infertility, and gynecomastia; 43.6% had sexual dysfunction. Testosterone levels were low in 45%. Mean stature was above the 50th percentile, and 62.5% had BMI ≥25.0 kg/m2. In conclusion, the diagnosis of Klinefelter syndrome seems to be made earlier nowadays probably because pediatricians are more aware that boys and adolescents with neuro-developmental disorders and cryptorchidism are at increased risk. The increasing use of prenatal diagnosis has also decreased the mean age at diagnosis and allowed to get insight into the evolution of previously undiagnosed cases, which probably represent the mildest forms. In adults average height and weight are slightly higher than those in the normal population. Bone mineral density is mildly affected, more at the spine than at the femoral neck level, in less than half of cases

Safety of standardised treatments for haematologic malignancies as regards to testicular endocrine function in children and teenagers

Study question: Does standardised treatments used in children and adolescents with haematologic malignancies, including acute lymphoblastic (ALL) or myeloid leukaemia (AML) and non-Hodgkin lymphoma (NHL), affect endocrine function of the developing testes? Summary answer: Therapy of haematologic malignancies do not provoke an overt damage of Sertoli and Leydig cell populations, as revealed by normal levels of anti-Müllerian hormone (AMH) and testosterone, but a mild primary testicular dysfunction may be observed, compensated by moderate gonadotropin elevation, during pubertal development. What is known already: Evidence exists on the deleterious effect that chemotherapy and radiotherapy have on germ cells, and some attention has been given to the effects on Leydig and Sertoli cells of the adult gonads, but information is virtually non-existent on the effects of oncologic treatment on testicular somatic cell components during childhood and adolescence. Study design, size, duration: A retrospective, analytical, observational study included 97 boys with haematological malignancies followed at two tertiary paediatric public hospitals in Buenos Aires, Argentina, between 2002 and 2015. Participants/materials, setting, methods: Clinical records of males aged 1-18 years, referred with the diagnoses of ALL, AML or NHL for the assessment of gonadal function, were eligible. We assessed serum levels of AMH and FSH as biomarkers of Sertoli cell endocrine function and testosterone and LH as biomarkers of Leydig cell function. Main results and the role of chance: All hormone levels were normal in the large majority of patients until early pubertal development. From Tanner stage G3 onwards, while serum AMH and testosterone kept within the normal ranges, gonadotropins reached mildly to moderately elevated values in up to 35.9% of the cases, indicating a compensated Sertoli and/or Leydig cell dysfunction, which generally did not require hormone replacement therapy. Limitations, reasons for caution: Serum inhibin B determination and semen analysis were not available for most patients; therefore, we could not conclude on potential fertility impairment or identify whether primary Sertoli cell dysfunction resulted in secondary depleted spermatogenesis or whether primary germ cell damage impacted Sertoli cell function. Wider implications of the findings: The regimens used in the treatment of boys and adolescents with ALL, AML or NHL in the past two decades seem relatively safe for endocrine testicular function; nonetheless, a mild primary testicular endocrine dysfunction may be observed, usually compensated by slightly elevated gonadotropin secretion by the pituitary in adolescents, and not requiring hormone replacement therapy. No clinically relevant risk factor, such as severity of the disease or treatment protocol, could be identified in association with the compensated endocrine dysfunction. Study funding/competing interest(s): This work was partially funded by grants PIP 11220130100687 of Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and PICT 2016-0993 of Fondo para la Investigación Científica y Tecnológica (FONCYT), Argentina. R.A.R., R.P.G. and P.B. have received honoraria from CONICET (Argentina) for technology services using the AMH ELISA. L.A.A. is part-time employee of CSL Behring Argentina. The other authors have no conflicts of interest to disclose.Fil: Grinspon, Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Arozarena, María. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Prada, Silvina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bargman, Graciela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Sanzone, María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Morales Bazurto, Marjorie. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gutiérrez, Marcela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bedecarras, Patricia Gladys. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Kannemann, Ana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Elena, Graciela O.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Gottlieb, Silvia Elisa. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; ArgentinaFil: Berenstein, Ariel José. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Ropelato, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bergadá, Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Aversa, Luis A.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Rey, Rodolfo Alberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentin

Broad Balmer Wings in BA Hyper/Supergiants Distorted by Diffuse Interstellar Bands: Five Examples in the 30 Doradus Region from the VLT-FLAMES Tarantula Survey

Extremely broad emission wings at Hβ and Hα have been found in VLT-FLAMES Tarantula Survey data for five very luminous BA supergiants in or near 30 Doradus in the Large Magellanic Cloud. The profiles of both lines are extremely asymmetrical, which we have found to be caused by very broad diffuse interstellar bands (DIBs) in the longward wing of Hβ and the shortward wing of Hα. These DIBs are well known to interstellar but not to many stellar specialists, so that the asymmetries may be mistaken for intrinsic features. The broad emission wings are generally ascribed to electron scattering, although we note difficulties for that interpretation in some objects. Such profiles are known in some Galactic hyper/supergiants and are also seen in both active and quiescent Luminous Blue Variables (LBVs). No prior or current LBV activity is known in these 30 Dor stars, although a generic relationship to LBVs is not excluded; subject to further observational and theoretical investigation, it is possible that these very luminous supergiants are approaching the LBV stage for the first time. Their locations in the HRD and presumed evolutionary tracks are consistent with that possibility. The available evidence for spectroscopic variations of these objects is reviewed, while recent photometric monitoring does not reveal variability. A search for circumstellar nebulae has been conducted, with an indeterminate result for one of them

Heart failure in COVID-19 patients: prevalence, incidence and prognostic implications

Aims: Data on the impact of COVID-19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking. The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID-19 infection and a prior diagnosis of heart failure (HF). Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline-directed medical therapy (GDMT) and worse outcomes during hospitalization. Methods and results: Data for a total of 3080 consecutive patients with confirmed COVID-19 infection and follow-up of at least 30 days were analysed. Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs. 2.1%; P < 0.001) and had higher levels of N-terminal pro brain natriuretic peptide. In addition, patients with previous CHF had higher mortality rates (48.7% vs. 19.0%; P < 0.001). In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF. Arrhythmias during hospital admission and CHF were the main predictors of AHF. Patients developing AHF had significantly higher mortality (46.8% vs. 19.7%; P < 0.001). Finally, the withdrawal of beta-blockers, mineralocorticoid receptor antagonists and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in-hospital mortality. Conclusions: Patients with COVID-19 have a significant incidence of AHF, which is associated with very high mortality rates. Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID-19 diagnosis. The withdrawal of GDMT was associated with higher mortalit

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Biomarcadores de hipogonadismo masculino en la infancia y la adolescencia

El eje hipotálamo-hipófiso-testicular es activo en la vida fetal y durante los primeros meses de la vida posnatal: la hipófisis secreta hormona luteinizante (LH) y folículo-estimulante (FSH), mientras que el testículo produce testosterona y factor insulino-símil 3 (INSL3) en las células de Leydig y hormona anti-Mülleriana (AMH) e inhibina B en las células de Sertoli. En la infancia, los niveles séricos de gonadotrofinas, testosterona y factor INSL3 disminuyen a valores prácticamente indetectables, pero los de AMH e inhibina B permanecen altos. En la pubertad, se reactivan las gonadotrofinas y la producción de testosterona e INSL3, aumenta la inhibina y disminuye la AMH, como signo de maduración de la célula de Sertoli. Sobre la base del conocimiento de la fisiología del desarrollo del eje, es posible utilizar clínicamente estos biomarcadores para interpretar la fisiopatología y diagnosticar las diferentes formas de hipogonadismo que pueden presentarse en la infancia y la adolescencia