Novas perspectivas no diagnóstico do hipogonadismo pediátrico masculino: a importância do AMH como marcador de células de Sertoli

Sertoli cells are the most active cell population in the testis during infancy and childhood. In these periods of life, hypogonadism can only be evidenced without stimulation tests, if Sertoli cell function is assessed. AMH is a useful marker of prepubertal Sertoli cell activity and number. Serum AMH is high from fetal life until mid-puberty. Testicular AMH production increases in response to FSH and is potently inhibited by androgens. Serum AMH is undetectable in anorchidic patients. In primary or central hypogonadism affecting the whole gonad and established in fetal life or childhood, serum AMH is low. Conversely, when hypogonadism affects only Leydig cells (e.g. LHb mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.b mutations, LH/CG receptor or steroidogenic enzyme defects), serum AMH is normal or high. In pubertal males with central hypogonadism, AMH is low for Tanner stage (reflecting lack of FSH stimulus), but high for the age (indicating lack of testosterone inhibitory effect). Treatment with FSH provokes an increase in serum AMH, whereas hCG administration increases testosterone levels, which downregulate AMH. In conclusion, assessment of serum AMH is helpful to evaluate gonadal function, without the need for stimulation tests, and guides etiological diagnosis of pediatric male hypogonadism. Furthermore, serum AMH is an excellent marker of FSH and androgen action on the testis.As células de Sertoli são a população de células mais ativa nos testículos durante a primeira e segunda infância. Neste período, o hipogonadismo só pode ser evidenciado sem o uso de testes estimulatórios se a função das células de Sertoli for avaliada. O AMH é um marcador útil do número e da atividade das células de Sertoli no período pré-puberal. A concentração sérica de AMH é alta da metade da vida fetal até a metade da puberdade. A produção de AMH pelos testículos aumenta em resposta ao FSH e é potencialmente inibida por androgênios. O AMH sérico não é detectável em pacientes anorquídicos. No hipogonadismo central ou primário afetando a gônada inteira, ou estabelecido na vida fetal ou infância, a concentração de AMH sérica é baixa. Por outro lado, quando o hipogonadismo afeta apenas as células de Leydig (por exemplo, nas mutações, LHb, defeitos do receptor de LH/CG ou das enzimas esteroidogênicas), a concentração de AMH sérico é normal ou alta. Em meninos púberes com hipogonadismo central, a concentração de AMH é baixa para o estágio na escala de Tanner (refletindo a falta de estímulo pelo FSH), mas alta para a idade (indicando a falta do efeito inibidor da testosterona). O tratamento com FSH provoca um aumento do AMH sérico, enquanto a administração de hCG aumenta os níveis de testosterona, que fazem a downregulation do AMH. Em conclusão, a concentração sérica de AMH é útil na avaliação da função gonadal, excluindo a necessidade de testes estimulatórios, e direciona o diagnóstico etiológico do hipogonadismo pediátrico masculino. Além disso, o AMH sérico é um marcador excelente da ação do FSH e dos androgênios nos testículosFil: Grinspon, Romina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; 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; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Biología Celular e Histología; Argentin

Fibromyalgia: A Unifying Neuroendocrinologic Model for Understanding Its Pathophysiology

Fibromyalgia is believed to affect at least 2% of the population. Despite advances in the scientific understanding of the derangements of central and peripheral pain processing mechanisms in fibromyalgia, no current models of its pathophysiology account for the other clinical conditions associated with it such as fatigue, migraine headache, irritable bowel syndrome, and sleep cycle abnormalities. A neuroendocrinologic model of fibromyalgia is presented that accommodates both its known central and peripheral pain mechanisms as well as the myriad of hormonal, visceral, and psychological symptoms associated with that disorder. This model also provides a unifying pathophysiologic basis of fibromyalgia and chronic muscle pain, and offers the potential for developing new avenues of research and treatment for these enigmatic, frequently disabling medical conditions

NPY Levels In Type 1 Diabetic Men of Different Duration.

Background: The aim of the present study was to evaluate whether the different duration of type 1 diabetes mellitus influences basal NPY secretion. Design: The NPY concentrations were measured in sixty-eight men with insulin-dependent diabetes mellitus (IDDM) (duration: group 1 (n.21) <5 years (range 2-4 years); group 2 (n.24) >5 years and <10 years (range: 6-9 years); group 3 (n.29) >10 years (range: 11-14 years)) and in age matched normal control subjects (n. 30). Results: The NPY levels were significantly lower in group 3 than in group 2 and 1 and in the control group, in group 2 than in group 1 and in the control group and in group 1 than control group. Conclusion: These results support the view that the duration of diabetes may have a modulatory role in the decreased basal NPY secretion observed in diabetics

Anorexia nervosa and reproduction: connecting brain to gonads

Anorexia nervosa (AN) is a psychiatric disorder that predominantly affects young women and is characterized by low caloric intake and a major dissatisfaction with one’s body image. It is often overlooked and, while patients and family seek medical help, emaciation and nutritional misbalances may become extreme and potentially life threatening. Among the many somatic complications, an accumulation of early endocrine adaptations occurs, leading to functional amenorrhea and impaired reproduction as a result of dysfunction of the hypothalamic-pituitary-ovarian axis. Even though these conditions are reversible, long-term consequences may affect the fertility of women with AN and can lead to maternal and fetal complications during pregnancy and birth. This review presents the clinical particularities of reproduction in the context of AN, along with the possible pathophysiological mechanisms involved

Human Pancreas GH-Releasing Factor Analog Restores High-Amplitude GH Pulses in CNS Lesion-Induced GH Deficiency

Lesions of the ventromedial-arcuate (VMH-ARC) region of the hypothalamus result in impaired growth accompanied by a marked suppression in spontaneous GH secretory bursts. We studied the effects of an analog of the recently characterized human pancreas GH-releasing factor hpGRF (1-40) on GH secretory dynamics in freely moving chronically cannulated rats bearing electrolytic lesions of the VMH-ARC. Intravenous administration of the hpGRF analog (hpGRFa) caused a dramatic surge of GH within 5 min; plasma GH levels rose to values as high as 2900 ng/ml and remained significantly elevated for 15-30 min post treatment. The simultaneous iv administration of somatostatin-14 and hpGRFa resulted in a significant inhibition of the hpGRFa-induced GH release at 5 min but not at 15 min. These results clearly demonstrate that impaired GH secretion resulting from VMH-ARC lesions can be restored by hpGRF. The findings are promising in that hpGRF and its analogs may provide valuable agents for the diagnosis and treatment of disorders of growth secondary to CNS dysfunction

The unsolved case of “bone-impairing analgesics”. The endocrine effects of opioids on bone metabolism

The current literature describes the possible risks for bone fracture in chronic analgesics users. There are three main hypotheses that could explain the increased risk of fracture associated with central analgesics, such as opioids: 1) the increased risk of falls caused by central nervous system effects, including sedation and dizziness; 2) reduced bone mass density caused by the direct opioid effect on osteoblasts; and 3) chronic opioid-induced hypogonadism. The impact of opioids varies by sex and among the type of opioid used (less, for example, for tapentadol and buprenorphine). Opioid-associated androgen deficiency is correlated with an increased risk of osteoporosis; thus, despite that standards have not been established for monitoring and treating opioid-induced hypogonadism or hypoadrenalism, all patients chronically taking opioids (particularly at doses ≥100 mg morphine daily) should be monitored for the early detection of hormonal impairment and low bone mass density

The heartbreak of depression: 'Psycho-cardiac' coupling in myocardial infarction

Ample evidence identifies strong links between major depressive disorder (MDD) and both risk of ischemic or coronary heart disease (CHD) and resultant morbidity and mortality. The molecular mechanistic bases of these linkages are poorly defined. Systemic factors linked to MDD, including vascular dysfunction, atherosclerosis, obesity and diabetes, together with associated behavioral changes, all elevate CHD risk. Nonetheless, experimental evidence indicates the myocardium is also directly modified in depression, independently of these factors, impairing infarct tolerance and cardioprotection. It may be that MDD effectively breaks the heart's intrinsic defense mechanisms. Four extrinsic processes are implicated in this psycho-cardiac coupling, presenting potential targets for therapeutic intervention if causally involved: sympathetic over-activity vs. vagal under-activity, together with hypothalamic-pituitary-adrenal (HPA) axis and immuno-inflammatory dysfunctions. However, direct evidence of their involvement remains limited, and whether targeting these upstream mediators is effective (or practical) in limiting the cardiac consequences of MDD is unknown. Detailing myocardial phenotype in MDD can also inform approaches to cardioprotection, yet cardiac molecular changes are similarly ill defined. Studies support myocardial sensitization to ischemic insult in models of MDD, including worsened oxidative and nitrosative damage, apoptosis (with altered Bcl-2 family expression) and infarction. Moreover, depression may de-sensitize hearts to protective conditioning stimuli. The mechanistic underpinnings of these changes await delineation. Such information not only advances our fundamental understanding of psychological determinants of health, but also better informs management of the cardiac consequences of MDD and implementing cardioprotection in this cohort.Griffith Health, School of Medical ScienceNo Full Tex

Update on male reproductive endocrinology.

Practitioners of male reproductive and sexual medicine must have an intimate understanding of the physiology of male reproductive endocrinology, as such a knowledge is the cornerstone on which hormonal treatments are based. In this review, we highlight what is known about male reproductive endocrine physiology and the various control mechanisms for the system. We also discuss the limitations of our current understanding of the reproductive physiology. We hope that this review is helpful for male reproductive medicine practitioners in understanding the principles on which hormonal treatments are based

Developmental and functional effects of steroid hormones on the neuroendocrine axis and spinal cord

This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas.Fil: Zubeldia Brenner, Lautaro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Roselli, C. E.. Oregon Health and Science University Portland; Estados UnidosFil: Recabarren, S. E.. Universidad de Concepción; ChileFil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lara, H. E.. Universidad de Chile; Chil

Reduced hypothalamic-pituitary-adrenal axis activity in chronic multi-site musculoskeletal pain : partly masked by depressive and anxiety disorders

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