Hormonal Defects Are Common during Puumala Hantavirus Infection and Associate with Disease Severity and Biomarkers of Altered Haemostasis.

Central and peripheral hormone deficiencies have been documented during and after acute hantavirus infection. Thrombocytopenia and coagulation abnormalities are common findings in haemorrhagic fever with renal syndrome (HFRS). The associations between coagulation and hormonal abnormalities in HFRS have not been studied yet. Forty-two patients diagnosed with Puumala virus (PUUV) infection were examined during the acute phase and on a follow-up visit approximately one month later. Hormonal defects were common during acute PUUV infection. Overt (clinical) hypogonadism was identified in 80% of the men and approximately 20% of the patients had overt hypothyroidism. At the one-month follow-up visit, six patients had central hormone deficits. Acute peripheral hormone deficits associated with a more severe acute kidney injury (AKI), longer hospital stay and more severe thrombocytopenia. Half of the patients with bleeding symptoms had also peripheral hormonal deficiencies. Patients with free thyroxine levels below the reference range had higher D-dimer level than patients with normal thyroid function, but no thromboembolic events occurred. Acute phase hormonal abnormalities associate with severe disease and altered haemostasis in PUUV infection.

Intermittent Starvation Extends the Functional Lifetime of Primary Human Hepatocyte Cultures.

Primary human hepatocyte (PHH) cultures have become indispensable to mitigate the risk of adverse drug reactions in human patients. In contrast to dedifferentiating monocultures, coculture with nonparenchymal cells maintains PHH functions for 2-4 weeks. However, because the functional lifespan of PHHs in vivo is 200-400 days, it is desirable to further prolong PHH functions in vitro toward modeling chronic drug exposure and disease progression. Fasting has benefits on the longevity of organisms and the health of tissues such as the liver. We hypothesized that a culturing protocol that mimics dynamic fasting/starvation could activate starvation pathways and prolong PHH functional lifetime. To mimic starvation, serum and hormones were intermittently removed from the culture medium of micropatterned cocultures (MPCCs) containing PHHs organized onto collagen domains and surrounded by 3T3-J2 murine fibroblasts. A weekly 2-day starvation optimally prolonged PHH functional lifetime for 6+ weeks in MPCCs versus a decline after 3 weeks in nonstarved controls. The 2-day starvation also enhanced the functions of PHH monocultures for 2 weeks, suggesting direct effects on PHHs. In MPCCs, starvation activated 5' adenosine monophosphate-activated protein kinase (AMPK) and restricted fibroblast overgrowth onto PHH islands, thereby maintaining hepatic polarity. The effects of starvation on MPCCs were partially recapitulated by activating AMPK using metformin or growth arresting fibroblasts via mitomycin-C. Lastly, starved MPCCs demonstrated lower false positives for drug toxicity tests and higher drug-induced cytochrome-P450 activities versus nonstarved controls even after 5 weeks. In conclusion, intermittent serum/hormone starvation extends PHH functional lifetime toward enabling clinically relevant drug screening.

The effect of treatment on quality of life in patients with acromegaly: a prospective study.

OBJECTIVE: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. DESIGN: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. METHODS: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. RESULTS: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. CONCLUSION: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.

Zika Virus Infection in Hypothalamus Causes Hormone Deficiencies and Leads to Irreversible Growth Delay and Memory Impairment in Mice.

Zika virus (ZIKV) can cause microcephaly in the fetus. However, its effects on body growth and the development of children with postnatal ZIKV infection are largely unknown. To examine this, we intraperitoneally challenged mouse pups with ZIKV. Infection causes an irreversible growth delay and deficits in spatial learning and memory, with growth-relevant hormones significantly reduced during infection. These effects are associated with ZIKV RNA expression in the hypothalamus, blood, and brain but not in the pituitary and thyroid. Infection is also associated with hypothalamic inflammation, and ZIKV antigen is detectable in neuroendocrine cells producing thyrotropin-releasing hormone. Moreover, early administration of growth hormone could significantly improve growth delay. Our results demonstrate that ZIKV can infect the hypothalamus, causing multi-hormone deficiencies and delayed growth and development in a mouse model. Therefore, prospective multidisciplinary follow-up of ZIKV-infected children may be necessary to understand potential effects of this virus on childhood development.

Oxidative stress as a possible mechanism underlying multi-hormonal deficiency in chronic heart failure.

OBJECTIVE: Chronic Heart Failure (CHF) is associated with multi-hormonal derangement depicting a prevalence of catabolic vs. anabolic axes. Moreover, thyroid adaption is characterized by the reduced conversion of thyroxine to the active hormone triiodothyronine. On the other hand, hormones modulate synthesis and utilization of antioxidant systems. Therefore, hormonal failure can cause unbalance between reactive radical species and the defenses, resulting in oxidative stress (OS). OS is well described in CHF, but the relationship with the hormonal picture is not entirely known. In the present review, we firstly analyze the mechanisms of ROS production in the heart, discussing animal and human studies, and focusing on new discovered protective mechanisms such as sirtuins and fibroblast growth factor 21 (FGF21). The second section is dedicated to the role of main anabolic axes influencing antioxidant systems. Finally, we present some data supporting the hypothesis that OS could be the link between hormonal derangement and clinical outcome of CHF.

Analytical considerations and general diagnostic and therapeutic ramifications of milk hormones during lactation.

In this review, we will discuss the changes that occur in the mammary gland from pregnancy to lactation and the issues surrounding the analysis of circulating and milk hormones during the stages of lactogenesis. There is a cascade of events that must occur to achieve milk synthesis, milk ejection, and successful transfer to the breastfeeding infant. The adequacy and success of this process is no small measure and the assessment of milk production, the hormones involved in this process and the ability to properly diagnose conditions and causes of low milk supply are critical for the health and well-being of the mother-infant breastfeeding dyad. The normative data that have been amassed in past decades suggest that there are certain values or circulating concentrations of milk hormones, that if lacking or low, could explain low milk supply status. Yet, in looking more closely at the tests themselves, the certainly of what constitutes "normal" can vary depending on the preanalytical conditions that the blood or milk sample were obtained, the methods used in obtaining circulating or milk concentrations, and the standardization of how that result is expressed. The standardization of these aspects of breast milk physiology are essential for providing important normative data to health care professionals and researchers and will result in more consistent findings across multi-disciplinary platforms.

Hormones and Sarcopenia.

Sarcopenia is defined as the loss of muscle mass associated with a loss of muscle function, e.g., walking speed. A number of consensus definitions exist for sarcopenia with cut-off points being ethnically specific. A rapid screen test (SARC-F) is available and does not require different ethnic cut-off points. Sarcopenia leads to the development of frailty, disability and mortality. The prevalence of sarcopenia varies from 1-29% in community- dwelling and 14 to 33% in long-term care populations. Hormones play a role in the development of muscle mass and in the regulation of muscle strength. Testosterone appears to be the central hormone involved in the development of sarcopenia; it increases both muscle mass and activates satellite cells leading to increased muscle function. Growth hormone deficiency leads to the loss of muscle mass but not muscle strength. Lack of insulin or insulin resistance leads to accelerated development of sarcopenia. Vitamin D deficiency plays a role in the loss of muscle strength. A variety of other hormones appear to play minor roles in age-related alterations in muscle mass and function. At present, the treatment of sarcopenia is resistance exercise, leucine enriched essential amino acids or hydroxymethylbutyrate and vitamin D replacement.

Hormone disorder and vitamin deficiency in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASDs).

BACKGROUND: The aim of this study was to analyze thyroid hormones and antibodies, ferritin, vitamins B12 and D, adrenal and gonadal steroid levels, and celiac antibodies in children diagnosed with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). METHODS: Between February 2014 and July 2014, a total of 77 children and adolescents (31 girls, 46 boys) who were admitted to the Van Training and Research Hospital were included in the study. The study population was divided into three groups including ADHD (n=34), ASD (n=16), and age- and sex-matched healthy controls (n=27). The diagnosis of ADHD was made on the basis of Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) and DSM-4 Turkish version with the diagnostic interview and Disruptive Behavior Disorder Rating Scale (DBDRS). The diagnosis of ASD was based on the DSM-4 and DSM-5 Turkish version with the diagnostic interview and the Childhood Autism Rating Scale (CARS). The blood samples were obtained between 8:00 and 9:00 A.M. RESULTS: There was a statistically significant difference in vitamin B12 and D levels and ferritin values among the three groups. The ASD group had the highest ferritin and the lowest vitamins B12 and D levels. Vitamin D levels of the ADHD group were significantly lower compared to the healthy controls. CONCLUSIONS: Our study results highlight the importance of supplementation of vitamins B12 and D in the ASD and ADHD patients.

Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation.

BACKGROUND: Patients with pituitary stalk interruption syndrome (PSIS) are initially referred for hypoglycemia during the neonatal period or growth retardation during childhood. PSIS is either isolated (nonsyndromic) or associated with extra-pituitary malformations (syndromic). OBJECTIVE: To compare baseline characteristics and long-term evolution in patients with PSIS according to the initial presentation. STUDY DESIGN: Sixty-seven patients with PSIS were included. Data from subgroups were compared: neonates (n = 10) versus growth retardation patients (n = 47), and syndromic (n = 32) versus nonsyndromic patients (n = 35). RESULTS: Neonates displayed a more severe hormonal and radiological phenotype than children referred for growth retardation, with a higher incidence of multiple hormonal deficiencies (100% versus 34%; P = 0.0005) and a nonvisible anterior pituitary lobe (33% versus 2%; P = 0.0017). Regular follow-up of growth might have allowed earlier diagnosis in the children with growth retardation, as decreased growth velocity and growth retardation were present respectively 3 and 2 years before referral. We documented a progressive worsening of endocrine impairment throughout childhood in these patients. Presence of extra-pituitary malformations (found in 48%) was not associated with more severe hormonal and radiological characteristics. Growth under GH treatment was similar in the patient groups and did not vary according to the pituitary MRI findings. CONCLUSIONS: PSIS diagnosed in the neonatal period has a particularly severe hormonal and radiological phenotype. The progressive worsening of endocrine impairment throughout childhood justifies periodic follow-up to check for additional hormonal deficiencies.

Avaliação dos eletrolitos sódio, fósforo, cálcio ionizado, potássio, magnésio e cloro em cães com Hipotireoidismo / Evaluation of electrolytes sodium, phosphorus, ionized calcium, potassium, magnesium and chlorine in dogs with Hypothyroidism

A tireóide é considerada a glândula endócrina mais importante para a regulação metabólica e a deficiência dos hormônios produzidos por ela, chamada de hipotireoidismo, afeta múltiplas funções orgânicas. Com vistas às funções dos hormônios da glândula tireóide no metabolismo energético da célula formulou-se a hipótese deste estudo, que avaliou a homeostase eletrolítica, particularmente as concentrações séricas de sódio, fósforo, cálcio ionizado, potássio, magnésio e cloro em cães com hipotireoidismo. Para tal foram selecionados 10 cães com diagnóstico de hipotireoidismo primário adquirido e cinco cães hígidos como controle. O diagnóstico foi embasado nos dados de anamnese, exame físico e laboratorial de rotina, e por testes hormonais para avaliação da função tireoidiana. Os resultados foram analisados pelo Test t para a comparação entre duas médias. O nível de significância crítico para todas as análises estatísticas realizadas foi de p<0,05 (5%). Os resultados não mostraram alterações nos níveis séricos de sódio, potássio, cálcio ionizado, fósforo, cloro e magnésio na comparação entre animais sadios e diagnosticados com hipotireoidismo.

The thyroid is considered the most important gland for metabolic regulation and the hormone deficiency of this gland called hypothyroidism can cause multiple body function alteration. Based on the functions of the thyroid hormones on energy metabolism of the cell, we evaluated the electrolyte homeostasis, particularly serum concentrations of sodium, phosphorus, ionized calcium, potassium, magnesium and chlorine in dogs with hypothyroidism. For this, we selected 10 dogs diagnosed with primary acquired hypothyroidism and five healthy dogs as controls. The diagnosis was based on anamnesis, physical examination, laboratory routine exams, and hormonal tests to evaluate thyroid function. Results were analyzed by t test for comparison between two means. The critical level of significance for all statistical analyzes was set at p <0.05. The results showed no change in serum sodium, potassium, ionized calcium, phosphorus, chlorine and magnesium in dogs with hypothyroidism compared to healthy dogs.

Secondary service connection for diagnosable illnesses associated with traumatic brain injury. Final rule.

The Department of Veterans Affairs (VA) amends its adjudication regulations concerning service connection. This final rule acts upon a report of the National Academy of Sciences, Institute of Medicine (IOM), Gulf War and Health, Volume 7: Long-Term Consequences of Traumatic Brain Injury, regarding the association between traumatic brain injury (TBI) and five diagnosable illnesses. This amendment establishes that if a veteran who has a service-connected TBI also has one of these diagnosable illnesses, then that illness will be considered service connected as secondary to the TBI.

A psychological perspective on male rejuvenation.

Male rejuvenation, defined as a process in men to both limit the impact of aging on body image and experience greater virility, is growing among middle-aged and older men. While rejuvenation was primarily in the domain of the younger male athlete with the use of performance enhancing hormones or in the aging woman through the use of cosmetic surgery, it is now more common among middle-aged and older men. Male rejuvenation can occur both through aesthetic surgical means and hormonal manipulation through anabolic steroid use. In this article, the authors review the psychological issues and perceptions surrounding male aesthetic surgeries and the resulting alteration of perception by peers and family; highlight the motives and desires behind the use of anabolic hormones at often supra-physiologic levels, and the intent to improve body image; and clarify the needs that remain to be examined in future research in this field.

Scientific overview of hormone treatment used for rejuvenation.

A search for a hormonal fountain of youth has been hotly pursued over the last century, predominately by those who wish to market hormones to a gullible public. There is little or no benefit of hormone replacement in persons who do not have a hormone deficiency. Overall, the present state of the art suggests that the findings have been disappointing. In persons who fail to get adequate sunlight, and therefore have low vitamin D levels, vitamin D replacement appears to have positive effects, including decreasing mortality. Testosterone in hypogonadal males has a number of positive effects such as improving libido and erectile capacity, increasing strength and bone mineral density, and perhaps having a small effect on cognition. These effects need to be balanced against long-term side effects, the evidence for which studies are lacking. There is little evidence to recommend DHEA, pregnenolone, growth hormone, ghrelin, or melatonin to older persons. Overall, exercise, adequate exposure to sunlight, and adequate dietary protein appear to have at least as positive an effect as any of the hormones being used to rejuvenate older persons.

Introduction: male rejuvenation: what the reproductive specialist needs to know.

Androgens and other hormones are commonly being used by men in attempts to achieve a variety of health benefits that are often referred to "male rejuvenation." This series of articles will prepare the reproductive specialist to deal with these patients and their presented problems.

Effect of rejuvenation hormones on spermatogenesis.

OBJECTIVE: To review the current literature for the effect of hormones used in rejuvenation clinics on the maintenance of spermatogenesis. DESIGN: Review of published literature. SETTING: Not applicable. PATIENT(S): Men who have undergone exogenous testosterone (T) and/or anabolic androgenic steroid (AAS) therapies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Semen analysis, pregnancy outcomes, and time to recovery of spermatogenesis. RESULT(S): Exogenous testosterone and anabolic androgenic steroids suppress intratesticular testosterone production, which may lead to azoospermia or severe oligozoospermia. Therapies that protect spermatogenesis involve human chorionic gonadotropin (hCG) therapy and selective estrogen receptor modulators (SERMs). The studies examining the effect of human growth hormone (HGH) on infertile men are uncontrolled and unconvincing, but they do not appear to negatively impact spermatogenesis. At present, routine use of aromatase inhibitors is not recommended based on a lack of long-term data. CONCLUSION(S): The use of hormones for rejuvenation is increasing with the aging of the Baby Boomer population. Men desiring children at a later age may be unaware of the side-effect profile of hormones used at rejuvenation centers. Testosterone and anabolic androgenic steroids have well-established detrimental effects on spermatogenesis, but recovery may be possible with cessation. Clomiphene citrate, human growth hormone (HGH)/insulin-like growth factor-1 (IGF-1), human chorionic gonadotropin (hCG), and aromatase inhibitors do not appear to have significant negative effects on sperm production, but quality data are lacking.

Enhanced striatal ß1-adrenergic receptor expression following hormone loss in adulthood is programmed by both early sexual differentiation and puberty: a study of humans and rats.

After reproductive senescence or gonadectomy, changes occur in neural gene expression, ultimately altering brain function. The endocrine mechanisms underlying these changes in gene expression beyond immediate hormone loss are poorly understood. To investigate this, we measured changes in gene expression the dorsal striatum, where 17ß-estradiol modulates catecholamine signaling. In human caudate, quantitative PCR determined a significant elevation in ß1-adrenergic receptor (ß1AR) expression in menopausal females when compared with similarly aged males. No differences were detected in ß2-adrenergic and D1- and D2-dopamine receptor expression. Consistent with humans, adult ovariectomized female rats exhibited a similar increase in ß1AR expression when compared with gonadectomized males. No sex difference in ß1AR expression was detected between intact adults, prepubertal juveniles, or adults gonadectomized before puberty, indicating the necessity of pubertal development and adult ovariectomy. Additionally, increased ß1AR expression in adult ovariectomized females was not observed if animals were masculinized/defeminized with testosterone injections as neonates. To generate a model system for assessing functional impact, increased ß1AR expression was induced in female-derived cultured striatal neurons via exposure to and then removal of hormone-containing serum. Increased ß1AR action on cAMP formation, cAMP response element-binding protein phosphorylation and gene expression was observed. This up-regulation of ß1AR action was eliminated with 17ß-estradiol addition to the media, directly implicating this hormone as a regulator of ß1AR expression. Beyond having implications for the known sex differences in striatal function and pathologies, these data collectively demonstrate that critical periods early in life and at puberty program adult gene responsiveness to hormone loss after gonadectomy and potentially reproductive senescence.

Sex and hormonal influences on seizures and epilepsy.

Epilepsy is the third most common chronic neurological disorder. Clinical and experimental evidence supports the role of sex and influence of sex hormones on seizures and epilepsy as well as alterations of the endocrine system and levels of sex hormones by epileptiform activity. Conversely, seizures are sensitive to changes in sex hormone levels, which in turn may affect the seizure-induced neuronal damage. The effects of reproductive hormones on neuronal excitability and seizure-induced damage are complex to contradictory and depend on different mechanisms, which have to be accounted for in data interpretation. Both estradiol and progesterone/allopregnanolone may have beneficial effects for patients with epilepsy. Individualized hormonal therapy should be considered as adjunctive treatment in patients with epilepsy to improve seizure control as well as quality of life.

Reposição hormonal e exercício físico no tratamento da insuficiência cardíaca: revisão sistemática / Hormonal replacement and physical exercise in heart failure treatment: a systematic review

FUNDAMENTAÇÃO: A despeito do pleno uso da terapia farmacológica e não farmacológica, persistem as expressivas morbidade e mortalidade decorrentes da insuficiência cardíaca (IC). No contexto terapêutico é relevante a inibição das inadequadas adaptações neuro-hormonais e metabólicas, sendo bem conhecida a deficiência anabólica que se instala na IC. Mas somente recentemente surgiram alguns estudos sobre os benefícios que adviriam da terapia de reposição ou suplementação de testosterona (TRT). OBJETIVOS: Pesquisar estudos que abordem a TRT na insuficiência cardíaca (IC), em especial os desenvolvidos no cenário ideal de tratamento clínico, que inclui programa de exercício físico. MÉTODOS: Foram consultadas as bases de dados SciELO e PubMed, a base de dados Cochrane de Revisões Sistemáticas e o Registro de Ensaios Controlados da Colaboração Cochrane. RESULTADOS: Os poucos estudos sobre TRT em pacientes com IC evidenciaram melhora da função hemodinâmica, da resistência à insulina, da capacidade funcional e das respostas neuro-hormonal e neuromuscular, evidenciaram as controvérsias quanto à influência sobre o perfil inflamatório, e não constataram mudanças na função e na estrutura cardiovascular central. Entretanto, não foi encontrado nenhum estudo sobre TRT concomitante ao programa de exercícios físicos. CONCLUSÕES: O estágio atual de conhecimento, embora baseado em poucos estudos, permite considerar a TRT no tratamento de pacientes com IC. Não está bem definida a forma ideal da TRT, no que diz respeito à duração do tratamento, critérios de inclusão e exclusão etc. Existe uma grande lacuna na literatura, chamando atenção à inexistência de estudos sobre a TRT concomitante ao tratamento clínico pleno, que inclui um programa de exercícios físicos.

BACKGROUND: Despite the full use of pharmacological and non pharmacological therapy, morbidity and mortality incidence as a result from heart failure (HF) are still significantly persistent. In the therapeutic context is relevant the inhibition of the inadequate neuro-hormonal adaptations and metabolic, as well known the anabolic deficiency that develops in HF. But just recently some studies emerged about the benefits from the testosterone replacement or supplementation therapy (TRT). OBJECTIVE: Reviewing studies that address the TRT in heart failure (HF), particularly those developed in the ideal setting for clinical treatment, including physical exercise program. METHODS: It was analyzed the Scielo and Pubmed databases, Cochrane of Systematic Review and Clinical Control Trials from Cochrane Collaboration databases. RESULTS: The few studies about TRT in patients with HF showed improvement in of the hemodynamic function, insulin resistance, functional capacity and neuro-hormonal and neuromuscular responses, highlight the controversy regarding the influence on the inflammatory profile, and found no changes in function and structure in the central cardiovascular system. However, it has not been found studies about TRT associated with exercises program. CONCLUSION: the present state of knowledge, although based on a few studies, allows to considerate TRT in the treatment of patients with HF. It is not well-defined the ideal form of TRT, regarding to treatment duration, criteria for inclusion and exclusion, etc. There is a wide gap in the literature, calling attention to the lack of studies about TRT concomitant with full medical treatment, which includes an physical exercise program.