Endocrine Abstracts

Introduction: Long-lived mice with targeted disruption of the GHRH gene (GHRH knockout; GHRHKO) constitute a unique animal model of altered somatotrophic signaling and are characterized by reduced body mass and size, low plasma IGF1 and enhanced insulin sensitivity. These features are also observed in long-lived GH receptor knockout (GHRKO) mice, characterized by increased visceral obesity that usually promotes insulin resistance. GHRKO mice have also increased subcutaneous fa...

In the framework of close interactions between the immune and neuroendocrine systems, Growth Hormone (GH) has been proposed to exert significant effects on the immune system, but there is not yet a consensus about GH immunomodulatory properties. These studies investigated the immune and anti-infectious response of dwarf Ghrh−/− mice presenting a severe deficiency of the GHRH/GH/IGF-1 axis. In basal conditions, thymic parameters and T-cell respon...

Background: ACROSTUDY is an open-label, non-interventional post-authorization safety study that began in 2004 to evaluate safety in at least 1000 acromegaly patients treated with the GH receptor antagonist pegvisomant (PEGV). This commitment was fulfilled in Jan 2013. ACROSTUDY was later amended to enroll an additional 110 patients that were naïve/semi-naive to PEGV treatment. Semi-naïve patients are defined as not having received PEGV therapy for at least 6 months p...

Background: Cushing’s syndrome (CS) has numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole is a ketoconazole stereoisomer in clinical trials for treatment of CS.Methods: SONICS is a prospective, open-label, phase 3 maintenance-of-benefit study in adults with confirmed CS and mean urinary free cortisol (mUFC) of ≥1.5x upper limit of normal (ULN). Repeated hospitalization due to hyperglycemia or any complication related t...

Pituitary antibodies have been measured mainly to identify patients whose disease is caused or sustained by pituitary-specific autoimmunity. Although reported in over 100 publications, this antibody test has variable results and limited clinical utility. Our goals were to: identify major sources of variability; test them experimentally for establishing an optimized immunofluorescence protocol; assess prevalence and significance of pituitary antibodies in patients with pituitar...

Hypothalamic GH releasing hormone (GHRH) has hypnotic actions by increasing slow wave sleep (SWS) (non-rapid eye movement sleep, non-REM), which account for about 75% of sleep. Conversely, GH may stimulate the rapid eye movement sleep (REM). Patients with GH deficiency (GHD) often exhibit sleep problems leading to daytime fatigue and reduced quality of life (QoL). We have described a cohort of patients with isolated GHD (IGHD) due to GHRH resistance caused by a homozygous null...

Ocular function is fundamental for environmental adaptation and survival capacity. Growth factors are thought to be necessary to reach a mature eyeball and consequent adequate vision. However, the consequences of the deficiency of circulating growth hormone (GH) and its effector insulin-like growth factor I (IGF-I) on the physical aspects of the human eye are still debated. A model of untreated isolated GH deficiency (IGHD) may clarify this issue. The aim of this study was to ...

Background: The phase 3, open-label SONICS study of levoketoconazole demonstrated sustained reduction in mean urinary free cortisol (mUFC) in adults with endogenous Cushing’s syndrome (CS). The extended evaluation phase (Ext) of SONICS reported here further assessed long-term safety, tolerability, and benefit/risk of this treatment.Methods: SONICS consisted of dose-titration (150 – 600 mg BID to attain maximally tolerated dose for mUFC normal...

Mice with isolated GH deficiency (IGHD) due to GHRH receptor mutations live longer than their normal siblings with an extended healthspan, i.e., the period of life free from disabilities. Human IGHD individuals due to a mutation in the GHRH receptor gene from Itabaianinha, Brazil, has a normal lifespan with an extended healthspan (1). Our hypothesis is that their aging is accompanied by a delayed cognitive decline. Accordingly, we used the Literacy Independent Cognitive Assess...

Population aging has become a universal worldwide phenomenon. Developing countries (such as Portuguese-speaking countries, with a high rate of illiteracy) will see the greatest increase in the absolute number of elderly people, and dementia disorders will pose enormous challenges to public health in these countries. Although the decline in GH secretion with age has been associated with deleterious conditions of aging, our understanding is the opposite, that the decline in GH s...