Search Results
Search for other papers by Soraya Puglisi in
Google Scholar
PubMed
Search for other papers by Paola Perotti in
Google Scholar
PubMed
Search for other papers by Mattia Barbot in
Google Scholar
PubMed
Search for other papers by Paolo Cosio in
Google Scholar
PubMed
Search for other papers by Carla Scaroni in
Google Scholar
PubMed
Search for other papers by Antonio Stigliano in
Google Scholar
PubMed
Search for other papers by Pina Lardo in
Google Scholar
PubMed
Search for other papers by Valentina Morelli in
Google Scholar
PubMed
Search for other papers by Elisa Polledri in
Google Scholar
PubMed
Search for other papers by Iacopo Chiodini in
Google Scholar
PubMed
Search for other papers by Giuseppe Reimondo in
Google Scholar
PubMed
Search for other papers by Anna Pia in
Google Scholar
PubMed
Search for other papers by Massimo Terzolo in
Google Scholar
PubMed
Objective
Metyrapone has been approved for the treatment of patients with Cushing’s syndrome (CS), but only few retrospective clinical studies are available. The aim of our study was the prospective assessment of metyrapone as pre-operative treatment.
Design and methods
Before adrenalectomy, seven patients with ACTH-independent CS due to adrenal adenoma were prospectively treated with metyrapone for 3 months in three tertiary academic centers, with endocrine work-up and clinical evaluation at screening and at predefined evaluation time points (Days 14, 31, 48, 65, 82).
Results
In all patients, UFC levels decreased up to normal range from baseline to Day 82 (609 (188–1476) vs 69 (28–152) nmol/24 h, P < 0.02), with a reduction of serum and salivary cortisol levels, and no significant increase of plasma ACTH and serum DHEAS levels. Clinical improvement was reported on quality of life (+16.7 (+4.2; +52.00) points, P < 0.04) and pressure control (systolic pressure, −25 (−52; −10) mmHg, P < 0.01; diastolic pressure, −16 (−50; +2 mmHg), P < 0.03). No significant change in weight, electrolytes, glycemic and lipid profile was reported. Although in women a significant increase of testosterone and androstenedione was reported, no worsening of clinical hyperandrogenism was observed. All drug-related adverse events (nausea, fatigue, low grade fever, edema of lower limbs and facial rash) were grade 1 or 2 and generally transient.
Conclusions
This prospective pilot study demonstrated that metyrapone is effective in normalizing biochemical and clinical parameters in patients with CS due to adrenal adenoma before surgical intervention, with minimal side effects.
Assistance Publique Hôpitaux de Paris (APHP), Department of Endocrinology and Diabetes for Children, Bicêtre Paris-Sud, Le Kremlin Bicêtre, France
Search for other papers by Emmanuelle Motte in
Google Scholar
PubMed
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
Search for other papers by Anya Rothenbuhler in
Google Scholar
PubMed
Search for other papers by Stephan Gaillard in
Google Scholar
PubMed
Search for other papers by Najiba Lahlou in
Google Scholar
PubMed
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
Search for other papers by Cécile Teinturier in
Google Scholar
PubMed
Search for other papers by Régis Coutant in
Google Scholar
PubMed
APHP, Plateforme d’Expertise Maladies Rares Paris Sud, Bicêtre Paris Sud Hospital, Le Kremlin Bicêtre, France
Search for other papers by Agnès Linglart in
Google Scholar
PubMed
To investigate whether low-dose mitotane (up to 2 g/day) could be a temporary therapeutic alternative to transsphenoidal surgery (TSS) in pediatric Cushing’s disease (CD). Twenty-eight patients with CD aged 12.2 years (± 2.2) were referred to our center. We compared nine patients treated with mitotane alone for at least 6 months to 13 patients cured after surgery. Primary outcomes were changes in growth velocity, BMI and pubertal development. The following results were obtained: (1) Mitotane improved growth velocity z-scores (−3.8 (±0.3) vs −0.2 (±0.6)), BMI z-scores (2.1 (±0.5) vs 1.2 (±0.5) s.d.) and pubertal development. After 1 year on mitotane, the mean BMI z-score was not significantly different in both groups of patients. (2) Control of cortisol secretion was delayed and inconsistent with mitotane used as monotherapy. (3) Side effects were similar to those previously reported, reversible and dose dependent: unspecific digestive symptoms, concentration or memory problems, physical exhaustion, adrenal insufficiency and hepatitis. (4) In one patient, progressive growth of a pituitary adenoma was observed over 40 months of mitotane treatment, allowing selective adenomectomy by TSS. In conclusions, low-dose mitotane can restore growth velocity and pubertal development and decrease BMI in children with CD, even without optimal control of cortisol secretion. It may promote pituitary tumor growth thus facilitating second-line TSS. However, given its possibly life-threatening side effects (transient adrenal insufficiency and hepatitis), and in the absence of any reliable follow-up procedures, this therapy may be difficult to manage and should always be initiated and monitored by specialized teams.
Search for other papers by Nilesh Lomte in
Google Scholar
PubMed
Search for other papers by Tushar Bandgar in
Google Scholar
PubMed
Search for other papers by Shruti Khare in
Google Scholar
PubMed
Search for other papers by Swati Jadhav in
Google Scholar
PubMed
Search for other papers by Anurag Lila in
Google Scholar
PubMed
Search for other papers by Manjunath Goroshi in
Google Scholar
PubMed
Search for other papers by Rajeev Kasaliwal in
Google Scholar
PubMed
Search for other papers by Kranti Khadilkar in
Google Scholar
PubMed
Search for other papers by Nalini S Shah in
Google Scholar
PubMed
Background
Bilateral adrenal masses may have aetiologies like hyperplasia and infiltrative lesions, besides tumours. Hyperplastic and infiltrative lesions may have coexisting hypocortisolism. Bilateral tumours are likely to have hereditary/syndromic associations. The data on clinical profile of bilateral adrenal masses are limited.
Aims
To analyse clinical, biochemical and radiological features, and management outcomes in patients with bilateral adrenal masses.
Methods
Retrospective analysis of 70 patients with bilateral adrenal masses presenting to a single tertiary care endocrine centre from western India (2002–2015).
Results
The most common aetiology was pheochromocytoma (40%), followed by tuberculosis (27.1%), primary adrenal lymphoma (PAL) (10%), metastases (5.7%), non-functioning adenomas (4.3%), primary bilateral macronodular adrenal hyperplasia (4.3%), and others (8.6%). Age at presentation was less in patients with pheochromocytoma (33 years) and tuberculosis (41 years) compared with PAL (48 years) and metastases (61 years) (P<0.001). The presenting symptoms for pheochromocytoma were hyperadrenergic spells (54%) and abdominal pain (29%), whereas tuberculosis presented with adrenal insufficiency (AI) (95%). The presenting symptoms for PAL were AI (57%) and abdominal pain (43%), whereas all cases of metastasis had abdominal pain. Mean size of adrenal masses was the largest in lymphoma (5.5cm) followed by pheochromocytoma (4.8cm), metastasis (4cm) and tuberculosis (2.1cm) (P<0.001). Biochemically, most patients with pheochromocytoma (92.8%) had catecholamine excess. Hypocortisolism was common in tuberculosis (100%) and PAL (71.4%) and absent with metastases (P<0.001).
Conclusion
In evaluation of bilateral adrenal masses, age at presentation, presenting symptoms, lesion size, and biochemical features are helpful in delineating varied underlying aetiologies.
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Search for other papers by Fernando Aprile-Garcia in
Google Scholar
PubMed
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Search for other papers by María Antunica-Noguerol in
Google Scholar
PubMed
Search for other papers by Maia Ludmila Budziñski in
Google Scholar
PubMed
Search for other papers by Ana C Liberman in
Google Scholar
PubMed
Instituto de Investigación en Biomedicina de Buenos Aires – CONICET, Departamento de Fisiología, Partner Institute of the Max Planck Society, Buenos Aires, Argentina
Search for other papers by Eduardo Arzt in
Google Scholar
PubMed
Inflammatory responses are elicited after injury, involving release of inflammatory mediators that ultimately lead, at the molecular level, to the activation of specific transcription factors (TFs; mainly activator protein 1 and nuclear factor-κB). These TFs propagate inflammation by inducing the expression of cytokines and chemokines. The neuroendocrine system has a determinant role in the maintenance of homeostasis, to avoid exacerbated inflammatory responses. Glucocorticoids (GCs) are the key neuroendocrine regulators of the inflammatory response. In this study, we describe the molecular mechanisms involved in the interplay between inflammatory cytokines, the neuroendocrine axis and GCs necessary for the control of inflammation. Targeting and modulation of the glucocorticoid receptor (GR) and its activity is a common therapeutic strategy to reduce pathological signaling. Poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes the addition of PAR on target proteins, a post-translational modification termed PARylation. PARP1 has a central role in transcriptional regulation of inflammatory mediators, both in neuroendocrine tumors and in CNS cells. It is also involved in modulation of several nuclear receptors. Therefore, PARP1 and GR share common inflammatory pathways with antagonic roles in the control of inflammatory processes, which are crucial for the effective maintenance of homeostasis.
Search for other papers by Legh Wilkinson in
Google Scholar
PubMed
Search for other papers by Nicolette J D Verhoog in
Google Scholar
PubMed
Search for other papers by Ann Louw in
Google Scholar
PubMed
The development of resistance to glucocorticoids (GCs) in therapeutic regimens poses a major threat. Generally, GC resistance is congenital or acquired over time as a result of disease progression, prolonged GC treatment or, in some cases, both. Essentially, disruptions in the function and/or pool of the glucocorticoid receptor α (GRα) underlie this resistance. Many studies have detailed how alterations in GRα function lead to diminished GC sensitivity; however, the current review highlights the wealth of data concerning reductions in the GRα pool, mediated by disease-associated and treatment-associated effects, which contribute to a significant decrease in GC sensitivity. Additionally, the current understanding of the molecular mechanisms involved in driving reductions in the GRα pool is discussed. After highlighting the importance of maintaining the level of the GRα pool to combat GC resistance, we present current strategies and argue that future strategies to prevent GC resistance should involve biased ligands with a predisposition for reduced GR dimerization, a strategy originally proposed as the SEMOGRAM–SEDIGRAM concept to reduce the side-effect profile of GCs.
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Alexander V Amram in
Google Scholar
PubMed
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Stephen Cutie in
Google Scholar
PubMed
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, California, USA
Search for other papers by Guo N Huang in
Google Scholar
PubMed
Research conducted across phylogeny on cardiac regenerative responses following heart injury implicates endocrine signaling as a pivotal regulator of both cardiomyocyte proliferation and heart regeneration. Three prominently studied endocrine factors are thyroid hormone, vitamin D, and glucocorticoids, which canonically regulate gene expression through their respective nuclear receptors thyroid hormone receptor, vitamin D receptor, and glucocorticoid receptor. The main animal model systems of interest include humans, mice, and zebrafish, which vary in cardiac regenerative responses possibly due to the differential onsets and intensities of endocrine signaling levels throughout their embryonic to postnatal organismal development. Zebrafish and lower vertebrates tend to retain robust cardiac regenerative capacity into adulthood while mice and other higher vertebrates experience greatly diminished cardiac regenerative potential in their initial postnatal period that is sustained throughout adulthood. Here, we review recent progress in understanding how these three endocrine signaling pathways regulate cardiomyocyte proliferation and heart regeneration with a particular focus on the controversial findings that may arise from different assays, cellular-context, age, and species. Further investigating the role of each endocrine nuclear receptor in cardiac regeneration from an evolutionary perspective enables comparative studies between species in hopes of extrapolating the findings to novel therapies for human cardiovascular disease.
Search for other papers by Karim Gariani in
Google Scholar
PubMed
Diabetes Center, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Search for other papers by François R Jornayvaz in
Google Scholar
PubMed
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. NAFLD encompasses a whole spectrum ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. The latter can lead to hepatocellular carcinoma. Furthermore, NASH is the most rapidly increasing indication for liver transplantation in western countries and therefore represents a global health issue. The pathophysiology of NASH is complex and includes multiple parallel hits. NASH is notably characterized by steatosis as well as evidence of hepatocyte injury and inflammation, with or without fibrosis. NASH is frequently associated with type 2 diabetes and conditions associated with insulin resistance. Moreover, NASH may also be found in many other endocrine diseases such as polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or glucocorticoid excess, for example. In this review, we will discuss the pathophysiology of NASH associated with different endocrinopathies.
Search for other papers by Aneta Gawlik in
Google Scholar
PubMed
Search for other papers by Michael Shmoish in
Google Scholar
PubMed
Search for other papers by Michaela F Hartmann in
Google Scholar
PubMed
Search for other papers by Stefan A Wudy in
Google Scholar
PubMed
Search for other papers by Zbigniew Olczak in
Google Scholar
PubMed
Search for other papers by Katarzyna Gruszczynska in
Google Scholar
PubMed
Search for other papers by Ze’ev Hochberg in
Google Scholar
PubMed
Objective
Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the ‘steroid metabolomic signature’ of childhood nonalcoholic fatty liver disease.
Methods
Urinary samples of 85 children aged 8.5–18.0 years with BMI >97% were quantified for 31 steroid metabolites by GC-MS. The fingerprints of 21 children with liver disease (L1) as assessed by sonographic steatosis (L1L), elevated alanine aminotransferases (L1A) or both (L1AL), were compared to 64 children without markers of liver disease (L0). The steroidal signature of the liver disease was generated as the difference in profiles of L1 against L0 groups.
Results
L1 comparing to L0 presented higher fasting triglycerides (P = 0.004), insulin (P = 0.002), INS/GLU (P = 0.003), HOMA-IR (P = 0.002), GGTP (P = 0.006), AST/SGOT (P = 0.002), postprandial glucose (P = 0.001) and insulin (P = 0.011). L1AL showed highest level of T-cholesterol and triglycerides (P = 0.029; P = 0.044). Fasting insulin, postprandial glucose, INS/GLU and HOMA-IR were highest in L1L and L1AL (P = 0.001; P = 0.017; P = 0.001; P = 0.001). The liver disease steroidal signature was marked by lower DHEA and its metabolites, higher glucocorticoids (mostly tetrahydrocortisone) and lower mineralocorticoid metabolites than L0. L1 patients showed higher 5α-reductase and 21-hydroxylase activity (the highest in L1A and L1AL) and lower activity of 11βHSD1 than L0 (P = 0.041, P = 0.009, P = 0.019).
Conclusions
The ‘steroid metabolomic signature’ of liver disease in childhood obesity provides a new approach to the diagnosis and further understanding of its metabolic consequences. It reflects the derangements of steroid metabolism in NAFLD that includes enhanced glucocorticoids and deranged androgens and mineralocorticoids.
Search for other papers by Thomas Reinehr in
Google Scholar
PubMed
Search for other papers by Alexandra Kulle in
Google Scholar
PubMed
Search for other papers by Juliane Rothermel in
Google Scholar
PubMed
Search for other papers by Caroline Knop-Schmenn in
Google Scholar
PubMed
Search for other papers by Nina Lass in
Google Scholar
PubMed
Search for other papers by Christina Bosse in
Google Scholar
PubMed
Search for other papers by Paul-Martin Holterhus in
Google Scholar
PubMed
Objective
The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics.
Design
This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13–16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI and change of weight status.
Methods
We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendione-sulfate (DHEA-S), estrone and estradiol by LC–MS/MS steroid profiling at baseline and one year later.
Results
At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, whereas the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol and corticosterone concentrations. Weight loss in obese non-PCOS girls was associated with a significant decrease of DHEA-S, cortisol and corticosterone concentrations, whereas no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss.
Conclusions
The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, whereas glucocorticoids, mineralocorticoids, estrogens and precursors of androgens did not differ between obese girls with and without PCOS.
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Search for other papers by Rachel K Rowe in
Google Scholar
PubMed
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Department of Biology and Biochemistry, University of Bath, UK
Search for other papers by Benjamin M Rumney in
Google Scholar
PubMed
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Department of Biology and Biochemistry, University of Bath, UK
Search for other papers by Hazel G May in
Google Scholar
PubMed
Search for other papers by Paska Permana in
Google Scholar
PubMed
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona, USA
Search for other papers by P David Adelson in
Google Scholar
PubMed
Search for other papers by S Mitchell Harman in
Google Scholar
PubMed
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Search for other papers by Jonathan Lifshitz in
Google Scholar
PubMed
BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, Arizona, USA
Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, Arizona, USA
Search for other papers by Theresa C Thomas in
Google Scholar
PubMed
As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI.