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1. Association of adrenal steroids with metabolomic profiles in patients with primary and endocrine hypertension

Author

Robin Knuchel, Zoran Erlic, Sven Gruber, Laurence Amar, Casper K. Larsen, Anne-Paule Gimenez-Roqueplo, Paolo Mulatero, Martina Tetti, Alessio Pecori, Christina Pamporaki, Katharina Langton, Mirko Peitzsch, Filippo Ceccato, Aleksander Prejbisz, Andrzej Januszewicz, Christian Adolf, Hanna Remde, Livia Lenzini, Michael Dennedy, Jaap Deinum, Emily Jefferson, Anne Blanchard, Maria-Christina Zennaro, Graeme Eisenhofer, and Felix Beuschlein

Subjects
metabolomics, adrenal steroids, endocrine hypertension, primary hypertension, pheochromocytoma, primary aldosteronism, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

IntroductionEndocrine hypertension (EHT) due to pheochromocytoma/paraganglioma (PPGL), Cushing’s syndrome (CS), or primary aldosteronism (PA) is linked to a variety of metabolic alterations and comorbidities. Accordingly, patients with EHT and primary hypertension (PHT) are characterized by distinct metabolic profiles. However, it remains unclear whether the metabolomic differences relate solely to the disease-defining hormonal parameters. Therefore, our objective was to study the association of disease defining hormonal excess and concomitant adrenal steroids with metabolomic alterations in patients with EHT.MethodsRetrospective European multicenter study of 263 patients (mean age 49 years, 50% females; 58 PHT, 69 PPGL, 37 CS, 99 PA) in whom targeted metabolomic and adrenal steroid profiling was available. The association of 13 adrenal steroids with differences in 79 metabolites between PPGL, CS, PA and PHT was examined after correction for age, sex, BMI, and presence of diabetes mellitus.ResultsAfter adjustment for BMI and diabetes mellitus significant association between adrenal steroids and metabolites – 18 in PPGL, 15 in CS, and 23 in PA – were revealed. In PPGL, the majority of metabolite associations were linked to catecholamine excess, whereas in PA, only one metabolite was associated with aldosterone. In contrast, cortisone (16 metabolites), cortisol (6 metabolites), and DHEA (8 metabolites) had the highest number of associated metabolites in PA. In CS, 18-hydroxycortisol significantly influenced 5 metabolites, cortisol affected 4, and cortisone, 11-deoxycortisol, and DHEA each were linked to 3 metabolites.DiscussionsOur study indicates cortisol, cortisone, and catecholamine excess are significantly associated with metabolomic variances in EHT versus PHT patients. Notably, catecholamine excess is key to PPGL’s metabolomic changes, whereas in PA, other non-defining adrenal steroids mainly account for metabolomic differences. In CS, cortisol, alongside other non-defining adrenal hormones, contributes to these differences, suggesting that metabolic disorders and cardiovascular morbidity in these conditions could also be affected by various adrenal steroids.

Published
2024
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3. Microwave ablation of the adrenal gland for treatment of functioning adrenocortical tumours: porcine in vivo study

Author

Padraig Donlon, Hojjatollah Fallahi, Warren Beard Beard, Atif Shazad, Lindsay Heflin, Whitney Cox, Brooke Bloomberg, James Lillich, Chanran Ganta, Gerard O'Sullivan, Giuseppi Ruvio, Paula O'Shea, Martin O'Halloran, Punit Prakash, and Michael Dennedy

Subjects
Pathology, medicine.medical_specialty, medicine.anatomical_structure, business.industry, In vivo, Adrenal gland, Microwave ablation, Medicine, business
Published
2019
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5. Breast-feeding is associated with reduced postpartum maternal glucose intolerance after gestational diabetes

Author

O Reilly, M., Avalos, G., Michael Dennedy, O Sullivan, E. P., and Dunne, F. P.

Subjects
Adult, Blood Glucose, Adolescent, Postpartum Period, Middle Aged, Diabetes, Gestational, Breast Feeding, Logistic Models, Pregnancy, Surveys and Questionnaires, Glucose Intolerance, Humans, Female, Prospective Studies, Ireland
Abstract

Gestational diabetes mellitus (GDM) is associated with adverse foetal and maternal outcomes, and identifies women at risk of future Type 2 Diabetes Mellitus (T2DM). Breast-feeding may improve postpartum maternal glucose tolerance. We prospectively examined the prevalence of postpartum dysglycaemia after GDM and examined the effect of lactation on postpartum glucose tolerance. We compared postpartum 75g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT). Breast-feeding data was collected at time of OGTT. Postpartum OGTT results were classified as normal [fasting plasma glucose (FPG)5.6mmol/l, 2-h7.8 mmol/l] and abnormal [impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2-h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPGor = 7 mmol/l +/- 2h glucoseor = 11.1 mmol/l]. 6 (2.7%) with NGT in pregnancy had postpartum dysglycaemia compared to 57 (19%) with GDM in index pregnancy (p0.001). Non-European ethnicity (OR 3.40, 95% CI 1.45-8.02, p = 0.005), family history of T2DM (OR 2.14, 95% CI 1.06-4.32, p = 0.034) and gestational insulin use (OR 2.62, 95% CI 1.17-5.87 p = 0.019) were associated with persistent dysglycaemia. The prevalence of persistent hyperglycaemia was significantly lower in women who breast-fed versus bottle-fed postpartum (8.2% v 18.4%, p0.001). Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

6. The impact of maternal obesity on gestational outcomes

Author

Michael Dennedy, Avalos G, Reilly Mw, O., Sullivan Ep, O., and Fp, Dunne

Subjects
Adult, Blood Glucose, Analysis of Variance, Respiratory Distress Syndrome, Newborn, Adolescent, Cesarean Section, Postpartum Hemorrhage, Infant, Newborn, Pregnancy Outcome, Hypertension, Pregnancy-Induced, Middle Aged, Hypoglycemia, Body Mass Index, Congenital Abnormalities, Jaundice, Neonatal, Diabetes, Gestational, Pre-Eclampsia, Pregnancy, Birth Weight, Humans, Female, Obesity, Prospective Studies, Fetal Death, Ireland
Abstract

To investigate the effects of raised maternal BMI on pregnancy outcome in glucose tolerant women, using the IADPSG criteria. Prospective observational study of fetal and maternal outcome in a cohort of pregnant women recruited to a universal screening programme for gestational diabetes under the ATLANTIC-DIP partnership. Maternal outcomes included glucose, delivery mode, pregnancy induced hypertension (PIH), preeclampsia (PET), antepartum hemorrhage (APH) and postpartum hemorrhage (PPH). Fetal outcomes included birthweight, congenital malformation, fetal death, neonatal jaundice, hypoglycemia and respiratory distress. Increasing maternal BMI was associated with adverse pregnancy outcomes: higher cesarean section rates, pre-eclamptic toxemia, pregnancy induced hypertension, increased birth weight and congenital malformation. There was also an association between normal range glucose and emergency cesarean section, hypertension of pregnancy and birthweight. In spite of tightening criteria for hyperglycemia during pregnancy, raised BMI is associated with adverse pregnancy outcome.

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