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Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Department of Endocrinology and Metabolism, BSMMU, Dhaka, Bangladesh
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Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
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Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society’s clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.
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In critically ill adults, high plasma cortisol in the face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype. From 53 patients (0–36 months), plasma was obtained pre-operatively, intraoperatively, and on post-operative days 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (P < 0.0001) but no longer thereafter (P > 0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (P < 0.0001), glucocorticoid-treated patients had already suppressed ACTH intraoperatively (P ≤ 0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally activated HPA axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.
Significance statement
Glucocorticoids are often administered during pediatric cardiac surgery. In critically ill children, endogenous systemic glucocorticoid availability is elevated already upon ICU admission while ACTH levels are normal. This hormonal constellation suggests the presence of active feedback inhibition of ACTH. In this study, we have documented that intraoperative administration of glucocorticoids accelerates the suppression of ACTH, resulting in low plasma ACTH already upon ICU admission. Pre-operative plasma POMC, the ACTH precursor, but not ACTH, was increased. This is compatible with a centrally activated HPA axis prior to surgery in young children but reduced processing of POMC into ACTH within the pituitary. These findings suggest that glucocorticoid treatment in the context of pediatric cardiac surgery may amplify pre-existing impaired pituitary processing of the prohormone POMC.
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Vascular Laboratory, Cairo University, Cairo, Egypt
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Hypothyroidism is associated with increased risk of atherosclerosis. We assessed carotid intima-media thickness (CIMT), as a marker of atherosclerosis, and endothelial function in patients with hypothyroidism. We included 70 female patients with hypothyroidism in the study, 40 patients with overt and 30 patients with subclinical hypothyroidism. Forty, age- and sex-matched, subjects with normal thyroid functions were also included as a control group. CIMT was measured using high-resolution color-coded Doppler ultrasonography. Endothelial function was assessed by measuring the percent of change in blood flow following heat-mediated vasodilation using laser Doppler flowmetry. CIMT was significantly higher in patients with overt and subclinical hypothyroidism as compared with the control group (0.7 ± 0.2 and 0.6 ± 0.2 mm respectively vs 0.45 ± 0.07 mm, P < 0.001 for both). The percent of change in blood flow following heat-mediated vasodilation was significantly impaired in patients with overt and subclinical hypothyroidism as compared with the control group (328 ± 17 and 545 ± 406% respectively vs 898 ± 195%, P < 0.001 for both). The impairment was more significant in overt as compared with subclinical hypothyroidism (P = 0.014). CIMT negatively correlated with percent of change in blood flow following heat-mediated vasodilation in patients with overt and subclinical hypothyroidism (P < 0.001 for both). We concluded that CIMT is significantly higher in patients with overt and subclinical hypothyroidism compared with normal control subjects. Impairment of endothelial function is a contributing factor to the increased risk of atherosclerosis in both groups of patients.
Division of General Medicine, Istituto Auxologico Italiano, IRCCS, S. Giuseppe Hospital, Piancavallo di Oggebbio (VB), Italy
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Division of General Medicine, Istituto Auxologico Italiano, IRCCS, S. Giuseppe Hospital, Piancavallo di Oggebbio (VB), Italy
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Division of Endocrinology, Diabetology and Metabolism, Department of Medical Sciences, University of Turin, Turin, Italy
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The associative link relating insulin resistance (IR) and adipokines to the occurrence and phenotype of differentiated thyroid cancer (DTC) is unknown. The aim of this study was to evaluate the relationship between IR and adipokines in DTC patients, as compared with carriers of benign thyroid diseases (BTD) and healthy controls. This observational study enrolled 77 subjects phenotyped as DTC (N = 30), BTD (N = 27) and healthy subjects (N = 20). Each subject underwent preoperative analysis of anthropometric parameters, thyroid function and autoimmunity, insulin resistance (HOMA-IR) and levels of unacylated (UAG) and acylated ghrelin (AG), obestatin, leptin and adiponectin. Multivariate regression models were used to test the predictive role of metabolic correlates on thyroid phenotypes and DTC extension. The three groups showed similar age, gender distribution, smoking habit, BMI and thyroid parameters. Obestatin was significantly higher in DTC group compared to BTD (P < 0.05) and control subjects (P < 0.0001). DTC and BTD groups showed higher levels of UAG (P < 0.01) and AG (P < 0.05). Leptin levels were comparable between groups, whereas adiponectin levels were lower in DTC compared to BTD group (P < 0.0001) and controls (P < 0.01). In parallel, HOMA-IR was higher in DTC than BTD (P < 0.05) and control group (P < 0.01). Stepwise multivariable regression analysis showed that obestatin and UAG were independent predictors of DTC (P = 0.01 for both). In an analysis restricted to the DTC group, obestatin levels were associated with the absence of lymph node metastases (P < 0.05). Our results highlight a potential association between metabolic setting, circulating adipokines and thyroid cancer phenotype.
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The effects of water exercise on gut hormone concentrations and appetite currently remain unclear. The aim of the present study was to investigate the effects of treadmill walking in water on gut hormone concentrations and appetite. Thirteen men (mean ± s.d. age: 21.6 ± 2.2 years, body mass index: 22.7 ± 2.8 kg/m2, peak oxygen uptake (VO2peak): 49.8 ± 7.8 mL/kg per min) participated in the walking in water and on land challenge. During the study period, ratings of subjective feelings of hunger, fullness, satiety and motivation to eat were reported on a 100-mm visual analog scale. A test meal was presented after walking, and energy intake (EI) was calculated. Blood samples were obtained during both trials to measure glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and acylated ghrelin (AG) concentrations. Hunger scores (How hungry do you feel?) were significantly lower during the water trial than during the land trial (P < 0.05). No significant differences were observed in EI between water and land trials. GLP-1 concentrations were significantly higher in the water trial than in the land trial (P < 0.05). No significant differences were observed in PYY concentrations between water and land trials. AG concentrations were significantly lower in the water trial than in the land trial (P < 0.01). In conclusion, changes in gut hormone concentrations during walking in water contribute to the exercise-induced suppression of appetite and provide novel information on the influence of walking in water on the acute regulation of appetite.
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Background:
Evidence has demonstrated that visceral fat area (VFA) and subcutaneous fat area (SFA) had different influences on cardiovascular disease (CVD) risk in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between the visceral fat area (VFA) to subcutaneous fat area (SFA) ratio (V/S) and carotid atherosclerosis (CAS) in patients with T2DM.
Methods:
From January 2018 to May 2023, 1,838 patients with T2DM admitted to the National Metabolic Management Centre in our hospital were assigned to two groups based on comorbid CAS. Dual bioelectrical impedance analysis was used to measure the VAF and SFA, and the V/S was calculated. Patient characteristics and serum biochemical indices were compared between groups. Factors influencing comorbid CAS were determined, and correlations between V/S and other clinical indices were analyzed.
Results:
The group with comorbid CAS included 858 individuals and 980 without comorbid CAS. Those with comorbid CAS were older and had a longer disease duration, more significant systolic blood pressure, and greater V/S. The proportions of patients with comorbid hypertension increased significantly with the V/S ratio. The V/S ratio positively correlated with triglyceride (TG), low-density lipoprotein cholesterol levels, and waist circumference. According to binary logistic regression analysis, V/S was an independent risk factor for CAS.
Conclusion:
Elevated V/S is an independent risk factor for CAS in patients with T2DM.
Faculté de Chirurgie Dentaire, Université de Toulouse III, Toulouse, France
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CHU de Toulouse, Laboratoire d’Hématologie, Toulouse, France
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Faculté de Chirurgie Dentaire, Université de Toulouse III, Toulouse, France
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Estrogen–progestin therapy was previously considered as the standard of care for managing bothersome symptoms associated with menopause, but it increases risks of breast cancer and of thromboembolism. The combination of conjugated estrogen (CE) with bazedoxifene (BZA) named tissue-selective estrogen complex (TSEC) was designed to minimize or even abrogate the undesirable effects on breast, while maintaining the beneficial effects such as prevention of osteoporosis and suppression of climacteric symptoms. The risk on thromboembolism associated with TSEC is unknown, although the clinical available data are reassuring. The aim of this study was to define the impact of a chronic administration of CE, BZA or CE + BZA on hemostasis and thrombosis in ovariectomized mice. As expected, CE, but not BZA neither CE + BZA, induced uterine and vagina hypertrophy. As previously demonstrated for 17β-estradiol (E2), we found that CE (i) increased tail-bleeding time, (ii) prevented occlusive thrombus formation in injured carotid artery and (iii) protected against collagen/epinephrine-induced thromboembolism. Thus, whereas BZA antagonized CE action on reproductive tissues, it had no impact on the effect of CE on hemostasis, thromboembolism and arterial thrombosis in mice. CE + BZA shared the anti-thrombotic actions of CE in these mouse models. If a similar process is at work in women, CE combined with BZA could contribute to minimize the risk of thrombosis associated with hormone replacement therapy.
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Background
Most common incidentally detected sellar-suprasellar region (SSR) masses are pituitary adenomas, followed by craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma. Besides these, certain unusual SSR lesions can sometimes present as diagnostic challenges, where diagnosis is often made post-operatively on histopathology, the pre-operative suspicion of which might have influenced the management strategies. Series describing such masses are few.
Objective
To present clinical, biochemical, and radiological characteristics and management outcomes of rare SSR lesions other than pituitary adenomas, craniopharyngioma, rathke’s cleft cyst, hypophysitis, and meningioma.
Design, setting, patients
Retrospective case record analysis of patients with uncommon SSR masses (from January 2006 to December 2016).
Results
Our series consisted of ten patients, five with neoplastic and five with non-neoplastic lesions. Neoplastic masses included granular cell tumor (n = 2), astrocytoma (n = 1), malignant peripheral nerve sheath tumor (MPNST, n = 1), and metastasis from occult papillary carcinoma of thyroid (n = 1), while non-neoplastic masses were aspergillus abscess (n = 1), sterile abscess (n = 1), and tubercular abscess (n = 1), aneurysm of left internal carotid artery (n = 1), and ruptured dermoid cyst (n = 1). All patients (except one) presented with headache and/or visual disturbance. Only one patient had acromegaly while most others had hypopituitarism. We describe detailed MRI characteristics of each of the lesion. Seven patients underwent trans-sphenoidal surgery. Post-operatively, five patients had permanent diabetes insipidus, while two patients died in early post-operative period.
Conclusion
Our series expand the differential diagnostic considerations of SSR lesions. Most of the rare SSR masses present with symptoms of mass effects and hypopituitarism. Except for some non-neoplastic lesions like sellar abscesses, aneurysms, and dermoid cysts which can have some specific imaging characteristics that can provide clue to pre-operative diagnosis, most of the other neoplastic masses have overlapping radiological features, and pre-operative suspicion remains difficult.
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Abstract
GH and its principal mediator IGF1 have important effects on metabolic and cardiovascular (CV) status. While acquired GH deficiency (GHD) is often associated with increased CV risk, the consequences of congenital GHD are not known. We have described a large group of patients with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G>A) in the GH releasing hormone receptor gene, and shown that adult GH-naïve individuals have no evidence of clinically evident premature atherosclerosis. To test whether subclinical atherosclerosis is anticipated in untreated IGHD, we performed a cross-sectional study of 25 IGHD and 27 adult controls matched for age and gender. A comprehensive clinical and biochemical panel and coronary artery calcium scores were evaluated by multi-detector tomography. Height, weight, IGF1, homeostasis model assessment of insulin resistance, creatinine and creatininekinase were lower in the IGHD group. Median and interquartile range of calcium scores distribution was similar in the two groups: IGHD 0(0) and control 0(4.9). The vast majority of the calcium scores (20 of 25 IGHD (80%) and 18 of 27 controls (66.6%)) were equal to zero (difference not significant). There was no difference in the calcium scores classification. None of IGHD subjects had minimal calcification, which were present in four controls. Three IGHD and four controls had mild calcification. There were two IGHD individuals with moderate calcification and one control with severe calcification. Our study provides evidence that subjects with congenital isolated lifetime and untreated severe IGHD do not have accelerated subclinical coronary atherosclerosis.
University of Belgrade, Medical Faculty, Belgrade, Serbia
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University of Belgrade, Medical Faculty, Belgrade, Serbia
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Insitute of Medical Statistics and Informatics, Belgrade, Serbia
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University of Belgrade, Medical Faculty, Belgrade, Serbia
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University of Belgrade, Medical Faculty, Belgrade, Serbia
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University of Belgrade, Medical Faculty, Belgrade, Serbia
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Background
Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients.
Subjects and methods
Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP.
Results
Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT.
Conclusions
Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.
