Purpose
ACTH-secreting pheochromocytoma is a rare cause of ectopic Cushing’s syndrome, posing a clinical challenge for the severity of its clinical presentation, the difficulty in the prevention and ...the management of surgical complications. Sparse data are currently available about the optimal preoperative management of the severe symptoms due to both hypercortisolism and catecholamine excess, especially regarding the role and timing of medical therapies.
Methods
We present a series of three patients with ACTH-secreting pheochromocytoma. A brief review of the available literature evidence on the preoperative management of this rare clinical condition is also conducted.
Discussion
Patients with ACTH-secreting pheochromocytoma show peculiarities as compared to other forms of ACTH-dependent Cushing’s syndrome, in terms of clinical presentation, preoperative management, and peri- and post-surgical short-term outcome. Pheochromocytoma should be ruled out in patient with ectopic CS of unknown origin because of the high anesthesiologic risk of proceeding to surgery with an undiagnosed pheochromocytoma. Proper preoperative recognition of complications of both hypercortisolism and catecholamines excess is the key to prevent the morbidity and mortality of an ACTH-producing pheochromocytoma. In these patients the absolute priority is to control excessive cortisol secretion since the rapid correction of the hypercortisolism is the most effective treatment of all the related comorbidities and it is mandatory to prevent severe complications during surgery, opting if necessary for a “block-and-replace” regimen.
Conclusion
Our additional cases and this literature review could provide a better understanding of the complications to be evaluated at diagnosis and some suggestions on their management during the preoperative period.
Purpose
Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and ...the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs.
Methods
241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18–24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs.
Results
Denosumab significantly increased TBS values (from 1.270 to 1.323;
P
< 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282;
P
= 0.021). During treatment with BPs, TBS did not significantly change (
P
= 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (
P
= 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (
P
= 0.003), without significant differences in changes of BMD at any skeletal site.
Conclusions
TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.
Background
While low testosterone (T) was described as a predictor of unfavorable coronavirus-disease 19 (COVID-19) outcome in men, data concerning the role of T in women with severe acute ...respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are scant and limited to small cohorts. This study investigated the relationship between serum T values and outcomes of COVID-19 in a large female hospitalized cohort.
Methods
One-hundred-sixty-eight adult women (median age 77, range 18–100 years; 154 in post-menopause) hospitalized for COVID-19 were assessed for PaO2/Fio2 ratio, serum T and inflammatory parameters.
Results
Median duration for hospital stay was 14.2 days (range 1–115) with overall mortality of 26% (
n
= 44). Subjects who died were significantly older (
p
< 0.001), had significantly more comorbidities (
p
= 0.015) and higher serum T (
p
= 0.040), white blood cells (
p
= 0.007), c-reactive protein (CRP;
p
< 0.001), interleukin-6 (IL-6;
p
< 0.001), procalcitonin (PCT;
p
< 0.001), lactate dehydrogenase (LDH;
p
= 0.001), D-dimer (
p
= 0.035), fibrinogen (
p
= 0.038) and lower serum free-triiodothyronine (FT3;
p
< 0.001) and luteinizing hormone (LH;
p
= 0.024) values. In post-menopausal women, significant associations were observed between T levels and serum CRP (rho: 0.23;
p
= 0.002), IL-6 (rho: 0.41;
p
< 0.001), LDH (rho: 0.34;
p
< 0.001), D-Dimer (rho: 0.21;
p
= 0.008), PCT (rho: 0.26;
p
= 0.001) and HDL cholesterol (rho: – 0,22,
p
= 0.008). In multivariate regression analyses, serum T maintained the significant association with mortality after correction for age, coexistent comorbidities and serum LH and FT3, whereas it was lost after correction for inflammatory parameters.
Conclusion
In females, high serum T levels might be a mirror of inflammatory phenotype and worse COVID-19 course.
Purpose
Neuroendocrine neoplasms can occur as part of inherited disorders, usually in the form of well-differentiated, slow-growing tumors (NET). The main predisposing syndromes include: multiple ...endocrine neoplasias type 1 (MEN1), associated with a large spectrum of gastroenteropancreatic and thoracic NETs, and type 4 (MEN4), associated with a wide tumour spectrum similar to that of MEN1; von Hippel-Lindau syndrome (VHL), tuberous sclerosis (TSC), and neurofibromatosis 1 (NF-1), associated with pancreatic NETs. In the present review, we propose a reappraisal of the genetic basis and clinical features of gastroenteropancreatic and thoracic NETs in the setting of inherited syndromes with a special focus on molecularly targeted therapies for these lesions.
Methods
Literature search was systematically performed through online databases, including MEDLINE (via PubMed), and Scopus using multiple keywords’ combinations up to June 2022.
Results
Somatostatin analogues (SSAs) remain the mainstay of systemic treatment for NETs, and radiolabelled SSAs can be used for peptide-receptor radionuclide therapy for somatostatin receptor (SSTR)-positive NETs. Apart of these SSTR-targeted therapies, other targeted agents have been approved for NETs: the mTOR inhibitor everolimus for lung, gastroenteropatic and unknown origin NET, and sunitinib, an antiangiogenic tyrosine kinase inhibitor, for pancreatic NET. Novel targeted therapies with other antiangiogenic agents and immunotherapies have been also under evaluation.
Conclusions
Major advances in the understanding of genetic and epigenetic mechanisms of NET development in the context of inherited endocrine disorders have led to the recognition of molecular targetable alterations, providing a rationale for the implementation of treatments and development of novel targeted therapies.
Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
Sacubitril/valsartan (S/V) benefits in patients with heart failure and reduced ejection fraction (HFrEF) are partially ...related to cardiac reverse remodelling, in terms of volumes reduction and function improvement. Effects on vascular remodeling are less investigated.
Purpose
To evaluate cardiac and vascular remodelling in a cohort of patients with HFrEF after six months of therapy with S/V.
Methods
50 patients with HFrEF eligible to start a therapy with sacubitril/valsartan were enrolled. Clinical evaluation and standard and advanced echocardiography were performed at baseline and after six months of follow up (FU). Standard left ventricular dimension and function parameters, global longitudinal strain (GLS) were calculated. Non-invasive pressure-volume curves (P-V loop) estimation was assessed with an off-line dedicated software using ST-E derived time-resolved LV volumes and brachial pressure as input. The following hemodynamic parameters were calculated based on P-V loop curves: left ventricular elastance (Ees), arterial elastance (Ea) and ventricular-arterial coupling (VAC).
Results
At six months F/U, a reduction of NYHA class in the vast majority of patients was detected (NYHA Class ≥ II, baseline vs F/U = 100% vs 50%; p< 0,001). Systolic and diastolic blood pressure were lower, in comparison with baseline values (119 ± 16 vs 126 ± 11 mmHg; p = 0,002 and 71 ± 8 vs 78 ± 8 mmHg; p = 0,001, respectively). At echocardiographic evaluation, left ventricular end-diastolic and end-systolic volumes decreased (p< 0.001 and p< 0,001, respectively) and ejection fraction and GLS significantly improved (p< 0.001 and p < 0.001, respectively). Moreover, a significant reduction of Ea and a significant improvement of Ees and VAC were observed (p = 0.008, p< 0,001 and p< 0,001, respectively).
Conclusion
Therapy with S/V in HFrEF patients determines both cardiac and vascular remodelling reflecting the complex mechanisms behind clinical improvement. Abstract Figure.
Abstract
Funding Acknowledgements
Type of funding sources: None.
Background
Hemodynamic forces (HDFs) are the forces exchanged between the blood and the myocardium. Estimation of their magnitude and ...alignment could be a novel marker of cardiac dysfunction.
Purpose
To describe left ventricular (LV) HDFs values and distribution in patients with heart failure with reduced ejection fraction (HFrEF) and to compare them with those of a group of healthy controls.
Methods
A cohort of 26 non-ischemic patients with an initial diagnosis of HFrEF was enrolled. All of them underwent basal 2D echocardiography evaluation. Off-line HDFs estimation using a dedicated software based on speckle-tracking echocardiography was conducted. HDFs were normalized for the LV volume and expressed as a percentage of the force of gravity. HDFs were assessed over the entire cardiac cycle, in systole and diastole, both in apex to base (A-B) and latero-septal (L-S) directions. The distribution of LV HDFs was evaluated by L-S over A-B HDFs ratio (L-S/A-B HDFs ratio). HDFs of HFrEF patients were compared with those of 24 healthy volunteers.
Results
HFrEF patients showed smaller values of A-B HDFs during the entire cardiac cycle (5,2 ± 1,24% vs 12,3 ± 3,6%; p = 0,001), in systole (7,2 ± 2% vs 16,6 ± 6,3%; p = 0,001) and diastole (3,3 ± 0,8% vs 7,1 ± 3,6%; p = 0,001). Moreover, comparing HFrEF subjects with healthy volunteers , the former had lower L-S HDFs during the entire cardiac cycle (1,6 ± 0,4% vs 2 ± 0,7%; p= 0,022) and in systole (1,6 ± 0,5% vs 2,3 ± 0,8%; p = 0,003), while in diastole they showed inappropriate high values of L-S HDFs (1,7 ± 0,6% vs 1,8 ± 0,9%; p = 0,999). Consequently, HFrEF patients had higher values of L-S/A-B ratio during the entire cardiac cycle (32 ± 6,9 vs 15 ± 7,7; p = 0,001), in systole (23,5 ± 7,4 vs 14,7± 4,2; p = 0,001), but particularly in diastole (52 ± 10,8 vs 28 ± 13,6; p = 0,001), showing an important HDFs misalignment.
Conclusion
When compared with healthy controls, HFrEF patients presented intraventricular fluid alterations characterized by lower HDFs magnitude and a significant HDFs misalignment, especially in diastole. Further studies are needed to confirm these initial results and to assess the effects of therapy on these new parameters. Abstract Figure. Abstract Figure.
Abstract
Background
According to guidelines, implantable cardioverter defibrillator (ICD) is recommended in prevention of sudden cardiac death (SCD) in heart failure (HF) patients (pts). Guidelines ...have several limitations because ICD indication is based mainly on left ventricular ejection fraction (LVEF). Recently, 123-iodine metaiodobenzylguanidine imaging (123-I MIBG) seems to identify, independently from LVEF, pts at high risk of SCD: heart/mediastinum (H/M) ratio<1.6 and summed score (SS)>26.
Purpose
The aim is to assess the role of 123-I MIBG to predict malignant ventricular arrhythmias (VA) in HF pts
Methods
We enrolled 208 pts, admitted to our hospital with diagnosis of HF and LVEF≤35%, NYHA class II and III, who underwent 123-I MIBG imaging. H/M ratio of 1.6 was used as a cut-off to identify high risk (G1) versus low risk pts (G2). All pts underwent ICD implantation. Follow-up was performed at 24 months.
Results
138 patients were included in G1 and 70 patients in G2. All baseline characteristics were similar in the two groups (table 1). At 24 months follow-up VA events were recorded greater in G1 compared to G2 (21% vs 10%, p=0.04).
Table 1
G1
G2
P value
H/M ≤1.6 (N=138)
H/M >1.6 (N=70)
Age (years)
65±12
63±14
0.28
Male, N (%)
108 (78)
64 (91)
0.02
Diabetes mellitus type II, N (%)
54 (39)
14 (20)
0.01
Dyslipidemia, N (%)
58 (42)
30 (42)
0.64
LVEF (%)
30±5
31±4
0.14
Ischaemic CM, N (%)
85 (62)
30 (42)
0.012
Malignant VA, N (%)
30 (21)
7 (10)
0.04
SS
38±9
16±7
0.0001
H/M: heart mediastinum ratio; LVEF: left ventricular ejection fraction; CM: cardiomyopathy; VA: ventricular arrhythmias; SS: summed score.
Conclusion
Our results seem to confirm that 123-I MIBG uptake is associated with the occurrence of life-threatening VA in HF pts independently from LVEF. The use of 123-I MIBG could be a useful tool in the future to increase the specificity of the pts selection for ICD therapy.
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