Abstract
BACKGROUND
The effect of chronic use of renin–angiotensin–aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed ...to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19-related outcomes in hypertensive patients.
METHODS
A single-center study was conducted on 133 consecutive hypertensive subjects presenting to the emergency department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9 and 31 March 2020.
RESULTS
All patients were grouped according to their chronic antihypertensive medications (ACEIs, N = 40; ARBs, N = 42; not on RAAS inhibitors, N = 51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy, and need for noninvasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared with the non-RAAS population (odds ratio (OR) 0.25, confidence interval (CI) 95% 0.09–0.66, P = 0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI 95% 0.17–1.83, P = 0.341).
CONCLUSIONS
Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID-19-related morbidity and mortality.
Hyperprolactinemia may cause bone loss but data on fractures are scanty. The aim of this study was to evaluate the prevalence of vertebral fractures in women with prolactin (PRL)-secreting adenoma. ...In this cross-sectional study, 78 women (median age 45.5 years, range: 20–81) with PRL-secreting pituitary adenoma (66 with microadenoma and 12 with macroadenoma) and 156 control subjects, with normal PRL values and with comparable age to patients with hyperprolactinemia, were evaluated for vertebral fractures by a morphometric approach and for bone mineral density (BMD) by a dual-energy X-ray absorptiometry at lumbar spine. Vertebral fractures were shown in 25 patients with PRL-secreting adenoma (32.6%) and in 20 controls (12.8%,
P
< 0.001). Fractured patients were significantly older (
P
< 0.001) and had lower BMD T-score (
P
< 0.001), longer duration of disease (
P
< 0.001), higher serum PRL (
P
= 0.004) and lower serum IGF-I (
P
< 0.001) values as compared to patients who did not fracture. The prevalence of vertebral fractures was significantly (
P
< 0.001) higher in post-menopausal women with PRL-secreting adenoma as compared to pre-menopausal patients. Fractures occurred more frequently (
P
= 0.01) in patients with untreated hyperprolactinemia versus patients treated with cabergoline. Logistic regression analysis demonstrated that duration of disease maintained a significant correlation with vertebral fractures (odds ratio 1.16, C.I. 95% 1.02–1.33) even after correction for age, menopausal status, treatment with cabergoline, BMD, serum IGF-I and serum PRL values. Hyperprolactinemia is associated with high prevalence of radiological vertebral fractures in women with PRL-secreting adenoma.
Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism.
Objective: The objective of the study was to clarify ...whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury.
Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32).
Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency.
Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.
Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition ...(PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.
Summary
Background The majority of patients with acromegaly have large tumours and the outcome of conventional management remains poor.
Objective To investigate the clinical application of ...octreotide‐LAR as primary treatment in newly diagnosed patients with GH‐secreting pituitary tumours.
Design Open, prospective, multicentre, 24‐week follow‐up study.
Patients Thirty‐four patients were enrolled (20 men, 14 women; mean age, 50 years); 13 had microadenoma median tumour volume 327 mm3 (range 31–629 mm3), 21 had macroadenoma median tumour volume 1325 mm3 (range 503–11583 mm3).
Interventions Octreotide‐LAR at the dosage of 20 mg every 28 days for the first 12 weeks increased to 30 mg every 28 days to control GH and/or IGF‐I excess in 20 patients (64·7%).
Main outcome measures Primary endpoints were control of GH (fasting < 2·5 µg/l) and IGF‐I secretion (gender‐ and age‐normalized) and presence and entity of tumour mass shrinkage. Secondary endpoint was improvement of symptoms score.
Results In patients with micro‐ and macroadenomas GH levels decreased to < 2·5 µg/l in 84·6% and 45%, serum IGF‐I levels normalized for age and gender in 61·5% and 35% of cases. Failure in achieving either GH < 2·5 µg/l or normal IGF‐I levels was found in none of the patients with micro‐ and in 45% of patients with macroadenoma. Median tumour volume was reduced by 54% (range: −90% to +350%) in micro‐ and by 49% (range −94% to −14%) in macroadenomas. Headache, perspiration and osteo‐arthralgias disappeared in 21%, paresthesias in 38%, fatigue in 26% and carpal tunnel syndrome in 15%. The treatment was well tolerated: more frequent adverse events were gastrointestinal (in 44%).
Conclusions In both patients with micro‐ or macroadenoma, primary octreotide‐LAR treatment controls hormone excess, induces tumour shrinkage and improves symptoms of acromegaly with limited side effects and can be therefore successfully employed in patients with contraindications for surgery or in those who refuse surgery.
Background
Acromegalic patients have a higher risk of developing colorectal tumours (CRT). The common C677T polymorphism in methylenetetrahydrofolate reductase (
MTHFR
) gene is a well-documented CRT ...risk factor in the general population, but its role in acromegaly has never been examined.
Purpose
We investigated the influence of
MTHFR
C677T polymorphism, folate status and other lifestyle, nutritional and disease-specific variables on CRT risk in acromegaly.
Methods
Clinical data were collected from 115 acromegalic patients (25 with active disease) who underwent a complete colonoscopy. C677T
MTHFR
genotype, homocysteine, vitamin B
12
, insulin growth factor and insulin levels, as well as metabolic variables were evaluated.
Results
Colorectal tumours were identified in 51 patients (3 adenocarcinomas).
MTHFR
C677T distribution was in the Hardy–Weinberg equilibrium and similar in patients with or without CRT. There was a correlation between patients with TT genotype and CRT occurrence (Spearman’s test:
P
=
0.03), with an Odds Ratio (OR) of 1.32 (95 % CI 0.522–3.362,
P
NS
). A folate–
MTHFR
genotype interaction on CRT risk was found (
P
= 0.037): in the lower folate subgroup, TT patients showed a 2.4 higher OR for CRT (95 % CI 0.484–11.891;
P
NS) than C-allele carriers. Smoking (
P
= 0.007), increased HbA
1c
levels (
P
= 0.021), dyslipidaemia (
P
= 0.049), acromegaly control (
P
= 0.057), and folate–
MTHFR
genotype interaction (
P
= 0.088) were associated with CRT at multivariate analysis.
Conclusions
In this cohort of acromegalic patients, CRT risk is increased in 677TT
MTHFR
patients with low plasma folate levels. Smoking, high HbA
1c
levels, dyslipidaemia and disease activity were also associated with increased CRT risk.
Acromegaly is a rare disease. Improvements in lifespan in these patients have recently been reported due to transsphenoidal surgery (TSS), advances in medical therapy, and strict criteria for ...defining disease remission. This document reports the opinions of a group of Italian experts who have gathered together their prolonged clinical experience in the diagnostic and therapeutic challenges of acromegaly patients. Both GH and IGF-I (only IGF-I in those treated with Pegvisomant) are needed in the diagnosis and follow-up. Comorbidities (cardio-cerebrovascular disease, sleep apnea, metabolic derangement, neoplasms, and bone/joint disease) should be specifically addressed. Any newly diagnosed patient should be referred to a multidisciplinary team experienced in the treatment of pituitary adenomas.
Pituitary adenomas are neoplasms of the anterior pituitary lobe and account for 15-20% of all intracranial tumors. Although most pituitary tumors are benign they can cause severe symptoms related to ...tumor size as well as hypopituitarism and/or hypersecretion of one or more pituitary hormones. Most pituitary adenomas are sporadic, but it has been estimated that 5% of patients have a familial background. Germline mutations of the tumor suppressor gene aryl hydrocarbon receptor-interacting protein (AIP) predispose to hereditary pituitary neoplasia. Recently, it has been demonstrated that AIP mutations predispose to pituitary tumorigenesis through defective inhibitory GTP binding protein (Gαi) signaling. This finding prompted us to examine whether germline loss-of-function mutations in inhibitory guanine nucleotide (GTP) binding protein alpha (GNAI) loci are involved in genetic predisposition of pituitary tumors. To our knowledge, this is the first time GNAI genes are sequenced in order to examine the occurrence of inactivating germline mutations. Thus far, only somatic gain-of-function hot-spot mutations have been studied in these loci. Here, we have analyzed the coding regions of GNAI1, GNAI2, and GNAI3 in a set of young sporadic somatotropinoma patients (n = 32; mean age of diagnosis 32 years) and familial index cases (n = 14), thus in patients with a disease phenotype similar to that observed in AIP mutation carriers. In addition, expression of Gαi proteins was studied in human growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH)-secreting and non-functional pituitary tumors. No pathogenic germline mutations affecting the Gαi proteins were detected. The result suggests that loss-of-function mutations of GNAI loci are rare or nonexistent in familial pituitary adenomas.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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