Publications by authors named "Flavia Pugliese"

8 Publications

  • Page 1 of 1

Cardiovascular complications of mild autonomous cortisol secretion.

Best Pract Res Clin Endocrinol Metab 2021 Mar 23;35(2):101494. Epub 2021 Feb 23.

Department of Endocrine and Metabolic Diseases, IRCCS, Istituto Auxologico Italiano, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy. Electronic address:

Adrenal incidentalomas (AI) may be associated with a mild autonomous cortisol secretion (MACS) in up to one third of cases. There is growing evidence that MACS patients actually present increased risk of cardiovascular disease and higher mortality rate, driven by increased prevalence of known cardiovascular risk factors, as well as accelerated cardiovascular remodelling. Adrenalectomy seems to have cardiometabolic beneficial effects in MACS patients but their management is still a debated topic due to the lack of high-quality studies. Several studies suggested that so called "non-functioning" AI may be actually "functioning" with an associated increased cardiovascular risk. Although the individual cortisol sensitivity and peripheral activation have been recently suggested to play a role in influencing the cardiovascular risk even in apparently eucortisolemic patients, to date the degree of cortisol secretion, as mirrored by the cortisol levels after dexamethasone suppression test remains the best predictor of an increased cardiovascular risk in AI patients. However, whether or not the currently used cut-off set at 50 nmol/L for cortisol levels after dexamethasone suppression could be considered completely reliable in ruling out hypercortisolism remains unclear.
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http://dx.doi.org/10.1016/j.beem.2021.101494DOI Listing
March 2021

Normocalcemic primary hyperparathyroidism: an update.

Minerva Endocrinol 2020 Oct 26. Epub 2020 Oct 26.

Units of Endocrinology, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy -

Normocalcemic primary hyperparathyroidism (NPHPT) is diagnosed in the setting of elevated PTH concentrations with consistently normal albumin-adjusted and ionized serum calcium levels, in absence of secondary causes for elevated PTH concentrations. In order to confirm persistence of the hyperparathyroid state, PTH levels should be elevated on at least two occasions over a 3 to 6 months period. The prevalence of NPHPT depends on the population studied. Data from different studies are often not comparable; indeed, different criteria have been used to exclude secondary hyperparathyroidism. Notwithstanding such limits, the prevalence of NPHPT in studies including ionized calcium dosage was between 0.5% and 0.7%. Available data suggest that patients with NPHPT are likely to have more skeletal, kidney and metabolic complications compared to healthy subjects, but almost all studies suffer from possible misclassification of patients due to lack of ionized calcium dosage. The management of NPHPT is controversial in part due to lack of solid data about the natural history. However, surgical treatment is currently performed more frequently than in the past, although studies do not show, so far, a clear benefit from intervention.
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http://dx.doi.org/10.23736/S0391-1977.20.03215-0DOI Listing
October 2020

Mental Health in Patients With Adrenal Incidentalomas: Is There a Relation With Different Degrees of Cortisol Secretion?

J Clin Endocrinol Metab 2021 Jan;106(1):e130-e139

Unit for Bone Metabolism Diseases and Diabetes, Istituto Auxologico Italiano, IRCCS, Milan, Italy.

Context: Cushing's syndrome frequently causes mental health impairment. Data in patients with adrenal incidentaloma (AI) are lacking.

Objective: We aimed to evaluate psychiatric and neurocognitive functions in AI patients, in relation to the presence of subclinical hypercortisolism (SH), and the effect of adrenalectomy on mental health.

Design: We enrolled 62 AI patients (64.8 ± 8.9 years) referred to our centers. Subclinical hypercortisolism was diagnosed when cortisol after 1mg-dexamethasone suppression test was >50 nmol/L, in the absence of signs of overt hypercortisolism, in 43 patients (SH+).

Interventions: The structured clinical interview for the Diagnostic and Statistical Manual of Mental Disorders-5, and 5 psychiatric scales were performed. The Brief Assessment of Cognition in Schizophrenia (Verbal and Working Memory, Token and Symbol Task, Verbal Fluency, Tower of London) was explored in 26 patients (≤65 years).

Results: The prevalence of psychiatric disorders was 27.4% (SH+ 30.2% vs SH- 21.1%, P = 0.45). SH+ showed a higher prevalence of middle insomnia (by the Hamilton Depression Rating Scale) compared with SH- (51% vs 22%, P = 0.039). Considering the Sheehan Disability Scale, SH+ showed a higher disability score (7 vs 3, P = 0.019), higher perceived stress (4.2 ± 1.9 vs 2.9 ± 1.9, P = 0.015), and lower perceived social support (75 vs 80, P = 0.036) than SH-. High perceived stress was independently associated with SH (odds ratio [OR] = 5.46, confidence interval 95% 1.4-21.8, P = 0.016). Interestingly, SH+ performed better in verbal fluency (49.5 ± 38.9 vs 38.9 ± 9.0, P = 0.012), symbol coding (54.1 ± 6.7 vs 42.3 ± 15.5, P = 0.013), and Tower of London (15.1 vs 10.9, P = 0.009) than SH-. In 8 operated SH+, no significant changes were found.

Conclusions: Subclinical hypercortisolism may influence patients' mental health and cognitive performances, requiring an integrated treatment.
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http://dx.doi.org/10.1210/clinem/dgaa695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765655PMC
January 2021

Treatment of Acromegalic Osteopathy in Real-life Clinical Practice: The BAAC (Bone Active Drugs in Acromegaly) Study.

J Clin Endocrinol Metab 2020 09;105(9)

Endocrinology, Diabetology and Medical Andrology Unit, Osteoporosis and Metabolic Bone Disease Section, Humanitas Clinical and Research Center, IRCCS, Rozzano-Milan, Italy.

Background: Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting.

Objective: To evaluate whether in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly.

Study Design: Retrospective, longitudinal study including 9 tertiary care endocrine units.

Patients And Methods: Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ± 13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132).

Results: During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio [OR] 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007).

Conclusions: Bone active drugs may prevent VFs in patients with active acromegaly.
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http://dx.doi.org/10.1210/clinem/dgaa363DOI Listing
September 2020

Rare Somatic MEN1 Gene Pathogenic Variant in a Patient Affected by Atypical Parathyroid Adenoma.

Int J Endocrinol 2020 27;2020:2080797. Epub 2020 Apr 27.

Division of Medical Genetics, Fondazione IRCCS Casa Sollievo Della Sofferenza, San Giovanni Rotondo (FG), Italy.

Objective: Atypical parathyroid adenoma is a rare neoplasm, showing atypical histological features intermediate between classic benign adenoma and the rarest parathyroid carcinoma, whose the clinical behaviour and outcome is not yet understood or predictable. Up to date only two cases of atypical adenoma were found associated to a MEN1 syndrome, and only one was proved to carry a pathogenic variant of the MEN1 gene.

Design: We report the clinical, histologic, and molecular findings of a 44-year-old woman, presenting with a histologically proved atypical parathyroid adenoma with an apparent aggressive behaviour.

Methods And Results: CDC73 gene was screened at germline and somatic levels with no results. Whole exome sequencing performed on DNA extracted from blood leukocytes and tumour tissue revealed a somatic MEN1 gene heterozygous variant, c.912+1G > A, of the splicing donor site of exon 6. On immunohistochemistry, downregulation of the menin protein expression in the neoplastic cells was also observed.

Conclusions: We report the second case of a rare association of a somatic MEN1 gene mutation in a patient with atypical parathyroid adenoma. We suggest that MEN1 gene could be an underestimate genetic determinant of these rare histological entities, and we highlight the utility of a complete genetic screening protocol, by the use of next-generation sequencing technology in such undetermined clinical cases with no frank clinical presentation.
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http://dx.doi.org/10.1155/2020/2080797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201480PMC
April 2020

Molecular pathogenesis of parathyroid tumours.

Best Pract Res Clin Endocrinol Metab 2018 12 20;32(6):891-908. Epub 2018 Nov 20.

Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, Division of Medical Genetics, Italy. Electronic address:

Parathyroid tumors represent an elusive endocrine neoplasia, which lead to primary hyperparathyroidism, pHPT, a common endocrine calcium disorder characterized by hypercalcemia and normal-high parathormone secretion. Parathyroid tumours are benign adenomas or multiple glands hyperplasia in the vast majority (>99% of cases), while malignant neoplasms are rare (less than 1%). Despite pHPT is a common disorder, our knowledge about the genetic predisposition and molecular pathophysiology is limited to the familial syndromic forms of parathyroid tumour, that, however, represent not more than the 10% of all the cases; instead, the pathophysiology of sporadic forms remains an open field, although data about epigenetic mechanisms or private genes have been supposed. Here we present an overview of more recent acquisitions about the genetic causes along with their molecular mechanisms of benign, but also, malignant parathyroid tumours either in sporadic and familial presentation.
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http://dx.doi.org/10.1016/j.beem.2018.11.001DOI Listing
December 2018

Isolated pons involvement in Posterior Reversible Encephalopathy Syndrome: Case report and review of the literature.

eNeurologicalSci 2017 Mar 28;6:51-54. Epub 2016 Nov 28.

Neurology Unit, Department of Medicine, Research Center "Casa Sollievo della Sofferenza", San Giovanni Rotondo, FG, Italy.

Background: Posterior Reversible Encephalopathy Syndrome (PRES) is a clinical-radiological syndrome, usually reversible and with a favorable prognosis, which recognizes a variety of etiologies and clinical patterns and is likely due to an impairment in cerebral blood flow autoregulation. It is typically characterized by subcortical, predominantly parieto-occipital, vasogenic brain oedema in patients with acute-subacute neurological symptoms. Infratentorial oedema on neuroimaging has been mostly described in association with the typical supratentorial pattern and seldom as isolated.

Case Report: We report a case of PRES with isolated pons involvement on MRI. A woman affected by Turner syndrome, epilepsy, slight mental deficiency, obesity and hypothyroidism, experienced a progressive gait and standing impairment, worsening in the last 2 weeks. At admission blood pressure was 220/110 mmHg. Brain MRI showed a wide FLAIR signal hyperintensity on T2-weighted sequences affecting the entire pons, without contrast enhancement. Clonidine, doxazosine, furosemide and telmisartan were effective in restoring normal blood pressure. Pons hyperintensity completely resolved on MRI 3 weeks later, together with return to normal neurological examination.

Conclusions: Though isolated infratentorial involvement in PRES recognizes several causes, hypertension, which is a common feature in Turner syndrome, would have played a key role in our case with solely pons MRI T2-hyperintensity.
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http://dx.doi.org/10.1016/j.ensci.2016.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721558PMC
March 2017

Primary aldosteronism as a cause of secondary osteoporosis.

Eur J Endocrinol 2017 Nov 8;177(5):431-437. Epub 2017 Aug 8.

Endocrinology Unit.

Objective: Patients with primary aldosteronism (PA) have a high prevalence of osteoporosis (OP) and fractures (Fx). We evaluated the presence of PA in patients admitted to our metabolic bone disease outpatient clinic.

Design: Study conducted on an in- and outpatient basis in a referral Italian endocrinology unit.

Methods: A total of 2632 patients were evaluated. 2310 were excluded because they were taking drugs known to affect bone or mineralocorticoids metabolism or were diagnosed to have a secondary cause of osteoporosis. The remaining 322 subjects (304 females, 18 males) took part in the study. Bone mineral density (BMD) and thoracic and lumbar spine vertebral morphometry were performed by dual X-ray absorptiometry. All patients were screened for PA with aldosterone-to-renin ratio. In those who had positive results, confirmatory tests were performed.

Results: Among 322 subjects, 213 were osteoporotics and 109 were not. PA was diagnosed in eleven out of 213 osteoporotic patients (5.2%) and one out of 109 non-osteoporotic subjects (0.9%,  = 0.066). PA was observed in the 26.1% of patients with the concomitant presence of osteoporosis, hypertension and hypercalciuria. Compared with patients without PA, patients with PA had mean values of urinary calcium excretion, 4.8 ± 2.5 mmol/day vs 7.6 ± 3.2 mmol/day,  < 0.001 and serum PTH levels, 5.4 pmol/L vs 7.3 pmol/L,  < 0.01, significantly higher.

Conclusions: PA should be considered among the causes of secondary OP.
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http://dx.doi.org/10.1530/EJE-17-0417DOI Listing
November 2017
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