Publications by authors named "Andreea Liliana Serban"

6 Publications

  • Page 1 of 1

Case Report: A Challenging Localization of a Pulmonary Ectopic ACTH-Secreting Tumor in a Patient With Severe Cushing's Syndrome.

Front Endocrinol (Lausanne) 2021 9;12:687539. Epub 2021 Jul 9.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy.

Background: Ectopic adrenocorticotropic syndrome (EAS) is a rare cause of endogenous ACTH-dependent Cushing's syndrome, usually associated with severe hypercortisolism as well as comorbidities. Tumor detection is still a challenge and often requires several imaging procedures. In this report, we describe a case of an ectopic ACTH secretion with a misleading localization of the responsible tumor due to a concomitant rectal carcinoma.

Case Presentation: A 49-year-old man was referred to our Endocrinology Unit due to suspicion of Cushing's syndrome. His medical history included metastatic rectal adenocarcinoma, diagnosed 5 years ago and treated with adjuvant chemotherapy, radiotherapy and surgical resection. During follow-up, a thoracic computed tomography scan revealed two pulmonary nodules located in the superior and middle lobes of the right lung with a diameter of 5 and 10 mm, respectively. However, these nodules remained radiologically stable thereafter and were not considered relevant. All biochemical tests were suggestive of EAS (basal ACTH levels: 88.2 ng/L, nv 0-46; basal cortisol levels: 44.2 µg/dl, nv 4.8-19.5; negative response to CRH test and high dose dexamethasone suppression test) and radiological localization of the ectopic ACTH-secreting tumor was scheduled. The CT scan revealed a dimensional increase of the right superior lung nodule (from 5 to 12 mm). [Ga]-DOTA-TOC PET/CT scan was negative, while [F]-FDG-PET/CT showed a tracer accumulation in the superior nodule. After a multidisciplinary consultation, the patient underwent thoracic surgery that started with two atypical wedge resections of nodules. Frozen section analyses showed a neuroendocrine tumor on the right middle lobe nodule and a metastatic colorectal adenocarcinoma on the superior lesion. Then, a right superior nodulectomy and a right middle lobectomy with mediastinal lymphadenectomy were performed. The final histopathological examination confirmed a typical carcinoid tumor, strongly positive for ACTH. A post-surgical follow-up showed a persistent remission of Cushing's syndrome.

Conclusions: The present report describes a case of severe hypercortisolism due to EAS not detected by functional imaging methods, in which the localization of ACTH ectopic origin was puzzled by a concomitant metastatic rectal carcinoma. The multidisciplinary approach was crucial for the management of this rare disease.
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http://dx.doi.org/10.3389/fendo.2021.687539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299119PMC
July 2021

Tolvaptan in the Management of Acute Euvolemic Hyponatremia After Transsphenoidal Surgery: A Retrospective Single-Center Analysis.

Front Endocrinol (Lausanne) 2021 24;12:689887. Epub 2021 May 24.

Endocrinology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Introduction: Syndrome of inappropriate antidiuresis (SIAD) can be a complication of hypothalamus-pituitary surgery. The use of tolvaptan in this setting is not well established, hence the primary aim of this study was to assess the sodium correction rates attained with tolvaptan compared with standard treatments (fluid restriction and/or hypertonic saline). Furthermore, we compared the length of hospital stay in the two treatment groups and investigated the occurrence of overcorrection and side effects including osmotic demyelination syndrome.

Methods: We retrospectively reviewed 308 transsphenoidal surgical procedures performed between 2011 and 2019 at our hospital. We selected adult patients who developed post-operative SIAD and recorded sodium monitoring, treatment modalities and outcomes. Correction rates were adjusted based on pre-treatment sodium levels.

Results: Twenty-nine patients (9.4%) developed post-operative SIAD. Tolvaptan was administered to 14 patients (median dose 15 mg). Standard treatments were employed in 14 subjects (fluid restriction n=11, hypertonic saline n=1, fluid restriction and hypertonic saline n=2). Tolvaptan yielded higher adjusted sodium correction rates (12.0 mmolL/24h and 13.4 mmolL/48h) than standard treatments (1.8 mmolL/24h, p<0.001, and 4.5 mmolL/48h, p=0.004, tolvaptan). The correction rate exceeded 10 mmolL/24h or 18 mmolL/48h in 9/14 and 2/14 patients treated with tolvaptan, respectively, and in no patient who received standard treatments. No side effects including osmotic demyelination occurred. Tolvaptan was associated with a shorter hospital stay (1115 days, p=0.01).

Conclusions: Tolvaptan is more effective than fluid restriction (with or without hypertonic saline) and allows for a shortened hospital stay in patients with SIAD after transsphenoidal surgery. However, its dose and duration should be carefully tailored, and close monitoring is recommended to allow prompt detection of overcorrection.
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http://dx.doi.org/10.3389/fendo.2021.689887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181462PMC
May 2021

Procoagulant Imbalance in Klinefelter Syndrome Assessed by Thrombin Generation Assay and Whole-Blood Thromboelastometry.

J Clin Endocrinol Metab 2021 Mar;106(4):e1660-e1672

Fondazione IRCCS Ca' Granda Ospedale Maggiore, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy.

Context: Klinefelter syndrome (KS) is a condition at increased risk of thrombosis compared to 46,XY men.

Objective: This work aimed to investigate the coagulation balance of KS patients by thrombin generation assay (TGA) and thromboelastometry.

Methods: An observational, cross-sectional study was conducted at 3 tertiary endocrinological centers in Milan, Italy. Fifty-eight KS patients and 58 age-matched healthy controls were included. Anticoagulant or antiplatelet therapy and known coagulation disorders were exclusion criteria. TGA was performed in platelet-poor plasma (PPP) and platelet-rich plasma (PRP). Whole-blood thromboelastometry and activities of coagulation factors were assessed. Endogenous thrombin potential (ETP), the area under the thrombin generation curve, assessed with and without thrombomodulin (ETP-TM+ and ETP-TM-), and their ratio (ETP ratio), were considered as indexes of procoagulant imbalance.

Results: Patients with KS displayed higher PPP-ETP-TM+ (mean 1528 vs 0.1315 nM × min; P < .001), PPP-ETP ratio (0.78 vs 0.0.70; P < .001), factor (F)VIII (135% vs 0.107%; P = .001), fibrinogen (283 vs 0.241 mg/dL; P < .001), and FVIII/protein C ratio (1.21 vs 0.1.06; P < .05) compared to controls. Protein C was comparable in the 2 groups. Similar results were observed in PRP. The ETP ratio was positively associated with FVIII (ρ = 0.538, P < .001) in KS. Thromboelastometry parameters confirmed evidence of hypercoagulability in KS.

Conclusion: Patients with KS display a procoagulant imbalance expressed by increased thrombin generation both in PPP and PRP, which is at least in part explained by increased FVIII levels. The procoagulant imbalance, which was confirmed by thromboelastometry, may be responsible for the thrombotic events observed in these patients. Further investigation on the benefit/risk ratio of antithrombotic prophylaxis is warranted.
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http://dx.doi.org/10.1210/clinem/dgaa936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993570PMC
March 2021

Adrenal Insufficiency at the Time of COVID-19: A Retrospective Study in Patients Referring to a Tertiary Center.

J Clin Endocrinol Metab 2021 03;106(3):e1354-e1361

Endocrinology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy.

Context: Coronavirus disease 2019 (COVID-19) represents a global health emergency, and infected patients with chronic diseases often present with a severe impairment. Adrenal insufficiency (AI) is supposed to be associated with an increased infection risk, which could trigger an adrenal crisis.

Objective: Our primary aim was to evaluate the incidence of COVID-19 symptoms and complications in AI patients.

Design And Setting: We conducted a retrospective case-control study. All patients were on active follow-up and lived in Lombardy, Italy, one of the most affected areas.

Patients: We enrolled 279 patients with primary and secondary AI and 112 controls (patients with benign pituitary lesions without hormonal alterations). All AI patients had been previously trained to modify their replacement therapy on stress doses.

Intervention: By administering a standardized questionnaire by phone, we collected data on COVID-19 suggestive symptoms and consequences.

Results: In February through April 2020, the prevalence of symptomatic patients (complaining at least 1 symptom of viral infection) was similar between the 2 groups (24% in AI and 22.3% in controls, P = 0.79). Highly suggestive COVID-19 symptoms (at least 2 including fever and/or cough) also occurred equally in AI and controls (12.5% in both groups). No patient required hospitalization and no adrenal crisis was reported. Few nasopharyngeal swabs were performed (n = 12), as indicated by sanitary regulations, limiting conclusions on the exact infection rate (2 positive results in AI and none in controls, P = 0.52).

Conclusions: AI patients who are adequately treated and trained seem to display the same incidence of COVID-19-suggestive symptoms and disease severity as controls.
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http://dx.doi.org/10.1210/clinem/dgaa793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665569PMC
March 2021

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

Neuroendocrinology 2019 13;108(3):211-218. Epub 2019 Jan 13.

Endocrinology Unit, Ospedale Maggiore Policlinico, Fondazione IRCCS Ca' Granda, Milan, Italy.

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI).

Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD.

Patients And Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention.

Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence.

Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.
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http://dx.doi.org/10.1159/000496846DOI Listing
December 2019

Acromegaly is associated with increased cancer risk: a survey in Italy.

Endocr Relat Cancer 2017 09 14;24(9):495-504. Epub 2017 Jul 14.

Division of Endocrine and Metabolic DiseasesSan Luca Hospital, IRCCS Istituto Auxologico Italiano, Milan, Italy.

It is debated if acromegalic patients have an increased risk to develop malignancies. The aim of the present study was to assess the standardized incidence ratios (SIRs) of different types of cancer in acromegaly on a large series of acromegalic patients managed in the somatostatin analogs era. It was evaluated the incidence of cancer in an Italian nationwide multicenter cohort study of 1512 acromegalic patients, 624 men and 888 women, mean age at diagnosis 45 ± 13 years, followed up for a mean of 10 years (12573 person-years) in respect to the general Italian population. Cancer was diagnosed in 124 patients, 72 women and 52 men. The SIRs for all cancers was significantly increased compared to the general Italian population (expected: 88, SIR 1.41; 95% CI, 1.18-1.68,  < 0.001). In the whole series, we found a significantly increased incidence of colorectal cancer (SIR 1.67; 95% CI, 1.07-2.58,  = 0.022), kidney cancer (SIR 2.87; 95% CI, 1.55-5.34,  < 0.001) and thyroid cancer (SIR 3.99; 95% CI, 2.32-6.87,  < 0.001). The exclusion of 11 cancers occurring before diagnosis of acromegaly (all in women) did not change remarkably the study outcome. In multivariate analysis, the factors significantly associated with an increased risk of malignancy were age and family history of cancer, with a non-significant trend for the estimated duration of acromegaly before diagnosis. In conclusion, we found evidence that acromegaly in Italy is associated with a moderate increase in cancer risk.
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http://dx.doi.org/10.1530/ERC-16-0553DOI Listing
September 2017
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