Vertebral Fractures Associated with Spinal Sagittal Imbalance and Quality of Life in Acromegaly: A Radiographic Study with EOS 2D/3D Technology.

INTRODUCTION: Acromegaly is commonly complicated by arthropathy and skeletal fragility with high risk of vertebral fractures (VFs). OBJECTIVE: This study aimed to assess whether VFs may be associated with sagittal spine deformities, arthropathy, impaired quality of life (QoL), pain, and disability. METHODS: Thirty-eight patients with acromegaly (median age: 55 years, 20 males) and 38 matched control subjects were evaluated by a low-dose sagittal and coronal planes, X-ray imaging system (EOS®-2D/3D) for morphometric VFs, radiological signs of spine arthropathy, and spine deformities (Cobb thoracic index ≥40°, pelvic incidence minus lumbar lordosis ≥10°, pelvic tilt >20°, and sagittal vertical axis ≥4 cm) determining sagittal spine imbalance. Acromegalic patients were also evaluated by questionnaires for QoL (Acromegaly QoL Questionnaire [AcroQoL] and Short Form-36 [SF-36]) and pain and disability (Western Ontario and McMaster University [WOMAC]). RESULTS: Acromegalic patients showed higher prevalence of thoracic hyperkyphosis (i.e., Cobb thoracic index ≥40°; p = 0.04) and pelvic tilt >20° (p = 0.02) than control subjects. VFs were found in 34.2% of acromegalic patients (p = 0.003 vs. control subjects), in relationship with higher prevalence of hyperkyphosis (p = 0.03), pelvic tilt >20° (p = 0.04), sagittal vertical axis ≥4 cm (p = 0.03), and moderate/severe subchondral degeneration (p = 0.01). Moreover, patients with VFs had lower AcroQoL general health (p = 0.007) and SF-36 general health (p = 0.002) scores and higher WOMAC pain (p = 0.003) and global (p = 0.009) scores than patients who did not fracture. CONCLUSIONS: In acromegaly, VFs may be associated with spine deformities and sagittal imbalance, spine arthropathy, impaired QoL, and disability.

SARS-Cov-2 Infection: A New Risk Factor for Pituitary Apoplexy?

BACKGROUND: Pituitary apoplexy (PA) can arise from haemorrhage or ischaemia of pituitary tissue and is characterized by abrupt onset of headache, visual impairment and hypopituitarism. COVID-19 may be associated with various degrees of vascular complications and, recently, its relationship with PA has been suggested. Cases Presentation Case 1: A 64-year-old male with type 2 diabetes, hypertension and coronary heart disease was admitted to the ER, after several days of asymptomatic COVID-19 infection, with symptoms of PA of a known non-functioning pituitary macroadenoma. The hormonal panel was consistent with anterior panhypopituitarism and the sellar MRI showed haemorrhagic changes of macroadenoma tissue. Transsphenoidal resection of the pituitary lesion was carried out seven days after admission. Although a volumetric reduction of the lesion was apparent during follow-up, some degree of visual symptoms endured. Case 2: An 18-year-old, otherwise healthy, female presented to the ER with symptoms of PA of a recently-diagnosed non-functioning pituitary macroadenoma, after ten days of asymptomatic COVID-19 infection. Central hypocortisolism and hypothyroidism were diagnosed and, after six days, the lesion was surgically resected. At two months follow-up, clinical symptoms had completely resolved, and the hormonal panel was normal. CONCLUSION: Alongside known risk factors (hypertension, anticoagulation, pregnancy, surgery, etc.), COVID-19 infection might represent an emerging predisposing factor for PA onset. The two cases hereby presented are both significant: the first confirms the role of "classic" vascular predisposing factors for PA, while the second demonstrates that PA might arise also in young patients without known risk factors.

COVID19 infection and vaccination and the risk of pituitary apoplexy: an entangled yarn.

PURPOSE: Pituitary apoplexy (PA) has been increasingly reported in association with both infection from and vaccination for COVID19. Our aim was to analyse the available published cases and compare the clinical characteristics in the two groups (infection vs vaccination). METHODS: We systematically reviewed the published literature for all cases of PA associated with COVID19 infection or vaccination. We also presented two cases managed at our Centre. RESULTS: Collectively, fortythree cases were analysed. Patients with PA after COVID19 vaccination (n = 7), compared with patients with PA after COVID19 infection (n = 36), were significantly younger (p = 0.009) and had a more abrupt onset of PA (p = 0.022), but showed a milder hormonal involvement (p = 0.008) and a lower rate of persistent hypopituitarism during follow-up (p = 0.001). Patients in the vaccination group did not have clinical risk factors for PA, although this difference did not reach statistical significance. CONCLUSIONS: PA associated with COVID19 is a rare but clinically significant entity, although pathophysiological details of this association are lacking. Given the significantly different clinical presentation, we could speculate that PA induced by COVID19 vaccination might represent a distinct clinical entity, with different pathophysiological mechanism, compared to PA from COVID19 infection.

The Analytical Reliability of the Oral Glucose Tolerance Test for the Diagnosis of Gestational Diabetes: An Observational, Retrospective Study in a Caucasian Population.

The Oral Glucose Tolerance Test (OGTT) is currently the gold standard reference test for the diagnosis of gestational diabetes mellitus (GDM). Several critical issues related to analytical variables have challenged its reproducibility and accuracy. This study aimed to assess the analytical reliability of the OGTT for the diagnosis of GDM. A total of 1015 pregnant women underwent a 2 h 75 g OGTT between 24 and 28 weeks of gestation. As recommended by National Academy of Clinical Biochemistry, we considered the total maximum allowable error for glucose plasma measurement as <6.9%. Assuming the possibility of analytical errors within this range for each OGTT glucose plasma value, different scenarios of GDM occurrence were estimated. GDM prevalence with standard criteria was 12.2%, and no hypothetical scenarios have shown a comparable GDM prevalence. Considering all the three OGTT values estimated at the lowest or the highest allowed value according to total maximum allowable error, GDM prevalence significantly varied (4.5% and 25.3%, respectively). Our results indicate that the OGTT is not completely accurate for GDM diagnosis.

A Multicenter Cohort Study in Patients With Primary Empty Sella: Hormonal and Neuroradiological Features Over a Long Follow-Up.

Objective: primary empty sella (PES) represents a frequent finding, but data on hormonal alterations are heterogeneous, and its natural history is still unclear. Our aim was to evaluate the pituitary function of patients with PES over a long follow-up. Design: multicenter retrospective cohort study enrolling patients referred between 1984-2020 to five Pituitary Units, with neuroradiological confirmed PES and a complete hormonal assessment. Methods: we analyzed hormonal (including basal and dynamic evaluations), clinical and neuroradiological data collected at diagnosis and at the last visit (at least 6 months of follow-up). Results: we recruited 402 patients (females=63%, mean age=51.5 ± 16 years) with PES (partial, total, undefined in 66%, 13% and 21%, respectively). Hypopituitarism was present in 40.5% (hypogonadism=20.4%, hypoadrenalism=14.7%, growth hormone deficiency=14.7%, hypothyroidism=10.2%, diabetes insipidus=1.5%; multiple deficiencies=11.4%) and hypeprolactinemia in 6.5%. Interestingly, hormonal alterations were diagnosed in 29% of incidental PES. Hypopituitarism was associated with male sex (p=0.02), suspected endocrinopathy (p<0.001), traumatic brain injury (p=0.003) and not with age, BMI, number of pregnancies and neuroradiological grade. A longitudinal assessment was possible in 166/402 (median follow-up=58 months). In 5/166 (3%), new deficiencies occurred, whereas 14/166 (8.4%) showed a hormonal recovery. A progression from partial to total PES, which was found in 6/98 patients assessed with a second imaging, was the only parameter significantly related to the hormonal deterioration (p=0.006). Conclusions: this is the largest cohort of patients with PES reported. Hypopituitarism is frequent (40%) but hormonal deterioration seems uncommon (3%). Patients need to be carefully evaluated at diagnosis, even if PES is incidentally discovered.

Weight change and glycemic control in type 2 diabetes patients during COVID-19 pandemic: the lockdown effect.

PURPOSE: The aim of this study was to evaluate the impact of the COVID-19 lockdown occurred in Italy from March 9th to May 18th, 2020 on anthropometric parameters and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: One hundred twenty-eight consecutive patients with T2DM (median age 70 years, 74 males) were retrospectively evaluated at the end of the lockdown period. Data on metabolic control were collected at different time: within three months before the lockdown (visit 0) and within the first six weeks after it (visit 1). RESULTS: During the lockdown, a significant increase in body weight (from 79.7 ± 18.7 kg to 81.4 ± 19.4 kg, p < 0.001), body mass index (BMI, from 29.5 ± 6 kg/m2 to 30.1 ± 6.3 kg/m2, p < 0.001), waist circumference (from 103.8 ± 13 cm to 105 ± 13.6 cm, p < 0.001), fasting plasma glucose (FPG; from 138.1 ± 29.4 mg/dL to 146.6 ± 36.4 mg/dL) and glycated hemoglobin (HbA1c; from 7 ± 0.8 to 7.3 ± 0.9%, p < 0.001) was observed. Weight gain was directly associated with HbA1c increase (ß 0.085, C.I. 95% 0.05-0.121; p < 0.001) while insulin therapy resulted to be the only significant independent predictor of HbA1c worsening at the multivariate logistic regression analysis (OR 2.40, C.I. 1.06-5.45; p = 0.035). CONCLUSIONS: The lockdown due to COVID-19 pandemic had a negative impact on body weight and glucose control in T2DM patients, in particular in those on insulin treatment. This finding provides a further rationale to optimize the diabetes management during eventually new period of home confinement.

Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Italy.

OBJECTIVE: Diabetes may unfavorably influence the outcome of coronavirus disease 19 (COVID-19), but the determinants of this effect are still poorly understood. In this monocentric study, we aimed at evaluating the impact of type 2 diabetes, comorbidities, plasma glucose levels, and antidiabetes medications on the survival of COVID-19 patients. RESEARCH DESIGN AND METHODS: This was a case series involving 387 COVID-19 patients admitted to a single center in the region of Lombardy, the epicenter of the severe acute respiratory syndrome coronavirus 2 pandemic in Italy, between 20 February and 9 April 2020. Medical history, pharmacological treatments, laboratory findings, and clinical outcomes of patients without diabetes and patients with type 2 diabetes were compared. Cox proportional hazards analysis was applied to investigate risk factors associated with mortality. RESULTS: Our samples included 90 patients (23.3%) with type 2 diabetes, who displayed double the mortality rate of subjects without diabetes (42.3% vs. 21.7%, P < 0.001). In spite of this, after correction for age and sex, risk of mortality was significantly associated with a history of hypertension (adjusted hazard ratio [aHR] 1.84, 95% CI 1.15-2.95; P = 0.011), coronary artery disease (aHR 1.56, 95% CI 1.04-2.35; P = 0.031), chronic kidney disease (aHR 2.07, 95% CI 1.27-3.38; P = 0.003), stroke (aHR 2.09, 95% CI 1.23-3.55; P = 0.006), and cancer (aHR 1.57, 95% CI 1.08-2.42; P = 0.04) but not with type 2 diabetes (P = 0.170). In patients with diabetes, elevated plasma glucose (aHR 1.22, 95% CI 1.04-1.44, per mmol/L; P = 0.015) and IL-6 levels at admission (aHR 2.47, 95% CI 1.28-4.78, per 1-SD increase; P = 0.007) as well as treatment with insulin (aHR 3.05, 95% CI 1.57-5.95; P = 0.001) and ß-blockers (aHR 3.20, 95% CI 1.50-6.60; P = 0.001) were independently associated with increased mortality, whereas the use of dipeptidyl peptidase 4 inhibitors was significantly and independently associated with a lower risk of mortality (aHR 0.13, 95% CI 0.02-0.92; P = 0.042). CONCLUSIONS: Plasma glucose levels at admission and antidiabetes drugs may influence the survival of COVID-19 patients affected by type 2 diabetes.

Suboptimal medication adherence may favor the progression of vertebral fractures in women with post-menopausal osteoporosis treated with denosumab.

BACKGROUND: Medication adherence is a determinant of therapeutic outcomes in osteoporotic patients treated with bisphosphonates. In this monocentric study, we evaluated whether the regular drug administration may influence the effectiveness of denosumab in preventing vertebral fractures (VFs) in real-world clinical practice. METHODS: Two-hundred and four women (median age 75 years, range: 54-90 years) under treatment with denosumab for post-menopausal osteoporosis were longitudinally evaluated for incident radiological VFs and changes in lumbar spine bone mineral density (BMD) in relationship with medication adherence. All patients were persistent with denosumab treatment (i.e., maximum delay in administration of a single denosumab dose: 90 days). Patients were defined adherent to denosumab therapy when the drug was administered every 6 months ±28 days. RESULTS: One-hundred-seventy-three patients (84.4%) were adherent to denosumab therapy, whereas the remaining 31 patients (15.6%) received in delay one or more denosumab doses (cumulative delay: 52 days, range 29-183 days). Fourteen patients (6.9%) experienced incident VFs during the follow-up (median duration: 30 months, range: 18-48 months), in relationship with non-adherence to denosumab therapy (hazard ratio 4.44; 95% CI: 1.01-19.47) and smaller increase in lumbar spine BMD (hazard ratio 0.85, 95% CI: 0.76-0.94). CONCLUSIONS: In post-menopausal women at high risk of fractures, the small delay in the administration of denosumab (i.e., not uncommon in clinical practice) was associated with a significant increase in incidence of VFs. Preservation of standard dosing schedule appears to be an important determinant of denosumab effectiveness in the real-life clinical practice.

Medullary thyroid carcinoma treated with percutaneous ultrasound-guided radiofrequency ablation.

PURPOSE: Minimally invasive image-guided thermal ablation has been proposed as alternative to surgery for treatment of benign thyroid nodules and recurrent differentiated thyroid carcinoma. Here, we report for the first time the use of radiofrequency ablation (RFA) in a patient with non-metastatic medullary thyroid carcinoma (MTC) who did not undergo surgery due to high anesthesiological risk. METHODS AND RESULTS: A 64-year-old woman was referred to our institution for a routine endocrinological visit. No thyroid-related symptoms were present. She had a history of metabolic, cardiovascular and neurological diseases. On clinical examination, a nodular lesion of about 10 mm was palpable in the right thyroid lobe; ultrasonography (US) confirmed the presence of a 13 mm thyroid nodule in the lower pole of the right lobe, that was hypoechoic and with regular margins. Serum calcitonin (Ctn) level was significantly high (647 pg/mL). Fine-needle aspiration (FNA) of the thyroid nodule was negative for malignant cells, but the marked increase of Ctn level in the FNA wash-out fluid confirmed the diagnostic suspicion of MTC. Since patient refused surgery due to high anesthesiological risk, percutaneous US-guided RFA in single session was performed. At 6-months follow-up the serum Ctn level decreased from the initial value of 647 pg/mL, reaching near-normal range (15 pg/mL), and neck ultrasound showed a complete necrosis of the tumour. Afterward, serum Ctn slowly increased to 49 pg/mL at 15-month follow-up. The US performed at 6 and 12 months of follow-up revealed fibrotic tissue in place of the thyroid nodule, without evidence of cervical lymph-node metastases. CONCLUSIONS: This clinical case suggests that RFA may be effective and safe for treatment of MTC when surgery cannot be performed.