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Cristina Eller-Vainicher, Elisa Cairoli, Volha V Zhukouskaya, Valentina Morelli, Serena Palmieri, Alfredo Scillitani, Paolo Beck-Peccoz and Iacopo Chiodini

Objective

The prevalence of subclinical contributors to low bone mineral density (BMD) and/or fragility fracture is debated. We evaluated the prevalence of subclinical contributors to low BMD and/or fragility fracture in the presence of normal 25-hydroxyvitamin D (25OHVitD) levels.

Design

Prospective observational study.

Methods

Among 1095 consecutive outpatients evaluated for low BMD and/or fragility fractures, 602 (563 females, age 65.4±10.0 years) with apparent primary osteoporosis were enrolled. A general chemistry profile, phosphate, 25OHVitD, cortisol after 1-mg overnight dexamethasone suppression test, antitissue transglutaminase and endomysial antibodies and testosterone (in males) were performed. Serum and urinary calcium and parathyroid hormone levels were also evaluated after 25OHVitD levels normalization. Vertebral deformities were assessed by radiograph.

Results

In total, 70.8% of patients had low 25OHVitD levels. Additional subclinical contributors to low BMD and/or fragility fracture were diagnosed in 45% of patients, with idiopathic hypercalciuria (IH, 34.1%) and primary hyperparathyroidism (PHPT, 4.5%) being the most frequent contributors, apart from hypovitaminosis D. Furthermore, 33.2% of IH and 18.5% of PHPT patients were diagnosed only after 25OHVitD levels normalization. The subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D were associated inversely with age (odds ratio (OR) 1.02, 95% CI 1–1.04, P=0.04) and BMI (OR 1.1, 95% CI 1.05–1.17, P=0.0001) and directly with fragility fractures (OR 1.89, 95% CI 1.31–2.73, P=0.001), regardless of BMD.

Conclusions

Subclinical contributors to low BMD and/or fragility fracture besides hypovitaminosis D are present in more than 40% of the subjects with apparent primary osteoporosis. Hypovitaminosis D masks a substantial proportion of IH and PHPT patients.

Free access

Antonio Stefano Salcuni, Valentina Morelli, Cristina Eller Vainicher, Serena Palmieri, Elisa Cairoli, Anna Spada, Alfredo Scillitani and Iacopo Chiodini

Objective

Subclinical hypercortisolism (SH) is associated with increased risk of vertebral fractures (VFx). The effect on bone following recovery from SH is unknown.

Design

Of the 605 subjects consecutively referred for monolateral adrenal incidentalomas (AIs) to our outpatient clinics, 55 SH patients (recruited on the basis of the exclusion criteria) were enrolled. We suggested to all patients to undergo adrenalectomy, which was accepted by 32 patients (surgical group, age 61.3±8.1 years) and refused by 23 patients, who were followed with a conservative management (non-surgical group, age 65.4±7.1 years).

Methods

We diagnosed SH in patients with serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST) >5.0 μg/dl or with greater than or equal to two criteria among 1 mg-DST >3.0 μg/dl, urinary free cortisol >70 μg/24 h and ACTH <10 pg/ml. We assessed: bone mineral density (BMD) at lumbar spine (LS) and femoral neck (as Z-score) by dual-energy X-ray absorptiometry and the VFx presence by X-ray at baseline and at the end of follow up (surgical group 39.9±20.9 months and non-surgical group 27.7±11.1 months).

Results

The LS Z-score (ΔZ-score/year) tended to increase in the surgical group (0.10±0.20) compared with the non-surgical group (−0.01±0.27, P=0.08) and in the former, the percentage of patients with new VFx was lower (9.4%) than in the latter (52.2%, P<0.0001). Surgery in AI patients with SH was associated with a 30% VFx risk reduction (odds ratio 0.7, 95% CI 0.01–0.05, P=0.008) regardless of age, gender, follow up duration, 1 mg-DST, LS BMD, and presence of VFx at baseline.

Conclusion

In patients with monolateral AI and SH, adrenalectomy reduces the risk of VFx.

Free access

Antonio Stefano Salcuni, Vincenzo Carnevale, Claudia Battista, Serena Palmieri, Cristina Eller-Vainicher, Vito Guarnieri, Flavia Pugliese, Giuseppe Guglielmi, Gaetano Desina, Salvatore Minisola, Iacopo Chiodini and Alfredo Scillitani

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%, P = 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, P < 0.001 and serum PTH levels, 5.4 pmol/L vs 7.3 pmol/L, P < 0.01, significantly higher.

Conclusions

PA should be considered among the causes of secondary OP.

Free access

Valentina Morelli, Serena Palmieri, Andrea Lania, Alberto Tresoldi, Sabrina Corbetta, Elisa Cairoli, Cristina Eller-Vainicher, Maura Arosio, Massimiliano Copetti, Enzo Grossi and Iacopo Chiodini

Background

The independent role of mild autonomous cortisol secretion (ACS) in influencing the cardiovascular event (CVE) occurrence is a topic of interest. We investigated the role of mild ACS in the CVE occurrence in patients with adrenal incidentaloma (AI) by standard statistics and artificial neural networks (ANNs).

Methods

We analyzed a retrospective record of 518 AI patients. Data regarding cortisol levels after 1 mg dexamethasone suppression (1 mg DST) and the presence of obesity (OB), hypertension (AH), type-2 diabetes (T2DM), dyslipidemia (DL), familial CVE history, smoking habit and CVE were collected.

Results

The receiver-operating characteristic curve analysis suggested that 1 mg DST, at a cut-off of 1.8 µg/dL, had the best accuracy for detecting patients with increased CVE risk. In patients with 1 mg-DST ≥1.8 µg/dL (DST+, n = 223), age and prevalence of AH, T2DM, DL and CVE (66 years, 74.5, 25.9, 41.4 and 26.8% respectively) were higher than that of patients with 1 mg-DST ≤1.8 µg/dL (61.9 years, 60.7, 18.5, 32.9 and 10%, respectively, P < 0.05 for all). The CVE were associated with DST+ (OR: 2.46, 95% CI: 1.5–4.1, P = 0.01), regardless of T2DM, AH, DL, smoking habit, gender, observation period and age. The presence of at least two among AH, T2DM, DL and OB plus DST+ had 61.1% sensitivity in detecting patients with CVE. By using the variables selected by ANNs (familial CVE history, age, T2DM, AH, DL and DST+) 78.7% sensitivity was reached.

Conclusions

Cortisol after 1 mg-DST is independently associated with the CVE occurrence. The ANNs might help for assessing the CVE risk in AI patients.

Free access

Cristina Eller-Vainicher, Claudia Battista, Vito Guarnieri, Silvana Muscarella, Serena Palmieri, Antonio Stefano Salcuni, Giuseppe Guglielmi, Sabrina Corbetta, Salvatore Minisola, Anna Spada, Geoffrey N Hendy, David E C Cole, Iacopo Chiodini and Alfredo Scillitani

Objective

To examine factors, in addition to bone mineral density (BMD), such as the common calcium-sensing receptor (CASR) gene polymorphisms, associated with vertebral fracture (VFx) risk in primary hyperparathyroidism (PHPT).

Design and methods

A cross-sectional analysis of 266 Caucasian PHPT seen as outpatients. Serum calcium (sCa) phosphate metabolism parameters were measured. BMD was assessed by dual-energy X-ray absorptiometry (expressed as Z-score) at lumbar spine (Z-LS) and femoral neck, morphometric VFx by radiograph, and CASR A986S/R990G genotypes by PCR amplification and genomic DNA sequencing.

Results

Fractured patients (n=100, 37.6%) had lower sCa (10.8±0.7 mg/dl) and Z-LS BMD (−1.0±1.44), higher age (61±10 years), and prevalence (51%) of ≥1 S alleles of the CASR A986S single-nucleotide polymorphism (SNP; AS/SS), than those not fractured (n=166, 11.2±1.0 mg/dl, −0.57±0.97, 58±13 years, and 38% AS/SS, respectively, P<0.05 for all comparisons). Logistic regression, with VFx as dependent variable, showed independent risks associated with increased age (OR 1.03, 95% CI 1.01–1.06, P=0.006), decreased sCa (OR 1.86, 95% CI 1.28–2.7, P=0.001), and Z-LS BMD (OR 1.4, 95% CI 1.12–1.7, P=0.002) and presence of AS/SS (OR 1.8, 95% CI 1.1–2.9, P=0.05). The presence of two out of three factors (age ≥58 years, sCa <10.8 and Z-LS BMD≤−1.0, and AS/SS genotype) gave an overall OR of 4.2 (95% CI 2.25–7.85, P<0.0001).

Conclusions

In PHPT, VFx is associated positively with age, negatively with sCa and spinal BMD, and presence of at least one copy of the CASR A986S SNP.

Free access

Cristina Eller-Vainicher, Marcello Filopanti, Serena Palmieri, Fabio Massimo Ulivieri, Valentina Morelli, Volha V Zhukouskaya, Elisa Cairoli, Rosa Pino, Antonella Naccarato, Uberta Verga, Alfredo Scillitani, Paolo Beck-Peccoz and Iacopo Chiodini

Objective

In primary hyperparathyroidism (PHPT), vertebral fractures (VFx) occur regardless of bone mineral density (BMD) and may depend on decreased bone quality. Trabecular bone score (TBS) is a texture measurement acquired during a spinal dual-energy X-ray absorptiometry (DXA). Recently, TBS has been proposed as an index of bone micro-architecture.

Design

We studied 92 PHPT patients (74 females, age 62.1±9.7 years) and 98 control subjects. In all patients at baseline, in 20 surgically treated patients and in 10 conservatively treated patients after 24 months, TBS, spinal (lumbar spine (LS)) and femoral (total hip (TH) and femoral neck (FN)) BMD were assessed by DXA and VFx by spinal radiograph.

Results

PHPT patients had lower TBS (−2.39±1.8) and higher VFx prevalence (43.5%) than controls (−0.98±1.07 and 8.2% respectively, both P<0.0001). TBS was associated with VFx (odds ratio 1.4, 95% CI 1.1–1.9, P=0.02), regardless of LS-BMD, age, BMI and gender, and showed a better compromise between sensitivity (75%) and specificity (61.5%) for detecting VFx than LS-BMD, TH-BMD and FN-BMD (31 and 75%, 72 and 44.2%, and 64 and 65% respectively). In surgically treated patients, TBS, LS-BMD, TH-BMD and FN-BMD increased (+47±44.8,+29.2±34.1,+49.4±48.7 and +30.2±39.3% respectively, all P<0.0001). Among patients treated conservatively, TBS decreased significantly in those (n=3) with incident VFx (−1.3±0.3) compared with those without (−0.01±0.9, P=0.048), while BMD changes were not statistically different (LS 0.3±1.2 vs −0.8±0.9 respectively, P=0.19; TH 0.4±0.8 vs −0.8±1.4 respectively, P=0.13 and FN 0.4±0.9 vs −0.8±1.4 respectively, P=0.14).

Conclusions

In PHPT, bone quality, as measured by TBS, is reduced and associated with VFx and improves after surgery.