Relationship between insulin sensitivity and bone mineral density in primary hyperparathyroidism.

INTRODUCTION: Evidence of crosstalk between bone and insulin metabolism has been identified. In primary hyperparathyroidism (PHPT), scant data exist on this relationship. AIM: To evaluate the relationship between insulin levels or sensitivity and bone mineral density (BMD) in PHPT. SUBJECT AND METHODS: Two hundred and sixty-seven patients with PHPT without known diabetes mellitus were studied. Fasting blood glucose and insulin levels as well as BMD at lumbar spine, femoral neck and forearm were measured. Insulin sensitivity was assessed using Quantitative Insulin Sensitivity Check Index (QUICKI). The same parameters were measured 2 years (interquartile range 2·8 years) after surgery (PTX) in a subgroup of patients (n = 51). RESULTS: In univariate analysis, a positive relationship between insulin levels and BMD (R = 0·17, P < 0·03) or T-score (R = 0·20, P < 0·005) was found at femoral neck level. Consequently, a negative relationship between QUICKI and femoral BMD (R = -0·20, P < 0·01) or T-score (R = -0·21, P < 0·004) was found. In multivariate analysis, when femoral BMD was the dependent variable, age (beta = -0·35, P < 0·000004), BMI (beta = 0·39, P < 0·00001), PTH (beta = -0·18, P < 0·05) and QUICKI (R = -0·15, P < 0·05) had an independent effect (R(2) = 0·29). Insulin levels and QUICKI did not change after PTX. No relationship was found between QUICKI or insulin levels at the time of diagnosis and change in BMD at any site at follow-up. CONCLUSIONS: Our data show a weak relationship between insulin levels and/or insulin sensitivity and BMD in PHPT. However, the insulin state does not influence change in bone density after PTX in PHPT.

Vitamin D status in primary hyperparathyroidism: a Southern European perspective.

BACKGROUND: Vitamin D deficiency (VDD) is common in patients with primary hyperparathyroidism (pHPT), and this could affect the clinical expression of the disease. However, few North American or North European studies have addressed this issue, showing vitamin D repletion in only about one-third of the patients. SUBJECTS AND METHODS: Vitamin D status was evaluated both in an observational study in a series of 206 consecutive patients with pHPT at diagnosis and in a case-control analysis with 113 age- and sex-matched healthy blood donors. Vitamin D status was assessed by measuring plasma 25-hydroxy-vitamin D (25OHD) levels and was defined as VDD or severe VDD if 25OHD was <20 ng/ml (<50 nm) and <10 ng/ml (<25 nm), respectively. RESULTS: No seasonal variability was observed in 25OHD levels. VDD was observed in 75 of 206 patients (36·4%). The VDD was severe in 24 of 75 patients (11·7%). There was no difference in prevalence of VDD between men and women nor between asymptomatic and 'bone and stone' symptomatic patients. 25OHD levels was negatively correlated with parathyroid hormone, ionized calcium, and bone turnover markers, and positively correlated with phosphate. 25OHD levels were also positively correlated with bone mineral density at all sites measured. In the case-control study, the overall prevalence of VDD and severe VDD was higher in patients with pHPT compared with controls (33·6% vs 10·6%, P < 0·0001, and 8·8% vs 1·8%, P = 0·0337, respectively). CONCLUSIONS: Our study shows that VDD occurs in about one-third of patients with pHPT resident in a Southern European area, a lower figure than previously reported. Moreover, VDD is related to a more severe bone disease, and its prevalence is higher in patients with pHPT than in healthy matched subjects.

May an altered hypothalamo-pituitary-adrenal axis contribute to cortical bone damage in primary hyperparathyroidism?

Cortisol secretion has been reported to be increased in primary hyperparathyroidism (PHPT). Our aim was to evaluate circulating and urinary cortisol levels and the relationships with biochemical and bone parameters in patients with PHPT at the time of diagnosis. We studied 180 consecutive patients with PHPT (mean age +/- SD 60.0 +/- 13.2 years; F/M 140/40, BMI 25.8 +/- 4.8 kg/m(2)) and 56 subjects with incidentally discovered adrenal adenoma who served as controls (age 56.2 +/- 12.8 years, F/M 40/16, BMI 25.7 +/- 3.9 kg/m(2)). Serum morning and midnight cortisol and urinary free cortisol were measured in both groups. In PHPT patients bone mineral density was measured at the lumbar spine, femur, and forearm. Serum morning cortisol and urinary cortisol were similar in PHPT patients and controls, whereas midnight cortisol was higher in PHPT patients (5.3 +/- 4.7 vs. 2.9 +/- 0.9 microg/dL, P = 0.001). In this group, midnight cortisol correlated positively with age (r = 0.27, P = 0.008) and negatively with forearm (r = -0.36, P = 0.003) and total-femur T score (r = -0.30, P = 0.02). Multivariate regression analysis, including age, calcium, parathyroid hormone (PTH), and midnight cortisol as independent variables and forearm T score as dependent variable, indicated that age (beta = -0.29, P < 0.0001), PTH (beta = -0.33, P < 0.0001), and midnight cortisol (beta = -0.14, P < 0.04) were independently associated with forearm T score. Our findings show increased midnight cortisol levels in patients with PHPT, indicating a subtle alteration of the hypothalamo-pituitary-adrenal axis dynamics that is unrelated to the degree of disease activity; further data are needed to demonstrate the supplementary effect of this subtle alteration to bone damage in this condition.

Cardiotoxicity after anthracycline chemotherapy in breast carcinoma: effects on left ventricular ejection fraction, troponin I and brain natriuretic peptide.

UNLABELLED: Anthracyclines are among the most active drugs in breast cancer patients. We planned to evaluate the early and 2-year modification of left ventricular ejection fraction (LVEF) and the effects of chemotherapy on troponin I and neurohormonal assessment. METHODS: Patients with early breast cancer surgically treated and eligible to adjuvant chemotherapy were enrolled. All patients underwent clinical assessment, radionuclide ventriculography, troponin I and brain natriuretic peptide (BNP) measurements at baseline and one-month (T1), one year (T2) and 2-year (T3) after chemotherapy. Reductions of LVEF ≥ 10% or an overt heart failure were considered cardiovascular events. RESULTS: 53 patients, 52 females and 1 male, age 55.3 years were included and followed at T3. A significant reduction of LVEF was observed (from 62 ± 5.5% to 59.3 ± 8.6%, p=0.04) at T3; BNP increased (from 33.4 ± 41.5 pg/ml to 62.7 ± 94.7 pg/ml, p=0.005) at T1. Troponin I augmented at T1 (from 0.006 ± 0.01 ng/ml to 0.05 ± 0.04 ng/ml, p=0.0001) but normalized at T2 (0.005 ± 0.08 ng/ml; p=0.9). Only baseline BNP was nearly to be significantly correlated with T3 LVEF (p=0.07 HR 0.96-1) at multivariate analysis. In 13/53 patients (32.1%) LVEF showed ≥ 10% reduction at T3 (group A); in 40/53 patients (67.9%) LVEF was unchanged (group B). Patients in group A demonstrated higher baseline plasma BNP (p=0.02) and lower haemoglobin concentration (p=0.007) compared to patients in group B. CONCLUSIONS: LVEF and BNP modified early after anthracycline chemotherapy and LVEF did not recover at T3. In patients who developed left ventricular systolic dysfunction, a subclinical activation of neurohormonal profile was observed.

Unexpected results using rapid intraoperative parathyroid hormone monitoring during parathyroidectomy for primary hyperparathyroidism.

Rapid intraoperative parathyroid hormone (RIOPTH) monitoring predicts complete removal of all hypersecreting tissue by means of a significant parathyroid hormone (PTH) decrease. In this study we have tried to provide an explanation for some unexpected results of RIOPTH monitoring observed during a series of 125 conventional parathyroidectomies for primary hyperthyroidism, discussing the possible consequences on the surgical strategy. Three main groups can be recognized: (1) spikes: a PTH increase 10 minutes after removal of the diseased gland was observed in three patients; (2) false-negative results: six patients showed an inadequate PTH decreases at 10 minutes, three of them resulting in cure at 20 minutes (all six patients were cured at follow-up); (3) false-positive results: five patients with multiglandular disease showed a PTH decrease to a cure level despite excision of one adenoma only (in two of these patients a 20-minute sample showed a PTH increase soon after manipulation of the second adenoma). We concluded that the spike, almost certainly a consequence of manipulating the adenoma, when detected should be considered the "true" baseline value. False-negative results are to some extent related to undetected spikes. The assay used for RIOPTH determination and PTH half-life variability may also play a role. A false-negative result usually prolongs the surgical time. False-positive results are usually related to a double adenoma, one functionally prevailing over the other. Because in our experience manipulation of the second adenoma brought a PTH increase detected with RIOPTH monitoring, we believe that the second adenoma should be excised.

Effects of the addition of a low dose of spironolactone on brain natriuretic peptide plasma level and cardiopulmonary function in patients with moderate congestive heart failure.

BACKGROUND: The purpose of our study was to assess the effects of a low dose of spironolactone in patients with moderate congestive heart failure (CHF) on the plasma level of brain natriuretic peptide (BNP), echocardiographic left ventricular ejection fraction (LVEF), and cardiopulmonary function assessed by cardiopulmonary (CP) test. MATERIAL/METHODS: 51 CHF patients (74.5% males, mean age 60 years) underwent transthoracic echocardiography, CP test, and plasma BNP assay at the time of enrollment and after 6 months of standard therapy for CHF plus a low dose of spironolactone (group A). A control group (21 patients, group B) was treated using standard therapy only. All subjects were in NYHA class I-III and had LVEF < or = 40%. RESULTS: BNP concentration decreased significantly (from 45.7+/-57.4 pg/ml to 18.6+/-26.9 pg/ml at follow-up; p=0.01), and the NYHA class and LVEF improved (2.2+/-0.6 vs 1.7+/-0.5, p=0.0001; 27.7+/-7.2% vs 35.1+/-11%, p=0.001 respectively) in subjects in group A. In spite of clinical amelioration, peak oxygen consumption, oxygen pulse and anaerobic threshold in the CP test did not change significantly (16.6+/-5.7 ml/kg/min vs 17.1+/-5.3 ml/kg/min p=0.5; 8.8 +/- 4.3 ml/beat vs 9.5+/-3.6 ml/beat p=0.2; 0.75+/-0.2 ml/Kg/min vs 0.73+/-0.2 ml/Kg/min p=0.7). No differences were noticed in the control group. CONCLUSIONS: The addition of spironolactone reduced the BNP plasma level in patients with moderate CHF and increased LVEF. This therapy improved the NYHA class without modifying the functional parameters in the CP test.