Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

Impaired Immune Function in Patients With Chronic Postsurgical Hypoparathyroidism: Results of the EMPATHY Study.

CONTEXT: Despite the pivotal role of calcium signaling in immune response, little is known about immune function in patients affected by hypoparathyroidism. OBJECTIVE: This work aimed to evaluate immune function in hypoparathyroidism. METHODS: The Evaluation of iMmune function in Postsurgical and AuToimmune HYpoparathyroidism (NCT04059380) is a case-control, cross-sectional study set in an Italian referral center. Participants included 20 patients with postsurgical hypoparathyroidism (12 females) and 20 age- and sex-matched controls. Main outcome measures included calcium metabolism assessment, peripheral blood mononuclear cells (PBMC) profiling via flow cytometry, parathyroid hormone receptor 1 (PTHr1) expression analysis using immunofluorescence and PrimeFlow RNA assay, gene expression analysis via real-time polymerase chain reaction, cytokine measurement, and evaluation of infectious disease frequency and severity. RESULTS: Immune cell profiling revealed decreased monocytes, regulatory, naive, and total CD4+ T lymphocytes, which correlated with total calcium, ionized calcium, and PTH levels, in patients with hypoparathyroidism. Patients with hypoparathyroidism had a higher CD3-CD56+ natural killer (NK) cell count, which inversely correlated with calcium, PTH, and vitamin D levels. Furthermore, they exhibited decreased tumor necrosis factor (TNF) and granulocyte-macrophage colony-stimulating factor gene expression and decreased circulating TNF levels. Gene expression and immunofluorescence analysis confirmed PTHr1 expression in all PBMC lineages; however, the percentage of cells expressing PTHr1 was lower, whereas the intensity of PTHr1 expression in monocytes, total T lymphocytes, CD8+CD4+ and CD4+ T lymphocytes, and total NK cells was higher in patients with hypoparathyroidism. CONCLUSIONS: This study describes for the first time the immune alterations in patients with hypoparathyroidism receiving conventional therapies, supporting the immunoregulatory role of PTH and proposing an explanation for the increased susceptibility to infections observed in epidemiological studies.

Parathyroid carcinoma.

Parathyroid carcinoma (PC) is a rare disease with an indolent behavior due to the low malignant potential. The etiology is unknown. Somatic mutations of CDC73 gene, the same gene involved in the hyperparathyroidism-jaw tumor syndrome, can be identified in up to 70% of patients with PC and in one-third of cases the mutations are germline. Therefore, in patients who carry germline CDC73 gene mutations, its finding permits to identify the carriers among relatives and sometimes to early detect a parathyroid lesion in such subjects. The diagnosis of PC is commonly made after surgery, however there are some clinical/biochemical features that should raise the suspicion of PC, namely markedly elevated serum calcium and PTH levels, a large parathyroid lesion with suspected ultrasonographic features of malignancy, the damages of kidney and bones. The best chance of cure is the complete surgical resection with the en-bloc excision at the first operation, however several recurrences are often observed during the follow-up. Since PC is an indolent tumor with long-lasting survival and the death is due to complications of untreatable hypercalcemia, multiple surgical interventions with debulking of tumoral tissues along with medical treatment for reducing hypercalcemia are often needed. Patients with PC should be followed up along their lifetime.

Diagnostic accuracy of 3T magnetic resonance imaging in the preoperative localisation of parathyroid adenomas: comparison with ultrasound and 99mTc-sestamibi scans.

OBJECTIVES: To evaluate the diagnostic performance of 3TMRI in comparison with ultrasound (US) and 99mTc-sestamibi scan for presurgical localisation of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT). METHODS: Fifty-seven patients affected by PHPT were prospectively enrolled and underwent US, 99mTc-sestamibi and 3TMRI. T2-weighted and post-contrast T1-weighted Iterative decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) sequences were acquired. Diagnostic performance of US, 99mTc-sestamibi and MRI in localising PTAs to correct quadrant were compared according to surgical and pathological findings. RESULTS: According to surgical findings, US correctly localised 41/46 PTAs (sensitivity of 89.1%; specificity 97.5%; PPV 93.1% and NPV 95.6%); 99mTc-sestamibi correctly localised 38/46 PTAs (sensitivity 83.6%, specificity 98.3%, PPV 95% and NPV 93.7%). US and 99mTc-sestamibi combined had a sensitivity of 93.4% (43/46 PTAs), specificity of 98.3%, PPV 95% and NPV 98.3%. MRI correctly localised 45/46 PTAs (sensitivity 97.8%; specificity 97.5%; PPV 93.7% and NPV 99.2%). MRI was able to detect six adenomas missed by 99mTc-sestamibi and two adenomas missed by US. MRI and US were able to detect all enlarged parathyroid glands in patients with multiglandular disease. MRI identified six of seven ectopic adenomas. CONCLUSIONS: Our study demonstrated high diagnostic performance of 3T MRI in the preoperative PTAs quadrant localisation, as well as in patients with multiglandular disease and ectopic PTAs. MRI may be preferred to adequately select patient candidates for minimally invasive parathyroidectomy (MIP). KEY POINTS: • PTA(s) quadrant localisation by 3TMRI was more accurate than US+99mTc-sestamibi. • MRI identified all enlarged glands in multiglandular disease similarly to US. • MRI identified 6/7 ectopic PTAs similarly to 99mTc-sestamibi. • Presurgical PTA(s) localisation by 3TMRI select the optimal candidates for MIP.

HypoparaNet: A Database of Chronic Hypoparathyroidism Based on Expert Medical-Surgical Centers in Italy.

Hypoparathyroidism is a rare disease characterized by low serum calcium levels and absent or deficient parathyroid hormone level. Regarding the epidemiology of chronic hypoparathyroidism, there are limited data in Italy and worldwide. Therefore, the purpose of this study was to build a unique database of patients with chronic hypoparathyroidism, derived from the databases of 16 referral centers for endocrinological diseases, affiliated with the Italian Society of Endocrinology, and four centers for endocrine surgery with expertise in hypoparathyroidism, to conduct an epidemiological analysis of chronic hypoparathyroidism in Italy. The study was approved by the Institutional Review Board. A total of 537 patients with chronic hypoparathyroidism were identified. The leading etiology was represented by postsurgical hypoparathyroidism (67.6%), followed by idiopathic hypoparathyroidism (14.6%), syndromic forms of genetic hypoparathyroidism (11%), forms of defective PTH action (5.2%), non-syndromic forms of genetic hypoparathyroidism (0.9%), and, finally, other forms of acquired hypoparathyroidism, due to infiltrative diseases, copper or iron overload, or ionizing radiation exposure (0.7%). This study represents one of the first large-scale epidemiological assessments of chronic hypoparathyroidism based on data collected at medical and/or surgical centers with expertise in hypoparathyroidism in Italy. Although the study presents some limitations, it introduces the possibility of a large-scale national survey, with the final aim of defining not only the prevalence of chronic hypoparathyroidism in Italy, but also standards for clinical and therapeutic approaches.

Incidence and all-cause mortality for hip fracture in comparison to stroke, and myocardial infarction: a fifteen years population-based longitudinal study.

PURPOSE: This population-based study investigated the incidence, in-hospital and long-term all-cause mortality, for hip fracture (HipFx), stroke (STR), and myocardial infarction (MI) in residents hospitalized between 2000 and 2014. METHODS: Data about hospitalization were drawn from the administrative discharge database, whereas information about residents and all-cause mortality from the municipality of our town. Patients were followed-up from the first hospital admission until death or study end. For each cause, crude and age-adjusted all-cause mortality of men and women were compared by Mann-Whitney's test and Poisson models. Separate age-sex adjusted Cox models were estimated and the corresponding adjusted survival curves were drawn. RESULTS: Among 1292 hospitalizations (of 1109 patients), 434 were for HipFx, 526 for STR, 332 for MI (183 with and 149 without coronary revascularization -MIwCR and MIwoCR, respectively). The incidence of HipFx and STR did not vary over time, MI slightly increasing in men. Age-adjusted in-hospital mortality for HipFx was lower than for STR and MIwoCR in the whole sample and in women (p < 0.001), but not in men. After discharge, men with HipFx had shorter survival and higher crude and age-adjusted mortality rate than women. The estimated HRs(95%CI) in respect to patients with MIwCR (having the lowest mortality) were: 6.11(3.12-11.97), p < 0.001 for HipFx; 5.78(2.93-11.32), p < 0.001 for STR; 2.68(1.27-5.66), p = 0.010 for MIwoCR in the whole sample [HR: 16.58(6.70-40.98) p < 0.001 for HipFx; 7.35(3.01-17.93) p < 0.001 for STR, in men]. CONCLUSIONS: HipFx markedly impacts hospital care, and causes high in-hospital and long-term all-cause mortality, comparable to the two commonest non-tumor causes of death.

Vitamin D status in primary hyperparathyroidism: effect of genetic background.

Primary hyperparathyroidism (PHPT) is associated with hypovitaminosis D as assessed by serum total 25-hydroxyvitamin D (TotalD) levels. The aim of this study is to evaluate whether this is also the case for the calculated bioavailable 25-hydroxyvitamin D (BioD) or free 25-hydroxyvitamin D (FreeD), and whether the vitamin D status is influenced by genetic background. We compared vitamin D status of 88 PHPT patients each with a matched healthy family member sharing genetic background, i.e., first-degree relative (FDR), or not, namely an in-law relative (ILR). We compared TotalD and vitamin D-binding protein (DBP), using the latter to calculate BioD and FreeD. We also genotyped two common DBP polymorphisms (rs7041 and rs4588) likely to affect the affinity for and levels of vitamin D metabolites. TotalD was lower (p < 0.001) in PHPT (12.3 ± 6.6 ng/mL) than either family member group (FDR: 19.4 ± 12.1 and ILR: 23.2 ± 14.1), whether adjusted for DBP or not. DBP levels were also significantly lower (p < 0.001) in PHPT (323 ± 73 mg/L) versus FDR (377 ± 98) or ILR (382 ± 101). The differences between PHPT and control groups for TotalD, BioD, and FreeD were maintained after adjustment for season, gender, and serum creatinine. 25-hydroxyvitamin D, evaluated as total, free, or bioavailable fractions, is decreased in PHPT. No difference was seen between first-degree relative and in-law controls, suggesting that neither genetic nor non-genetic background greatly influences the genesis of the hypovitaminosis D seen in PHPT.

Assessment of trabecular bone score (TBS) in overweight/obese men: effect of metabolic and anthropometric factors.

The "trabecular bone score" (TBS) indirectly explores bone quality, independently of bone mineral density (BMD). We investigated the effects of anthropometric and metabolic parameters on TBS in 87 overweight/obese men. We assessed BMD and TBS by DXA, and some parameters of glucose metabolism, sex-and calciotropic hormone levels. Regression models were adjusted for either age and BMI, or age and waist circumference, or age and waist/hip ratio, also considering BMI >35 (y/n) and metabolic syndrome (MS) (y/n). Correlations between TBS and parameters studied were higher when correcting for waist circumference, although not significant in subjects with BMI >35. The analysis of covariance showed that the same model always had a higher adjusted r-square index. BMD at lumbar spine and total hip, fasting glucose, bioavailable testosterone, and sex hormone-binding globulin are the only covariates having a significant effect (p < 0.05) on the variations of TBS. The presence of MS negatively affected only the association between TBS and BMD at total hip. We did not find any significant effect of BMI >35 on TBS values or significant interaction terms between each covariate and either BMI >35 or the presence of MS. Obesity negatively affected TBS, despite unchanged BMD. Alterations of glucose homeostasis and sex hormone levels seem to influence this relationship, while calciotropic hormones have no role. The effect of waist circumference on TBS is more pronounced than that of BMI.

Short-term effects of glucagon-like peptide 1 (GLP-1) receptor agonists on fat distribution in patients with type 2 diabetes mellitus: an ultrasonography study.

AIMS: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) induce weight loss and reduction in adipose tissue, but the effects of GLP-1 RA on the distribution of fat deposits have been poorly investigated. METHODS: In 25 patients with type 2 diabetes (16 females and 9 males, mean age 63.5 ± 8.8 years), treated with GLP-1 RA (exenatide, n. 12; liraglutide, n.13), both before and 3 months after starting treatment, an abdominal ultrasonographic scan, with Doppler of renal arteries, and echocardiography were performed. Subcutaneous fat width (peri-umbilical and sub-xiphoid), deep fat deposits (pre-aortic, peri-renal, and epicardial), and renal resistive index (RI) were evaluated. RESULTS: GLP-1 RA induced highly significant (p < 0.001) decrease in BMI and in fat thickness at all the assessed sites, without differences between exenatide and liraglutide treatment. A slight decrease in RI (p = 0.055) was also found. The percent changes of fat thickness was different between sites (p < 0.025), and the changes in subcutaneous deposits showed no significant correlation (p = 0.064) with those of deep fat deposits. CONCLUSIONS: A short course of treatment with GLP-1 RA, besides weight loss, induces a redistribution of adipose tissue deposits, possibly contributing to a better cardiovascular risk profile in patients with type 2 diabetes mellitus.

Estimate of body composition by Hume's equation: validation with DXA.

We investigated how the Hume's equation, using the antipyrine space, could perform in estimating fat mass (FM) and lean body mass (LBM). In 100 (40 male ad 60 female) subjects, we estimated FM and LBM by the equation and compared these values with those measured by a last generation DXA device. The correlation coefficients between measured and estimated FM were r = 0.940 (p < 0.0001) and between measured and estimated LBM were r = 0.913 (p < 0.0001). The Bland-Altman plots demonstrated a fair agreement between estimated and measured FM and LBM, though the equation underestimated FM and overestimated LBM in respect to DXA. The mean difference for FM was 1.40 kg (limits of agreement of -6.54 and 8.37 kg). For LBM, the mean difference in respect to DXA was 1.36 kg (limits of agreement -8.26 and 6.52 kg). The root mean square error was 3.61 kg for FM and 3.56 kg for LBM. Our results show that in clinically stable subjects the Hume's equation could reliably assess body composition, and the estimated FM and LBM approached those measured by a modern DXA device.

Vitamin D supplementation: when and how?

The multiple effects of vitamin D on skeletal and extra-skeletal tissues increased the attention of scientists and public to the possible relationship between hypovitaminosis D and a variety of acute and chronic diseases. However, several points are still largely debated. In particular, the definition of optimal vitamin D status [as assessed by the circulating levels of 25-hydroxyvitamin D (25(OH)D)] remains controversial, and experts still disagree about several related outcomes: how to estimate the prevalence of vitamin D deficiency, when to start treatment, how to reach optimal 25(OH)D levels, which type of vitamin is preferable for supplementation, which dosing strategy is the better option. In this context, a matter of major debate is represented by the measurement of circulating level of 25(OH)D, whose determination is affected by the lack of standardization and by several technical problems. It has been recently hypothesized that free and bio-available, rather than total 25(OH)D, mostly determine its biological action. However, further evaluation of directly measured free 25(OH)D levels is needed, in order to establish its role in research and clinical practice. Finally, it is not yet defined if a threshold of optimal vitamin D status for reducing the risk of extra-skeletal diseases exists. Actually, it is plausible that the desired 25(OH)D level may vary widely, depending on the health outcome in question. However, this topic is uncertain, partly due to the lack of randomized controlled trials assessing the effect of vitamin D supplementation on extra-skeletal end-points.

Quality of life in patients with primary hyperparathyroidism.

The clinical picture of primary hyperparathyroidism (PHPT) has changed over the last three decades and many asymptomatic patients are now diagnosed through the unexpected finding of high serum calcium levels. However, though not yet considered as typical features of the disease and therefore not included in the guidelines for surgery, many data are available on neuropsycological manifestations and their impact on quality of life in asymptomatic patients. PHPT patients indeed show early experience nonspecific symptoms, such as weakness, depression, sleep disturbance, memory loss and anxiety. Although the underlining mechanisms have not been still identified, the prevalence of psychiatric and cognitive deficits has been investigated in many studies, as well as the possible association with quality of life and well-being improvement after surgery. This article aims to review the current knowledge on quality of life in PHPT patients before and after surgery and the possible clinical implications of these findings.

Assessment of fracture risk by the FRAX algorithm in men and women with and without type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: The FRAX algorithm is a diffuse tool to assess fracture risk, but it has not been clinically applied in European patients with diabetes. We investigated FRAX-estimated fracture risk in patients with type 2 diabetes mellitus (DM), compared with concomitantly enrolled control subjects. METHODS: In our multicentric cross-sectional study, we assessed the FRAX scores of 974 DM and 777 control subjects from three Italian diabetes outpatient clinics, and in DM. We tested the association between parameters and complications of the disease and FRAX scores. RESULTS: DM had significantly lower FRAX-estimated probability of both major osteoporotic fracture (MOF) and hip fracture (HF) than control subjects (6.35 ± 5.07% versus 7.75 ± 6.93%, p < 0.001, and 2.17 ± 3.07% versus 2.91 ± 4.56%, p = 0.023, respectively). When grouping by gender, such differences were found only in men. In DM, the frequency of previous fracture was higher than in control subjects (29.88% versus 20.46%, p < 0.001). In diabetic patients, age, sex, body mass index, HbA1c and hypoglycaemia are significantly associated with FRAX scores; gender-specific regression models differed. Among DM, the tree-based regression (classification and regression tree (CART)) analysis identified groups of patients with different mean FRAX scores. In female DM aged > 65 years with or without obesity, MOF > 20% was found in 5.66% and 13.53% and H > 3% in 40.57% and 63.91% of patients, respectively. CONCLUSIONS: Patients with DM had mean FRAX scores lower than control subjects, despite the higher number of previous fractures. Some features and complications of DM did associate with FRAX scores. Among DM patients, the CART analysis identified subgroups with higher FRAX scores. However, despite its potential utility, concerns still remain for using FRAX in DM patients.

Development of high-efficiency molecular adsorbent recirculating system: preliminary report.

Molecular Adsorbent Recirculating System (MARS) is a liver support system widely employed in the treatment of liver failure. The method is normally well tolerated. To develop a liver support system combining high efficiency and tolerability, we modified the MARS albumin circuit with the insertion of double adsorption units in parallel. Four patients have been treated with this modified method (high-efficiency MARS, HE MARS): two had very high serum bilirubin and two had very high total bile acids. After a single MARS session bilirubin was reduced more with HE MARS than standard MARS (from 27.6 to 52.3% in patient A and from 27.9 to 49.1% in patient B), and bile acid reduction increased from 40 to 59.8% in patient C and from 39.9 to 60% in patient D. The results of this preliminary investigation in only a very small number of patients do support the possibility of developing a liver support system that combines good tolerability and high efficacy.

Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia.

OBJECTIVE: Tumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D. CLINICAL CASE: Here, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection. CONCLUSIONS: We report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.

Management of endocrine disease: value and limitations of assessing vitamin D nutritional status and advised levels of vitamin D supplementation.

The growing attention to the role of vitamin D in skeletal and extra-skeletal diseases over the last decade induced an increased demand for vitamin D determination as well as a dramatic rise of sales of vitamin D supplement. However, several critical points in this field remain to be clarified. We lack a clear consensus about the definition of vitamin D deficiency, insufficiency, and sufficiency. The identification of different thresholds defining vitamin D status has relevant implications in clinical practice. In fact, the worldwide prevalence of low vitamin D status is highly varying according to the level of 25(OH)D utilized to define sufficiency. Therefore, the assessment of 25-hydroxyvitamin D levels may have a critical role, but a number of different technical problems associated with its determination may interfere in interpreting the results. The hydrophobic nature of vitamin D and the tight binding to its carrier (vitamin D binding protein), the different forms circulating in blood, and the issue of standardization are among the most important factors influencing the measurement of this metabolite. Another controversial point relies on the conflicting guidance on prevention and treatment of vitamin D deficiency endorsed by different medical and scientific communities. In particular, uncertainty exists about how to replete vitamin D stores, how to maintain normal 25(OH)D levels after repletion, which form of vitamin D is preferable for supplementation, and which route of administration and dosing regimens are advisable. Finally, concerns have been raised regarding vitamin D toxicity and its adverse effects.

Long-term bioavailability after a single oral or intramuscular administration of 600,000 IU of ergocalciferol or cholecalciferol: implications for treatment and prophylaxis.

CONTEXT: We previously showed that a single high dose of oral (po) cholecalciferol (D3) sharply increases serum 25-hydroxyvitamin D [25(OH)D]. OBJECTIVE: We evaluated the long-term bioavailability and metabolism of a single po or intramuscular (im) high dose of ergocalciferol (D2) or D3. DESIGN: This was a prospective intervention study. SETTING: The study was conducted in an ambulatory care setting. PATIENTS: Participants were 24 subjects with hypovitaminosis D. INTERVENTIONS: A single dose of 600,000 IU of po or im D2 or D3 was administered. MAIN OUTCOME MEASURES: Serum 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were measured at baseline and at days 30, 60, 90, and 120 by RIA. Serum 1,25(OH)2D2, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24,25-hydroxyvitamin D2 [24,25(OH)D2], and 24,25-hydroxyvitamin D3 [24,25(OH)D3] were measured by liquid chromatography-tandem mass spectrometry in a subgroup of patients receiving the po formulations. RESULTS: The areas under the curve of 25(OH)D after D3 were significantly higher than those after D2 (P < .0001). Serum 25(OH)D basal difference significantly increased at day 30 with po D2 and D3 (P < .01 and P < .0001) and up to day 90 with po D3 (P < .01). The im formulations produced a slow increased, and values peaked at day 120 relative to the other time points (P < .0001). We found a decrease in 1,25(OH)2D at day 30 (P < .05) and up to day 120 (P < .001) and an increase in 1,25(OH)2D2 at day 30 (P < .01) and up to day 120 (P < .01) after po D2. Oral D2 and D3 produced increases in 24,25(OH)D2 and 24,25(OH)D3, respectively, at day 30 (P < .001). CONCLUSIONS: A po dose of 600,000 IU of D2 or D3 is initially more effective in increasing serum 25(OH)D than the equivalent im dose and is rapidly metabolized. Our RIA assay for 1,25(OH)2D may not recognize 1,25(OH)2D2.

Parathyroidectomy eliminates arrhythmic risk in primary hyperparathyroidism, as evaluated by exercise test.

OBJECTIVE: To investigate whether parathyroidectomy (PTx) reverses risk factors for arrhythmias related to the QT dynamic changes evaluated during bicycle ergometry exercise test (ET). METHODS: Twenty-four postmenopausal women with primary hyperparathyroidism (PHPT) (mean age 60.08.4 years) and 30 sex- and age-matched controls underwent ET, echocardiography, and biochemical evaluation. The following stages were considered during ET: rest, peak exercise, and recovery. The patients were randomized to two groups: 12 underwent PTx (group A) and 12 were followed-up conservatively (group B). After 6 months, the patients were studied again. RESULTS: Groups A and B showed no differences in mean baseline biochemical values, echocardiographic parameters, and QTC interval. PHPT patients showed an increased occurrence of ventricular premature beats (VPBS) during ET compared with controls (37.0 vs 6.6%, P=0.03). Serum calcium level was a predictor of VPBS (P=0.05). Mean value of QTC was in the normal range at baseline (Group A: 401±16.9; group B: 402.25±13.5 ms) but significantly lower than controls (417.8±25.1 ms, P<0.01). A negative correlation was found between QTc and calcium values (P=0.03). Physiological reduction of QTc interval from rest to peak exercise was not observed in PHPT patients before surgery. After PTx, group A had a significant reduction in VPBs compared with baseline (at baseline, 5 of 12 vs none of 12 patients after PTx, P=0.03) and a restored normal QT adaptation during ET. Group B showed no significant changes after a 6-month period. CONCLUSIONS: PTx reduces the occurrence of VPBs and restored the QTc adaptation during ET.