Intraoperative parathyroid hormone (PTH) testing in patients with primary hyperparathyroidism and PTH levels in the normal range.

BACKGROUND: Primary hyperparathyroidism is a common endocrine disorder. Hypercalcemia with normal PTH levels is very unusual and can lead to diagnostic difficulties. There are very few very few studies in the literature and all with limited numerical samples. The goal of the present study was to determine the real incidence and characteristics of primary hyperparathyroidism with normal PTH and to evaluate if intraoperative PTH testing is useful in these patients. METHODS: We performed a retrospective review of 314 patients who had undergone parathyroidectomy to treat primary hyperparathyroidism between January 2002 and December 2016. Patients were divided in two groups according to biochemical preoperative findings: in Group A were included patients with normal serum PTH, in Group B those with increased serum PTH. RESULTS: Nine patients (3.7%) were included in group A and 235 in group B. Patients in group A were younger (51.5 ± 12.9 years vs 59.6 ± 12.5); preoperative serum calcium and the incidence of coexisting thyroid disease were similar between the two groups. Symptomatic patients were more frequent in Group A (77.8% vs 39.1%; p = 0.048). There were no significant differences regarding preoperative localization studies and surgical procedure. Intraoperative PTH determination demonstrated sensitivity of 86% in group A and 97% in group B, specificity and positive predictive value of 100% in both the groups, negative predictive value of 67% in group A and 79% in group B. Histopathological examination demonstrated a single gland disease in 8 (88.9%) patients in group A and a multi gland disease in 1 (11.1%), in group B single gland disease was found in 218 (92.8%) patients and multi gland disease in 17 (7.2%). Unsuccessful surgery with persistent or recurrent hyperparathyroidism occurred in 1 (11.1%) patient in group A and 4 (1.7%) in group B. CONCLUSIONS: Primary hyperparathyroidism with normal PTH is rare but physicians should be aware of this possibility in patients with hypercalcaemia. Patients with normal PTH levels are younger and more frequently symptomatic. Intraoperative PTH testing plays an important role in the operative management even in such patients.

Bone mass preservation with high-dose cholecalciferol and dietary calcium in HIV patients following antiretroviral therapy. Is it possible?

OBJECTIVE: To evaluate whether treatment with 100,000 IU/month (equivalent to 3200 IU/day) of cholecalciferol and 1 g/day of dietary calcium supplementation in HIV patients following different cART regimens yields normal levels of vitamin D3 and PTH as well as whether changes in bone mineral density are clinically significant. METHODS: Consecutive HIV patients following different cART regimens received 100,000 IU/month (equivalent to 3200 IU/day) of cholecalciferol and 1 g/day of dietary calcium supplementation. The participants underwent BMD assessment via dual energy X-ray absorptiometry of the spine and hip at baseline (T0) and after 24 months (T1). Levels of 25(OH) vitamin D3 and parathyroid hormone (PTH) were assessed at T0 and T1. Quantitative variables were assessed with a paired t-test, independent t-test or analysis of variance, as appropriate. A chi-squared analysis was used to assess the association between qualitative variables. A p-value <0.05 was considered significant. Patients were divided into three groups depending on the cART regimen. RESULTS: A total of 79 patients were included (40 males, 51% and 39 females, 49%), with a mean age of 46.6 (SD ±11.2) years, a baseline CD4 count of 649 cells/µl and a mean 25 hydroxycholecalciferol (25(OH) D3) value of 25 + 10 ng/ml. After 24 months, the 25(OH) D3 increased to 40 + 11 ng/ml. The initial BMDs at T0 were estimated as 0.919 (±0.27) and 0.867 (±0.14) g/cm2 at the spine and hip, respectively. After 24 months, the BMD was 0.933 (±0.15) g/cm2 at the spine and 0.857 (±0.14) g/cm2 at the hip. Based on a BMD change exceeding 3%, a worsening was observed in 23% of patients at the spine and 27% at the hip, whereas stability or improvement was demonstrated in 77% of patients at the spine and 73% at the hip. Subgrouping patients based on antiretroviral therapy indicated that, at T1, there was a statistically significant increase in vitamin D3 concentration in all patients, while PTH concentration was not significantly reduced in patients taking tenofovir or efavirenz. BMD stability or improvement was demonstrated in 77% of patients at the spine and 73% at the hip after 24 months. The multivariate analysis confirms a decrease in vitamin D3 and an increase in PTH levels in smokers, as well higher vitamin D3 concentrations in males and lower spine BMDs in menopausal females. CONCLUSION: The proposed protocol of cholecalciferol and dietary calcium supplementation is safe and valid for correcting vitamin D abnormalities in almost all patients as well as reducing PTH levels in a high percentage of patients; however, it is not sufficient for normalization, particularly in patients exposed to tenofovir or efavirenz. At the spine, no significant BMD change was found in any of the therapy groups. At the hip, our data confirm a modest negative effect on bone mass caused by tenofovir and efavirenz.

Exploring the Role of Killer Cell Immunoglobulin-Like Receptors and Their HLA Class I Ligands in Autoimmune Hepatitis.

BACKGROUND: Natural killer cells are involved in the complex mechanisms underlying autoimmune diseases but few studies have investigated their role in autoimmune hepatitis. Killer immunoglobulin-like receptors are key regulators of natural killer cell-mediated immune responses. METHODS AND FINDINGS: KIR gene frequencies, KIR haplotypes, KIR ligands and combinations of KIRs and their HLA Class I ligands were investigated in 114 patients diagnosed with type 1 autoimmune hepatitis and compared with a group of 221 healthy controls. HLA Class I and Class II antigen frequencies were compared to those of 551 healthy unrelated families representative of the Sardinian population. In our cohort, type 1 autoimmune hepatitis was strongly associated with the HLA-B18, Cw5, DR3 haplotype. The KIR2DS1 activating KIR gene and the high affinity HLA-C2 ligands were significantly higher in patients compared to controls. Patients also had a reduced frequency of HLA-Bw4 ligands for KIR3DL1 and HLA-C1 ligands for KIR2DL3. Age at onset was significantly associated with the KIR2DS1 activating gene but not with HLA-C1 or HLA-C2 ligand groups. CONCLUSIONS: The activating KIR gene KIR2DS1 resulted to have an important predictive potential for early onset of type 1 autoimmune hepatitis. Additionally, the low frequency of the KIR-ligand combinations KIR3DL1/HLA-Bw4 and KIR2DL3/HLA-C1 coupled to the high frequency of the HLA-C2 high affinity ligands for KIR2DS1 could contribute to unwanted NK cell autoreactivity in AIH-1.

Can antiretroviral therapy modify the clinical course of HDV infection in HIV-positive patients?

BACKGROUND: Infection with hepatitis delta virus (HDV) affects approximately 6-14.5% of patients coinfected with HIV-1 and HBV, showing a more aggressive clinical course compared with an HIV-negative population. There is no universally approved treatment for chronic hepatitis D (CHD) in HIV-infected patients. Antiretroviral therapy (ART) containing tenofovir has been recently associated with HDV suppression. Our aim was to evaluate whether the outcome of CHD in HIV-infected patients can be favourably influenced by ART including reverse transcriptase inhibitors. METHODS: The clinical course of four HBV/HDV/HIV-coinfected patients receiving ART were retrospectively examined. RESULTS: HDV RNA became undetectable in all patients after a variable period of ART along with the disappearance of hepatitis B surface antigen in two of them, and an increase in CD4(+) T-cell count. In all patients, virological changes were associated with improved liver function tests and clinical features. CONCLUSIONS: We suggest that ART regimens including drugs active against HBV could have beneficial effects on the clinical course of CHD in patients with HIV-1 by favouring immunological reconstitution.

Intraoperative parathyroid hormone assay during focused parathyroidectomy: the importance of 20 minutes measurement.

BACKGROUND: Parathyroid hormone (PTH) monitoring during the surgical procedure can confirm the removal of all hyperfunctioning parathyroid tissue, as the half-life of PTH is approximately 5 min. The commonly applied Irvin criterion is reported to correctly predict post-operative calcium levels in 96-98% of patients. However, the PTH baseline reference concentration is markedly influenced by surgical manipulations during preparation of the affected glands, interindividual variability of the PTH half-life and modifications in the physiological state of the patient during surgery. The aim of this study was to evaluate the possible impact of the measurement of intraoperative PTH 20 minutes after surgery. METHODS: Between 2003 and 2012, 188 patients underwent a focused parathyroidectomy associated to rapid intraoperative PTH assay monitoring. Blood samples were collected: 1) at pre-incision time, 2) at 10 min after gland excision and 3) at 20 min after excision, if a sufficient reduction of PTH value was not observed. On the bases of the Irvin criterion, an intra-operative PTH drop>50% from the highest either pre-incision or pre-excision level after parathyroid excision was considered a surgical success. RESULTS: A >50% decrease of PTH after gland excision compared to the highest pre-excision value occurred in 156/188 patients (83%) within 10 min and in further 12/188 after 20 minutes (6.4%). In the remaining 20 patients (10.6%) values of PTH remained substantially unchanged or decreased less than 50% and for this reason bilateral neck exploration was performed. An additional pathologic parathyroid was removed in 9 cases, a third in one. In the other 10 cases further neck exploration by a standard cervical approach was negative and in four of these persistent postoperative hypercalcemia was demonstrated. The overall operative success was 97.3%. Intraoperative PTH monitoring was accurate in predicting operative success or failure in 96.3% of patients. CONCLUSIONS: The 20 minutes PTH measurement appears very useful, avoiding unnecessary bilateral exploration and the related risk of complications with only a slight increase of the duration of surgery and of the costs. PTH values decreasing appeared to be influenced by surgical manipulations during minimally invasive parathyroidectomy.