High PTH Levels Research Articles

A Striking Finding during Intraoperative Jugular Vein Sampling in a Case of Parathyroid Adenoma with Low-Normal Serum Intact Parathyroid Hormone Levels

Aim: Primary hyperparathyroidism (PHP) is the most common cause of hypercalcemia based on outpatient clinic. The diagnosis of PHP is generally straightforward with high intact parathyroid hormone (iPTH) and hypercalcemia. But, PHP does not always exhibit those biochemical features. Less known phenotype of PHP is the hypercalcemia with normal level of iPTH. We report a case of parathyroid adenoma with low normal peripheral iPTH and high jugular PTH levels presenting as hypercalcemia. Our aim was to discuss the different mechanisms of such an entity with the guidance of the literature. Case: A thirty-six year old woman who has type 2 diabetes mellitus was admitted to the hospital with the diagnosis of acute pancreatitis. On laboratory examination serum calcium and iPTH levels were as follows: 10.6, 10.7, 10.9 mg/dL and 28.8, 33.3, 31.7 pg/mL, respectively. Twenty-four hour calcium excretion was 403 mg/day; serum phosphor was 2.3 mg/dL. Based on the findings of hypercalcemia, hypercalciuria, positive sonographic and scintigraphic images, operation was performed with the possible diagnosis of PHP. PTH measurement was taken from the right jugular vein. Intraoperative PTH was 634 pg/mL. Histopathological examination revealed as parathyroid adenoma. Postoperative hypocalcemia didn’t occur and postoperative calcium and iPTH levels were normal. Conclusion: Clinicians should be aware of the presence of low-normal iPTH in PHP. If the clinical suspicion of PHP is high as in our case, surgery should be performed after exclusion of other causes of hypercalcemia.

Gene-by-Diet Interactions Affect Serum 1,25-Dihydroxyvitamin D Levels in Male BXD Recombinant Inbred Mice.

1,25-Dihydroxyvitamin D (1,25[OH]2D) regulates calcium (Ca), phosphate, and bone metabolism. Serum 1,25(OH)2D levels are reduced by low vitamin D status and high fibroblast growth factor 23 (FGF23) levels and increased by low Ca intake and high PTH levels. Natural genetic variation controls serum 25-hydroxyvitamin D (25[OH]D) levels, but it is unclear how it controls serum 1,25(OH)2D or the response of serum 1,25(OH)2D levels to dietary Ca restriction (RCR). Male mice from 11 inbred lines and from 51 BXD recombinant inbred lines were fed diets with either 0.5% (basal) or 0.25% Ca from 4 to 12 weeks of age (n = 8 per line per diet). Significant variation among the lines was found in basal serum 1,25(OH)2D and in the RCR as well as basal serum 25(OH)D and FGF23 levels. 1,25(OH)2D was not correlated to 25(OH)D but was negatively correlated to FGF23 (r = -0.5). Narrow sense heritability of 1,25(OH)2D was 0.67 on the 0.5% Ca diet, 0.66 on the 0.25% Ca diet, and 0.59 for the RCR, indicating a strong genetic control of serum 1,25(OH)2D. Genetic mapping revealed many loci controlling 1,25(OH)2D (seven loci) and the RCR (three loci) as well as 25(OH)D (four loci) and FGF23 (two loci); a locus on chromosome 18 controlled both 1,25(OH)2D and FGF23. Candidate genes underlying loci include the following: Ets1 (1,25[OH]2D), Elac1 (FGF23 and 1,25[OH]2D), Tbc1d15 (RCR), Plekha8 and Lyplal1 (25[OH]D), and Trim35 (FGF23). This report is the first to reveal that serum 1,25(OH)2D levels are controlled by multiple genetic factors and that some of these genetic loci interact with the dietary environment.

The DOPPS Practice Monitor for US Dialysis Care: PTH Levels and Management of Mineral and Bone Disorder in US Hemodialysis Patients

In the US DPM sample, median PTH levels increased 32%, from August 2010 through April 2011 and have remained relatively stable since then. Black patients carry a disproportionate burden of PTH levels above 600 pg/ml (29%; vs. 17% among nonblacks). This finding warrants particular attention, since such high PTH levels have consistently been associated with adverse outcomes6–14 and the association between severe hyperparathyroidism and mortality appeared consistent in both racial groups. While we had postulated that the PPS may have led to lower utilization of MBD-related intravenous drugs, vitamin D prescription remained stable over time. Rather, the increase in PTH levels seem to have been driven mainly by adoption of more liberal PTH targets, as reported in the medical director survey. However, PTH levels >600 are above any currently recommended guidelines and likely represent a modifiable risk factor for adverse outcomes. Clinicians should take this into account especially when treating black patients, since nearly a third of them presented such high levels in the US DOPPS sample.

Bone Mineral Accrual Is Associated With Parathyroid Hormone and 1,25-Dihydroxyvitamin D Levels in Children and Adolescents.

Rapid bone accrual and calcium demands during puberty may result in compensatory increases in PTH and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels; however, these relations have not been established in longitudinal studies. To determine whether greater bone accrual velocity is associated with greater PTH and 1,25(OH)2D levels in healthy children and adolescents. Prospective cohort study with baseline PTH, 25-hydroxyvitamin D [25(OH)D], and 1,25(OH)2D levels and dual-energy x-ray absorptiometry whole-body bone mineral content (BMC) accrual over 12 months. Secondary analyses examined bone biomarkers and tibia quantitative computed tomography midshaft cortical-BMC. A total of 594 healthy participants, ages 5-21 years, with longitudinal measures in a subset of 145 participants. PTH and 1,25(OH)2D levels. PTH levels were higher during Tanner stages 3 and 4 compared to Tanner 1 (P < .05) in males and females and were inversely and significantly associated with 25(OH)D levels and dietary calcium intake. In multivariable analyses, greater bone accrual [measured directly as change in dual-energy x-ray absorptiometry-BMC (P < .001) or quantitative computed tomography-BMC (P < .05), or indirectly as growth velocity (P < .05) or greater bone-formation biomarker level (P < .01)] was associated with higher PTH levels, independent of 25(OH)D level and dietary calcium intake. Similar associations were observed between these direct and indirect indices of bone accrual and 1,25(OH)2D levels. PTH levels rise in midpuberty, in association with multiple measures of bone accrual. This is consistent with compensatory increases in PTH to drive 1,25(OH)2D production and calcium absorption during periods of increased calcium demands. Additional studies are needed to address PTH effects on bone modeling and remodeling during growth and development.

Parathyroid Hormone Levels May Predict Nonalcoholic Steatohepatitis in Morbidly Obese Patients.

Background:Obesity as a worldwide health problem is associated with nonalcoholic steatohepatitis (NASH). Since severe liver injury may be present in asymptomatic obese patients and a definite diagnosis of nonalcoholic steatohepatitis can only be made after an invasive procedure of liver biopsy, there is a need for noninvasive methods to predict the probability of NASH.Objectives:To investigate the role of vitamin D endocrine system in predicting the probability of presence of NASH in asymptomatic morbidly obese candidates of bariatric surgery.Patients and Methods:From December 09 to March 11, every patient undergoing bariatric surgery had a liver biopsy. Nonalcoholic steatohepatitis was diagnosed using the Lee’s criteria, the baseline labs obtained and the association between laboratory data and presence of NASH assessed.Results:Forty-six patients (34 women, aged 36.5 ± 10.6 years) were analyzed. The mean levels of liver enzymes were significantly higher in the group with NASH (P value < 0.01). In an unadjusted logistic model, PTH was the only variable in vitamin D endocrine system which was significantly associated with NASH (odds ratio (OR): 1.04, 95%CI: 1.01 - 1.07). After adjustment for possible confounding factors, age (OR: 1.22, 95%CI: 1.00 - 1.50) and PTH (OR: 1.08, 95%CI: 1.01 - 1.16) were predictive factors for NASH (P value < 0.05).Conclusions:Elevated serum PTH level was the predictive factor for NASH in morbidly obese patients. Also, we reported elevated serum liver enzymes, high serum PTH levels and older age as predictors of NASH in patients seeking obesity surgical treatments.

Hypertension, Antihypertensive Medications, and Risk of Incident Primary Hyperparathyroidism.

Hypertension is associated with higher PTH levels, and specific antihypertensive medications may modulate PTH. Whether hypertension or the use of specific antihypertensive medications influences the risk of developing incident primary hyperparathyroidism (P-HPTH) is not known. The purpose of this study was to investigate whether a history of hypertension and the use of specific antihypertensive medications determine the risk for developing P-HPTH in a large prospective study. A longitudinal prospective cohort of female nurses in the Nurses' Health Study I (n = 75 600), who did not have P-HPTH at baseline and completed a questionnaire assessment of lifetime history of P-HPTH were followed from 1986 to 2008. Most participants were white and postmenopausal. The study was a nationwide cohort study. Incident P-HPTH was assessed initially via questionnaire and then was confirmed by medical record review. Cox proportional hazards models were used to adjust for potential confounders. We documented 347 incident cases of P-HPTH during 1 719 416 person-years of follow-up. The age-adjusted relative risk (RR) for incident P-HPTH associated with hypertension was 1.80 (95% confidence interval [CI], 1.43-2.26), and the multivariate-adjusted RR was 1.45 (95% CI, 1.10-1.91). Among participants with a history of hypertension, the use of furosemide, when compared with the use of other antihypertensive medications, was associated with increased risk for developing P-HPTH; age-adjusted RR for incident P-HPTH was 1.79 (95% CI, 1.15-2.79) and multivariate-adjusted RR was 1.71 (95% CI, 1.08-2.71). In a large longitudinal prospective cohort study of mostly older white women, a history of hypertension and use of furosemide were associated with a significantly higher risk of developing P-HPTH.

Temporal relationship between vitamin D status and parathyroid hormone in the United States.

BackgroundInterpretation of parathyroid hormone (iPTH) requires knowledge of vitamin D status that is influenced by season.ObjectiveCharacterize the temporal relationship between 25-hydroxyvitamin D3 levels [25(OH)D3] and intact iPTH for several seasons, by gender and latitude in the U.S. and relate 25-hydrovitamin D2 [25(OH)D2] levels with PTH levels and total 25(OH)D levels.MethodWe retrospectively determined population weekly-mean concentrations of unpaired [25(OH)D2 and 25(OH)D3] and iPTH using 3.8 million laboratory results of adults. The 25(OH)D3 and iPTH distributions were normalized and the means fit with a sinusoidal function for both gender and latitudes: North >40, Central 32–40 and South <32 degrees. We analyzed PTH and total 25(OH)D separately in samples with detectable 25(OH)D2 (≥4 ng/mL).FindingsSeasonal variation was observed for all genders and latitudes. 25(OH)D3 peaks occurred in September and troughs in March. iPTH levels showed an inverted pattern of peaks and troughs relative to 25(OH)D3, with a delay of 4 weeks. Vitamin D deficiency and insufficiency was common (33% <20 ng/mL; 60% <30 ng/mL) as was elevated iPTH levels (33%>65 pg/mL). The percentage of patients deficient in 25(OH)D3 seasonally varied from 21% to 48% and the percentage with elevated iPTH reciprocally varied from 28% to 38%. Patients with detectable 25(OH)D2 had higher PTH levels and 57% of the samples with a total 25(OH)D > 50 ng/mL had detectable 25(OH)D2.Interpretation25(OH)D3 and iPTH levels vary in a sinusoidal pattern throughout the year, even in vitamin D2 treated patients; 25(OH)D3, being higher in the summer and lower in the winter months, with iPTH showing the reverse pattern. A large percentage of the tested population showed vitamin D deficiency and secondary hyperparathyroidism. These observations held across three latitudinal regions, both genders, multiple-years, and in the presence or absence of detectable 25(OH)D2, and thus are applicable for patient care.

Predictors of persistent post transplant hyperparathyroidism (HPTx)

Post transplant persistent Hyperparathyroidism (HPTx) increases the risk for transplant complications. Purpose: to identify risk factors for HPTx in the first post transplant year. Methods: Retrospective analysis of medical records from renal transplant recipients from July/2008 to December/2010. Inclusion criteria: serum PTH ≥500 pg/ml at transplant and normal 1-year graft function (serum creatinine ≤ 2mg/dL). From a group of 224 renal transplants, 69 (30%) fulfilled the inclusion criteria, and they were divided in 2 groups, according to the serum PTH after 1 year of transplant: control, 1-year P TH&lt;150 p g/ml ( n=32) a nd P ersistent H yperparathyroidism, H PTx, 1 -year P TH ≥ 1 50 p g/ml ( n= 3 7). Data analyzed: serum calcium (Ca), phosphate (Pi), alkaline phosphatase (AP), PTH and glomerular filtration rate (GFR) at transplant, and 3, 6 and 12 months post transplant. Results: At transplant, the groups were comparable as to age, Pi and PTH. However, the length of the dialysis (78 40 vs. 50 34 months, p&lt;0.05) and Ca (8,9 0.9 vs. 8,5 0,6mg/dL, p&lt;0.05) were higher in the HPTx group. After 3 months post transplant, HPTx group maintained higher PTH levels (365.4 176.2 vs. 166.9 92.2pg/mL, p&lt;0.05), and AP (175 145 vs. 109 52UI, p&lt;0.05), than controls, despite of the comparable Ca, Pi, and GFR. From the 6th post transplant month, the HPTx group persisted with hypercalcemia (10.2 0.7 vs. 9.9 0.5mg/dL, p&lt;0.05) and low phosphate (2.6 0.5 vs. 2.9 0.7, p&lt;0.05) with higher AP and PTH levels than in controls (p&lt;0.05). At the end of the 1 post transplant year, HPTx group persisted with hypercalcemia, despite the recovery of the graft function while in the control group, the GFR recovery was associated with normalization of the bone mineral metabolism parameters. Conclusion: HPTx was associated with longer pre transplant dialysis therapy and higher Ca at transplant. Higher PTH and AP post transplant levels at the 3rd month were associated with persistent hyperparathyroidism, as well as persistent hypercalcemia and low phosphate, despite of the GFR recovery.

Cinacalcet Hydrochloride: a new dose schedule in the Management of Secondary Hyperparathyroidism in Indian Chronic Kidney Disease Patients

Analgesic Nephropathy: A neglected cause of Chronic Kidney DiseaseYusra Habib Khan, Azmi Sarriff, Amer Hayat Khan, Azreen Syazril Adnan, Tauqeer Hussain Mallhi

The combination of vitamin D deficiency and mild to moderate chronic kidney disease is associated with low bone mineral density and deteriorated femoral microarchitecture: results from the KNHANES 2008-2011.

Although mild to moderate chronic kidney disease (CKD) and vitamin D deficiency are prevalent in the elderly population worldwide and are associated with sarcopenia, their influence on bone mineral density (BMD) has not been determined. The objective of the study was to determine the combined effects of vitamin D deficiency and CKD on BMD in the elderly population and their relationships with sarcopenia and PTH levels. This was a cross-sectional study with nationally representative samples of 6949 subjects aged 55 years or older from the Korea National Health and Nutrition Examination Surveys conducted between 2008 and 2011. The study population was divided into four groups according to vitamin D and CKD status. The combined association of CKD and vitamin D deficiency [25(OH)D<20 ng/mL] with osteopenia or osteoporosis was assessed, and the status of PTH and the sarcopenic index (appendicular skeletal muscle mass as a percentage of body weight or appendicular skeletal muscle mass per weight) as a measure of sarcopenia were evaluated. BMD in the total hip and femoral neck as well as femoral bone geometry was markedly deteriorated in stage 3 and 4 CKD subjects with vitamin D deficiency compared with other groups. Regardless of gender, these subjects also had higher levels of PTH and increased prevalence of sarcopenia. Multivariable logistic regression analyses demonstrated that CKD subjects with vitamin D deficiency showed a significantly increased risk of osteoporosis or osteopenia [odds ratios 1.49 and 2.06 (1.81 and 2.65) at the femur neck and total hip, respectively, in women (men)], which was mainly associated with elevated levels of PTH and sarcopenia in these groups. The combination of mild to moderate CKD and vitamin D deficiency was significantly associated with low BMD in a geriatric population, linked with hyperparathyroidism and sarcopenia.

Interpretation of Plasma PTH Concentrations According to 25OHD Status, Gender, Age, Weight Status, and Calcium Intake: Importance of the Reference Values

Reference values for plasma PTH assessment were generally established on small samples of apparently healthy subjects, without considering their 25-hydroxyvitamin D (25OHD) status or other potential modifiers of PTH concentration. Our objective was to assess ranges of plasma PTH concentration in a large sample of adults, stratifying by 25OHD status, age, gender, weight status, and calcium intake. This cross-sectional survey is based on 1824 middle-aged Caucasian adults from the Supplémentation en Vitamines et Minéraux Antioxydants study (1994). Plasma PTH and 25OHD concentrations were measured by an electrochemoluminescent immunoassay. Extreme percentiles of plasma PTH concentrations were assessed specifically in subjects who had plasmatic values of 25OHD of 20 ng/mL or greater and 30 ng/mL or greater. Among subjects with 25OHD status of 20 ng/mL or greater, the 97.5th percentile of plasma PTH concentration was 45.5 ng/L. By using this value as a reference, 5% of the subjects with plasma 25OHD less than 20 nmol/L had a high plasma PTH level, reflecting secondary hyperparathyroidism. Among vitamin D-replete subjects (25OHD status of 20 ng/mL or greater), the 97.5th percentile of plasma PTH was higher in overweight/obese subjects (51.9 vs 43.5 ng/L among normal weight subjects). The reference value for plasma PTH defined in this vitamin D-replete population was far below the value currently provided by the manufacturer (65 ng/L) and varied according to overweight status. These results may contribute to improve the diagnosis of primary and secondary hyperparathyroidism and subsequent therapeutic indication.

Vitamin D Treatment in Primary Hyperparathyroidism: A Randomized Placebo Controlled Trial

Low 25-hydroxyvitamin D levels are common in patients with primary hyperparathyroidism (PHPT) and associated with higher PTH levels and hungry bone syndrome after parathyroidectomy (PTX). However, concerns have been raised about the safety of vitamin D supplementation in PHPT. We aimed to assess safety and effects on calcium homeostasis and bone metabolism of supplementation with high doses of vitamin D in PHPT patients. This was an investigator-initiated double-blind, randomized, placebo-controlled, parallel-group trial from a single center. Forty-six PHPT patients were recruited, with a mean age of 58 (range 29-77) years, and 35 (76%) were women. Intervention included daily supplementation with 70 μg (2800 IU) cholecalciferol or identical placebo for 52 weeks. Treatment was administered 26 weeks before PTX and continued for 26 weeks after PTX. PTH, calcium homeostasis, and bone metabolism were evaluated. Preoperatively, 25-hydroxyvitamin D increased from 50 to 94 nmol/L in the treatment group and decreased from 57 to 52 nmol/L in the placebo group (P < .001). Compared with placebo, vitamin D decreased PTH significantly by 17% before PTX (P = .01), increased lumbar spine bone mineral density by 2.5% (P = .01), and decreased C-terminal β-CrossLaps by 22% (P < .005). The trabecular bone score did not change in response to treatment, but improved after PTX. Postoperatively, PTH remained lower in the cholecalciferol group compared with the placebo group (P = .04). Plasma creatinine and plasma and urinary calcium did not differ between groups. Daily supplementation with a high vitamin D dose safely improves vitamin D status and decreases PTH in PHPT patients. The vitamin D treatment is accompanied by reduced bone resorption and improved bone mineral density before operation.

Serum parathyroid hormone is a new potential risk factor in multiple myeloma.

We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1) pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3 pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (≥68.3 pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients.

Atypical ultrasound features of parathyroid tumours may bear a relationship to their clinical and biochemical presentation.

ObjectivesTo describe atypical ultrasound features of parathyroid lesions and correlate them with clinical presentation and histopathology.Materials and methodsRetrospective review of 264 patients with primary hyperparathyroidism who underwent ultrasound imaging prior to parathyroidectomy was performed. Patients with atypical ultrasound findings (n = 26) were identified; imaging findings were correlated with clinical presentation and histopathology.ResultsTwenty-one (80 %) lesions were adenomas, two (8 %) were adenomas with cellular atypia, and three (11.5 %) were carcinomas. Seventeen (65 %) lesions showed cystic change; five (19 %) of them had >50 % cystic change. These lesions were adenomas with cystic degeneration. Cystic degeneration had significant positive correlation with the lesion size and PTH level, but cystic adenomas correlated negatively with lesion weight. Six (23 %) lesions were isoechoic and one (4 %) was hyperechoic; histology predominantly revealed haemorrhage, hyalinisation and fibrosis; one lesion showed fat deposition and another had multiple granulomas within the adenoma. Twenty (83 %) lesions had heterogeneous echotexture and showed combinations of acinar dilatation, necrosis, haemorrhage and fibrosis. Heterogeneous lesions tended to be significantly larger and heavier, and they were associated with higher PTH levels. Four (15 %) lesions had calcifications. Scintigraphy was concordant in 22 (96 %), n = 23. One scintigraphy-negative lesion was a cystic parathyroid adenoma.ConclusionAtypical ultrasound features of parathyroid lesions pose a diagnostic challenge. Awareness of these features would help improve lesion detection.Teaching points Cystic change is significantly related to the size, weight and measured parathyroid hormone levels.Cystic change in parathyroid tumours indicated a slightly higher risk of malignancy.Heterogeneous parathyroid adenomas are larger in size and heavier, and they have higher PTH levels.Awareness of atypical ultrasound features will improve preoperative clinical prediction.

Serum Level Of Parathyroid Hormone Is Associated With Risk Factors and Clinical Outcomes In Multiple Myeloma

BackgroundParathyroid hormone (PTH) is synthesized and secreted by the chief cells of the parathyroid gland. PTH has a positive impact on hematopoietic stem cells by indirectly decreasing hematopoietic cell apoptosis, and is currently being investigated as a potential therapeutic to stimulate hematopoiesis and enhance bone marrow engraftment. According to previous study, it was hypothesized that elevated PTH may mediate the induction of multiple myeloma (MM) through the biologic effects of IL-6. However, there was no comprehensive study regarding clinicopathological implications of PTH in MM. This study investigated the pathological and clinical implications of serum PTH in MM patients and relationship with other risk factors of MM. Patients and MethodsA total of 115 patients who were newly diagnosed with MM were enrolled between 2006 and 2012. Serum PTH level was measured by automated 2-site chemiluminescent sandwich assay (Abbott Diagnostics). The medical parameters were reviewed for age, sex, PTH, plasma cell percentage in bone marrow, serum M protein, immunoglobulin level, free light chain (FLC) - kappa and lambda, FLC ratio, calcium, creatinine, hemoglobin, albumin, beta-2 microglobulin, lactate dehydrogenase (LDH), international staging system (ISS) stage, international myeloma working group (IMWG) response, chromosome abnormality, bone lesion, treatment outcome, and so on. The collected data was analyzed by PASW 18.0. We performed Spearman's correlation analysis, Mann Whitney U-test, Kruskall Wallis test, time dependent Cox regression analysis, survival analysis by Kaplan-Meier method, etc. ResultsSerum PTH level of 115 myeloma patients was 24.7±34.9 (ranged 0.0-284.1) pg/mL. Serum level of IgG, IgM, FLC-lambda, albumin, and LDH was in positive correlation with serum PTH. Age, plasma cell percentage, M protein, IgA, FLC-kappa, FLC ratio, calcium, creatinine, hemoglobin, and beta-2 microglobulin showed negative correlation with PTH. Among those above, IgM (rho=0.190, p=0.045) and calcium (rho=-0.220, p=0.043) revealed statistically significant correlation with serum PTH. Serum PTH level in MM patients was not significantly different according to the group of IMWG response (p=0.450) and ISS stage (p=0.414). Meanwhile, there was no significant difference of PTH according to chromosomal abnormality (p=0.353), bone lesion (p=0.207), and disease progression (p=0.322). Besides, only calcium level was meaningfully different (p=0.016) by the comparison of clinical parameters between MM patient's group with high PTH level and non-high PTH group (cut-off PTH level=68.3 pg/mL, Mann Whitney U-test). Relative to non-high PTH (<68.3 pg/mL) group, the hazard ratio was higher for group with high PTH level (≥68.3 pg/ml) ([HR] 3.037; p=0.524; 95% CI, 0.100∼92.586; Table 1). With regard to the prognostic implication of serum PTH value, the patient group with above 68.3 pg/mL showed moderate, inferior progression free survival (PFS) than non-high PTH group (median, 5 months vs. 13 months, p=0.056, Fig.1B). However, no overall survival (OS) differences were found between high PTH group and non-high PTH group (Fig. 1A). Interestingly, subgroup analysis showed that patients with high PTH level significantly had an inferior PFS than those with non-high PTH level. In detail, the subgroup were as follows; patients who reached the complete remission (CR) state (N=25) defined by IMWG response criteria at the end of follow up period (median, 3 months vs. 41 months, p=0.001, Fig.1C), patients (N=41) who belonged to ISS stage II (median, 1 months vs. 15 months, p=0.006, Fig.1D), patients (N=97) with no chromosome abnormality (median, 4 months vs. 15 months, p=0.034, Fig.1E), patients (N=28) who have undergone transplantation (median, 3 months vs. 18 months, p=0.009, Fig.1F). ConclusionThis study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. Disclosures:No relevant conflicts of interest to declare.

Studio EVOLVE: un'altra delusione per i Nefrologi?

Il calciomimetico Cinacalcet è ormai in uso da alcuni anni per il trattamento dell'iperparatiroidismo secondario (IPTS) nei pazienti dializzati, permettendo una buona riduzione dei livelli di paratormone. Nell'ottica di valutare un suo possibile effetto benefico nel migliorare la prognosi cardio-vascolare dei pazienti dializzati, è stato condotto lo studio randomizzato “Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events” (EVOLVE). Sono stati randomizzati a ricevere Cinacalcet o placebo 3883 pazienti dializzati affetti da iperparatiroidismo secondario moderato-severo, valutando come end-point compositi primari la mortalità e gli episodi di infarto mio-cardico, l'ospedalizzazione per angina instabile, lo scompenso cardiaco ed eventi vascolari periferici. Nell'analisi “intention-to-treat”, a causa di una bassa potenza statistica, non sono state rilevate differenze significative tra i due bracci dello studio, a fronte di una più elevata incidenza di ipocalcemia, nausea e vomito nei soggetti in terapia con il calciomimetico. I dati dello studio EVOLVE hanno sicuramente deluso la comunità nefrologica, che si sarebbe aspettata dei risultati positivi. La mancanza di risultati conclusivi e i costi elevati suggeriscono un uso giudizioso del Cinacalcet. Non di meno, anche se mancano dati conclusivi su “hard end-point”, ci sembra poco saggio negare strategie terapeutiche che includano il Cinacalcet ai pazienti con severo IPTS con elevati livelli di PTH (PTH &gt;800 pg/mL) refrattari alla terapia standard e/o ipercalcemia e/o calcifilassi e/o elevato rischio chirurgico alla paratiroidectomia.

Hyperparathyroïdie par autonomisation d’une autogreffe de parathyroïde dans l’avant-bras : le rôle de la scintigraphie

We report the case of a 36-year old patient, referred for parathyroid imaging in a context of hyperparathyroidism. He had a history of congenital bilateral renal hypoplasia treated by four successive transplantations, the last one in July 2011. In 1990, a total parathyroidectomy with autologous parathyroid tissue graft in the right forearm has been performed for secondary hyperparathyroidism. However, hypocalcaemia persisted (2.78mmol/L), associated with high levels of PTH (1329pg/mL), even after the last renal transplantation. Neck ultrasound and parathyroid scintigraphy images did not show any cervical or thoracic ectopic parathyroid tissue, while right forearm incidences revealed a high uptake focus corresponding to the autonomisation of the parathyroid transplanted tissue. A brief review of the literature evaluating the benefits of this type of intervention is presented.

Vitamin D, parathyroid hormone and muscle impairment in myotonic dystrophies

Parathyroid function in Myotonic Dystrophy (DM) patients has been poorly investigated. Parathyroid and muscle parameters were assessed in 31 male DM1 (44±2years), 13 male DM2 (56±2years) and 32 healthy controls. Hyperparathyroidism was diagnosed in 18% of patients without differences between DM types. In all DM patients, hyperparathyroidism was associated with normocalcemia but one with hypercalcemia. DM patients presented significantly higher PTH and lower vitamin D (25OHD) compared with controls, also considering seasonality. Severe vitamin D deficiency (25OHD<10ng/ml) was diagnosed in 40% and hypovitaminosis D (25OHD<30ng/ml) occurred in 88% of DM patients. About one-third of DM1 presented hypophosphatemia associated with elevated PTH levels. Serum 25OHD levels negatively correlated with PTH and with body fat mass. Considering DM1 patients, serum PTH levels positively correlated with CTG triplet repeats. Furthermore, PTH levels negatively correlated with total modified Medical Research Council (MRC) and positively with Muscular Impairment Rating Scale (MIRS). By contrast, in DM2 patients muscle assessment did not show any correlation with parathyroid function. In conclusion, we arrived at the following: 1) severe vitamin D deficiency is common in DM patients and it is associated with secondary hyperparathyroidism; 2) primary hyperparathyroidism, though rare, may occur; 3) increased adiposity in DM may be a risk factor for hypovitaminosis D; and 4) high serum PTH levels may indicate a muscle impairment, at least in DM1.

Parathyroid carcinoma and hungry bone syndrome

We hereby report two patients with parathyroid carcinoma presenting extremely high calcium and PTH levels, severe bone disease, and palpable neck mass at diagnosis. They both underwent parathyroidectomy, and one of them evolved to lung metastasis. Important hypocalcemia was observed after surgery in both: after parathyroidectomy in one patient, and only after surgical removal of the metastasis in the other. Both required intravenous calcium replacement, thus revealing hungry bone syndrome (HBS). HBS usually reflects rapid mineralization after correction of hyperparathyroidism. The more severe the bone disease before surgery, the more prone the patient is to HBS after surgery. Despite being an unfavorable outcome, HBS state suggests that surgical removal of hypersecretory parathyroid tissue was accomplished. In this study, HBS was observed in both patients, who presented severe bone disease prior to surgery. HBS would be expected post-operatively in successful parathyroid carcinoma removal.

Correlates of parathyroid hormone concentration in hemodialysis patients

The implications of chemical hyperparathyroidism on bone and mineral metabolism measures in maintenance hemodialysis (MHD) are not well known. We hypothesized that a higher serum intact parathyroid hormone (iPTH) level is associated with the higher likelihood of hyperphosphatemia, hyperphosphatasemia [high serum alkaline phosphatase (ALP) levels] and hypercalcemia. Over an 8-year period (July 2001-June 2009), we identified 106 760 MHD patients with iPTH and calcium (Ca), phosphorous (P) and ALP data from a large dialysis clinic. Logistic regression models were examined to assess the association between serum iPTH increments and the likelihood of hyperphosphatemia (P ≥5.5 mg/dL), hypercalcemia (Ca ≥10.2 mg/dL) and hyperphosphatasemia (ALP ≥120 U/L). Patients were 61 ± 16 years old and included 45% women, 59% diabetics and 33% Blacks. Compared with an iPTH level of 100 to <200 pg/mL, patients with an iPTH level of 600-700, 700 to <800 and ≥800 pg/mL had 122% (OR: 2.22, 95% CI: 2.04-2.41), 153% (OR: 2.53, 95% CI: 2.29-2.80) and 243% (OR: 3.43, 95% CI: 3.22-3.66) higher risk of hyperphosphatemia, respectively, and had 109% (OR: 2.09, 95% CI: 1.93-2.26), 130% (OR: 2.30, 95% CI: 2.10-2.52) and 376% (OR: 4.76, 95% CI: 4.50-5.04) higher risk of hyperphosphatasemia, respectively. Compared with an iPTH level of 100 to <200 pg/mL, both the low iPTH (<100 pg/mL, OR: 2.45, 95% CI: 2.27-2.64) and the high iPTH (≥800 pg/mL: OR: 2.13, 95% CI: 1.95-2.33) levels were associated with hypercalcemia. Higher levels of iPTH are incremental correlates of hyperphosphatemia and hyperphosphatasemia, whereas both very low and high PTH levels are linked to hypercalcemia. If these associations are causal, correction of hyperparathyroidism may have overarching implications on bone and mineral disorders in MHD patients.