Mean Intact Parathyroid Hormone Levels Research Articles

Outcome of supplementation of vitamin D on intact parathyroid hormone level in chronic kidney disease patients

Background: Secondary hyperparathyroidism is present in majority of patients with estimated glomerular filtrate rate less than 60 mL/min/1.73 m2. Sustained elevated parathyroid hormone level can cause osteitis-fibrosa-cystica, fracture, hypercalcemia, hyperphosphatemia, and calciphylaxis. Kidney Disease Improving Global Outcome guidelines for Chronic Kidney Disease Mineral and Bone Disorder 2017 recommends treatment with calcitriol or vitamin D analogue if parathyroid hormone level is progressively increasing and remains persistently above the upper limit despite correction of modifiable factors.
 Objectives: The objective of this study was to determine the mean change in intact parathyroid hormone aftercalcitriol supplementation in patients with chronic kidney disease (stage 3 to 5).
 Methodology: This prospective observational study enrolled 92 patients with chronic kidney disease stage 3 to 5, not under maintenance hemodialysis. Patients who had intact parathyroid hormone level more than 200 pg/ml, serum phosphate level less than 4.5 mg/dl and corrected serum calcium less than 9.5 mg/dl were selected for the study. They were supplemented with oral calcitriol 0.25μg thrice weekly for three months and intact parathyroid hormone level was measured after three months.
 Results: Mean intact parathyroid hormone level before supplementation was 332.91 ± 96.046pg/ml and after three months of supplementation with calcitriol was 176.49 ±53.764pg/ml. This finding was statistically significant (Correlation: 0.471, p-value less than 0.05). Thus, supplementation of calcitriol reduced the mean intact parathyroid hormone level in the chronic kidney disease patients in our study.
 Conclusion: Calcitriol supplementation seems to be an effective measure to reduce intact parathyroid hormone level in chronic kidney disease patients when it remains persistently high despite correction of modifiable factors.

Head-to-head comparison of the new calcimimetic agent evocalcet with cinacalcet in Japanese hemodialysis patients with secondary hyperparathyroidism

Secondary hyperparathyroidism (SHPT) leads to cardiovascular calcification, which affects survival and quality of life in patients with chronic kidney disease. Cinacalcet is used to control SHPT, but it may induce gastrointestinal symptoms, resulting in lower adherence and insufficient dosages. Therefore, a need exists to develop new calcimimetics that cause fewer gastrointestinal symptoms. Here we conducted a phase 3, randomized, double-blind, double-dummy trial for a head-to-head comparison of the efficacy and safety of evocalcet, a new oral calcimimetic, to the established cinacalcet. Japanese patients with SHPT on hemodialysis were randomized to receive evocalcet or cinacalcet (317 patients each) for 30 weeks. The primary efficacy endpoint was non-inferiority of evocalcet to cinacalcet in the proportion of patients achieving a mean intact parathyroid hormone level of 60 to 240 pg/mL from week 28 to 30 (non-inferiority margin,-15%, per protocol set analyses). In the evocalcet and cinacalcet groups, 72.7% and 76.7%, respectively, achieved the target intact parathyroid hormone level (between-group difference:-4.0% [95% confidence interval-11.4%, 3.5%], for non-inferiority). The incidence of gastrointestinal-related adverse events was 18.6% and 32.8%, respectively (between-group difference:-14.2% [-20.9%,-7.5%], significant for superiority). Thus, the non-inferiority of evocalcet to cinacalcet in suppressing intact parathyroid hormone with fewer gastrointestinal-related adverse events was demonstrated. Hence, evocalcet may be a favorable alternative to existing calcimimetics for management of SHPT.

Abstract 10756: Chronic Kidney Disease in Long-term Survivors After Fontan Palliation

Background: The Fontan operation is a palliative procedure for children with congenital single ventricle heart disease. With advances in prenatal diagnosis and surgical techniques, more children are surviving into adulthood with unique cardiovascular physiology. Little is currently known about long-term kidney function in these patients. Hypothesis: We hypothesize that long-term survivors after Fontan palliation will have a higher prevalence of chronic kidney disease (CKD) compared to healthy controls. Methods: We performed a retrospective cohort study of subjects evaluated through the Single Ventricle Survivorship Program (SVSP) at the Children’s Hospital of Philadelphia between July 1, 2010 and December 5, 2014 and healthy children similar in sex and age. The primary outcome was CKD, defined as eGFR <90 ml/min/1.73m2 calculated with age-appropriate estimating equations using creatinine and cystatin C. Secondary outcomes included proteinuria and hyperparathyroidism. Results: The Fontan cohort included 68 subjects with mean age of 13.9 years (SD 5.8) at SVSP visit who were 11.2 years (SD 5.7) from Fontan operation. The healthy cohort included 70 patients with mean age of 15.9 years (SD 3.9). Mean eGFR was 102.6 versus 101.9ml/min/1.73m2 (p=0.89) in pediatric Fontan versus healthy subjects using the complete CKiD equation, and 128.5 versus 129.7ml/min/1.73m2 (p=0.56) in adult Fontan versus healthy subjects using the CKD-EPI creatinine and cystatin formula. 10% of Fontan subjects had an eGFR<90 ml/min/1.73m2. Mean intact parathyroid hormone level was higher at 68.0pg/mL (SD 35.4) in the Fontan group compared to 26.0pg/mL (SD 13.6) in the healthy group. Proteinuria was found within 34% of the Fontan group compared to 4.6% within the control group. Conclusion: We found that 10% of subjects have eGFR <90ml/min/1.73m2 after Fontan palliation which would indicate CKD if this remained persistent over time. Although the majority of the cohort had normal kidney function by eGFR, we found a higher proportion with proteinuria and increased parathyroid hormone levels which may indicate early kidney disease. Future studies will focus on evaluating changes in kidney function over time in long-term survivors after Fontan palliation.

Vitamin D Deficiency and Seasonal and Inter-day Variation in Circulating 25-hydroxyvitamin D and Parathyroid Hormone Levels in Indoor Daytime Workers: A Longitudinal Study

Seasonal variation in circulating 25-hydroxyvitamin D (25OHD) levels related to seasonal and inter-day fluctuation in sunlight ultraviolet irradiation, may lead to misjudgments concerning 25OHD status in individual workers around threshold levels. Here, to examine seasonal and inter-day variations in plasma 25OHD, we conducted a longitudinal study involving indoor daytime workers. Subjects were four male indoor daytime workers aged 32-57 yr working in Kawasaki City, Japan. Blood samples were obtained on six days within two two-week periods in February and October, 2008. Plasma 25OHD, serum intact parathyroid hormone (PTH) and 1α,25-dihydroxyvitamin D [1α,25(OH)(2)D] were measured. Individual monthly mean 25OHD levels were 16-56% higher in October than in February (p=0.03), while individual monthly mean intact PTH levels were 15-41% lower in October (p=0.09). No seasonal change was observed in 1α,25(OH)(2)D (p=0.62). Notably, nearly all measured 25OHD levels in February were lower than the reference value of 20 ng/ml. Our study identified the occurrence of seasonal variation in circulating 25OHD and intact PTH levels, even after accounting for inter-day variability, and hypovitaminosis D in wintertime in indoor daytime male workers in Japan. Due to this variability, single spot measurements of 25OHD may lead to misjudgment of workers' vitamin D status.

Hypovitaminosis D and Bone Mineral Density in Human Immunodeficiency Virus-Infected Men from India, with or without Antiretroviral Therapy

To study the vitamin D status and bone mineral density (BMD) in men infected with human immunodeficiency virus (HIV) in a tertiary care center from southern India. We conducted a cross-sectional study of 35 HIV-infected men (between 20 and 50 years old) receiving highly active antiretroviral therapy (HAART) (group 1) in comparison with 35 age- and body mass index-matched HIV-positive antiretroviral therapy-naïve men (group 2) and 35 HIV-negative healthy control subjects (group 3). A significantly greater proportion (P = .002) of patients (74%) in the HAART group had vitamin D deficiency (<20 ng/mL) in comparison with the other 2 groups (37% in each group). The mean intact parathyroid hormone level was higher (P<.001) and the mean duration of exposure to sunlight was lower (P = .001) in the HAART group than in the other 2 groups. By logistic regression analysis, HAART was found to be significantly associated with vitamin D deficiency. The BMD in the femoral neck was significantly lower in men with HIV infection who were receiving HAART in comparison with the other 2 groups (P = .006). On multivariate logistic regression, older age, low body mass index, and high parathyroid hormone levels emerged as factors significantly associated with decreased BMD at the femoral neck. A significant proportion of patients receiving HAART had vitamin D deficiency. The secondary hyperparathyroidism probably due to vitamin D deficiency is an important contributing factor for the observed changes in BMD. Vitamin D deficiency noted in this group is probably multifactorial, and further research is needed to determine whether the effect of HAART on vitamin D metabolism is an additional causative factor and what benefit vitamin D supplementation might confer in these patients.

CHANGES IN THE SERUM BONE METABOLISM MARKERS OF ELDERLY ALCOHOLICS DURING ABSTINENCE

CHANGES IN THE SERUM BONE METABOLISM MARKERS OF ELDERLY ALCOHOLICS DURING ABSTINENCE

Coronary Artery Calcification in Patients with Primary Hyperparathyroidism in Comparison with Control Subjects from the Multi-Ethnic Study of Atherosclerosis

To determine whether coronary artery calcification (CAC) is increased in patients with primary hyperparathyroidism (pHPT) because of the presence of hypercalcemia, which has been shown in vitro to promote vascular calcification. Electron beam computed tomography of the coronary arteries was performed on 20 patients with pHPT referred to our endocrinology clinic for evaluation of hypercalcemia. All patients were nonsmokers, with normal renal function, no history of diabetes, and no history of coronary artery disease. CAC in the patients with pHPT was compared with that in population-based control subjects from the Multi-Ethnic Study of Atherosclerosis (MESA). Two methods of analysis were used: (1) calculation of the odds ratio of CAC and (2) a nested case-control (1:4) study. One patient with pHPT had a history of nephrolithiasis; the other 19 patients were asymptomatic. The mean age (+/- SD) of the patients with pHPT was 57.3 +/- 9.1 years, the mean serum calcium concentration was 2.68 +/- 0.18 mmol/L, and the mean intact parathyroid hormone level was 119 +/- 76.5 pg/mL. Of the 20 patients, 14 had CAC scores of zero. The odds ratio for measurable CAC in the presence of pHPT in comparison with that in the MESA control subjects was 0.17, which was not significant. In the matched analysis, the CAC scores for the patients with pHPT did not differ significantly from those for the MESA control subjects (P = 0.25 with use of the Wilcoxon test). We found no evidence for a difference in CAC in patients with pHPT in comparison with the population-based control subjects in this small pilot study.

Preoperative Evaluation of Thyroid Pathology in Patients with Primary Hyperparathyroidism

In parathyroidectomy, it has been recognized that a shift to a minimally invasive procedure may be accompanied by a possibility of missing thyroid pathology. However, only a few findings concerning preoperative thyroid evaluation have been reported. We investigated the prevalence of concomitant thyroid pathology by preoperative neck ultrasonography (US) in patients with primary hyperparathyroidism. There were 85 patients (66 women, 19 men; mean age 57 years) in the study group. The mean preoperative calcium level was 11.2mg/dL, and the mean intact parathyroid hormone level was 206 pg/mL. All patients underwent neck US following fine-needle aspiration biopsy (FNAB). Of the 85 patients, 21 (24.7%) had thyroid nodules. Among 21 patients with thyroid nodules, 9 (10.6%) had malignant thyroid tumors, while 12 (14.1%) patients had benign thyroid nodules including multinodular goiter. Of the 9 patients with malignant thyroid nodules, 4 had papillary carcinomas with lymph node metastases. The prevalence of thyroid disease associated with hyperparathyroidism is high, and evaluation of the thyroid pathology by US enables the shift from bilateral neck exploration to the minimally invasive parathyroid surgery.

Tertiary hyperparathyroidism: histologic patterns of disease and results of parathyroidectomy.

Patients with tertiary hyperparathyroidism (THPT) commonly have parathyroid hyperplasia and should have a bilateral neck exploration with subtotal or total parathyroidectomy with autotransplantation to obtain long-term cure. A retrospective cohort study. Tertiary referral medical center. Thirty-four consecutive patients (21 women and 13 men; mean age, 48 years) who underwent neck exploration for THPT. Sites and histologic pattern of parathyroid disease, and postoperative normalization of serum calcium and parathyroid hormone levels. Twenty-seven patients underwent initial bilateral neck exploration and 7 patients underwent repeat neck exploration for persistent or recurrent THPT. The mean serum total calcium level was 11.2 mg/dL (2.8 mmol/L) (range, 10.3-13.5 mg/dL [2.6-3.4 mmol/L]) and the mean intact parathyroid hormone level was 355 ng/L (range, 95-1236 ng/L). The THPT was due to 4-gland hyperplasia in 33 patients and a single adenoma in only 1 patient. The parathyroid glands were in the normal position in 23 patients and in ectopic locations in 11 patients (8 intrathymic, 1 carotid sheath, 1 tracheoesophageal groove, and 1 intramuscular). Preoperative localizing studies did not identify ectopic or supernumerary glands in any of the patients (ultrasonography, 14 patients; technetium Tc 99m sestamibi, 15; and magnetic resonance imaging, 7). Persistent (n = 5) and recurrent (n = 2) THPT was more common in patients who had an initial 1- or 2-gland excision instead of subtotal or total parathyroidectomy with autotransplantation (P<.001). Four patients had transient hypocalcemia (<8.0 mg/dL [<2.0 mmol/L]), and no other permanent complications or deaths occurred. Biochemical cure was achieved in 94% of patients with a mean follow-up of 4.8 years. Tertiary hyperparathyroidism is usually due to multiple hyperplastic parathyroid glands, and patients who have initial limited parathyroidectomy have a higher risk of persistent or recurrent THPT.

Vitamin D and calcium dysregulation in the polycystic ovarian syndrome

Over the past 30 years, numerous studies in invertebrates and vertebrates have established a role of calcium in oocyte maturation as well as in the resumption and progression of follicular development. Polycystic ovarian syndrome (PCO) is characterized by hyperandrogenic chronic anovulation, theca cell hyperplasia, and arrested follicular development. The aim of this observational study was to determine whether vitamin D and calcium dysregulation contribute to the development of follicular arrest in women with PCO, resulting in reproductive and menstrual dysfunction. Thirteen premenopausal women (mean age 31 ± 7.9 years) with documented chronic anovulation and hyperandrogenism were evaluated. Four women were amenorrheic and nine had a history oligomenorrhea, two of whom had dysfunctional bleeding. Nine had abnormal pelvic sonograms with multiple ovarian follicular cysts. All were hirsute, two had alopecia, and five had acanthosis nigricans. The mean 25 hydrovitamin D was 11.2 ± 6.9 ng/ml [normal (nl): 9–52], and the mean 1,25 dihydroxyvitamin D was 45.8 ± 18 pg/ml, with one woman with a 1,25 dihydroxyvitamin D <5 pg/ml (nl: 15–60). The mean intact parathyroid hormone level was 47 ± 19 pg/ml (nl: 10–65), with five women with abnormally elevated parathyroid hormone levels. All were normocalcemic (9.3 ± 0.4 mg/dl). Vitamin D repletion with calcium therapy resulted in normalized menstrual cycles within 2 months for seven women, with two experiencing resolution of their dysfunctional bleeding. Two became pregnant, and the other four patients maintained normal menstrual cycles. These data suggest that abnormalities in calcium homeostasis may be responsible, in part, for the arrested follicular development in women with PCO and may contribute to the pathogenesis of PCO.

A prospective study of calcium metabolism in exertional heat stroke with rhabdomyolysis and acute renal failure.

Intensive training in a humid and warm environment can cause exertional heat stroke (ExHS) and rhabdomolysis (RBD) in military recruits. To investigate the role of vitamin D and monomeric calcitonin (CT) on the calcium metabolism in ExHS with RBD and acute renal failure (ARF), we studied 21 recruits with ExHS (mean age 21.4 years), 7 of which had ARF. Another 11 age-matched recruits with heat exhaustion (HE) and 11 healthy subjects were selected as controls. Our results showed that in 14 ExHS patients without ARF, mean serum creatinine (Cr) levels were significantly higher (151.16 vs. 106.08 mumol/l, p < 0.01), whereas serum osteocalcin (OC) levels were significantly lower (2.22 vs. 4.65 micrograms/l, p < 0.01) than in healthy controls. In 7 patients with ExHS and ARF, the mean serum Cr (774.38 vs. 105.20 mumol/l, p < 0.01), phosphorus (P) (2.26 vs. 1.26 mmol/l, p < 0.05), creatine phosphokinase (CPK) 274,143.97 vs. 85.78 IU/l, p < 0.05), intact parathyroid hormone (I-PTH) (299.81 vs. 18.66 ng/l, p < 0.05) and CT (13.58 vs. 6.63 ng/l, p < 0.01) levels on admission were significantly higher while the mean ionized calcium (iCa) levels were significantly lower than the healthy controls (0.9 vs. 1.18 mmol/l, p < 0.01). The mean serum 25-hydroxyvitamin D [25(OH)D] levels were not significantly different from healthy controls. However, mean serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels and the ratio of 1,25(OH)2D to 25(OH)D were significantly lower than healthy controls throughout the whole course of ARF. None of the 7 patients with ExHS and ARF developed hypercalcemia during the diuretic phase. Their mean serum I-PTH levels decreased significantly from 299 to 18 ng/l during the recovery phase (p < 0.05). Our study seems to suggest that the abnormal calcium metabolism in this unique patient group is in part caused by persistently decreased renal production of 1,25(OH)2D, although increased monomeric CT levels were associated with hypocalcemia. However, whether or not a causal relationship exists merits further investigation.