Lower Parathyroid Hormone Concentrations Research Articles

7337 High Parathyroid Hormone (PTH) Due To Immunoassay Interference

Abstract Disclosure: V.A. Mendpara: None. A.J. McShane: None. L.Z. Khan: None. Background: PTH levels are not always accurate. This case illustrates immunoassay interference in a female with markedly abnormal PTH values. Understanding immunoassay interference in diverse hormonal assessments can prevent diagnostic inaccuracies. Clinical Case: A 63-year-old female with osteopenia underwent serum parathyroid hormone (PTH) testing as part of a thorough bone evaluation. The initial PTH level revealed an abnormal level of 4008 pg/mL (normal range: 15 to 65 pg/mL). The follow-up PTH level with the same assay continued to result in elevated values of >5000 pg/mL. The medication list was negative for biotin use, which is a well-known interfering substance in the PTH assay. Clinical evaluation was negative for hyperparathyroidism symptoms, and thyroid/parathyroid ultrasound was normal, as were serum levels of phosphate, vitamin D, and calcium. No PTH values had been checked for patients in the past after an extensive review of prior records. The initial PTH testing used the Roche Elecsys PTH STAT assay. To investigate a potential immunoassay interference, the following studies were performed: First, the sample was diluted with polyethylene glycol (PEG) to precipitate large molecular weight proteins; second, the sample was treated with a commercial heterophilic blocking reagent (Scantibodies Laboratory); and lastly, the sample was assayed utilizing a different PTH vendor (Siemens Atellica, chemiluminescent immunoassay). The PEG and heterophilic blocking treatments resulted in significantly lower PTH concentrations of 895.6 and 40.7 pg/mL, respectively. We do not anticipate a change in PTH levels in samples supplemented with blocking reagents or PEG without interference. The result from Siemens’ assay was markedly lower at 43.4 pg/mL. Both the Siemens and Roche assays employ mouse antibodies; however, the antibodies are proprietary between the vendors. This results in potentially different anti-mouse antibody epitope targets. Due to a history of advanced ovarian cancer, the patient was taking Oregovomab, a murine monoclonal antibody, as therapy for her advanced disease. It is unclear if this medication resulted in assay interference, but it is possible. Discussion: In summary, the discrepancy in PTH assay results highlights the need to consider immunoassay interference, particularly in patients with a history of cancer on immunotherapy agents. Our case highlights the importance of the clinician’s review of medications when assessing patients. While prior PTH assays were not conducted before the patient started Oregovomab, the potential development of interfering antibodies warrants consideration. Clinicians should be vigilant for atypical results and collaborate closely with laboratory professionals, as detecting interfering substances can result in misdiagnosis. Presentation: 6/2/2024

No Impairment in Bone Turnover or Executive Functions in Well-Treated Preschoolers with Phenylketonuria-A Pilot Study.

Patients with phenylketonuria (PKU) present signs of impaired executive functioning and bone health in adolescence and adulthood, depending in part on the success of therapy in childhood. Therefore, nine children with well-treated PKU (4-7 years old, 22.2% ♀, seven with a full set of data, two included into partial analysis) and 18 age-, gender- and season-matched controls were analyzed for differences in executive functioning and bone parameters in plasma. Plasma was analyzed with commercially available kits. Cognitive performance in tonic alertness, visuo-spatial working memory, inhibitory control and task switching was assessed by a task battery presented on a touch screen. Regarding cognition, only the performance in incongruent conditions in inhibitory control was significantly better in children with PKU than in controls. No further differences in cognitive tests were detected. Furthermore, no significant difference in the bone turnover markers osteocalcin, undercarboxylated osteocalcin and CTX were detected between children with PKU and controls, while children with PKU had a significantly higher vitamin D concentration (69.44 ± 12.83 nmol/L vs. 41.87 ± 15.99 nmol/L, p < 0.001) and trended towards lower parathyroid hormone concentrations than controls (48.27 ± 15.16 pg/mL vs. 70.61 ± 30.53 pg/mL, p = 0.066). In this small group of well-treated preschoolers with PKU, no impairments in cognitive performance and bone turnover were observed, while vitamin D supplementation of amino acid supplements seems to be sufficient to achieve good vitamin D status.

Severe hypocalcemia, an atypical presentation after thyroid cancer surgery, about a case

Hypoparathyroidism, secondary to postoperative thyroid cancer, is characterized by hypocalcemia, hyperphosphatemia, and hypercalciuria due to low concentrations of parathyroid hormone. The prevalence in the United States is 23 to 37 cases/100,000 people/year. Complications develop in 78 % of cases after cervical surgery; 75 % resolve spontaneously in the first 6 months, while the remaining 25 % resolve permanently; no incidence data were obtained in Bolivia. Treatment requires long-term oral calcium with citrate, calcium carbonate, and vitamin D analogs (calcitriol and alfacalcidol); in complex cases, calcium can be used intravenously (calcium gluconate); Some patients do not respond to standard treatment. In this way, the unusual clinical case of a 38-year-old male patient with a history of papillary thyroid carcinoma, post-total thyroidectomy, with a clinical picture of 48 hours of evolution characterized by pain at the cervical level, associated with a Trosseau sign, is presented. (+) and frank signs of respiratory distress with laryngeal spasm, which required management in the intensive care unit (ICU), correction of severe hypocalcemia, with calcium gluconate IV and calcium plus vitamin D PO; presenting an optimal evolution, graduating on the fourth day; He was subsequently discharged from the hospital two weeks later in good general condition.

Uremic xerosis among patients on maintenance hemodialysis: Prevalence and correlation with clinical and laboratory markers

Xerosis, characterized by dry skin, is a frequent manifestation in patients undergoing maintenance hemodialysis. Understanding the prevalence of xerosis in this population and exploring its associations with various clinical and laboratory parameters is crucial for comprehensive patient care. The present study aimed to estimate the prevalence of xerosis in patients undergoing maintenance hemodialysis and to investigate the association between xerosis and various clinical and laboratory parameters, with a specific focus on serum copeptin as a surrogate for antidiuretic hormone.&#x0D; Methods. This cross-sectional observational study was conducted at the Hemodialysis Clinic of the Basrah Nephrology and Transplantation Center from March 1, 2022, to September 1, 2022. The prevalence of xerosis and its correlation with clinical characteristics and serum copeptin status were analyzed.&#x0D; Results. The study findings indicate that among the 48 patients undergoing maintenance hemodialysis, with an average age of 59.8 ± 8.8 years, 60.4% presented with xerosis. Serum copeptin levels, measuring 3.8 ± 2 ng/mL, showed a significant association with diuretic usage and serum parathyroid hormone (PTH) (p &lt; 0.001 and p = 0.031, respectively). Notably, no correlations were observed with other demographic or laboratory parameters, despite the tendency of serum copeptin levels to be higher in females and patients with low serum albumin and PTH concentrations.&#x0D; Conclusions. In summary, xerosis was prevalent in 60.4% of patients undergoing maintenance hemodialysis and demonstrated a positive correlation with diuretic use and serum PTH levels.

A Rapid Intraoperative Parathyroid Hormone Assay Based on the Immune Colloidal Gold Technique for Parathyroid Identification in Thyroid Surgery.

ObjectiveA novel immunochromatographic test strip method was developed to detect tissue parathyroid hormone (PTH) using the immune colloidal gold technique (ICGT). The accuracy and application value of this method for intraoperative parathyroid identification were evaluated.MethodsSerum samples were collected to measure PTH by both ICGT and electrochemiluminescence immunoassay (ECLIA). Patients who underwent unilateral and total thyroidectomy were enrolled to evaluate the feasibility and clinical efficacy of rapid intraoperative identification of parathyroid glands via PTH determination using ICGT. Two sample preparation methods, fine needle aspiration (FNA) and tissue block homogenate (TBH), were used for PTH-ICGT analysis.ResultsBablok analysis showed a linear relationship between the serum PTH measurements obtained by ICGT and ECLIA. Non-parathyroid tissues had much lower PTH concentrations (14.8 ± 2.1 pg/ml, n = 97) detected by ICGT, compared to the parathyroid gland tissues (955.3 ± 16.1 pg/ml, n = 79; P < 0.0001), With biopsy results as the standard, ICGT showed higher diagnosis rates as compared with direct visual inspection, for identifying both parathyroid glands (97.4 vs. 78.2%) and non-parathyroid tissues (100 vs. 68.9%). The cut-off values for parathyroid identification by FNA and TBH methods were 63.99 and 136.30 pg/ml, respectively. The detection time was 2 min by TBH method for in vitro tissue detection and 6 min by FNA method for in situ tissue detection, both of which were faster than traditional intraoperative cryopathological examination (usually >30 min). Intraoperative application of ICGT method was associated with higher postoperative serum calcium and blood PTH levels at 1 and 3 months as well as a lower incidence of postoperative transient hypocalcemia, as compared with direct visual inspection.ConclusionPTH-ICGT assay shows high potential as a rapid, novel alternative for intraoperative parathyroid identification.

Associations between Osteocalcin, Calciotropic Hormones, and Energy Metabolism in a Cohort of Chinese Postmenopausal Women: Peking Vertebral Fracture Study

Objective The endocrine function of bone in energy metabolism may be mediated by the osteocalcin (OC). We examined the association between OC and energy metabolism among Chinese postmenopausal women. Design and Setting. A cross-sectional cohort study enrolling 1635 participants was conducted using data from the Peking Vertebral Fracture study. Partial correlation analysis was performed to explore the correlation of OC, parathyroid hormone (PTH), or 25-hydroxyvitamin D (25(OH)D) with glycemic and lipid metabolic parameters. A logistic regression model was used to investigate the association of OC, PTH, or 25(OH)D with the prevalence of diabetes and dyslipidemia. Results Serum levels of OC, PTH, and 25(OH)D were all positively correlated with serum cholesterol levels, whereas only OC was negatively associated with serum glucose level. In the logistic regression model, both OC and PTH were negatively associated with the prevalence of diabetes (odds ratio [OR], 95% confidence interval [95% CI]: 0.967, 0.948–0.986 for OC and 0.986, 0.978–0.994 for PTH). No significant association was found between 25(OH)D and diabetes. Both OC and 25(OH)D, rather than PTH, were associated with abnormalities of high cholesterol levels, such as hypercholesterolemia and high LDL-C levels. Further classifying the population based on the median value of OC and PTH, low OC and low PTH subgroup had the highest OR, 95% CI for diabetes (1.873, 1.287–2.737) and the lowest OR, 95% CI for hypercholesterolemia (0.472, 0.324–0.688) and for high LDL-C (0.538, 0.376–0.771). Conclusion Among Chinese postmenopausal women, a lower serum level of OC was associated with a higher prevalence of diabetes and lower serum cholesterol levels, and a low PTH concentration could magnify these associations.

Establish pre-clinical diagnostic efficacy for parathyroid hormone as a point-of-surgery-testing-device (POST)

Measuring the Parathyroid hormone (PTH) levels assists in the investigation and management of patients with parathyroid disorders. Rapid PTH monitoring is a valid tool for accurate assessment intraoperatively. Rapid Electro-Analytical Device (READ) is a point-of-care device that uses impedance change between target and capture probe to assess the PTH concentration in undiluted patient plasma samples. The aim of this work focuses on evaluating the analytical performance of READ platform to Roche analyzer as a prospective clinical validation method. The coefficient of variation (CV) for intra-assay imprecision was < 5% and inter-assay imprecision CV was < 10% for high (942 pg/mL) and low (38.2 pg/mL) PTH concentration. Functional sensitivity defined at 15% CV was 1.9 pg/mL. Results obtained from READ platform correlated well (r = 0.99) with commercially available clinical laboratory method (Roche Diagnostics) to measure PTH concentrations with a turn-around time of less than 15 min. Furthermore, the mean bias of 7.6 pg/mL determined by Bland–Altman analysis, showed good agreement between the two methods. We envision such a sensing system would allow medical practitioners to facilitate targeted interventions, thereby, offering an immediate prognostic approach as the cornerstone to delivering successful treatment for patients suffering from primary hyperparathyroidism.

Permanent postoperative hypoparathyroidism: an analysis of prevalence and predictive factors for adequacy of control in a cohort of 260 patients.

Recent guidelines for the treatment of hypoparathyroidism emphasize the need for long-term disease control, avoiding symptoms and hypocalcaemia. Our aim has been to analyze the prevalence of poor disease control in a national cohort of patients with hypoparathyroidism, as well as to evaluate predictive variables of inadequate disease control. From a nation-wide observational study including a cohort of 1792 patients undergoing total thyroidectomy, we selected 260 subjects [207 women and 53 men, aged (mean ± SD) 47.2±14.8 years] diagnosed with permanent hypoparathyroidism. In every patient demographic data and details on surgical procedure, histopathology, calcium (Ca) metabolism, and therapy with Ca and calcitriol were retrospectively collected. A patient was considered not adequately controlled (NAC) if presented symptoms of hypocalcemia or biochemical data showing low serum Ca levels or high urinary Ca excretion. Two hundred and twenty-one (85.0%) patients were adequately controlled (AC) and 39 (15.0%) were NAC. Comparison between AC and NAC patients did not show any significant difference in demographic, surgical, and pathological features. Rate of hospitalization during follow-up was significantly higher among NAC patients in comparison with AC patients (35.9% vs. 10.9%, P<0.001). Dose of oral Ca and calcitriol were also significantly higher in NAC subjects. In a subgroup of 129 patients with serum parathyroid hormone (PTH) levels available, we found that NAC patients exhibited significantly lower postoperative PTH concentrations than AC patients [median (interquartile range) 3 (1.9-7.8) vs. 6.9 (3.0-11) pg/mL; P=0.009]. In a nation-wide cohort of 260 subjects with definitive hypoparathyroidism, 15% of them had poor disease control. These patients required higher doses of oral Ca and calcitriol, had higher rate of hospitalization during follow-up and showed lower PTH concentrations in the postoperative period.

Race, Ancestry, and Vitamin D Metabolism: The Multi-Ethnic Study of Atherosclerosis.

A comprehensive characterization of racial/ethnic variations in vitamin D metabolism markers may improve our understanding of differences in bone and mineral homeostasis and the risk of vitamin D-related diseases. Describe racial/ethnic differences in vitamin D metabolism markers and their associations with genetic ancestry. In a cross-sectional study within the Multi-Ethnic Study of Atherosclerosis (MESA), we compared a comprehensive panel of vitamin D metabolism markers across self-reported racial/ethnic groups of Black (N = 1759), White (N = 2507), Chinese (N = 788), and Hispanic (N = 1411). We evaluated associations of proportion African and European ancestry with this panel of markers in Black and Hispanic participants using ancestry informative markers. Latent class analysis evaluated associations between patterns of vitamin D measurements with race/ethnicity. Compared with Black participants, White participants had significantly higher serum concentrations of 25-hydroxyvitamin D and fibroblast growth factor-23; lower concentrations of parathyroid hormone and 1,25-dihydroxyvitamin D; circulating vitamin D metabolite ratios suggesting lower CYP27B1 and higher CYP24A1 activity; higher urinary concentrations of calcium and phosphorus with higher urinary fractional excretion of phosphorus; and differences in vitamin D binding globulin haplotypes. Higher percent European ancestry was associated with higher 25-hydroxyvitamin D and lower parathyroid hormone concentrations among Black and Hispanic participants. Latent classes defined by vitamin D measurements reflected these patterns and differed significantly by race/ethnicity and ancestry. Markers of vitamin D metabolism vary significantly by race/ethnicity, may serve to maintain bone and mineral homeostasis across ranges of 25-hydroxyvitamin D production, and be attributable, at least partly, to genetic ancestry.

SAT-LB71 Is Late Diagnosis of Postsurgical Hypoparathyroidism the Rule, Not the Exception?

Background The most prevalent etiology for hypoparathyroidism is postsurgical. In the literature, years or even decades of delay for the diagnosis have been reported, with sometimes extremely low calcium levels and dramatic clinical manifestations including heart failure and seizures requiring treatment in the emergency room or intensive care unit. Often,,typical“ hypocalcemic symptoms are absent in these patients. Methods In this retrospective Austrian single-center cohort at the Medical University of Graz, we identified patients with low parathyroid hormone concentration (<25 pg/ml) and hypocalcemia using the hospital information system during 2004 and 2014. The time between neck surgery and the first reported diagnosis of postsurgical hypoparathyroidism and/or available low calcium levels was collected. Results We identified a total of 119 patients treated between 2004 and 2014 at our institution. Most patients were women (78%), the average age was 61 ± 17 years. 12% had nonsurgical etiologies (ie. AIRE or 22q11 mutations), and 88% had postsurgical hypoparathyroidism (n=105). The median time between surgery and diagnosis of hypoparathyroidism was 5.5 years (range 0 -67 years). Only a third of all patients was diagnosed within the first year after surgery. Paresthesia and tetany were present in most patients at diagnosis, but in extreme hypocalcemia, other,,non-classic“ symptoms including severe heart failure, dyspnea and seizures appeared to be more prevalent. Conclusion Our data suggest that diagnosis of permanent postoperative hypoparathyroidism is often delayed, as in our Austrian retrospective cohort the time lag between surgery and diagnosis or onset of hypoparathyroidism was often years or even decades. Whether this is truly a delayed occurrence of the disease or a delayed diagnosis of a condition already present for years or a combination of both can not be answered with our data, but certainly merits more intense research in the future.

C-terminal telopeptide of type I collagen, osteocalcin, alkaline phosphatase, and parathyroid hormone in healthy and hospitalized foals

Hypocalcemia is a common finding in critically ill equine patients. Parathyroid hormone (PTH) helps to maintain calcium homeostasis in hypocalcemic patients by promoting renal calcium reabsorption and bone resorption. Increased serum PTH concentrations have been reported in critically ill people and animals, including horses and foals. It is unknown whether increased secretion of PTH is associated with markers of bone turnover in hospitalized foals. The goals of this study were to measure markers of bone resorption (C-terminal telopeptide of type I collagen [CTX-I]) and bone formation (osteocalcin [OCN]; alkaline phosphatase [ALP]) and to determine their association with PTH concentrations, disease severity, and mortality in hospitalized foals. This prospective, multicenter, cross-sectional study was conducted on 75 newborn foals ≤3 d old divided into hospitalized (n = 65; 41 septic; 24 sick nonseptic) and healthy (n = 10) groups. Blood samples were collected on admission to measure serum CTX-I, OCN, and PTH concentrations and ALP activity. Data were analyzed by nonparametric methods and univariate logistic regression. Serum CTX-I and PTH concentrations were significantly higher, whereas OCN concentrations were lower, in septic compared with healthy foals (P < 0.05). Serum ALP activity was not different between groups; however, it was lower in hospitalized and septic foals with low OCN concentrations (P < 0.05). In hospitalized foals, PTH concentrations were positively correlated with CTX-I concentrations and inversely associated with ALP activity (P < 0.05). High CTX-I and low OCN concentrations were associated with disease severity (P < 0.05). Hospitalized nonsurviving foals had significantly lower OCN concentrations compared with survivors (P < 0.05), but CTX-I concentrations were not associated with survival. Hospitalized foals with PTH concentrations >12.4 pmol/L were more likely to die (OR = 1.5; 95% CI = 1.1–4.16; P < 0.05). Elevated PTH and CTX-I together with reduced OCN concentrations and ALP activity in sick foals indicates that bone resorption is increased during critical illness, which may be a compensatory mechanism to correct hypocalcemia or reflect a response to systemic inflammation and metabolic imbalances. Bone resorption could negatively impact skeletal development in the growing foal. Low OCN and high PTH concentrations were predictors of nonsurvival in hospitalized foals.

MON-525 Cardiovascular Status in Chronic Hypoparathyroidism: A Prospective Single-Center Analysis in 143 Patients

Introduction: Chronic hypoparathyroidism (HPT) is characterized by low concentrations of parathyroid hormone (PTH) resulting in low calcium and high phosphate levels. Even though it is well known that long-term complications such as renal insufficiency, nephrocalcinosis and brain calcifications can occur in HPT, the risk of cardiovascular diseases still remains unclear. Objective: To perform a systematic assessment of cardiovascular function and long-term complications in a well characterized cohort of patients with HPT. Methods: 143 patients with chronic HPT (disease duration >6 months) were included and systematically examined regarding comorbidities as well as cardiovascular events. Participants were assessed by electrocardiogram, renal ultrasound, 24-hour blood pressure measurement and laboratory analysis. Results: Out of 143 patients (56±13yr, 76% female) 90% had postoperative HPT. 94% received treatment with calcium and/or activated vitamin D. Albumin-corrected serum calcium was below <2.0 mmol/l in 31% of patients. Prevalence of any of the following cardiovascular diseases: coronary heart disease, angina pectoris, myocardial infarction, heart failure, atrial fibrillation was 11%. 52% of patients with HPT had a history of hypertension. Mean blood pressure during 24-hour measurement (n=108) was at 130±17/80±12 mmHg. No significant differences in prevalence of hypertension (57% vs. 41%), 24 hour blood pressure (130±15/80±8 vs. 130±13/81±8 mmHg), or levels of NT-proBNP (n=101; 73, IQR 113 vs. 76, IQR 92 pg/ml) between normo- and hypocalcemic patients could be detected. QT-interval (n=131) was significantly prolonged in hypocalcemic patients (441±35 vs. 415±29 ms, p<0.001). Regarding further comorbidities 12% reported a history of kidney stones, 3.6% had nephrocalcinosis in renal ultrasound, 21% had a glomerular filtration rate lower than 60 ml/min/1,73m2 and 13% suffered from cataract. Conclusion: Here we report a high prevalence of hypertension in patients with HPT independend of their calcium levels. However, further comparison to the general German population, as well as prospective evaluation of cardiovascular events is needed to further establish the relevance of cardiovascular comorbidities in HPT.

Effects of vitamin D supplementation on markers for cardiovascular disease and type 2 diabetes: an individual participant data meta-analysis of randomized controlled trials

Evidence from randomized controlled trials (RCTs) for the causal role of vitamin D on noncommunicable disease outcomes is inconclusive. The aim of this study was to investigate whether there are beneficial or harmful effects of cholecalciferol (vitamin D3) supplementation according to subgroups of remeasured serum 25-hydroxyvitamin D [25(OH)D] on cardiovascular and glucometabolic surrogate markers with the use of individual participant data (IPD) meta-analysis of RCTs. Twelve RCTs (16 wk to 1 y of follow-up) were included. For standardization, 25(OH)D concentrations for all participants (n=2994) at baseline and postintervention were re-measured in bio-banked serum samples with the use of a certified liquid chromatography-tandem mass spectrometry method traceable to a reference measurement procedure. IPD meta-analyses were performed according to subgroups of remeasured 25(OH)D. Main outcomes were blood pressure and glycated hemoglobin (HbA1c). Secondary outcomes were LDL, HDL, and total cholesterol and triglycerides; parathyroid hormone (PTH); fasting glucose, insulin, and C-peptide; and 2-h glucose. In secondary analyses, other potential effect modifiers were studied. Remeasurement of 25(OH)D resulted in a lower mean 25(OH)D concentration in 10 of 12 RCTs. Vitamin D supplementation had no effect on the main outcomes of blood pressure and HbA1c. Supplementation resulted in 10-20% lower PTH concentrations, irrespective of the 25(OH)D subgroups. The subgroup analyses according to achieved 25(OH)D concentrations showed a significant decrease in LDL-cholesterol concentrations after vitamin D supplementation in 25(OH)D subgroups with <75, <100, and <125nmol of -0.10 mmol/L (95% CI: -0.20, -0.00 mmol/L), -0.10 mmol/L (95% CI: -0.18, -0.02 mmol/L), and -0.07 mmol/L (95% CI: -0.14, -0.00 mmol/L), respectively. Patient features that modified the treatment effect could not be identified. For the main outcomes of blood pressure and HbA1c, the data support no benefit for vitamin D supplementation. For the secondary outcomes, in addition to its effect on PTH, we observed indications for a beneficial effect of vitamin D supplementation only on LDL cholesterol, which warrants further investigation. This trial was registered at www.clinicaltrials.gov as NCT02551835.

Parathyroid Hormone is Related to Dysplasia and a Higher Rate of Distal Colorectal Adenoma in Women but Not Men.

Molecular and clinical observations provide evidence for a potential role of parathyroid hormone (PTH) in colorectal cancer development. We therefore aimed to assess the association of PTH with regard to colorectal cancer precursor lesions. A cohort of 1432 participants, 777 men, 58.4 ± 9.6 years and 701 women, 59.1 ± 10.6 years, undergoing screening colonoscopy were allocated to PTH serum concentrations either above or below 55 ng/L. The number, localization, size, and histology of the polypoid lesions detected during screening colonoscopy were recorded according to PTH serum concentrations. Serum PTH concentrations were not different between men and women. Women with PTH serum concentrations above the cut-off had significantly more adenomas (13/40; 32.5%) of the distal colon compared to women below the cut-off (91/659; 13.8%; P = 0.001). Additionally, the rate of dysplasia in adenomas of the distal colon was higher in women with high compared to low PTH concentrations (P = 0.001). These findings remained robust after adjustments for serum vitamin D, age, plasma creatinine, BMI, diabetes, and liver steatosis. No associations were observed between serum PTH concentrations and colorectal lesions in men. These data suggest that elevated PTH serum concentrations might have a role in colorectal cancer development as indicated by higher rates of adenomas, specifically with dysplasia, in women. The role of PTH in colon carcinogenesis and its sex specificity deserve further study.

Stimulation of glucose transport in osteoblastic cells by parathyroid hormone and insulin-like growth factor I

Insulin and parathyroid hormone (PTH) regulate glucose metabolism in bone cells. In order to differentiate between the effects of these hormones and to compare the potency of insulin with that of insulin-like growth factor (IGF) I, we treated rat bone-derived osteoblastic (PyMS) cells for different time periods and at different concentrations with insulin, IGF I, or PTH, and measured [1-(14)C]-2-deoxy-D-glucose (2DG) uptake and incorporation of D-[U-(14)C] glucose into glycogen. 2DG uptake was Na-independent with an apparent affinity constant (K (M)) of ~2 mmol/l. Expression of the high affinity glucose transporters (GLUT), GLUT1 and GLUT3 but not of GLUT4, was found by Northern and Western analysis. Similar to the findings with primary rat osteoblasts, but distinct from those in rat fibroblasts, 2DG uptake and glycogen synthesis were increased in this cell line after exposure to low concentrations (0.1 nmol/l and above) of PTH. IGF I at low doses (0.3 nmol/l and above) or insulin at higher doses (1 nmol/l and above) stimulated 2DG uptake and [(3)H] thymidine incorporation into DNA. 2DG transport was enhanced already after 30 min of IGF I treatment whereas the effect of PTH became significant after 6 h. It is concluded that IGF I rather than insulin may be a physiological regulator of 2DG transport and glycogen synthesis in osteoblasts.

Low prevalence of vitamin D deficiency among adolescents with anorexia nervosa

Fifty adolescents with AN and 200 healthy girls underwent vitamin D screening. Girls with AN reported exceptional compliance with vitamin D supplementation and PTH concentrations were lower. Vitamin D deficiency was less common in the group with AN, but when race was considered, the trend was no longer significant. The objective of this study was to determine whether patients with anorexia nervosa (AN) are more compliant with supplementation and have a lower prevalence of vitamin D deficiency than healthy controls. Fifty adolescents with AN and 200 controls were compared using anthropometric and lifestyle data, serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations, and prevalence of vitamin D deficiency. The prevalence of deficiency (<20 ng/mL) was 2% in the AN group vs. 24% among controls (p = 0.003). 25OHD was similar among white participants with AN and white controls (39.5 vs. 36.0 ng/mL, p = 0.20), but higher than in non-white controls (20.6 ng/mL). Significantly more girls with AN reported vitamin D supplementation (86%) than the full control (14%) or white subgroup (27%) (p < 0.001). Participants with AN had lower PTH concentrations than controls, (27.8 vs. 47.4 pg/mL, p = 0.009), a trend that lost significance after age and race adjustment (41.7 pg/mL, p = 0.12). Compared to healthy controls, adolescents with AN had a lower prevalence of vitamin D deficiency and PTH concentration. However, 25OHD and PTH concentrations were similar after adjustment for race and age. The trend of lower PTH levels in adolescents with AN, accompanied by exceptional compliance with supplementation, may have bone health implications for these patients.

Unexpected Serum Parathyroid Hormone Profiles in Some Patients with Primary Hyperparathyroidism

Third-generation parathyroid hormone (PTH) assays have been reported to measure only intact PTH(1-84), in contrast to second-generation assays, which also detect PTH(7-84) fragments. Higher PTH measurements were observed with third- than with second-generation PTH assays in a few patients with either severe primary hyperparathyroidism or parathyroid carcinoma. We analyzed biological data [second- and third-generation PTH assays, 25-hydroxyvitamin D (25-OHD), calcium, and phosphate concentrations] obtained before and after surgery for 2 groups of patients selected from a large series of consecutive patients with primary hyperparathyroidism (PHPT): 7 female patients with surgically and histologically confirmed PHPT (group 1) and a matched group (group 2). For group 1 but not group 2, PTH concentrations measured by third-generation PTH assays before surgery were higher than those measured by the second-generation assays. Circulating 25-OHD, calcium, and phosphate concentrations were similar in both groups. In addition, PTH values measured with the third-generation PTH assays in group 1 decreased after surgery. Our results confirm that third-generation PTH assays do not measure only PTH(1-84). The frequency of this unexpected finding of markedly lower PTH concentrations than previously reported was approximately 5% in patients with PHPT without malignancy. We do not know whether the presence of this unexpected profile is predictive of malignancy.

Hypercalcaemia associated with granulomatous lymphadenitis and elevated 1,25 dihydroxyvitamin D concentration in a dog

A seven-year-old Labrador was presented with weight loss and mild generalised lymphadenopathy. Histopathology of an excised lymph node by the referring veterinarian demonstrated granulomatous lymphadenitis. At the time of referral, fine-needle aspirates of the lymph nodes confirmed the presence of ongoing granulomatous inflammation. Further investigations revealed marked hypercalcaemia, a low parathyroid hormone concentration, a parathyroid hormone related protein concentration within the reference range, and an elevated serum concentration of 1,25 dihydroxyvitamin D. An underlying cause of the granulomatous lymphadenitis could not be identified. The clinical signs, hypercalcaemia and elevated serum concentrations of 1,25 dihydroxyvitamin D resolved following prednisolone treatment. In contrast to dogs, hypercalcaemia occurred secondarily to granulomatous disease and elevated 1,25 dihydroxyvitamin D concentrations is a well-recognised condition in human beings. To the authors' knowledge, this is the first case report to describe elevated serum calcium and 1,25 dihydroxyvitamin D concentrations in a dog with histologically confirmed granulomatous disease.

Calcium, Calcium Regulatory Hormones, and Calcimimetics

Calcemia is a risk factor for cardiovascular (CV) events in dialyzed patients. The relation between serum calcium and cardiovascular events is continuous and linear. Calcium plays a potent role in the genesis of cardiovascular dysfunction, particularly by promoting vascular calcification. Parathyroid hormone (PTH) also is associated with increased CV risk in both primary and secondary hyperparathyroidism. There is a nonlinear relationship between PTH and CV risk; both high and low PTH concentrations increase CV risk. The CV risk profile (BP, dyslipidemia) is strikingly ameliorated by the administration of calcimimetics. Apart from lowering PTH, whether calcimimetics have intrinsic effects on CV risk profile is unknown.

Stimulation of Extracellular Signal-regulated Kinases and Proliferation in Rat Osteoblastic Cells by Parathyroid Hormone Is Protein Kinase C-dependent

Parathyroid hormone (PTH) is known to have both catabolic and anabolic effects on bone. The dual functionality of PTH may stem from its ability to activate two signal transduction mechanisms: adenylate cyclase and phospholipase C. Here, we demonstrate that continuous treatment of UMR 106-01 and primary osteoblasts with PTH peptides, which selectively activate protein kinase C, results in significant increases in DNA synthesis. Given that ERKs are involved in cellular proliferation, we examined the regulation of ERKs in UMR 106-01 and primary rat osteoblasts following PTH treatment. We demonstrate that treatment of osteoblastic cells with very low concentrations of PTH (10(-12) to 10(-11) m) is sufficient for substantial increases in ERK activity. Treatment with PTH-(1-34) (10(-8) m), PTH-(1-31), or 8-bromo-cAMP failed to stimulate ERKs, whereas treatment with phorbol 12-myristate 13-acetate, serum, or PTH peptides lacking the N-terminal amino acids stimulated activity. Furthermore, the activation of ERKs was prevented by pretreatment of osteoblastic cells with inhibitors of protein kinase C (GF 109203X) and MEK (PD 98059). Treatment of UMR cells with epidermal growth factor (EGF), but not PTH, promoted tyrosine phosphorylation of the EGF receptor. Transient transfection of UMR cells with p21(N17Ras) did not block activation of ERKs following treatment with low concentrations of PTH. Thus, activation of ERKs and proliferation by PTH is protein kinase C-dependent, but stimulation occurs independently of the EGF receptor and Ras activation.