ResearchPad - parathyroid-hormone Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[A new neuropeptide insect parathyroid hormone iPTH in the red flour beetle <i>Tribolium castaneum</i>]]> Vertebrate parathyroid hormone (PTH) and its receptors have been extensively studied with respect to their function in bone remodeling and calcium metabolism. Insect parathyroid hormone receptors (iPTHRs) have been previously described as counterparts of vertebrate PTHRs, however, they are still orphan receptors for which the authentic ligands and biological functions remain unknown. We describe an insect form of parathyroid hormone (iPTH) by analyzing its interactions with iPTHRs. Identification of this new insect peptidergic system proved that the PTH system is an ancestral signaling system dating back to the evolutionary time before the divergence of protostomes and deuterostomes. We also investigated the functions of the iPTH system in a model beetle Tribolium castaneum by using RNA interference. RNA interference of iPTHR resulted in defects in wing exoskeleton maturation and fecundity. Based on the differential gene expression patterns and the phenotype induced by RNAi, we propose that the iPTH system is likely involved in the regulation of exoskeletal cuticle formation and fecundity in insects.

<![CDATA[SAT-405 Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP): A Useful Tool?]]> Background: PHP is a common disorder, and regardless of being an asymptomatic entity, often leads to bone loss and osteoporosis. TBS is a software-based assessment method of trabecular bone structure of the spine based on the analysis of pixels in dual energy x-ray absorptiometry (DXA) images. The aim of this study was to evaluate TBS measurements in combination with DXA values by searching for more accurate bone fragility risk assessment among PHP patients.

Methods: From June/2017 to January/2019, all patients who met the criteria for PHP diagnosis prior to surgery were selected to take part in this study. Control group was composed by non-family related healthy volunteers. Bone mineral density (BMD) by DXA (DXA; Hologic QDR 4500) at the lumbar spine, total hip, femoral neck, distal third of the non-dominant radius and TBS values by InSight were determined in 64 PHP patients and 63 controls. Total and ionized calcium, PTH, 25-hydroxyvitamin D (25(OH)D), creatinine, alkaline phosphatase, P1NP and CTX were measured in all patients and control group.

Results: Primary hyperparathyroidism patients presented significant lower BMD values in all evaluated sites compared to controls. TBS measurements were also statistically different among PHP patients and controls (mean TBS PHP=1233 vs TBS controls= 1280, p=0.044). Patients and controls didn’t differ in age, sex, menopausal state or BMI (body mass index). Osteoporosis diagnosis by DXA analysis was observed in 50% of PHP patients and in 26.6% of controls. Self-reported or image-diagnosed fracture occurred in 15 PHP (23.4%) patients and in 11 (17.5%) controls. Among these fractures, vertebral fracture account for 9 (14%) in PHP group and 4 (6.3%) in controls. ROC curve analysis showed that the TBS value < 1187 is associated to significant high risk of vertebral fracture (sensibility 87.5%, specificity 67.3%) among PHP patients.

Conclusion: TBS, used as a complement to DXA measurements, is a useful tool to better assess fragility risk among PHP patients.

<![CDATA[SAT-390 Preoperative Parathyroid Ultrasound Imaging - Pitfalls and Ways to Improve Diagnostic Accuracy]]> Introduction: Parathyroid ultrasound (US) is commonly used for pre-operative imaging to facilitate focused parathyroid surgery. It provides point-of-care imaging without ionizing radiation and is less expensive compared to nuclear scintigraphy or computed tomography (CT). Parathyroid US is, however, operator skill and experience dependent. Methods: The charts of all patient who underwent parathyroid surgery between 2016 and 2018 were reviewed. Investigators reviewed the pre-operative US images and correlated these findings with pathology reports, operative notes and with results of CT and nuclear scintigraphy imaging. The US characteristics of parathyroid lesions were described. Results: In total 146 patients underwent parathyroid surgery during the three-year study period. The average age of the cohort was 55.1 +/- 15.1 years and the male to female ratio was 1:2.6. The average pre-operative serum calcium and PTH levels were 11.6 +/- 0.9 mg/dL and 310.9 +/-305 pg/ml, respectively. 134 out of 138 patients with preoperative PTH US had images available for review by investigators. Compared to the pre-operative read that identified 106 lesions, 19 additional parathyroid lesions were identified: seven (36.8%) were easily identifiable lesions with typical US features, 3 (15.8%) were easily identifiable lesions with atypical US features, 5 (26.3%) were lesions adherent to the thyroid gland and 9 (47.4%) were small lesions that were likely only identified by the investigators due to knowledge of the final pathology and intraoperative findings. Forty-seven parathyroid lesions could not be identified by investigators and one or more of the following reasons were determined as possible explanations: lesion was small in size (14.9%), presence of a large thyroid gland (27.7%), location of the lesion deep in the neck or at an ectopic location (21.3%). The quality of stored images was inadequate in 31.9% of these cases. After review, 67.1% (compared to the actual detection rate of 61.3%) of parathyroid lesions should have been identified on preoperative US. Sixty percent of parathyroid lesions were left sided and 66.9% were inferior in location. The shapes observed were oval (48.8%), conforming (50.4%) or elongated (<1%) and echogenicity was hypoechoic (86.8%) or isoechoic (13.2%). Only a small percentage had a target sign (6.6%) or were partially cystic (7.4%). 74.8% demonstrated a feeding vessel and 33.6% had vascular arborization or scattered vascularity. Conclusions: While parathyroid lesions with typical US feature and locations are easily identified, the common reasons for failure to identify a lesion include atypical features, small size, slender configuration and adherence to the thyroid gland. Being aware of these possibilities can improve detection rate. Parathyroid lesions are also less likely to be identified when present deep in the neck or at an ectopic location outside of the neck.

<![CDATA[SAT-393 Cognitive Function Evaluation in an Italian Cohort of Patients with Post-Operative Hypoparathyroidism]]> Post-operative hypoparathyroidism (PoHypo) is the most common cause of hypoparathyroidism and it is the result of accidental parathyroid removal/injury during neck surgery. The lack of PTH alters calcium homeostasis and patients are at risk of renal complications, bone involvement, infections and psychiatric syndromes. Conventional therapy, that includes calcium supplements and activated vitamin D, does not restore the complete calcium homeostasis. From a neuropsychological point of view, patients complain with neurocognitive symptoms such as “brain fog”, impaired ability to focus, memory loss, depression. Poor quality of life (QoL), evaluated by non-specific questionnaires, has been demonstrated in these patients. The aim of this study is to evaluate the cognitive function by neuropsychological specific tests in patients with PoHypo and matched controls and their relationship with biochemical parameters. This is a prospective monocentric study; we enrolled outpatients who underwent total thyroidectomy for malignant cured disease, 34 with chronic (>6 months) PoHypo (mean age 50.7 ys) and 31 without PoHypo (mean age 49.9 ys). The two groups did not differ significantly in TSH; PoHypo group had a relatively controlled serum calcium adjusted for albumin (SAlbCa) levels in therapy (mean 8.8±0.1mg/dl, 4 patients with <8.2 mg/dl) and control group had normal SAlbCa levels (9.4 ±0.2mg/dl). In PoHypo patients a significant correlation was found between serum calcium, SAlbCa levels and the scores at the Trail-Making Test_A (a specific test evaluating attention capacity; r= -0.36; p<.05, r= -0.37; p<.05) and at the Semantic Fluency Test (validated for cognitive function; r= 0.32; p<.05, r= 0.34; p<.05). No significant correlations were found in the control group. A median split based on serum calcium levels (> or < than 9 mg/dl) was performed in both patients groups. PoHypo patients with serum calcium levels <9 mg/dl performed worse than PoHypo patients with calcium>9mg/dl, either at the Trail-Making Test_A (scores:34.00 vs 21.05, p<.05) and Semantic Fluency Test (39.62 vs 47.4, p<.05). Moreover, PoHypo patients with serum calcium <9 mg/dl performed worse than matched control patients, either at the Trail-Making Test_A (scores:34.00 vs 27.61, p<.05) and Semantic Fluency Test (39.62 vs 46.16, p<.05). These findings suggest that PoHypo patient’s performance in cognitive tests is worse than matched controls and that this is correlated with serum calcium levels.

<![CDATA[SAT-389 Clinical and Biochemical Characterization of Risk Factors for Vertebral Fractures in Patients with Hypoparathyroidism]]> Background: Persistent hypoparathyroidism (PH) is a rare disease due to an impaired secretion of PTH, mostly occurring as a complication of total thyroidectomy. Calcium and calcitriol are currently the most common and inexpensive therapies, although not all the patients easily achieve control of the disease. Recently, our group has reported that BMI at diagnosis can predict calcitriol resistance in PH. Very few studies have been performed with fractures as primary endpoint in hypoparathyroidism, and we still not know if PH could be predisposing to an increased risk of morphometric fractures and possible clinical and biochemical predicting factors. Patients and methods: To that end we retrospectively evaluated the anthropometric, biochemical and fracture characteristics in 71 consecutive patients with PH (F/M= 62/9; median age 58.7 yrs, range: 29-87; 67 with post-surgical PH and 4 with autoimmune PH). All patients were hypoparathyroid from at least one year (median duration of disease: 9 yrs., range: 1-41) and were under standard treatment with calcium and active vitamin D analogs (calcitriol). For each patient anthropometric data (BMI=kg/m2; N= Normal weight patients <25; OO= Obese and overweight patients with BMI > 25) were collected, as well as biochemical parameters, such as calcium (mg/dl) and 25 OH vitamin D (25OHD expressed as ng/ml). We considered well controlled (C) patients with calcium between 8.2 and 9.2 mg/dl and not controlled (NC) under 8.2 or above 9.2 mg/dl. Vertebral fractures (VF) were assessed by a quantitative morphometric approach by using images provided by DXA and classified according to Genant classification. Results: Thirteen out of 71 patients (18%) were fractured. We showed a positive linear correlation in the overall population between BMI and calcitriol intake (p=0.006, CI 95% [1.2-6.9]) while no significant difference in prevalence of VF in OO vs N group (8/40 vs 5/31, p=0.76) was found. However, almost half (6/13, 45%) of patients with VF were OO NC. Moreover, 86% of NC vs only 30% of C fractured patients (6/7 vs 2/6) were OO Discussion: We report a high prevalence of VF in hypoparathyroidism. Moreover, we confirm that increased BMI is associated with higher needs of calcitriol to obtain calcium control. Interestingly, our data suggest for the first time that OO hypoparathyroid patients with NC disease are those at highest risk of fracture. Therefore, in this subset of patients a more intensive and proactive biochemical and bone monitoring should be adviced if these results will be confirmed in larger studies.

<![CDATA[SAT-394 Concordant Parathyroid Imaging; Frequency and Predictors of Concordance and Its Impacts on Cure]]> Introduction: Accurate pre-operative imaging of a parathyroid adenoma facilitates minimally invasive surgery for primary hyperparathyroidism, increases cure rate and reduces perioperative complications. The two most commonly deployed preoperative localization studies are ultrasonography (US) and parathyroid scintigraphy using 99m-techentium sestamibi (RN). Patients who have concordant results between the two studies (most studies report concordance rate of 60%) usually undergo minimally invasive surgery whilst those with non-concordance scan results often need bilateral open neck surgery.Objectives: We did a retrospective assessment of the clinical, biochemical and imaging parameters of patients who had parathyroid surgery in our hospital to assess (a) the sensitivity and positive predictive value (PPV) of US and RN scans (b) the frequency of concordance between the two imaging studies (c) the clinical and laboratory predictors of concordance and (d) the impact of concordance on the cure rate.Method: 155 patients who were operated for PHPT between January 2011 and January 2019 were included. All patients underwent preoperative localization with US and RN imaging. The sensitivity and PPV of the 2 imaging procedures in detecting a parathyroid adenoma were determined by correlating the imaging findings of both scans with the composite information obtained from surgical findings and post-operative biochemical results to indicate cure. The patients with concordant and non-concordant imaging findings were compared for surgical cure rate, serum calcium and parathormone level, and the volume and weight of the adenoma.Results: The sensitivity and PPV of US were 80.9% and 82.8% and for RN scan 78.7% and 87.8% respectively. There was no statistically significant difference in the accuracy between the two modalities. 93(60%) patients had concordant and 62(40%) patients had non-concordant scan results, which included true discordance and non-localization by one or both scans. Cure rate in concordant and non-concordant scans were 96.8% and 83.7% respectively (p=0.02, chi-square). In comparison to patients with non-concordant imaging, patients with concordant imaging had higher level of serum calcium (mean 3.02 vs 2.86, p=0.04), the resected adenoma was larger in volume (mean 3109mm3 vs 2083mm3, p=0.05) and was heavier (mean 1.59 vs 1.10 p=ns). However there was no difference in the age or serum PTH level between the 2 groups of patients.Conclusion: Both US and RN imaging have similarly high sensitivity and PPV in identifying a parathyroid adenoma and our figures were comparable to the published literature. When the two studies are concordant a significantly higher surgical success rate is obtained. Patients with higher serum calcium and larger adenomas are more likely to demonstrate concordant imaging.

<![CDATA[SAT-400 Pregnancy Outcome in Women with Hypoparathyroidism:Aswedishpopulation-Based Cohort Study]]> Context: The majority of patients with hypoparathyroidism (HypoPT) are women. It is not known whether the presence of hypoparathyroidism influences the pregnancy outcomes. Sweden has excellent conditions for research in this area, with high-quality population-based registers covering essentially all inpatient care and birth records. In this study, data were linked from the Swedish National Patient Register and Swedish Medical Birth Register to examine the potential influence of maternal hypoPT on the number of childbirths and various pregnancy outcomes.

Design and Setting: Population-based cohort study in Sweden.

Patients: Through the Swedish National Patient Register and the Total Population Register, we identified 1267 women with HypoPT and 12 670 age-matched controls who gave birth between 1997 and 2016.

Results: There was no significant difference in mean age at delivery for women with HypoPT (32 (SD, 5.2)) years and controls (32.5 (5.0)). There were significantly more women with HypoPT who smoked at baseline (p= 0.007) and within 3 months of pregnancy (p=0.022) compared to controls. Significantly more women with HypoPT had part time work or were not working during pregnancy compared to controls (p = 0.002). The mean number of infants per woman was 0.30 (SD, 0.62) in the HypoPT group and 0.33 (SD, 0.60) in the control group (p=0.644). Compared with the control group, the risk of elective cesarean section was higher in the HypoPT group (p=0.002). However, there was no difference in the proportion of women undergoing an acute cesarean section between cases and controls (p=0.754). The mean pregnancy duration in women with HypoPT was 38.87 (2.11) weeks compared to 39.23 (2.04) weeks for the controls (p= 0.001). Infants born to mothers with HypoPT were significantly shorter (p=0.016), but no difference was seen in weight or head circumference compared to infants born to controls. No difference was observed in prevalence of small- or large-for gestational age compared to controls. There were no differences between groups with respect to infant sex or Apgar scores at 1, 5 and 10 min, congenital malformations or stillbirth. There was furthermore no difference in pain medication use by mothers during delivery between the groups (p=0,733).

Conclusion: The majority of women with HypoPT had normal pregnancy outcomes, and the overall risks must be considered to be low. Still, our findings are of importance for antenatal counseling in women with HypoPT as their risk for elective cesarean section was significantly higher compared with controls. Their children were shorter and the higher rate of smoking among HypoPT women may be an additional risk factor.

<![CDATA[Prevalence and treatment of gout among patients with chronic kidney disease in the Irish health system: A national study]]>


Gout is a common inflammatory arthritis associated with adverse clinical outcomes. Under treatment is common in the general population. The aim of this study was to determine the prevalence of gout and its treatment among patients with chronic kidney disease (CKD).


We conducted a multi-centre cross sectional study of patients (n = 522) who attended specialist nephrology clinics in Ireland. Standardized data collection tool recorded clinical characteristics and medication use at clinic visits and kidney function was assessed with standardised creatinine measurements and Estimated Glomerular Filtration Rate (eGFR). The prevalence of gout and the corresponding use of urate lowering therapies (ULT) were determined. Multivariate logistic regression explored correlates of gout expressed as Odds Ratios (OR) and 95% Confidence Intervals (CI) adjusting for demographic and clinical characteristics.


Overall prevalence of gout was 16.6% and increased significantly from 7.5% in Stage 1–2 CKD to 22.8% in stage 4–5 CKD, P< 0.005. Prevalence increased with age (P < 0.005) and was higher in men than women (19.1% versus 10.3% P< 0.005). Overall, 67.9% of gout patients with CKD were treated with ULT, and the percentage increased with advancing stage of CKD from 55.6% in Stage 1–2 to 77.4% in Stage 4–5, P<0.005. Multivariable modelling identified men (vs women), OR, 1.95 (0.95–4.03), serum albumin, OR 1.09 (1.02–1.16) per 1 g/L lower, poorer kidney function, OR 1.11 (1.01–1.22) per 5 ml/min/1.73m2 lower, and rising parathyroid hormone levels, OR 1.38 (1.08–1.77) per 50 pg/ml higher as disease correlates.


Gout is common in CKD and increases with worsening kidney function in the Irish health system. Over two thirds of patients with gout were receiving ULT, increasing to 77% of patients with advanced CKD. Greater awareness of gout in CKD, its treatment and the effectiveness of treatment strategies should be vigorously monitored to improve patient outcomes.

<![CDATA[Different duration of parathyroid hormone exposure distinctively regulates primary response genes Nurr1 and RANKL in osteoblasts]]>

Parathyroid hormone (PTH) exerts dual effects, anabolic or catabolic, on bone when administrated intermittently or continuously, via mechanisms that remain largely unknown. PTH binding to cells induces PTH-responsive genes including primary response genes (PRGs). PRGs are rapidly induced without the need for de novo protein synthesis, thereby playing pivotal roles in directing subsequent molecular responses. In this study, to understand the role of PRGs in mediating osteoblastic cellular responses to PTH, we investigated whether various durations of PTH differentially induce PRGs in primary osteoblasts and MC3T3-E1. Nurr1 and RANKL, PRGs known for their anabolic and catabolic roles in bone metabolism respectively, presented distinctive transient vs. sustained induction kinetics. Corroborating their roles, maximum induction of Nurr1 was sufficiently achieved by brief PTH in as little as 30 minutes and continued beyond that, while maximum induction of RANKL was achieved only by prolonged PTH over 4 hours. Our data suggested distinctive regulatory mechanisms for Nurr1 and RANKL: PKA-mediated chromatin rearrangement for transcriptional regulation of both PRGs and ERK-mediated transcriptional regulation for RANKL but not Nurr1. Lastly, we classified PRGs into two groups based on the induction kinetics: The group that required brief PTH for maximum induction included Nur77, cox-2, and Nurr1, all of which are reported to play roles in bone formation. The other group that required prolonged PTH for maximum induction included IL-6 and RANKL, which play roles in bone resorption. Together, our data suggested the crucial role of PRG groups in mediating differential osteoblastic cellular responses to intermittent vs. continuous PTH. Continued research into the regulatory mechanisms of PKA and ERK for PRGs will help us better understand the molecular mechanisms underlying the dual effects of PTH, thereby optimizing the current therapeutic use of PTH for osteoporosis.

<![CDATA[SAT-387 Testing for Parathyroid Hormone: Performances of a Novel Fully Chemiluminescent Automated Assay]]> <![CDATA[SAT-402 Investigating Analogues of Parathyroid Hormone (PTH) and PTH-Related Peptide (PTHrP) to Improve Anabolic: Catabolic Response Ratios Using UMR106-01 Osteocytic Cells]]> 100nM). Removing the first amino acid of PTH to PTH2-34 drastically decreases the effectiveness of the peptide (OPG, SOST and RANKL IC50 – no effect, IL6 EC50 > 100nM). These results indicate the importance of the N-terminal amino acid for PTH affinity and efficacy and suggest that Tyr1PTH1-34 may offer the best combination of bone stimulation without causing hypercalcemia.References 1 A.Gupta, L. March. (2016) Treating osteoporosis, Aust Prescr 2 Chen X, et al. (2018) Osteoblast–osteoclast interactions. Connect. Tissue Res 3 Tu KN, et al. (2018) Osteoporosis: A review of treatment options. P T ]]> <![CDATA[SAT-397 Characteristics and Outcomes of Severe Hypercalcemia Related Admissions - a Single Centre 5 Years’ Experience]]> <![CDATA[SAT-404 Neonatal Hypocalcemic Seizures in Offspring of a Mother with Familial Hypocalciuric Hypercalcemia Type 1 (FHH1)]]> <![CDATA[SAT-398 The Use of Imaging in Primary Hyperparathyroidism]]> <![CDATA[SAT-395 Correlations Between Biochemical Parameters and Trabecular Bone Score (TBS) in Primary Hyperparathyroidism (PHP) Patients]]> <![CDATA[SAT-LB71 Is Late Diagnosis of Postsurgical Hypoparathyroidism the Rule, Not the Exception?]]> <![CDATA[SAT-408 Bioactivity of Long Acting PTH Fusion Molecules Tested in a Novel Non-Surgical Animal Model of Hypoparathyroidism]]> <![CDATA[SAT-403 Is Most “Primary” Hyperparathyroidism Both Tertiary and Preventable?]]> 30N=100 patients/armVisits q90 daysBone densitometry [including lateral spine] qyearTelopeptides, Crosslinks, Alkaline Phosphatase, UV/Pcalcium/creatinine,Flat PlatesExclusion: Pcreatinine>2.0,mg/dl, Ca++>10.0 mg/dl,Familial HPTHInclusion: PTH >70 pg/mlPrimary Efficacy Variable: Number of documented cases of Hypercalcemic HyperparathyroidismSecondary Variables: Mortality, Kidney stones, Bone density, Fractures ]]> <![CDATA[SAT-LB72 Design of the PaTH Forward Phase 2 Trial of TransCon PTH, a Long-Acting PTH, in Patients With Hypoparathyroidism]]> <![CDATA[SAT-392 The Role of β-arrestin2 in Bone Catabolic Response to Hyperparathyroidism In Vivo]]>