scholarly journals A case of a hemodialysis patient with secondary hyperparathyroidism who was resistant to etelcalcetide treatment but not to cinacalcet hydrochloride

2021 ◽  
Author(s):  
Hironori Nakamura ◽  
Masanori Tokumoto ◽  
Mariko Anayama ◽  
Shigekazu Kurihara ◽  
Yasushi Makino ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Binding Sites ◽  
Hemodialysis Patient ◽  
Total Parathyroidectomy ◽  
Maximal Dose ◽  
Intact Pth ◽  
Casr Gene ◽  
First Case ◽  
Cinacalcet Hydrochloride ◽  
Pth Level

AbstractAlthough both cinacalcet and etelcalcetide are calcimimetics that directly inhibit parathyroid hormone (PTH) secretion by activating the calcium (Ca)-sensing receptor (CaSR), their binding sites are different. We report a first case of a hemodialysis (HD) patient with secondary hyperparathyroidism (SHPT), in whom cinacalcet, but not etelcalcetide, could reduce serum intact PTH (i-PTH) levels. A HD patient received total parathyroidectomy (PTx) with auto-transplantation 16 years earlier. Due to SHPT relapse, cinacalcet was started at 7 years after PTx. His i-PTH levels had been controlled with both 75–100 mg of cinacalcet and 4.5 μg/week of calcitriol for a year before switching from cinacalcet to etelcalcetide. At 1 month following the switch, his serum i-PTH level increased to 716 pg/mL. The dose of etelcalcetide was gradually increased and finally reached the maximal dose of 45 mg/week. Because even the maximal dose of etelcalcetide for > 4 months did not reduce his serum i-PTH levels to < 700 pg/mL, etelcalcetide was switched to 50 mg/day of cinacalcet, which reduced the levels to 208 pg/mL at 2 months after the switch. Genomic sequencing test using whole blood revealed no mutation in the portion including Cys 482 of CaSR gene. The patient was resistant to etelcalcetide treatment but not to cinacalcet, suggesting the possibility that the enlarged parathyroid gland has some change in the portion including Cys 482 in the CaSR gene. Therefore, considering the possibility of etelcalcetide resistance during SHPT treatment should be kept in mind.

scholarly journals Intact parathyroid hormone levels localize causative glands in persistent or recurrent renal hyperparathyroidism: A retrospective cohort study

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0248366
Author(s):  
Takahisa Hiramitsu ◽  
Toshihide Tomosugi ◽  
Manabu Okada ◽  
Kenta Futamura ◽  
Norihiko Goto ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Area Under The Curve ◽  
Parathyroid Glands ◽  
Total Parathyroidectomy ◽  
Renal Hyperparathyroidism ◽  
Intact Pth ◽  
Receiver Operating Characteristic Curves ◽  
Detailed Imaging ◽  
Forearm Autograft ◽  
Pth Level

Persistent or recurrent renal hyperparathyroidism may occur after total parathyroidectomy and transcervical thymectomy with forearm autograft under continuous stimulation due to uremia. Parathyroid hormone (PTH) levels may reflect persistent or recurrent renal hyperparathyroidism because of the enlarged autografted parathyroid glands in the forearm or remnant parathyroid glands in the neck or mediastinum. Detailed imaging requires predictive localization of causative parathyroid glands. Casanova and simplified Casanova tests may be convenient. However, these methods require avascularization of the autografted forearm for >10 min with a tourniquet or Esmarch. The heavy pressure during avascularization can be incredibly painful and result in nerve damage. An easier method that minimizes the burden on patients in addition to predicting the localization of causative parathyroid glands was developed in this study. Ninety patients who underwent successful re-parathyroidectomy for persistent or recurrent renal hyperparathyroidism after parathyroidectomy between January 2000 and July 2019 were classified according to the localization of causative parathyroid glands (63 and 27 patients in the autografted forearm and the neck or mediastinum groups, respectively). Preoperatively, intact PTH levels were measured from bilateral forearm blood samples following a 5-min avascularization of the autografted forearm. Cutoff values of the intact PTH ratio (intact PTH level obtained from the non-autografted forearm before re-parathyroidectomy/intact PTH level obtained from the autografted forearm before re-parathyroidectomy) were investigated with receiver operating characteristic curves to localize the causative parathyroid glands. Intact PTH ratios of <0.310 with an area under the curve (AUC) of 0.913 (95% confidence interval [CI]: 0.856–0.970; P < 0.001) and >0.859 with an AUC 0.744 (95% CI: 0.587–0.901; P = 0.013) could predict causative parathyroid glands in the autografted forearm and the neck or mediastinum with diagnostic accuracies of 81.1% and 83.3%, respectively. Therefore, we propose that the intact PTH ratio is useful for predicting the localization of causative parathyroid glands for re-parathyroidectomy.

scholarly journals Neonatal Severe Hyperparathyroidism: Novel Insights From Calcium, PTH, and the CASR Gene

2019 ◽  
Vol 105 (4) ◽  
pp. 1061-1078 ◽  
Author(s):  
Stephen J Marx ◽  
Ninet Sinaii
Keyword(s):  
Parathyroid Hormone ◽  
Secondary Hyperparathyroidism ◽  
Evidence Synthesis ◽  
Low Grade ◽  
Total Parathyroidectomy ◽  
High Grade ◽  
Casr Gene ◽  
Calcium Insufficiency

Abstract Context Neonatal severe hyperparathyroidism (NSHPT) is rare and potentially lethal. It is usually from homozygous or heterozygous germline-inactivating CASR variant(s). NSHPT shows a puzzling range of serum calcium and parathyroid hormone (PTH) levels. Optimal therapy is unclear. Evidence acquisition We categorized genotype/phenotype pairings related to CASRs. For the 2 pairings in NSHPT, each of 57 cases of neonatal severe hyperparathyroidism required calcium, PTH, upper normal PTH, and dosage of a germline pathogenic CASR variant. Evidence synthesis Homozygous and heterozygous NSHPT are 2 among a spectrum of 9 genotype/phenotype pairings relating to CASRs and NSHPT. For the 2 NSHPT pairings, expressions differ in CASR allelic dosage, CASR variant severity, and sufficiency of maternofetal calcium fluxes. Homozygous dosage of CASR variants was generally more aggressive than heterozygous. Among heterozygotes, high-grade CASR variants in vitro were more pathogenic in vivo than low-grade variants. Fetal calcium insufficiency as from maternal hypoparathyroidism caused fetal secondary hyperparathyroidism, which persisted and was reversible in neonates. Among NSHPT pairings, calcium and PTH were higher in CASR homozygotes than in heterozygotes. Extreme hypercalcemia (above 4.5 mM; normal 2.2–2.6 mM) is a robust biomarker, occurring only in homozygotes (83% of that pairing). It could occur during the first week. Conclusions In NSHPT pairings, the homozygotes for pathogenic CASR variants show higher calcium and PTH levels than heterozygotes. Calcium levels above 4.5 mM among NSHPT are frequent and unique only to most homozygotes. This cutoff supports early and robust diagnosis of CASR dosage. Thereby, it promotes definitive total parathyroidectomy in most homozygotes.

scholarly journals The impact of CASR A990G polymorphism in response to cinacalcet treatment in hemodialysis patients with secondary hyperparathyroidism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jaruwan Ngamkam ◽  
Somratai Vadcharavivad ◽  
Nutthada Areepium ◽  
Titinun Auamnoy ◽  
Kullaya Takkavatakarn ◽  
...  
Keyword(s):  
Secondary Hyperparathyroidism ◽  
Hemodialysis Patients ◽  
Serum Phosphate ◽  
Clinical Factors ◽  
Calcium Sensing Receptor ◽  
Intact Pth ◽  
Baseline Serum ◽  
Calcium Sensing ◽  
The Impact ◽  
Pth Level

AbstractThe objective of this study was to determine the impact of calcium sensing receptor (CASR) A990G genetic polymorphism on parathyroid hormone (PTH) lowering response to cinacalcet treatment when controlling for significant influencing clinical factors. This retrospective study was conducted on 135 Thai hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). CASR A990G genotypes were determined. The patients were identified as either G carriers (heterozygous or homozygous CASR 990G allele carriers) or noncarriers (homozygous CASR 990A carriers). Tested covariates were baseline PTH level (bPTH), baseline serum phosphate (bPhos), baseline serum calcium (bCa), baseline calcitriol equivalent dose (bCtriol), baseline ergocalciferol dose (bErgo), and age. The ANCOVA showed that intact PTH levels after 12 weeks of cinacalcet treatment (PTHw12) was significantly lower among G carriers compared with noncarriers after controlling for bPTH, bPhos, bCtriol, and bErgo (F(1, 127) = 15.472, p < 0.001), with the adjusted mean difference of 253.7 pg/mL. The logistic regression analysis revealed that the odds of a G carrier achieving 30% PTH reduction after 12-week cinacalcet treatment were 3.968 times greater than the odds for a noncarrier after adjusting for bPhos, bCtriol, and age. In conclusion, the CASR A990G polymorphism significantly influences cinacalcet response in HD patients with SHPT.

scholarly journals Hypocalcemic cardiomyopathy after parathyroidectomy in a patient with uremia: A case report and literature review

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052094211
Author(s):  
Wei Zhang ◽  
Feng Xue ◽  
Quandong Bu ◽  
Xuemei Liu
Keyword(s):  
Heart Failure ◽  
Case Report ◽  
Secondary Hyperparathyroidism ◽  
Calcium Supplementation ◽  
Severe Heart Failure ◽  
Cardiac Complications ◽  
Refractory Heart Failure ◽  
First Case ◽  
Insight Into

Hypocalcemia is a rare, but reversible, cause of dilated cardiomyopathy. Although cardiomyopathy may cause severe heart failure, calcium supplementation can reverse heart failure. We report here a patient with uremia and secondary hyperparathyroidism, who was complicated by persistent hypocalcemia and refractory heart failure. The cardiac failure was refractory to treatment with digitalis and diuretics, but dramatically responded to calcium therapy and restoration of normocalcemia. As a result, the patient was eventually diagnosed with hypocalcemic cardiomyopathy. To the best of our knowledge, this is the first case of this disease to be reported in a patient with uremia. Findings from our case may help clinicians to better understand hypocalcemic cardiomyopathy. Our case might also provide new insight into long-term cardiac complications and prognoses of patients undergoing parathyroidectomy due to secondary hyperparathyroidism.

scholarly journals Contrasting PTH Response of Denosumab Use in Dialysis Patients: A Report of 2 Cases

Pharmacy ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 59
Author(s):  
Soo Min Jang ◽  
Smitha Anam ◽  
Tara Pringle ◽  
Paul Lahren ◽  
Sergio Infante
Keyword(s):  
Calcium Release ◽  
Hemodialysis Patient ◽  
Compensatory Mechanism ◽  
Normal Range ◽  
Mineral And Bone Disorder ◽  
Bone Disorder ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients ◽  
Pth Level

A common complication of end-stage renal disease (ESRD) is mineral and bone disorder. Yet, many anti-osteoporotic drugs are contraindicated in ESRD patients. Denosumab, a monoclonal antibody, does not require renal dose adjustment. However, its use is uncertain due to a lack of safety and efficacy of data in this population. Two hemodialysis patient cases of contrasting responses in parathyroid hormone (PTH) after denosumab administration were observed. Patient 1, a 62-years-old male received denosumab 60 mg at Day 0. His calcium decreased from 8.8 mg/dL to 6.8 mg/dL on Day 30. The PTH level increased from 265 pg/mL to 372 pg/mL after 30 days. Calcium and PTH levels approached normal range after increasing doses of vitamin D/calcium supplements, and calcitriol. Patient 2, a 72-years-old male on hemodialysis also received denosumab 60 mg on Day 0. His baseline calcium and PTH were 9.2 mg/dL and 420 pg/mL, respectively. On Day 30, his calcium level decreased (6.8 mg/dL) but, PTH level drastically increased (>5000 pg/mL). Denosumab commonly causes hypocalcemia and hyperparathyroidism since it inhibits osteoclast activation, reduces calcium release from bone and increases PTH levels as a compensatory mechanism. With a wait-and-watch approach, Patient 2’s levels approached the normal range (calcium 9.6 mg/dL and PTH 274 pg/mL at Day 90).

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