Vascular Effects of Parathyroid Hormone (PTH)

Rambausek, M.; Ritz, Eberhard; Rascher, Wolfgang; Kreusser, Willi; Mann, Johannes F.E.; Kreye, V. A. W.; Mehls, Otto

doi:10.1007/978-1-4684-4259-5_64

Cited by 28 publications

(6 citation statements)

References 17 publications

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“…There are limited data suggesting that PTH may cause impaired endothelial dysfunction in PHPT. While short‐term administration of PTH causes a dose‐dependent transient vasodilation, chronic continuous PTH infusion results in vasoconstriction and hypertension . PTH, even within the normal range, has been prospectively associated with cardiovascular mortality and increased PTH levels are independently associated with impaired endothelial function in elderly men with CHF .…”

Section: Discussionmentioning

confidence: 99%

Endothelial function in mild primary hyperparathyroidism

Carrelli

Walker

Tullio

et al. 2013

Clinical Endocrinology

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Background It is not known if endothelial dysfunction, an important early event in the pathogenesis of atherosclerosis, is present in mild primary hyperparathyroidism (PHPT) and if so, whether it improves following parathyroidectomy. Design We measured flow-mediated vasodilation (FMD), which estimates endothelial function by ultrasound imaging, in patients prior to and 6 and 12 months after parathyroidectomy. Results Forty-five patients with mild PHPT [80% female, 61 ± 1 (mean ± SE) years, serum calcium 2.65 ± 0.03 mmoL/L (10.6 ± 0.1 mg/dL), PTH 10.5 ± 0.7 pmol/L (99 ± 7 pg/mL), 25-hydroxyvitamin D (25OHD) 70.3 ± 3.7 nmol/L (28.2 ± 1.5 ng/mL)] were studied. Baseline FMD was normal (4.63 ± 0.51%; reference mean: 4.4 ± 0.1%), and was not associated with serum calcium, PTH, or 25OHD levels. In the group as a whole, FMD did not change after surgery (6 mo: 4.38 ± 0.83%, p=0.72; 12 mo: 5.07±0.74%, p=0.49). However, in those with abnormal baseline FMD (<2.2%; N=15), FMD increased by 350%, normalizing by 6 months after surgery (baseline: 0.81 ± 0.19%; 6 mo: 3.18 ± 0.79%, p = 0.02 versus baseline; 12 mo: 3.68± 1.22%, p = 0.04 versus baseline). Baseline calcium, PTH, and 25OHD levels did not differ between those with abnormal versus normal FMD, nor did these indices predict postoperative change in FMD. Conclusions FMD is generally normal in patients with mild PHPT and is unchanged one year after parathyroidectomy. Although FMD may normalize after surgery in patients with baseline abnormalities, data do not support using endothelial dysfunction as an indicator for parathyroidectomy.

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Section: Discussionmentioning

confidence: 99%

Endothelial function in mild primary hyperparathyroidism

Carrelli

Walker

Tullio

et al. 2013

Clinical Endocrinology

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“…Our group and others have reported that PTH levels were positively associated with carotid (6) and aortic stiffness (38, 39). As chronic continuous PTH infusion results in vasoconstriction and hypertension (40, 41), the PTH reduction after surgery might affect smooth muscle cell proliferation or function, resulting in reduced inflammation and improved vascular function. We did not find that baseline PTH or calcium, or changes in either measure predicted the postoperative decline in stiffness.…”

Section: Discussionmentioning

confidence: 99%

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism

Walker

Rundek

Homma

et al. 2012

European Journal of Endocrinology

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Objective We recently demonstrated that mild primary hyperparathyroidism (PHPT) is associated with increased carotid intima-media thickness (IMT) and stiffness, and increased aortic valve calcification. It is unclear whether parathyroidectomy (PTX) improves these abnormalities. The purpose of this study was to determine whether cardiovascular abnormalities in PHPT improve with PTX. Design Forty-four patients with PHPT were studied using carotid ultrasound and transthoracic echocardiography before and after PTX. Carotid IMT, carotid plaque and stiffness, left ventricular mass index (LVMI), myocardial and valvular calcification, and diastolic function were measured before, 1- and 2-year post-PTX. Results Two years after PTX, increased carotid stiffness tended to decline to the normal range (17%, P =0.056) while elevated carotid IMT did not improve. Carotid plaque number and thickness, LVMI and cardiac calcifications did not change after PTX, while some measures of diastolic function (isovolumic relaxation time (IVRT) and tissue Doppler peak early diastolic velocity) worsened within the normal range. Indices did improve in patients with cardiovascular abnormalities at baseline. Increased carotid stiffness improved by 28% (P=0.004), a decline likely to be of clinical significance. More limited improvements also occurred in elevated IMT (3%, P=0.017) and abnormal IVRT (13%, P<0.05), a measure of diastolic dysfunction. Conclusions In mild PHPT, PTX led to modest changes in some cardiovascular indices. Improvements were mainly evident in those with preexisting cardiovascular abnormalities, particularly elevated carotid stiffness. These findings are reassuring with regard to current international guidelines that do not include cardiovascular disease as a criterion for PTX.

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“…In this post hoc analysis of the PaTHway trial, mean eGFR increased by 9.3 mL/min/1.73 m 2 with palopegteriparatide treatment over 52 weeks and by 7.6 mL/min/1.73 m 2 in participants randomized to placebo during the blinded treatment period who received open-label palopegteriparatide from weeks 26 to 52. The largest changes in eGFR in the palopegteriparatide group occurred during the first 4 weeks and were potentially due to a combination of PTH-driven tubular reabsorption of calcium and excretion of phosphate, the vasodilatory effects of PTH on the renal vasculature [ 16 ], and the net effect of PTH on glomerular hemodynamics [ 17 , 18 ]. Additionally, a significant reduction in the dose of conventional therapy (including almost complete independence from active vitamin D and a 70% reduction in the dose of elemental calcium by week 4), and therefore, reduction in calcium influx and excretion could be contributing factors.…”

Section: Discussionmentioning

confidence: 99%

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

Rejnmark,

Gosmanova,

Khan

et al. 2024

Adv Ther

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Introduction Individuals with chronic hypoparathyroidism managed with conventional therapy (active vitamin D and calcium) have an increased risk for renal dysfunction versus age- and sex-matched controls. Treatments that replace the physiologic effects of parathyroid hormone (PTH) while reducing the need for conventional therapy may help prevent a decline in renal function in this population. This post hoc analysis examined the impact of palopegteriparatide treatment on renal function in adults with chronic hypoparathyroidism. Methods PaTHway is a phase 3 trial of palopegteriparatide in adults with chronic hypoparathyroidism that included a randomized, double-blind, placebo-controlled 26-week period followed by an ongoing 156-week open-label extension (OLE) period. Changes in renal function over 52 weeks (26 weeks blinded + 26 weeks OLE) were assessed using estimated glomerular filtration rate (eGFR). A subgroup analysis was performed with participants stratified by baseline eGFR < 60 or ≥ 60 mL/min/1.73 m 2 . Results At week 52, over 95% (78/82) of participants remained enrolled in the OLE and of those, 86% maintained normocalcemia and 95% achieved independence from conventional therapy (no active vitamin D and ≤ 600 mg/day of calcium), with none requiring active vitamin D. Treatment with palopegteriparatide over 52 weeks resulted in a mean (SD) increase in eGFR of 9.3 (11.7) mL/min/1.73 m 2 from baseline ( P < 0.0001) and 43% of participants had an increase ≥ 10 mL/min/1.73 m 2 . In participants with baseline eGFR < 60 mL/min/1.73 m 2 , 52 weeks of treatment with palopegteriparatide resulted in a mean (SD) increase of 11.5 (11.3) mL/min/1.73 m 2 ( P < 0.001). One case of nephrolithiasis was reported for a participant in the placebo group during blinded treatment; none were reported through week 52 with palopegteriparatide. Conclusion In this post hoc analysis of the PaTHway trial, palopegteriparatide treatment was associated with significantly improved eGFR at week 52 in addition to previously reported maintenance and normalization of serum and urine biochemistries. Further investigation of palopegteriparatide for the preservation of renal function in hypoparathyroidism is warranted. Trial Registration ClinicalTrials.gov NCT04701203. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-024-02843-8.

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Vascular Effects of Parathyroid Hormone (PTH)

Cited by 28 publications

References 17 publications

Endothelial function in mild primary hyperparathyroidism

Endothelial function in mild primary hyperparathyroidism

Effect of parathyroidectomy on subclinical cardiovascular disease in mild primary hyperparathyroidism

Palopegteriparatide Treatment Improves Renal Function in Adults with Chronic Hypoparathyroidism: 1-Year Results from the Phase 3 PaTHway Trial

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