Hyperparathyroidism, arterial hypertension and aortic stiffness: a possible bidirectional link between the adrenal cortex and the parathyroid glands that causes vascular damage?

Abstract

P rimary hyperparathyroidism (PPTH) isgenerally thought to be a common endocrine disorder. However, it represents an uncommon endocrine cause of arterial hypertension, with a likely prevalence among hypertensive patients of less than 0.01%-an imprecise estimate because of the lack of prospective studies.However, between 56% and 80% of the patients with PPTH have high blood pressure (BP) and display hypertension-related target organ damage. On the basis of large studies from Scandinavia, a high rate of cardiovascular complications and mortality that has been consistently observed in PPTH patients compared with patients with essential hypertension without PPTH; this can be related to an excess organ damage in PPTH patients. 1 Despite these findings, the mechanisms by which PPTH is associated with hypertension and increased cardiovascular risk remain poorly understood and somewhat intriguing. In fact, parathyroid hormone (PTH) exerts a vasodilatory effect in different models 2,3 and induces an endothelium-dependent vasodilatory effect through increased nitric oxide production, 4,5 both of which are effects that would be expected to decrease, rather than increase, BP. However, PPTH has also been associated with endothelial dysfunction, which is usually due to reduced nitric oxide bioactivity, and represents a hallmark of high BP and many other conditions that are associated with increased cardiovascular risk. In contrast with this finding, increased levels of markers that are downstream of nitric oxide signaling, which were normalized after parathyroidectomy, have also been documented in PPTH patients. 6 Therefore, it has been proposed that increased nitric oxide bioactivity is a compensatory mechanism that counteracts the pressor effects of PTH-induced increases in intracellular calcium. 6 In this issue of the journal, Rosa et al. 7 report on their investigation of PPTH patients based on measurements of pulse wave velocity (PWV) before and after surgical treatment of PPTH; PWV is an index of aortic stiffness and hypertension-related target organ damage, which is recommended by the current guidelines of the ESC/ESH as part of the standard evaluation of hypertensive patients because it conveys information that is useful for risk stratification purposes. Interestingly, they found that PWV was higher in PPTH patients than in essential hypertensive patients, which suggests that excess PTH changes the mechanical properties of the arterial walls. However, this important finding is not consistent with the results of another recent study from Israel: compared with control subjects who were matched for age, gender and CV risk factors, neither the patients with full-blown (hypercalcemic) PPTH nor those with mild (normocalcemic) PPTH showed increased arterial stiffness, as assessed by several indices, including the PWV. 8 Although these inconsistencies could reflect either a selection bias, involving differences in ethnicity, overall cardiovascular risk profile, stage of PPTH disease in the patients and/or different selectio...

Interactions between adrenal-regulatory and calcium-regulatory hormones in human health

“…As with hypertension, arterial stiffness has been previously linked to maladaptive RAAS activity and can be improved with RAAS blockade [55, 56], implicating the RAAS as one of several potential mediators of the adverse vascular phenotypes observed in PHPT. Other proposed mechanisms include indirect effects via hypertension and renal dysfunction, as well as direct effects of elevated PTH levels and/or the accompanying hypercalcemia [53, 57]. …”

Hyperparathyroidism Can Be Useful in the Identification of Primary Aldosteronism Due To Aldosterone-Producing Adenoma

“…9,10 Moreover, given the emerging evidence implicating hyperparathyroidism as a cardiovascular risk factor, 10 it could be that the high serum PTH found in this study contributes both to the excess cardiovascular damage and to the persistent hyperaldosteronism of PA patients. Therefore, the provoking findings of this study should prompt further research on a larger population of different ethnicities with the aim of conclusively proving whether raised PTH is a marker of APA.…”

“…Accordingly, there is an unmet need of a better strategy for selecting patients more likely to have an APA to be submitted to adrenal vein sampling (AVS). After the pilot reports of secondary hyperparathyroidism in patients with PA 2,3 and also with secondary aldosteronism attributed to congestive heart failure, [4][5][6] we and others recently documented an elevation of serum parathyroid hormone (PTH) levels in large cohorts of patients with confirmed PA. 7,8 These observations are of great interest given the adverse cardiovascular consequences of excess PTH, which is now appreciated as a cardiovascular risk factor, 9,10 and also because of the evidence that PTH can exert a secretagogue effect on aldosterone. In vitro studies consistently showed that PTH concentration-dependently increases aldosterone in rat, 11 bovine, and human dispersed adrenocortical cells 12,13 and enhanced the secretagogue effect of angiotensin II on aldosterone.…”

Primary Hyperparathyroidism With Concurrent Primary Aldosteronism

“…4 Therefore, it would be expected to lower rather than to raise blood pressure. 5 The mechanisms by which excess PTH increases blood pressure remained obscure until Mazzocchi et al 6 reported that PTH stimulates in vitro the secretion of aldosterone from human adrenocortical cells in a concentrationdependent manner. These findings suggested that PTH acts as an aldosterone secretagogue that might be involved in causing human PA.…”