Pulse wave velocity in primary hyperparathyroidism and effect of surgical therapy

P rimary aldosteronism (PA) is a common cause of secondary hypertension, because it involves 11.2% of referred hypertensive patients. 1 Primary hyperparathyroidism (PPTH) is much less common, with a prevalence that, albeit imprecisely known, is probably Ͻ0.01% in unselected hypertensives. However, arterial hypertension develops in the majority (56% to 80%) of the PPTH patients, 2 which can explain why they are held to be at increased risk for cardiovascular complications and death. 3 The association of PPTH with arterial hypertension and increased cardiovascular risk would appear to be paradoxical, inasmuch as the parathyroid hormone (PTH) has been described to induce vasodilation through endothelium-independent mechanisms. 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. However, whether this mechanism, although appealing, could be involved in causing human PA and might explain the development of arterial hypertension in patients with PPTH remained unsupported by any clinical data.We herein report on a patient who presented with resistant arterial hypertension and was found to have PA. Unilateral adrenalectomy resulted in cure of the PA and control of blood pressure despite a tapering of antihypertensive treatment, but the patient developed hyperparathyroidism caused by a PTHsecreting adenoma that was surgically removed. Gene expression and immunohistochemistry studies unveiled the expression of type 1 PTH receptor in the aldosterone-producing adrenocortical nodules and of the mineralocorticoid receptor (MR) in the nuclei of parathyroid adenoma cells. This latter finding was confirmed in a series of normal human parathyroid glands. Thus, this unique case and the related findings support the notion that undetected hyperfunctioning of the parathyroid gland can contribute to maintaining hyperaldosteronism in PA. It also suggests the existence of a bidirectional link between the adrenocortical zona glomerulosa and the parathyroid gland, which can be relevant for the regulation of calcium metabolism and blood pressure. CaseA 68-year-old man was referred for chest pain and resistant hypertension (Figure 1). The patient had a 10-year history of hypertension, which had become resistant to therapy with atenolol at 100 mg, amlodipine at 10 mg, doxazosin at 4 mg, potassium canrenoate at 25 mg, hydrochlorothiazide at 12.5 mg, and telmisartan at 80 mg daily. He had a family history of primary (essential) hypertension and a personal history of previous cigarette smoking, dyslipidemia, paroxysmal atrial fibrillation, and coronary artery disease that was treated with percutaneous transluminal coronary angioplasty and stenting 2 years before. Physical...

show abstract

“…It also suggests that PTH could play a role in causing the stiffening of large arteries, as suggested recently. 31 …”

Section: Discussionmentioning

confidence: 99%

Primary Hyperparathyroidism With Concurrent Primary Aldosteronism

et al. 2011

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: P Rimary Hyperparathyroidism (Ppth) Ismentioning

confidence: 99%

“…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 selection criteria for the controls, it should be emphasized that in the study by Rosa et al, 7 removal of parathyroid adenoma and correction of PPTH were followed by resolution of the increased PWV and a decrease in BP. Therefore, that excess PTH per se has a major detrimental effect on the arterial wall, as shown by increased BP and induced stiffening of the aorta.…”

Section: P Rimary Hyperparathyroidism (Ppth) Ismentioning

confidence: 99%

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

Rossi

2010

Hypertens Res

View full text Add to dashboard Cite

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...

show abstract

“…Areal bone mineral density (BMD) (g/cm 2 ; bone mineral content relative to projection area) was measured by DXA (Hologic Discovery W; Hologic Inc., Bedford, MA, USA) at the proximal femur, with a hyperparathyroidism [9][10][11] . Also, Rubin et al 12) found a positive correlation between PTH levels and aortic stiffness in patients with mild primary hyperparathyroidism; however, other studies in patients with primary hyperthyroidism did not confirm the association between PTH levels and aPWV 10,13,14) .…”

Section: Clinical Evaluation and Bone Mineral Densitymentioning

confidence: 99%

“…Exposure to traditional cardiovascular risk factors has been viewed as the key contributor to arterial stiffening 7,8) . Recently, a number of studies have investigated the association between parathyroid hormone (PTH) levels and aortic stiffness in different clinical settings [9][10][11][12][13][14][15][16] . Some studies have found that aPWV is increased in patients with primary…”

Section: Introductionmentioning

confidence: 99%