Hypertension is often observed in patients with hyperparathyroidism. Whether hyperparathyroidism causes the hypertension is questionable and the nature of the mechanism is unknown. Parathyroid hormone functions to maintain Ca⁺⁺ levels in the blood. PTH is stimulated by low Ca⁺⁺ levels in the blood and leads to Vitamin D activation, increased Ca⁺⁺ absorption in the gut, increased bone reabsorption, increased Ca⁺⁺ reabsorption in the kidney and increased PO₄^- excretion in the urine. The net result of PTH activity is an increase in blood Ca⁺⁺ levels without an increase in PO₄^-. Hypertension could be caused by an increase in total peripheral resistance or an increase in blood volume. PTH can cause hypertension by increasing either of these two factors.

In their review article, Nussdorfer et al cite findings that PTH increases ACTH release. ACTH in turn increases blood levels of mineralocorticoids and glucocorticoids. As levels of the mineralocorticoid aldosterone rise, the kidney will retain more salt, thereby increasing blood volume and leading to an increase in blood pressure. Nussdorfer et al further cite studies that show PTH stimulates arginine-vasopressin release. AVP is a potent vasoconstrictor that also acts on the kidney to increase blood volume. The former affect would effect an increase in total peripheral resistance, contributing to hypertension.

In another article, Mazzocchi et al, show that PTH acts directly on dispersed adrenal cortex cells to stimulate aldosterone and cortisol production. They show that this activation is a direct result of PTH stimulation by showing a complete inhibition of the stimulation with a PTH receptor inhibitor. Furthermore, they show that ACTH does not mediate this activation; the application of an ACTH receptor inhibitor did not attenuate the response to PTH. Mazzocchi et al also investigated the signal pathway activated by PTH. PTH stimulates increases in cyclic AMP and IP3, which in turn activate protein kinase A and protein kinase C respectively. They show PTH activation of adenylate cyclase and phopholipase C by measuring increases in cyclic AMP and IP3 with PTH stimulation. They also show that specific inhibitors of adenylate cyclase and phopholipase C inhibit production of cAMP and IP3 respectively. Furthermore, Mazzocchi et al show that the two inhibitors together abolish the PTH induction of aldosterone and cortisol. Specific inhibitor of pkA and pkC administered together also abolish PTH stimulation of cortisol and aldosterone.

Studies show that PTH causes increases in arginine-vasopressin and aldosterone. Both these hormones would lead to increases in blood volume, which would ultimately lead to hypertension. Additionally, arginine-vasopressin would increase total peripheral resistance, further contributing to hypertension. PTH induction of these hormones may be the cause of the hypertension associated with hyperparathyroidism. These studies do not prove that hyperparathyroidism causes hypertension and the fact that only thirty percent of patients with hyperparathyroidism present hypertension generates further doubt as to the causal relationship of the two. Several questions remain; why does PTH induce hormones that increase blood volume? Does this serve a physiological function or is it an evolutionary accident?