Primary Hyperparathyroidism With Concurrent Primary Aldosteronism

Abstract

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...

Furosemide stimulation of parathormone in humans: role of the calcium-sensing receptor and the renin-angiotensin system

“…Indeed, calcium sensing receptors are expressed in juxtaglomerular cells in mice [23] and rats [18]. Recent findings in humans indicate that there is a tight link between the RAAS and the parathyroid glands, suggesting that the RAAS may mediate the furosemide effect on PTH secretion [4,15,16,19,20,22,29]. In a previous experimental study, we demonstrated that administration of the calcimimetic RS568 inhibited renin secretion in rats and blunted the renin response induced by furosemide [18].…”

Bone and Mineral Metabolism in Patients with Primary Aldosteronism

“…Moreover, these researchers demonstrated the expression of the mineral corticoid receptors (MR) in both PTH secreting adenoma and in parathyroid tissue [11], and the MR was predominantly located in the nucleus of the parathyroid cells, indicating that aldosterone participate in a “tonic” regulation of PTH synthesis and secretion. Finally, Tomaschitz et al [7] showed that patients with PA are with secondary hyperparathyroidism that can be successfully treated with either mineral corticoid receptor antagonists or adrenal surgery.…”

Double hit! A unique case of resistant hypertension

“…Gene expression and immunohistochemistry studies show PTH receptors in APAs and MR receptors in parathyroid cells. The significance of experimental studies demonstrating the expression of the PTH receptor in the cytoplasm of APA cells lies in the hypothesis that PTH may directly influence the synthesis of aldosterone and thus provide a pathway to describe the persistent state of hyperaldosteronism and hypertension in similar cases 8. The mechanism driving persistent hyperaldosteronism is an area of uncertainty.…”

“…The evaluation of PA in this case is on the basis of resistant hypertension without evidence of hypokalaemia or adrenal incidentaloma. Of interest, in a study of hypertensive patients, hypokalaemia was observed in 48% of patients with APA and only 17% of those with IHA 8. It is widely accepted that hypokalaemia is not a required diagnostic criteria of PA, but the distinction between IHA from low-renin primary (essential) hypertension remains an area of debate.…”

“…The underlying mechanism linking excess PTH to increased blood pressure has been shown in vitro where PTH stimulates secretion of aldosterone from human adrenocortical cells in a concentration-dependent fashion 8. Gene expression and immunohistochemistry studies have subsequently demonstrated expression of type 1 PTH receptors in the cytoplasm of APA cells in a patient with PA and concurrent PPTH, providing evidence that PTH could influence the synthesis of aldosterone.…”