Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas

Abstract

In order to investigate the possible existence of abnormal calcium metabolism and parathyroid function in primary aldosteronism (PA), we have compared the calcium/parathyroid hormone (PTH) profile of patients with PA with the profile of healthy normotensive subjects and of patients with essential hypertension (EH). Furthermore, we have evaluated the effects of spironolactone and the surgical removal of aldosterone-producing adenomas on the calcium/PTH profile in the PA patients. Four groups of 10 subjects each participated in the study: 1) hypertensive patients with PA, 2) patients with low-renin EH (LREH), 3) patients with normal-renin EH (NREH), 4) normotensive healthy subjects (NS). The four groups were well-matched for age, sex, body mass index, and renal function. The three hypertensive groups were also matched closely for blood pressure values and for duration of hypertension. In all subjects, after 1 week of a controlled intake of Na and K, the following parameters were measured: urine excretion of Na, K, Ca, Mg, and P, plasma levels of K, Mg, inorganic P, total calcium and ionized calcium, and plasma renin activity, aldosterone concentration, and intact PTH. Blood pressure and laboratory parameters were determined again in all the PA patients after 1 month of 100 mg daily spironolactone administration, and in four out of the 10 PA patients 2 months after surgical removal of aldosterone-producing adenomas. All of these subjects had undergone the same controlled intake of Na and K indicated above. Serum intact PTH was higher in PA patients than in the other three groups (P < .01), and serum ionized calcium was significantly higher in normotensive subjects than in the three hypertensive groups (v PA P < .01, v LREH and v NREH P < .05). An increase in serum ionized calcium and a decrease in PTH level were associated with both spironolactone administration (P < .001) and surgical treatment (P < .05). These results suggest the presence of calcium metabolism alterations in both PA and EH patients, but that these alterations are more exaggerated in PA, so that higher PTH levels are needed for maintaining low-normal levels of serum ionized calcium.

Modulation of Renal Calcium Handling by 11β-Hydroxysteroid Dehydrogenase Type 2

“…Moreover, the fractional excretion of Ca 2ϩ was higher during GA compared with baseline, indicating that the increase in calciuria was a consequence of decreased tubular reabsorption. Thus, the present observation is consistent with the reduced concentration of serum ionized Ca 2ϩ and increased urinary Ca 2ϩ excretion reported in patients with primary aldosteronism (13,14).…”

“…The higher urinary Ca 2ϩ excretion observed during inhibi- tion of 11␤HSD2 is consistent with the increased calciuria observed in both animals (27) and humans (28) after long-term mineralocorticoid administration, as well as with the higher Ca 2ϩ excretion reported in patients with primary aldosteronism compared with that in normotensive control subjects (14,29). However, this increase in urinary Ca 2ϩ excretion associated with mineralocorticoid excess does not seem due to direct effects of aldosterone.…”

“…Alterations of calcium metabolism and parathyroid function, namely reduced concentration of serum ionized calcium (Ca 2ϩ ), increased urinary Ca 2ϩ excretion, and elevated circulating level of parathyroid hormone (PTH), have been reported in both essential hypertension (11,12) and primary aldosteronism (13,14). Serum Ca 2ϩ increases rapidly after adrenalectomy in patients with aldosteronoma (13), suggesting a direct effect of the steroid hormone.…”

Primary Hyperparathyroidism Associatiated with Aldosterone-Producing Adrenocortical Adenoma and Breast Cancer: Relation to MEN1 Gene

“…They reported that serum calcium levels tend to be low, and plasma PTH levels tend to be high in patients with primary aldosteronism. The abnormalities were corrected after administration of spironolactone or surgical treatment (15), suggesting that primary aldosteronism is associated with mild secondary hyperparathyroidism. Coupled with these observations, serum calcium levels should be interpreted with caution in patients with primary aldosteronism, because hypercalcemia may be masked in the presence of aldosterone excess.…”

“…Both changes may lead to lowered serum calcium levels. Of relevance are studies by Resnick and Laragh (14), and by Rossi et al (15). They reported that serum calcium levels tend to be low, and plasma PTH levels tend to be high in patients with primary aldosteronism.…”