Carlos Fardella

Intracellular calcium and blood pressure: Comparison between primary hyperparathyroidism and essential hypertension

Intracellular calcium has been reported to be increased in essential hypertension, and thought to play a role in its genesis through facilitation of vascular smooth muscle contraction. Since hypertension is more prevalent in primary hyperparathyroidism, intracellular calcium may also be increased in this condition. To investigate whether the hyperparathyroid condition, i.e., hypercalcemia and increased PTH per se, could be associated with high intracellular calcium, we measured intracellular calcium in platelets with the Quin-2 AM fluorometric method in 11 normotensive patients with primary hyperparathyroidism, 15 patients with essential hypertension, and 18 normal controls, all matched for age and sex. We repeated the measurements in 9 of the hyperparathyroid patients after successful surgery. We found that intracellular calcium was higher in normotensive patients with primary hyperparathyroidism than in normal controls (198±24 vs 113±11 nM, p<0.05), but lower than in patients with essential hypertension (198±24 vs 286±38 nM, p<0.05). Successful removal of a parathyroid adenoma decreased intracellular calcium from 215±22 to 116±19 nM, (p<0.01 ). In the patients with primary hyperparathyroidism, intracellular calcium was strongly correlated with the levels of PTH (r=0.87, p<0.01), but not with the total serum calcium levels (r=0.04, NS). The decrease in intracellular calcium after parathyroidectomy was also strongly correlated with the decrease in PTH (r=0.84, p<0.01), but not with the decrease in total serum calcium (r=0.16, NS). In the patients with essential hypertension, intracellular calcium correlated well with systolic (r=0.69, p<0.01), diastolic (r=0.76, p<0.01) and especially mean arterial pressure (r=0.86, p<0.01). There was no correlation between blood pressure and intracellular calcium in the patients with primary hyperparathyroidism. We conclude that normotensive patients with primary hyperparathyroidism, as well as patients with essential hypertension, can have increased concentrations of intracellular calcium in platelets. The correction of the hyperparathyroid condition normalizes intracellular calcium concentration. The close correlation between PTH and intracellular calcium suggests that PTH may act as a ionophore for calcium entry into cells. Whether the increased levels of intracellular calcium may reflect a pre-hypertensive condition in normotensive patients with primary hyperparathyroidism remains to be determined.

A−6G Variant of Angiotensinogen Gene and Aldosterone Levels in Hypertensives

Recently, a novel mutation in the promoter region of the angiotensinogen gene that involves the presence of an adenine instead of a guanine 6 bp upstream from the transcription initiation site (A(-6)G) has been shown to induce an increase in gene transcription. The aim of this study was to determine the prevalence of the A(-6)G mutation in essential hypertensive patients and to correlate it with aldosterone and renin activity levels. We studied 191 hypertensives. We measured levels of aldosterone (plasma and urinary) and plasma renin activity. We determined the variants A and G using a mutagenically separated polymerase chain reaction technique. In 191 hypertensives, the A variant was detected in 266 of 382 (69.6%) and the G variant in 116 of 382 alleles (30.4%). Plasma aldosterone was significantly higher in patients homozygous for AA than in those homozygous for GG (369+/-208 versus 246+/-142 pmol/L). Urinary aldosterone was significantly higher in homozygous AA than in AG or GG patients (62.4+/-39.4 versus 50.8+/-25.2 and 37.4+/-22.3 nmol/d, respectively). When the patients were grouped according to the presence or absence of the A allele, the aldosterone levels and the plasma aldosterone/plasma renin activity ratio were significantly higher in patients with the A allele. The presence of the A variant was associated with higher levels of aldosterone. These results suggest that the presence of the A variant could determine the appearance of arterial hypertension through higher transcription activity of the angiotensinogen gene and concomitant aldosterone production.

Adrenal macrotumors diagnosed by computed tomography

Adrenal tumors larger than 6 cm are unusual but show a greater incidence of malignant etiologies than smaller adrenal tumors. The scarce information about adrenal macrotumors (AMT) induced us to study prospectively all patients who were seen in our clinic during the period 1984–1988 and were diagnosed by computed tomography (CT) to have an adrenal mass ≥ 6 cm. The clinical characteristics, including the main complaint, tumoral secretory activity, CT findings and histologic diagnosis from 18 patients are described; they represented a 0.3% of the total amount of abdominal CT studies performed. Seventy-two % of AMT resulted to be non Cortisol or catecholamines secreting masses, and from them, a 38% corresponded to malignant etiologies characterized by marked and rapid weight loss. Four out of five hormone secreting AMT corresponded to pheochromocytomas, while the fifth one resulted to be a bilateral macronodular hyperplasia secreting Cortisol. In two cases AMT did not correspond to a genuine adrenal mass, resulting to be a malignant histocytoma in one case and a hydatidic cyst in other one. When performed in two occasions, a percutaneous needle biopsy was a valuable diagnostic tool, permitting to diagnose a lymphoma and a tuberculoma. In conclusion: 1) AMT correspond mainly to non Cortisol or catecholamines secreting tumors, often malignant; 2) not all AMT diagnosed by CT correspond to true adrenal masses; 3) percutaneous needle biopsy can be a helpful procedure for diagnosing nonfunctioning solid AMT.