Type II benign osteopetrosis (Albers-Schönberg disease) caused by a novel mutation in CLCN7 presenting with unusual clinical manifestations.

A 16-year-old male patient with type II autosomal dominant benign osteopetrosis (ADO) was genotyped and found to harbor a novel mutation in exon 25 of the gene encoding for the osteoclast-specific chloride channel, CLCN7, inherited from the father, who was asymptomatic. The patient had normal biochemical findings and acid-base balance, except for increased serum levels of creatine kinase, lactic dehydrogenase, and the bone formation markers bone alkaline phosphatase isoenzyme, osteocalcin and N-terminal type I collagen telopeptide/creatinine ratio. Unusual generalized osteosclerosis was observed together with a canonical increase in vertebral and pelvis bone mass. An affected first grade cousin presented with normal biochemical findings and a milder osteosclerotic pattern of the pelvis. At the cellular level, cultured osteoclasts from the patient showed increased motility, with lamellipodia, membrane ruffling and motile pattern of podosome distribution, all of which could have contributed to functional impairment of bone resorption. The present report documents a novel mutation of the CLCN7 gene causing osteopetrosis in a radiologically uncertain form of the diseases, with apparent incomplete penetrance.

Severity of human hypertension in relation to the age in which high blood pressure makes its presumptive appearance.

PURPOSE: The present study investigates the properties of blood pressure (BP) circadian rhythm (CR) in newly-diagnosed hypertensives (NDH) as a function of the chronological age in which hypertension became manifest. MATERIALS AND METHODS: The study was performed on 141 NDH (71 males and 70 females, ranging in age from 24 year to 79 years), who were monitored in their 24-h BP via a non-invasive, ambulatory, automated recorder. The relation between the properties of BP CR and the age of the development of hypertension was investigated via the Clinospectror method, a trend analysis (periodic-linear regression method) for rhythmic biophenomena. RESULTS: A trend was detected for each one of the three properties of BP CR in relation with the age in which high BP made its appearance. As a matter of fact, the daily mean level (mesor) of BP CR was seen to be progressively less pronounced. The amplitude was found to show a progressive increment of its extent. The acrophase was seen to show a progressive antemeridian rotation of its timing. CONCLUSIONS: These trends suggest that hypertension tends to be less severe when its development occurs in subjects older in age. Such a less pronounced severity is, however, accompanied by a more pronounced oscillation of BP values during the 24-h of the day. Such a higher circadian variability, in turn, tends to show its highest expression during the morning hours of the day.

Adrenomedullin concentrations are elevated in plasma of patients with primary hyperparathyroidism.

The aim of the study was to evaluate plasma adrenomedullin (AM) concentration in primary hyperparathyroidism (PHP) and its effect on the regulation of blood pressure. Forty-one patients with PHP (25 normotensive and 16 hypertensive), and 31 healthy subjects (HS) were included in the study. As expected the total and ionized calcium and i-PTH serum levels were significantly higher in patients with PHP than in HS (P <.001). No significant difference was found in calcium-phosphorus metabolism parameters between normotensive and hypertensive PHP patients. Serum i-PTH levels correlated positively with systolic blood pressure (SBP) (r = 0.510; P <.02), diastolic blood pressure (DBP) (r = 0.586; P <.01) and heart rate (HR) (r = 0.486; P <.043) only in hypertensive PHP patients. Overall, mean plasma AM concentrations were significantly higher in PHP patients (16.1 +/- 7.9 pg/mL) than in HS (11.3 +/- 4.8 pg/mL) (P <.003) and correlated with i-PTH (r = 0.430; P <.005). However, in hypertensive PHP patients plasma AM levels (22.5 +/- 4.7 pg/mL) were higher than in normotensive PHP patients (11.6 +/- 1.8 pg/mL) (P <.001) and correlated with DBP (r = 0.902, P <.0029). In HS no correlation was found between plasma AM values and biohumoral, hormonal, or hemodynamic parameters. In conclusion, we demonstrated that in patients with PHP, plasma AM concentrations are increased and correlate with i-PTH and blood pressure values. We suggest that increased AM levels could be a compensatory factor in the defence mechanism against further blood pressure elevation.

[High circulating levels of adrenomedullin and endothelin-1 in obesity associated with arterial hypertension]. / Elevati livelli circolanti di adrenomedullina e di endotelina-1 nell'obesità associata ad ipertensione arteriosa.

BACKGROUND: The aim of the study was to investigate the behavior of two endothelial vasoactive peptides, adrenomedullin (vasodilator) and endothelin-1 (vasoconstrictor), in human obesity with and without arterial hypertension. METHODS: The study was carried out on 30 obese subjects (body mass index > 27 kg/m2) divided into two groups: 15 normotensive obese patients (10 males, 5 females, mean age 42 +/- 12 years) and 15 hypertensive obese patients (9 males, 6 females, mean age 42 +/- 13 years). The control group consisted of 21 normal subjects (12 males, 9 females, mean age 38 +/- 12 years) and of 16 patients with essential hypertension (10 males, 6 females, mean age 41 +/- 12 years) but without organ damage. All studied subjects were taking a normocaloric (20-22 kcal/kg/day), normosodic (120-140 mEq/day) and normopotassic (50-60 mEq/day) diet. Between 8.00 and 9.00 a.m., a venous blood sample was taken for the determination (radioimmunoassay) of plasma adrenomedullin and endothelin-1 concentrations. RESULTS: Plasma adrenomedullin levels in normal subjects (13.7 +/- 6.1 pg/ml) were similar to those in normotensive obese patients (14.8 +/- 7.2 pg/ml), whereas in hypertensive obese patients (22.5 +/- 9.1 pg/ml) and in those with essential hypertension (22.7 +/- 8.2 pg/ml) levels were significantly higher (ANOVA = 0.000, p < 0.05) than those of normal subjects and of normotensive obese patients. Moreover, endothelin-1 plasma concentrations were found to be significantly higher (ANOVA = 0.000, p < 0.05) in hypertensive obese patients (10.3 +/- 2.7 pg/ml) compared to normal subjects (6.5 +/- 2.4 pg/ml), normotensive obese patients (8.3 +/- 1.5 pg/ml) and to those with essential hypertension (8.5 +/- 2.9 pg/ml). In patients with essential hypertension, a positive correlation (r = 0.493, p < 0.05) was found between adrenomedullin and endothelin-1 plasma levels. CONCLUSIONS: These results revealed that in human obesity associated with arterial hypertension there is an increased production of plasma adrenomedullin and endothelin-1 that, with their opposite vasoactive properties (vasodilation/vasoconstriction), can contribute to this pathological association.

Plasma levels of endothelin-1 increase in patients with sarcoidosis and fall after disease remission.

BACKGROUND: Sarcoidosis is a chronic systemic disease, characterized by an imbalance of immunity processes and the presence of granuloma. Endothelin-1, a new vasoactive and bronchoconstrictive peptide, is a powerful mitogen for smooth muscle cells and fibroblasts and plays a role in the inflammation state. We postulate that endothelin-1 has a role in sarcoidosis. METHODS: We studied the behaviour of circulating levels of endothelin-1 in 20 patients with sarcoidosis and its correlation with some biochemical parameters of activity disease, such as erythrocyte sedimentation rate (ESR) and serum angiotensin-converting enzyme (SACE). We measured serum levels of ESR, SACE, calcium and plasma endothelin-1 levels in all patients at the beginning of the study and one again in 9 patients with clinical-biochemical remission of disease after steroid treatment. RESULTS: In patients with sarcoidosis, circulating levels of endothelin-1, SACE and ESR were significantly higher (p<0.001) than those of healthy subjects. Moreover, in patients with pulmonary involvement, there was a significant statistical difference (p<0.001) between endothelin-1 levels and radiological stage compared to normal subjects. In the 9 patients with remission of disease, both endothelin-1 levels and parameters of activity disease normalized. CONCLUSIONS: Our results seem to suggest that the increase of plasma endothelin-1 levels in active sarcoidosis can represent an expression of the endothelial dysfunction and reflect the picture of cellular activation.

[Incidentalomas of the adrenal glands. Personal cases and review of the literature]. / Incidentalomi del surrene. Casistica personale e revisione della letteratura.

BACKGROUND: The growing use of sensitive non-invasive methods to image the abdomen such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI), have resulted in increasing recognition of adrenal incidentalomas. METHODS: In this study, we report the clinical, endocrine and radiologic evaluation of 75 patients (50 women and 25 men, mean age 56 +/- 14 years) with adrenal incidentaloma (size 1 to 18 cm, mean 3 +/- 2.5 cm). None of the patients showed any symptoms or clinical signs that might indicate the existence of adrenal dysfunction. The patients underwent basal and dynamic evaluation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin-aldosterone system, and adrenomedullary function. Moreover, CT and MRI scan and Iodo-cholesterol (NP-59) scintigraphy were performed. RESULTS: The endocrine evaluation indicated 11 cases of pre-clinical Cushing's syndrome, 2 cases of pheochromocytoma and 62 not-functionally adrenal masses. On the basis of endocrine and morphologic data, 29 patients underwent surgical treatment: 20 adrenocortical adenoma, 2 pheochromocytomas, 2 not-cortisol-secreting adrenal carcinomas, 1 adrenal lymphoma, 1 adrenal metastasis, 1 myelolipoma, 1 hemorrhage and 1 pseudocystis. CONCLUSIONS: In conclusion, patient with an incidentally discovered mass has to be investigated to detect malignancy and subtle hormonal overproduction, to select the cases for surgical treatment.