Different patterns of steroid secretion in patients with adrenal incidentaloma.

We previously found that a remarkable number of patients with adrenal incidentaloma display partially autonomous cortisol secretion. The amount of hypercortisolism is insufficient to give clinical expression, but enough to inhibit, in some cases, normal adrenal tissue. Other researchers found with high frequency a partial deficiency of 21-hydroxylase. The aim of the present study was to make a combined evaluation of these aspects of adrenal steroidogenesis. Twenty patients (6 men and 14 women, aged 25-74 yr; median, 59 yr) with incidentally discovered adrenal masses were studied. All had an adrenal adenoma histologically proven or diagnosed on the basis of size (< or = 4.0 cm in all but 1) and computed tomography picture (hypodense homogeneous mass with well defined margins). The following parameters were used to evaluate the ACTH-cortisol axis: overnight 1-mg dexamethasone suppression (4 nonsuppressors), ovine CRH stimulation (blunted ACTH-cortisol response in 2 cases), circadian serum cortisol rhythm (blunted night/day ratio in 4 and increased 24-h mean in 1), and 24-h urinary free cortisol excretion (always within the normal range). Three patients had 2 concomitant alterations, and 5 had a single abnormality. Partial deficiency of 21-hydroxylase was assumed in 6 patients who showed an exaggerated 17-hydroxyprogesterone response to ACTH, with a peak value of more than 10 ng/mL (> 30 nmol/L), according to New's nomogram. No abnormalities of the ACTH-cortisol axis were found in these patients, with the exception of low amplitude cortisol rhythm in 1 case. Therefore, 2 distinct patterns, dysregulated and partially autonomous cortisol secretion, on the one hand, and reduced 21-hydroxylase activity, on the other, can be found in a high number of patients bearing an adrenal incidentaloma. They appear mutually exclusive, and the differentiation by endocrine testing is quite clear. Serum dehydroepiandrosterone sulfate was below the third percentile in 13 of 20 patients and could represent a specific marker of cortical adenomas. This finding was evenly distributed among patients with subclinical hypercortisolism or partial enzymatic defect; therefore, low serum dehydroepiandrosterone sulfate is not readily attributable to suppressed ACTH secretion, which actually occurs in only some patients with subclinical hypercortisolism.

Doppler echocardiographic patterns in patients with acromegaly.

Cardiovascular problems have long been recognized as responsible for an increased morbidity and mortality in patients with acromegaly. The aim of the present study was to evaluate echocardiographically the prevalence of cardiomyopathy in a cohort of acromegalic patients and to analyze the results in relation to demographic, clinical and hormonal data. This study, a retrospective controlled clinical trial, was performed in 25 acromegalic patients, 12 men and 13 women aged 26-66 years (mean: 52.6). Fifteen patients had an active disease, 10 were cured by previous pituitary surgery. The same echocardiographic parameters were analyzed in 50 healthy subjects aged 30-70 years (mean: 51.4). Serum GH was determined on at least 4 samples drawn over 24 hours and plasma IGF-I on a single point. Standardized parameters of diastolic and systolic function were evaluated by real-time Doppler echocardiography. Twelve patients with active acromegaly underwent also 48-hour ECG registering. Left ventricular (LV) hypertrophy was found in 14/25 patients (56%). No difference was found between patients with active disease (53%) and patients with cured acromegaly (60%). LV mass index was significantly increased in acromegalics in comparison with healthy subjects (137 +/- 43 g/m2 vs 96 +/- 16 g/m2, p < 0.01) and also the indices of LV diastolic function were significantly impaired. Asymmetric septal hypertrophy was found only in one patient. Hypertension was detected in 9/25 patients (36%) without difference between patients with active or cured disease (40% vs 30%, NS). No significant correlation was found between hormonal or clinical data and echocardiographic findings. During Holter monitoring, heart rate of acromegalics was not significantly different from that of controls (78 +/- 12 bpm vs 72 +/- 10 bpm, NS) and only isolated supraventricular or ventricular premature complexes (Lown class 1) were detected. In conclusion, this study provides evidence of subclinical LV dysfunction in acromegaly in the absence of other known causes of heart disease and no significant difference in echocardiographic pattern was apparent between active or cured acromegalics.

Adrenal incidentaloma, a five year experience.

Since 1989, 45 patients 26 females and 19 males, aged 19-79 years (median 58) bearing incidentally discovered adrenal masses were studied. Endocrine work-up included determination of urinary catecholamines and their metabolites, measurement of plasma renin activity and aldosterone levels in clino- and orthostatic posture, basal and dynamic (dexamethasone-suppression, o-CRH stimulation) evaluation of hypothalamic-pituitary-adrenal (HPA) axis. The most frequent finding was the reduction of DHEA-S levels below the 3rd percentile of controls in 19 (42%) patients. As a whole group, DHEA-S levels were significantly lower in patients than in controls: 68 (5-1000) micrograms/dL vs 208 (34-326) micrograms/dL; p < 0.001. Three patients (7%) had high 24-h mean serum cortisol levels and 6 (14%) had blunted day-night amplitude of cortisol rhythm. Defective dexamethasone suppressibility was found in 15% of patients vs 8% of controls (p < 0.05). ACTH and cortisol responses after o-CRH did not significantly differ between patients and controls although blunted ACTH responses were found in 22% of cases. The above mentioned endocrine alterations could be accounted for by autonomous cortisol secretion by the adrenal nodule at a rate not sufficient to give clinical expression but able to inhibit to some extent the HPA axis. These results indicate that silent cortisol hypersecretion is frequently observed in patients with adrenal incidentaloma even if progression to overt Cushing's syndrome seems unlikely, at least in a short-term follow-up. From a mere cost-benefit ratio, the evaluation of DHEA-S levels and dex-suppression has sufficient sensitivity to identify the occurrence of silent hypercortisolism.

[The clinical evaluation of the hypocholesterolemic effects of an inhibitor of cholesterol synthesis: mevalonic acid]. / Valutazione clinica degli effetti ipocolesterolemizzanti di un inibitore della sintesi del colesterolo: l'acido mevalonico.

Twenty eight patients with heterozygous familial hypercholesterolemia were treated with mevalonic acid (an inhibitor of cholesterol synthesis) for 45 days. Patients received a daily dose of 750 to 1500 mg mevalonic acid depending on plasma cholesterol levels. Results showed a significant reduction in cholesterol values whereas no significant difference was observed in HDL cholesterol and triglyceride levels.