Cabergoline (CAB) treatment is an effective, safe and well tolerated approach for hyperprolactinemia. We investigated the efficacy of 24-month treatment with CAB in 37 patients with previously untreated PRL-secreting pituitary adenoma and evaluated the hormonal and neuroradiological changes after the discontinuation of long-term therapy. Eleven patients with macroprolactinoma (1M/10F) and 26 with microprolactinoma (4M/22F) started treatment taking 0.25 mg CAB twice a week for 4 weeks. The dose was increased stepwise in 0.5 mg increments until reaching lowest maximally effective and tolerated dose. CAB was withdrawn before the end of the study in 6 women who became pregnant and in one patient who showed a slight increase of the macroadenoma at MRI. During treatment, PRL levels decreased significantly in macro (11.1+/-1.1 vs 407.8+/-98.3 microg/l, p<0.001) and microprolactinomas (11.1+/-1.6 vs 193.8+/-23.4 microg/l, p<0.05) and normalized in all macro and in 23/26 microprolactinomas. In 3 cases PRL levels decreased but did not normalize because the appearance of side effects, such as nausea or hypotension, prevented the increase of the dose of CAB. The effective dose of drug correlated significantly with basal serum PRL levels (p<0.05) and with the pituitary tumor size (p<0.05). A significant decrease of the mean adenoma size was evident for macro (6.9+/-1.8 vs 16.0+/-1.8 mm, p<0.001) and microprolactinomas (3.0+/-0.5 vs 6.5+/-0.4 mm, p<0.001) at MRI. The tumor disappeared in 4 macroadenomas and in 11 microadenomas after 12 months of treatment. CAB withdrawal was followed by serum PRL increase in 13 cases after 3 months, in 6 after 6 months, in 2 after 9 months, and in one patient at the 12th month. Five patients showed normoprolactinemia with negative MRI after one year. Regular menses were restored in 7/10 macroprolactinomas and in all oligo-amenorrhoic patients with microadenoma; serum testosterone levels normalized in 2/3 hypogonadic men. Five out of 6 women become pregnant and had uneventful pregnancies which resulted in deliveries of normal babies. In conclusion, this study confirms the effectiveness and safety of CAB for patients with PRL-secreting pituitary adenoma and suggests that it can be considered a first choice treatment.

In our study, the integrated evaluation of FS and AS showed that 41% of acromegalics are at risk for coronary atherosclerosis and that coronary calcifications were evident in about half of them despite the fact that myocardial infarction was not more frequent in acromegalic patients than the general population. Moreover, the control of acromegaly did not influence significantly the extent of coronary atherosclerosis.

Objective: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. Design: We studied 26 patients (nine male, 17 female; 42.5^12.7 years, mean^S.E.) with ACTHsecreting pituitary macroadenoma (tumor diameter: 11-40 mm). Methods: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78^10 months. Results: Before surgery, dexa decreased ACTH (. 50% of baseline) in only 14/22 patients. The CRHstimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P , 0.05) and cured (P , 0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P , 0.02) and in normalized patients (P , 0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. Conclusions: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

Primary empty sella (PES) is a very frequent neuroradiological finding in the general population, that can induce hypopituitarism. Some studies focused on the association of PES with GH deficiency (GHD) or hypogonadotropic hypogonadism (HH), while data regarding the involvement of hypothalamic-pituitary-thyroid (HPT) axis, despite sporadic reports of central hypothyroidism, or the occurrence of hypoadrenalism (HA) are scanty. In this study, thyroid function and TSH response to exogenous TRH injection (TRH/TSH) were investigated in 43 patients [10 men and 33 women; aged (mean +/- SD), 48+/-12 yr] with PES: 22 patients had total and 21 partial PES. Forty healthy subjects (9 men and 31 women; aged 46+/-12 yr) were enrolled as a control group. Central hypothyroidism was found only in 2/43 cases, whereas one patient showed primary hypothyroidism. In euthyroid patients, mean serum TSH levels were significantly lower than controls (TSH: 1.0+/-0.7 vs 1.4+/-0.6 mU/l, p<0.01) and 79% of them showed abnormal TRH/TSH responses (TRH test was performed in 34 euthyroid patients: 17 cases with total and 17 cases with partial PES), but mean serum free T4 (FT4) and free T3 (FT3) values were not significantly lower than controls (FT4: 15.9+/-0.4 vs 15.0+/-2.1 pmol/l, p=NS; FT3: 5.3+/-1.2 vs 5.8+/-1.5 pmol/l, p=NS). Moreover, no significant differences were evident in mean serum TSH, FT4 and FT3 between patients with total and partial PES (TSH: 1.1+/-0.7 vs 0.9+/-0.8 mU/l, p=NS; FT4: 16.3+/-2.6 vs 15.7+/-2.2 pmol/l, p=NS; FT3: 5.4+/-1.3 vs 5.2+/-0.8 pmol/l, p=NS) and the TRH/TSH peak was impaired or exaggerated/delayed in 9 and 3 patients with total and in 12 and 3 cases with partial PES. No significant differences in the prevalence of abnormal TRH/TSH responsiveness were found between patients with partial or total PES (chi2=1.6, p=NS). Other impairment of pituitary function was detected in 23/43 patients: GHD was present in 15 cases, HH in 11 and central HA in 5 patients. Isolated or combined hypopituitarism was present in 17 and in 6 patients, respectively. In conclusion, pituitary dysfunction is very frequent in patients with PES, but central hypothyroidism occurs rarely. The entity of arachnoid herniation into the sellar fossa does not play a significant role on the degree of HPT axis dysfunction.

Cushing's syndrome (CS) is associated with high cardiovascular risk. The aim of this study was to analyze intimal media thickness (IMT) in patients with CS and compare them with subjects matched for similar conventional and independent cardiovascular risk factors. Twenty eight patients with CS (mean age: 40.7 +/- 2.5 y) and 28 subjects (mean age: 41.1 +/- 14 y) matched for sex, age, smoking habit, body mass index, blood pressure levels, glucose and lipid metabolism were evaluated. IMT was measured at right and left common carotid (CC), carotid bulb (BC), aorta (Ao) and femoral (F) levels by B-echo-Doppler ultrasonography. Although parameters of cardiovascular risk factors did not differ statistically between patients and controls, IMT was significantly increased (right and left CC-IMT, p < 0.05; right and left BC-IMT, p < 0.01, Ao-IMT p < 0.05) and wall plaques were more common (14.2 % VS. 7.1 %) in patients. In CS patients, CC-IMT and F-IMT correlated positively and significantly with fasting glucose (right CC-IMT: r (2) = 0.37, p = 0.05; left CC-IMT: r (2) = 0.43, p = 0.02; right F-IMT: r (2) = 0.57; p < 0.01; left F-IMT: r (2) = 0.47, p = 0.01) and HOMA index (left CC-IMT: r (2) = 0.64, p < 0.01 and left F-IMT: r (2) = 0.48, p < 0.05). The CS patients' waist-to-hip ratio (WHR) was evaluated and correlated positively and significantly with CC-IMT (right: r (2) = 0.53, p = 0.01 and left: r (2) = 0.44, p = 0.05). No correlation was found between IMT and cortisol levels, however. In conclusion, patients with CS have more severe atherosclerotic damage than a population matched for similar cardiovascular risk factors. Multiple events related to long-term cortisol effects on metabolism and at vascular and endothelial sites may increase the risk of cardiovascular damage in patients with CS.