Cardiovascular accidents represent the most important cause of death in patients with Cushing’s syndrome. This prospective study aims at evaluating carotid arteries by echo-Doppler ultrasonography and clinical and metabolic markers of atherosclerosis in 25 patients with Cushing’s disease (CD) before and after 1 yr of remission. Thirty-two sex- and age-matched subjects (control-1) and 32 body mass index-matched subjects (control-2) served as controls. At diagnosis, CD patients had higher body mass index, waist to hip ratio (WHR), total, low-density lipoprotein-cholesterol and total/high-density lipoprotein (HDL) ratio, glucose and insulin, as well as lower HDL-cholesterol than control-1; they had higher WHR and total/HDL ratio and lower HDL-cholesterol than control-2. They also had higher intima-media thickness (IMT), and lower systolic lumen diameter and distensibility coefficient (DC) than either control group. Atherosclerotic plaques were detected in 31.2% of patients, 0 control-1, and 6.2% of control-2 subjects. One year after remission, WHR, LDL-cholesterol, and IMT significantly decreased, whereas systolic lumen diameter and DC significantly increased. However, all of the above parameters were still abnormal compared with control-1, but not control-2. A significant correlation was found between WHR, glucose and insulin levels, and right and left carotid IMT. WHR was the best predictor of left IMT and left DC in active, but not in cured, patients. The duration of hypercortisolism was the best predictor of right DC in active but not in cured patients. In conclusion, patients with CD have severe atherosclerotic damage. The persistence of a metabolic syndrome, vascular damage, and atherosclerotic plaques after cortisol level normalization makes these subjects still at high cardiovascular risk despite disease remission.

Context: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism. Objective: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury. Design and Patients: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32). Results: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency. Conclusion: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

Whether the withdrawal of treatment in patients with nontumoral hyperprolactinemia, microprolactinomas, or macroprolactinomas is safe and effective has been unclear. We performed an observational, prospective study of cabergoline (a dopamine-receptor agonist) withdrawal in such patients. The study population included 200 patients — 25 patients with nontumoral hyperprolactinemia, 105 with microprolactinomas, and 70 with macroprolactinomas. Withdrawal of cabergoline was considered if prolactin levels were normal, magnetic resonance imaging (MRI) showed no tumor (or tumor reduction of 50 percent or more, with the tumor at a distance of more than 5 mm from the optic chiasm, and no invasion of the cavernous sinuses or other critical areas), and if follow-up after withdrawal could be continued for at least 24 months. Recurrence rates two to five years after the withdrawal of cabergoline were 24 percent in patients with nontumoral hyperprolactinemia, 31 percent in patients with microprolactinomas, and 36 percent in patients; with macroprolactinomas. Renewed tumor growth did not occur in any patient; in 10 female patients (22 percent) and 7 male patients (39 percent) with recurrent hyperprolactinemia, gonadal dysfunction redeveloped. In all diagnostic groups, prolactin levels at the time of recurrence were significantly lower than at diagnosis (P<0.001). The Kaplan–Meier estimated rate of recurrence at five years was higher among patients with macroprolactinomas and those with microprolactinomas who had small remnant tumors visible on MRI at the time of treatment withdrawal than among patients whose MRI scans showed no evidence of tumor at the time of withdrawal (patients with macroprolactinomas, 78 percent vs. 33 percent, P=0.001; patients with microprolactinomas, 42 percent vs. 26 percent, P=0.02). Cabergoline can be safely withdrawn in patients with normalized prolactin levels and no evidence of tumor. However, because the length of follow-up in our study was insufficient to rule out a delayed increase in the size of the tumor, we suggest that patients be closely monitored, particularly those with macroprolactinomas, in whom renewed growth of the tumor may compromise vision.

Objective: The diagnosis of growth hormone (GH) deficiency (GHD) in adults is based on a reduced peak GH response to provocative tests, such as the insulin tolerance test (ITT) and the GH-releasing hormone-arginine (GHRH-ARG) test. However, the cut-off limits of peak GH response in lean subjects are not reliable in obese patients; this is noteworthy since adult GHD is often associated with obesity. Aim of this study was to evaluate the diagnostic cut-off limits of peak GH response to the GHRH-ARG test in overweight and obese as well as in lean population. Design and methods: The GH responses to the GHRH-ARG test were studied in 322 patients with organic hypothalamic-pituitary disease and in 318 control subjects. Patients were subdivided into two groups on the basis of the number of pituitary hormone deficits, except for GH deficiency: (a) patients with total pituitary hormone deficit (TPHD) and (b) patients without or with no more than two pituitary hormone deficits (PHD). Both patients and control subjects were divided into three subgroups according to body mass index (BMI): lean (BMI <25 kg/m²), overweight (BMI ≥25 and <30 kg/m²) and obese (BMI ≥30 kg/m²). TPHD patients were assumed to be GH deficient, whereas PHD patients may include subjects with either normal or impaired GH secretion. The statistical analysis was carried out by the Receiver-Operating Characteristic curve analysis (Medcalc 7.2). The diagnostic cut-off points were calculated for lean, overweight and obese subjects to provide optimal separation of GH-deficient patients and control subjects according to two criteria: (1) a balance between high sensitivity and high specificity; (2) to provide the highest pair of sensitivity/specificity values for GH deficiency. Results: In the lean population the best pair of values, with highest sensitivity as 98.7% and highest specificity as 83.7%, was found using a peak GH cut-off point of 11.5 μg/l. In the overweight population the best pair of values, 96.7 and 75.5%, respectively, was found using a peak GH cut-off point of 8.0 μg/l. In the obese population the best pair of values, 93.5 and 78.3%, respectively, was found using a peak GH cut-off point of 4.2 μg/l. Applying the above mentioned cut-off points, among PHD patients we found that 80 subjects (72%) were GHD whereas 31 (28%) had normal GH secretion. Conclusions: In conclusion the GHRH-ARG test is a reliable tool for the diagnosis of adult GH deficiency in lean, overweight and obese patients, provided that specific BMI-related cut-off limits are assumed.