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Objective: To determine whether characteristics and outcomes of Italian patients in the observational global Hypopituitary Control and Complication Study (HypoCCS) differed according to the degree of GH deficiency (GHD)., Design: Patients were grouped by tertiles of stimulated GH peak concentration at baseline (Group A lowest tertile, n = 342; Group B middle tertile, n = 345; Group C highest tertile, n = 338)., Results: Baseline demographics, lipid levels, body mass index categories and mean Framingham cardiovascular risk indexes were similar in the three groups and remained substantially unchanged over time, with no subsequent significant between-group differences (except mean levels of triglycerides increased in the highest tertile group). GHD was adult-onset for >75% of patients in all groups. The percentage of patients with multiple pituitary deficiencies was higher in Group A than in the other groups; isolated GHD was reported with highest frequency in Group C. Patients in Group A received the lowest mean starting dose of GH. Hyperlipidaemia at baseline was reported in 35·1%, 31·1% and 24·7% of patients in groups A, B and C, respectively (P = 0·029). Mean duration of GH treatment was 7·21, 5·45 and 4·96 years, respectively. The proportion of patients with adverse events did not differ significantly between groups, with a low prevalence over time of diabetes and cancer., Conclusions: In Italian patients from HypoCCS, the level of GH deficit did not influence changes over time in metabolic parameters or adverse event profile, despite differences in GHD severity at baseline and in the starting GH dose., (© 2015 John Wiley & Sons Ltd.)

Objective: Antipituitary (APA) but not antihypothalamus antibodies (AHA) have been investigated in patients with idiopathic hypopituitarism. This study searched for APA and AHA in some of these patients to investigate whether pituitary or hypothalamic autoimmunity could play a role in their pituitary dysfunction., Design: Sixty-six patients with selective idiopathic hypopituitarism were studied: 27 with ACTH deficiency, 20 with GH deficiency and 19 with hypogonadotropic hypogonadism. Twenty patients with hypopituitarism secondary to hypophysectomy and 50 healthy subjects were enrolled as controls., Measurements: Antipituitary and AHA were evaluated by indirect immunofluorescence in sera of patients and controls. Positive sera were retested by a four-layer double immunofluorescence to identify the cells targeted by these antibodies., Results: Antipituitary were present at high titre in 4 of 27 patients with ACTH deficiency (14·8%), 4 of 20 with GH deficiency (26%) and 5 of 19 with hypogonadotropic hypogonadism (21%) and targeted, respectively, corticotrophs, somatotrophs and gonadotrophs. AHA were found at high titre only in 5 patients with ACTH deficiency (18·5%), mostly targeting corticotrophin-releasing hormone-secreting cells; none of these 5 patients resulted positive for antipituitary antibodies. Among the controls, only 1 hypophysectomized patient resulted APA positive at low titre., Conclusions: Our results suggest that in patients with selective idiopathic hypopituitarism, detection of APA or AHA could better characterize an autoimmune process involving the pituitary or hypothalamus, respectively. In particular, detection of antibodies targeting selectively ACTH-secreting or corticotrophin-releasing hormone-secreting cells may differentiate, respectively secondary from tertiary variants of autoimmune hypoadrenalism., (© 2011 Blackwell Publishing Ltd.)

Context: Approximately one-third of patients with acromegaly have concomitant hypertension. The outcome of hypertension after treatment of acromegaly is unknown., Objective: To evaluate the role of GH and IGF-I control on systolic (SBP) and diastolic blood pressure (DBP) levels., Patients: One hundred and five hypertensive patients (60 women, 45 men) with active disease receiving treatment for hypertension at their diagnosis of acromegaly., Design: Observational, retrospective, multicentre., Measurements: At diagnosis and after 24 months (median) of treatment we measured serum GH and IGF-I levels, blood pressure levels, left ventricular (LV) mass index (LVMi), early-to-late mitral flow velocity (E/A, as a measure of diastolic function) and LV ejection fraction (LVEF, as a measure of systolic function)., Results: At the diagnosis of acromegaly, hypertension was mild in 41.1% and severe in 58.9%. Serum GH and IGF-I levels did not differ in patients with mild or severe hypertension. After 24 months of treatment, all patients had a notable decrease in both GH and IGF-I levels, and achieved significantly lower levels of DBP, heart rate and LVMi; 76 patients (71%) had achieved control of GH and IGF-I levels. Only the patients with controlled acromegaly achieved significantly lower SBP levels and significantly improved cardiac systolic and diastolic function. A higher dose of antihypertensive drugs and/or an increased number of drugs to control hypertension were significantly greater in patients with uncontrolled (32.3%) than in those with controlled acromegaly (7.8%; P = 0.004)., Conclusion: Hypertensive patients with controlled acromegaly achieved improved control of hypertension and of cardiac diastolic and systolic function. The use of antihypertensive drugs was significantly less in patients achieving control of acromegaly.

Objective: Acromegaly is a chronic disease caused by increased GH secretion and associated with a greater risk of developing both benign and malignant tumours. In the present study we evaluated the prevalence of thyroid disorders and thyroid malignancies in a series of acromegalic subjects., Design and Patients: We studied, retrospectively, a continuous series of 125 acromegalic patients referred to the Endocrinology Centres at the University Hospitals of Catania and Ferrara, Italy, over a 22-year period., Measurements: Diagnosis and management of acromegaly were based on standardized criteria. In all patients thyroid function and morphology were evaluated by serum free T4, free T3, TSH measurements and ultrasound scanning, respectively. Fine-needle aspiration biopsy (FNAB) was performed in all solid-mixed thyroid nodules of diameter greater than 1 cm. IGF-1 expression was assessed by semiquantitative immunohistochemical analysis in some patients with differentiated thyroid cancer., Results: Abnormal thyroid function was found in eight cases (6%). A diffuse or nodular goitre was present in 102 cases (82%). Thyroidectomy was performed in 17 patients. Histological examination revealed a differentiated thyroid cancer in seven of the patients. No significant association of thyroid cancer with GH or IGF-1 levels was found. Semiquantitative assessment of IGF-1 expression by immunohistochemistry revealed a more intense staining in thyroid cancer from acromegalic subjects than in papillary thyroid cancer from nonacromegalic subjects., Conclusions: The frequency of thyroid disorders in our series of acromegalic subjects was similar to that previously observed in these patients. However, the prevalence of thyroid cancer was not only strikingly elevated (5.6%) in comparison to the estimated prevalence in the general population (0.093%), but it was even higher than that reported for acromegalic subjects. Sustained exposure to high serum IGF-1 levels is likely to play a role in the development of thyroid cancer in this disease. An additive role for the autocrine/paracrine action of locally produced IGF-1 is also possible. Our results suggest that thyroid function and morphology should be carefully monitored in all acromegalic patients.

Objective: Acquired hypopituitarism in adults is obviously suspected in patients with primary hypothalamic-pituitary diseases, particularly after neurosurgery and/or radiotherapy. That brain injuries (BI) can cause hypopituitarism is commonly stated and has been recently emphasized but the management of BI patients does not routinely include neuroendocrine evaluations., Aim: To clarify the occurrence of hypopituitarism in patients after traumatic brain injury (TBI) or subarachnoid haemorrhage (SAH) 3 months after the BI., Subjects and Methods: The occurrence of hypopituitarism in conscious patients after traumatic brain injury [TBI, n = 100, 31 women, 69 men; age 37.1 +/- 1.8 years; body mass index (BMI) 23.7 +/- 0.4 kg/m(2); Glasgow Coma Scale (GCS) 3-15] or subarachnoid haemorrhage [SAH, n = 40, 14 men, 26 wpmen, 51.0 +/- 2.0 years; 25.0 +/- 0.6 kg/m(2); Fisher's scale 1-4] was studied in a multicentre study 3 months after the BI. All patients underwent wide basal hormonal evaluation; the GH/IGF-I axis was evaluated by GHRH + arginine test and IGF-I measurement., Results: In TBI patients, some degree of hypopituitarism was shown in 35%. Total, multiple and isolated deficits were present in 4, 6 and 25%, respectively. Diabetes insipidus was present in 4%. Secondary adrenal, thyroid and gonadal deficit was present in 8, 5 and 17%, respectively. Severe GH deficiency (GHD) was the most frequent pituitary defect (25%). In SAH patients, some degree of hypopituitarism was shown in 37.5%. Despite no total hypopituitarism, multiple and isolated deficits were present in 10 and 27.5%, respectively. Diabetes insipidus was present in 7.5%. Secondary adrenal, thyroid and gonadal deficit was present in 2.5, 7.5 and 12.5%, respectively. Severe GHD was the most frequent defect (25%)., Conclusions: TBI and SAH are conditions associated with high risk of acquired hypopituitarism. The pituitary defect is often multiple and severe GHD is the most frequent defect. Thus neuroendocrine evaluations are always mandatory in patients after brain injuries.