Agnese Cattaneo

Bone demineralization in adult thalassaemic patients: contribution of GH and IGF‐I at different skeletal sites

Background and objective  GH and IGF‐I exert an important role in the control of bone formation, as shown by decreased bone mineral density and increased fracture risk in adult hypopituitary patients untreated for GH deficiency (GHD). Different degrees of bone demineralization are frequently reported in patients affected by β‐thalassaemia. Considering the high prevalence of GHD recently observed by our group among adult thalassaemic patients, we elected to study the possible role of GH–IGF‐I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease.

Growth hormone deficiency (GHD) in adult thalassaemic patients

Background and objective  Short stature and growth hormone deficiency (GHD) are frequent occurrences in thalassaemic children, while data on the prevalence of GHD in adult patients are lacking. Therefore, we elected to study the growth hormone and insulin‐like growth factor‐I (GH–IGF‐I) axis in a large group of adult thalassaemic subjects.

The pituitary-adrenal axis in adult thalassaemic patients.

OBJECTIVE We previously described in young thalassaemic patients an altered cortisol and ACTH responsiveness suggesting an impaired adrenocortical reserve. Owing to iron overload, a worsening of adrenal function should be expected in adult patients. DESIGN In 124 adults with beta-thalassaemia, urinary free cortisol (UFC) and plasma ACTH levels were determined and compared with those measured in 150 controls. In 45 patients, cortisol was measured in response to: i) tetracosactide 1 microg as an i.v. bolus (low-dose test, LDT) and ii) tetracosactide 250 microg infused i.v. over 8 h (high-dose test, HDT). RESULTS UFC and serum cortisol were within the reference range in all patients. Conversely, basal plasma ACTH values were above the upper limit of the normal range in 19 patients. There were no statistically significant differences in the mean values of UFC, basal serum cortisol and plasma ACTH between patients and controls. A subnormal cortisol response to the LDT was registered in 18 out of 56 patients. Three of these patients also displayed a subnormal response to the HDT, together with elevated baseline plasma ACTH levels. In the LDT, a positive correlation was found between basal and peak cortisol values (P<0.0001). The latter were negatively correlated with basal ACTH values in both LDT (P<0.0001) and HDT (P<0.0001). CONCLUSIONS Adult thalassaemic patients often present a subtle impairment of adrenocortical function. This may become clinically relevant in case of major stressful events. Thus, we recommend an assessment of adrenocortical function in all adult thalassaemic patients.

The diagnosis of GH deficiency in obese patients: a reappraisal with GHRH plus arginine testing after pharmacological blockade of lipolysis

BACKGROUND The diagnosis of GH deficiency (GHD) in obese patients is complicated by the reduced GH secretion associated with overweight. A GH response to GHRH+arginine lower than 4.2 microg/l is currently considered indicative of GHD in obesity. The aim of the study was to investigate the effect of acute pharmacological blockade of lipolysis on the GH response to GHRH+arginine in obese patients. PATIENTS AND METHODS Two groups of patients were studied: 12 obese patients with proven GHD and 14 patients with essential obesity. On separate occasions, two tests were carried out in each patient: GHRH+arginine and GHRH+arginine preceded by acipimox. RESULTS The mean GH peak after GHRH+arginine was significantly lower in hypopituitary patients than in subjects with essential obesity. Acipimox significantly increased the mean GH response in patients with essential obesity, but not in hypopituitary subjects. All hypopituitary patients and 7/14 patients with essential obesity displayed GH peaks lower than 4.2 microg/l after GHRH+arginine: the GH response to the test increased after acipimox pretreatment in five of these seven essentially obese subjects. After acipimox administration, free fatty acids (FFAs) significantly fell in both groups with comparable mean absolute decreases. All IGF1 values were normal in both groups of subjects. CONCLUSIONS Our study has demonstrated that the acipimox-induced acute reduction of circulating FFA levels increases mean somatotropin response to GHRH+arginine in patients with essential obesity, whereas it has no effect in hypopituitary subjects. The current criterion for the diagnosis of GHD in obese patients may be misleading. Indeed, subjects affected by third degree obesity, like most of our patients, may be erroneously classified as really GH-deficient and started on an expensive unjustified treatment. It appears therefore that the current criteria for the diagnosis of GHD in obesity should be reconsidered in the light of further studies also taking into account different body mass index groups.

Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I

Background: The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. Aim: To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. Subjects and methods: Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 µg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. Results: ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 µg/l. All patients with basal GH>3.9 µg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 µg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. Conclusions: Our results show that baseline GH levels >3.9 µg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 µg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.