Efficacy of long-term growth hormone therapy in short children with reduced growth hormone biological activity.

AIM: The optimal GH regimen, in terms of cost-effectiveness, in children with normal GH immunoreactivity but reduced bioactivity is still debated. METHODS: In 12 GH-deficient (GHD) and 12 bioinactive GH children undergoing GH treatment we evaluated the increase in growth velocity, the difference between target height and final stature and the incremental cost-effectiveness ratio. RESULTS: We found a significant (p < 0.05) increase in growth velocity in both groups during the first year of GH treatment (non- GHD: from -1.7 to 5.4 SDS; GHD: from -1.46 to 4.74 SDS). There was no statistically significant variation between the two groups in the difference between final height and target height. We did not find any significant difference in cost/height gain between GHD (1925.28 ± 653.15 euro) and bioinactive GH children (1639.55 ± 631.44 euro). There were also no significant differences in cost/year of therapy between GHD (12347.68 ± 2018.1 euro) and bioinactive GH children (11355.08 ± 1747.61 euro). CONCLUSION: In children with reduced GH biological activity, confirmed by the increase of serum IGF-I levels during generation test, the cost of GH treatment is justified by the positive results obtained in growth and adult height as in classical GHD patients.

Growth factors decrease in subjects with mild to moderate Alzheimer's disease (AD): potential correction with dehydroepiandrosterone-sulphate (DHEAS).

The integrity of neuroprotection is an important component against the development of cognitive disorders and AD. Within this context, DHEAS would seem to have some positive metabolic and endocrine effects to delay brain aging by recovering the impairment of neuroprotective growth factors. In the present study we measured by ELISA the secretion of insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), and transforming growth factor-beta1 (TGFbeta1) in the supernatants of cultured circulating peripheral blood mononuclear cells (PBMC) from which natural killer cells (NK) were separated (PBMC-NK) (pg/ml/7.75x10(6) cells) in healthy subjects and in age-matched patients with mild to moderate AD. The growth factors were measured in spontaneous conditions and after stimulation with growth hormone (GH) 1 microg/ml (IGF-1), lipopolysaccharide (LPS) 1 microg/ml (VEGF) and glucose 10 microM (TGF(beta1). AD group demonstrated at baseline a severe reduction of IGF-1 (3.7+1.2 pg/ml after GH), VEGF (63+/-18 pg/ml spontaneous and 210+/-65 pg/ml after LPS) and TGF(beta1 (33+/-10 pg/ml spontaneous and 75+/-12 pg/ml after glucose) secretions compared to healthy elderly subjects (IGF-1, 9.5+/-2.8 pg/ml after GH, p<0.001; VEGF, 117+/-38 pg/ml spontaneous, p<0.001 and 690+/-120 pg/ml after LPS, p<0.001; and TGF(beta1, 73+/-21 pg/ml spontaneous, p<0.001 and 169+/-53 pg/ml after glucose, p<0.001). Significant positive correlations between IGF-1 and VEGF concentrations were found both in healthy subjects (r=0.87, p<0.001) and in AD subjects (r=0.87, p<0.001). The co-incubation of NK cells with DHEAS (10(6) M/ml/cells) significantly increase IGF-1, VEGF and TGF (beta1 production, reaching in AD group the normal concentrations found in healthy subjects (IGF-1, 7.9 + 2.4 pg/ml after GH; VEGF, 105+/-31 pg/ml spontaneous and 670+/-112 pg/ml after LPS; and TGFfbeta1, 68+/-18 pg/ml spontaneous and 155+/-48 pg/ml after glucose). These data suggested that DHEAS is able to increase the immunoendocrine production of neuroprotective growth factors, which is reduced in AD subjects, so suggesting a new approach in the treatment of dementia.

Life expectancy in Alzheimer's disease (AD).

Survival following a diagnosis of AD is important information for health planners, caregivers, patients, and their families. AD is associated with variable, but shortened life expectancy. Knowing the expected survival time may empower people with AD and their families, but clinicians currently have limited predictive information. A better knowledge about prognosis in patients affected by AD and related disorders should be of paramount importance in order to improve care plans and assist in medical decisions, above all for patients in the moderate-severe stages of the disease. Life expectancy for patients with AD can vary between 3 to 10 years. Many studies have tried to identify predictive factors that can be of help for clinicians. The main predictor of life expectancy is the age. Therefore caregivers, patients, and their families could plan on a median life span as long as 7 to 10 years for patients whose conditions are diagnosed when they are in their 60s and early 70s, to only about 3 years or less for patients whose conditions are diagnosed when they are in their 90s. Dementias with prominent psychiatric-behavioral manifestations and gait impairment have a faster progression compared to AD. However the many variables that influence life expectancy make difficult to define prognosis at the bedside and more studies are needed to assist clinicians in they daily routine with patients and caregivers.

Rituximab induces distinct intraorbital and intrathyroidal effects in one patient satisfactorily treated for Graves' ophthalmopathy.

Hyperthyroid Graves' disease (GD) is a B-cell-mediated disease caused by antibodies stimulating the thyroid stimulating hormone (TSH) receptor (TRAb). A proportion of patients (40-60%) present with an associated ophthalmopathy (TAO), a progressive inflammatory autoimmune disease of the retroorbital tissue. We thought that the anti-CD20 monoclonal antibody rituximab (RTX), by inducing transient B-cell depletion, may potentially modify the active inflammatory phase of TAO. One patient with GD and TAO in its active phase and unresponsive to steroid, was treated with RTX. Whereas the ophthalmopathy responded to RTX therapy and a decrease in the clinical activity score from 5 to 2 was observed during the B-cell depletion, serum antithyroid antibodies, and in particular serum TRAb, were not affected by therapy. When the patient underwent total thyroidectomy, we found B-cells in the thyroid tissue specimens. The eye disease remained stable (clinical activity score=2) and the patient subsequently underwent orbital decompression to correct proptosis of the eye. At that time we did not find lymphocytes in any of the orbital tissue specimens. We believe that RTX therapy in GD may cause amelioration of ophthalmopathy by depleting total lymphocyte population in the orbit, but not lymphocyte depletion in thyroid tissue with consequent unchanged serum TRAb levels.