Hypopituitarism (GHD) and neurodegenerative diseases.

Neurodegenerative diseases are a major focus of scientific and clinical interest because of their increasing medical and social importance. Due to the intimate connections between central nervous and endocrine systems, it is reasonable to suspect that important, and in some cases clinically relevant, endocrine modifications may accompany the progression of neurodegenerative diseases. Data on endocrine modifications in different neurodegenerative diseases have been reported, but results have often been non-conclusive, or conflicting. Accumulating evidence suggests that the GH/IGF-I axis is involved in the regulation of brain growth, development, and metabolism and in the regulation of muscle function. Dysfunctions in GH/IGF-I axis in most of neurodegenerative diseases are therefore reviewed. Alterations of this system could be actors in the complex network leading to (at least some) neurodegenerative diseases. A thorough effort in investigating every possible involvement is warranted, in the light of future therapeutic strategies.

Primary hyperparathyroidism is associated with marked impairment of GH response to acylated ghrelin.

BACKGROUND: Impaired GH secretion is a common finding in patients with primary hyperparathyroidism (PHP). Ghrelin displays strong GH-releasing action, mainly at the hypothalamic level. OBJECTIVE: To evaluate secretory response of GH to ghrelin in PHP patients. PATIENTS: Fifteen patients [11 women/4 men, mean age 54 years, range 32-70 years, body mass index (BMI) 25.0 +/- 0.7 kg/m(2)] affected with PHP due to single parathyroid adenoma and 35 normal age-matched subjects (23 women/12 men, mean age 58 years, range 35-68 years, BMI 24.1 +/- 1.1 kg/m(2)). METHODS: A measure of 1 microg/kg body weight i.v. acylated ghrelin or 1 microg/kg body weight i.v. GH releasing hormone (GHRH) followed by 0.5 g/kg body weight i.v. arginine (ARG) hydrochloride were administered to all subjects on alternate days in order to evaluate GH response. RESULTS: Mean serum GH peak after GHRH + ARG was 32.6 +/- 7.8 and 17.4 +/- 4.0 microg/l, in controls and PHP patients, respectively (P < 0.05). Mean serum GH peak after ghrelin was 70.4 +/- 31.5 and 16.8 +/- 1.9 microg/l, in controls and PHP patients, respectively, (P < 0.001). Using ROC curves, a serum GH peak > 22 microg/l after ghrelin stimulation might be considered as a cut-off value for identifying normal subjects. Ten (67%) PHP patients have impaired GH response to GHRH + ARG and 13 (87%) to ghrelin. Serum GH peak after ghrelin or GHRH + ARG was unrelated to serum IGF-1, PTH or ionized calcium concentrations. CONCLUSIONS: The present data confirm that GH secretion is impaired in PHP patients using the potent GH secretagogue ghrelin and suggest that impaired GH secretion is likely due to a deleterious effect of hypercalcaemia at the hypothalamic level in PHP patients.

Impairment of GH secretion in amyotrophic lateral sclerosis is not affected by riluzole treatment.

Amyotrophic lateral sclerosis (ALS), the most common motor neurone disorder in human adults, is characterized by selective and progressive degeneration of upper and lower motor neurones in the central nervous system. The main currently available drug for ALS treatment is riluzole, a compound that acts through inhibition of glutamate release, postsynaptic receptor activation, and voltage-sensitive channel inhibition. GH secretion, evaluated by GHRH+arginine (ARG) test, has recently been reported to be impaired in most untreated ALS patients. The aim of the present study was to evaluate whether riluzole administration could interfere with GH secretion and therefore with the diagnosis of adult GH deficiency. Ten patients (6 males, 4 females, mean age 59+/-11 yr) were studied performing GHRH+ARG test before and 3 months after starting riluzole treatment (100 mg/day). Blood samples for GH were collected at baseline, at 30 and 60 min. Both before and during riluzole treatment, 5 patients showed GH deficiency and 5 patients had a normal GH response according to body mass index (BMI). Mean peak GH levels were similar before and during riluzole treatment (13.4+/-10 vs 14.2+/-10.1 microg/l, p=ns). No significant correlation was observed between GH concentrations and age, BMI, disease duration, severity or clinical (bulbar/spinal) form. In conclusion, the present data confirm that GH secretion is impaired in a new series of ALS patients and indicate that riluzole treatment does not interfere with GH secretion. Thus, evaluation of GH secretion in ALS patients can also be performed without withdrawing riluzole treatment.

[Influenza vaccination in health care workers of a university hospital in Milan]. / La vaccinazione antiinfluenzale nel personale sanitario dell'Ospedale L. Sacco di Milano.

The study analyses the percentage of influenza vaccination in health care workers of a big university hospital in Milan during the season 2006/2007. The percentage of vaccinated subjects was 19.8%. The frequency of vaccination has also been assessed according to sex, age, job and school title. Observed data indicates that the number of vaccinated sanitary workers is far below the levels reached in other European countries and in the USA. Thus, in order to reach a higher adhesion to vaccination programs, sensitisation campaigns are necessary.

Growth hormone secretion in primary and secondary hyperparathyroidism.

Primary hyperparathyroidism (PHP) is associated with impaired GH secretion. Whether this effect is due to hypercalcemia or to increased serum PTH concentration is unclear. However, patients with familial hypocalciuric hypercalcemia (FHH), who have normal PTH and increased serum calcium concentrations, also have an impaired GH secretion, suggesting that calcium rather than PTH is responsable for this effect on GH secretion. To further investigate this issue, 10 consecutive patients with secondary hyperparathyroidism (SHP) due to vitamin D deficiency were evaluated by the GH response to GHRH+arginine (Arg) test. A group of 60 consecutive untreated PHP patients served as controls. Mean GH response to GHRH+Arg test was 15.8+/-14 microg/l and 37.5+/-16 microg/l (p<0.001) in PHP and in SHP patients, respectively. Forty-two out of 60 (70%) PHP patients had a suppressed or blunted GH response, whereas all SHP patients had normal GH response. The results of the present study confirm and extend our previous observations that PHP is associated with an impaired GH secretion in the majority of cases, and indicate that SHP patients have no abnormality of GH secretion. Thus, hypercalcemia rather than increased serum PTH is responsible for the abnormality of GH secretion.

Microvascular density and vascular endothelial growth factor expression in normal pituitary tissue and pituitary adenomas.

Microvessel density (MVD) represents a measure of angiogenesis and may be used as an indicator of neoplastic aggressiveness. Vascular endothelial growth factor (VEGF) plays a pivotal role as angiogenic promoter by stimulating endothelial cell proliferation and migration and enhancing vascular permeability. The aim of this study was to investigate MVD and VEGF expression in human pituitary adenomas and normal pituitary gland tissues by immunohistochemistry, and to correlate data with clinical characteristics. Fragments from 46 pituitary adenomas (18 non-functioning, 12 ACTH-secreting, 12 GH-secreting, 4 PRL-secreting) and 19 specimens of normal anterior pituitary gland obtained at surgery were evaluated. MVD in normal anterior pituitary was significantly higher than in tumors (69.2 +/- 28.5 vs 29.3 +/- 19.7; p < 0.0001). Within adenomas, no difference was found in MVD when different histotype, size, sex, age, rate of recurrence or medical pre-surgical treatment were considered. The degree of vascularity was somewhat related only to clinical invasiveness, as evaluated by pre-surgical MRI grading (grade 0 p < 0.05 vs grade 1 and vs grade 2). No statistically significant difference in VEGF expression was found between normal tissue and adenomas and among tumors of different histotype (p = 0.3978). Size, sex, age, rate of recurrence and medical pre-surgical treatment did not influence VEGF expression. No correlation was found between MVD and VEGF expression. In conclusion, MVD was reduced in pituitary adenomas with respect to normal gland. VEGF expression is however well preserved in adenomas and this might contribute to adequate tumoral vascular supply with complex mechanisms other than endothelial cells proliferation.

Impairment of GH secretion in adults with primary empty sella.

Primary empty sella (PES) is generally not associated with overt endocrine abnormalities, although mild hyperprolactinemia and, in children, deficient GH secretion have been reported. The aim of this multi-center collaborative study was to evaluate basal and stimulated GH secretion in a large series of adult PES patients. The study group consisted of 51 patients [41 women and 10 men, age range: 20-78 yr; (mean+/-SD) 47+/-11 yr]; results were compared with those in normal subjects (Ns) (Ns: no.=110, 55 women, age: 20-50 yr, 37+/-14 yr), and in hypopituitaric patients (HYP) with GH deficiency (HYP: no.=44,17 women, age: 20-72, 49+/-16 yr). Baseline IGF-I levels and GH responses to insulin-induced hypoglycemia (insulin tolerance test, ITT) and/or GHRH+arginine (ARG) stimulation tests were evaluated. PES patients were also subdivided according to BMI in lean (BMI <28 kg/M2 no.=22) or obese (BMI >28 kg/m2 no.=29). PES patients had serum total IGF-I concentrations (mean+/-SE: 142.2+/-9.6 ng/ml) higher than HYP patients (77.4+/-6.4 ng/ml, p<0.001), but lower than Ns (213.3+/-17.2 ng/ml, p<0.005), with no differences between lean and obese PES subjects. The increase in serum GH concentrations following ITT and/or GHRH+ARG stimulation tests, although higher than that observed in HYP patients, was markedly reduced with respect to Ns. No difference was observed in the GH response to provocative tests between lean and obese PES patients. When individual GH responses to ITT or GHRH+ARG were taken into account, a large proportion of PES patients (52% after ITT, 61% after GHRH+ARG) showed a GH peak increase below the 1st centile of normal limits. Serum IGF-I levels in PES patients with blunted GH responses to provocative tests were significantly (p<0.001) lower in PES patients with normal GH responses, and a positive correlation was observed between IGF-I levels and serum GH peak concentrations after GHRH+ARG. In conclusion, the results of the present study provide evidence that adult PES patients often have an impairment of GH secretion, as indicated by the blunted GH response to ITT and GHRH+ARG provocative tests, and by the reduction in serum IGF-I levels. These changes are independent of body mass.

GH secretion is impaired in patients with primary hyperparathyroidism.

The activity of the GH/IGF-I axis as a function of parathyroid activity and calcium metabolism in humans has never been assessed. To address this issue, we studied 18 patients (5 men, 13 women; age range, 23-76 yr; mean, 61 yr) with primary hyperparathyroidism (PHP) due to solitary parathyroid adenoma. GH secretion was evaluated by serum IGF-I levels, spontaneous mean GH secretion over two morning hours, and GH response to arginine (ARG) alone or combined with GHRH. In five patients, serum GH concentrations were measured every 20 min for 24 h, and deconvolution analysis was performed. A group of 35 age- and sex-matched normal subjects served as controls. Mean serum IGF-I levels in PHP were lower than in normal controls, and in six PHP patients individual serum IGF-I levels were below the age-related normal range. The mean (+/-SE) peak GH response to ARG alone in PHP patients was significantly lower than in normal subjects (4.0 +/- 1.0 vs. 22.0 +/- 1.3 microg/liter; P < 0.001). Likewise, the mean (+/-SE) peak GH response to ARG plus GHRH was reduced in PHP patients (9.9 +/- 0.9 vs. 38.0 +/- 3.5 microg/liter; P < 0.001). The mean GH concentration over two morning hours in PHP was lower (0.20 +/- 0.05 vs. 1.34 +/- 0.31 microg/liter; P < 0.001). The mean GH concentration over 24 h in five PHP patients was lower than in six normal controls (0.3 +/- 0.1 vs. 0.7+/- 0.1 microg/liter; P < 0.05); the deconvolution analysis showed that 24-h GH production rate (3.0 +/- 1.7 vs. 28.2 +/- 4.7 microg/liter.d; P < 0.05) and mean secretory burst mass (1.2 +/- 0.7 vs. 10.5 +/- 2.6 microg/liter; P < 0.05), but not pulse frequency, were lower in PHP patients than in normal controls. GH half-life and approximate entropy values of 24-h GH profiles were similar in PHP patients and normal controls. No correlation was found between serum-ionized calcium or PTH levels and spontaneous or stimulated GH levels in PHP patients. In conclusion, this study demonstrates that PHP patients have a reduction in both spontaneous and stimulated GH secretion. Accordingly, PHP should be mentioned as a further example of a metabolic condition in which GH secretion in adults is reduced.

Primary hyperparathyroidism is associated with an impaired secretion of growth hormone but not of the other anterior pituitary hormones.

We have recently reported that GH secretion is impaired in primary hyperparathyroidism (PHP). No systematic assessment of the whole anterior pituitary function in PHP is available. In this study, anterior pituitary function was evaluated in basal and stimulated conditions in a series of 12 consecutive women with PHP. Serum GH secretion was decreased in 9 of 12 PHP patients (75%) confirming our previous results in different series of PHP patients. Instead, at variance, secretion of all the other anterior pituitary hormones was normal. Thus, PHP is associated with an impaired secretion of GH, but not of the other anterior pituitary hormones. The reason why only GH secretion is affected in PHP is unknown.