Mentha arvensis L., is an aromatic herb that belongs to the Lamiaceae family and is widely used in medicinal applications, essential oil applications, and food flavoring. The extract of M. arvensis has been reported to exert sedative-hypnotic, anti-inflammatory, anti-fungal, and anti-bacterial effects. However, its effects on bone metabolism have not yet been studied. Here, we investigated the effects of the water extract of M. arvensis (WEMA) on osteoclast formation in vitro and bone loss in an ovariectomized mouse model. We found that WEMA inhibited osteoclast differentiation by directly acting on osteoclast precursor cells. WEMA inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced the expression of cellular oncogene fos (c-Fos) and nuclear factor of activated T cells c1 (NFATc1), crucial transcription factors for osteoclast differentiation, by suppressing RANKL-induced activation of early signaling pathways such as those of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). In addition, oral administration of WEMA suppressed ovariectomy-induced trabecular bone loss in mice. We additionally identified phytochemicals in WEMA that are known to have anti-osteoclastogenic or anti-osteoporotic properties. Collectively, these results suggest that WEMA is a promising herbal candidate that can be used to prevent or treat postmenopausal osteoporosis.

The diagnosis of GH deficiency (GHD) in adults is established by laboratory testing in patients with an appropriate clinical history of hypothalamic pituitary disease. As the measurement of IGF-I and IGFBP-3 levels as well as the spontaneous GH secretion are not considered reliable parameters, the diagnosis of GHD in adults may be established by GH provocative tests, provided that a reproducible test with clear normative limits is available. The insulin tolerance test (ITT) is a reliable diagnostic test in adults, but is contraindicated in several clinical conditions which are often observed in adult patients with suspected GHD. The other classic GH provocative tests, except the glucagon test, have a poor diagnostic utility and should be abandoned. GHRH combined with arginine or GH secretagogues represent a potent, safe, reproducible and reliable test which should be preferable to the ITT as a first-choice diagnostic test for GHD.

Secretion of growth hormone (GH) is excessive in acromegaly, but also in a number of other pathological states such as anorexia nervosa, insulin-dependent diabetes mellitus (IDDM), liver cirrhosis, depression, renal failure and GH-insensitivity syndrome. Abnormalities in the neuroendocrine control of GH secretion and/or a state of insensitivity to GH contribute to hypersecretion of GH in these states, with the possible exception of acromegaly, which appears to be a primary pituitary disease. GH hypersecretion may also occur in neonates or adolescents with tall stature, thus reflecting particular physiological or paraphysiological conditions. In the cohort of brain neurotransmitters, catecholamines and acetylcholine reportedly play a major role in the control of neurosecretory GH-releasing hormone (GHRH) and somatostatin (SS)-producing neurons, and hence GH secretion.

In the literature, few studies analyze the effect of GH therapy on height, preferring a more indirect approach, where factors influencing the total pubertal and pre-pubertal growth in GH-deficient patients are evaluated and subsequently used to estimate the overall effect at the end of the therapy; unfortunately, this approach does not quantify the real growth gain in treated patients. Using a non-parametric Empirical Bayes approach, our study analyzes the growth response to GH treatment in a homogeneous cohort of 317 patients with pituitary GH deficiency who were enrolled during their pre-pubertal stage in the GH Piedmont Registry (Italy), between January 2000–October 2008, and have at least 2 yr of follow-up. To estimate the growth curve for males and females, a non-parametric regression model was fitted, applying Empirical Bayes techniques. A validation of the model was also performed. Improvement was evident in both genders, since both males and females mean growth curve, which started below the 3 rd percentile at the beginning of the therapy, reached the 10 th percentile of the Tanner curve at the end of observation (17 yr old for males and 14 yr old for females); the estimation procedure achieved a good precision. The methodological approach allows for fitting a model able to evaluate longitudinally the response to GH treatment, by means of estimating the overall growth curve, even in presence of sparse information about children heights.

Objective: The aim of this study is to estimate the annual incidence and prevalence rate of the GH treatment exposure in patients under the age of 18 treated for hypopituitarism or isolated GH deficiency (GHD) in Piedmont, during the period January 1, 2002 to December 31, 2004. Methods: The selection criteria for recombinant human GH (rhGH) treatment in childhood were approved by the Ministry of Health in Italy in the yr 1998. The present analysis is based on data from the Registry of subjects receiving GH therapy (GH Registry) made up of the 918 pediatric patients (age <18 yr) with a diagnosis of GHD (excluding Prader-Willi and Turner syndromes and other conditions), diagnosed in the period January 1, 2002–December 31, 2004. The case series has been described as regards the number of cases per year of diagnosis; the prevalence and incidence rates, calculated per 10,000 (‱) inhabitants, are given for each year of the study period. Results: The prevalence rate increases slightly from 8.62‱ in 2002 to 9.44‱ in 2004 and the incidence rates estimated were 2.49‱, 1.86‱ and 1.97‱ in the yr 2002, 2003 and 2004, respectively. Conclusion: The Piedmont GH Registry represents the first database available in Italy and could set an example for the other Italian regions as well.

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/m(2)), overweight (BMI > or = 25 and <30 kg/m(2)) and obese (BMI > or =30 kg/m(2)). 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 mug/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 mug/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 mug/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.

To verify if the entity of the peak GH responses to the GHRH+arginine (ARG) test is able to show different degree forms of GH deficiency (GHD), we linked these responses with the number of other anterior pituitary deficits. These anterior pituitary deficits were also related with IGF-I levels. To this purpose, we studied a large cohort of lean patients with pituitary disease of different etiologies [86 males and 68 females; age: mean±SEM 41.5±1.2 yr, body mass index (BMI) <25 kg/m2]. The patients were subdivided into 4 groups according to the increasing number of hormone deficiencies: isolated GHD (HYPO1, no.=28) or GHD plus one, two or three additional hormones (gonadotrophin, ACTH, and TSH) deficiencies (HYPO2, no.=20; HYPO3, no.=15; HYPO4, no.=91). Peak GH responses to the GHRH+ARG test and IGF-I levels showed a clear difference among the groups ( p <0.01 and p<0.001, respectively). A significant difference was found between HYPO1 and HYPO4 for IGF-I levels ( p <0.05), and between HYPO1 and HYPO4 and between HYPO2 and HYPO4 for the GHRH+ARG test ( p <0.005). Considering only the patients who underwent both GHRH+ARG test and insulin tolerance test (ITT) (no.=70), the pattern of the peak GH responses to the GHRH+ARG test was the same of the whole group of patients, while no statistical difference was found with ITT. Our data show that the peak GH responses to the GHRH+ARG test and the IGF-I levels are linked to the severity of hypopituitarism, expressed by the number of increasing anterior pituitary deficits. This association is lost if the evaluation of the GH status is performed by the ITT. In all, the GHRH+ARG test and measurement of IGF-I are able to evidence different degrees of GHD in adult patients with pituitary disease.

Unlike normal subjects, in patients with anorexia nervosa (AN) the GH response to GHRH is refractory to the increasing and inhibitory effect of cholinergic agonists and antagonists, respectively. This cholinergic impairment could reflect malnutrition-induced exhaustion of acetylcholine (Ach) precursors. We studied whether treatment with glycerophosphocholine (GLY), an Ach precursor, could disclose the potentiating effect of pyridostigmine (PD) on the GH response to GHRH in AN. In 6 young women with AN (AW) we studied the GH response to iv GHRH (1.0 μg/kg) alone and combined with oral PD (120 mg) before and after 1 month of oral treatment with GLY (400 mg thrice daily). Eight age-matched normal women (NW) were studied as controls. Before GLY, basal GH levels in AW were higher ( p <0.05) than in NW. The GH response to GHRH in AW was higher ( p <0.05) than in NW. PD failed to modify the GHRH-induced GH rise in AW, while it enhanced it in NW ( p <0.05). One month treatment with GLY in AW did not modify the GH response to GHRH either alone or combined with PD. This study shows the existence of a derangement in the cholinergic control of somatotroph function in AN and indicates that treatment with Ach precursors does not exert any effect on this impairment. This could reflect primary alterations of cholinergic neurons, though the effectiveness of more prolonged treatment and/or higher doses of cholinergic precursors needs to be verified.

The diagnosis of acromegaly, in an appropriate clinical context, usually relies on lack of GH suppression below 1 μg/l during OGTT coupled with elevated IGF-I levels. On the other hand, in normal subjects glucose-induced inhibition of GH secretory bursts without any further decrease of interpulse GH levels had already been shown. Based on the foregoing, we aimed to compare the diagnostic reliability of OGTT-induced GH nadir with that recorded during 3-h spontaneous GH secretion. In 59 acromegalic patients (17 male and 42 female, age, mean±SE 51.5±1.9, range 21–76 yr) and in 82 normal subjects (43 male and 39 female, age, mean±SE 35.7±1.5, range 15–72 yr) GH secretion was evaluated every 30 min from 0 to 180 min during slow saline infusion or OGTT (75 g at 0 min). A nadir GH concentration below 1 μg/l was recorded in all normal subjects either during OGTT or saline infusion if GH secretion was evaluated over 180 min. In contrast in acromegalic patients a nadir GH concentration below 1 μg/l never occurred in both conditions. This study shows that a 3-h spontaneous GH profile is as reliable as OGTT in the diagnosis of active acromegaly.

Anorexia nervosa is a syndrome with multifactorial etiology in which several genetic, biologic, psychological and social factors are involved. Patients affected by anorexia nervosa (AN) may develop multiple endocrine abnormalities, e.g. amenorrhea, hypothalamus-pituitary-adrenal axis hyperactivity, low T3 syndrome and peculiar changes of somatotroph axis function. These endocrine abnormalities are also found after prolonged starvation and may represent an adaptive response developed in order to save energy and proteins. It is still a matter of debate whether these endocrine changes are etiologic or secondary. In fact, several evidences suggest the existence in AN of hypothalamus functional alterations, which may be involved in the development and maintenance of the food intake disorder; on the other hand, the increased CRH secretion seems to be secondary to malnutrition as well as GH hypersecretion coupled to low IGF-I levels; the latter is a common finding in AN, as well as in other undernutrition and malabsorption conditions, type 1 diabetes mellitus, liver cirrhosis and catabolic states. Hypothalamic amenorrhea, which is one of the diagnostic criteria for AN, is not linked only to the reduction of body weight but reflects also deep alterations of gonadotropin secretory pattern. Low T3 syndrome is frequently found in AN; on the other hand, an iodide-induced hypothyroidism is quite uncommon. T3 reduction in AN seems to be an adaptive response to prolonged starvation; however the presence of a simultaneous central dysregulation cannot be excluded. Finally, AN patients frequently show defects in urinary concentration or dilution with inappropriate secretion of antidiuretic hormone, which may be due to intrinsic defects in the neurohypophysis or to abnormalities of its regulatory afferent neurons.

It is widely accepted that the classical dose of 250.0 μg ACTH (1–24) (tetracosactin) is clearly supra-maximal while 1.0 and 0.03 μg have been shown as the maximal and the lowest stimulatory ACTH doses for cortisol (F) secretion in normal young subjects. Testing with low ACTH dose would better evaluate adrenal sensitivity to corticotropin. The aims of the present study were: a) to clarify the adrenal sensitivity to ACTH in patients with different duration of corticotroph insufficiency by testing with low and very low tetracosactin doses; and b) to evaluate diagnostic implication regarding the ability of ACTH tests to distinguish patients with corticotroph insufficiency from normal subjects. In 24 hypopituitaric patients (HYPOPIT, 15 male and 9 female, age 22–50 yr, BMI: 22–26 kg/m 2 ) with corticotrophin deficiency we studied the F, DHEA and aldosterone (A) responses to challenges with low ACTH doses (0.06 or 0.5 μg iv at 0 min) followed by 250 μg iv (at +60 min). The results in HYPOPIT were compared with those recorded in 12 normal controls (NS, 6 male and 6 female, age 22–34 yr, BMI: 20–25 kg/m 2 ). Basal F and DHEA levels in HYPOPIT were lower than in NS, while A levels were similar in both groups. The F responses to ACTH in HYPOPIT were dose-independent and markedly lower ( p <0.0001) than in NS. After the 0.06 and 0.5 μg ACTH dose, 16% of HYPOPIT patients showed δF peak within the range of normal response. No HYPOPIT showed δF peak within the normal range after 250 μg ACTH. The DHEA responses to ACTH in HYPOPIT were dose-independent and markedly lower than in NS ( p <0.0001). Overlap between individual DHEA responses in HYPOPIT and NS was present after 0.06 μg and 0.5 μg but not after 250 μg tetracosactin. The A responses in HYPOPIT were dose-dependent and overlapped with those in NS. The adrenal responses to ACTH in HYPOPIT were not associated with the duration of the disease. In conclusion, the present study shows that the mean F and DHEA but not the A responses to ACTH (1–24) are markedly impaired in hypopituitaric patients with corticotroph insufficiency independently of the duration of the disease. The impaired F and DHEA response to ACTH is also independent of the dose, suggesting the existence of relatively enhanced sensitivity of the fasciculata and reticularis adrenal zone to ACTH but meantime remarkable impairment of the adrenal function due to corticotrophin deficiency. In the present study, testing with submaximal ACTH doses did not distinguish patients with secondary adrenal insufficiency from normal subjects.

Alprazolam (AL), a benzodiazepine which activates gamma-amino butyrric acid (GA-BA)-ergic receptors, exerts a clear inhibitory effect on the activity of the hypothalamo-pitu-itary-adrenal (HPA) axis and is able to markedly reduce the ACTH response to metyrapone-induced inhibition of glucocorticoid feedback. It has been suggested that its inhibitory action could be regulated by CRH or AVP mediated mechanisms. However, the effect of benzodi-azepines on the HPA response to CRH or AVP is contradictory. It has been shown that benzodi-azepines have specific receptors on the adrenal gland but it is unclear if they mediate biological effects in humans. In order to further clarify the mechanisms underlying the inhibitory effect of benzodiazepine on HPA axis in humans, we studied the effect of AL (0.02 mg/kg po at −90 min) or placebo in 7 healthy young volunteers (7 female, age: 26–34 yr; wt: 50–58 kg, BMI 20–22 kg/m 2 ) on: 1) the ACTH and cortisol responses to hCRH (2.0 μg/kg iv at 0 min) or AVP (0.17 U/kg im at 0 min); 2) the cortisol, aldosterone and DHEA responses to ACTH 1–24 (0.06 and 250 μg iv at 0 and 60 min, respectively). After placebo, the ACTH and cortisol responses to hCRH (peaks, mean±SE: 29.8± 4.4 pg/ml and 199.3±19.6 μg/l) were similar to those recorded after AVP (31.7±6.5 pg/ml and 164.8±18.0 μg/l); the cortisol response to 0.06 μg ACTH (190.4±11.8 μg/l) was similar to that recorded after hCRH and AVP but lower ( p <0.01) than that after 250 μg ACTH (260.6±17.4 μg/l). AL did not modify the ACTH response to both hCRH (42.5±7.1 pg/ml) and AVP (33.3±2.7 pg/ml), which even showed a trend toward increase. AL also failed to significantly modify the cortisol response to both hCRH (156.3±12.7 μg/l) and AVP (119.4±14.5 μg/l), which, on the other hand, showed a trend toward decrease. The cortisol peaks after 0.06 μg ACTH were significantly reduced ( p <0.02) by AL pre-treatment (115.0±7.7 μg/l) which, in turn, did not modify the cortisol response to the subsequent ACTH bolus (214.7±16.6 μg/l). The DHEA and aldos-terone responses to all the ACTH doses were not significantly modified by AL. In conclusion, these data show that the HPA response to AVP as well as to hCRH is refractory to the inhibitory effect of AL which, in turn, blunts the cortisol response to low ACTH dose. These findings suggest that both CRH- and AVP-mediated mechanisms could underlie the CNS-mediated inhibitory effect of AL on HPA axis; in the meantime, these results suggest that benzodiazepines could also act on adrenal gland by blunting the sensitivity of the fasciculata zone to ACTH.

Acromegaly is frequently associated with the presence of thyroid disorders, however the exact prevalence is still controversial. An Italian multicenter study was performed on 258 patients with active acromegaly (high levels of IGF-I and lack of suppression of serum GH levels below 2 μg/l after an OGTT). The control group was represented by 150 patients affected by non-functioning and PRL-secreting pituitary adenomas. Two hundred and two out of 258 acromegalic patients (78%) were affected by thyroid disorders with a significantly higher prevalence with respect to the control group (27%, p <0.0001). One hundred and three patients presented (39.9%) non-toxic nodular goiter, 46 (17.8%) non-toxic diffuse goiter, 37 (14.3%) toxic nodular goiter, 1 toxic diffuse goiter (0.4%), 12 (4.6%) Hashimoto’s thyroiditis, 3 (1.2%) thyroid cancer. Two patients presented a co-secreting TSH pituitary adenoma. Thirty-six patients had been previously treated for various thyroid abnormalities. Among the 222 acromegalic patients never treated for thyroid disorders thyroid ultrasonography was performed on 194 subjects. Thyroid volume in patients with thyroid abnormalities was 28±17.5 ml (median 23) while it was 10.8±3.6 ml (median 10) in patients without thyroid disorders ( p <0.0001). Thyroid volume was correlated with the estimated duration of acromegaly (r=0.7, p <000.1), but not with age or with serum GH, IGF-I and TSH concentrations. Thyroid volume was higher in acromegalic patients than in the above control population (23.5±16.9 ml vs 13.9±12.8 ml, p <0.0001). In 62 acromegalic patients 101 fine-needle biopsies of thyroid nodules were performed; 7 nodules were suspicious and the patients were submitted to thyroid surgery: papillary thyroid carcinoma was found in 3 patients. In conclusion, in a large series of acromegalic patients an increased prevalence of thyroid disorders (78%), particularly non-toxic nodular goiter, has been observed. Thyroid volume, evaluated by ultrasonography, was correlated to the estimated duration of acromegaly. Finally, the prevalence of thyroid carcinoma was slightly increased than in the general population.

Il GH, oltre alla sua attività sui processi di crescita, esercita importanti azioni metaboliche e strutturali. Quest’evidenza spiega perché il deficit di GH (GHD) determini non solo una compromissione dell’accrescimento in età pediatrica ma anche una sindrome metabolica e alterazioni funzionali di vari organi e sistemi nel paziente adulto ipopituitarico. Tale sindrome non si presenta con segni e sintomi specifici, ma mostra un’analogia fortissima con la sindrome plurimetabolica e determina un chiaro aumento dei fattori di rischio per la malattia cardiovascolare. La qualità di vita è nel comples so compromessa ed è stato dimostrato chiaramente che un appropriato trattamento sostitutivo giova al paziente in termini di normalizzazione delle alterazioni sopra descritte. Sebbene il quadro clinico non si caratterizzi per segni e sintomi patognomonici, in un appropriato contesto clinico (la patologia ipotalamo-ipofisaria) la diagnosi di GHD è facilmente dimostrabile attraverso test di stimolo della secrezione somatotropa. Il trattamento sostitutivo richiede dosi minime di GH biosintetico da definirsi sul piano individuale. Come ogni terapia sostitutiva a dosi ottimizzate il trattamento non è a rischio di effetti collaterali ed è verosimilmente da mantenersi per tutta la vita.

Animal studies indicate that mineralocorticoid receptors (MR) in the hippocampus play a major role in the glucocorticoid feedback control of the hypothalamo-pituitary-adrenal (HPA) axis. Specifically, MR mediate the proactive feedback of glucocorticoids in the maintenance of basal HPA activity. The stimulatory effect of intra cerebroventricular and intrahippocampal MR blockade on the HPA axis in animals has been clearly shown, whereas the effect of systemic administration of mineralocorticoid antagonists in humans is still contradictory. To clarify this point, in seven normal young women (aged 25-32 yr; body mass index, 19.0-23.0 kg/m(2)) we studied the effects of canrenoate (CAN; 200 Ng as iv bolus at 2000 h, followed by 200 mg infused in 500 mt saline over 4 hup to 2400 h) or placebo (saline, 1.0 mt as iv bolus at 2000 h, followed by 500 mt over 4 h up to 2400 h) on the spontaneous ACTH, cortisol, dehydroepiandrosterone (DHEA) and aldosterone secretion as well as on the ACTH, cortisol, and:DHEA responses to human CRH (2.0 mug/kg as iv bolus at 2200 h) or arginine vasopressin (AVP; 0.17 U/kg as im bolus at 2200 h). Blood samples were taken every 15 min from 2000-2400 h. During placebo, spontaneous ACTH and cortisol levels showed progressive decreases (P < 0.05) from 2000-2400 h (baseline us. nadir, mean +/- SEM, 2.0 +/- 0.3 us. 1.4 +/- 0.2 pmol/L and 115.1 +/- 23.7 us. 63.5 +/- 24.3 nmol/L), whereas DHEA and aldosterone levels did not change. CRH induced clear increases in ACTH, cortisol, and DHEA levels (peaks, mean +/- SEM, 7.1 +/- 1.1 vs. 1.6 +/- 0.2 pmol/L, 322.9 +/- 19.5 vs. 92.8 +/- 24.5 nmol/L, and 44.2 +/- 2.7 vs. 20.0 +/- 3.0 nmol/L; P < 0.05). Similarly, AVP elicited significant increases in ACTH, cortisol, and DHEA levels (3.8 +/- 0.3 vs. 1.5 +/- 0.1 pmol/L, 211.9 +/- 27.2 vs. 67.7 +/- 9.7 nmol/L, and 51.6 +/- 4.0 vs. 16.3 +/- 2.0 nmol/L; P < 0.05). During CAN treatment, ACTH, cortisol, and DHEA levels showed progressive rises, which begun at approximately 60 min and peaked between 2300 and 2400 h (ACTH, 3.4 +/- 0.4 vs. 1.1 ir 0.3 pmol/L; cortisol, 314.5 +/- 49.6 vs. 123.3 +/- 13.2 nmol/L; DHEA, 52.0 +/- 8.8 vs. 21.0 +/- 2.3 nmol/L; P < 0.05 us. baseline as well as vs. the same time points during placebo). Aldosterone secretion was not modified by CAN. The ACTH, cortisol, and DHEA responses to human CRH were enhanced by CAN (10.0 +/- 1.7 pmol/L, 462.2 +/- 36.9 nmol/L, and 66.3 +/- 8.8 nmol/L), although statistical significance (P < 0.05) was obtained for cortisol and DHEA only. Also the ACTH, cortisol and DHEA responses to AVP were amplified by CAN (8.0 +/- 2.6 pmol/L, 324.0 +/- 34.8 nmol/L, and 77.8 +/- 4.0 nmol/L); again, statistical significance (P < 0.05) was obtained for cortisol and DHEA only. In conclusion, our study shows that, the blockade of MR by CAN significantly enhances the activity of the HPA axis in humans, indicating a physiological role for MR in its control. These results also suggest that the stimulatory effect of CAN an HPA axis is mediated by concomitant modulation of CRH and AVP release.

Either in children or in adults, arginine (ARG) alone and combined with GHRH (GHRH + ARG) are reliable tests for the diagnosis of GH deficiency. The procedures of these tests generally include GH measurement every 15 min from baseline up to 90–120 min. Aim of our study was to verify if the procedure of these tests could be usefully shortened in clinical practice. To this goal we have studied 173 normally growing children and adolescents (C, 117 M and 56 F, age: 11.3 ± 0.4 yr.) and 125 young and middle aged normal adults (A, 68 M and 57 F, age: 30.0 ± 0.6 yr.). ARG alone test was performed by 81 C and 33 A (0.5 g/kg arginine, iv, from 0 to +30 min, up to a maximum of 30 g) while GHRH (1 μg/kg iv bolus at 0 min) + ARG test was performed by 92 C and 92 A. After ARG alone, taking into account data from +15 to +105 min, GH values above the 3rd centile limit of arbitrary cut-off (7 or 10 μg/1 in C and 5 μg/1 in A) occurred in 85% or 64% and 94% subjects, respectively. After GHRH + ARG test, taking into account only data at +30, +45, +60 min GH values above the 3rd centile limit (20 μg/1 in C and 16.5 μg/1 in A) occurred in 99% of subjects in both groups. Taking into account only these 3 timing points, the percentage of GH peak above the third centile limits after ARG alone was never higher than 60% in C and 85% in A. In conclusion, this study shows that single GHRH + arginine test can be reliably performed in a shortened procedure which makes easier the clinical practice and further reduces costs.

Insulin-induced hypoglycemia (ITT) is currently the “gold-standard” test for the diagnosis of adult growth hormone deficiency (GHD). ITT is often contraindicated, however, particularly in conditions that are also common in patients with suspected GHD. Used alone, GH-releasing hormone (GHRH) has no diagnostic value owing to within-subject variability and the inability to distinguish GHD from normal subjects. When combined with arginine, however, GHRH becomes a potent and reproducible test, which is unaffected by gender and aging, showing excellent specificity. The GHRH+ arginine (ARG) test distinguishes GHD patients from normal subjects and is at least as sensitive as ITT, provided that appropriate cutoff limits are considered. Its reliability for retesting GHD has also been demonstrated. The GHRH+ARG test can also be performed in a shorter procedure, resulting in potential for cost reduction. Synthetic GH secretagogues (GHSs) possess a strong and reproducible GH-releasing effect and synergize with GHRH. The combination of GHRH and a peptidyl GHS, such as hexarelin or GH-releasing peptide-6, has recently been shown as another reliable test for the diagnosis of adult GHD, again provided that the cutoff limit is appropriate to the potency of the test. Thus, GHRH combined with either arginine or GHS is a potential tool for the diagnosis of adult GHD.