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Biomedical subjects

Gianluca Aimaretti

Publications and source records attributed to Gianluca Aimaretti.

At least 19 recordsLinked to original sources
PubMed2006

Response to long-term growth hormone therapy in short children with reduced GH bioactivity.

BACKGROUND/AIMS: The aim of the present study was to investigate whether short children with normal growth hormone (GH) immunoreactivity, but reduced bioactivity (bioinactive GH) could benefit from rhGH treatment as GH deficient (GHD) patients. METHODS: We evaluated 12 pre-pubertal children (8 M, 4 F), with GH deficiency-like phenotype showing normal serum GH peak levels (>10 ng/ml), measured by immunofluorimetric assay (IFMA-GH), in contrast with a reduced GH bioactivity (bio-GH), evaluated using the Nb(2) cells. We also evaluated 15 age-matched GHD pre-pubertal children (11 M, 4 F) with serum GH peak <5 ng/ml. Both groups were treated with rhGH therapy at the dose of 0.23 mg/kg/week s.c. RESULTS: Serum bio-GH/IFMA-GH ratio at peak time for each patient during the provocative test was significantly lower in bioinactive GH than in GHD children (0.29 vs. 2.05, p = 0.00001). Recombinant human GH therapy induced a significant (p < 0.001) increase in growth rate in both groups during the first 2 years. In the third year of treatment, while growth rate in GHD children is maintained, in bioinactive GH patients it decreases remaining, however higher compared to the pre-treatment one. CONCLUSIONS: Short rhGH therapy given to selected bioinactive GH children improve growth rate and might result in greater final adult height.

Body Height↗
PubMed2005

Traumatic brain injury and hypopituitarism.

Results of recent and ongoing studies have made it clear that brain injuries like traumatic brain injury (TBI) pose substantial risk to pituitary function, perhaps even greater risk than previously believed. Patients with TBI should be screened both prospectively and retrospectively for isolated, multiple and even total pituitary deficits. It is well known that, patients with "classical" hypopituitarism (due to primary hypothalamic-pituitary pathologies) do benefit from hormonal replacement therapy. It has been suggested that patients with TBI-induced hypopituitarism may benefit with appropriate hormonal replacement receiving replacement therapy such as anti-diuretic hormone (ADH), glucocorticoid and thyroid hormones when needed. Gonadal and recombinant human growth hormone (rhGH) replacement therapy should also be introduced if there are deficiencies demonstrated and even reconfirmed in a second step. The signs and symptoms of post-TBI hypopituitarism may be masked by what has been assumed to be merely the post-traumatic syndrome. By increasing awareness among physicians of the risks of brain injuries-induced endocrinopathies and the need for appropriate endocrinological testing, it may be possible to improve the quality of life and enhance the rehabilitation prospects for these patients. In most instances, these patients are first seen and treated by trauma surgeons and neurosurgeons, and subsequently by rehabilitation physicians; they must be knowledgeable about the risks of hypopituitarism so that they can determine which patients are candidates for screening for hypopituitarism. In addition, endocrinologists and internists must be educated about TBI-induced hypopituitarism and encouraged to actively share their expertise with other physicians.

Brain Injuries↗
PubMed2005

Residual pituitary function after brain injury-induced hypopituitarism: a prospective 12-month study.

CONTEXT: Traumatic brain injury (TBI) and subarachnoid hemorrhage (SAH) are conditions at high risk for the development of hypopituitarism. OBJECTIVE: The objective of the study was to clarify whether pituitary deficiencies and normal pituitary function recorded at 3 months would improve or worsen at 12 months after the brain injury. DESIGN AND PATIENTS: Pituitary function was tested at 3 and 12 months in patients who had TBI (n = 70) or SAH (n = 32). RESULTS: In TBI, the 3-month evaluation had shown hypopituitarism (H) in 32.8%. Panhypopituitarism (PH), multiple (MH), and isolated (IH) hypopituitarism had been demonstrated in 5.7, 5.7, and 21.4%, respectively. The retesting demonstrated some degree of H in 22.7%. PH, MH, and IH were present in 5.7, 4.2, and 12.8%, respectively. PH was always confirmed at 12 months, whereas MH and IH were confirmed in 25% only. In 5.5% of TBI with no deficit at 3 months, IH was recorded at retesting. In 13.3% of TBI with IH at 3 months, MH was demonstrated at 12-month retesting. In SAH, the 3-month evaluation had shown H in 46.8%. MH and IH had been demonstrated in 6.2 and 40.6%, respectively. The retesting demonstrated H in 37.5%. MH and IH were present in 6.2 and 31.3%, respectively. Although no MH was confirmed at 12 months, two patients with IH at 3 months showed MH at retesting; 30.7% of SAH with IH at 3 months displayed normal pituitary function at retesting. In SAH, normal pituitary function was always confirmed. In TBI and SAH, the most common deficit was always severe GH deficiency. CONCLUSION: There is high risk for H in TBI and SAH patients. Early diagnosis of PH is always confirmed in the long term. Pituitary function in brain-injured patients may improve over time but, although rarely, may also worsen. Thus, brain-injured patients must undergo neuroendocrine follow-up over time.

Adult↗
PubMed2005

Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment.

CONTEXT: Poor sensitivity of IGF binding protein (IGFBP)-3 assessment in the work-up of GH deficiency (GHD) has been ascribed to the equal affinity of IGFBP-3 for IGF-I and IGF-II and to IGFBP-3 proteolysis. OBJECTIVE: The objective of this study was to determine the IGF-II GH dependency and IGFBP-3 proteolysis in patients with GHD from childhood to young adulthood. DESIGN: This study was cross-sectional. SETTING: This was a national multicenter study performed in university hospitals. PATIENTS: One hundred thirty-one subjects (chronological age, 1.3-25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were studied. INTERVENTIONS: IGF-I, IGF-II, and IGFBP-3 serum concentrations were measured by immunoradiometric assay. IGFBP-3 circulating forms were assessed by Western immunoblot (WIB) analysis. MAIN OUTCOME MEASURES: Main outcome measures were sensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements. RESULTS: Sensitivity and specificity of IGFBP-3 measurement were 27 and 100%, respectively. IGFBP-3 sensitivity was 46% in young adulthood. Sensitivity and specificity of IGF-I were 69 and 81%, respectively. Sensitivity and specificity of IGF-II assessment were 23 and 97%, respectively. IGFBP-3 WIB revealed the presence of the intact form and the major 29-kDa fragment in both GHD and subjects with idiopathic short stature. In patients with GHD, WIB showed the presence of an additional smaller IGFBP-3 fragment migrating at approximately 18 kDa. CONCLUSIONS: Our results suggest that in children and young adults with GHD, the low GH dependency of IGF-II together with IGFBP-3 proteolytic activity yielding the 18-kDa fragment concur to reduce the sensitivity of IGFBP-3 assessment, ultimately making it too inaccurate as a screening test in the work-up of GHD.

Adolescent↗
PubMed2005

Variations of pituitary function over time after brain injuries: the lesson from a prospective study.

Traumatic Brain Injury (TBI) and Subarachnoid Haemorrhage (SAH) are conditions at high risk to develop hypopituitarism as pointed out by many papers in scientific literature. But most of the papers were referred to retrospective evaluations, not considering the possible evolution of the pituitary function over time. Aim of our studies was to clarify whether pituitary deficiencies and normal pituitary function recorded at short term follow-up (3 months), would improve or worsen, respectively, at long term (12 months after the brain injury). In a multicenter study protocol, in patients who suffered TBI (n = 70; 50 Males, 20 Females; age 39.31 +/- 2.4 years; BMI 23.8 +/- 0.4 kg/m(2)) or SAH (n = 32; 12M, 20F; age: 51.9 +/- 2.2 year; BMI: 24.7 +/- 0.6 kg/m(2)) we tested 3 and 12 months after the pathological events the pituitary function. In TBI patients, the 3 month evaluation had shown some degree of hypopituitarism in 32.8% and the 12 months retesting demonstrated some degree of hypopituitarism in 22.7%. Total hypopituitarism was always confirmed at 12 months while Multiple and Isolated deficits recorded at 3 months was confirmed in nearly 25% only of the patients. On the other hand, in 5.5% of TBI with normal pituitary function at 3 months Isolated deficits were recorded at 12 months testing. Moreover, in 13.3% of TBI with Isolated deficit at 3 months Multiple hypopituitarism was demonstrated at 12 months retesting. In SAH patients, the 3 months evaluation had shown some degree of hypopituitarism in 46.8% and the 12 month retesting demonstrated some degree of hypopituitarism in 37.5%. No multiple hypopituitarism recorded at 3 months was confirmed at 12 months, but 2 patients with isolated deficits at 3 months showed multiple hypopituitarism at 12 month retesting. At 12 as well as at 3 months, both in TBI and SAH patients, the most common deficit was severe GHD (>20%) followed by secondary hypogonadism and then hypoadrenalism and hypothyroidism. In all, in patients who experienced TBI or SAH the risk to develop hypopituitarism is very high; early diagnosis of total hypopituitarism is always confirmed at the long term follow-up; however pituitary function in brain injured patients may improve over time, because, isolated and even multiple pituitary insufficiencies recorded at short term can be transient; on the other hand normal pituitary function recorder at short term may, become impaired 12 months after the injury. Thus, brain injured patients must undergo neuroendocrine follow-up over time in order to monitoring pituitary function and eventually providing appropriate placement.

Adrenal Insufficiency↗
PubMed2005

IGFs and IGFBPs in adult growth hormone deficiency.

In the current guidelines for the diagnosis of adult GH deficiency (GHD) it is stated that, within the appropriate clinical context, it has to be shown by provocative tests only. But the diagnostic value of measuring IGF-I levels has been recently revisited. It has been confirmed that normal IGF-I levels do not rule out severe GHD in adults. However, it has also been emphasized that very low IGF-I levels in patients highly suspected for GHD (and without malnutrition, liver disease or hypothyroidism) could be considered definite evidence for severe GHD. This assumption particularly applies to patients with childhood-onset, severe GHD or with multiple hypopituitarism acquired in adulthood. The value of measuring IGF-I levels for monitoring the efficacy and the adequacy of rhGH replacement remains definitely accepted.

Adult↗
PubMed2005

Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement.

OBJECTIVE: A consensus exists that severe growth hormone deficiency (GHD) in adults is defined by a peak GH response to insulin-induced hypoglycemia (insulin tolerance test, ITT) of less than 3 microg/l based on a cohort of subjects with a mean age of 45 years. DESIGN AND METHODS: By considering one of the following two criteria for the diagnosis of probable permanent GHD, i.e. the severity of GHD (suggested by the presence of multiple pituitary hormone deficiencies (MPHD)) or the magnetic resonance (MR) imaging identification of structural hypothalamic-pituitary abnormalities, 26 patients (17 males, 9 females, mean age 20.8 +/- 2.3 years, range 17-25 years) were selected for re-evaluation of the GH response to ITT and their IGF-I concentration. Eight subjects had isolated GHD (IGHD) and 18 had MPHD. Normative data for peak GH were obtained after ITT in 39 healthy subjects (mean age 21.2 +/- 4.4 years, range 15.1-30.0 years) and the reference range for IGF-I was calculated using normative data from 117 healthy individuals. RESULTS: Mean peak GH response to ITT was significantly lower in the 26 patients (1.8+/-2.0 microg/l, range 0.1-6.1 microg/l) compared with the 39 controls (18.5 +/- 15.5 microg/l, range 6.1-84.0 microg/l; P < 0.0001). One subject with septo-optic dysplasia had a peak GH response of 6.1 microg/l that overlapped the lowest peak GH response obtained in normal subjects. There was an overlap for IGF-I SDS between subjects with IGHD and MPHD, as well as with normal controls. The diagnostic accuracy of a peak GH response of 6.1 microg/l showed a 96% sensitivity with 100% specificity. The maximum diagnostic accuracy with IGF-I SDS was obtained with a cut-off of -1.7 SDS (sensitivity 77%, specificity 100%) while an IGF-I < or = - 2.0 SDS showed a sensitivity of 62%. CONCLUSION: Our data show that the cut-off value of the peak GH response to ITT of less than 3 microg/l or 5 microg/l and of IGF-I of less than -2.0 SDS are too restrictive for the diagnosis of permanent GH deficiency in the transition period. We suggest that permanent GHD could be investigated more accurately by means of an integrated analysis of clinical history, the presence of MPHD, IGF-I concentration and the MR imaging findings of structural hypothalamic-pituitary abnormalities.

Adolescent↗
PubMed2005

The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index.

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.

Adult↗
PubMed2004

Traumatic brain injury and subarachnoid haemorrhage are conditions at high risk for hypopituitarism: screening study at 3 months after the brain injury.

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.

Adult↗
PubMed2004

Insulin sensitivity in growth hormone-deficient children: influence of replacement treatment.

OBJECTIVE: In adults, excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed children. The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of GH-deficient children treated with GH for a period of 6 years. PATIENTS AND DESIGN: One hundred and twenty-eight children (40 females, 88 males) were included in the study. At the beginning of treatment chronological age was 8.9 +/- 3.2 years, height standard deviation score (SDS) -2.43 +/- 0.90 and body mass index (BMI) SDS 0.18 +/- 1.60. At the end of the study chronological age was 13.0 +/- 2.9 years, height SDS -1.24 +/- 1.27 and BMI SDS 0.23 +/- 1.54. GH was administered at a mean weekly dosage of 0.3 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICKI). RESULTS: No cases of impaired GT or diabetes were recorded during the follow-up period. IS, already lower than in controls before starting treatment with GH, decreased significantly during the first year of therapy (QUICKI: 0.346 +/- 0.033 vs. 0.355 +/- 0.044, P < 0.05), with no further decrease in the following years. No correlation was found between QUICKI, BMI, years of treatment and onset of puberty. CONCLUSIONS: GH treatment in GH-deficient children does not lead to an impaired GT or type 2 diabetes mellitus, although it does significantly decrease IS.

Blood Glucose↗
PubMed2004

Insulin-like growth factor I levels and the diagnosis of adult growth hormone deficiency.

The current guidelines state that, within the appropriate clinical context, the diagnosis of adult growth hormone (GH) deficiency must be made biochemically using provocative tests. Measurement of insulin-like growth factor I (IGF-I) and binding protein 3 (IGFBP-3) levels cannot always distinguish between healthy and GH-deficient individuals. In particular, IGFBP-3 as a marker of GH status is clearly less sensitive than IGF-I and there is general agreement that its measurement does not provide useful diagnostic information. However, the diagnostic value of measuring IGF-I levels has been revisited recently. It has been confirmed that normal IGF-I levels do not rule out severe GH deficiency (GHD) in adults, in whom the diagnosis has therefore to be based on the demonstration of severe impairment of the peak GH response to provocative tests. It has also been emphasized that very low IGF-I levels in patients with high suspicion of GHD could be considered to be definite evidence for severe GHD. This assumption particularly applies to patients with childhood-onset, severe GHD or with multiple hypopituitary deficiencies acquired in adulthood. In addition, the use of IGF-I levels to monitor the efficacy and adequacy of recombinant human GH replacement remains widely accepted.

Adult↗
PubMed2004

Insulin sensitivity in Turner's syndrome: influence of GH treatment.

OBJECTIVE: Excessive GH secretion may lead to secondary diabetes mellitus, while prolonged GH treatment may accelerate the onset of type 2 diabetes mellitus in predisposed individuals. Turner's syndrome (TS) patients are a population at risk since they have reduced glucose tolerance (GT) spontaneously and because they are usually treated with high doses of GH. DESIGN AND METHODS: The aim of the study was to evaluate insulin sensitivity (IS) and glucose tolerance (GT) in a group of TS patients treated with GH for a period of 6 years. Forty-seven TS girls were included in the study. GH was administered at a mean weekly dosage of 0.35 mg/kg, injected subcutaneously over 6-7 days. GT was assessed according to the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. IS was evaluated with the quantitative insulin sensitivity check index (QUICK-I). RESULTS: No significant increase of impaired GT was observed in the patients during the follow-up period, while a reduced IS was detected. IS in TS patients was already lower than in prepubertal controls (P<0.001) before starting treatment and further decreased during the first year of therapy (P<0.05), and then remained stable over the following years. No correlation was found between QUICK-I, body mass index, years of treatment, onset and duration of puberty. One patient became diabetic during the course of treatment. CONCLUSIONS: GH treatment in TS girls does not significantly increase the prevalence of impaired GT or type 2 diabetes mellitus, while it does, however, decrease IS.

Child↗
PubMed2004

GHRH and GH secretagogues: clinical perspectives and safety.

The diagnosis and treatment of growth hormone deficiency (GHD), as well as the possibility of counteracting somatopause and age-related changes in body composition, structural functions, and metabolism, prompted interest in potential clinical uses of GH-releasing hormone (GHRH) and GH secretagogues (GHS). GHD often reflects hypothalamic GHRH deficiency and it has been clearly demonstrated that the age-related decline in the function of the GH/IGF-I axis reflects a reduction in hypothalamic function as evidenced by the preservation of the releasable pool of pituitary GH in aged subjects. The effectiveness of recombinant human GH (rhGH) is well established, but it is also recognized that GH replacement does not mimic physiological GH secretion which theoretically would be restored by GHRH and/or GHS. At present, it has been clearly demonstrated that GHRH and/or GHS represent reliable tools for the diagnosis of GHD. On the other hand, neither GHRH nor GHS has been shown to provide effective alternatives to rhGH for the treatment of GHD. Although GHRH and/or GHS represent the most logical approaches for the restoration of the GH/IGF-I axis to a youthful level of activity and for counteracting the somatopause, this hypothesis has never been proven definitively. Conceptually, GHRH replacement would be the most physiological approach and its safety is guaranteed, provided an appropriate dose is used, in order to avoid hyperactivity of the GH/IGF-I axis. However, a long-acting preparation is needed. On the other hand, GHS, e.g., ghrelin analogues, could be considered as a function of their selectivity of action. However, ghrelin has a wide spectrum of endocrine and non-endocrine actions at both central and peripheral levels. Thus, non-selective GHS, although available in orally active forms, could elicit unforeseen side effects. Previous studies with GHRH and/or GHS in aging patients provided encouraging results. However, it still remains to be definitively demonstrated that aged subjects would benefit from chronic treatment with these molecules.

Adult↗
PubMed2003

The effectiveness of arginine + GHRH test compared with GHRH + GHRP-6 test in diagnosing growth hormone deficiency in adults.

OBJECTIVE: The objective of this study is to investigate the performance of two novel tests in diagnosing growth hormone deficiency in adults. PATIENTS: Fifty patients presenting with long-standing hypopituitarism and two control groups consisting of 50 healthy subjects in each group [age-, sex- and body mass index (BMI)-matched] participated in a multicentre study. All underwent two provocative tests on different days within 3 months apart: (i) a combined GHRH + GHRP-6 test and (ii) arginine + GHRH test. Main outcome measures were sensitivity, specificity and areas under receiver operating characteristic curves (ROC) for GHRH + GHRP-6 and arginine + GHRH tests in the diagnosis of GH deficiency in adults. RESULTS: A peak GH level after GHRH + GHRP-6, under 15.0 microg/l had a sensitivity of 94.4% and specificity of 98.8% for diagnosing GHD and area under the ROC curve was 0.99 (95% confidence interval 0.95-0.99). For peak GH levels after arginine + GHRH, a level under 9.6 microg/l had a sensitivity of 88.4% and specificity of 95% and area under the ROC curve of 0.96 (95% confidence interval 0.91-0.98). The relationship between the increment in serum GH following GHRH + GHRP-6 and arginine + GHRH test was positive, i.e. r = 0.749, P = 0.001.Thus, there was high concordance between both tests. CONCLUSION: Both GHRH + GHRP-6 and/or arginine + GHRH test may serve as an alternative to the ITT in diagnosing GHD in adults.

Adult↗
PubMed2002

Endocrine responses to ghrelin in adult patients with isolated childhood-onset growth hormone deficiency.

OBJECTIVE: Ghrelin, a 28 amino acid acylated peptide, is a natural ligand of the GH secretagogues (GHS) receptor (GHS-R), which is specific for synthetic GHS. Similar to synthetic GHS, ghrelin strongly stimulates GH secretion but also displays significant stimulatory effects on lactotroph and corticotroph secretion. It has been hypothesized that isolated GH deficiency (GHD) could reflect hypothalamic impairment that would theoretically involve defect in ghrelin activity. PATIENTS: In the present study, we verified the effects of ghrelin (1 microg/kg i.v.) on GH, PRL, ACTH and cortisol levels in adult patients with isolated severe GHD [five males and one female, age (mean +/- SEM) 24.7 +/- 2.6 years, BMI 25.7 +/- 2.7 kg/m2]. In all patients, the GH response to insulin-induced hypoglycaemia (ITT, 0.1 IU regular insulin i.v.) and GH releasing hormone (GHRH) (1 microg/kg i.v.) + arginine (ARG, 0.5 g/kg i.v.) was also studied. The hormonal responses in GHD were compared with those in age-matched normal subjects (NS, seven males, age 28.6 +/- 2.9 years, BMI 22.1 +/- 0.8 kg/m2). RESULTS: IGF-I levels in GHD were markedly lower than in NS (69.8 +/- 11.3 vs. 167.9 +/- 19.2 microg/l, P < 0.003). Ghrelin administration induced significant increase in GH, PRL, ACTH and cortisol levels in all GHD. In GHD, the GH response to ghrelin was higher (P < 0.05) than that to GHRH + ARG, which, in turn, was higher (P < 0.05) than that to ITT (9.2 +/- 4.1 vs. 5.3 +/- 1.7 vs. 1.4 +/- 0.4 microg/l). These GH (1 microg/l = 2 mU/l) responses in GHD were markedly lower (P < 0.0001) than those in NS (ghrelin vs. GHRH + ARG vs. ITT 92.1 +/- 16.7 vs. 65.3 +/- 8.9 vs. 17.7 +/- 3.5 microg/l). In GHD, the highest individual peak GH response to ghrelin was markedly lower than the lowest peak GH response in NS (28.5 vs. 42.9 microg/l). GHD and NS showed overlapping PRL (1 microg/l = 32 mU/l) (10.0 +/- 1.4 vs. 14.9 +/- 2.2 microg/l), ACTH (22.3 +/- 5.3 vs. 18.7 +/- 4.6 pmol/l) and cortisol responses (598.1 +/- 52.4 vs. 486.9 +/- 38.9 nmol/l). CONCLUSIONS: This study shows that ghrelin is one of the most powerful provocative stimuli of GH secretion, even in those patients with isolated severe GHD. In this condition, however, the somatotroph response is markedly reduced while the lactotroph and corticotroph responsiveness to ghrelin is fully preserved, indicating that this endocrine activity is fully independent of mechanisms underlying the GH-releasing effect. These results do not support the hypothesis that ghrelin deficiency is a major cause of isolated GH deficiency but suggest that ghrelin might represent a reliable provocative test to evaluate the maximal GH secretory capacity provided that appropriate cut-off limits are assumed.

Adrenocorticotropic Hormone↗
PubMed2002

Ghrelin and synthetic GH secretagogues.

Ghrelin, a 28-amino-acid acylated peptide, produced mainly by the stomach, displays strong growth hormone-(GH)-releasing activity mediated by the hypothalamus-pituitary growth hormone potential secretagogue (GHS) receptor which had been shown to be specific for a family of synthetic, orally active GHS. GHS are reliable provocative tests for the diagnosis of GH deficiency but, as orally active growth-promoting agents, they are not comparable with human recombinant GH in terms of efficacy. The usefulness of GHS in anabolic, anti-ageing drug intervention in the somatopause is still unclear. GHS also act on central and peripheral receptors and show other actions, including an orexigenic effect, an influence on gastroentero-pancreatic functions, and cardiovascular and anti-proliferative effects. Ghrelin mediates the neuroendocrine and metabolic response to starvation. Taking into account its orexigenic effect, GHS analogues acting as agonists or antagonists on appetite could represent a new drug intervention for eating disorders.

Adrenocorticotropic Hormone↗