S. Loche | Università degli Studi di Cagliari (original) (raw)
Papers by S. Loche
The Endocrinologist, 2000
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > ...
Peptides, 1983
Intravenously administered synthetic hpGRF 1-40 at doses of 0.1, 0.33 and 1.0 microgram/kg increa... more Intravenously administered synthetic hpGRF 1-40 at doses of 0.1, 0.33 and 1.0 microgram/kg increased plasma GH in a dose-dependent fashion in 4 normal prepubertal children. hpGRF 1-40 at the dose of 1.0 microgram/kg stimulated GH release, though to a lesser extent than in normals, in 7 children with isolated GH-deficiency (IGHD) but failed to do so in a patient with craniopharyngioma. In all normal children and 6/7 patients with IGHD, hpGRF 1-40 at all doses used induced a clear and sustained lowering of plasma prolactin levels; this effect was lacking in the patient with craniopharyngioma. hpGRF 1-40 had no effect on plasma FSH, LH, TSH or glucose levels nor did it influence pulse rate, blood pressure, or body temperature. These results indicate that hpGRF 1-40 is a potent stimulus to GH release in normal prepubertal children and holds promise for treatment of GH-deficient children. In addition, in both normal children and children with IGHD, hpGRF 1-40 is a potent suppressor of prolactin levels.
The Journal of Pediatrics, 2002
To test the hypothesis that normalization of the growth hormone (GH) response to stimulation in p... more To test the hypothesis that normalization of the growth hormone (GH) response to stimulation in patients with GH deficiency (GHD) and normal magnetic resonance imaging (MRI) of the hypothalamic-pituitary area might occur earlier than at attainment of final height. Prepubertal children with short stature (21 boys and 12 girls; age, 5.2-10 years), in whom a diagnosis of GHD was based on a GH response <10 microg/L after 2 pharmacologic tests (clonidine, arginine, or insulin hypoglycemia), and normal MRI of the hypothalamic-pituitary area were studied. After 1 to 6 months, all children underwent reevaluation of GH secretion by means of one of the provocative tests previously used. During that time, none of the children received GH therapy or entered puberty. A GH response > or =10 microg/L after retesting was found in 28 patients, and a GH response <10 microg/L was found in 5. In 9 patients, the peak GH response at diagnosis was <7 microg/L to both tests used. In 8, the GH response at retesting was > or =10 microg/L and was 9.0 microg/L in the remaining child. We suggest that patients with pathologic GH responses to provocative tests but normal MRI should be reevaluated and followed up before a diagnosis of GHD is firmly established.
Journal of Endocrinological Investigation, 2006
For personal use only © 2 0 0 6 , E d i t r i c e K u r t i s © 2006, Editrice Kurtis.
The Journal of Clinical Endocrinology & Metabolism, 2009
Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH... more Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P < 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P < 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.
The Journal of Clinical Endocrinology & Metabolism, 2010
The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young chil... more The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P < 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.
The Journal of Clinical Endocrinology & Metabolism, 1999
Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD... more Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD) or with multiple pituitary hormone deficiencies (MPHD). To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, we evaluated BMD at the lumbar spine and femoral neck; circulating insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels in 101 adult hypopituitary patients and 35 sex- and age-matched healthy subjects. On the basis of the GH response to arginine plus GHRH (ARG+/-GHRH), patients were subdivided into 4 groups: group 1 included 41 patients with a GH peak below 3 microg/L (0.9 +/- 0.08 microg/L), defined as very severe GHD; group 2 included 25 patients with a GH peak between 3.1-9 microg/L (4.7 +/- 0.4 microg/L), defined as severe GHD; group 3 included 18 patients with a GH peak between 9.1-16.5 microg/L (11.0 +/- 0.3 microg/L), defined as partial GHD; and group 4 included 17 patients with a GH peak above 16.5 microg/L (28.3 +/- 4.3 microg/L), defined as non-GHD. In all 35 controls (group 5), the GH response after ARG+/-GHRH was above 16.5 microg/L (40.7 +/- 2.2 microg/L). In patients in group 1, circulating IGF-I (P < 0.001), IGFBP-3 (P < 0.05), osteocalcin (P < 0.001), and urinary Ntx levels (P < 0.001) were lower than those in group 3-5, which were not different from each other; the t score at the lumbar spine (-1.99 +/- 0.2) and that at the femoral neck (-1.86 +/- 0.3) were lower than those in groups 3 (-0.5 +/- 0.7, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), 4 (-0.5 +/- 0.2, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), and 5 (-0.5 +/- 0.2, P < 0.001 and 0.0 +/- 0.02, P < 0.001, respectively). In patients in group 2, circulating IGF-I and IGFBP-3 levels were not different from those in group 1, whereas the t scores at the lumbar spine (-1.22 +/- 0.3) and femoral neck (-0.9 +/- 0.3) were significantly higher and lower, respectively, than those in groups 1 and 5 (P < 0.05) but not those in groups 3 and 4, and serum osteocalcin and urinary Ntx levels were significant higher than those in group 1 and lower than those in groups 3-5 (P < 0.001). To evaluate the effect of isolated GHD vs. MPHD, patients were subdivided according to the number of their hormonal deficits, such as panhypopituitarism with (10 patients) or without (31 patients) diabetes insipidus, GHD with 1 or more additional pituitary deficit(s) (36 patients), isolated GHD (7 patients), 1-2 pituitary hormone deficit(s) without GHD (10 patients), and normal anterior pituitary function (7 patients). The t score at the lumbar spine and femoral neck and the biochemical parameters of bone turnover were not significantly different among the different subgroups with similar GH secretions. A significant correlation was found between the GH peak after ARG+GHRH and IGF-I, osteocalcin, urinary Ntx levels, and the t score at the lumbar spine, but not that at the femoral neck level. A significant correlation was also found between plasma IGF-I levels and the t score at the lumbar spine and femoral neck, serum osteocalcin, and urinary Ntx. Multiple correlation analysis revealed that the t score at the lumbar spine, but not that at the femoral neck, was more strongly predicted by plasma IGF-I levels (t = 3.376; P < 0.005) than by the GH peak after ARG+GHRH (t = -0.968; P = 0.338). In conclusion, a significant reduction of BMD associated with abnormalities of bone turnover parameters was found only in patients with very severe or severe GHD, whereas normal BMD values were found in non-GHD hypopituitary patients. These abnormalities were consistently present in all patients with GHD regardless of the presence of additional hormone deficits, suggesting that GHD plays a central role in the development of osteopenia in hypopituitary patients.
The Journal of Clinical Endocrinology & Metabolism, 1999
GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 Ϯ 3.2 yr in 3... more GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 Ϯ 3.2 yr in 35 young adults with childhood-onset GH deficiency (GHD). The patients were subdivided into 4 groups according to their first pituitary magnetic resonance imaging (MRI) findings: group I, 11 patients with isolated GHD (IGHD) and normal pituitary volume (280 Ϯ 59.4 mm 3 ); group II, 7 patients with IGHD and small pituitary gland (163.1 Ϯ 24.4 mm 3 ; P ϭ 0.0009 vs. group I); group III, 13 patients (5 with IGHD and 8 with multiple pituitary hormone deficiency) with congenital hypothalamic-pituitary abnormalities such as pituitary hypoplasia (95.8 Ϯ 39.3 mm 3 ; P Ͻ 0.00001 vs. group I and P ϭ 0.003 vs. group II), pituitary stalk agenesis, and posterior pituitary ectopia; and group IV, 4 patients with multiple pituitary hormone deficiency secondary to craniopharyngioma. Pituitary MRI and GH secretory status were reevaluated after GH withdrawal using arginine, insulin induced-hypoglycemia, and sequential arginine-insulin tests. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were determined at the time of retesting and 6, 12, and 24 months after discontinuation of treatment in the patients with permanent GHD and after 6 months in those with normal GH responses to stimulation. The patients in groups I and II showed a normal response to stimulation after completion of GH
The Journal of Clinical Endocrinology & Metabolism, 1998
In this study, we report the clinical presentation, response to medical treatment, and long-term ... more In this study, we report the clinical presentation, response to medical treatment, and long-term follow-up of 26 patients with prolactinoma (15 macro- and 11 micro-adenomas) diagnosed at the age of 7-17 yr. All patients were first treated with bromocriptine (BRC) at doses ranging from 2.5-20 mg/day orally. BRC was discontinued for intolerance and/or resistance to the drug and was replaced by quinagolide (CV) at doses ranging from 0.075-0.6 mg/day or by cabergoline at doses ranging from 0.5-3.5 mg/week orally. Two patients received external conventional radiotherapy after surgery. In 7 prepubertal males and 6 females with macroprolactinoma, headache and/or visual defects were the first symptoms. All females presented with primary or secondary amenorrhea. Growth arrest was observed in a male patient with microadenoma, whereas all the remaining patients had normal heights, and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 12 patients (3 males and 9 females) and gynecomastia in 4 males. Mean serum PRL concentration (+/-SE) at the time of diagnosis was 1080 +/- 267 microg/L in patients with macroadenoma and 155 +/- 38 microg/L in patients with microadenoma. In 10 patients, BRC normalized PRL levels and caused variable, but significant, tumor shrinkage. CV normalized PRL concentrations and reduced tumor size in 5 patients. Cabergoline normalized PRL concentrations in 7 of 10 patients resistant to CV. Pregnancy occurred in 2 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Only 4 patients are still moderately hyperprolactinemic. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in 7 patients, 5 of whom underwent surgery. Four patients became GH deficient in adult age. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.
Growth Hormone & IGF Research, 1998
European Journal of Endocrinology, 2007
Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to... more Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. Design: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). Patients and methods: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 mg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Results: Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 mg/l, IQR: 3.9-11.3 mg/l) was significantly higher in patients with VPS (10.9 mg/l, IQR: 2.4-15.1 mg/l) than in those with PSA (IQR: 2.3-6.7 mg/l; PZ0.001). It was significantly higher in subjects with isolated GHD (12.5 mg/l, IQR: 10.8-15.5 mg/l) than in those with multiple pituitary hormone deficiencies (5.15 mg/l, IQR: 2.4-9.0 mg/l; PZ0.003). No correlation was found between the GH peak after ghrelin and body mass index. Conclusion: The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamicpituitary connections.
European Journal of Endocrinology, 1989
We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase ... more We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase inhibitor, on the GHRH-induced GH rise in 11 obese children and in 8 age-matched controls. The GH response to GHRH (hpGRF 1-40, 1 microgram/kg iv), evaluated both as maximum GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with pyridostigmine bromide (60 mg orally 60 min before the GHRH injection) significantly increased both baseline GH levels and the GH response to GHRH in all the obese subjects, so that their mean baseline GH, peak GH levels and integrated area under the curve after pyridostigmine bromide plus GHRH were similar to those of the control children after GHRH. Also in control children pyridostigmine bromide increased (though not significantly) baseline GH levels. and caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after pyridostigmine bromide plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Mean baseline Sm-C levels were significantly higher in the obese than in control children. These data show that enhancement of cholinergic neurotransmission, likely in the hypothalamus, counteracts the blunted GH response to GHRH present in the obese children, and that in simple obesity the potential of the pituitary to make a secretory response to a direct GH secretagogue is preserved.
European Journal of Endocrinology, 2005
Objectives: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic... more Objectives: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamicpituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic -pituitary -adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences. Design and methods: In this study we evaluated the integrity of the HPA in 24 patients (age 4.2 -31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency. Results: At a cortisol cut-off for a normal response of 550 nmol/l (20 mg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2 -135.2 nmol/l (2.4-4.9 mg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST. Conclusion: We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re -assessment of adrenal function.
Clinical Endocrinology, 2003
BACKGROUND Osteoporosis is a frequent, severe and often underestimated consequence of long-term h... more BACKGROUND Osteoporosis is a frequent, severe and often underestimated consequence of long-term hypercortisolism, often presenting as bone fracture. OBJECTIVE This prospective study was designed to evaluate whether the abnormalities of bone mass and turnover can be similarly reversed in adolescent and adult patients with Cushing's disease, after correction of hypercortisolism. PATIENTS AND METHODS Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured at diagnosis and 2 years after cure of Cushing's disease (CD) in six patients with childhood-onset and nine with adulthood-onset disease. Fifteen age-, sex-and body mass index (BMI)matched healthy subjects served as controls. RESULTS At diagnosis, BMD Z scores at lumbar spine and OC levels were lower (2·3 ± ± ± ± 0·1 vs. − − − − 0·2 ± ± ± ± 0·01; P < 0·01 and 1·6 ± ± ± ± 0·1 vs. 9·6 ± ± ± ± 1·2; P < 0·01 respectively) while urinary Ntx levels were significantly higher (139·9 ± ± ± ± 6·1 vs. 82·0 ± ± ± ± 1·6; P < 0·01) in CD patients than in controls. Among CD patients, similar values of Z scores ( − − − − 2·4 ± ± ± ± 0·3 vs. − − − − 2·2 ± ± ± ± 0·1, P = 0·4) and OC levels (1·7 ± ± ± ± 0·2 vs. 1·6 ± ± ± ± 0·2, P = 0·6) were observed in adolescent and adults patients, whereas urinary Ntx levels were significantly higher (159·7 ± ± ± ± 7·9 vs. 125·9 ± ± ± ± 3·3, P < 0·001) in the former than in the latter group. Two years after remission from hypercortisolism, OC levels ( P < 0·001) and lumbar BMD Z scores ( − − − − 2·2 ± ± ± ± 0·3, P < 0·05; and − − − − 1·9 ± ± ± ± 0·2; P < 0·01, respectively) increased significantly, while urinary Ntx levels reduced significantly ( P < 0·001) in both adolescent and adult patients. However, biochemical markers and Z scores of BMD remained significantly suppressed compared to controls.
Clinical Endocrinology, 1986
The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH-releasing hor... more The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH-releasing hormone (GHRH) has been evaluated in children with constitutional growth delay. Five subjects, four males and one female, aged 11.0-17.1 years were given oxandrolone 0.1 mg/kg p.o. daily for 2 months, and underwent acute administration of GHRH (GRF 1-40, 1 microgram/kg i.v.) before and after withdrawal of oxandrolone therapy. GHRH administration induced a much greater GH response, evaluated either as a peak plasma GH levels or plasma GH integrated area, after than it did before oxandrolone treatment. These findings indicate that in children with constitutional growth delay oxandrolone increases the sensitivity of somatotrophs to exogenous GHRH and, likely, to the endogenously-released neurohormone.
Journal of Applied Genetics, 2008
The Endocrinologist, 2000
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > ...
Peptides, 1983
Intravenously administered synthetic hpGRF 1-40 at doses of 0.1, 0.33 and 1.0 microgram/kg increa... more Intravenously administered synthetic hpGRF 1-40 at doses of 0.1, 0.33 and 1.0 microgram/kg increased plasma GH in a dose-dependent fashion in 4 normal prepubertal children. hpGRF 1-40 at the dose of 1.0 microgram/kg stimulated GH release, though to a lesser extent than in normals, in 7 children with isolated GH-deficiency (IGHD) but failed to do so in a patient with craniopharyngioma. In all normal children and 6/7 patients with IGHD, hpGRF 1-40 at all doses used induced a clear and sustained lowering of plasma prolactin levels; this effect was lacking in the patient with craniopharyngioma. hpGRF 1-40 had no effect on plasma FSH, LH, TSH or glucose levels nor did it influence pulse rate, blood pressure, or body temperature. These results indicate that hpGRF 1-40 is a potent stimulus to GH release in normal prepubertal children and holds promise for treatment of GH-deficient children. In addition, in both normal children and children with IGHD, hpGRF 1-40 is a potent suppressor of prolactin levels.
The Journal of Pediatrics, 2002
To test the hypothesis that normalization of the growth hormone (GH) response to stimulation in p... more To test the hypothesis that normalization of the growth hormone (GH) response to stimulation in patients with GH deficiency (GHD) and normal magnetic resonance imaging (MRI) of the hypothalamic-pituitary area might occur earlier than at attainment of final height. Prepubertal children with short stature (21 boys and 12 girls; age, 5.2-10 years), in whom a diagnosis of GHD was based on a GH response &amp;amp;amp;amp;amp;amp;amp;lt;10 microg/L after 2 pharmacologic tests (clonidine, arginine, or insulin hypoglycemia), and normal MRI of the hypothalamic-pituitary area were studied. After 1 to 6 months, all children underwent reevaluation of GH secretion by means of one of the provocative tests previously used. During that time, none of the children received GH therapy or entered puberty. A GH response &amp;amp;amp;amp;amp;amp;amp;gt; or =10 microg/L after retesting was found in 28 patients, and a GH response &amp;amp;amp;amp;amp;amp;amp;lt;10 microg/L was found in 5. In 9 patients, the peak GH response at diagnosis was &amp;amp;amp;amp;amp;amp;amp;lt;7 microg/L to both tests used. In 8, the GH response at retesting was &amp;amp;amp;amp;amp;amp;amp;gt; or =10 microg/L and was 9.0 microg/L in the remaining child. We suggest that patients with pathologic GH responses to provocative tests but normal MRI should be reevaluated and followed up before a diagnosis of GHD is firmly established.
Journal of Endocrinological Investigation, 2006
For personal use only © 2 0 0 6 , E d i t r i c e K u r t i s © 2006, Editrice Kurtis.
The Journal of Clinical Endocrinology & Metabolism, 2009
Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH... more Few studies have addressed the diagnostic role of the glucagon test in children with suspected GH deficiency (GHD). The objective of the study was to investigate the diagnostic value of the glucagon test as an alternative test to insulin tolerance test (ITT) and arginine in GHD children younger than 6 yr. This study was conducted in two pediatric endocrinology centers. Forty-eight children (median age 4.2 yr, median height -3.0 sd score) with GHD confirmed by a peak GH to ITT and arginine less than 10 microg/liter (median 4.7 and 3.4 microg/liter, respectively) underwent a glucagon stimulation test. Magnetic resonance imaging showed normal hypothalamic-pituitary anatomy in 24 children, isolated anterior pituitary hypoplasia in seven, and structural hypothalamic-pituitary abnormalities in 17. Median GH peak response to glucagon (13.5 microg/liter) was significantly higher than that observed after ITT and arginine (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). GH peak after glucagon was less than 10 microg/liter in 20 subjects (group 1) and greater than 10 microg/liter in 28 subjects (group 2) without significant clinical or biochemical differences between the two groups. Median GH peak after glucagon was similar between patients with multiple pituitary hormone deficiency and those with isolated GHD and between subjects with and without structural hypothalamic-pituitary abnormalities. The magnitude of the GH peak after glucagon was negatively correlated to age at diagnosis (rho = -0.636, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001). This study shows that glucagon has an effective GH-releasing activity and can be used to evaluate somatotroph function in young children with short stature. Normative data for this test in young children need to be established before its use in clinical practice.
The Journal of Clinical Endocrinology & Metabolism, 2010
The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young chil... more The accuracy of the glucagon test in the diagnosis of central adrenal insufficiency in young children has not yet been definitively established. The aim of this study was to investigate the diagnostic accuracy of the glucagon test as an alternative to the insulin tolerance test (ITT) in children with GH deficiency under 6 yr of age. This was a prospective study conducted in two Pediatric Endocrinology Centers. Forty-eight children (median age, 4.2 yr) with GH deficiency confirmed by a peak GH to ITT and arginine less than 10 microg/liter were enrolled: 24 with normal hypothalamic-pituitary anatomy, seven with isolated anterior pituitary hypoplasia, and 17 with structural hypothalamic-pituitary abnormalities at magnetic resonance imaging. Twelve subjects had central adrenal insufficiency defined by a peak cortisol response of less than 20 microg/dl to ITT. All children underwent a glucagon stimulation test with blood sampling for cortisol and glucose (time 0 to 180 min) after the im administration of 30 microg/kg of glucagon. The mean peak cortisol after glucagon was not significantly different from that obtained after ITT in the whole cohort (25.9 vs. 26.0 microg/dl; P = 0.908), and it was significantly reduced in patients with structural hypothalamic-pituitary abnormalities (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Receiver operating characteristic curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cutoff to glucagon of 14.6 microg/dl (sensitivity, 66.67%; specificity, 100%; area under the curve = 0.91; 95% confidence interval, 0.82-0.99). Using this cutoff, 91.67% of the patients were correctly classified. This study shows that glucagon is an accurate and safe diagnostic test for adrenal function in young children who are at risk for adrenal insufficiency.
The Journal of Clinical Endocrinology & Metabolism, 1999
Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD... more Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD) or with multiple pituitary hormone deficiencies (MPHD). To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, we evaluated BMD at the lumbar spine and femoral neck; circulating insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels in 101 adult hypopituitary patients and 35 sex- and age-matched healthy subjects. On the basis of the GH response to arginine plus GHRH (ARG+/-GHRH), patients were subdivided into 4 groups: group 1 included 41 patients with a GH peak below 3 microg/L (0.9 +/- 0.08 microg/L), defined as very severe GHD; group 2 included 25 patients with a GH peak between 3.1-9 microg/L (4.7 +/- 0.4 microg/L), defined as severe GHD; group 3 included 18 patients with a GH peak between 9.1-16.5 microg/L (11.0 +/- 0.3 microg/L), defined as partial GHD; and group 4 included 17 patients with a GH peak above 16.5 microg/L (28.3 +/- 4.3 microg/L), defined as non-GHD. In all 35 controls (group 5), the GH response after ARG+/-GHRH was above 16.5 microg/L (40.7 +/- 2.2 microg/L). In patients in group 1, circulating IGF-I (P < 0.001), IGFBP-3 (P < 0.05), osteocalcin (P < 0.001), and urinary Ntx levels (P < 0.001) were lower than those in group 3-5, which were not different from each other; the t score at the lumbar spine (-1.99 +/- 0.2) and that at the femoral neck (-1.86 +/- 0.3) were lower than those in groups 3 (-0.5 +/- 0.7, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), 4 (-0.5 +/- 0.2, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), and 5 (-0.5 +/- 0.2, P < 0.001 and 0.0 +/- 0.02, P < 0.001, respectively). In patients in group 2, circulating IGF-I and IGFBP-3 levels were not different from those in group 1, whereas the t scores at the lumbar spine (-1.22 +/- 0.3) and femoral neck (-0.9 +/- 0.3) were significantly higher and lower, respectively, than those in groups 1 and 5 (P < 0.05) but not those in groups 3 and 4, and serum osteocalcin and urinary Ntx levels were significant higher than those in group 1 and lower than those in groups 3-5 (P < 0.001). To evaluate the effect of isolated GHD vs. MPHD, patients were subdivided according to the number of their hormonal deficits, such as panhypopituitarism with (10 patients) or without (31 patients) diabetes insipidus, GHD with 1 or more additional pituitary deficit(s) (36 patients), isolated GHD (7 patients), 1-2 pituitary hormone deficit(s) without GHD (10 patients), and normal anterior pituitary function (7 patients). The t score at the lumbar spine and femoral neck and the biochemical parameters of bone turnover were not significantly different among the different subgroups with similar GH secretions. A significant correlation was found between the GH peak after ARG+GHRH and IGF-I, osteocalcin, urinary Ntx levels, and the t score at the lumbar spine, but not that at the femoral neck level. A significant correlation was also found between plasma IGF-I levels and the t score at the lumbar spine and femoral neck, serum osteocalcin, and urinary Ntx. Multiple correlation analysis revealed that the t score at the lumbar spine, but not that at the femoral neck, was more strongly predicted by plasma IGF-I levels (t = 3.376; P < 0.005) than by the GH peak after ARG+GHRH (t = -0.968; P = 0.338). In conclusion, a significant reduction of BMD associated with abnormalities of bone turnover parameters was found only in patients with very severe or severe GHD, whereas normal BMD values were found in non-GHD hypopituitary patients. These abnormalities were consistently present in all patients with GHD regardless of the presence of additional hormone deficits, suggesting that GHD plays a central role in the development of osteopenia in hypopituitary patients.
The Journal of Clinical Endocrinology & Metabolism, 1999
GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 Ϯ 3.2 yr in 3... more GH secretion was reevaluated after completion of GH treatment at a mean age of 19.2 Ϯ 3.2 yr in 35 young adults with childhood-onset GH deficiency (GHD). The patients were subdivided into 4 groups according to their first pituitary magnetic resonance imaging (MRI) findings: group I, 11 patients with isolated GHD (IGHD) and normal pituitary volume (280 Ϯ 59.4 mm 3 ); group II, 7 patients with IGHD and small pituitary gland (163.1 Ϯ 24.4 mm 3 ; P ϭ 0.0009 vs. group I); group III, 13 patients (5 with IGHD and 8 with multiple pituitary hormone deficiency) with congenital hypothalamic-pituitary abnormalities such as pituitary hypoplasia (95.8 Ϯ 39.3 mm 3 ; P Ͻ 0.00001 vs. group I and P ϭ 0.003 vs. group II), pituitary stalk agenesis, and posterior pituitary ectopia; and group IV, 4 patients with multiple pituitary hormone deficiency secondary to craniopharyngioma. Pituitary MRI and GH secretory status were reevaluated after GH withdrawal using arginine, insulin induced-hypoglycemia, and sequential arginine-insulin tests. Serum insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) were determined at the time of retesting and 6, 12, and 24 months after discontinuation of treatment in the patients with permanent GHD and after 6 months in those with normal GH responses to stimulation. The patients in groups I and II showed a normal response to stimulation after completion of GH
The Journal of Clinical Endocrinology & Metabolism, 1998
In this study, we report the clinical presentation, response to medical treatment, and long-term ... more In this study, we report the clinical presentation, response to medical treatment, and long-term follow-up of 26 patients with prolactinoma (15 macro- and 11 micro-adenomas) diagnosed at the age of 7-17 yr. All patients were first treated with bromocriptine (BRC) at doses ranging from 2.5-20 mg/day orally. BRC was discontinued for intolerance and/or resistance to the drug and was replaced by quinagolide (CV) at doses ranging from 0.075-0.6 mg/day or by cabergoline at doses ranging from 0.5-3.5 mg/week orally. Two patients received external conventional radiotherapy after surgery. In 7 prepubertal males and 6 females with macroprolactinoma, headache and/or visual defects were the first symptoms. All females presented with primary or secondary amenorrhea. Growth arrest was observed in a male patient with microadenoma, whereas all the remaining patients had normal heights, and pubertal development was appropriate for their age. Spontaneous or provocative galactorrhea was observed in 12 patients (3 males and 9 females) and gynecomastia in 4 males. Mean serum PRL concentration (+/-SE) at the time of diagnosis was 1080 +/- 267 microg/L in patients with macroadenoma and 155 +/- 38 microg/L in patients with microadenoma. In 10 patients, BRC normalized PRL levels and caused variable, but significant, tumor shrinkage. CV normalized PRL concentrations and reduced tumor size in 5 patients. Cabergoline normalized PRL concentrations in 7 of 10 patients resistant to CV. Pregnancy occurred in 2 patients while on treatment. Pregnancies were uncomplicated, and the patients delivered normal newborns at term. Only 4 patients are still moderately hyperprolactinemic. Impairment of other pituitary hormone secretion was documented at the time of diagnosis in 7 patients, 5 of whom underwent surgery. Four patients became GH deficient in adult age. In conclusion, the medical treatment with dopaminergic compounds is effective and safe in patients with prolactinoma with onset in childhood, allowing preservation of the anterior pituitary function.
Growth Hormone & IGF Research, 1998
European Journal of Endocrinology, 2007
Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to... more Objectives: Evaluation of GH response to ghrelin in patients with GH deficiency (GHD) may help to elucidate the site and mechanism of action of ghrelin. We aimed to investigate the GH-releasing effect of ghrelin in children and young adults with childhood-onset GHD. Design: All subjects underwent ghrelin testing and neuro-imaging examination. Magnetic resonance imaging evidenced the presence of a vascular pituitary stalk (VPS) or its complete absence (PSA). Patients and methods: Seventeen prepubertal children and nine adult patients with childhood-onset GHD were selected for the study. The children were enrolled at a median age of 5.8 years. The adult subjects were included at a median age of 23.3 years. The diagnosis of GHD in the adult patients had been established at a median age of 8.5 years. Ghrelin was administered at a dose of 1 mg/kg body weight, i.v. at time zero, and blood for GH determination was obtained at 0, 15, 30, 45, 60, 75, 90, 105 and 120 min. Results: Median GH response after ghrelin was similar between children and adults. Median peak GH response to ghrelin (7.45 mg/l, IQR: 3.9-11.3 mg/l) was significantly higher in patients with VPS (10.9 mg/l, IQR: 2.4-15.1 mg/l) than in those with PSA (IQR: 2.3-6.7 mg/l; PZ0.001). It was significantly higher in subjects with isolated GHD (12.5 mg/l, IQR: 10.8-15.5 mg/l) than in those with multiple pituitary hormone deficiencies (5.15 mg/l, IQR: 2.4-9.0 mg/l; PZ0.003). No correlation was found between the GH peak after ghrelin and body mass index. Conclusion: The GH response to ghrelin in patients with congenital hypopituitarism depends on the degree of the anatomical abnormalities and lends further support to the assumption that the main action of the peptide is exerted at the hypothalamic level and requires the integrity of hypothalamicpituitary connections.
European Journal of Endocrinology, 1989
We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase ... more We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase inhibitor, on the GHRH-induced GH rise in 11 obese children and in 8 age-matched controls. The GH response to GHRH (hpGRF 1-40, 1 microgram/kg iv), evaluated both as maximum GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with pyridostigmine bromide (60 mg orally 60 min before the GHRH injection) significantly increased both baseline GH levels and the GH response to GHRH in all the obese subjects, so that their mean baseline GH, peak GH levels and integrated area under the curve after pyridostigmine bromide plus GHRH were similar to those of the control children after GHRH. Also in control children pyridostigmine bromide increased (though not significantly) baseline GH levels. and caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after pyridostigmine bromide plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Mean baseline Sm-C levels were significantly higher in the obese than in control children. These data show that enhancement of cholinergic neurotransmission, likely in the hypothalamus, counteracts the blunted GH response to GHRH present in the obese children, and that in simple obesity the potential of the pituitary to make a secretory response to a direct GH secretagogue is preserved.
European Journal of Endocrinology, 2005
Objectives: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamic... more Objectives: Patients with organic growth hormone deficiency (GHD) or with structural hypothalamicpituitary abnormalities may have additional anterior pituitary hormone deficits, and are at risk of developing complete or partial corticotropin (ACTH) deficiency. Evaluation of the integrity of the hypothalamic -pituitary -adrenal axis (HPA) is essential in these patients because, although clinically asymptomatic, their HPA cannot appropriately react to stressful stimuli with potentially life-threatening consequences. Design and methods: In this study we evaluated the integrity of the HPA in 24 patients (age 4.2 -31 years at the time of the study) with an established diagnosis of GHD and compared the reliability of the insulin tolerance test (ITT), short synacthen test (SST), low-dose SST (LDSST), and corticotropin releasing hormone (CRH) test in the diagnosis of adrenal insufficiency. Results: At a cortisol cut-off for a normal response of 550 nmol/l (20 mg/dl), the response to ITT was subnormal in 11 subjects, 6 with congenital and 5 with acquired GHD. Four patients had overt adrenal insufficiency, with morning cortisol concentrations ranging between 66.2 -135.2 nmol/l (2.4-4.9 mg/dl) and typical clinical symptoms and laboratory findings. In all these patients, a subnormal cortisol response to ITT was confirmed by LDSST and by CRH tests. SST failed to identify one of the patients as adrenal insufficient. In the seven asymptomatic patients with a subnormal cortisol response to ITT, the diagnosis of adrenal insufficiency was confirmed in one by LDSST, in none by SST, and in five by CRH tests. The five patients with a normal cortisol response to ITT exhibited a normal response also after LDSST and SST. Only two of them had a normal response after a CRH test. In the seven patients with asymptomatic adrenal insufficiency mean morning cortisol concentration was significantly higher than in the patients with overt adrenal insufficiency. ITT was contraindicated in eight patients, and none of them had clinical symptoms of overt adrenal insufficiency. One of these patients had a subnormal cortisol response to LDSST, SST, and CRH, and three exhibited a subnormal response to CRH but normal responses to LDSST and to SST. Conclusion: We conclude that none of these tests can be considered completely reliable for establishing or excluding the presence of secondary or tertiary adrenal insufficiency. Consequently, clinical judgment remains one of the most important issues for deciding which patients need assessment or re -assessment of adrenal function.
Clinical Endocrinology, 2003
BACKGROUND Osteoporosis is a frequent, severe and often underestimated consequence of long-term h... more BACKGROUND Osteoporosis is a frequent, severe and often underestimated consequence of long-term hypercortisolism, often presenting as bone fracture. OBJECTIVE This prospective study was designed to evaluate whether the abnormalities of bone mass and turnover can be similarly reversed in adolescent and adult patients with Cushing's disease, after correction of hypercortisolism. PATIENTS AND METHODS Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels were measured at diagnosis and 2 years after cure of Cushing's disease (CD) in six patients with childhood-onset and nine with adulthood-onset disease. Fifteen age-, sex-and body mass index (BMI)matched healthy subjects served as controls. RESULTS At diagnosis, BMD Z scores at lumbar spine and OC levels were lower (2·3 ± ± ± ± 0·1 vs. − − − − 0·2 ± ± ± ± 0·01; P < 0·01 and 1·6 ± ± ± ± 0·1 vs. 9·6 ± ± ± ± 1·2; P < 0·01 respectively) while urinary Ntx levels were significantly higher (139·9 ± ± ± ± 6·1 vs. 82·0 ± ± ± ± 1·6; P < 0·01) in CD patients than in controls. Among CD patients, similar values of Z scores ( − − − − 2·4 ± ± ± ± 0·3 vs. − − − − 2·2 ± ± ± ± 0·1, P = 0·4) and OC levels (1·7 ± ± ± ± 0·2 vs. 1·6 ± ± ± ± 0·2, P = 0·6) were observed in adolescent and adults patients, whereas urinary Ntx levels were significantly higher (159·7 ± ± ± ± 7·9 vs. 125·9 ± ± ± ± 3·3, P < 0·001) in the former than in the latter group. Two years after remission from hypercortisolism, OC levels ( P < 0·001) and lumbar BMD Z scores ( − − − − 2·2 ± ± ± ± 0·3, P < 0·05; and − − − − 1·9 ± ± ± ± 0·2; P < 0·01, respectively) increased significantly, while urinary Ntx levels reduced significantly ( P < 0·001) in both adolescent and adult patients. However, biochemical markers and Z scores of BMD remained significantly suppressed compared to controls.
Clinical Endocrinology, 1986
The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH-releasing hor... more The effect of treatment with oxandrolone, an anabolic steroid, on GH response to GH-releasing hormone (GHRH) has been evaluated in children with constitutional growth delay. Five subjects, four males and one female, aged 11.0-17.1 years were given oxandrolone 0.1 mg/kg p.o. daily for 2 months, and underwent acute administration of GHRH (GRF 1-40, 1 microgram/kg i.v.) before and after withdrawal of oxandrolone therapy. GHRH administration induced a much greater GH response, evaluated either as a peak plasma GH levels or plasma GH integrated area, after than it did before oxandrolone treatment. These findings indicate that in children with constitutional growth delay oxandrolone increases the sensitivity of somatotrophs to exogenous GHRH and, likely, to the endogenously-released neurohormone.
Journal of Applied Genetics, 2008