F. Prodam - Academia.edu (original) (raw)
Papers by F. Prodam
Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been r... more Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. Methods: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. Results: ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P <0.02) and impaired fasting glucose or glucose tolerance (P <0.001). Higher cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. Conclusions: In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations.
Journal of Endocrinological Investigation, 2014
Journal of endocrinological investigation, 2008
The most updated guidelines for the diagnosis of adult GH deficiency (GHD) come from the GH Resea... more The most updated guidelines for the diagnosis of adult GH deficiency (GHD) come from the GH Research Society Consensus Workshop held in Sydney, Australia, in 2007. Regarding who to test for GHD, advice should be extended from primitive hypothalamic- pituitary diseases and cranial irradiation to include brain injuries (Traumatic Brain Injury in particular). Regarding how to test for GHD, the insulin tolerance test (ITT) remains a provocative test of reference; among classical provocative test, glucagon test has also been validated. Above all, GHRH + arginine and GHRH + GH-secretagogues are now considered, at least, as reliable as ITT for the diagnosis of adult GHD. Interestingly, it is now accepted that very low IGF-I represents definite evidence of severe GHD in congenital forms of GHD and also in patients with acquired multiple hypopituitarism. These patients would skip provocative test; however, as normal IGFI levels do not rule out severe GHD, patients suspected for hypopituitari...
PLoS ONE, 2014
Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (... more Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on b-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 mg/kg per h) or saline in eight normal subjects (age (meanGS.E.M.), 29.6G2.4 years; body mass index (BMI), 22.4G1.7 kg/m 2 ), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P!0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG 0-960 min : 79.0G1.7!10 3 mg/dl per min vs saline 0-960 min : 87.5G3.8!10 3 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min : 28.4G0.5!10 3 mg/dl per min vs saline 180-660 min : 33.2G1.1 !10 3 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG 0-960 min : 0.3G0.02!10 3 mEq/l per min vs saline 0-960 min : 0.6G0.05!10 3 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties.
Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary ... more Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary masses. They often originate from breast or lung carcinomas and may resemble a nonfunctioning pituitary adenoma both clinically and radiologically. Here we describe a patient with pituitary metastasis from follicular thyroid carcinoma and discuss the unique features of these lesions. A 45-year-old woman was admitted to the emergency rescue room of our hospital with a 2-month history of progressive headache and blurred vision. Evaluation revealed right eye amaurosis, with a mild abducens and oculomotor palsy. Pituitary magnetic resonance imaging showed a mass that was hypo-intense in T1-weighted and hyper-intense in T2-weighted-images, located from the sphenoid sinus up to chiasmatic cisterns, raising and deflecting the optic chiasm, down to hypopharynx region, and distorting the cavernous sinuses. No evidence of anterior or posterior hypopituitarism was recorded. The immediate trans-sphenoidal surgery was uncomplicated with partial improvement of the visual fields and headache. Histopathology revealed a metastasis with well-differentiated follicular thyroid architecture. Total thyroidectomy and lymph node dissection was performed with a final histopathological diagnosis of follicular thyroid carcinoma. Subsequently, her headache became more severe. 131-I ablation treatments were performed 15 days and 12 months after thyroidectomy with decrease in headache and a decline in serum thyroglobulin levels. Pituitary metastases from thyroid carcinoma are very uncommon. As this patient illustrates, they tend to produce symptoms relating to space-occupying expansion in the parasellar region rather than to those due to destruction of the pituitary gland. Although rare, pituitary metastases caused by thyroid malignancy should be considered in patients with expanding parasellar lesions if they have thyroid cancer or uncharacterized thyroid diseases. They are unlikely to be amenable to complete resection and should be considered for 131-I treatment, perhaps avoiding the need for extensive neurological surgery.
Endocrine Abstracts, 2014
Hormone Research, 2003
Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amo... more Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.
![Research paper thumbnail of Corrigendum to “Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism” [Growth Horm. IGF Res. 23 (4) (2013) 109–113]](https://attachments.academia-assets.com/39108803/thumbnails/1.jpg)
](Growth Hormone & IGF Research, 2014
European Journal of Endocrinology, 2012
Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (... more Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on b-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 mg/kg per h) or saline in eight normal subjects (age (meanGS.E.M.), 29.6G2.4 years; body mass index (BMI), 22.4G1.7 kg/m 2 ), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P!0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG 0-960 min : 79.0G1.7!10 3 mg/dl per min vs saline 0-960 min : 87.5G3.8!10 3 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min : 28.4G0.5!10 3 mg/dl per min vs saline 180-660 min : 33.2G1.1 !10 3 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG 0-960 min : 0.3G0.02!10 3 mEq/l per min vs saline 0-960 min : 0.6G0.05!10 3 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties.
European Journal of Endocrinology, 2013
Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for ove... more Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing regimens were effective but resulted in supraphysiological levels of IGF1 and increased incidence of side effects. Current practice has moved towards individualised regimens, starting with low GH doses and gradually titrating the dose according to the level of serum IGF1 to achieve an optimal dose. Here we present the evidence supporting the dosing recommendations of current guidelines and consider factors affecting dose responsiveness and parameters of treatment response. The published data discussed here lend support for the use of low GH dosing regimens in adult GHD. The range of doses defined as &amp;amp;amp;amp;amp;amp;amp;#39;low dose&amp;amp;amp;amp;amp;amp;amp;#39; in the studies discussed here (∼1-4 mg/week) is in accordance with those recommended in current guidelines and encompasses the dose range recommended by product labels.
Clinical Endocrinology, 2002
Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an... more Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester in serine-3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone-releasing hormone (GHRH) and non-natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non-natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH-releasing effect of ghrelin in humans have not been fully clarified. To this aim we enrolled six normal young volunteers [age (mean +/- SEM) 28.9 +/- 3.1 year; body mass index 22.3 +/- 1.0 kg/m2). In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at -45 min) or free fatty acids (FFA) load [lipid-heparin emulsion, Li-He, Intralipid 10% 250 ml + heparin 2500 U i.v. from -30 to +120 min] as well as of arginine (ARG, 0.5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1.0 micro g/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li-He and ARG on the GH response to GHRH-29 (1.0 micro g/kg i.v. at 0 min). The GH response to ghrelin (auc 5452.4 +/- 991.3 micro g/l/h) was higher (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that after GHRH (1519.4 +/- 93.3 micro g/l/h). The GH response to GHRH was inhibited by OGTT (450.7 +/- 81.1 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and almost abolished by Li-He (230.0 +/- 63.6 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) while was markedly potentiated by ARG (2520.4 +/- 425.8 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The GH response to GHRH + ARG, however, was lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153.1 +/- 781.9 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) as well as by Li-He (3158.8 +/- 426.7 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) but these responses remained higher (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324.3 +/- 1275.5 micro g/l/h). For GH 1 micro g/l = 2 mU/l. In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non-natural GHS acts, at least partially, by antagonizing SS activity.
European Journal of Endocrinology, 2007
Objective: To define the appropriate diagnostic cut-off limits for the GH response to GHRHCargini... more Objective: To define the appropriate diagnostic cut-off limits for the GH response to GHRHCarginine (ARG) test and IGF-I levels, using receiver operating characteristics (ROC) curve analysis, in late adolescents and young adults. Design and methods: We studied 152 patients with childhood-onset organic hypothalamic-pituitary disease (85 males, age (meanGS.E.M.): 19.2G0.2 years) and 201 normal adolescents as controls (96 males, age: 20.7G0.2 years). Patients were divided into three subgroups on the basis of the number of the other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A consisted of 35 panhypopituitary patients (17 males, age: 21.2G0.4 years), subgroup B consisted of 18 patients with only one or with no more than two pituitary hormone deficits (7 males, age: 20.2G0.9 years); and subgroup C consisted of 99 patients without any known hormonal pituitary deficits (60 males, age: 18.2G0.2 years). Both patients and controls were lean (body mass index, BMI!25 kg/m 2 ). Patients in subgroup A were assumed to be GHD, whereas in patients belonging to subgroups B and C the presence of GHD had to be verified. Results: For the GHRHCARG test, the best pair of highest sensitivity (Se; 100%) and specificity (Sp; 97%) was found choosing a peak GH of 19.0 mg/l. For IGF-I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a cut-off point of 160 mg/l (SDS: K1.3). Assuming 19.0 mg/l to be the cut-off point established for GHRHCARG test, 72.2% of patients in subgroup B and 39.4% in subgroup C were defined as GHD. In patients belonging to group B and C and with a peak GH response !19 mg/l to the test, IGF-I levels were lower than 160 mg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients respectively predicting severe GHD in 85.7% of panhypopituitary patients (subgroup A). Conclusions: In late adolescent and early adulthood patients, a GH cut-off limit using the GHRHCARG test lower than 19.0 mg/l is able to discriminate patients with a suspicion of GHD and does not vary from infancy to early adulthood.
Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been r... more Background: The hypothalamic-pituitary-adrenal (HPA) axis, and in particular cortisol, has been reported to be involved in obesity-associated metabolic disturbances in adults and in selected populations of adolescents. The aim of this study was to investigate the association between morning adrenocorticotropic hormone (ACTH) and cortisol levels and cardiovascular risk factors in overweight or obese Caucasian children and adolescents. Methods: This cross-sectional study of 450 obese children and adolescents (aged 4 to 18 years) was performed in a tertiary referral center. ACTH, cortisol, cardiovascular risk factors (fasting and post-challenge glucose, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, and hypertension) and insulin resistance were evaluated. All analyses were corrected for confounding factors (sex, age, puberty, body mass index), and odds ratios were determined. Results: ACTH and cortisol levels were positively associated with systolic and diastolic blood pressure, triglycerides, fasting glucose and insulin resistance. Cortisol, but not ACTH, was also positively associated with LDL-cholesterol. When adjusted for confounding factors, an association between ACTH and 2 h post-oral glucose tolerance test glucose was revealed. After stratification according to cardiovascular risk factors and adjustment for possible confounding factors, ACTH levels were significantly higher in subjects with triglycerides ≥90th percentile (P <0.02) and impaired fasting glucose or glucose tolerance (P <0.001). Higher cortisol levels were found in subjects with blood pressure ≥95th percentile and LDL-cholesterol ≥90th percentile. Overall, the highest tertiles of ACTH (>5.92 pmol/l) and cortisol (>383.5 nmol/l) although within the normal range were associated with increases in cardiovascular risk factors in this population. Conclusions: In obese children and adolescents, high morning ACTH and cortisol levels are associated with cardiovascular risk factors. High ACTH levels are associated with high triglyceride levels and hyperglycemia, while high cortisol is associated with hypertension and high LDL-cholesterol. These specific relationships suggest complex mechanisms through which the HPA axis may contribute to metabolic impairments in obesity, and merit further investigations.
Journal of Endocrinological Investigation, 2014
Journal of endocrinological investigation, 2008
The most updated guidelines for the diagnosis of adult GH deficiency (GHD) come from the GH Resea... more The most updated guidelines for the diagnosis of adult GH deficiency (GHD) come from the GH Research Society Consensus Workshop held in Sydney, Australia, in 2007. Regarding who to test for GHD, advice should be extended from primitive hypothalamic- pituitary diseases and cranial irradiation to include brain injuries (Traumatic Brain Injury in particular). Regarding how to test for GHD, the insulin tolerance test (ITT) remains a provocative test of reference; among classical provocative test, glucagon test has also been validated. Above all, GHRH + arginine and GHRH + GH-secretagogues are now considered, at least, as reliable as ITT for the diagnosis of adult GHD. Interestingly, it is now accepted that very low IGF-I represents definite evidence of severe GHD in congenital forms of GHD and also in patients with acquired multiple hypopituitarism. These patients would skip provocative test; however, as normal IGFI levels do not rule out severe GHD, patients suspected for hypopituitari...
PLoS ONE, 2014
Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (... more Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on b-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 mg/kg per h) or saline in eight normal subjects (age (meanGS.E.M.), 29.6G2.4 years; body mass index (BMI), 22.4G1.7 kg/m 2 ), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P!0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG 0-960 min : 79.0G1.7!10 3 mg/dl per min vs saline 0-960 min : 87.5G3.8!10 3 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min : 28.4G0.5!10 3 mg/dl per min vs saline 180-660 min : 33.2G1.1 !10 3 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG 0-960 min : 0.3G0.02!10 3 mEq/l per min vs saline 0-960 min : 0.6G0.05!10 3 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties.
Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary ... more Metastatic carcinomas to the pituitary gland are uncommon, occurring in only 1% of the pituitary masses. They often originate from breast or lung carcinomas and may resemble a nonfunctioning pituitary adenoma both clinically and radiologically. Here we describe a patient with pituitary metastasis from follicular thyroid carcinoma and discuss the unique features of these lesions. A 45-year-old woman was admitted to the emergency rescue room of our hospital with a 2-month history of progressive headache and blurred vision. Evaluation revealed right eye amaurosis, with a mild abducens and oculomotor palsy. Pituitary magnetic resonance imaging showed a mass that was hypo-intense in T1-weighted and hyper-intense in T2-weighted-images, located from the sphenoid sinus up to chiasmatic cisterns, raising and deflecting the optic chiasm, down to hypopharynx region, and distorting the cavernous sinuses. No evidence of anterior or posterior hypopituitarism was recorded. The immediate trans-sphenoidal surgery was uncomplicated with partial improvement of the visual fields and headache. Histopathology revealed a metastasis with well-differentiated follicular thyroid architecture. Total thyroidectomy and lymph node dissection was performed with a final histopathological diagnosis of follicular thyroid carcinoma. Subsequently, her headache became more severe. 131-I ablation treatments were performed 15 days and 12 months after thyroidectomy with decrease in headache and a decline in serum thyroglobulin levels. Pituitary metastases from thyroid carcinoma are very uncommon. As this patient illustrates, they tend to produce symptoms relating to space-occupying expansion in the parasellar region rather than to those due to destruction of the pituitary gland. Although rare, pituitary metastases caused by thyroid malignancy should be considered in patients with expanding parasellar lesions if they have thyroid cancer or uncharacterized thyroid diseases. They are unlikely to be amenable to complete resection and should be considered for 131-I treatment, perhaps avoiding the need for extensive neurological surgery.
Endocrine Abstracts, 2014
Hormone Research, 2003
Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amo... more Ghrelin is a 28-amino-acid peptide predominantly produced by the stomach. Substantially lower amounts were detected in bowel, pancreas, kidneys, the immune system, placenta, testes, pituitary, and hypothalamus. Ghrelin displays strong growth hormone (GH)-releasing action mediated by the activation of the so-called GH secretagogue (GHS) receptor (GHS-R) type 1a. GHS-R are concentrated in the hypothalamus-pituitary unit but are also distributed in other central and peripheral tissues. Apart from the potent GH-releasing action, ghrelin has other actions including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, influence on exocrine and endocrine pancreatic function as well as on glucose metabolism, cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system. The discovery of ghrelin opened many new perspectives of research in neuroendocrinology and metabolism, and even also in other fields of internal medicine as gastroenterology, immunology, oncology and cardiology. The possibility that ghrelin and/or GHS analogs, acting as either agonists or antagonists on different activities, might have clinical impact is obviously suggested and is receiving great attention.
Growth Hormone & IGF Research, 2014
European Journal of Endocrinology, 2012
Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (... more Objective: To clarify the metabolic effects of an overnight i.v. infusion of unacylated ghrelin (UAG) in humans. UAG exerts relevant metabolic actions, likely mediated by a still unknown ghrelin receptor subtype, including effects on b-cell viability and function, insulin secretion and sensitivity, and glucose and lipid metabolism. Design: We studied the effects of a 16-h infusion (from 2100 to 1300 h) of UAG (1.0 mg/kg per h) or saline in eight normal subjects (age (meanGS.E.M.), 29.6G2.4 years; body mass index (BMI), 22.4G1.7 kg/m 2 ), who were served, at 2100 and 0800 h respectively, with isocaloric balanced dinner and breakfast. Glucose, insulin, and free fatty acid (FFA) levels were measured every 20 min. Results: In comparison with saline, UAG induced significant (P!0.05) changes in glucose, insulin, and FFA profiles. UAG infusion decreased glucose area under the curve (AUC) values by 10% (UAG 0-960 min : 79.0G1.7!10 3 mg/dl per min vs saline 0-960 min : 87.5G3.8!10 3 mg/dl per min) and the AUC at night by 14% (UAG 180-660 min : 28.4G0.5!10 3 mg/dl per min vs saline 180-660 min : 33.2G1.1 !10 3 mg/dl per min). The overall insulin AUC was not significantly modified by UAG infusion; however, insulin AUC observed after meals was significantly increased under the exposure to UAG with respect to saline at either dinner or breakfast. The FFA AUC values were decreased by 52% under the exposure to UAG in comparison with saline (UAG 0-960 min : 0.3G0.02!10 3 mEq/l per min vs saline 0-960 min : 0.6G0.05!10 3 mEq/l per min). Conclusions: Exposure to the i.v. administration of UAG improves glucose metabolism and inhibits lipolysis in healthy volunteers. Thus, in contrast to the diabetogenic action of AG, UAG displays hypoglycemic properties.
European Journal of Endocrinology, 2013
Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for ove... more Recombinant human GH has been licensed for use in adult patients with GH deficiency (GHD) for over 15 years. Early weight- and surface area-based dosing regimens were effective but resulted in supraphysiological levels of IGF1 and increased incidence of side effects. Current practice has moved towards individualised regimens, starting with low GH doses and gradually titrating the dose according to the level of serum IGF1 to achieve an optimal dose. Here we present the evidence supporting the dosing recommendations of current guidelines and consider factors affecting dose responsiveness and parameters of treatment response. The published data discussed here lend support for the use of low GH dosing regimens in adult GHD. The range of doses defined as &amp;amp;amp;amp;amp;amp;amp;#39;low dose&amp;amp;amp;amp;amp;amp;amp;#39; in the studies discussed here (∼1-4 mg/week) is in accordance with those recommended in current guidelines and encompasses the dose range recommended by product labels.
Clinical Endocrinology, 2002
Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an... more Ghrelin, a 28 amino acid peptide purified from the stomach and showing a unique structure with an n-octanoyl ester in serine-3 residue, is a natural ligand of the GH secretagogue (GHS) receptor (GHS-R) and strongly stimulates GH secretion. In humans, ghrelin is more potent than growth hormone-releasing hormone (GHRH) and non-natural GHS such as hexarelin. Moreover, ghrelin shows a true synergism with GHRH, has no interaction with hexarelin and, similarly to non-natural GHS, is partially refractory to the inhibitory effect of exogenous somatostatin (SS). Despite this evidence, the mechanisms underlying the GH-releasing effect of ghrelin in humans have not been fully clarified. To this aim we enrolled six normal young volunteers [age (mean +/- SEM) 28.9 +/- 3.1 year; body mass index 22.3 +/- 1.0 kg/m2). In all subjects we studied the effects of glucose (OGTT, 100 g oral glucose at -45 min) or free fatty acids (FFA) load [lipid-heparin emulsion, Li-He, Intralipid 10% 250 ml + heparin 2500 U i.v. from -30 to +120 min] as well as of arginine (ARG, 0.5 g/kg infused from 0 to +30 min) on the GH response to human ghrelin (1.0 micro g/kg i.v. at 0 min) administration. These results were compared with those obtained by studying the effects of OGTT, Li-He and ARG on the GH response to GHRH-29 (1.0 micro g/kg i.v. at 0 min). The GH response to ghrelin (auc 5452.4 +/- 991.3 micro g/l/h) was higher (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that after GHRH (1519.4 +/- 93.3 micro g/l/h). The GH response to GHRH was inhibited by OGTT (450.7 +/- 81.1 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) and almost abolished by Li-He (230.0 +/- 63.6 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) while was markedly potentiated by ARG (2520.4 +/- 425.8 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05). The GH response to GHRH + ARG, however, was lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that to ghrelin alone. The GH response to ghrelin was blunted by OGTT (2153.1 +/- 781.9 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) as well as by Li-He (3158.8 +/- 426.7 micro g/l/h, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) but these responses remained higher (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) than that to GHRH alone. On the other hand, ARG did not modify the GH response to ghrelin (6324.3 +/- 1275.5 micro g/l/h). For GH 1 micro g/l = 2 mU/l. In humans, ghrelin exerts a strong stimulatory effect on GH secretion which is partially refractory to the inhibitory effect of both glucose and FFA load and is not enhanced by ARG. These factors almost abolish and potentiate, respectively, the GH response to GHRH, at least partially, via modulation of hypothalamic SS release. Thus, our findings agree with the hypothesis that ghrelin as well as non-natural GHS acts, at least partially, by antagonizing SS activity.
European Journal of Endocrinology, 2007
Objective: To define the appropriate diagnostic cut-off limits for the GH response to GHRHCargini... more Objective: To define the appropriate diagnostic cut-off limits for the GH response to GHRHCarginine (ARG) test and IGF-I levels, using receiver operating characteristics (ROC) curve analysis, in late adolescents and young adults. Design and methods: We studied 152 patients with childhood-onset organic hypothalamic-pituitary disease (85 males, age (meanGS.E.M.): 19.2G0.2 years) and 201 normal adolescents as controls (96 males, age: 20.7G0.2 years). Patients were divided into three subgroups on the basis of the number of the other pituitary hormone deficits, excluding GH deficiency (GHD): subgroup A consisted of 35 panhypopituitary patients (17 males, age: 21.2G0.4 years), subgroup B consisted of 18 patients with only one or with no more than two pituitary hormone deficits (7 males, age: 20.2G0.9 years); and subgroup C consisted of 99 patients without any known hormonal pituitary deficits (60 males, age: 18.2G0.2 years). Both patients and controls were lean (body mass index, BMI!25 kg/m 2 ). Patients in subgroup A were assumed to be GHD, whereas in patients belonging to subgroups B and C the presence of GHD had to be verified. Results: For the GHRHCARG test, the best pair of highest sensitivity (Se; 100%) and specificity (Sp; 97%) was found choosing a peak GH of 19.0 mg/l. For IGF-I levels, the best pair of highest Se (96.6%) and Sp (74.6%) was found using a cut-off point of 160 mg/l (SDS: K1.3). Assuming 19.0 mg/l to be the cut-off point established for GHRHCARG test, 72.2% of patients in subgroup B and 39.4% in subgroup C were defined as GHD. In patients belonging to group B and C and with a peak GH response !19 mg/l to the test, IGF-I levels were lower than 160 mg/l (or less than 1.3 SDS) in 68.7 and 41.6% of patients respectively predicting severe GHD in 85.7% of panhypopituitary patients (subgroup A). Conclusions: In late adolescent and early adulthood patients, a GH cut-off limit using the GHRHCARG test lower than 19.0 mg/l is able to discriminate patients with a suspicion of GHD and does not vary from infancy to early adulthood.