Biomedical subjects

Massimo Scacchi

Publications and source records attributed to Massimo Scacchi.

6 recordsLinked to original sources

PubMed2007

The dexamethasone-suppressed corticotropin-releasing hormone stimulation test and the desmopressin test to distinguish Cushing's syndrome from pseudo-Cushing's states.

OBJECTIVE: Cushing's syndrome (CS), when fully expressed, is easily diagnosed. Mild cases, however, may require careful distinction from pseudo-Cushing's states as may occur in depression, alcoholism, polycystic ovary disease and visceral obesity. The aim of the present study is a reappraisal of the diagnostic accuracy of the two tests most commonly used to differentiate CS from pseudo-Cushing's: corticotropin-releasing hormone (CRH) stimulation after low dose dexamethasone administration and desmopressin stimulation. DESIGN: The study population comprised 32 patients with CS and 23 with pseudo-Cushing's evaluated retrospectively. METHODS: Urinary free cortisol (UFC), serum cortisol at midnight and after low dose dexamethasone (1 mg overnight and 2 mg over two days) were measured. Further, patients were tested with dexamethasone + CRH and desmopressin and the diagnostic performances of the two tests were compared in the entire series as well as in patients with mild hypercortisolism only (i.e. UFC < 690 nmol/24 h). RESULTS: As expected, measurement of UFC, assessment of cortisol rhythmicity and inhibition after 1 mg/2 mg dexamethasone failed to clearly classify patients with pseudo-Cushing's. Administration of CRH following 2-mg dexamethasone achieved 100% sensitivity but 62.5% specificity. Conversely, desmopressin testing correctly classified all but two patients with pseudo-Cushing's (90% specificity) with 81.5% sensitivity. Diagnostic accuracy was comparable in the subgroup with mild hypercortisolism (21 CS, all 23 pseudo-Cushing's patients). Desmopressin offered an incremental diagnostic effectiveness of 35.8/million inhabitants compared with dexamethasone + CRH as a second-line test. CONCLUSIONS: Neither of the two tests guarantees absolute diagnostic accuracy. The specificity of dexamethasone + CRH is less brilliant than previously reported and appears to be inferior to desmopressin stimulation. The greatest diagnostic effectiveness results from the low-dose dexamethasone test combined with the desmopressin test. Skilful use of dynamic testing and balanced clinical judgement are necessary to distinguish between Cushing's syndrome and pseudo-Cushing's.

Adolescent↗

PubMed2006

Pericardial effusion requiring pericardiocentesis in a girl with anorexia nervosa.

OBJECTIVE: Silent pericardial effusion is frequently observed in patients with anorexia nervosa. The nature of the pericardial fluid could never be established, as pericardiocentesis was ethically unfeasible. METHOD: We describe the case of a girl with anorexia nervosa in whom an initial, clinically irrelevant pericardial effusion increased rapidly, making pericardiocentesis necessary to prevent cardiac tamponade. RESULTS: It was thus possible to exclude the inflammatory or infectious nature of the pericardial fluid, although the pathogenesis of this cardiac alteration remains obscure. CONCLUSION: Echocardiographic examination appears to be strongly advisable in patients with anorexia nervosa.

Adolescent↗

PubMed2006

Acromegaly.

Acromegaly is a slowly progressive disease characterized by 30% increase of mortality rate for cardiovascular disease, respiratory complications and malignancies. The estimated prevalence of the disease is 40 cases/1000000 population with 3-4 new cases/1000000 population per year. The biochemical diagnosis is based upon the demonstration of high circulating levels of GH and IGF-I. A random GH level lower than 0.4 microg/l and an IGF-I value in the age- and sex-matched normal range makes the diagnosis of acromegaly unlikely. In doubtful cases, the lack of GH suppressibility below 1 microg/l (0.3 microg/l according to recent reports) after an oral glucose load will confirm the diagnosis. A pituitary adenoma is demonstrated in most cases by CT scan or MRI. A negative X-ray finding or the presence of empty sella do not exclude the diagnosis. Cardiovascular complications (acromegalic cardiomyopathy and arterial hypertension) should be looked for and, if present, followed-up by echocardiography and 24h-electrocardiogram. Sleep apnoea, when clinically suspicious, should be confirmed by polisomnography. At the moment of diagnosis all patients should undergo colonscopy. Lipid profile should be obtained and glucose tolerance evaluated. Surgery, radiotherapy and medical treatment represent the therapeutic options for acromegaly. The outcome of transsphenoidal surgery is far better for microadenomas (80-90%) than for macroadenomas (less than 50%), which unluckily represent more than 70% of all GH-secreting pituitary tumours. Therefore, pituitary surgery is the first line treatment for microadenomas. Medical therapy is based on GH-lowering drugs (somatostatin receptor agonists and, in some cases, dopaminergic agents) and GH receptor antagonists (pegvisomant). The former are traditionally indicated after unsuccessful surgery and while awaiting the effectiveness of radiation therapy. However, GH-lowering drugs are also used as primary therapy when surgery is contraindicated or in the case of large GH-secreting macroadenomas which are not likely to be completely removed by surgery. These compounds may also be indicated in the preoperative management of some acromegalic patients in order to lower the risk of surgical and anaesthetic complications. For the moment pegvisomant is indicated for patients resistant to the GH-lowering drugs and there is no evidence for drug-induced enlargement of the pituitary tumour. In order to avoid this possibility, however, a combination of pegvisomant and GH-lowering compound can also be conceived. With pegvisomant, IGF-I plasma levels are the marker of therapeutic efficacy and normalize in 97% of patients. Radiotherapy is employed sparingly due to the number of side effects (80% of hypopituitarism). It is indicated after unsuccessful surgical and/or medical treatment and allows the control of hormonal secretion and tumour growth in approx. 40% and 100% of cases, respectively. Acromegaly is defined as controlled when, in the absence of clinical activity, IGF-I levels are in the age- and sex-matched normal range and GH is normally suppressible by the oral glucose load.

Acromegaly↗

PubMed2006

Effects of treatment with somatostatin analogues on QT interval duration in acromegalic patients.

OBJECTIVE: Cardiovascular disease is a major contributor to the increased mortality of acromegalic patients. Prolongation of the QT interval is considered an established risk factor for potentially fatal cardiac arrhythmias, an event frequently observed in acromegaly. Changes in ventricular repolarization have been observed with the use of octreotide, one of the somatostatin analogues (SSA) currently used for the medical treatment of this disease. Furthermore, octreotide is listed among the drugs able to prolong the QT interval. Thus, we elected to study the effects of long-term SSA administration on QT duration and left ventricular mass (LVM) in a group of acromegalic patients. DESIGN AND PATIENTS: In a retrospective study, 30 acromegalic patients (19 women and 11 men, aged 25-77 years) were studied under basal conditions; 24 of them (15 women and nine men, aged 25-77 years) were studied again after 3-63 months of treatment (median 18 months) with SSA. Twenty-four healthy volunteers served as controls. MEASUREMENTS: Patients and controls underwent electrocardiographic (ECG) analysis, and QT interval duration corrected for heart rate (QTc) was established according to the Bazett formula. In 17 of the SSA-treated patients, M- and B-mode echocardiography for the assessment of LVM index (LVMi) was performed. RESULTS: Baseline QTc was significantly longer in patients than in controls. SSA administration was followed by a significant decrease in QTc, which reached a mean value similar to that measured in the controls. In particular, treatment with SSA normalized QTc in three out of the six patients with abnormally elevated values at baseline. After treatment, a significant reduction in heart rate was recorded, while LVMi displayed a slight but not significant decrease. CONCLUSIONS: Acromegalic patients frequently display an abnormally prolonged QT interval, a known risk factor for potentially fatal arrhythmias. Treatment of these patients with SSA is able to improve and even normalize this alteration, probably contributing to the beneficial effects of these drugs on cardiac rhythm in this endocrine disorder. The inclusion of octreotide in the list of drugs that may increase QTc should be reconsidered as regards its indication in acromegaly.

Acromegaly↗

PubMed2003

Nutritional status in the neuroendocrine control of growth hormone secretion: the model of anorexia nervosa.

Growth hormone (GH) plays a key role not only in the promotion of linear growth but also in the regulation of intermediary metabolism, body composition, and energy expenditure. On the whole, the hormone appears to direct fuel metabolism towards the preferential oxidation of lipids instead of glucose and proteins, and to convey the energy derived from metabolic processes towards the synthesis of proteins. On the other hand, body energy stores and circulating energetic substrates take an important part in the regulation of somatotropin release. Finally, central and peripheral peptides participating in the control of food intake and energy expenditure (neuropeptide Y, leptin, and ghrelin) are also involved in the regulation of GH secretion. Altogether, nutritional status has to be regarded as a major determinant in the regulation of the somatotropin-somatomedin axis in animals and humans. In these latter, overweight is associated with marked impairment of spontaneous and stimulated GH release, while acute dietary restriction and chronic undernutrition induce an amplification of spontaneous secretion together with a clear-cut decrease in insulin-like growth factor I (IGF-I) plasma levels. Thus, over- and undernutrition represent two conditions connoted by GH hypersensitivity and GH resistance, respectively. Anorexia nervosa (AN) is a psychiatric disorder characterized by peculiar changes of the GH-IGF-I axis. In these patients, low circulating IGF-I levels are associated with enhanced GH production rate, highly disordered mode of somatotropin release, and variability of GH responsiveness to different pharmacological challenges. These abnormalities are likely due not only to the lack of negative IGF-I feedback, but also to a primary hypothalamic alteration with increased frequency of growth hormone releasing hormone discharges and decreased somatostatinergic tone. Given the reversal of the above alterations following weight recovery, these abnormalities can be seen as secondary, and possibly adaptive, to nutritional deprivation. The model of AN may provide important insights into the pathophysiology of GH secretion, in particular as regards the mechanisms whereby nutritional status effects its regulation.

Animals↗

PubMed2003

Somatostatin infusion withdrawal: studies in the acute and recovery phase of anorexia nervosa, and in obesity.

OBJECTIVE: Changes in GH/IGF-I axis activity occur in both anorexia nervosa (AN) and obesity (OB). A GH hypersecretory state with very low plasma IGF-I levels is present in AN, whereas in morbid OB, GH secretion is dull and plasma IGF-I levels are generally preserved. Endogenous GHRH activity in AN and OB has never been directly studied, although indirect evidence would indicate that GHRH function is altered in either condition, possibly enhanced and reduced respectively. Somatostatin (SS) infusion withdrawal (SSIW) is followed by a rebound rise of plasma GH in animals and humans, an event which, allegedly, is mediated by endogenous GHRH release. METHODS: In the present study, 28 young women, eight with active AN (A-AN), six with AN in the recovery phase (R-AN), eight with morbid OB, and six healthy age-matched normal weight subjects (NW), were studied. All subjects underwent, on different occasions, the following two tests: (i) acute GHRH injection (1 microg/kg, i.v.); (ii) infusion of SS (9 microg/kg per h i.v. over 60 min), with blood samples drawn prior to and at different intervals after drug injections. Plasma GH levels were measured at each time interval in all sessions, and, in addition, baseline plasma estradiol, free triiodothyronine, TSH, IGF-I and insulin were measured at -30 min. RESULTS: Baseline plasma GH concentrations were significantly higher in A-AN than in NW (4.7+/-0.7 vs 2.1+/-0.6 microg/l, P<0.01). Baseline GH levels in R-AN were also higher than in NW, but the difference did not reach statistical significance (5.6+/-1.7 microg/l, not significant (NS)). Baseline plasma GH concentrations were significantly lower in OB than in NW (0.3+/-0.1 microg/l, P<0.01). GHRH-stimulated GH release was significantly higher in A-AN than in NW (mean change in area under the curve (DeltaAUC) 1904.9+/-626.1 vs 613.9+/-75.9 microg/l per min, P<0.01), whereas no statistically significant difference was present between R-AN and NW (mean DeltaAUC 638.2+/-293.0 microg/l per min, NS); in OB, GHRH failed to evoke a plasma GH rise (mean DeltaAUC 239.8+/-89.9 microg/l per min vs A-AN, R-AN, and NW, P<0.01). SS infusion markedly reduced plasma GH concentrations in both A-AN and R-AN and, to a lesser extent, in NW, but failed to do so in OB. In A-AN, SSIW was followed by a plasma GH rise markedly higher than that present in NW (mean DeltaAUC 193.0+/-42.3 vs 60.1+/-11.4 microg/l per min, P<0.01), whereas in R-AN the GH response after SSIW was nearly superimposable on that registered in NW (mean DeltaAUC 72.9+/-22.8 microg/l per min, NS). There were no changes in plasma GH levels after SSIW in OB (mean DeltaAUC 22.8+/-9.7 microg/l per min). In all groups, DeltaAUCs of the GH response to GHRH and after SSIW were highly positively correlated (r=0.7, P<0.01). CONCLUSIONS: These data support the view that a high endogenous GHRH tone, which subsides in the recovery phase of the disease, is present in AN, whereas GHRH hypofunction, possibly associated with pituitary impairment, might indicate OB.

Adolescent↗