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Rosario Pivonello

Publications and source records attributed to Rosario Pivonello.

At least 19 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

Treatment with growth hormone receptor antagonist in acromegaly: effect on cardiac structure and performance.

AIM: The aim of the current study was to evaluate the effect of short-term (6 months) and long-term (18 months) treatment with pegvisomant on cardiac structure and performance in patients with acromegaly. PATIENTS: Seventeen patients (nine women, eight men, 27-61 yr) with active acromegaly entered and 12 completed the long-term study. After a baseline evaluation, including measurement of hemodynamic, biochemical, and hormonal parameters, and a standard Doppler echocardiography, treatment with pegvisomant was started at the initial dose of 10 mg/d, increasing by 5 mg/d every 6 wk on the basis of IGF-I levels until normalization or the achievement of a maximal dose of 40 mg/d. RESULTS: After short-term treatment, IGF-I levels were normalized in 10 of the 17 (59%) patients. Left ventricular mass index (LVMi) was significantly decreased without changes in diastolic and systolic performance. After long-term treatment, IGF-I levels were normalized in 10 of the 12 (83%) patients. Blood glucose and serum insulin levels were decreased compared with baseline. LVMi was further decreased compared with short-term treatment, so that the prevalence of left ventricle hypertrophy decreased from 50% at baseline to 17% after 18 months of treatment. Moreover, ejection fraction as well as early to late (atrial) peak velocity ratio (E/A) were significantly increased, whereas isovolumic relaxation time was significantly decreased compared with baseline, demonstrating an improvement of both diastolic and systolic function. A significant correlation was found between the change in IGF-I levels and that of left ventricular ejection fraction. In general, the prevalence of cardiac insufficiency was present in 13 of the 17 (76%) patients at baseline and in one (8%) patient after 18 months of treatment. CONCLUSIONS: Long-term treatment with the GH receptor antagonist improves acromegalic cardiomyopathy by decreasing cardiac hypertrophy and enhancing diastolic and systolic function, and consequently partially or completely reverting the cardiac insufficiency.

Acromegaly↗
PubMed2006

Dopamine receptor expression and function in corticotroph ectopic tumors.

BACKGROUND: Dopamine receptor (DR) expression and dopamine agonist (DA) effectiveness have never been demonstrated in neuroendocrine tumors associated with ectopic ACTH syndrome (EAS). AIM: The aim of the current study was to evaluate DR and particularly D2 subtype expression in neuroendocrine tumors associated with EAS and to evaluate the in vivo effectiveness of the DA cabergoline in the treatment of EAS. PATIENTS AND METHODS: Six ACTH-secreting neuroendocrine tumors, including four lung, one pancreatic, and one thymic carcinoid, were used for the evaluation of D2 expression by immunohistochemistry. DR subtypes and D2 isoforms and number were evaluated by RT-PCR in three cases of persistent EAS after surgery. These patients were treated with cabergoline at the dose of 3.5 mg/wk for 6 months. Clinical parameters, hormonal levels, and tumor size were monitored during the treatment period. RESULTS: At immunohistochemistry, D2 was expressed in five (83.3%) tumors. At RT-PCR, D2 was confirmed in all three cases but at variable numbers, whereas D4 was expressed in two cases. D(2long) was expressed in all three cases, together with D(2short) in one case. A normalization of urinary cortisol levels was found in two patients (66.7%) after 3 months of treatment. However, treatment escape was demonstrated in one of these patients afterward. CONCLUSION: The results of this study demonstrated that DR are expressed in neuroendocrine tumors associated with EAS and that cabergoline treatment could be effective in controlling cortisol excess in a subgroup of patients with EAS. Further studies on a larger number of patients are mandatory to confirm the usefulness of DA in EAS.

ACTH Syndrome, Ectopic↗
PubMed2006

Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients.

CONTEXT: Primary treatment with depot octreotide and lanreotide induces tumor shrinkage in newly diagnosed patients with acromegaly. OBJECTIVE: The objective of the study was to evaluate clinical predictors of tumor shrinkage. DESIGN: This was an analytical, observational, open, prospective study. SUBJECTS: The study included 99 patients: 13 with microadenoma and 86 with macroadenoma (25 enclosed, 32 extrasellar, 29 invasive). MAIN OUTCOME MEASURES: Age, gender, estimated disease duration, body mass index, GH and IGF-I levels, and tumor volume at diagnosis and after 12 months of treatment were measured. Percentage of GH, IGF-I, and tumor size changes from baseline were also analyzed. Tumor changes were scored as absent (+/- 0-25%), mild (+/- 25.1-50%), moderate (+/- 50.1-75%), or notable (75%). INTERVENTIONS: Sixty patients (60.6%) received depot octreotide im (20-30 mg every 28 d), and 39 patients (39.4%) received lanreotide im (60-90 mg every 28 d). RESULTS: Basal tumor volume and maximal tumor diameter correlated with age, disease duration, and GH levels. After 12 months, GH levels were controlled (</=2.5 microg/liter) in 57.6%, IGF-I levels in 45.5%, and both in 42.4%. Shrinkage was absent in 22 patients (22.2%), mild in 31 (31.1%), moderate in 30 (30.3%), and notable in 14 patients (14.1%). Two patients (not responding to treatment) had a mild tumor increase (by 34 and 31.2%, respectively). Basal and posttreatment tumor volumes were highly correlated (r = 0.79, P < 0.0001). At the multistep regression analysis, the percent IGF-I decrease (t = 2.6; P = 0.011) was the best predictor of posttreatment tumor volume, followed by patients' age (t = 2.1; P = 0.042) and percent GH decrease (t = 2.0; P = 0.044). CONCLUSIONS: Most patients with acromegaly (75.5%) had 25% or greater tumor shrinkage after 12 months of primary somatostatin analog therapy: significant increase of tumor mass occurred in only 2.1% of patients (uncontrolled during treatment). Best predictor of tumor shrinkage was posttreatment IGF-I.

Acromegaly↗
PubMed2006

The natural history of partial growth hormone deficiency in adults: a prospective study on the cardiovascular risk and atherosclerosis.

BACKGROUND: Partial GH deficiency (GHD) in adults is poorly studied. OBJECTIVE: The objective of the study was to investigate the natural history and clinical implications of partial GHD. STUDY DESIGN: This was an analytical, observational, prospective, case-control study. PATIENTS: Twenty-seven hypopituitary patients (15 women, ages 20-60 yr) and 27 controls participated in the study. MAIN OUTCOME MEASURES: Measures included GH peak after GHRH plus arginine [(GHRH+ARG), measured by immunoradiometric assay]; IGF-I (measured after ethanol extraction) z-sd score (SDS); glucose, insulin, total cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride levels; and common carotid arteries intima-media thickness (IMT) measured periodically. RESULTS: At study entry, partial GHD patients had significantly lower IGF-I and HDL-cholesterol levels and homeostasis model assessment index than controls. During the 60 months of median follow-up, 11 patients had severe GHD (40.7%), seven normalized their GH response (25.9%), and nine showed persistently partial GHD (33.3%). Patients with developed severe GHD at baseline had similar age and body mass index and lower GH peak (11.5 +/- 1.8 vs. 14.3 +/- 1.5 and 12.8 +/- 1.1 microg/liter, P = 0.008) and IGF-I SDS (-0.88 +/- 0.48 vs. 0.15 +/- 0.58 and -0.42 +/- 0.78; P = 0.01) than the patients with normal GH secretion or partial GHD. Severe GHD was accompanied by decreased IGF-I SDS and increased total to HDL cholesterol ratio, triglycerides, homeostasis model assessment index, and carotid intima-media thickness; normalization of GH secretion was accompanied by increased IGF-I SDS. By receiving-operator characteristic analysis, predictors of severe GHD were a baseline GH peak after GHRH+ARG of 11.5 microg/liter (sensitivity 64%, specificity 94%) and a baseline IGF-I SDS of -0.28 (sensitivity 91%, specificity 63%). CONCLUSIONS: Of 27 patients with partial GHD after pituitary surgery, 40.7% developed severe GHD and 25.9% normalized their GH response. With the assay used, changes in the GH peak response to GHRH+ARG were accompanied by changes in the IGF-I SDS, metabolic profile, and carotid IMT. A peak GH of 11.5 microg/liter or less and IGF-I SDS -0.28 or less were highly predictive of delayed deterioration of GH secretion.

Adult↗
PubMed2006

Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status.

INTRODUCTION: The effects of endogenous cortisol (F) excess on bone mass and vertebral fractures have still not been thoroughly investigated. The aim of this cross-sectional case-control study was to investigate factors influencing bone demineralization and vertebral fractures in different conditions of F excess, i.e. Cushing's disease and adrenal and ectopic Cushing's syndrome. MATERIALS AND METHODS: Eighty consecutive patients and 80 controls were prospectively enrolled: 37 patients (21 females) with pituitary ACTH-secreting adenoma, 18 (14 females) with adrenocortical adenoma, 15 (11 females) with adrenal carcinoma of mixed secretion, and 10 (three females) with ectopic ACTH secretion. The groups had similar age. At diagnosis, bone mineral density (BMD) was determined by the dual-energy x-ray absorptiometry technique at the lumbar spine (L1-L4) and femoral neck; vertebral fractures were investigated by standard spinal radiographs. RESULTS: When comparing the groups with different etiology of F excess, the patients with ectopic ACTH secretion had higher F and lower BMD values than the other subgroups. Morning F (P = 0.03) and testosterone levels (P = 0.04) correlated with lumbar BMD. Vertebral fractures were found in 61 (76%) of the patients, were multiple in 52 (85%) of the cases, and clinically evident in 32 (52%). Only multiple fractures were more frequent in patients with ectopic ACTH hypersecretion (P < 0.05). Lumbar spine BMD was the best predictor of vertebral fractures (P < 0.01). Surprisingly, amenorrheic and eumenorrheic women had similar BMD values and fracture prevalence. CONCLUSION: A high prevalence (76%) of vertebral fracture was revealed, regardless of the etiology of the patients' hypercortisolism. The harmful effects of F excess at the spine were partly counterbalanced by the increased androgen production but were not affected by gonadal status in women.

Adenoma↗
PubMed2006

Multiple system atrophy is distinguished from idiopathic Parkinson's disease by the arginine growth hormone stimulation test.

OBJECTIVE: Multiple system atrophy (MSA) may be difficult to distinguish from idiopathic Parkinson's disease (PD). Our aim was to evaluate the accuracy of the arginine growth hormone (GH) stimulation test in distinguishing between MSA and PD in large populations of patients. METHODS: We measured the GH response to arginine in 69 MSA (43 MSAp [parkinsonism as the main motor feature] and 26 MSAc [cerebellar features predominated]) patients, 35 PD patients, and 90 healthy control subjects. We used receiver-operating curve analysis to establish the arginine cutoff value that best differentiated between MSA and PD. RESULTS: The GH response to arginine was significantly lower (p < 0.01) in MSA than in either PD patients or control subjects. At a cutoff level of 4 microg/L, arginine distinguished MSAp from PD with a sensitivity and specificity of 91% and MSAc from PD with a sensitivity of 96% and specificity of 91%. The arginine test had a positive predictive value for MSA of 95%. The GH response to arginine was not affected by disease duration or severity, MSA motor subtype, pyramidal signs, response to dopaminergic therapy, or magnetic resonance imaging findings. INTERPRETATION: The GH response to arginine differentiates MSA from PD with a high diagnostic accuracy. The results suggest an impairment of cholinergic central systems modulating GH release in MSA.

Antiparkinson Agents↗
PubMed2006

First-line octreotide-LAR therapy induces tumour shrinkage and controls hormone excess in patients with acromegaly: results from an open, prospective, multicentre trial.

BACKGROUND: The majority of patients with acromegaly have large tumours and the outcome of conventional management remains poor. OBJECTIVE: To investigate the clinical application of octreotide-LAR as primary treatment in newly diagnosed patients with GH-secreting pituitary tumours. DESIGN: Open, prospective, multicentre, 24-week follow-up study. PATIENTS: Thirty-four patients were enrolled (20 men, 14 women; mean age, 50 years); 13 had microadenoma [median tumour volume 327 mm(3) (range 31-629 mm(3))], 21 had macroadenoma [median tumour volume 1,325 mm(3) (range 503-11,583 mm(3))]. Interventions Octreotide-LAR at the dosage of 20 mg every 28 days for the first 12 weeks increased to 30 mg every 28 days to control GH and/or IGF-I excess in 20 patients (64.7%). MAIN OUTCOME MEASURES: Primary endpoints were control of GH (fasting < 2.5 microg/l) and IGF-I secretion (gender- and age-normalized) and presence and entity of tumour mass shrinkage. Secondary endpoint was improvement of symptoms score. RESULTS: In patients with micro- and macroadenomas GH levels decreased to < 2.5 microg/l in 84.6% and 45%, serum IGF-I levels normalized for age and gender in 61.5% and 35% of cases. Failure in achieving either GH < 2.5 microg/l or normal IGF-I levels was found in none of the patients with micro- and in 45% of patients with macroadenoma. Median tumour volume was reduced by 54% (range: -90% to +350%) in micro- and by 49% (range -94% to -14%) in macroadenomas. Headache, perspiration and osteo-arthralgias disappeared in 21%, paresthesias in 38%, fatigue in 26% and carpal tunnel syndrome in 15%. The treatment was well tolerated: more frequent adverse events were gastrointestinal (in 44%). CONCLUSIONS: In both patients with micro- or macroadenoma, primary octreotide-LAR treatment controls hormone excess, induces tumour shrinkage and improves symptoms of acromegaly with limited side effects and can be therefore successfully employed in patients with contraindications for surgery or in those who refuse surgery.

Acromegaly↗
PubMed2006

Pulsed tissue Doppler identifies subclinical myocardial biventricular dysfunction in active acromegaly.

OBJECTIVE: The aim of this study was to assess the role of pulsed tissue Doppler (TD) to identify left (LV) and right ventricular (RV) myocardial regional involvement in acromegaly. PATIENTS AND MEASUREMENTS: Thirty active acromegaly patients, free of diabetes mellitus, thyroid dysfunction, valvular and coronary heart disease, clinically overt heart failure, and 30 sex- and age-matched healthy controls underwent standard Doppler echocardiography and pulsed TD, by placing the sample volume at the level of basal posterior septum, LV lateral mitral annulus and RV lateral tricuspid annulus. Myocardial systolic (S(m)) and diastolic velocities (E(m)/A(m) ratio) and time-intervals of relaxation (RT(m)), precontraction (PCT(m)) and contraction (CT(m)) and the PCT(m)/CT(m) ratio were measured at each level. RESULTS: The two groups had similar heart rate, whereas acromegaly patients had higher body mass index, systolic and diastolic blood pressure, LV mass and impaired Doppler indexes of LV and RV diastolic function, without any difference in the global systolic function. At TD, acromegaly patients showed significantly delayed RT(m) and PCT(m,) reduced E(m)/A(m), S(m) and increased PCT(m)/CT(m) of posterior septum, mitral annulus and tricuspid annulus in comparison with controls. By separate multilinear regression analyses, after adjusting for body mass index, heart rate, diastolic blood pressure and LV mass index, age was the main independent determinant of tissue Doppler diastolic but not of systolic indexes. CONCLUSIONS: In active acromegaly, pulsed TD confirms LV and RV diastolic abnormalities detectable by standard Doppler, additionally identifying subclinical biventricular impairment of systolic function.

Acromegaly↗
PubMed2006

Age changes the diagnostic accuracy of mean profile and nadir growth hormone levels after oral glucose in postoperative patients with acromegaly.

BACKGROUND: This analytical, retrospective study was designed to select cut-off thresholds of mean GH levels during a diurnal profile and nadir GH levels after oral glucose tolerance test (OGTT) according to age to diagnose surgical remission of acromegaly. METHODS: One hundred forty-one patients (76 women, aged 44 +/- 15 years and 65 men, aged 43 +/- 13 years) were included in this study. For the purpose of this study, remission was based on insulin-like growth factor-I (IGF-I) levels in the normal range for age. Diagnostic accuracy was analysed by receiving-operator characteristics (ROC) curves in the entire series, and in young (20-40 years), middle-aged (41-60 years) and older patients (> 60 years), separately. RESULTS: Sixty patients (42.6%) had normal IGF-I levels after surgery. In the entire series, in young and in middle-aged patients, the ROC analysis showed that optimum cut-off for mean GH levels was 2.3 microg/l (diagnostic accuracy range, 94-97%) whereas that for nadir GH after OGTT were, respectively, 0.85, 0.9 and 0.8 microg/l (diagnostic accuracy range, 90-95%). In the older patients, the optimum cut-off selected for mean GH levels was 1.4 microg/l and that for nadir GH after OGTT was 0.5 microg/l (diagnostic accuracy, 100% for both). The comparative analysis of the ROC curves did not show any significant difference between mean GH and nadir GH after OGTT (P = 0.21). CONCLUSIONS: The criteria currently accepted for diagnosing post-surgical remission of acromegaly have high diagnostic accuracy only in the patients aged below 60 years. In older patients, lower cut-offs (i.e. = 1.4 microg/l for fasting GH and = 0.5 microg/l for nadir GH after OGTT) predict normal IGF-I levels. Mean GH levels during a diurnal profile have similar diagnostic accuracy of nadir GH levels after OGTT. This suggests that OGTT is not necessary to establish surgical cure.

Acromegaly↗
PubMed2006

Acromegaly and the cardiovascular system.

Acromegaly is characterized by an increased cardiovascular morbidity and mortality. In fact, growth hormone and insulin-like growth factor-I excess induces a specific cardiomyopathy. The heart is involved from the very early stages of the disease in which the hyperkinetic syndrome (high heart rate and increased systolic output) takes place. Frequently, if the disease is untreated for many years or unsuccessfully treated, concentric biventricular hypertrophy and diastolic dysfunction can develop and, at least, lead to diastolic congestive heart failure. Rhythm disturbances and valve dysfunction are also frequently described in acromegaly. The coexistence of other complications, such as diabetes and arterial hypertension, can induce the worsening of acromegalic cardiomyopathy. Control of acromegaly by surgery or pharmacotherapy could improve cardiovascular morbidity thanks to decreasing left ventricular mass and reducing cardiac dysfunction. In conclusion, an early diagnosis and a careful evaluation of cardiac function, morphology and activity seem to be mandatory in acromegaly.

Acromegaly↗
PubMed2006

Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance.

OBJECTIVE: We aimed to investigate the efficacy of pegvisomant in patients with acromegaly resistant to long-term (> or = 24-month), high-dose treatment with octreotide-LAR (40 mg/month) or lanreotide (120 mg/month). DESIGN: This was an open, prospective study. SUBJECTS AND METHODS: We studied 16 patients with acromegaly (nine women; aged 28-61 years). The main outcome measures were IGF-I levels, blood pressure, glucose tolerance and safety (liver function and tumor size). Pegvisomant was given at doses of 10-40 mg s.c. daily. Dose titration was performed every month by IGF-I assay. RESULTS: Three patients spontaneously stopped pegvisomant treatment after 6-9 months because of poor compliance; from the measurement of serum pegvisomant, another patient was found not to inject herself properly. After 6 months, IGF-I levels decreased by 63 +/- 19% (767.8 +/- 152.9 vs 299.8 +/- 162.9 microg/l, P < 0.0001, t-test); serum IGF-I levels normalized in 57%. After 12 months, IGF-I levels normalized in nine (75%) patients and were reduced by over 50% in another three (25%). The mean tumor volume remained stable during the study (1198 +/- 1234 vs 1196 +/- 1351 mm(3), P = 0.37): it did not change ( +/- 25% vs basal) in nine patients, increased by 39.4% and 40.8% in two and decreased by 30.8-46.5% in four. The total/high-density lipoprotein (HDL):cholesterol ratio (from 4.4 +/- 1.0 to 3.7 +/- 0.6, P = 0.0012), glucose levels (from 5.6 +/- 1.2 to 4.4 +/- 1.4 mmol/l, P = 0.026), insulin levels (from 12.4 +/- 6.7 to 8.1 +/- 3.0 mUl/l, P = 0.0023) and homeostasis model assessment (HOMA) index (from 3.4 +/- 2.1 to 1.9 +/- 1.0, P = 0.0017) decreased. CONCLUSIONS: Treatment for 12 months with pegvisomant normalized IGF-I levels, and improved cardiovascular risk parameters and insulin sensitivity in patients with acromegaly resistant to long-term, high-dose treatment with somatostatin analogs. The tolerance of treatment was good.

Acromegaly↗
PubMed2006

Growth hormone stimulation tests in the differential diagnosis of Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is a common neurodegenerative disorder whose differential diagnosis from other forms of atypical parkinsonism, for instance multiple system atrophy (MSA) or progressive supranuclear palsy, may be difficult, especially in the early stages. Growth hormone stimulation tests have been recently reported to be useful in the differential diagnosis between IPD and MSA. Both clonidine, an alpha(2)-adrenoceptor agonist, and arginine, an amino acid activating the cholinergic system, have been used to assess growth hormone response in patients with IPD and MSA. This review summarizes the results of several studies and discusses the validity of these tests in the differential diagnosis of parkinsonisms.

Adrenergic alpha-Agonists↗
PubMed2005

Partial surgical removal of growth hormone-secreting pituitary tumors enhances the response to somatostatin analogs in acromegaly.

CONTEXT: Surgery is a cornerstone in the treatment of acromegaly, but its efficacy in large, invasive tumors is scant. OBJECTIVE: The objective of this study was to investigate whether partial surgical removal of GH-secreting pituitary tumors enhances the response rate to somatostatin analogs (SSA; sc octreotide, slow-release octreotide, and lanreotide). DESIGN: This was a multicenter, open, retrospective study. SETTING: The study was performed at university hospitals. SUBJECTS AND METHODS: Eighty-six patients (42 women and 44 men; age, 42 +/- 14 yr) with acromegaly were studied. INTERVENTIONS: Patients underwent two courses of octreotide, lanreotide, or slow-release octreotide treatments before and after surgery of at least 6 months. MAIN OUTCOME MEASURE: The main outcome measure was normal IGF-I levels for age. RESULTS: Presurgical SSA treatment significantly decreased GH and IGF-I levels in all patients. GH levels were less than 2.5 microg/liter in 12 patients (14%); IGF-I levels normalized in nine (10%). After surgery, GH and IGF-I levels further decreased in all patients; tumor removal was greater than 75% in 50 (58%), 50.1-75% in 21 (24%), 25.1-50% in 10 (12%), and less than 25% in five patients (6%). Preoperatively, pituitary function was impaired in 12 patients (14%). Postsurgical SSA treatment lowered GH levels to less than 2.5 microg/liter in 49 (56%) and normalized IGF-I levels in 48 patients (55%). The success rate was significantly increased compared with that before surgery (P < 0.0001). GH (r = -0.48; P < 0.0001) and IGF-I levels (r = -0.38; P = 0.0003) after postsurgery SSA treatment correlated with the amount of tumor surgically removed. After surgery, pituitary function was impaired in 28 patients (32.6%) and was improved in 12 patients (13.9%). The cumulative prevalence of pituitary deficiency did not change during the study (normal function from 40 to 42%; deficiency from 60 to 58%). CONCLUSIONS: Surgical tumor removal (>75%) enhances the response to SSAs without impairing pituitary function. Our data indicate that surgical debulking has a significant place in the treatment algorithm of acromegaly.

Acromegaly↗
PubMed2005

Sulfur amino acids in Cushing's disease: insight in homocysteine and taurine levels in patients with active and cured disease.

BACKGROUND: Cushing's syndrome is associated with an increased cardiovascular risk. Although a series of cardiovascular risk factors have been identified, sulfur amino acids (SAAs), recently indicated as independent cardiovascular risk factors, have been poorly investigated in patients with Cushing's syndrome. AIM: The aim of this cross-sectional controlled study was to evaluate serum and urinary levels and urinary excretion rate (ER) of SAAs in patients with Cushing's disease (CD) during the active disease and after long-term disease remission. SUBJECTS AND METHODS: Forty patients with CD (20 with active disease and 20 with cured disease for at least 5 yr) and 40 controls entered the study. Serum and urinary concentrations and urinary ER of SAAs, namely methionine, cystine, homocysteine, and taurine, were measured by means of cationic exchange HPLC. Serum folic acid and vitamin B12 levels were also evaluated in patients and controls and correlated to SAA levels. RESULTS: CD patients with active disease had higher serum and urinary concentrations of cystine and homocysteine, and lower serum and higher urinary concentrations and ER of taurine than cured patients and controls. Vitamin B12 levels were significantly decreased in patients with active disease compared with cured patients and controls, whereas folic acid levels were slightly decreased in patients than in controls. In patients with active CD, urinary cortisol concentrations were significantly and inversely correlated to serum taurine and directly correlated to taurine urinary ER, and fasting serum glucose levels were significantly correlated to taurine urinary ER. At the multiple regression analysis, urinary cortisol concentrations were the best predictors of taurine ER. CONCLUSIONS: CD is associated with hyperhomocysteinemia and hypotaurinemia. Glucocorticoid excess, acting directly or indirectly, seems to be the most responsible for this imbalance in SAA levels. The long-term disease remission is accompanied by normalization of SAA levels. Hyperhomocysteinemia and hypotaurinemia might contribute to the increased cardiovascular risk of CD.

Adult↗
PubMed2005

Recombinant thyrotropin-induced orbital uptake of [111In-diethylenetriamine-pentacetic acid-D-Phe1]octreotide in a patient with inactive Graves' ophthalmopathy.

Here we describe the case of a 60-yr-old nonsmoking woman with a history of Graves' disease associated with papillary thyroid carcinoma. After tumor removal, during the diagnostic follow-up for thyroid cancer, there was evidence of severe Graves' ophthalmopathy (GO) successfully treated with iv glucocorticoids. After this treatment, GO entered inactive status. The patient was then reevaluated for thyroid cancer with human recombinant TSH (rTSH). Orbital [111In-diethylenetriamine-pentacetic acid (DTPA)-D-phe1]octreotide scan was also performed, and results were negative. Shortly after rTSH administration, a moderate and transient pain behind the eye globes at rest and during eye movement was reported, with an increase in the activity score but without further GO progression. Twenty-four hours after rTSH administration, the patient was submitted to a second [111In-DTPA-D-phe1]octreotide scan, revealing significant orbital uptake, likely related to rapid accumulation of activated lymphocytes with inflammatory cytokines or fibroblasts expressing somatostatin receptors in the orbital tissue or interstitial edema due to the inflammation process. At last follow-up performed after 1 yr, there was no evidence of active thyroid cancer or changes in GO severity and/or activity, and orbital [111In-DTPA-D-phe1]octreotide uptake was negative. This case further supports the involvement of TSH receptor in the pathogenesis of GO. It also confirms the usefulness of orbital [111In-DTPA-D-phe1]octreotide scan to evaluate GO activity.

Female↗
PubMed2005

Short-term effects of growth hormone (GH) treatment or deprivation on cardiovascular risk parameters and intima-media thickness at carotid arteries in patients with severe GH deficiency.

To explore early effects of GH treatment or deprivation on cardiovascular risk factors and carotid intima-media thickness (IMT), we designed this randomized, cross-over study in 34 adult patients with severe GH deficiency. At study entry, the patients were randomized into two groups (A and B); group A (n = 17) received appropriate replacement therapy including GH at standard doses for 6 months and then were withdrawn from GH for the subsequent 6 months; group B (n = 17) received appropriate replacement therapy excluding GH for 6 months with the addition of GH in the subsequent 6 months. After the first 6 months, we observed a significant increase in IGF-I levels and of high-density lipoprotein (HDL)-cholesterol together with a significant decrease in diastolic blood pressure, the total/HDL-cholesterol ratio, and C-reactive protein in the patients in group A, whereas vascular parameters did not significantly change. In the patients in group B, none of the parameters studied significantly changed. After 6 months of GH withdrawal in the patients in group A, a significant decrease in IGF-I levels, a significant increase in the total/HDL-cholesterol ratio and C-reactive protein, and a trend toward an impairment of carotid IMT and peak velocities were observed. In the patients in group B, the addition of GH to the standard replacement induced a significant increase in IGF-I levels together with a decrease in systolic and diastolic blood pressure, total cholesterol and total/HDL-cholesterol ratio, and C-reactive protein, and an increase in HDL-cholesterol levels with a trend toward an improvement of vascular parameters. At the end of the study, mean IMT was significantly lower than at baseline both in group A (from 0.88 +/- 0.28 to 0.85 +/- 0.27 mm, P = 0.0003) and in group B (from 0.83 +/- 0.21 to 0.80 +/- 0.20 mm, P = 0.003). In conclusion, 6 months of GH replacement has beneficial effects whereas 6 months of GH deprivation has detrimental effects on cardiovascular risk factors and atherosclerosis. These findings support the indication for GH replacement in severe GH deficiency adult patients.

Adult↗