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A Colao

Publications and source records attributed to A Colao.

At least 19 recordsLinked to original sources
PubMed2002

Lymphocyte subset pattern in acromegaly.

Immune function in acromegalic patients has been poorly investigated. The aim of this study was to evaluate the main surface antigen clusters of circulating lymphocytes in acromegaly. One hundred patients with active acromegaly (55 women and 45 men, aged 20-70 yr) and 200 healthy subjects sex- and age-matched with the patients (110 women and 90 men, aged 20-70 yr) were enrolled in this study. All patients and controls were born and live in Southern Italy. No patient had received octreotide, bromocriptine or corticosteroids for at least 3 months before entering the study. The analysis of lymphocyte subset pattern was performed by flow cytometry and fluorescein isothiocyanate or phycoerythrin directly conjugated monoclonal antibodies specific for the cell surface antigen clusters (CD) representing T-cell population as a whole (CD3), T helpers (CD4), T suppressors (CD8), natural killer cells (CD16) and B-cell population as a whole (CD19). Acromegalics had significantly increased levels of CD3 (67.1+/-7.2 vs 64.3+/-8.8%; p=0.03) and CD4 (37.8+/-3.5 vs 36.4+/-4.3%; p=0.004) and decreased levels of CD8 (31.4+/-3.3 vs 33.7+/-8.2%; p<0.01) and CD19 (12.1+/-3.1 vs 15.2+/-5.1; p=0.01) without age-difference. The results of the current study demonstrate an increase in T-cell activity together with a decrease in B-cell activity in a very large series of patients with active acromegaly. These data further support the existence of abnormalities of the immune system in patients with chronic GH/IGF-1 excess.

Acromegaly↗
PubMed2002

Evaluation of circulating levels and renal clearance of natural amino acids in patients with Cushing's disease.

Although the hypercortisolism-induced impairment of protein homeostasis is object of several studies, a detailed evaluation of the complete amino acid profile of patients with Cushing's syndrome (CS) has never been performed. The aim of the current open transversal controlled study was to evaluate serum and urinary concentrations as well as renal clearance of the complete series of natural amino acids and their relationship with glucose tolerance in patients with Cushing's disease (CD). Twenty patients with CD (10 active and 10 cured) and 20 sex- and age-matched healthy controls entered the study. Measurement of serum and urinary levels of the complete series of natural amino acids was performed in all patients analyzed by cationic exchange high performance liquid cromatography (HPLC) after 2 weeks of a standardized protein intake regimen. The renal clearance (renal excretion rate) of each amino acid was calculated on the basis of the serum and urinary concentrations of creatinine and the specific amino acid. Fasting glucose and insulin levels, glucose and insulin response to standard glucose load, insulinogenic and homeostasis model insulin resistance (Homa-R) indexes were also evaluated and correlated to the circulating levels and renal clearances of each amino acid. Significantly higher serum (p<0.01) and urinary (p<0.05) levels of alanine and cystine, lower serum and higher urinary levels of leucine, isoleucine and valine (p<0.05) and higher renal excretion rates of leucine, isoleucine and valine (p<0.01) were found in patients with active CD than in patients cured from the disease and in controls. No difference was found between cured patients and controls. Creatinine clearance was similar in active and cured patients and in controls. In patients with active CD, urinary cortisol levels were significantly correlated to urinary cystine levels (r=0.85; p<0.01) and renal excretion rate of leucine (r=-0.76; p<0.05), isoleucine (r=-0.76; p<0.05) and valine (r=-0.66; p<0.05). Fasting blood glucose levels were significantly correlated to serum alanine levels (r=0.70; p<0.05). Although Homa-R was significantly correlated to BMI in active patients (r=0.74 p<0.05), it was not correlated to amino acid levels. In conclusion, the results of the current study demonstrate that patients with CD have significant changes in serum and urinary concentration of several amino acids and changes in renal clearance of some specific amino acids. Normalization of cortisol levels restored the amino acid profile.

Adult↗
PubMed2002

Very delayed hyponatremia after surgery and radiotherapy for a pituitary macroadenoma.

Severe hyponatremia (118 mmol/l) with natriuresis, consistent with cerebral salt wasting syndrome (CSWS), occurred 38 days after transsphenoidal surgery in a 59-year-old woman affected by a pituitary non-functioning macroadenoma. From the 35th day after surgery, she showed progressive polyuria, hypotension and hyponatremia associated with natriuresis, decreased plasma and increased urinary osmolality. The clinical examination revealed signs of dehydration and gradual decline in the level of consciousness. The anterior pituitary function was normal due to appropriate replacement of thyroid and adrenal axis. The patient was treated with saline administration until normal natremia and water balance were restored and neurological symptoms had completely disappeared. This case focuses on the unusually prolonged time of development of post-surgery hyponatremia, despite delayed symptomatic hyponatremia being reported to commonly occur 7 days after transsphenoidal surgery. Therefore, we would advise not to limit the periodic follow-up of the hydroelectrolytic balance to the first two weeks after surgery, but to prolong it until after discharge from hospital. In fact, an early diagnosis is of great importance to prevent permanent neurological damage or death. Since CSWS and syndrome of inappropriate secretion of ADH, the two disorders alternatively imputed to generate post-surgical hyponatremia, are characterized by different pathogenic mechanisms and require opposing therapeutic approaches, the occurrence of extracellular volume dilution or of increased sodium renal loss should be carefully investigated. The evidences in favor of CSWS, the possible mechanisms behind the syndrome and diagnosis and management of patients with post-transsphenoidal surgery CSWS are discussed.

Adenoma↗
PubMed2001

Estrogens and health in males.

Estrogen receptor concentrations are higher in the male reproductive tract than in other organs. Brain structure, neuronal organization and behavioral sex differences result from brain conversion of testosterone into estradiol within the brain. Estrogens modulate hormonal secretion at pituitary level and immune function at thymus level. Estrogens promote vasodilatatory and protective effects on the cardiovascular system by acting on the vascular smooth muscle and endothelium. Adult men with mutations in genes for estrogen receptor or aromatase are affected by osteopenia and tall stature, open epiphysis, which is corrected by estrogen treatment. Over the past few years there has seen a decline in sperm concentration, which has been attributed to exposure of fetal testes to estrogens. Many substances have estrogen-like properties and inhibit the action of estradiol or testosterone action. In conclusion, estrogens play a pivotal role in men also. In particular, taking in account their prevalent origin from testosterone aromatization at tissue and peripheral levels the presence and the distribution of the two receptors (ERalpha and ERbeta) are responsible for different responses in physiological and pathological conditions.

Adult↗
PubMed2001

In vivo and in vitro effects of octreotide, quinagolide and cabergoline in four hyperprolactinaemic acromegalics: correlation with somatostatin and dopamine D2 receptor scintigraphy.

OBJECTIVE: GH and PRL cosecretion frequently occurs in acromegaly and the sensitivity of both hormones to somatostatin analogs (SA) and dopamine agonists (DA) alone or in combination, is still debated. This study was designed to evaluate the in vivo and in vitro sensitivity to SA and/or DA and correlate the response in terms of hormone suppression to the results of in vivo somatostatin and dopamine receptor scintigraphy and to the immunohistochemical findings. DESIGN AND PATIENTS: Scintigraphy using 111In-DTPA-D-Phe(1)-OCT (111In-OCT) and 123I-methoxybenzamide (123I-IBZM) was performed in four patients with acromegaly and high circulating GH, PRL and IGF-I levels. The results were correlated with the response to long-term treatment with octreotide (OCT), quinagolide (QN) and/or cabergoline (CAB), to the in vitro hormone suppression by OCT and DA in primary cultures from the pituitary tumors and to the immunohistochemical findings. RESULTS: The first patient showed high tumour uptake of 111In-OCT and 123I-IBZM, the second high uptake of only 111In-OCT, while the third one showed faint tumour uptake of only 123I-IBZM, and the fourth a faint uptake of 111In-OCT. In the first and in the fourth patients OCT or CAB administered alone failed to normalize hormone levels while the combined treatment induced circulating GH, IGF-I and PRL normalization. In the second patient OCT administered alone normalized hormone levels while QN reduced PRL levels only. In the third patient both OCT and QN, alone or in combination, failed to normalize hormone levels. However, in this patient GH and PRL suppression was significantly greater after QN than OCT treatment. After medical therapy, all the patients were operated on. Immunohistochemistry showed diffuse GH and focal PRL staining in the first patient, while diffuse GH and PRL staining in the remaining three. In vitro, OCT significantly suppressed GH secretion in the four primary pituitary tumor cultures, while PRL secretion was significantly suppressed only in the second and the fourth cases. Dopamine agonists (DA) significantly suppressed PRL release in all the cultures, while GH secretion was significantly suppressed in three out of four. CONCLUSIONS: These four acromegalics, presenting similar clinical findings and comparable peripheral hormone levels, showed different responsiveness to SA and DA. Moreover, during the in vitro study on primary tumor cell cultures, OCT and DA displayed an inhibiting activity on GH and PRL secretion positively correlated with the response observed in vivo. This evidence together with the in vivo receptor imaging study suggest the existence of somatostatin and/or dopamine D2 receptor heterogeneity in this class of pituitary tumors. The new potent DA might be primarily considered in the medical treatment of hyperprolactinemic acromegalics, while SA alone or in combination with DA in case of ineffective hormone suppression.

Acromegaly↗
PubMed2001

Central diabetes insipidus and heart: effect of acute arginine vasopressin deficiency and replacement treatment with desmopressin on cardiac performance.

Besides its effects on water balance, arginine vasopressin (AVP) increases peripheral vascular resistance and decreases cardiac output, mainly by decreasing heart rate. The current study was designed to evaluate cardiac performance in patients with central diabetes insipidus (CDI), focusing on the acute effects of desmopressin replacement withdrawal and its subsequent reinstatement in patients with CDI. Twelve patients with CDI and 12 sex- and age-matched healthy subjects entered the study. All patients were receiving treatment with intranasal desmopressin at standard doses. All patients and controls were assessed for water balance, by measuring plasma osmolality and total body water, anterior pituitary function, heart rate, systolic and diastolic blood pressure. Left ventricular (LV), end-diastolic and end-systolic diameters (LVEDD, LVESD) and volumes (LVEDV, LVESD), end-diastolic and end-systolic interventricular septum thickness (EDIVST, ESIVST) and posterior wall thickness (LVEDPWT, LVESPWT), and mass (LVM) were measured by echocardiography. Moreover, LV systolic function was assessed by measuring the ejection fraction (EF), the fractional shortening (FS), the Suga index, the stroke volume and the cardiac output, while LV diastolic function was assessed by measuring early (M1) and late (M2) maximal transmitral blood flow velocities, the ratio between M1 and M2, the mitral deceleration time (MDT) and the isovolumetric relaxation time. All parameters were assessed in the patient group 24 h after discontinuing treatment with nasal desmopressin (baseline study) and 1 week after re-starting replacement treatment, while in the control group before (baseline study) and after 1-week of a nasally administered placebo. At baseline, compared to controls, patients with CDI had increased plasma osmolality (P < 0.01), plasma ACTH (P < 0.01), serum (P < 0.01) and urinary cortisol (P < 0.01) levels, and heart rate (P < 0.05), and decreased total body water (P < 0.05). Systolic and diastolic blood pressure and the other anterior pituitary hormones were similar in patients and controls. At echo-cardiography, EDIVST (P < 0.05), ESIVST (P < 0.01), LVEDPWT (P < 0.05) and LVESPWT (P < 0.01), EF (P < 0.01), Suga index (P < 0.05), FS (P < 0.05), M2 (P < 0.01) and IRT (P < 0.05) were significantly higher while LVESD (P < 0.01), LVESV (P < 0.01), LVEDD (P < 0.05), LVEDV (P < 0.05), M1 (P < 0.05), and M1/M2 (P < 0.01) were significantly lower in patients than in controls. LVM, stroke volume and cardiac output, were similar in patients and controls. In the patient group, after 1 week of replacement treatment with desmopressin, all echocardiographic parameters were normalized, except IVT, LVPWT and the diastolic parameters that were still abnormal compared to controls. No difference was found in any of the parameters in the control group one week after placebo administration. Patients with central diabetes insipidus have increased heart rate and left ventricular contractility, and impaired diastolic function. The altered heart rate and left ventricular contractility, reversible after desmopressin replacement, is likely to be due to stimulation of sympathetic nervous activity, induced by the hypovolemia associated with arginine vasopressin deficiency. Conversely, the impairment of diastolic function, persistent after desmopressin replacement, probably relates to a stable impairment of the left ventricular compliance.

Administration, Intranasal↗
PubMed2001

Growth hormone and the heart.

Impaired cardiovascular function has recently been demonstrated to potentially reduce life expectancy both in GH deficiency and excess. Experimental and clinical studies have supported the evidence that GH and IGF-I are implicated in cardiac development. In most patients with acromegaly a specific cardiomyopathy, characterized by myocardial hypertrophy with interstitial fibrosis, lympho-mononuclear infiltration and areas of monocyte necrosis, results in biventricular concentric hypertrophy. In contrast, patients with childhood or adulthood-onset GH deficiency (GHD) may suffer both from structural cardiac abnormalities, such as narrowing of cardiac walls, and functional impairment, that combine to reduce diastolic filling and impair left ventricular response to peak exercise. In addition, GHD patients may have an increase in vascular intima-media thickness and a higher occurrence of atheromatous plaques, that can further aggravate the haemodynamic conditions and contribute to increased cardiovascular and cerebrovascular risk. However, several lines of evidence have suggested that the cardiovascular abnormalities can be partially reversed by suppressing GH and IGF-I levels in acromegaly or after GH replacement therapy in GHD patients. Recently, much attention has been focussed on the ability of GH to increase cardiac mass suggesting its possible use in the treatment of chronic nonendocrine heart failure. In fact, GH administration can induce an improvement in haemodynamic and clinical status in some patients. Although these data need to be confirmed in more extensive studies, such promising results seem to open new perspectives for GH treatment in humans.

Acromegaly↗
PubMed2001

Increased arterial intima-media thickness by B-M mode echodoppler ultrasonography in acromegaly.

BACKGROUND: Patients with acromegaly have an increased morbidity and mortality for cardiovascular diseases. Despite the increasing evidence for the existence of a specific cardiomyopathy in acromegaly, the presence of vascular abnormalities has been never investigated. OBJECTIVE: To evaluate the cardiovascular risk and premature atherosclerosis in acromegaly. SUBJECTS: Forty-five patients with acromegaly and 30 sex- and age-matched healthy subjects were included in this study: 30 patients were studied at the diagnosis of acromegaly and were in active disease (GH 59.3 +/- 10.2 mU/l, IGF-I 733 +/- 57.6 microg/l) while 15 patients were studied after surgery and/or radiotherapy and were cured from the disease (GH 4.5 +/- 0.7 mU/l, IGF-I 172.4 +/- 16.9 microg/l). METHODS: Body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), serum total, LDL- and HDL-cholesterol, triglycerides, and fibrinogen levels, prothrombin time (PT), activated partial thromboplastin time (APTT), glucose and insulin levels (fasting and after glucose load) were measured in all patients and controls. By echodoppler ultrasonography, blood systolic (SPV) and diastolic (DPV) peak velocity, and resistance index (RI) were measured at both common and internal carotid arteries where presence, size and location of atherosclerotic plaques were evaluated by B-Mode ultrasonography. Intima-media thickness (IMT) of both common carotids was measured by M-Mode ultrasonography. RESULTS: SBP, but not DBP, was significantly higher in patients with active disease than in cured patients and controls (P = 0.003). Hypertension was found in nine (30%) patients with active disease, in two (13.3%) of those cured from acromegaly and in none of controls (chi2 = 10.81, P < 0.004). Fasting blood glucose levels were significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Circulating insulin levels were significantly higher in patients with active disease than in cured patients and controls (P < 0.001) and in cured patients than in controls (P < 0.001). Glucose tolerance abnormalities were found in 13 (43.3%) patients with active disease, in four (26.6%) patients with inactive disease and in four controls (13.3%) (chi2 = 6.71, P = 0.03). Total blood cholesterol levels were similar in the three groups, LDL-cholesterol and triglycerides levels were significantly higher, whereas HDL-cholesterol levels were significantly lower both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Serum fibrinogen levels were significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). No difference was found in PT and APTT levels among the three groups. At the level of right and left common carotid arteries, IMT was significantly higher both in patients with active disease and in those cured from the disease than in controls (P < 0.001). Both right and left SPV, but not DPV, were significantly higher in patients with active disease than in those cured from the disease and in controls (P < 0.01). Well defined carotid wall plaques were detected in two patients (6.6%) with active disease, in one patient cured from the disease (6.6%) and in two controls (6.6%). At the level of right and left internal carotid arteries, SPV, DPV and RI were similar among the three groups. Well defined carotid wall plaques were detected in three patients with active disease (10%), two patients cured from the disease (13.3%) and in one control (3.3%). CONCLUSIONS: A significant increase of IMT of both common carotid arteries was observed in patients with active acromegaly, this was also found in those cured from acromegaly. However, the prevalence of well defined carotid plaques was not increased in both groups of patients with acromegaly as compared to controls. On this basis, heart more than vessels seems to be affected by chronic GH and IGF-I excess in acromegaly.

Acromegaly↗
PubMed2001

Neuroendocrine aspects of immunolymphoproliferative diseases.

Exchange of information occurs between cells of neuroendocrine and immune systems. Neuroendocrine hormones may modulate lymphoid cell activities, including proliferation and mitogenesis, and immune cells may produce neuropeptides as well. Neuropetide Y is synthesized in B-cell leukaemia lymphoblasts, while substance P immunoreactivity has been detected in neoplastic haematological samples of different types of leukaemias. The presence of receptors for neuropeptides on different animal and human lymphoid cell lines, as well as in several types of animal and human lymphoproliferative diseases has been demonstrated. Species variability in receptor distribution has been shown as well. Receptor expression in immune cells may be regulated by changes in microenvironmental conditions, it may also be related to the activation and/ or proliferation state of cells. Vasoactive intestinal peptides receptors have been detected in myeloma cells, while somatostatin receptors have been first detected in vitro on resting lymphocytes and cells of the monocyte/macrophage lineage, and later on human activated lymphocytes and on lymphoblastic leukaemia cells. Somatostatin receptors have been found in biopsies from patients with malignant lymphomas. Tumor localization in non-Hodgkin lymphomas and Hodgkin's disease can be visualized by in vivo somatostatin receptor scintigraphy, contributing to establish the diagnosis and the stage of the disease. Recently. somatostatin receptors have been in vivo and in vitro detected in human thymic tumors. Although treatment of lymphoproliferative diseases with somatostatin analogs is a little explored field, partial remission was found in patients with low-grade non-Hodgkin lymphoma and cutaneous T-cell lymphoma, and a successful treatment with octreotide has been reported in patients with thymoma. Specific somatostatin receptors present in progenitors of immune cells are not expressed in the mature phenotype, while they can be detected in transformed cell lines. The possibility that this phenomenon is caused by oncogene expression cannot be ruled out. Moreover, preliminary data showed a developmental expression of somatostatin receptors in lymphoid cells, suggesting a potential role for neuropeptide receptors as differentiation markers. Although controlled studies are warranted to investigate the efficacy of the currently available analogs, somatostatinergic compounds may be of interest in the treatment of lymphoproliferative malignancies. A promising approach in refractory patients with somatostatin receptor positive malignant lymphomas may be radionuclide-targeted and cytotoxic analog therapy. These concepts increase the possibility of a wider antitumor treatment with ligands for neuroepeptide receptors than in established 'classic' neuroendocrine tumors.

Cell Differentiation↗
PubMed2001

Growth hormone secretion after baclofen administration in different phases of the menstrual cycle in healthy women.

AIM: The aim of this study was to investigate the effect of baclofen administration on growth hormone (GH) secretion during different phases of the menstrual cycle. METHODS: Twelve healthy women (33.6 +/- (SD) 2.8 years; range 23-40 years) with regular menstrual cycles were enrolled. The phases of the menstrual cycle were determined using transvaginal ultrasonography (TV-US) and detecting hormonal serum levels. Plasma GH levels were evaluated during the early follicular, periovulatory and luteal phases of the cycle before and after the baclofen challenge test. RESULTS: After acute baclofen administration, GH levels increased significantly (p < 0.001) compared to basal values during the periovulatory and luteal phases, while no significant variation was detected during the early follicular phase. In addition, plasma GH levels resulted significantly (p < 0.001) higher during the luteal phase than during the periovulatory phase. CONCLUSION: Acute baclofen administration induces a significant increase in plasma GH levels in healthy females during the periovulatory and luteal phases, but not during the early follicular phase. These data suggest a modulator role of plasma sex steroids levels on GH release induced by baclofen.

Administration, Oral↗
PubMed2001

Resistance to cabergoline as compared with bromocriptine in hyperprolactinemia: prevalence, clinical definition, and therapeutic strategy.

To evaluate the prevalence of resistance to cabergoline treatment, we studied 120 consecutive de novo patients (56 macroadenoma, 60 microadenoma, 4 nontumoral hyperprolactinemia) treated with cabergoline (CAB) compared with 87 consecutive de novo patients (28 macroadenoma, 44 microadenoma, 15 nontumoral hyperprolactinemia) treated with bromocriptine (BRC) for 24 months. Resistance was evaluated as inability to normalize serum PRL levels (first end point) and to induce tumor shrinkage (second end point). After 24 months, PRL normalization and tumor shrinkage after CAB and BRC treatments, respectively, were obtained in 82.1% and 46.4% of macroprolactinomas (P < 0.001) and in 90% vs. 56.8% of microprolactinomas (P < 0.001). The median doses of CAB and BRC able to fulfill the two criteria of treatment success were 1 mg/wk and 7.5 mg/d in macroprolactinomas, 1 mg/wk and 5 mg/d in microprolactinomas, and 0.5 mg/wk and 3.75 mg/d in nontumoral hyperprolactinemia. Hyperprolactinemia persisted in 17.8% of macroprolactinomas, 10% of microprolactinomas, and after CAB at doses of 5-7 mg/wk and in 53.6% of macroprolactinomas, 43.2% of microprolactinomas, and 20% of nontumoral hyperprolactinemic patients, after BRC at doses of 15-20 mg/d. In these resistant macro- and microprolactinomas, the maximal tumor diameter was reduced by 43.7 +/- 3.6% and 22.1 +/- 3.7% and by 59.3 +/- 7.1% and 4.3 +/- 2.1% after CAB and BRC, respectively (P < 0.001). In conclusion, long-term CAB treatment induced the successful control of hyperprolactinemia associated with tumor shrinkage in a higher proportion of patients than did BRC treatment. In a small number of patients (i.e. 17.8% of macroprolactinomas and 10% of microprolactinomas), however, CAB treatment did not normalize serum PRL levels despite reducing tumor mass, even at very high doses. Therefore, an absence of tumor shrinkage cannot be considered as end point to indicate resistance to CAB, and increasing the dose of CAB higher than 3 mg/wk does not seem to be helpful in controlling PRL hypersecretion.

Adenoma↗
PubMed2001

Is the acromegalic cardiomyopathy reversible? Effect of 5-year normalization of growth hormone and insulin-like growth factor I levels on cardiac performance.

Acromegalic patients are considered to be exposed to a doubled mortality rate, mostly for cardiovascular diseases. This open prospective study was designed to evaluate whether the impairment of cardiac performance could be reversed by the long-term suppression of GH and insulin-like growth factor I (IGF-I) levels. Eighteen patients with active acromegaly were studied before and 5 yr after surgery, followed by sc octreotide in 11 patients. Disease control (GH levels < or =1 microg/L after glucose load or < or =2.5 microg/L after fasting, respectively, together with normalized IGF-I levels for age) was achieved in seven patients after surgery and in six patients after 0.3--0.6 mg/day sc octreotide. Five patients were not controlled during the 5-yr follow-up. Cardiac performance at rest and at peak exercise was assessed by equilibrium radionuclide angiography at study entry and 5 yr after surgery alone or plus octreotide. Thirty-six sex- and age-matched healthy subjects served as controls. At study entry, patients had a lower left ventricular ejection fraction (LVEF) at peak exercise and LVEF exercise-induced changes, exercise duration, and capacity than controls (P < 0.001). After 5 yr of treatment, a significant decrease of resting heart rate (P = 0.03) and a significant increase of LVEF at peak exercise (P = 0.003) was found in patients achieving disease control. LVEF response at peak exercise worsened in none of the patients with controlled disease and in three patients with uncontrolled disease (60%) (chi(2) = 5.5; P = 0.02). Diastolic filling, exercise duration, and workload did not significantly change during the 5-yr follow-up. No difference was found between patients controlled by surgery alone or by surgery plus octreotide. This 5-yr prospective study demonstrated that the LVEF response at peak exercise improved in all patients achieving disease control, while it was worsened in 60% of uncontrolled ones. These results strengthen the need of a stable suppression of GH and IGF-I hypersecretion to restore a normal cardiac performance in acromegaly.

Acromegaly↗
PubMed2001

Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency.

Adult GH deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to unfavorable lipid profile, hyperfibrinogenemia, and impairment of cardiac performance. This prospective controlled cohort study evaluated the effects of 12-month GH replacement on lipid profile, fibrinogen levels, cardiac mass by echocardiography, and performance by equilibrium radionuclide angiography. To this end we studied 20 patients (11 men and 9 women, aged 19-40 yr), 10 with childhood-onset (co-) and 10 with adult-onset (ao-) disease, and 20 sex- and age-matched healthy subjects. At study entry, insulin-like growth factor I (IGF-I; P < 0.0001) and high density lipoprotein (HDL) cholesterol (P < 0.0001) levels, left ventricular mass index (LVMi; P < 0.0001), ejection fraction (LVEF) at rest (P = 0.001) and at peak exercise (P < 0.0001), peak ejection rate (P = 0.005), and exercise duration (P < 0.0001) and capacity (P = 0.002) were lower, whereas total cholesterol (P = 0.02), triglycerides (P = 0.003), and fibrinogen (P = 0.005) levels were higher in patients than in controls. After 12 months, increases in IGF-I (P < 0.0001) and HDL cholesterol levels (P = 0.04), LVMi (P < 0.0001), LVEF at peak exercise (P < 0.0001), and exercise duration (P = 0.009) and capacity (P = 0.003) and decreases in total cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001), triglycerides (P < 0.0001), and fibrinogen (P = 0.01) levels were found in all patients, without any difference between co- and ao-GHD. At the end of treatment, however, total cholesterol, triglycerides, and fibrinogen levels were still higher, and HDL cholesterol levels, IGF-I levels, and LVEF at rest and at peak exercise were lower in patients than in controls. In conclusion, GH replacement for 12 months significantly improved lipid profile, decreased fibrinogen levels, and increased LVMi and LVEF in young adults with co- or ao-GHD. However, lipid profile, fibrinogen levels, and systolic function remained abnormal compared with those in age- and sex-matched controls, suggesting that a longer period of GH replacement is necessary to normalize cardiovascular parameters and reverse the cardiovascular risk of these patients.

Adolescent↗
PubMed2001

Long-term effects of depot long-acting somatostatin analog octreotide on hormone levels and tumor mass in acromegaly.

The effects of a 12- to 24-month treatment with depot long-acting octreotide (OCT-LAR) on hormone profile, tumor mass, and clinical symptoms were reported in 36 patients with active acromegaly [GH, 34.2 +/- 5.6 microg/L; insulin-like growth factor I (IGF-I), 784.5 +/- 40.4 microg/L]. Fifteen patients were de novo whereas 21 had previously undergone unsuccessful surgery. Serum GH (P < 0.0001) and IGF-I levels (P < 0.0001) significantly decreased as early as after the first injection of OCT-LAR and progressively declined during the 12-24 months of treatment both in de novo and in operated patients. At the last follow-up, GH hypersecretion was controlled (< or =2.5 microg/L) in 69.4% whereas normal IGF-I levels were achieved in 61.1% of patients. GH and IGF-I suppression during OCT-LAR treatment was similar in de novo and operated patients as shown by nadir GH (2.3 +/- 0.6 vs. 2.2 +/- 0.6 microg/L) and IGF-I (323.1 +/- 34.9 vs. 275.5 +/- 33.0 microg/L), percent suppression of GH (92.7 +/- 2.0 vs. 85.9 +/- 3.3%) and IGF-I (57.4 +/- 4.9 vs. 61.5 +/- 4.6%), and prevalence of GH (73.3 vs. 76.2%) and IGF-I (53.3 vs. 71.4%) control. A decrease in tumor volume was observed in 12 of 15 de novo patients, whereas no shrinkage was detected in 4 of 9 operated patients. No patient had tumor reexpansion during OCT-LAR treatment. Significant clinical improvement was obtained in all patients; heart rate, systolic blood pressure, and diastolic blood pressure significantly decreased in the entire population. A mild but significant increase of blood glucose levels, followed by a decrease of serum insulin levels, was observed after 3 months of treatment: this effect subsided with treatment continuation. OCT-LAR treatment was well tolerated by most patients. In conclusion, long-term treatment with OCT-LAR was effective in controlling GH and IGF-I hypersecretion in most patients with acromegaly, when applied either as primary therapy or as adjunctive therapy after surgery. Tumor shrinkage was observed in de novo patients during OCT-LAR treatment, suggesting that it can be successfully applied as primary therapy in patients bearing invasive tumors, who are less likely to be cured after surgery.

Acromegaly↗
PubMed2001

Usefulness of different biochemical markers of the insulin-like growth factor (IGF) family in diagnosing growth hormone excess and deficiency in adults.

The diagnostic approach to acromegaly and GH deficiency frequently includes measurement of several components of the insulin-like growth factor (IGF) system. IGF-I levels are reported to be good predictors of active and cured acromegaly, but are commonly found within the normal age-adjusted range in adult GH-deficient (GHD) patients. Circulating concentrations of IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and free IGF-I reflect the GH secretory status, but their diagnostic accuracy is still debated. In this study serum levels of total and free IGF-I, IGFBP-3, ALS, and IGFBP-3-IGF-I and IGFBP-3-ALS complexes were determined in patients previously diagnosed with active (n = 67) or inactive (n = 16) acromegaly and adult GHD (n = 34) and compared with results obtained in 58 healthy controls. In healthy subjects, IGF-I, IGFBP-3, ALS, and both IGFBP-3 complexes declined with age; a correlation was found between IGF-I and IGFBP-3 (r = 0.59; P < 0.001), ALS (r = 0.67; P < 0.001), and free IGF-I (r = 0.40; P < 0.05). Active acromegalic patients showed a significant increase in all parameters tested. IGF-I concentrations were above +2 SD in 100% of patients, whereas slightly lower sensitivities were shown for IGFBP-3 (85%), ALS (88%), and free IGF-I (94%). In this group, IGF-I exhibited a slightly higher correlation with IGFBP-3 (r = 0.83; P < 0.001) than with ALS levels (r = 0.78; P < 0.001). In cured acromegalic patients, we observed the normalization of all parameters but free IGF-I levels. Adult GHD patients showed a significant reduction of all hormones. Unlike active acromegalic patients, all parameters had only a modest sensitivity in GHD; suppression below -2 SD was observed in 41% of GHD patients for IGF-I, 47% for IGFBP-3, 32% for ALS, and 35% for free IGF-I measurements. Previous radiotherapy and GH peak response below 3 microg/L were associated with significantly lower IGF-I, IGFBP-3, and ALS levels. IGF-I levels were significantly correlated to ALS (r = 0.68; P < 0.001) and IGFBP-3 (r = 0.64; P < 0.001) as well as with free IGF-I (r = 0.67; P < 0.001) levels. By multiple regression analysis, the number of anterior pituitary hormones impaired was the most predictive indicator of IGF-I, IGFBP-3, and free IGF-I levels in GHD patients; conversely, the GH peak response better anticipated ALS concentrations. The pattern of IGFBP-3 complexes paralleled previous hormonal findings. In active acromegalic patients, IGFBP-3-IGF-I levels were 5.4-fold higher than in controls and were above +2 SD in 95% of patients, whereas IGFBP-3-ALS levels were elevated in 15% of cases. On the other hand, both IGFBP-3 complexes were able to predict GHD in only a minority of cases. Taken together, these data support the diagnostic role of IGF-I in acromegaly and suggest that free IGF-I and the IGFBP-3-IGF-I complex can assist diagnostic strategies in this condition. All markers are of limited predictive value in adult GHD, as hormonal values are commonly found within the normal limits. In these patients, low IGFBP-3 and IGF-I concentrations can add further clinical information on the residual GH activity.

Acromegaly↗
PubMed2001

Inferior petrosal sinus sampling in the differential diagnosis of Cushing's syndrome: results of an Italian multicenter study.

OBJECTIVE: To evaluate the diagnostic accuracy of inferior petrosal sinus sampling (IPSS) in the differential diagnosis of ACTH-dependent Cushing's syndrome as compared with pituitary imaging techniques. DESIGN AND METHODS: We retrospectively studied the diagnostic accuracy of basal and post corticotropin-releasing hormone (CRH) IPSS, magnetic resonance imaging and computed tomography in distinguishing pituitary from ectopic ACTH secretion in 97 Cushing's syndrome patients: 74 with Cushing's disease (CD) and 10 with ectopic ACTH secretion (EAS). Thirteen patients were excluded because of unconfirmed diagnosis. The difference between IPSS and pituitary imaging techniques in the correctly localized pituitary adenoma in the patients with CD was also investigated. RESULTS: The basal ACTH inferior petrosal sinus:periphery (IPS:P) ratio was > or = 2 in 63/74 patients with CD (85%), and in 1/10 EAS patients (10%); after stimulation with CRH, the ratio was > or = 3 in 60/68 patients with CD (88%) and < 3 in all patients with EAS. The basal and post-CRH ACTH IPS:P ratios had a diagnostic accuracy of 86% and 90% respectively. The diagnostic accuracy of IPSS with both ratios was significantly higher than magnetic resonance imaging (50%) and computed tomography (40%). The IPS:P ratio suggested by receiver-operator characteristic (ROC) analysis that better distinguished CD from EAS was 2.10 for the basal and 2.15 for the post-CRH ratios. Using these cut-offs, the specificity of basal ratio and the sensitivity of the post-CRH test rose to 100% and 93% respectively. Diagnostic accuracy remained substantially unchanged for the basal ratio (87% vs 86%), while it rose from 90% to 94% for the post-CRH ratio. The sensitivity of IPSS was significantly higher than that of magnetic resonance and computerized tomography. IPSS was less reliable in identifying the adenoma site found at surgery than magnetic resonance imaging or computed tomography (65% vs 75% and 79% respectively). CONCLUSION: In conclusion, IPSS improved the diagnostic performance of imaging techniques. It can help in excluding transsphenoidal surgery in EAS patients. More striking results were obtained when a > or = 2.1:1 basal ratio or a > or = 2.15:1 post-CRH ratio were considered as criteria to distinguish between patients with CD and EAS. To establish correctly the location of the pituitary adenoma, IPSS is less reliable than imaging techniques.

Adrenocorticotropic Hormone↗