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Annamaria Colao

Publications and source records attributed to Annamaria Colao.

At least 127 records · Page 7Linked to original sources
PubMed2002

High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases.

BACKGROUND: The progressively increasing number of long-term survivors after allogeneic bone marrow transplantation (allo-BMT) led researchers to focus on the early and late complications of this procedure. Endocrine dysfunction occurred mostly in patients who had undergone total body irradiation (TBI) as part of pretransplantation treatment. The extent to which chemotherapy and immune system derangement affect endocrine function in allo-BMT recipients is still unclear. METHODS: Forty consecutive patients (21 women, 19 men) with hematologic diseases surviving 12 or more months after allo-BMT from HLA-identical siblings were studied. Patients' age at transplantation ranged from 13 to 45 years and their post-BMT follow-up lasted 12-62 months. The conditioning regimen BUCY2 was employed. Graft versus host disease (GVHD) was observed in the acute form in 13 patients and in the chronic form in 26. The function of hypothalamic-pituitary-gonad, thyroid, somatotrophic, and adrenal axes was assessed. RESULTS: The most common endocrine dysfunction was ovarian insufficiency (95% of women), followed by an increase in follicle-stimulating hormone in 47% of men, indicating spermatogenesis damage. Hormone replacement therapy was contraindicated in three women because of chronic liver GVHD and it was ineffective partially in four others because of reduced intestinal or cutaneous absorption. Thyroid dysfunction occurred in 47.5% of patients and included low T3 syndrome, chronic thyroiditis, and transient subclinical hyperthyroidism and subclinical hypothyroidism. Adrenal function was abnormal in 10%, mostly related to the prolonged corticosteroid treatment. IGF-I was lower than age-reference values in 27% of all patients and in 38% of those with chronic GVHD. Thyroid, adrenal, and IGF-I impairments were more frequent in patients with chronic GVHD than in patients without this disease (P = 0.048). CONCLUSIONS: A high prevalence of endocrine dysfunction was detected in a cohort of allo-BMT recipients not treated by TBI. Although gonadal failure was likely related to intensive myeloablative treatments, thyroid, adrenal, and IGF-I impairments were late events, suggesting that immunosuppressive treatment and immune system derangement may play a role in the development of endocrine dysfunction after allografting.

Adolescent↗
PubMed2002

Severe impairment of bone mass and turnover in Cushing's disease: comparison between childhood-onset and adulthood-onset disease.

BACKGROUND: Osteoporosis is an important, frequently unrecognized consequence of hypercortisolism. OBJECTIVE: To evaluate whether the age of onset of hypercortisolism influences its effects on bone mass and turnover. SUBJECTS: 10 with childhood-onset (co) and 18 with adulthood-onset (ao) Cushing's disease (CD); 28 age-, sex- and body mass index (BMI)-matched healthy subjects served as controls. STUDY DESIGN: Open, cross-sectional controlled. MEASUREMENTS: Bone mineral density (BMD) at lumbar spine, serum osteocalcin (OC), and urinary N-telopeptides of type I collagen (Ntx) levels. RESULTS: BMD at lumbar spine was significantly lower in all CD patients than in controls (Z score, -2.3 +/- 0.1 vs. -0.2 +/- 0.01; P < 0.001). co-CD and ao-CD patients had similar values of bone mass when expressed as Z score (-2.6 +/- 0.4 vs. -2.1 +/- 0.2; P = 0.27) or as BMD (0.728 +/- 0.03 vs. 0.78 +/- 0.03 g/cm2; P = 0.25). In particular, osteoporosis was observed in 16 patients (57.1%) [eight adolescents (80%) and eight adults (44.4%)] and none of the controls; osteopenia was found in two co-CD patients (20%) and none of the healthy adolescents, 10 ao-CD patients (55.6%) and four healthy adults (14.3%) (chi2 = 7.87, P < 0.01; chi2 = 2.99, P = 0.09, respectively). In co-CD and ao-CD patients, serum OC levels were similar and significantly lower than in controls (P < 0.01); urinary Ntx levels were significantly higher than in controls (P < 0.001) and were significantly higher in co-CD than in ao-CD patients (P < 0.001). No significant correlation was found between urinary cortisol levels, serum cortisol and age and lumbar Z score values, while a significant correlation was found between Ntx levels and disease duration (r = 0.434; P = 0.021) and plasma cortisol (r = 0.440; P = 0.019). CONCLUSIONS: Cushing's disease causes bone loss and abnormalities of bone turnover both in childhood-onset and in adulthood-onset patients. A strict follow-up of bone mass and turnover is mandatory in all patients with Cushing's disease to prevent fractures later in life and specific treatment for bone loss is strongly suggested.

Adolescent↗
PubMed2002

(99m)Technetium pentavalent dimercaptosuccinic acid scintigraphy in the follow-up of clinically nonfunctioning pituitary adenomas after radiotherapy.

BACKGROUND: It is still difficult to differentiate pituitary adenoma remnants from postradiotherapy fibrosis by computed tomography (CT) or magnetic resonance imaging (MRI), especially in patients with clinically nonfunctioning pituitary adenomas (NFA), lacking circulating markers to follow disease progression or cure. OBJECTIVE: We investigated the usefulness of scintigraphy with technetium-99m pentavalent dimercaptosuccinic acid [(99m)Tc(V)DMSA], shown previously to detect most pituitary GH- and PRL-secreting adenomas and NFA, with tumour-to-background ratios (T/B) as high as 25-fold. PATIENTS: Eighteen patients with NFA (study group), 10 patients with GH- and three patients with PRL-secreting adenomas (control group), all of whom had undergone previous surgery. DESIGN: The study was an open longitudinal design. Pituitary CT/MRI and (99m)Tc(V)DMSA scintigraphy was performed before and 1, 3 and 5 years after conventional radiotherapy. Tumour size was measured as maximal diameter of the residual lesion, while uptake of (99m)Tc(V)DMSA was measured as a T/B ratio. RESULTS: At study entry, pituitary (99m)Tc(V)DMSA uptake was found in 13 NFA (72.2%), seven GH-secreting (70%) and all PRL-secreting adenomas; remnant tumour was documented by CT/MRI in all 31 patients. Maximal remnant diameter was significantly higher in patients with positive (13.3 +/- 0.9 mm) than in those with negative scintigraphy (7.0 +/- 0.3 mm, P < 0.001). During the 5-year follow-up postradiotherapy, a significant decrease in (99m)Tc(V)DMSA uptake (9.7 +/- 0.8 vs. 3.2 +/- 0.5, P < 0.0001) occurred in all but three patients. Two NFA patients died of tumour invasion 19 and 36 months after radiotherapy and one acromegalic patient had no change in his hormone levels. In the eight negative patients (five NFA and three GH), scintigraphy remained negative throughout follow-up. A remarkable shrinkage of the remnant tumour was observed in both the patients with negative (from 7.0 +/- 0.3 to 1.9 +/- 0.6 mm, P < 0.001) and in those with positive scintigraphy (from 13.3 +/- 0.9 to 7.3 +/- 0.6 mm, P < 0.001). At the end of the study, CT/MRI showed evident remnant tumour in 13 of 16 NFA (81.2%), nine GH-secreting (90%) and all three prolactinomas (100%), while the scintigraphy was negative (T/B < 1) or faintly positive (T/B 1-2) in eight of 16 NFA (50%), five GH-secreting (50%) and one prolactinoma (33.3%). CONCLUSIONS: Functional imaging of pituitary remnant adenomas (> 10 mm in size) by (99m)Tc(V)DMSA depicts viable pituitary adenoma remnants. This approach may be of clinical value in patients with clinically nonfunctioning adenomas to monitor the effects of radiotherapy.

Adenoma↗
PubMed2002

Effectiveness of combined GnRH analogue plus raloxifene administration in the treatment of uterine leiomyomas: a prospective, randomized, single-blind, placebo-controlled clinical trial.

BACKGROUND: Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms. METHODS: After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method. RESULTS: After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period. CONCLUSIONS: In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes.

Delayed-Action Preparations↗
PubMed2002

Quantitative and functional expression of somatostatin receptor subtypes in human thymocytes.

We recently demonstrated the expression of somatostatin (SS) and SS receptor (SSR) subtype 1 (sst1), sst2A, and sst3 in normal human thymic tissue and of sst1 and sst2A on isolated thymic epithelial cells (TEC). We also found an inhibitory effect of SS and octreotide on TEC proliferation. In the present study, we further investigated the presence and function of SSR in freshly purified human thymocytes at various stages of development. Thymocytes represent a heterogeneous population of lymphoid cells displaying different levels of maturation and characterized by specific cell surface markers. In this study, we first demonstrated specific high-affinity 125I-Tyr(11)-labeled SS-14 binding on thymocyte membrane homogenates. Subsequently, by RT-PCR, sst2A and sst3 mRNA expression was detected in the whole thymocyte population. After separation of thymocytes into subpopulations, we found by quantitative RT-PCR that sst2A and sst3 are differentially expressed in intermediate/mature and immature thymocytes. The expression of sst3 mRNA was higher in the intermediate/mature CD3+ fraction compared with the immature CD2+CD3- one, whereas sst2A mRNA was less abundant in the intermediate/mature CD3+ thymocytes. In 7-day-cultured thymocytes, SSR subtype mRNA expression was lost. SS-14 significantly inhibited [3H]thymidine incorporation in all thymocyte cultures, indicating the presence of functional receptors. Conversely, octreotide significantly inhibited [3H]thymidine incorporation only in the cultures of immature CD2+CD3- thymocytes. Subtype sst3 is expressed mainly on the intermediate/mature thymocyte fraction, and most of these cells generally die by apoptosis. Because SS-14, but not octreotide, induced a significant increase in the percentage of apoptotic thymocytes, it might be that sst3 is involved in this process. Moreover, sst3 has recently been demonstrated on peripheral human T lymphocytes, which derive directly from mature thymocytes, and SS analogs may induce apoptosis in these cells. Interestingly, CD14+ thymic cells, which are cells belonging to the monocyte-macrophage lineage, selectively expressed sst2A mRNA. Finally, SSR expression in human thymocytes seems to follow a developmental pathway. The heterogeneous expression of SSR within the human thymus on specific cell subsets and the endogenous production of SS as well as SS-like peptides emphasize their role in the bidirectional interactions between the main cell components of the thymus involved in intrathymic T cell maturation.

Apoptosis↗
PubMed2002

Bone involvement in eugonadal male patients with adrenal incidentaloma and subclinical hypercortisolism.

Adrenal incidentalomas (AI) are not associated, by definition, with clinically evident syndromes; however, some AI patients may show biochemical indexes of subclinical hypercortisolism (SH). Previous data on female AI patients indicated that SH may lead to bone loss, at least at spine. No data are available on bone involvement in samples of only AI male patients. We measured bone metabolism and bone mineral density at spine and femur by dual-energy x-ray absorptiometry in 38 consecutive eugonadal male AI patients and 38 healthy matched control subjects. Patients were subdivided according to the presence or absence of SH (group SH+ and group SH-, respectively). Mean Z-score levels of spinal bone mineral density measured by dual-energy x-ray absorptiometry were lower (P < 0.05) in group SH+ (-0.42 +/- 1.62) in comparison with group SH- (0.6 +/- 1.13) and controls (0.47 +/- 1.06). Thus, in order for the most appropriate management to be individually tailored, bone mass evaluation is strongly indicated in AI male patients with SH, irrespective of their gonadal status.

Absorptiometry, Photon↗
PubMed2002

Raloxifene administration in women treated with gonadotropin-releasing hormone agonist for uterine leiomyomas: effects on bone metabolism.

This prospective randomized, single-blind, placebo-controlled clinical trial was performed to evaluate the efficacy of raloxifene in preventing the bone loss associated with GnRH agonist (GnRH-a) administration. One hundred premenopausal women with uterine leiomyomas were treated with leuprolide acetate depot at a dosage of 3.75 mg/d for 28 d and then randomized into two groups to receive raloxifene hydrochloride at 60 mg/d (group A) or placebo (1 tablet/d; group B). Bone mineral density (BMD) and serum bone metabolism markers were evaluated at admission and after six treatment cycles. Posttreatment BMD differed significantly from baseline BMD in group B but not in group A. BMD was significantly higher in group A than in group B. In group A, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were unchanged vs. baseline. Differently, posttreatment concentrations of these bone turnover markers were significantly lower in group B compared with baseline and group A values. In conclusion, raloxifene prevents GnRH-a related bone loss in premenopausal women with uterine leiomyomas.

Adult↗
PubMed2002

Long-lasting bone damage detected by dual-energy x-ray absorptiometry, phalangeal osteosonogrammetry, and in vitro growth of marrow stromal cells after allogeneic stem cell transplantation.

Bone complications after allogeneic stem cell transplant (allo-SCT) include osteoporosis, fractures, and osteonecrosis. We investigated bone abnormalities in long-term survivors after busulfan cyclophosphamide-conditioning regimen, followed by human leukocyte antigen-identical sibling SCT. Bone density was measured by dual-energy x-ray absorptiometry at lumbar spine (LS) and femoral neck (FN) and phalangeal osteosonogrammetry (OSG) in 41 patients 1-10 yr after allo-SCT. Using colony-forming units-fibroblast (CFU-F) assay, we analyzed the repopulating capacity of clonogenic fibroblast progenitors belonging to the osteogenic stromal lineage. LS and FN bone mineral density (BMD) and phalangeal densitometric values were significantly reduced, compared with 188 healthy controls (P < 0.001). Decrease in T-score less than 1 SD was documented in 29% and 52% of patients at the LS and FN, respectively. OSG detected densitometric values with a T-score less than 1 SD in 68% of transplanted patients. The patients examined within the first 3 yr after transplant showed low BMD, which remained stable at FN and improved at LS. Phalangeal densitometry was low up to 10 yr after transplant. CFU-F was found permanently depressed and unable to give rise to a confluent stroma. Low serum osteocalcin levels were present throughout the whole follow-up period. A significant correlation was found between densitometric values detected by both techniques and CFU-F growth in vitro. Osteonecrosis was associated with lower FN BMD, and phalangeal densitometry correlated inversely with duration of amenorrhea and chronic graft vs. host disease requiring long-lasting steroid therapy. In conclusion, dual-energy x-ray absorptiometry and phalangeal OSG may provide complementary information on bone density after allo-SCT. Prolonged severe impairment of femoral BMD and phalangeal densitometry suggest that bone loss may persist for many years after transplant. Inability to regenerate a normal number of osteoblastic precursors in the stromal stem cell compartment may in part account for severe long-lasting posttransplant decrease in bone mass.

Absorptiometry, Photon↗
PubMed2002

Leptin concentrations in GH deficiency: the effect of GH insensitivity.

Disorders of GH secretion are known to impair the physiological lipostat and to affect the secretion of leptin, a sensitive marker of regional fat accumulation and total body composition. In both children and adults with GH deficiency (GHD), leptin levels are increased proportionately with enhanced adiposity. In GHI, mutations of the GH receptor gene result in a phenotype similar to GHD, with increased adiposity and unfavorable lipid profiles. To examine the impact of different forms of growth disorders on leptin production, we measured leptin levels in 22 GHI patients homozygous for the E180 splice mutation (15 females and 7 males, aged 8-37 yr) and compared results with those obtained in 20 subjects heterozygous for the mutation (11 females and 9 males, aged 7-54), 17 idiopathic GHD patients (6 females and 11 males, aged 3-34), and 44 normal subjects (25 females and 19 males, aged 7-45). After the baseline evaluation, all subjects received two 7-d GH treatments at doses of 0.025 and 0.050 mg/kg x d in random order. Leptin, IGF-I, and IGF-binding protein-3 (IGFBP-3) were assayed by specific immunoassays. IGF-I and IGFBP-3 levels were significantly lower (P < 0.0001) in homozygous GHI and GHD patients compared with either controls or GHI heterozygotes. Circulating leptin levels were significantly higher in homozygous GHI patients than in normal controls (20.7 +/- 4.2 vs. 8.7 +/- 1.4 microg/liter) as well as when compared with heterozygous GHI subjects (14.4 +/- 3.4 microg/liter) and GHD patients (9.8 +/- 1.6 microg/liter; P < 0.01). Similar results were obtained when leptin was normalized for body mass index. When subjects were subgrouped by gender, leptin levels were significantly higher (P < 0.05) in GHI females than in females of all other groups and were significantly increased in GHD males (P < 0.01 vs. control males). Within the study groups, females had significantly higher leptin levels than males in controls (12.7 +/- 2 vs. 3.3 +/- 1 microg/liter; P < 0.001) and homozygous GHI patients (28.7 +/- 5.3 vs. 6.9 +/- 2.3 microg/liter; P < 0.05), but not in heterozygous GHI (20.1 +/- 5.4 vs. 7.3 +/- 2.4 microg/liter; P < 0.06) and GHD (10.9 +/- 2.6 vs. 9.2 +/- 2.1 microg/liter) patients. By multivariate analysis, log-normalized leptin levels were best predicted by gender and body mass index in homozygous GHI patients as well as in normal subjects. During the 1-wk courses of GH therapy, serum IGF-I and IGFBP-3 levels significantly increased (P < 0.0001) in GHD patients, heterozygous GHI patients, and control subjects at both GH doses. Inversely, leptin levels did not change significantly during either course of GH administration in the groups examined. These data demonstrate that leptin is increased in patients affected with long-standing homozygous GHI, probably reflecting abnormalities of body composition and metabolism typical of this condition.

Adolescent↗
PubMed2002

The cardiovascular risk of adult GH deficiency (GHD) improved after GH replacement and worsened in untreated GHD: a 12-month prospective study.

Increased cardiovascular morbidity and mortality were reported in GH deficiency (GHD), and GH replacement can ameliorate cardiac abnormalities of adult GHD patients. To test the potential progression of untreated GHD on the cardiovascular risk and cardiac function, cardiovascular risk factors, cardiac size, and performance were prospectively evaluated in 15 GHD patients (age, 18-56 yr) who were treated with recombinant GH at the dose of 0.15-1.0 mg/d, 15 GHD patients (age, 18-56 yr) who refused GH replacement, and 30 healthy subjects (age, 18-53 yr). Electrocardiogram, systolic and diastolic blood pressure, and heart rate measurement, serum IGF-I, total cholesterol, low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, and fibrinogen level assay, echocardiography, and equilibrium radionuclide angiography were performed basally and after 12 months. At study entry, low IGF-I levels, unfavorable lipid profile, and inadequate cardiac and physical performance were found in GHD patients compared with controls. After 12 months of GH treatment, IGF-I levels normalized; HDL-cholesterol levels, left ventricular (LV) mass index (LVMi), left ventricular ejection fraction (LVEF) at peak exercise, peak filling rate, exercise duration and capacity significantly increased; total- and LDL-cholesterol levels significantly decreased. After 12 months in GH-untreated GHD patients, IGF-I levels remained stable, and HDL-cholesterol levels, LVEF both at rest and at peak exercise, and exercise capacity were further reduced; total- and LDL-cholesterol levels increased slightly. LVEF at rest and its response at peak exercise normalized in 60 and 53.3%, respectively, of GH-treated patients and in none of the GH-untreated patients. In conclusion, 12 months of GH replacement normalized IGF-I and improved lipid profile and cardiac performance in adult GHD patients. A similar period of GH deprivation induced a further impairment of lipid profile and cardiac performance. This finding strongly supports the need of GH replacement in adult GHD patients.

Adult↗
PubMed2002

Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis.

This prospective randomized, double-blind, placebo-controlled, clinical trial was performed to evaluate the effectiveness of estrogens plus low-dose alendronate on bone metabolism. A total of 150 surgically postmenopausal women with osteoporosis were randomized in three groups: group A, micronized E2 (2 mg/d) plus standard-dose alendronate (10 mg/d); group B, micronized E2 plus low-dose alendronate (5 mg/d); and group C, micronized E2 plus placebo (one tablet per day). In all women, bone mineral density (BMD) and serum bone metabolism markers were assessed at admission and every 6 months for 2 yr. After 2 yr, BMD significantly increased compared with baseline in all groups. The percentage BMD change was significantly higher in groups A and B than in group C. The differences in BMD detected between groups A and B were not statistically significant. Since the 6-month follow-up and throughout the study, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were significantly reduced in all groups. Serum bone alkaline phosphatase levels significantly decreased in groups A and B, without difference between them, in comparison with group C. In conclusion, in surgically postmenopausal osteoporotic women treated with estrogen replacement, the addition of alendronate at a low dose of 5 mg daily induces a gain of bone mass not significantly different in comparison with that obtained using a standard dose of 10 mg daily.

Alendronate↗
PubMed2002

Cardiovascular consequences of early-onset growth hormone excess.

Acromegaly has relevant effects on the cardiovascular system, but few data deal with the early effects of GH and IGF-I excess. To study the early stage of acromegalic cardiomyopathy and give indirect evidence of the mechanisms underlying GH and IGF-I action on the human heart, 25 patients with uncomplicated acromegaly [15 young subjects with short-term (< or =5 yr) disease and 10 with long-term (>5 yr) disease] and 25 sex- and age-matched controls were studied. Cardiovascular risk parameters were studied by standard methods; cardiac morphology by M-mode and Doppler echocardiography, cardiac function at rest and at peak exercise by equilibrium radionuclide angiography, and vascular disease at common carotid arteries by Doppler ultrasonography. In the patient group these measurements were repeated after 6 months of treatment with octreotide-LAR (20-40 mg, im, every 28 d). Glucose, glycosylated hemoglobin, insulin, low density lipoprotein cholesterol, triglycerides, and fibrinogen levels were higher, and high density lipoprotein cholesterol levels were lower in acromegalic patients than in controls. Resting blood pressure was similar in patients and controls, whereas heart rate at rest and systolic blood pressure at peak exercise were higher in the patients. The left ventricular mass index was higher in acromegalic patients than in controls (123.3 +/- 8.9 vs. 81.5 +/- 4.3 g/m(2); P < 0.001); seven patients had left ventricular hypertrophy. Diastolic function was similar in the two groups. The ejection fraction at rest, but not at peak exercise, was significantly increased in the patients compared with controls. As a consequence the exercise-induced changes in the ejection fraction were lower in patients than controls (8.7 +/- 1.1% vs. 21.9 +/- 3.5%; P < 0.001). At common carotid ultrasonography, young patients with acromegaly had increased diastolic peak velocity and increased intima media thickness, even if neither patient nor controls had atherosclerotic plaques. Six months after OCT-LAR treatment, GH and IGF-I levels remarkably decreased in all patients; 8 (53.3%) achieved disease control. Insulin, total cholesterol, and fibrinogen levels reduced, whereas high density lipoprotein cholesterol levels increased. Both at rest and at peak exercise, heart rate significantly decreased, whereas systolic and diastolic blood pressures did not change. The left ventricular mass index was significantly reduced, but it was still higher than the control value (101.6 +/- 3.5 g/m(2); P < 0.01). The left ventricular ejection fraction at rest was significantly reduced, but its response at peak exercise was increased (16.3 +/- 2.4%), becoming similar to the control value. At common carotids, the intima media thickness of right and left arteries was significantly reduced as was the diastolic peak velocity without any change in systolic peak velocity. Short-term GH excess, despite causing enhanced cardiac performance at rest, reduces cardiac performance on effort and impairs vascular morphology. These deleterious effects of early-onset acromegaly are ameliorated by suppressing GH/IGF-I levels for 6 months.

Acromegaly↗
PubMed2002

Early vascular alterations in acromegaly.

Acromegaly is associated with increased cardiovascular mortality; however, little is known about the early atherosclerotic changes occurring in such patients. Endothelial function, in the form of flow-mediated dilation (FMD) of the brachial artery, and intima-media thickness (IMT) of the carotid artery were measured by B-Mode ultrasound in: 1) 18 patients with active acromegaly; 2) 12 subjects cured from acromegaly; 3) 18 subjects without acromegaly, each of them matched to an acromegalic patients for age, sex, risk factors and treatments; and 4) 10 healthy subjects. Results are expressed as median plus (25th, 75th) percentile. In active acromegalic patients, FMD was 5.7 (3.9, 7.7)%, significantly lower than in both healthy subjects (P < 0.01) and matched controls (P < 0.01). No difference between groups was observed for endothelium-independent vasodilation. Acromegalic patients had also higher IMT than healthy controls (P < 0.05), whereas no difference was observed with matched controls. In cured acromegalic patients, FMD was 9.2 (7.7, 10.5)%, significantly lower (P < 0.01) than in healthy controls but higher (P < 0.01) than in active patients. No difference in IMT was observed between active and cured patients. In conclusion, patients with acromegaly have functional and morphological vascular alteration that seems, at least in part, dependent on the GH excess itself.

Acromegaly↗
PubMed2002

The cardiovascular risk of GH-deficient adolescents.

To investigate the onset of the cardiovascular impairment in patients with GH deficiency (GHD), we prospectively studied cardiovascular risk parameters, cardiac mass and performance (by echocardiography) in 10 adolescent patients (5 with isolated GHD and 5 with multiple GHD) who reached their final height before GH replacement withdrawal, 6 months after GH replacement withdrawal, and 6 months after GH treatment was restarted, and in 10 sex- and age-matched controls. At study entry, when compared with controls, GHD adolescents had lower IGF-I levels (although still in the normal age range) and high-density lipoprotein (HDL)-cholesterol levels, higher total/HDL-cholesterol ratio, lower triglyceride levels, higher fibrinogen levels, and lower heart rate, systolic blood pressure, and early-to-late mitral flow velocity ratio (E/A). Left ventricular (LV) mass index and ejection fraction were normal. Six months after GH withdrawal, IGF-I levels decreased remarkably in all cases (from 176.6 +/- 8.3 to 77.5 +/- 8.9 microg/liter; P < 0.001), whereas low-density lipoprotein-cholesterol and triglyceride levels significantly increased. The total/HDL-cholesterol ratio (from 3.89 +/- 0.1 to 4.74 +/- 0.2; P < 0.05) and fibrinogen levels (from 261 +/- 7.1 to 287.5 +/- 6.4 mg/dl; P < 0.05) also significantly increased compared with study entry, without any change in the other parameters. In contrast, both LV mass index (from 94.2 +/- 1.6 to 87.8 +/- 1.7 g/m(2); P = 0.05) and E/A (from 1.32 +/- 0.05 to 1.12 +/- 0.03; P < 0.01) decreased, although remaining in the normal range. Six months after restarting GH replacement (at a median dose of 10 micro g/kg x d), lipid and cardiac parameters were brought back to the levels measured at study entry, but in no patient did IGF-I levels reach the 50th centile for age. HDL-cholesterol levels (P < 0.0001), heart rate (P < 0.05), systolic blood pressure (P < 0.01), LV ejection fraction (P < 0.005), and E/A (P < 0.0001) remained lower, whereas total/HDL-cholesterol ratio (P < 0.01), triglycerides, and fibrinogen levels (P < 0.05) remained higher than controls. In conclusion, GH discontinuation is inappropriate in adolescents with severe GHD, inducing impairment of lipid profile and cardiac morphology and performance. Because the results on the cardiovascular system and on the lipid profile were suboptimal, it is likely that the GH dose in severe GHD adolescents should be higher.

Adolescent↗
PubMed2002

Dopamine receptor agonists for treating prolactinomas.

Prolactinomas are the most common hormone-secreting pituitary tumours and cause infertility and gonadal and sexual dysfunction in both sexes. The approach to prolactinomas has changed in the last 25 years thanks to the availability of dopaminergic drugs characterised by a potent prolactin-inhibitory effect, a tumour shrinking effect associated with a satisfactory tolerability. In more recent years, cabergoline 1-[(6-allelylergolin-8beta-yl)carbonyl]-1-[3-(dimethylamino) propyl]-3-ethyl-urea an ergoline derivative with potent, selective and long-lasting inhibitory activity on prolactin release, has been used to suppress prolactin secretion in women with hyperprolactinaemia. Cabergoline was shown to be significantly more effective than bromocriptine in inducing a complete biochemical response and clinical efficacy and was better tolerated than bromocriptine in the majority of patients. Notable tumour shrinkage until tumour disappearance was observed during cabergoline treatment in most patients with macroprolactinoma and it was also proven effective in patients resistant to or with a poor response to bromocriptine. In view of the limited data on cabergoline-associated pregnancies and the long half-life of the drug, it is currently recommended that women hoping to become pregnant, once ovulatory cycles have been established, should discontinue cabergoline therapy 1 month before they intend to conceive. However, no data concerning negative effects on pregnancy or offspring have been reported. The great efficacy of this compound together with its excellent tolerability makes this drug the current treatment of choice for the majority of patients with hyperprolactinaemic disorders.

Aminoquinolines↗
PubMed2002

Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly.

OBJECTIVE: To evaluate the effect of a 6-month treatment with slow-release lanreotide (LAN) on cardiovascular risk and atherosclerosis in 24 normotensive patients with active acromegaly (GH=67.4 +/- 12.6 mU/l, IGF--I=866.0 +/- 55.8 microg/l) and 24 healthy subjects sex-, age- and body mass index-matched with the patients (as controls). DESIGN: Open, prospective, multicenter. METHODS: The following were measured before and after 6 months of LAN treatment (dose 60-90 mg/month): fasting GH, IGF-I, LDL, HDL and total cholesterol, triglyceride, glucose, glycosylated hemoglobin, insulin and fibrinogen levels, intima-media thickness (IMT) and blood systolic and diastolic peak velocity (SPV and DPV respectively) in both common carotids. RESULTS: At study entry, insulin, total and LDL cholesterol, triglyceride and fibrinogen levels were higher while HDL cholesterol levels were lower in patients than in controls. At the right (0.88 +/- 0.04 vs 0.77 +/- 0.03 mm, P=0.05) and left (0.93 +/- 0.03 vs 0.78 +/- 0.02 mm, P=0.01) common carotid IMT was significantly higher in patients than in controls; 12 patients and two controls showed an IMT of > or = 1 mm (chi(2)=8.2, P=0.004). After 6 months of LAN treatment, disease control was achieved in 15 patients (62.5%). Insulin, triglyceride and fibrinogen levels were significantly decreased, and a trend toward a decrease of IMT in the right (from 0.90 +/- 0.05 to 0.78 +/- 0.04 mm, P=0.06) and left (from 0.95 +/- 0.04 to 0.84 +/- 0.04 mm, P=0.06) common carotid arteries was observed only in patients with disease control, while SPV and DPV did not change. CONCLUSIONS: LAN treatment for 6 months significantly lowered GH, IGF-I, insulin and fibrinogen levels and reduced IMT of both common carotid arteries in normotensive patients with acromegaly.

Acromegaly↗
PubMedDate not supplied

Pregnancy outcome after cabergoline treatment in early weeks of gestation.

We collected information on 61 pregnancies in 50 women treated with cabergoline. These pregnancies resulted in 12 (19.7%) early terminations (five induced abortions, six spontaneous abortions, one hydatidiform mole) and 49 (80.3%) live births. In one case, malformations were suspected by a gynecologist based on ultrasound at 12 gestational weeks and the pregnancy was terminated; additional information was not available. There was one case of trisomy 18. The frequency of spontaneous and induced abortions and major congenital malformations was comparable with rates in the general population. The data did not indicate any potential adverse effect of the drug on pregnancy. The data from this study in combination with previous reports can exclude a congenital malformation risk greater than 10% associated with pregnancy exposure to cabergoline.

Abnormalities, Drug-Induced↗