Relationship between blood pressure and glucose tolerance in acromegaly.

BACKGROUND: Hypertension represents a well-known risk factor for cardiovascular diseases. The pathogenesis of hypertension in acromegaly is commonly viewed as multifactorial, but the possible influence of metabolic disorders on blood pressure (BP) in affected patients is largely unknown. OBJECTIVE: The aim of the present study was to evaluate the impact of glucose metabolism abnormalities on BP values in a series of patients with active acromegaly. DESIGN: An open multicentre prospective study. PATIENTS: Sixty-eight patients with active disease, aged 47.5 +/- 11.7 years, have been studied. Thirty-nine had normal glucose tolerance (NGT), 16 impaired glucose tolerance (IGT) and 13 suffered from diabetes mellitus (DM). MEASUREMENTS: Mean clinical BP values were calculated as the mean of BP values obtained by sphygmomanometric measurement in three separate occasions and mean 24-h, diurnal and nocturnal systolic (SBP) and diastolic (DBP) values were obtained by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Patient's age and the degree of glucose tolerance abnormalities were found to significantly and independently influence BP values. All clinical and ABPM SBP and DBP values significantly increased with age by linear regression (P < 0.02 for all BP values, 0.30 < or = R < or = 0.43), and the independent influence of this parameter on BP values was confirmed by mutivariate analysis. Similarly, the independent influence of glucose tolerance abnormalities on BP values was confirmed when introducing age as a covariable in a multivariate analysis, and patients with DM presented significantly higher clinical SBP and 24-h, diurnal and nocturnal SBP and DBP than patients with NGT (P < 0.02 for clinical SBP, P < 0.015 for all ABPM values, respectively). In addition, patients with DM showed significantly higher 24-h, diurnal and nocturnal DBP than those with IGT (P < 0.05 in all cases). In contrast, no significant difference was found between NGT and IGT patients. No significant influence of disease duration, BMI, GH, IGF-I, or fasting and 2-h post glucose load insulinaemia on BP values was observed. CONCLUSIONS: Abnormalities of glucose metabolism significantly contribute to increase systolic blood pressure and especially diastolic blood pressure in acromegalic patients. Careful control of blood pressure and of risk factors for developing systemic hypertension, with special reference to glucose tolerance, is mandatory to decrease cardiovascular morbidity and mortality in such patients.

Radioiodine and percutaneous ethanol injection in the treatment of large toxic thyroid nodule: a long-term study.

Surgery is generally recommended for large thyroid toxic nodules (TTNs). When surgery is not applicable, both radioactive iodine (RAI) and percutaneous ethanol injection (PEI) are alternative treatments. In this retrospective study, the long-term efficacy of nonsurgical treatments was evaluated in 43 patients with TTN, selected on the basis of presence of hyperthyroidism and a fairly large nodule (3- and 4-cm in diameter) completely inhibiting controlateral lobe captation during scintigraphy. Twenty-one patients were treated by RAI (administered dose 670+/-160 MBq; range 555-925) and twenty-two were treated by PEI (6+/-1 sessions; range 5-9). FT4, FT3, thyrotropin (TSH), and nodule volume were assessed before and at fixed intervals after treatment. Median follow-up was 36 months (range, 12-84). Compared to baseline values, with both therapies, serum FT4, FT3, and nodule volume were decreased (p < 0.01) and serum TSH was increased (p < 0.01), after 3 months and during the entire follow-up. Nodule volume reduction percentage was 66.8+/-22.0 and 78.4+/-18.0, in the RAI- and PEI-treated groups, respectively. At the end of follow-up, 34 patients were euthyroid (16 RAI- and 18 PEI-treated). Four RAI-treated patients (19%) showed slightly high TSH levels (4.2-5.3 mU/L), whereas three PEI-treated patients (13.6%) still had suppressed TSH levels, although being clinically asymptomatic. One RAI-treated patient (4.8%) showed overt hypothyroidism during the follow-up period and was then treated with L-thyroxin. One patient (4.6%), who was initially cured by PEI, became newly hyperthyroid during the follow-up period. Both treatments were well-tolerated. In conclusion, both of these nonsurgical treatments are effective and may be chosen also for relatively large TTNs. Specifically, RAI seems to be more effective for treating hyperthyroidism but has minimal sequelae of subclinical or clinical hypothyroidism, while, after PEI treatment the possibility of stable subclinical hyperthyroidism or hyperthyroidism relapse should be taken into account.

CPAP nasofaringeo en el fallo respiratoruio agudo pediátrico, un mmétodo de ventilación no invasica(VNI)adaptado a nuestra economía / Nasopharyngeal CPAP in pediatric respiratory failure: a non invasive ventilation procedure adapted to our economical situation

Objetivo:Valorar el efeto de CPAP nasofaríngeo como forma de ventilación no invasiva(VNI)en pacientes pediátricos con fallo respiratorio agudo con indicación de ARM.Diseño:descriptivo,prospectivo,no randomizado.Pacientes y métodos:Ingresaron todos los pacientes con(FRA)debido a patología respiratoria en que luego de haberse optimizado las medidas de soporte y tratamiento,tuvieron indicación de ARM.Se excluyeron pacientes con inestabilidad hemodinámica o con compromiso neurológica(Glasgow<8o incapacidad de proteger vía aérea)Se colocó tubo nasofaríngeo y se administró CPAP usando respiradores de flujo contínuo.Se controló FC,FR,score de silverman,saturación,ph,Pa02,PC02,previo al ingreso de VNI y luego cada cuatro horas.Se consideró fracaso a la necesidad de instituir ARM convencional.Conclusiones:El CPAP nasofaríngeo fue útil para evitar la ARM.Mejoró significativamente las variables fisiológicas estudiadas.Dado que es una medida de bajo riesgo y con potenciales beneficios significativos en la evolución de los pacientes,puede ser una alternativa antes de instituir ARM.Además la estrategia usada está al alcance de todas las terapias

CPAP nasofaríngeo en el fallo respiratorio agudo pediátrico, un método de ventilación no invasiva (VNI) adaptado a nuestra economía / Nasopharyngeal CPAP in pediatric respiratory failure: a non invasive ventilation procedure adapted to our economical situation

Objetivo:Valorar el efeto de CPAP nasofaríngeo como forma de ventilación no invasiva(VNI)en pacientes pediátricos con fallo respiratorio agudo con indicación de ARM.Diseño:descriptivo,prospectivo,no randomizado.Pacientes y métodos:Ingresaron todos los pacientes con(FRA)debido a patología respiratoria en que luego de haberse optimizado las medidas de soporte y tratamiento,tuvieron indicación de ARM.Se excluyeron pacientes con inestabilidad hemodinámica o con compromiso neurológica(Glasgow<8o incapacidad de proteger vía aérea)Se colocó tubo nasofaríngeo y se administró CPAP usando respiradores de flujo contínuo.Se controló FC,FR,score de silverman,saturación,ph,Pa02,PC02,previo al ingreso de VNI y luego cada cuatro horas.Se consideró fracaso a la necesidad de instituir ARM convencional.Conclusiones:El CPAP nasofaríngeo fue útil para evitar la ARM.Mejoró significativamente las variables fisiológicas estudiadas.Dado que es una medida de bajo riesgo y con potenciales beneficios significativos en la evolución de los pacientes,puede ser una alternativa antes de instituir ARM.Además la estrategia usada está al alcance de todas las terapias

Percutaneous ethanol injection may be a definitive treatment for symptomatic thyroid cystic nodules not treatable by surgery: five-year follow-up study.

We present a prospective study on the long-term efficacy of percutaneous ethanol injection (PEI) treatment for thyroid cystic nodules. Among patients referred for symptomatic thyroid cystic nodules who had relapsed after two aspirations or whose nodules could not be aspirated due to the thickness of the cystic fluid, PEI was given when surgery was either refused or contraindicated. Forty-three patients were treated; the mean basal volume of the cysts was 38.4 mL. The purpose of the study was to evaluate long-term efficacy of PEI treatment on: (1) amelioration of symptoms and signs of local compression and (2) nodule volume reduction. In three subjects (7%), PEI failed to induce a significant (>50%) nodule reduction, so that surgical treatment was performed. In 40 patients (93%), an impressive nodule shrinkage was observed, reaching a plateau after 24 months (volume reduction = 91.9%+/-11.4%). A new PEI session was needed in two patients in whom a recurrence was noted within the first 6 months. After 6 months, no significant (> or =1 mL volume) nodule regrowth was observed up to 60 months. Both symptoms and tracheal displacement rapidly (within 1 month) and significantly (p<0.01) improved. After PEI, mild pain was the only side effect observed. No suspicious cytology was observed in any residual nodule greater than 1 mL 6 and 24 months after the last PEI session. Our data suggest that PEI is a first-line safe, effective, probably definitive, treatment for cystic thyroid nodules for which surgery is either refused or contraindicated.

Losses of hemifield contrast sensitivity in patients with pituitary adenoma and normal visual acuity and visual field.

OBJECTIVE: To detect early losses of contrast sensitivity (CS) in patients with pituitary adenomas, before the occurrence of visual acuity and visual field defects. METHODS: CS has been evaluated in both hemifields of 28 patients with different kinds of pituitary adenoma (mainly intrasellar) and normal visual acuity and visual field, as well as in 15 age-matched controls. Two different stimuli were used: a coarse (0.3 c/deg) dynamic (10 Hz) grating and a finer (2 c/deg) static grating. RESULTS: On average, CS and/or hemifield asymmetry were reduced in patients, whereas perimetric sensitivity was normal. CS losses were more frequent for 2 c/deg static-, as compared with 0.3 c/deg, 10 Hz stimuli. However selective losses for either stimuli were also found. CS losses did not correlate with anatomical measurements (size, chiasm involvement) of tumors as established by MRI scans. CONCLUSIONS: CS evaluation may provide a simple and effective tool for early detection and monitoring of visual dysfunction in patients with pituitary adenoma. The lack of correlation between CS losses and chiasm involvement suggests causes different from chiasmal compression for visual dysfunction.

Treatment of large cold benign thyroid nodules not eligible for surgery with percutaneous ethanol injection.

We studied the effect of percutaneous ethanol injection (PEI) in the treatment of cold, cytologically benign, large (>10 mL) thyroid nodules (CBNs) in 41 patients. The end-point of our study was to evaluate the efficacy of PEI on: 1) local symptomatology, assessed by an arbitrary symptom score; and 2) nodule volume and tracheal displacement (at ultrasonography). Follow-up ranged from 12-36 (21 +/- 9) months. Symptom score was significantly reduced (P < 0.01) after 6 months and at the end of the follow-up (2.1 +/- 0.3 vs. 0.2 +/- 0.5 and vs. 0.2 +/- 0.4). A significant (P < 0.01) nodule volume reduction was observed, without differences between solid or mixed CBNs; the reduction was 50% or more in 92.7% of patients. Neither clinical parameters nor pretreatment nodule ultrasonographic features were related to nodule reduction. Disappearance or significant reduction (>0.5 cm) of tracheal displacement was obtained in 61% and in 39% of patients, respectively. One patient experienced prethyroid region edema, pain, and mild fewer, which reversed within 1 week; and one patient had dysphonia, caused by vocal cord palsy, which reversed spontaneously within 1 month. At the end of the follow-up, nodules with just necrotic material at cytology showed a greater (P < 0.05) volume reduction than nodules with residual benign thyroid cells. Our data suggest that PEI is a safe and effective treatment of large CBNs, although sometimes serious side effects do occur.

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer.

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T4) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T4. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T4 or results of thyroid function tests. Our data show that carefully monitored l-T4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur.

Pre-Cushing's syndrome not recognized by conventional dexamethasone suppression-tests in an adrenal "incidentaloma" patient.

Pre-Cushing's syndrome has been recently diagnosed in 6-12% of patients affected with incidentally discovered adrenal masses. Some of these patients have been described to show transient hypoadrenalism after surgery, similarly to those affected with overt Cushing's syndrome. We studied a 70-year-old male patient with a large left adrenal mass, incidentally discovered, who displayed 24-h urinary free cortisol levels at the upper limit of the normal range, normal dexamethasone overnight and low-dose suppression tests and not suppressed ACTH levels, increased 17-hydroxyprogesterone response to ACTH stimulation and low upright plasma renin activity with normal serum aldosterone levels; furthermore, DHEAS level was low and 75 Selenium-cholesterol scintigraphy showed unilateral uptake concordant with the side of the mass. Soon after left adrenalectomy, he complained of acute hypoadrenalism requiring cortisol replacement therapy: ten months after surgery he is still hypoadrenal. Moreover, stimulated 17-hydroxyprogesterone and plasma renin activity in clino- and orthostatic posture have become normal. We propose that conventional dexamethasone suppression-tests may be not enough sensitive in this kind of patients and that in selected cases the absence of controlateral uptake at scintigraphy may be more reliable in predicting post-surgical hypoadrenalism.

Percutaneous ethanol injection of large thyroid cystic nodules.

To evaluate the effect of percutaneous ethanol injection (PEI) in the treatment of large compressive thyroid cystic nodules (TCN), we studied 20 patients, potential candidates for surgery (tracheal displacement, nodule volume over 10 mL at ultrasonography) and not cured by aspiration alone: 14 experienced a recurrence after two complete evacuations of cystic fluid (watery nodules, WN); in six an aspiration was impossible because the cystic fluid was very thick (viscous nodules, VN). To exclude malignancy, both cytocentrifugate from WN and the smears from VN were examined. WN were treated with 1-4 sessions of conventional PEI; in VN a first PEI session was performed with the purpose of reducing the density of cystic fluid; then if cystic fluid was successfully aspirated, one or more PEI sessions were performed. Thyroid palpation, ultrasonography with nodule volume assessment, and assays for FT3, FT4, and TSH were performed 1 and 6 months after the last PEI. At month 6, 17 patients (85%) had volume reduction of more than 90% of the initial nodule volume; in 2 patients (10%) there was a reduction between 50 and 90%, and in one patient (5%) an appreciable swelling persisted after 3 injections. Nodule volume was significantly decreased below baseline at month 1 (10.9 +/- 13.3 vs 39 +/- 24 mL, p < 0.001), with a further reduction at month 6 (5 +/- 11.7 mL, p < 0.01 vs 1st month value). In most of the nodules the cystic portion completely disappeared; the residual tissue showed fibrous features, often with calcifications. In 11 patients follow-up was prolonged over the sixth month (15 +/- 4 months); the nodule volume did not significantly differ from the sixth month (3 +/- 2.2 mL) and the end of the follow-up (2.8 +/- 2.3 mL). In conclusion, we demonstrate that PEI may be a safe and effective procedure in the treatment of large TCN.

Nonfunctioning adenomas of the pituitary.

The term "nonfunctioning" pituitary adenomas (NFPA) implies heterogeneity, since it relies on a clinical definition that is mainly related to tumor mass. The first complaint is often of impaired visual function, and despite the secretion of gonadotropins, hypogonadism is frequent. NFPA must be differentiated from prolactinomas, because of the therapeutic implications, but although prolactin (PRL) levels greater than 200 ng/mL indicate prolactinoma, PRL levels of 100 to 150 ng/mL are equivocal. An assessment of gonadotropin response to gonadotropin-releasing hormone (GnRH) is of no use, but the thyrotropin-releasing hormone (TRH) test is invaluable. NFPA are monoclonal in origin, but genetic mutations data have not clarified their etiology, which remains largely unknown. Proliferating cell nuclear antigen expression is increased in recurrent adenomas, as is abnormality and overexpression of the protein kinase C family in aggressive tumors. Mutations of tumor-suppressor genes, such as the p53 and Rb genes, and of the metastasizing suppressor gene nm23, have been found in invasive tumors. Immunohistochemistry data confirm that most NFPA originate from gonadotroph cells; many NFPA are negative for all anterior pituitary hormones tested, although isolated or clustered cells are often positive for glycoprotein hormones or their subunits. Silent gonadotroph and also silent growth hormone (GH) or corticotroph tumors can constitute the anatomical basis for clinical NFPA. The heterogeneity of the immunohistochemistry data is reflected in the receptor complex of these tumors. Dopaminergic receptors have recently been visualized in vivo and there are also receptors for TRH or GnRH, since levels of alpha or beta subunits and intact gonadotropins increase after TRH or GnRH stimulation. As a result, three second-line pharmacological approaches have been tried: dopamine agonists, octreotide, and GnRH superagonists or antagonists, with tumor shrinkage of up to 11% to 20%. However, surgery should be tried first.

Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?

OBJECTIVE: A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with 'burned-out' disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. DESIGN: Longitudinal prospective study of previously untreated patients with GD. PATIENTS: Thirty-nine consecutive patients aged 10-72 years were treated with methimazole (MMI) for 12-24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. MEASUREMENTS: Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. RESULTS: Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2 +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. CONCLUSIONS: Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.

Alcohol inhibits 11-beta-hydroxysteroid dehydrogenase activity in rat kidney and liver.

Male Wistar rats were treated with different ethanol concentrations diluted in drinking water in order to evaluate the effect of acute ethanol intoxication on 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity in liver and kidney tissue homogenates. Rats with the highest ethanol consumption (15% ethanol supplementation) showed a significant decrease in both hepatic and renal 11 beta-OHSD activity as compared to the control group (p < 0.005). In the same group, aldosterone plasma levels were significantly lower than in controls (p < 0.01), while corticosterone (B) plasma levels were slightly higher, suggesting that the increase in intrarenal B concentrations, probably related to the acute ethanol consumption, might be responsible for a nonspecific B mineralocorticoid activity.

Hormonal and immunological pattern in a patient with acquired immunodeficiency syndrome related complex and Cushing's syndrome.

A case of Cushing's syndrome in a 24-yr-old homosexual with an AIDS-related complex is reported. In this patient certain symptoms common to both diseases, i.e. weakness, myalgia and muscle atrophy were accentuated, whereas other symptoms pathognomic of the human immunodeficiency virus (HIV) infection, i.e. lymphoadenopathies and weight loss, were less pronounced by the high levels of circulating adrenal steroids. Ketoconazole was administered po in order to block adrenal steroidogenesis, the drug caused a remarkable fall of cortisol serum concentrations, but was unable to modify significantly the immunological pattern of the patient. Our data suggest that changes of serum adrenal steroid levels have little effect on the immune network of patients with AIDS.

Increased spontaneous release of tumor necrosis factor-alpha/cachectin in headache patients. A possible correlation with plasma endotoxin and hypothalamic-pituitary-adrenal axis.

Tumor Necrosis Factor-alpha/cachectin (TNF-alpha/cachectin), Lipopolysaccharide (LPS), ACTH, beta-Endorphin (beta-EPH), and Cortisol (F) levels were determined in 33 Headache patients: 22 patients were affected with Migraine (M) and 11 patients with Chronic Type Tension Headache (CTTH). TNF-alpha/cachectin serum level was detected in 15 out of 22 migraneous patients and in no CTTH patients. Plasma LPS was observed in 11 out of 15 TNF-alpha/cachectin positive migraneous patients (73%) and in 3 out of 11 CTTH patients (27%). A negative correlation was observed between TNF-alpha/cachectin values and either ACTH or beta-EPH. In the group of migraneous patients the presence of serum TNF-alpha/cachectin showed a sensibility of .6 and a specificity of 1. The endocrine and immunological implications concerning these data are discussed.