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Diabetes & Metabolism - In Press.Proof corrected by the author Available online since samedi 23 decembre 2017

Glucocorticoid (GC) therapy is the most common cause of adrenal insufficiency (AI). The real prevalence of AI after GC is unknown but it could involve more than 30% of patients. Some gene variation has been associated with the variability of hypothalamic-pituitary-adrenal (HPA) axis and this issue could contribute to the individual variation of adrenal function after GC treatment. Symptoms and signs of AI are nonspecific and frequently the diagnosis is delayed. Dosage, duration of treatment, administration route and serum cortisol value are not completely useful to predict AI. Clinical estimation of HPA suppression is difficult and biochemical testing is needed to confirm the diagnosis of AI. The different tapering regimens are based on a very low quality of evidence and considering the sizable individual variation, it is improbable that future research will find a secure GC tapering schedule for all patients. The aim of this review is to address the most important aspects in management of GC withdrawal in light of current knowledge.

Background Neuroendocrine tumors (NETs) are an unusual family of neoplasms with a wide and complex spectrum of clinical behavior. Here, we present the first report of a National Cancer Registry of gastroenteropancreatic neuroendocrine tumors from a Southern European country. Patients and methods Data was provided online at www.retegep.net by participating centers and assessed for internal consistency by external independent reviewers. Results The study cohort comprised 907 tumors. The most common tumor types were carcinoids (55%), pancreatic nonfunctional tumors (20%), metastatic NETs of unknown primary (9%), insulinomas (8%) and gastrinomas (4%). Forty-four percent presented with distant disease at diagnosis, most often those from small intestine (65%), colon (48%), rectum (40%) and pancreas (38%), being most unusual in appendix primaries (1.3%). Stage at diagnosis varied significantly according to sex, localization of primary tumor, tumor type and grade. Overall 5-year survival was 75.4% (95% confidence interval 71.3% to 79.5%) and was significantly greater in women, younger patients and patients with hormonal syndrome and early stage or lower grade tumors. Prognosis also differed according to tumor type and primary tumor site. However, stage and Ki-67 index were the only independent predictors for survival. Conclusion This national database reveals relevant information regarding epidemiology, current clinical practices and prognosis of NETs in Spain, providing valuable insights that may contribute to understand regional disparities in the incidence, patterns of care and survival of this heterogeneous disease across different continents and countries.

El Grupo de Trabajo de Neuroendocrinologia de la Sociedad Espanola de Endocrinologia y Nutricion (SEEN) ha desarrollado y potenciado en los ultimos anos diferentes subgrupos. El Registro Espanol de Acromegalia (REA) ha continuado su labor incrementando los registros, lo que ha permitido aumentar los datos de morbilidad y mortalidad de esta enfermedad. Igualmente, en el presente ano se ha procedido a la creacion de una nueva aplicacion online con mejoras, tanto en su aspecto formal como de actualizacion de los datos recogidos. El Registro Espanol de Tumores Gastroenteropancreaticos (RETEGEP), en el que participan diferentes especialidades medicas, ha experimentado un aumento significativo de registros, aunque desde la endocrinologia el numero de nuevos casos se ha estabilizado. Por otra parte, se ha llevado a cabo la creacion del Grupo Espanol de Tumores Neuroendocrinos, bajo los auspicios de la Sociedad Espanola de Oncologia Medica y la propia SEEN. El Registro de Neoplasias Endocrinas Multiples tipo 1, por el contrario, se halla en una trayectoria dificil, que obliga a una reflexion de su futuro. El subgrupo de trabajo del sindrome de Cushing, que tambien pertenece al Grupo de Trabajo de Neuroendocrinologia, ha tomado en el ultimo ano nuevo impulso, con estructuracion tanto de su composicion como de sus objetivos. Por ultimo, el Grupo de Trabajo de Neuroendocrinologia de la SEEN ha desarrollado, en el presente ano, la elaboracion de guias clinicas del diagnostico y el tratamiento del prolactinoma y de otros estados de hiperprolactinemia, de la acromegalia y de la deficiencia de hormona de crecimiento del adulto, que vieron la luz en el primer numero de esta revista del ano 2005. Se estan ultimando las guias clinicas de 3 nuevas enfermedades, y se estan en proyecto otras tantas para el curso proximo. El grupo se halla abierto al apoyo y la colaboracion de todos los socios de la SEEN.

Concepto. Cuadro clinico derivado de la exposicion cronica y aumentada a los glucocorticoides. Etiopatogenia. La ACTH plasmatica permite categorizar al sindrome de Cushing en dependiente, bien de origen hipofisario o ectopico, o bien independiente de origen primario suprarrenal. Manifestaciones clinicas. Sindrome de Cushing y sindrome metabolico. Muchos de los signos y sintomas del sindrome de Cushing son muy frecuentes en la poblacion general. Ello implica que con frecuencia se plantee el diagnostico del sindrome y se deba realizar el despistaje de este. Diagnostico. El diagnostico del sindrome de Cushing obliga a la aplicacion de diversos pasos de forma gradual. Tras el despistaje y el diagnostico sindromico, se realizan las pruebas para determinar la etiologia del sindrome. Con relativa frecuencia las pruebas no son concluyentes y esto obliga a efectuar pruebas mas especificas. Tecnicas de imagen. La resonancia es la tecnica de imagen de eleccion en la caracterizacion morfologica del sindrome de Cushing de origen hipofisario. La tomografia axial computarizada es la exploracion de imagen para la visualizacion de las glandulas adrenales. Tratamiento del sindrome de Cushing. La cirugia hipofisaria es la tecnica de eleccion en el sindrome de Cushing de origen hipofisario. Sin embargo, el cuadro presenta con frecuencia situaciones de persistencia o recidiva de la enfermedad. La patologia adrenal primaria tiene en la mayor parte de los casos una indicacion de cirugia adrenal. Se revisa, asimismo, el papel de la radioterapia hipofisaria, y el tratamiento medico.

Although lipoprotein abnormalities of the nephrotic syndrome are assumed to be related to the presence of proteinuria, this topic has not been investigated extensively. We measured lipoproteins from 19 nonuremic patients during and after remission of the nephrotic syndrome in an effort to determine the extent of their putative atherogenicity. As expected, disturbances involved primarily the apoprotein B-containing lipoproteins. No patient showed serum lipoprotein(a) [Lp(a)] < 300 mg/L during the acute phase. Lp(a) concentrations correlated significantly with those of apoprotein B, and both values decreased dramatically with the remission of the nephrotic syndrome. Surprisingly, despite the resolution of proteinuria, concentrations of intermediate-density lipoproteins and Lp(a) remained above normal in hypertriglyceridemic patients, suggesting a residual effect of nephrosis in the overall lipoprotein transport. Accumulation of atherogenic remnants should be considered a characteristic of the hyperlipidemia of the nephrotic syndrome, and aggressive treatment to reduce proteinuria is mandatory.

The reported efficacy of treatments for acromegaly varies depending on reference centers and national registries. The aim of this study was to describe clinical management of this disease and to assess the efficacy of treatments used in standard clinical practice.An epidemiological, observational, longitudinal, multicenter study was performed in adult patients with newly diagnosed acromegaly (n = 74) seen by 38 Spanish endocrinologists who collected during routine clinic visits data on disease treatment and control during 2 years of follow-up.Pituitary surgery and treatment with somatostatin analogs were the first choice therapies in 76% and 24% of patients respectively, with no differences related to tumor size. Surgery achieved disease control in 27% of operated patients. After surgery failure, the preferred therapeutic option were somatostatin analogs, which normalized insulin-like growth factor-1(IGF-I) in 52% of patients and achieved disease control criteria in more than 40% of patients. At the end of follow-up, normal IGF-I levels were found in 63% and 53% of patients with microadenomas and macroadenomas respectively. Only 19% of patients with macroadenoma met disease control criteria without requiring drug treatment, which was required by 85% of them at some time during follow-up.Surgery is the preferred initial treatment for patients with acromegaly, regardless of tumor size. Treatment efficacy in actual clinical practice is far from the success rates reported by reference centers.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

The aims of this study are to identify prognostic factors of differentiated thyroid carcinoma and to validate the application of prognostic classifications obtained by others studies to another population.The survival of 208 patients with differentiated thyroid carcinoma (129 papillary and 79 follicular carcinoma) was calculated by the Kaplan-Meier method. The mean follow-up was 7.5 years (1-17.7). Cox-proportional hazard model was used for variables influencing on survival (Mantel-Cox method). In addition, the EORTC, AGES, AJC, AMES and DeGroot classifications were tested.The independent prognostic factors identified were patient age60 years, tumor size6 cm and the presence of distant metastases. The absence of poor prognostic factors defined the low risk group (153 patients, survival 97% at 17.7 years of follow-up). The application of the other prognostic classifications differentiated several risk groups not in accordance with those obtained in the initial population.In this series of patients with thyroid carcinoma the main prognostic factors were age, tumor size and the presence of distant metastases. However, there are pitfalls in applying the prognostic classifications of published studies to another population.

The parathyrine related protein (PTH-RP) is very similar, both in structure and in function, to the PTH and is considered as a mediator in humoral hypercalcemia in cancer. The aim of this study was to know the clinical value of PTH-RP measurement.Serum PTH-RP concentrations were studied in 22 healthy subjects, 13 patients with primary hyperparathyroidism, 9 patients with solid neoplasms and normocalcemia, 26 patients with solid neoplasms and hypercalcemia and 4 patients with hematologic neoplasms and hypercalcemia. The PTH-RP was quantified by a competitive radioimmunoassay technique using a specific antibody of the PTH-RP 1-40 fragment. Intact parathyrine (i-PTH) was quantified by an IRMA method using 2 polyclonal antibodies (INCSTAR).Fifteen (68%) of the healthy controls presented undetectable serum PTH-RP concentrations. The serum PTH-RP concentration was normal in all those patients with hyperparathyroidism. Elevated serum PTH-RP values were not found in patients with solid neoplasms and normocalcemia or in those with hematologic neoplasms and hypercalcemia. High values of PTH-RP were observed in 8 out of 9 (88%) of the patients with solid neoplasms and hypercalcemia with bone metastasis and in 7 out of 11 (63%) of the patients with bone involvement.Serum parathyrine-related protein was found to be high in a large proportion of patients with solid neoplasms and hypercalcemia. Serum PTH-RP determination is useful in the clinical investigation of patients with hypercalcemia. Even in patients with bone metastasis, hypercalcemia may have a humoral background.

We studied 355 patients with Grave's disease to characterize transient hypothyroidism and its prognostic value following 131I therapy.The patients received therapeutic 131I treatment as follows: 333 received a dose10 mCi (6.6 +/- 1.9 mCi) and 22 received a dose10 mCi (12.8 +/- 2.9 mCi). Diagnosis of transient hypothyroidism was based on low T4, regardless of TSH within the first year after 131I followed by recovery of T4 and normal TSH.After administration of10 mCi 131I, 40 patients developed transient hypothyroidism during the first year; transient hypothyroidism was symptomatic in 15. There was no transient hypothyroidism after high doses (10 mCi) of 131I. Iodine-131 uptake70% at 2 hr before treatment was a risk factor for developing transient hypothyroidism (Odds ratio 2.8, 95% confidence interval 0.9-9.4). At diagnosis of transient hypothyroidism, basal TSH levels were high (51%), normal (35%) or low (14%); therefore, the transient hypothyroidism was not centralized. If hypothyroidism developed during the first 6 mo after basal TSH45 mU/liter ruled out transient hypothyroidism.The development of transient hypothyroidism and its hormonal pattern did not influence long-term thyroid function. Since no prognostic factors reliably predicted transient hypothyroidism before 131I or at the time of diagnosis, if hypothyroidism appears within the first months after 131I, the reevaluation of thyroid function later is warranted to avoid unnecessary chronic replacement therapy.

The usefulness of the concentration of salivary 17-hydroxyprogesterone (17-OHPRG) in the diagnosis of congenital adrenal hyperplasia by partial deficiency of 21-hydroxylase was studied. As a biologic medium, saliva has important advantages such as facility in sample collection and the avoidance of the stress of venous puncture.Salivary 17-OHPRG was measured by a direct solid phase radioimmunoassay. A control group made up of 28 males and 26 females was studied. The group of patients included 30 women, 10 of them with a previous diagnosis of partial deficit of 21-hydroxylase. Basal values were established in the control group and were compared with those found in the patients in whom a stimulation test with adrenocorticotropin (ACTH) was performed collecting blood and saliva samples.The levels of 17-OHPRG observed in the patients with partial deficiency of 21-hydroxylase were significantly higher than those found in the control group and in the group with hirsutism, including both basal levels and those following stimulation. The correlation between the values found in blood and saliva was very significant.The measure of 17-hydroxyprogesterone in saliva by a method of direct radioimmunoassay is a valid alternative test to serum measure in both basal conditions and following a stimulation test.

Forty-two patients with the nephrotic syndrome were grouped according to the absence or presence of renal failure and/or diabetes mellitus. All patients had a similar degree of hypoalbuminemia and urinary protein losses. A lipid and apoprotein pattern was generated in serum and ultracentrifugally isolated lipoproteins. Low-density lipoprotein composition was essentially normal in uremic patients while in the other patients with the nephrotic syndrome, a considerable lipid enrichment was noted. The very-low-density lipoprotein content in lipids was uniformly increased in nephrotic patients irrespective of the presence of complications. High-density lipoprotein cholesterol and serum apolipoprotein A I and E concentration was significantly reduced in uremic patients with respect to normal subjects and to the other groups considered. Serum apolipoprotein A II and B levels were also decreased in uremics. All patients had increased serum apoprotein C II and C III concentration. We conclude that diabetes mellitus does not affect the pattern of hyperlipoproteinemia of nephrotic syndrome while the characteristic lipoprotein and apoprotein pattern of uremia is present irrespective of nephrosis in uremic, nondiabetic patients.

Sixteen cases of newly diagnosed Addison disease were studied by CT scan. An initial diagnosis was performed according to the clinical data of each patient, and a second diagnosis after examining the abdominal CT scan. According to the second diagnosis there were six patients with primary adrenal failure of probable autoimmune origin, six tuberculosis, two metastatic, one undetermined and one hemorrhagic. The second diagnosis coincided with the first one in 10 cases (62.5%), but was different in six cases (37.5%). Information obtained by CT scan modified the therapeutic attitude in 4 cases (25%). The main morphologic patterns of adrenal glands in CT scan (atrophy, calcification and enlargement) are commented as well as the importance of CT scan in the study of the more common etiologies of Addison's disease (tuberculosis, autoimmune, neoplastic metastasis and hemorrhage). It is concluded that the information obtained by CT scan is important in the etiological diagnosis of Addison disease and it is advised to perform it in all newly diagnosed cases.

The effect of lovastatin on the hyperlipidemia induced in rats with experimental nephrotic syndrome was investigated; toxicity and the effects on common blood chemistry parameters were also assessed. Hyperlipoproteinemia in this particular model is associated with an increase in hepatic synthesis of lipoproteins, and treatment with lovastatin could be the most suitable, since the drug inhibits cellular cholesterol synthesis. Lovastatin treatment resulted in a considerable reduction in plasma cholesterol and triglyceride levels. The decrease in cholesterol levels with treatment was mainly confined to the low-density lipoproteins (LDL) although there was a reduction in the nephrotic-syndrome-induced incremental level of high-density lipoprotein cholesterol. Other lipoprotein fractions were unaffected by lovastatin. LDL apoprotein B was increased in both groups of rats, but to a lesser degree in the lovastatin-treated group, suggesting a double effect, inhibition of both, cholesterol and apoprotein synthesis. Both groups of rats showed a certain degree of renal impairment as shown by significant elevations in plasma urea and creatinine levels. Hepatic damage was also observed, chemically and microscopically, in both groups of rats, being more pronounced in those rats treated with lovastatin in which a 50% mortality ensued after 2 weeks of treatment. At the dosage used this may have some implications in its therapeutic use in certain conditions.

With puromycin aminonucleoside-induced nephrotic syndrome (NS) in rats, twofold elevated levels of lipoproteins were observed. These levels were not related to proteinuria or to plasma albumin levels. Ultrastructural lesions induced in the kidneys by puromycin aminonucleoside were consistent with NS, while there was little or no hepatic involvement. Apolipoprotein B (apo B) kinetic measurements using homologous 125I-labeled low density lipoproteins (LDL) demonstrated a higher synthetic rate in nephrotic rats relative to controls (6.18 +/- 1.86 micrograms x g-1 x d-1 v 3.94 +/- 0.66 micrograms x g-1 x d-1 respectively, P less than .005), while the fractional catabolic rate was only marginally reduced (1.64 +/- 0.28 pools x day-1 in NS v 1.83 +/- 0.37 pools x day-1 in controls, P less than 0.4). These results indicate that in rats with experimentally induced NS, the expanded apo B-LDL pool results from increased synthesis of this apoprotein while no significant role can be ascribed to alterations in its catabolism. These data are consistent with our preliminary findings in NS in humans.

Serum gonadal hormones, gonadotrophins and zinc levels were studied in thirteen men aged 29-62 yr with chronic renal failure undergoing haemodialysis. All patients had decreased libido and impotence. Serum testosterone levels in patients (18.5 +/- 1.3 (SEM) nmol/l) were significantly lower (p less than 0.05) than in the control group (24.1 +/- 2.2 (SEM) nmol/l) although salivary testosterone levels were strictly within the normal range. Mean serum 17-beta-oestradiol and luteinizing hormone levels (0.19 +/- 0.03 (SEM) nmol/l, and 57.4 +/- 13.1 (SEM) IU/l, respectively) were significantly higher (p less than 0.05 and p less than 0.005, respectively) than in the control group (0.11 +/- 0.02 (SEM) nmol/l and 14.8 +/- 1.9 (SEM) IU/l, respectively). Mean progesterone and follicle-stimulating hormone levels in patients were not significantly different from those of control subjects. Mean prolactin values in patients (1,019 +/- 285 (SEM) mIU/l) were significantly higher (p less than 0.01) than in the control group (211 +/- 24 (SEM) mIU/l). Serum prolactin levels in five patients were extremely high (above 1,200 mIU/l). There was no statistically significant difference in serum zinc levels between patients and controls. As salivary testosterone is normal, it seems that hyperprolactinaemia and raised serum 17-beta-oestradiol levels may be responsible, at least in part, for sexual dysfunction in male patients with chronic renal failure receiving haemodialysis.

Four cases of women with biliary infection caused by Haemophilus influenzae type b are reported. The patients had underlying benign or malignant disease of the biliary tract. Haemophilus influenzae was isolated in pure culture from bile in all cases and also from blood cultures in three cases. The clinical condition of three patients was not severe, two of them recovering after surgery without antibiotic therapy. The fourth patient died of septic shock which occurred after liver biopsy. The frequency of biliary infections caused by Haemophilus influenzae has probably been underestimated because of the special nutritional requirements of this microorganism. The route by which Haemophilus influenzae reaches the biliary tract is not fully understood.

Plasmatic levels of cholesterol and triglycerides in each lipoprotein fraction, ultracentrifugally isolated, as well as the plasma apoprotein A and B levels, were assessed in 13 healthy male body-builders. A dietary interview was performed in order to valorate the nutritional status of these subjects. The diet in body-builders was substantially different from that of the control group. The intake calories, proteins, total lipids and cholesterol was significantly higher; the intake of saturated fatty acids was significantly (p

We report two cases of ascending muscular weakness progressing to areflexic quadriplegia caused by severe derangement of potassium homeostasis. The first patient presented with a 17-alpha-hydroxylase deficiency and severe hypokalemia. The second case had primary adrenocortical deficiency (Addison's disease) and extreme hyperkalemia. Complete recovery ensued after correction of the metabolic disorder in both cases. The role of potassium in the pathophysiology of neuromuscular excitation is discussed. We conclude that when neuromyopathy is present, metabolic causes should be considered and the serum potassium determined.