Ana Chico

Cushing's disease and pregnancy: Report of six cases

We describe six pregnancies in five patients with Cushings disease --four had undergone transsphenoidal surgery, with improvement but no cure of their hypercortisolism; the other woman became pregnant during initial work up. At conception, none of the patients were receiving specific treatment for hypercortisolism. Mean free urinary cortisol (FUC) prior to pregnancy was 430 nmol/24 h (normal range: 51-280). In two patients, FUC throughout pregnancy increased significantly, but no clinical progression was observed. FUC measured in 20 healthy pregnant women was found to rise above the normal non-pregnant range ( < 280 nmol/24 h) in the second (mean +/- 2 S.D. = 463 +/- 256 nmol/24 h; P < 0.01) and third trimester (424 +/- 210 nmol/24 h; P < 0.05). However, in the Cushing patients values were higher. Two pregnancies ended in spontaneous abortions, one resulted in an ectopic pregnancy, and the remaining three were followed to term of which one developed third trimester gestational diabetes, and her baby developed neonatal sepsis which resolved uneventfully. We conclude that despite high abortion and ectopic pregnancy rates, a remarkably uneventful and uncomplicated outcome with no clinical progression of cushingoid symptoms, was observed in two of the three pregnancies followed to term, despite significant increases in FUC.

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Abstract.Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.

Glycemic control and perinatal outcomes of pregnancies complicated by type 1 diabetes: influence of continuous subcutaneous insulin infusion and lispro insulin.

AIMS This study compared glycemic control and maternal and fetal outcomes in pregnant women with type 1 diabetes mellitus (T1DM) treated with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) using regular (RI) or lispro (LP) insulin. METHODS Three hundred fifteen consecutive singleton pregnancies of T1DM women using the same insulin program since before pregnancy (196 MDI with NPH + RI, 16 MDI with NPH + LP, 44 CSII with RI, 59 CSII with LP) were studied. Variables of glycemic control assessed included glycated hemoglobin, mean blood glucose (MBG), and insulin doses in each trimester, diabetic ketoacidosis, and hypoglycemic comas. Variables of pregnancy outcome included miscarriage, preterm birth, large or small for gestational age (LGA or SGA, respectively) newborns, and perinatal mortality. Multiple linear regression and logistic regression analysis were used. RESULTS Groups differed in baseline and glycemic control but not in maternal or fetal outcomes. In multivariate analysis, LP was associated with higher second trimester MBG and lower rate of hypoglycemic coma, CSII with higher third trimester MBG, and CSII + LP with lower insulin requirements and lower rate of hypoglycemic coma. As to pregnancy outcomes, LP was associated with lower risk of preterm birth and higher risk of SGA, CSII with lower risk of SGA and higher risk of LGA and perinatal mortality, and CSII + LP with higher risk of miscarriage. CONCLUSIONS Pregnant women with T1DM using LP and/or CSII had different characteristics. LP with or without CSII was independently associated with fewer hypoglycemic comas, whereas impact of LP/CSII on the fetus had a favorable or an unfavorable influence depending on the specific outcome.

Silent myocardial ischemia is associated with autonomic neuropathy and other cardiovascular risk factors in type 1 and type 2 diabetic subjects, especially in those with microalbuminuria

The prevalence of silent myocardial ischemia (SMI) seems to be above average in diabetic subjects. As routine screening is costly, identifying high-risk populations is mandatory. This study aimed to estimate the prevalence of SMI in diabetic subjects and in controls and to define the diabetic population at risk. We studied 353 asymptomatic caucasian subjects (217 with diabetes and 136 controls matched by age, sex, and cardiovascular risk factors) with normal resting ECG. The diabetic group included 39 type 1 and 178 type 2 diabetics (age 57±11 yr, 162 males/55 females). Subjects performed the Treadmill Test (TT) and, when abnormal, underwent single-photon emission computed tomography (SPECT) with exercise testing or dipyridamole injection. Coronary angiography was performed if the SPECT was suggestive of ischemia. TT was positive in 16 (8.5%) diabetics: 3 with type 1 and 13 with type 2. No controls had positive TT. SPECT was performed in 13 subjects and was positive in 10; angiography was performed in 7 and identified significant lesions in all cases. Patients with SMI were older and had a higher prevalence of autonomic neuropathy, hypertension, and dyslipidemia than those without. Microalbuminuria was also higher in the SMI group (613±211 vs 72±245 mg/d; p<0.05). We conclude that diabetic patients aged over 60 with autonomic neuropathy and other cardiovascular risk factors should be screened for the presence of SMI especially if they have increased microalbuminuria.

ProAct Study: New Features of Insulin Pumps Improve Diabetes Management and Glycemic Control in Patients after Transition of Continuous Subcutaneous Insulin Infusion Systems

BACKGROUND Continuous subcutaneous insulin infusion (CSII) patients experience switches of pump systems on a regular basis. We investigated the impact of transition from older pumps to the Accu-Chek(®) Combo system (Roche Diagnostics Deutschland GmbH, Mannheim, Germany) on a patients glycemic control and diabetes management. PATIENTS AND METHODS In total, 299 patients (172 female, 127 male; mean±SD age, 39.4±15.2 years; CSII duration, 7.0±5.2 years) were enrolled by 61 European sites into this uncontrolled prospective trial. Glycemic control, safety, and diabetes management parameters were measured at baseline and after 3 and 6 months. Changes from baseline were analyzed. RESULTS After transition to the new insulin pump, mean±SD hemoglobin A1c (HbA1c) values decreased from 7.8±1.1% (baseline) to 7.7±1.1% (end point). The proportion of patients with HbA1c <7.0% was slightly higher at the end of the study (29.6%) than at baseline (25.2%), whereas the proportion of patients with HbA1c >8.0% decreased (baseline, 36.2%; end point, 32.7%; P<0.05). The number of hypoglycemic episodes (blood glucose<70 mg/dL) improved slightly during the study (baseline, 40.4±34.0 events/quarter; end point, 39.2±33.9 events/quarter). Glycemic control improved significantly in the group with an initial HbA1c >8.0% (-0.46%; P<0.001) and remained solidly stable in the group with an initial HbA1c <7% (+0.04%; not significant). Short-term (<3 years) pump users (n=48) had a larger HbA1c decrease (-0.40%) than long-term (≥3 years) users (n=251) (-0.07%; P<0.05). The number of blood glucose measurements increased (3.7±1.9/day vs. 4.4±1.8/day; P<0.05), whereas the number of insulin boluses decreased (5.1±1.9/day vs. 4.6±1.5/day; P<0.05) during the study. CONCLUSIONS Transition from older pump systems to the Accu-Chek Combo system in a large patient population resulted in stable glycemic control with significant improvements in HbA1c in patients with unsatisfactory baseline HbA1c and shorter pump use. Increased frequency of self-monitoring of blood glucose and decrease of bolus frequency could suggest a more confident diabetes management and a reduced need for correction boluses.

A novel germline mutation in exon 5 of the multiple endocrine neoplasia type 1 gene

Abstract The autosomal dominant multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by neoplasia of parathyroids, anterior pituitary, and gastrointestinal and pancreatic neuroendocrine tissues. Recently the gene responsible for the MEN1 syndrome has been identified on chromosome region 11q13. Most of the described mutations are nucleotide substitutions and small deletions affecting exons 2 and 3, causing protein truncation. Only one mutation in exon 5 has been found, and this corresponds to a MEN1 sporadic case. Small insertions are also rare. We studied a MEN1 family composed of five members, two of whom were clinically affected. We found a new germline 1 basepair insertional mutation affecting the exon 5 of the MEN1 gene in the two members affected in this MEN1 family.

Molecular diagnosis of von Hippel‐Lindau disease in a kindred with a predominance of familial phaeochromocytoma

OBJECTIVE To study the presence of germline mutations in the von Hippel‐Lindau gene (vhl ) in a kindred with a predominance of familial phaeochromocytoma in order to confirm the diagnosis of von Hippel‐Lindau disease (VHLD) as well as to identify asymptomatic members.

Changes in Insulin Requirements From the Onset of Continuous Subcutaneous Insulin Infusion (CSII) Until Optimization of Glycemic Control

Aims: The aim was to evaluate changes in insulin requirements from onset of continuous subcutaneous insulin infusion (CSII) until glucose optimization in type 1 diabetes and to determine patient characteristics to be considered when CSII is implemented. Materials and methods: We retrospectively analyzed 74 type 1 diabetic patients over a follow-up of 5 months after starting CSII. Patients without a decrease in HbA1c levels at the end of follow-up were excluded. We compared total daily doses (TDD), basal/bolus distribution, basal diurnal/nocturnal proportion, number of basal segments, and HbA1c levels in relation to sex, age, body mass index (BMI), diabetes duration, and indication for CSII. Results: At follow-up, HbA1c decreased by 0.75%, TDD decreased by 18%, basal rate was 60% of TDD, and diurnal basal rate was 60% of total basal rate. Insulin requirements were higher in males and in obese patients. Female patients and patients with longer diabetes duration showed a higher percentage of basal insulin. The number of basal segments was 4.9 ± 2.9. Basal requirements were higher in the second half of the nocturnal period. The dawn phenomenon was more relevant in men. Improvements in glycemic control were more marked in younger patients, in patients with higher HbA1c, in patients using more basal segments, and in patients initiating CSII for glucose control before pregnancy. Conclusions: Sex, diabetes duration, and BMI should be considered when initiating CSII. Our findings may help clinicians in clinical decision making regarding CSII therapy.

Lipoprotein(a) concentrations and non-insulin-dependent diabetes mellitus: relationship to glycaemic control and diabetic complications

UNLABELLED The aim of our study was to determine the lipoprotein(a) (Lp(a)) levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate Lp(a) concentrations in relation to glycaemic control and diabetic complications. We evaluate in a cross-sectional study a total of 103 NIDDM patients (52 males and 51 females; mean age of 62.5 years; mean of diabetes duration: 12 years) referred to our hospital because of poor glycaemic control, and a group of 108 non-diabetic subjects (57 males and 51 females). RESULTS mean Lp(a) concentration did not significantly differ between NIDDM patients and non-diabetic subjects (11.1 +/- 14 vs. 16.2 +/- 14 mg/dl). The distribution of Lp(a) levels was highly skewed towards the lower levels in both groups, being over 30 mg/dl in only 6% of NIDDM patients and 12% of controls. Patients with Lp(a) levels over 10 mg/dl had lower haemoglobin Alc (HbA1c) than patients with Lp(a) levels over 10 mg/dl (8.5% vs. 10.4%; P < 0.01). Lp(a) concentration was positively correlated with body mass index (BMI) (P < 0.05) and HbA1c (P < 0.05). No association was found between Lp(a) and sex, age, other lipidic parameters, microalbuminuria, type of treatment and presence of cardiovascular disease. These findings may suggest that glycaemic control could have a modulatory role on Lp(a) concentration in NIDDM patients. In this study, diabetic complications did not seem to be associated with higher Lp(a) concentrations.

Molecular Pathology of Multiple Endocrine Neoplasia Type I: Two Novel Germline Mutation; and Updated Classification of Mutations Affecting MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined development of tumors in several endocrine glands and other tissues. The MEN1 gene was recently identified and isolated by positional cloning. This gene was screened in two unrelated MEN1 Spanish kindreds (with four affected members and seven asymptomatic members) using single-strand conformation polymorphism, DNA sequencing, and restriction enzyme analysis. Two novel germline mutations were identified: a missense in exon 2 (H139R) and a splice-site in intron 9 (1461-2A>C). These findings allowed us to identify the MEN1 carriers among the seven asymptomatic members analyzed. An updated review of the mutations and polymorphisms found in the analysis of the MEN1 gene is provided. The report of all germline mutations causing MEN1 and easy access to this updated information are both of special diagnostic interest, because this greatly facilitates the task of attributing the disorder to a specific mutation found in a given MEN1 family. This is especially helpful in the critical differentiation of missense mutations from nonsynonymous polymorphisms that fit the pattern of segregation of the disease, but do not cause it.