Roberto Negro

The control of blood glucose in the critical diabetic patient: a neuro-fuzzy method

Conventional algorithms for regulating insulin infusion rates in those critical diabetic patients submitted to parenteral glucose and insulin infusions do not allow to approach near normal blood glucose (BG) levels since traditional control systems are not fully effective in complex nonlinear systems as BG control is. Thus, we applied fuzzy logic principles and neural network techniques to modify intravenous insulin administration rates during glucose infusion. Forty critically ill, fasted diabetic subjects submitted to glucose and potassium infusion entered the study. They were randomly assigned to two treatment regimes: in group A, insulin infusion rates were adjusted, every 4 h at any step between -1.5 and +1.5 U/h, according to a neuro-fuzzy nomogram; in control group B, insulin infusion rates were modified according to a conventional algorithm. In group A, BG was lowered below 10 mmol/l faster than in group B (8.2+/-0.7 vs. 13+/-1.8 h, P<.02). Mean BG was 7.8+/-0.2 in group A and 10.6+/-0.3 mmol/l in group B (P<.00001). BG values below 4.4 mmol/l were: A=5.8% and B=10.2%. BG values lower than 2.5 mmol/l had never been observed. In conclusion, the neuro-fuzzy control system is effective in improving the BG control in critical diabetic patients without increasing either the number of BG determinations or the risk of hypoglycemia.

Laser ablation is more effective for spongiform than solid thyroid nodules. A 4-year retrospective follow-up study

Abstract Purpose: Laser ablation (LA) is used as therapeutic modality for reducing the volume of large benign thyroid nodules. The aim of this retrospective study was to assess the efficacy of LA therapy in patients with benign non-functioning thyroid nodules in a 4-year follow-up and evaluate whether different compactness of nodules may influence the final shrinkage. Patients and methods: Fifty-six euthyroid patients (42 females; mean age 54.7 ± 11.7 years) with benign cold thyroid solitary nodules or a dominant nodule within a multinodular goitre underwent LA between July 2009 and March 2012. Nodule volume, thyroid function test and ultrasound were monitored at baseline, and at 3, 6 and 12 months after the procedure, then annually. Results: With a mean baseline volume of 15.7 ± 11.7 mL, nodule volume decreased by 55.5% (6.5 ± 5.7 mL) 4 years after LA (p < .01). Nodules had a significant decrease at 3 and 6 months, thereafter they remained stable, with an insignificant tendency to re-growth at 48 months. Thyroid functions and antibodies were unchanged throughout the follow-up. When dividing nodules into solid and spongiform, the former decreased at 6 months, remained stable up to 24 months, but showed a non-significant tendency to increase thereafter. Spongiform nodules progressively decreased up to 48 months. The difference in nodules’ reduction between solid and spongiform nodules was significant from 3 months (p = .04) and became even more significant up to 48 months (p = .001). Conclusions: The LA technique succeeded in reducing thyroid nodules by about 50% at 4 years, but was more effective for spongiform than solid nodules.

Thyroid Dysfunction and Pregnancy: Where Are We Five Years Later?

This issue of the JCEM presents new guidelines for addressing thyroid dysfunction during pregnancy and the postpartum period (1). These guidelines follow on those published 5 yr ago, highlighting the importance of this topic and reflecting the knowledge gained in the last few years. The text discusses and gives recommendations related to maternal and fetal aspects of hypothyroidism, hyperthyroidism, autoimmunity, thyroid nodules and cancer, iodine nutrition, and postpartum thyroiditis. A final paragraph is dedicated to the issue of screening for thyroid dysfunction in pregnancy. As in the previous version, the new guidelines focus attention on either the pregnant woman or the fetus; there is no doubt that in this field, we need more randomized controlled trials (RCT) to assess the obstetrical impact of thyroid disease, but also studies that evaluate long-term outcomes such as child intelligence quotient (IQ), especially in cases of maternal subclinical hypothyroidism (2). Of about 140 references in the new guidelines, 20% date from 2007 (the year the previous guidelines were published). What have these new references added, and what are the gray areas that require further investigation? The present guidelines confirm the suggestion of treating subclinical autoimmune hypothyroidism with levothyroxine (LT4) because the potential benefits from treatment outweigh the risk of potential adverse events. Association studies have yielded conflicting results regarding outcomes such as miscarriage, hypertension, placental abruption, and preterm delivery, and to date, one singlecenter RCT has demonstrated a significant reduction in obstetrical and neonatal complications when subclinically hypothyroid women are treated from the first trimester (3, 4). The panel also recommends treating antibody-negative women who have subclinical hypothyroidism. Despite the absence of relevant RCT, this recommendation seems reasonable given that independent of thyroid autoimmunity, an increased TSH level is associated with a miscarriage risk, and an elevated TSH at the beginning of pregnancy may predispose the mother to further impairment of thyroid function in the following months. “Partial replacement therapy” with LT4 is also suggested in cases of isolated hypothyroxinemia, although at the discretion of the physician. This recommendation directly leads to another point examined in the guidelines: awareness about the possible inaccuracy of serum free T4 (FT4) measurement in pregnancy. The absence of a universally accepted trimester-specific reference range (and the common absence of each single laboratory-specific reference range) is an issue that makes defining cutoff values difficult and complicates clear identification of isolated hypothyroxinemia as a clinical entity. The issue of the potential inaccuracy of FT4 dosage, other than complicating the distinction between subclinical and overt hypothyroidism, is also reported in the hyperthyroidism section, where the guidelines recommend maintaining maternal thyroid FT4 levels at the upper limit of the nonpregnant reference range. An alternative suggestion is to use total T4, or the free T4 index (“adjusted T4”), at 1.5-fold the upper limit, given that many laboratories unfortunately have definitively dismissed total T4 measurement. Regarding hyperthyroidism, the new guidelines confirm the suggestion of using propylthiouracil in the first trimester and methimazole (MMI) in the second and the third trimesters because of the increased risk of malformations associated with the use of MMI [further confirmed by a very recent paper published in the JCEM (5)]. Like the American Thyroid Association (ATA)-American Association of Clinical Endocrinologists (AACE) guide-

Percutaneous Ethanol Injection in Combination with Laser Ablation for a 100 ml Partially Cystic Thyroid Nodule

Until nonsurgical techniques like laser ablation (LA) or radiofrequency became available, patients suffering from large nodules with compressive symptoms were addressed to surgery. We describe the case of a 59-year-old woman with a large, partially cystic thyroid nodule having a volume of about 100 ml. As the patient refused surgery, despite her constant local discomfort, such large partially cystic nodule underwent several percutaneous ethanol injections (PEI) and then was submitted to LA. The combination of these two procedures allowed firstly complete disappearance of the cystic component and secondly a significant reduction of thyroid nodule, which finally measured 17 ml in volume (82% reduction compared to baseline). This case demonstrates that even in very large partially cystic nodules LA preceded by PEI represents a valid alternative to surgery.

Outcome, Pain Perception, and Health-Related Quality of Life in Patients Submitted to Percutaneous Ethanol Injection for Simple Thyroid Cysts

Thyroid cysts are usually benign lesions that when voluminous may induce cosmetic concerns or local discomfort. Percutaneous ethanol injection (PEI) has been demonstrated to be effective for shrinkage of such cysts. In this retrospective study, we evaluated the efficacy, pain perception, and health-related quality of life (HRQL) in patients submitted to PEI for pure cystic lesions. We reviewed the data of 101 patients who underwent ≤3 PEI. In the whole group of patients, the volume reduction was 66% after the first, 74.4% after the second, and 79.4% after the third PEI treatment. 55.4% had a cystic volume ≤ 10 ml; 85.7% of cysts ≤ 10 ml were cured by just one PEI. The number of PEI was significantly higher in the >30.0 ml group; this latter group obtained the smallest percent reduction versus baseline after the first PEI when compared with smaller cysts. The sensation of pain reported during PEI was absent in 78.3% of cases, and HRQL significantly improved from pre- to the posttreatment. PEI is a safe and effective technique for pure cystic lesions. In addition, HRQL significantly improves, providing a further support for this procedure.

Ultrasound Risk Categories for Thyroid Nodules and Cytology Results: A Single Institution’s Experience after the Adoption of the 2016 Update of Medical Guidelines by the American Association of Clinical Endocrinologists and Associazione Medici Endocrinologi

Objectives In 2016, the American Association of Clinical Endocrinologists (AACE) and Associazione Medici Endocrinologi (AME) released updated guidelines for the diagnosis and management of thyroid nodules. The aim of this study was to evaluate the AACE/AME recommendations for FNA in clinical practice, by comparing the (US) stratification risk and indications for FNA with cytologic results. Methods From May to December 2016, we collected the cytologic results from FNAs of nodules that were classified using a three-tier US category system (low, intermediate, and high risk). Results We obtained 859 FNAs from 598 patients: 341 (39.7%) from low, 489 (56.9%) from intermediate, and 29 (3.4%) from high risk nodules. Of these, 88.5% and 74.9% of low and intermediate risk nodules, respectively, were cytologically benign, whereas 84.6% of high risk nodules had a moderate-to-elevated risk of malignancy or were malignant. If FNAs had been limited to intermediate risk nodules >20 mm, we would have missed 13/17 (76.5%) nodules that had moderate-to-elevated risk of malignancy or were malignant (11/13 were malignant based on histology). Conclusions A nonnegligible number of cytologically malignant nodules or nodules that were suspected to be malignant would be missed if intermediate US risk nodules <20 mm were not biopsied.