Simple meal announcements and pramlintide delivery versus carbohydrate counting in type 1 diabetes with automated fast-acting insulin aspart delivery: a randomised crossover trial in Montreal, Canada.

BACKGROUND: In type 1 diabetes, carbohydrate counting is the standard of care to determine prandial insulin needs, but it can negatively affect quality of life. We developed a novel insulin-and-pramlintide closed-loop system that replaces carbohydrate counting with simple meal announcements. METHODS: We performed a randomised crossover trial assessing 14 days of (1) insulin-and-pramlintide closed-loop system with simple meal announcements, (2) insulin-and-placebo closed-loop system with carbohydrate counting, and (3) insulin-and-placebo closed-loop system with simple meal announcements. Participants were recruited at McGill University Health Centre (Montreal, QC, Canada). Eligible participants were adults (aged ≥18 years) and adolescents (aged 12-17 years) with type 1 diabetes for at least 1 year. Participants were randomly assigned in a 1:1:1:1:1:1 ratio to a sequence of the three interventions, with faster insulin aspart used in all interventions. Each intervention was separated by a 14-45-day wash-out period, during which participants reverted to their usual insulin. During simple meal announcement interventions, participants triggered a prandial bolus at mealtimes based on a programmed fixed meal size, whereas during carbohydrate counting interventions, participants manually entered the carbohydrate content of the meal and an algorithm calculated the prandial bolus based on insulin-to-carbohydrate ratio. Two primary comparisons were predefined: the percentage of time in range (glucose 3·9-10·0 mmol/L) with a non-inferiority margin of 6·25% (non-inferiority comparison); and the mean Emotional Burden subscale score of the Diabetes Distress Scale (superiority comparison), comparing the insulin-and-placebo system with carbohydrate counting minus the insulin-and-pramlintide system with simple meal announcements. Analyses were performed on a modified intention-to-treat basis, excluding participants who did not complete all interventions. Serious adverse events were assessed in all participants. This trial is registered on ClinicalTrials.gov, NCT04163874. FINDINGS: 32 participants were enrolled between Feb 14, 2020, and Oct 5, 2021; two participants withdrew before study completion. 30 participants were analysed, including 15 adults (nine female, mean age 39·4 years [SD 13·8]) and 15 adolescents (eight female, mean age 15·7 years [1·3]). Non-inferiority of the insulin-and-pramlintide system with simple meal announcements relative to the insulin-and-placebo system with carbohydrate counting was reached (difference -5% [95% CI -9·0 to -0·7], non-inferiority p<0·0001). No statistically significant difference was found in the mean Emotional Burden score between the insulin-and-pramlintide system with simple meal announcements and the insulin-and-placebo system with carbohydrate counting (difference 0·01 [SD 0·82], p=0·93). With the insulin-and-pramlintide system with simple meal announcements, 14 (47%) participants reported mild gastrointestinal symptoms and two (7%) reported moderate symptoms, compared with two (7%) participants reporting mild gastrointestinal symptoms on the insulin-and-placebo system with carbohydrate counting. No serious adverse events occurred. INTERPRETATION: The insulin-and-pramlintide system with simple meal announcements alleviated carbohydrate counting without degrading glucose control, although quality of life as measured by the Emotional Burden score was not improved. Longer and larger studies with this novel approach are warranted. FUNDING: Juvenile Diabetes Research Foundation.

Plurihormonal pituitary adenoma cosecreting ACTH and GH: a rare cause of Cushing's disease.

Plurihormonal pituitary adenomas are rare forms of pituitary adenomas that express more than one hormone. The most common association is with growth hormone (GH) and prolactin. Cosecretion of GH and adrenocorticotrophic hormone (ACTH) is rare with only 25 reported cases in literature. Most presented with features of GH excess, and only four presented with Cushing's disease. We report a case of a woman in her 30s with recurrent plurihormonal pituitary macroadenoma cosecreting GH and ACTH, diagnosed during workup for polycystic ovarian syndrome, and both times presenting uniquely with Cushing's disease. Biochemical testing showed GH excess and hypercortisolism. She underwent transsphenoidal surgery twice and immunohistochemistry showed positive staining for GH and ACTH on both occasions. We aim to raise more awareness of this rare type of pituitary adenoma, shed light on the importance of recognising rare presentations and highlight the necessity of rigorous follow-up given morbidity and potentially higher mortality risk.

A Case Report of Hyperestrogenism in Prader-Willi Syndrome.

OBJECTIVE: Prader-Willi syndrome (PWS) is associated with multiple endocrinopathies, including hypogonadism. The mechanism underlying hypogonadism in PWS is thought to be secondary to hypothalamic dysfunction, primary gonadal defect, or a combination of both. Here, we present a case of hyperestrogenism in PWS due to concomitant polycystic ovary syndrome (PCOS) and therapeutic considerations regarding hormone replacement therapy (HRT). CASE REPORT: An 18-year-old woman with PWS transferred to adult care from pediatrics was found to have hyperestrogenism (specifically, elevated estrone with normal estradiol levels). Additionally, she demonstrated oligomenorrhea and hyperandrogenism, meeting diagnostic criteria for PCOS. After 3 months of therapy with cyclic medroxyprogesterone alone, she developed normal withdrawal bleeding. DISCUSSION: Given the elevated estrone and normal estradiol levels, our patient's hyperestrogenism is thought to be a direct result of her hyperandrogenism due to peripheral conversion. Prolonged exposure to unopposed estrogen is an established risk factor for endometrial cancer development in PCOS; thus, this was taken into account regarding her HRT, and she was treated with cyclic progesterone alone. CONCLUSION: Women with PWS are typically treated with combined estrogen and progesterone HRT; however, our case, a unique presentation of PCOS in PWS, demonstrated the importance of tailoring HRT to a patient's specific needs.

A fully artificial pancreas versus a hybrid artificial pancreas for type 1 diabetes: a single-centre, open-label, randomised controlled, crossover, non-inferiority trial.

BACKGROUND: For people with type 1 diabetes, there is currently no automated insulin delivery system that does not require meal input. We aimed to assess the efficacy of a novel faster-acting insulin aspart (Fiasp) plus pramlintide fully closed-loop system that does not require meal input. METHODS: In this open-label, randomised controlled, crossover, non-inferiority trial we compared the Fiasp (Novo Nordisk, Bagsværd, Denmark) plus pramlintide closed-loop system with no meal input (fully artificial pancreas) and the Fiasp-alone closed-loop system with precise carbohydrate counting (hybrid artificial pancreas). Adults (≥18 years) who had a clinical diagnosis of type 1 diabetes for at least 12 months, had glycated haemoglobin 12% or lower, and had been on insulin pump therapy for at least 6 months were enrolled at McGill University Health Centre, Montreal, QC, Canada. The Fiasp plus pramlintide fully closed-loop system delivered pramlintide in a basal-bolus manner with a fixed ratio of 10 µg:U relative to insulin. A research staff member counted the carbohydrate content of meals to input in the hybrid closed-loop system. Participants completed the two full-day crossover interventions in a random order allocated by a computer-generated code implementing a blocked randomisation (block size of four). The primary outcome was the percentage of time spent within the glucose target range (3·9-10·0 mmol/L), with a 6% non-inferiority margin, assessed in all participants who completed both interventions. This trial is registered with ClinicalTrials.gov, NCT03800875. FINDINGS: Between Feb 8, 2019, and Sept 19, 2020, we enrolled 28 adults, of whom 24 completed both interventions and were included in analyses. The percentage of time spent in the target range was 74·3% (IQR 61·5-82·8) with the fully closed-loop system versus 78·1% (66·3-87·5) with the hybrid Fiasp-alone closed-loop system (paired difference 2·6%, 95% CI -2·4 to 12·2; non-inferiority p=0·28). Eight (33%) participants had at least one hypoglycaemia event (<3·3 mmol/L) with the fully closed-loop system compared with 14 (58%) participants with the hybrid closed-loop system (2200-2200 h). Non-mild nausea was reported by three (13%) participants and non-mild bloating by one (4%) participant with the fully closed-loop system compared with zero participants with the hybrid closed-loop system. INTERPRETATION: The Fiasp plus pramlintide fully closed-loop system was not non-inferior to the Fiasp-alone hybrid closed-loop system for the overall percentage of time in the glucose target range. However, participants still spent a high percentage of time within the target range with the fully-closed loop system. Outpatient studies comparing the fully closed-loop hybrid systems with patient-estimated, rather than precise, carbohydrate counting are warranted. FUNDING: Diabetes Canada.

Fully Automated Artificial Pancreas for Adults With Type 1 Diabetes Using Multiple Hormones: Exploratory Experiments.

OBJECTIVES: A fully automated insulin-pramlintide-glucagon artificial pancreas that alleviates the burden of carbohydrate counting without degrading glycemic control was iteratively enhanced until convergence through pilot experiments on adults with type 1 diabetes. METHODS: Nine participants (age, 37±13 years; glycated hemoglobin, 7.7±0.7%) completed two 27-hour interventions: a fully automated multihormone artificial pancreas and a comparator insulin-alone artificial pancreas with carbohydrate counting. The baseline algorithm was a model-predictive controller that administered insulin and pramlintide in a fixed ratio, with boluses triggered by a glucose threshold, and administered glucagon in response to low glucose levels. RESULTS: The baseline multihormone dosing algorithm resulted in noninferior time in target range (3.9 to 10.0 mmol/L) (71%) compared with the insulin-alone arm (70%) in 2 participants, with minimal glucagon delivery. The algorithm was modified to deliver insulin and pramlintide more aggressively to increase time in range and maximize the benefits of glucagon. The modified algorithm displayed a similar time in range for the multihormone arm (79%) compared with the insulin-alone arm (83%) in 2 participants, but with undesired glycemic fluctuations. Subsequently, we reduced the glucose threshold that triggers glucagon boluses. This resulted in inferior glycemic control for the multihormone arm (81% vs 91%) in 2 participants. Thereafter, a model-based meal-detection algorithm to deliver insulin and pramlintide boluses closer to mealtimes was added and glucagon was removed. The final dual-hormone system had comparable time in range (81% vs 83%) in the last 3 participants. CONCLUSION: The final version of the fully automated system that delivered insulin and pramlintide warrants a randomized controlled trial.

Trends in National Canadian Guideline Recommendations for the Screening and Diagnosis of Gestational Diabetes Mellitus over the Years: A Scoping Review.

Canada's largest national obstetric and diabetology organizations have recommended various algorithms for the screening of gestational diabetes mellitus (GDM) over the years. Though uniformity across recommendations from clinical practice guidelines (CPGs) is desirable, historically, national guidelines from Diabetes Canada (DC) and the Society of Obstetricians and Gynaecologists of Canada (SOGC) have differed. Lack of consensus has led to variation in screening approaches, rendering precise ascertainment of GDM prevalence challenging. To highlight the reason and level of disparity in Canada, we conducted a scoping review of CPGs released by DC and the SOGC over the last thirty years and distributed a survey on screening practices among Canadian physicians. Earlier CPGs were based on expert opinion, leading to different recommendations from these organizations. However, as a result of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, disparities between DC and the SOGC no longer exist and many Canadian physicians have adopted their recent recommendations. Given that Canadian guidelines now recommend two different screening programs (one step vs. two step), lack of consensus on a single diagnostic threshold continues to exist, resulting in differing estimates of GDM prevalence. Our scoping review highlights these disparities and provides a step forward towards reaching a consensus on one unified threshold.

Maternal Sleep-Disordered Breathing in Pregnancy and Increased Nocturnal Glucose Levels in Women with Gestational Diabetes Mellitus.

BACKGROUND: Women with hyperglycemia during pregnancy are at high risk for adverse perinatal outcomes. Maternal sleep-disordered breathing (SDB) during pregnancy is common and is a risk factor for gestational diabetes mellitus (GDM). However, the relationship between SDB severity and glucose control is unknown. RESEARCH QUESTION: Is there an association between SDB severity and glucose levels as assessed by continuous glucose monitoring in GDM? STUDY DESIGN AND METHODS: Women with GDM underwent sleep recordings and 72-hour continuous glucose monitoring. Linear mixed models were used to estimate the association of the apnea-hypopnea index (AHI), rapid eye movement (REM)-AHI, and non-REM-AHI with mean glucose levels during nighttime (two periods: 11 pm to 3 am and 3 am to 6 am), daytime (8 am to 9 pm), and 24-hours. Models were adjusted for BMI and antihyperglycemic medications. RESULTS: In 65 participants who were 35 ± 5 (mean ± SD) years of age with BMI of 33 ± 7 kg/m2, 31% were undergoing insulin and/or metformin therapy. A ten-unit increase in AHI was associated with elevated nocturnal glucose levels (11 pm to 3 am: 0.20 mmol/L [95% CI, 0.04-0.40]) with persistent elevations into the morning (8 am: 0.26 mmol/L [95% CI, 0.08-0.4]) when adjusted for BMI and medications. REM-AHI was also associated with higher nocturnal and morning glucose levels, whereas non-REM was not. AHI was not associated with either mean daytime or 24-hour glucose levels. INTERPRETATION: Greater severity of SDB was associated with higher nocturnal and morning glucose levels in women with GDM.

A Pilot Randomized-Controlled Trial on the Effect of CPAP Treatment on Glycemic Control in Gestational Diabetes: Study Design and Methods.

Background: Gestational diabetes (GDM) is associated with adverse short- and long-term maternal and fetal outcomes. Observational data support a link between sleep-disordered breathing (SDB) during pregnancy and GDM. However, it is unknown whether treatment of SDB with continuous positive airway pressure (CPAP) improves glucose control in this patient population. In addition, CPAP adherence and feasibility as a treatment option in pregnancy is unknown. This pilot randomized, controlled trial aims to primarily determine the feasibility of CPAP treatment in pregnant women with SDB and GDM. This study is also investigating the effect of SDB treatment on 24-h glucose profiles as an exploratory outcome. Objectives: To describe the study methodology in this ongoing study of pregnant women with GDM and SDB. Patients and Methods: Pregnant women with GDM and SDB defined by apnea-hypopnea index (AHI) ≥10 (Chicago Scoring Criteria) on level 2 polysomnography are randomized to either auto titrating CPAP (experimental group) or a nasal dilator strip (control group) until delivery. The primary outcome, objectively-assessed adherence to CPAP, is measured over the course of the treatment period using device-specific software. Recruitment and retention rates will be calculated to assess the feasibility for planning future trials. Twenty-four hour glucose profiles are measured over a 72-h period using the continuous glucose monitoring (CGM) system, before and after the intervention. Conclusion: The results of this study will be highly informative to determine whether CPAP is a feasible treatment for pregnant women with GDM and SDB, a specialized population at risk for substantial comorbidity. The trial results will ultimately be useful in planning future SDB treatment trials in pregnancy and GDM. The study is registered on clinicaltrials.gov (NCT02245659).

Health behaviour changes in partners of women with recent gestational diabetes: a phase IIa trial.

BACKGROUND: We recently demonstrated that a gestational diabetes history in mothers is associated with higher postpartum incident diabetes not only in mothers but also in fathers. In the present study, we examined changes in health behaviours and cardiometabolic profiles in both mothers and partners who participated in a diabetes prevention program within 5 years of a gestational diabetes pregnancy. METHODS: Couples were enrolled into a 13-week program that included 5 half-day group sessions and web/telephone-based support between sessions. It was designed in consultation with patients and previously studied in mothers. We computed mean changes from baseline (95% CI) for physical activity, eating, and sleep measures, and cardiometabolic parameters (fasting and 2-h post glucose load plasma glucose, BMI, blood pressure) in both partners and mothers. RESULTS: Among 59 couples enrolled, 45 partners (76%) and 47 mothers (80%) completed final evaluations. Baseline cardiometabolic measures averaged within normal limits. Similar to mothers, partners increased physical activity (+ 1645 steps/day, 95%CI 730, 2561; accelerometer assessed moderate-to-vigorous physical activity + 36.4 min/week, 95% CI 1.4, 71.4) and sleep duration (+ 0.5 h/night, 95% CI 0.1, 0.9) and reduced the sodium-to-potassium ratio of food intake (- 0.09 95% CI -0.19, - 0.001). No conclusive changes were observed in glucose measures or insulin resistance; in analyses combining mothers and partners, systolic blood pressure decreased (- 2.7 mmHg, 95% CI -4.4, - 1.0). CONCLUSIONS: Partners and mothers demonstrated improved physical activity, sleep, and dietary quality. Baseline cardiometabolic profiles averaged at normal values and there were no changes in glucose or insulin resistance; some blood pressure impact was observed. While strategies need to be developed to attract participants at higher cardiometabolic risk, this study demonstrates that partners of women within 5 years of a gestational diabetes diagnosis can be recruited and do achieve health behaviour change. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02343354 (date of registration: January 22, 2015).

Carotid femoral pulse wave velocity in type 2 diabetes and hypertension: capturing arterial health effects of step counts.

OBJECTIVE: Optimal medication use obscures the impact of physical activity on traditional cardiometabolic risk factors. We evaluated the relationship between step counts and carotid-femoral pulse wave velocity (cfPWV), a summative risk indicator, in patients with type 2 diabetes and/or hypertension. RESEARCH DESIGN AND METHODS: Three hundred and sixty-nine participants were recruited (outpatient clinics; Montreal, Quebec; 2011-2015). Physical activity (pedometer/accelerometer), cfPWV (applanation tonometry), and risk factors (A1C, Homeostatic Model Assessment-Insulin Resistance, blood pressure, lipid profiles) were evaluated. Linear regression models were constructed to quantify the relationship of steps/day with cfPWV. RESULTS: The study population comprised 191 patients with type 2 diabetes and hypertension, 39 with type 2 diabetes, and 139 with hypertension (mean ±â€ŠSD: age 59.6 ±â€Š11.2 years; BMI 31.3 ±â€Š4.8 kg/m; 54.2% women). Blood pressure (125/77 ±â€Š15/9 mmHg), A1C (diabetes: 7.7 ±â€Š1.3%; 61 mmol/mol), and low-density lipoprotein cholesterol (diabetes: 2.19 ±â€Š0.8 mmol/l; without diabetes: 3.13 ±â€Š1.1mmol/l) were close to target. Participants averaged 5125 ±â€Š2722 steps/day. Mean cfPWV was 9.8 ±â€Š2.2 m/s. Steps correlated with cfPWV, but not with other risk factors. A 1000 steps/day increment was associated with a 0.1 m/s cfPWV decrement across adjusted models and in subgroup analysis by diabetes status. In a model adjusted for age, sex, BMI, ethnicity, immigrant status, employment, education, diabetes, hypertension, medication classes, the mean cfPWV decrement was 0.11 m/s (95% confidence interval -0.2, -0.02). CONCLUSIONS: cfPWV is responsive to step counts in patients who are well controlled on cardioprotective medications. This ability to capture the 'added value' of physical activity supports the emerging role of cfPWV in arterial health monitoring.

Hypothalamic hamartoma associated with central precocious puberty and growth hormone deficiency.

Hypothalamic hamartomas (HHs) are tumors generally associated with isolated central precocious puberty (CPP). To our knowledge, we report a unique case of a girl with HH associated with CPP and growth hormone deficiency. This case highlights the complex interaction between HHs and the hypothalamic-pituitary-gonadal axis. It also emphasizes the value of close follow-up of growth velocity in these patients even after treatment of the CPP.

Strategies to optimize participation in diabetes prevention programs following gestational diabetes: a focus group study.

OBJECTIVE: We performed a qualitative study among women within 5 years of Gestational Diabetes (GDM) diagnosis. Our aim was to identify the key elements that would enhance participation in a type 2 diabetes (DM2) prevention program. RESEARCH DESIGN AND METHODS: Potential participants received up to three invitation letters from their GDM physician. Four focus groups were held. Discussants were invited to comment on potential facilitators/barriers to participation and were probed on attitudes towards meal replacement and Internet/social media tools. Recurring themes were identified through qualitative content analysis of discussion transcripts. RESULTS: Among the 1,201 contacted and 79 eligible/interested, 29 women attended a focus group discussion. More than half of discussants were overweight/obese, and less than half were physically active. For DM2 prevention, a strong need for social support to achieve changes in dietary and physical activity habits was expressed. In this regard, face-to-face interactions with peers and professionals were preferred, with adjunctive roles for Internet/social media. Further, direct participation of partners/spouses in a DM2 prevention program was viewed as important to enhance support for behavioural change at home. Discussants highlighted work and child-related responsibilities as potential barriers to participation, and emphasized the importance of childcare support to allow attendance. Meal replacements were viewed with little interest, with concerns that their use would provide a poor example of eating behaviour to children. CONCLUSIONS: Among women within 5 years of a GDM diagnosis who participated in a focus group discussion, participation in a DM2 prevention program would be enhanced by face-to-face interactions with professionals and peers, provision of childcare support, and inclusion of spouses/partners.

Diabetic muscle infarction in a 57 year old male: a case report.

BACKGROUND: Diabetic muscle infarction is a rare complication of diabetes mellitus (DM) and is often misdiagnosed as cellulitis. This complication is usually associated with poor disease prognosis and high mortality with previous studies reporting a risk of 50% recurrence or another macrovascular complication occurring within one year. Thus, there needs to be greater awareness of this complication of diabetes. CASE PRESENTATION: In the current work, we present a case report and literature review of DMI occurring in a calf of a 57 year old male. However, unlike the suspected trend, our patient has performed well after this incident and has not sustained another macrovascular event now > 15 month since his original diabetic muscle infarction. CONCLUSION: Even though diabetic muscle infarction is an uncommon condition, it is important to consider this diagnosis in a diabetic patient. We hope that our findings and literature review will aid clinicians to better diagnose and manage this condition.

Menin missense mutants encoded by the MEN1 gene that are targeted to the proteasome: restoration of expression and activity by CHIP siRNA.

CONTEXT: In multiple endocrine neoplasia type 1 (MEN1) characterized by tumors of parathyroid, enteropancreas, and anterior pituitary, missense mutations in the MEN1 gene product, menin, occur in a subset of cases. The mutant proteins are degraded by the proteasome. However, whether their expression and activity can be restored is not known. OBJECTIVE: Our objective was to functionally characterize a panel of 16 menin missense mutants, including W423R and S443Y identified in new MEN1 families, with respect to protein stability, targeting to the proteasome and restoration of expression by proteasome inhibitors and expression and function by small interfering RNA technology. METHODS: Flag-tagged wild-type (WT) and missense menin mutant expression vectors were transiently transfected in human embryonic kidney (HEK293) and/or rat insulinoma (Rin-5F) cells. RESULTS: The majority of mutants were short-lived, whereas WT menin was stable. Proteasome inhibitors MG132 and PS-341 and inhibition of the chaperone, heat-shock protein 70 (Hsp70), or the ubiquitin ligase, COOH terminus of Hsp70-interacting protein (CHIP), by specific small interfering RNA, restored the levels of the mutants, whereas that of WT menin was largely unaffected. Inhibition of CHIP restored the ability of mutants to mediate normal functions of menin: TGF-ß up-regulation of the promoters of its target genes, the cyclin-dependent kinase inhibitors p15 and p21 as well as TGF-ß inhibition of cell numbers. CONCLUSION: When the levels of missense menin mutants that are targeted to the proteasome are normalized they may function similarly to WT menin. Potentially, targeting specific components of the proteasome chaperone pathway could be beneficial in treating a subset of MEN1 cases.

Ultrasound-guided fine-needle aspiration thyroid biopsies in the otolaryngology clinic.

OBJECTIVE: To assess the efficacy of ultrasound-guided thyroid fine-needle aspiration biopsies (USFNABs) performed in the office setting by an otolaryngologist and to evaluate the specimen adequacy of USFNABs performed in patients whose initial palpation-guided fine-needle aspiration biopsies (PGFNABs) were nondiagnostic. DESIGN: Retrospective chart review. SETTING: Royal Victoria Hospital-McGill University Health Centre, Montreal. METHODS: This is a retrospective analysis of 76 USFNABs performed by an otolaryngologist on consecutive patients over a 6-month period. Each patient had a previous nondiagnostic PGFNAB. Biopsies were performed using a 20-gauge fine needle with a Mylab25 Biosound Esoate ultrasound machine. Samples were then classified according to the adequacy of sample and pathologic findings. MAIN OUTCOME MEASURE: Specimen adequacy rate. RESULTS: Sixty-six patients underwent 76 USFNABs. The sample included 57 females and 9 males (mean age 51.1 and 55.4 years, respectively). The specimen adequacy rate was 90.8% (69 of 76). Among the adequate specimens, 2 (2.6%) were malignant, 6 (7.9%) were suspicious for malignancy, 43 (56.6%) were benign, and 18 (23.7%) were follicular or Hürthle cell lesions (indeterminate). CONCLUSION: Our experience demonstrates that USFNAB performed in the clinic by an otolaryngologist is a promising tool for improving specimen adequacy for nodules initially classified as nondiagnostic. USFNAB also avoids the need for radiologic consultation, thus improving efficacy in the workup of nodules.

Predictors of malignancy in preoperative nondiagnostic biopsies of the thyroid.

OBJECTIVE: To determine whether preoperative variables can be used to predict malignancy for thyroid nodules with follicular, Hürthle, or nondiagnostic cytology on fine-needle aspiration biopsy (FNAB). MATERIALS AND METHODS: Retrospective analysis of 77 consecutive patients selected for total or subtotal thyroidectomy for follicular, Hürthle, or nondiagnostic lesions of the thyroid in two university hospitals. Eleven clinical variables, as well as nodule size, multiplicity, and ultrasound calcifications, were correlated with final histopathologic diagnosis of benign or malignant disease. Analysis was preformed using the Pearson chi-square test. RESULTS: The overall rate of malignancy in our series was 61% (n = 47). FNABs classified as follicular or Hürthle lesions without cellular atypia had a significantly lower risk of malignancy (49% vs 71%; p = .05). Patients who presented with a solitary nodule and FNAB cellular atypia displayed an increased risk of malignancy (92% vs 55%; p = .011). The rate of malignancy was higher for patients with a positive family history (100% vs 59%), a solitary nodule (73% vs 53%), cellular atypia (76% vs 54%), or intrathyroidal calcifications on ultrasonography (71% vs 57%), although none were found to be statistically significant (p > .05). Male gender, age > 45 years, nodule size > 3 cm, mass effect symptoms, and radiation exposure to the neck were not associated with malignancy in our series. CONCLUSION: When presented with follicular, Hürthle, or nondiagnostic biopsies for thyroid nodules, thyroid surgeons should rely systematically on sonographic findings and cytopathologic features to guide their management approach.

Long-term cabergoline therapy is not associated with valvular heart disease in patients with prolactinomas.

Ergot-derived dopamine receptor agonists, especially pergolide and cabergoline, have been associated with an increased risk of valvular heart disease in patients treated for Parkinson's disease. Cabergoline at lower doses than those employed in Parkinson's disease is widely used in patients with prolactinomas, because of its high efficacy and tolerability; however, its safety with regard to cardiac valve disease is unknown. In order to assess the prevalence of cardiac valve regurgitation in patients with prolactinomas treated with long-term cabergoline, we performed a prospective and multicentric study including four university centers in the province of Quebec. A transthoracic echocardiogram was performed in 70 patients with prolactinomas treated with cabergoline for at least 1 year (duration of treatment, 55 +/- 22 months; cumulative dose 282 +/- 271 mg, mean +/- SD) and 70 control subjects matched for age and sex. Valvular regurgitation was graded according to the American Society of Echocardiography recommendations as mild, moderate, or severe. Moderate valvular regurgitation was found in four patients (5.7%) and five control subjects (7.1%) (P = 0.73). No patient had severe valvular regurgitation. There was no correlation between the presence of significant heart-valve regurgitation and cabergoline cumulative dose, duration of cabergoline treatment, prior use of bromocriptine, age, adenoma size, or prolactin levels. Our results show that low doses of cabergoline seem to be a safe treatment of hyperprolactinemic patients. However, in patients with prolonged cabergoline treatment, we suggest that echocardiographic surveillance may be warranted.

Incidence and histopathological behavior of papillary microcarcinomas: study of 429 cases.

OBJECTIVE: We aim to present papillary microcarcinoma (PMC) incidence at a university teaching hospital, to compare characteristics of PMC in relation to size, and to assess for significant difference in PMC incidence among patients with non-PMC thyroid malignancies. MATERIALS AND METHODS: Pathology results were reviewed for consecutive total thyroidectomies between 2002 and 2007 (n = 860). Statistical significance was calculated using chi(2) or, when unavailable, Fisher exact test. RESULTS: PMC was found in 429 cases, which is 49.9 percent of all total thyroidectomies. In PMC > or =5 mm, 25.1 percent had extrathyroidal extension vs 9.1 percent for <5 mm (P < 0.001). When 4 mm is used as a threshold, P value was 300-fold smaller. Incidence in patients with any non-PMC thyroid malignancy was 51.6 percent against 47.2 percent in all other patients (P = 0.203). CONCLUSIONS: In this study, PMC was found in 49.9 percent of patients, which, to our knowledge, is higher than any other reported incidence. A threshold of > or =4 mm was more significant than 5 mm for carrying increased risk for extrathyroidal spread. There was no significant difference in PMC incidence in patients with malignant vs benign disease.