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a Division of Endocrinology and Metabolism, Department of Medicine, Queen’s University, Kingston, Ontario, Canada b Winnipeg Regional Health Authority, Health Sciences Centre Winnipeg, Winnipeg, Manitoba, Canada c Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Mississauga, Ontario, Canada d Medicine and Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada e Division of Endocrinology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada f Section of Endocrinology and Metabolism, John Buhler Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada g McGill Nutrition and Food Science Centre, McGill University, Montreal, Quebec, Canada

The syndrome of pituitary apoplexy has been reported to occur after the administration of several different medications. We report a case in which pituitary apoplexy developed shortly after the administration of leuprolide in a patient with prostate cancer. Leuprolide is a potent gonadotrophin releasing hormone (GnRH) analogue used to suppress leuteotrophic hormone (LH) and testosterone levels in patients with metastatic prostate cancer. LH and testosterone levels actually rise in the first week after its administration before becoming suppressed. We suspect that this acute stimulating effect of leuprolide is linked to the acute onset of pituitary apoplexy in a patient with a possible gonadotrophoma.

At an annual continuing medical education (CME) event, the subject of the management of asthma in pregnancy was taught to attendees using a lecture format and, in consecutive years, a small group interactive teaching format was used. For both years of the study, knowledge retention was assessed by comparing multiple choice test scores on a pretest, a post-test, taken shortly after the educational intervention, and a follow-up test taken 3 months after the educational intervention. Scores showed a significant improvement following the lecture and small group teaching formats for the post-test and follow-up tests. Scores at the preteaching and post-teaching tests were similar for the lecture and small group teaching formats. The scores on the follow-up test, however, were slightly better for the lecture group compared with the small group teaching format, although the difference was small and not significant. We conclude, therefore, that in a CME setting the lecture format of teaching compared favorably with small group learning in terms of knowledge retention.

Background: Intensive glycemic control has been associated with reduced morbidity and mortality in critically ill patients. Web-based, patientspecific insulin nomograms may facilitate improved glucose control. Objective: To compare 2 algorithms for individualizing insulin infusion therapy (a web-based system [Glucommander method] and a standard paper-based nomogram) in a cardiovascular surgery intensive care unit (ICU). Methods: In this prospective, before–after cohort study, measures of glycemic control for 50 patients receiving insulin according to the Glucommander system were compared with a control group ( n = 50) who received insulin according to the standard paper-based nomogram used in the cardiovascular surgery ICU. Results: There was no significant difference between the 2 groups with respect to time to target blood glucose (5.1–8.0 mmol/L), percentage of time within the target range, or mean amplitude of glucose excursion. Patients in the intervention group spent less time above the target range ( p = 0.007) and more time below the target range ( p < 0.001), and the mean glucose was lower in this group compared with the control group (7.9 versus 8.6 mmol/L, p = 0.002). The percentage of blood glucose measurements below 4 mmol/L was higher in the intervention group than in the control group (3.7% versus 1.4%, p = 0.003). Satisfaction surveys revealed that the program was well accepted by the nursing staff in the cardiovascular surgery ICU. Conclusions: A web-based insulin nomogram was an easy-to-use instrument for achieving tighter glucose control for patients in the cardiovascular surgery ICU. Use of the Glucommander system led to lower mean blood glucose but an increase in episodes of hypoglycemia. RESUME Contexte : La regulation intensive de la glycemie a ete associee a une reduction de la morbidite et de la mortalite chez les patients gravement malades. Des nomogrammes personnalises d’ajustement posologique de l’insuline accessibles sur le Web pourraient faciliter la regulation de laglycemie. Objectif : Comparer deux algorithmes de personnalisation de la perfusion d’insuline (nomogramme en ligne [methode Glucommander ] et nomogramme standard sur papier) dans une unite de soins intensifs (USI) chirurgicaux cardiovasculaires. Methodes : Dans cette etude prospective de cohortes avant-apres, on a compare les mesures de la regulation glycemique chez 50 patients dont le debit de perfusion d’insuline a ete adapte au moyen du systeme Glucommander a ceux du groupe temoin ( n = 50) qui ont recu l’insuline selon le nomogramme standard sur papier, a l’USI chirurgicaux cardiovasculaires. Resultats : On n’a observe aucune difference significative entre les deux groupes pour ce qui est du temps d’obtention des valeurs glycemiques cibles (5,1 a 8,0 mmol/L), du pourcentage de temps ou la glycemie est demeuree dans la plage des valeurs cibles et de l’amplitude moyenne de la variation des valeurs de la glycemie. Dans le groupe Glucommander , la glycemie est demeuree moins longtemps au-dessus de la plage des valeurs cibles ( p = 0,007) et plus longtemps au-dessous de la plage des valeurs cibles ( p < 0,001), et sa valeur moyenne etait moins elevee que dans le groupe temoin (7,9 contre 8,6 mmol/L, p = 0,002). Le pourcentage de mesures de la glycemie au-dessous de 4 mmol/L etait plus eleve dans le groupe Glucommander que dans le groupe temoin (3,7 % contre 1,4 %, p = 0,003). Des sondages sur la satisfaction ont revele que le programme etait bien accepte par le personnel infirmier de l’USI chirurgicaux cardiovasculaires. Conclusions : Le nomogramme en ligne etait facile a utiliser pour obtenir une regulation plus serree de la glycemie chez les patients de l’USI chirurgicaux cardiovasculaires. Le recours au systeme Glucommander s’est traduit par des valeurs glycemiques moyennes moins elevees, mais par une augmentation des episodes d’hypoglycemie.

Objectives Radioiodine ablation for the treatment of thyroid cancer is traditionally performed after preparing patients by inducing hypothyroidism. Exogenous stimulation of thyroid-stimulating hormone (TSH) using recombinant human TSH (rhTSH) avoids hypothyroidism and hastens the clearance of radioiodine from the patient. These advantages are achieved without jeopardizing the success rate of remnant ablation. An economic analysis was performed to place the increased acquisition cost of rhTSH in the context of the health benefits achieved and the earlier discharge from radioprotection. Methods Markov modeling, using 17 individual weekly cycles, was used to assess the incremental cost per quality-adjusted life-year (QALY) associated with exogenous stimulation. Clinical inputs were largely sourced from a multicenter, randomized, controlled trial comparing remnant ablation success after either rhTSH or hypothyroid preparation. The model applied Canadian unit costs, taking a societal perspective. Additional costs associated with rhTSH were considered in the context of the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier administration of ablation after surgery, and earlier discharge from the radio-protective ward because of faster radioiodine clearance following rhTSH preparation. The model duration avoided the need for discounting. Results The additional benefits of rhTSH (0.0576 QALY) are obtained with an incremental cost of CDN$87, generating an incremental cost per QALY of CDN$1520. Deterministic one-way and two-way sensitivity analyses demonstrated the result to be robust. Conclusions The use of rhTSH before radioiodine ablation represents a reasonable allocation of costs, with the benefits to patients, hospitals, and society as a whole, obtained at modest cost.

To report the initial experience with combined 18F-fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) imaging for suspected recurrent papillary differentiated thyroid cancer (DTC) at Sunnybrook Health Sciences Centre (SHSC), Toronto.Single institution retrospective study.Consecutive patients from SHSC who underwent FDG PET/CT imaging for suspected recurrent DTC over a period of 2.5 years were identified and their charts reviewed.Qualitative appraisal of FDG PET/CT imaging in suspected recurrent DTC.Sixteen patients (14F, 2M) were identified accounting for 17 FDG PET/CT scans. Three scans (18%) in 3 different patients were reported as suspicious for recurrent disease in the neck (1-3 lesions) and were considered "positive". All were subsequently confirmed pathologically (4-13 positive lymph nodes post operatively). Prior conventional imaging was abnormal in two patients. Two patients had an elevated non-stimulated thyroglobulin (TG)10 ng/mL (4.9 and 9.4). The remaining patient had a TG0.3 ng/mL but was anti-TG antibody positive (84 IUx10-3/L). With a median follow up of 15 months (range 7-36) there were no false positive or negative scans. Incidental pathology (breast cancer, large bowel polyps) was identified on a further 2/17 scans (12%).FDG PET/CT imaging is able to detect recurrent DTC in patients with low TG levels. It can complement conventional imaging findings and exclude distant FDG-avid metastases prior to surgery. It may underestimate the number of positive lymph nodes in the neck. Occult pathology may be identified with whole body FDG PET/CT.

To determine the hormonal response to acute spinal cord injury, serial serum samples were collected from 18 patients with acute spinal cord injury and from 14 control patients with spinal fractures without cord injury. The first sample was taken within 24 hours of injury, the second at 24-48 hours; and the third at 7 days for determination of thyroxine (T4), free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), T3 uptake (T3U), thyroid stimulating hormone (TSH), thyroxine binding globulin (TBG), growth hormone (GH), cortisol, and insulin. Significant increases were observed in rT3 levels and transient changes were observed in the T4 and T3 levels in the spinal cord injured group but not in the group with spinal fractures alone. The changes in the spinal cord injured patients are consistent with the 'low T3 syndrome'. However, the persisting rise of rT3 at 7 days was an unexpected finding. In addition to the cord injury, these changes may also be related to dexamthasone administration and nutritional factors.

Clinical trials using antihyperglycemic medications to improve glycemic control have not demonstrated the anticipated cardiovascular benefits. Low-glycemic index diets may improve both glycemic control and cardiovascular risk factors for patients with type 2 diabetes but debate over their effectiveness continues due to trial limitations.To test the effects of low-glycemic index diets on glycemic control and cardiovascular risk factors in patients with type 2 diabetes.A randomized, parallel study design at a Canadian university hospital research center of 210 participants with type 2 diabetes treated with antihyperglycemic medications who were recruited by newspaper advertisement and randomly assigned to receive 1 of 2 diet treatments each for 6 months between September 16, 2004, and May 22, 2007.High-cereal fiber or low-glycemic index dietary advice.Absolute change in glycated hemoglobin A(1c) (HbA(1c)), with fasting blood glucose and cardiovascular disease risk factors as secondary measures.In the intention-to-treat analysis, HbA(1c) decreased by -0.18% absolute HbA(1c) units (95% confidence interval [CI], -0.29% to -0.07%) in the high-cereal fiber diet compared with -0.50% absolute HbA(1c) units (95% CI, -0.61% to -0.39%) in the low-glycemic index diet (P.001). There was also an increase of high-density lipoprotein cholesterol in the low-glycemic index diet by 1.7 mg/dL (95% CI, 0.8-2.6 mg/dL) compared with a decrease of high-density lipoprotein cholesterol by -0.2 mg/dL (95% CI, -0.9 to 0.5 mg/dL) in the high-cereal fiber diet (P = .005). The reduction in dietary glycemic index related positively to the reduction in HbA(1c) concentration (r = 0.35, P.001) and negatively to the increase in high-density lipoprotein cholesterol (r = -0.19, P = .009).In patients with type 2 diabetes, 6-month treatment with a low-glycemic index diet resulted in moderately lower HbA(1c) levels compared with a high-cereal fiber diet. Trial Registration clinicaltrials.gov identifier: NCT00438698.

Twelve depressed adolescents and 12 controls matched for age, sex, Tanner stage, time of menstrual cycle (females), weight, and time of year assessed were studied over 3 nights. Measurements for cortisol, thyroid stimulating hormone, and growth hormone were made on serum collected at 10 p.m., 12 midnight, 1 a.m., 2 a.m., 3 a.m., 4 a.m., and 6 a.m. in eight pairs and every 20 minutes from 8 p.m. to 7 a.m. in four pairs. Cortisol secretion did not significantly differentiate the groups. Thyroid stimulating hormone secretion was significantly elevated in the depressed group at one time point. Growth hormone secretion significantly differentiated the two groups at most time points, and the depressed adolescents significantly hypersecreted growth hormone (area under the curve). Implications for the diagnosis, etiology, and treatment of adolescent depression are discussed.

A radioreceptor assay for human thyroid stimulators has been employed in various groups of patients. The ability of Ig to displace the labeled TSH from the receptors is referred to as "TSH displacement activity (TDA)." In active Graves' disease, TDA was above normal in 76% of the cases, and in the remaining patients, it was above the 76th percentile, suggesting that thyroid-stimulating Ig (TSIg) may have been present in all cases, but not always demonstrable by this method. Significant TDA was not found in normal persons or in toxic or nontoxic nodular goiters. It was also negative in some patients with "euthyroid ophthalmic Graves' disease." In patients with Graves' disease controlled with antithyroid drugs, positive TDA accurately predicted the recurrence of hyperthyroidism in eight of nine cases from whom the drugs were withdrawn. Thus, TSIg appears to be a prerequisite of the hyperthyroidism of Graves' disease. Moreover, the remission of hyperthyroidism was due to the disappearance of TSIg (immunological remission) in most cases in this small series. Serum TDA may provide a means of detecting immunological remission. The exophthalmos of Graves' disease does not require thyroid-stimulating Ig.

Because the exact site of thyroid hormone absorption in man is not known, we assessed the absorption of oral [125I]Na-L-T4 in patients with varying lengths of intact bowel and correlated this absorption with bowel length. Two normal subjects and five patients with surgical bowel resections, all of whom were euthyroid, were studied. Each received a tracer dose of [125I]Na-L-T4 orally, and serial samples of serum were assayed for radioactivity both with and without butanol extraction. The peak serum radioactivity in normal subjects occurred 2 h post ingestion and was 15% and 17% of the administered dose per liter serum and 11% and 13%/liter serum in butanol-extracted serum, respectively. In patients with shortened bowel, the peak radioactivity both in serum and butanol extracted serum was decreased, ranging from 2%-7% and 0%-5%/liter, respectively. There was no absorption of labeled T4 in the patient with a duodenum only. No consistent relationship was found between absorption and bowel length distal to the duodenum.

A patient had an elevated serum total thyroxine (T4) free thyroxine (free T4), free T4 index, and T4/thyroxine-binding globulin ratio. The serum triiodothyronine (T3), as well as the thyrotrophin response to thyrotrophin-releasing hormone was normal and consistent with the clinical euthyroid status. The basis for the elevated serum total T4, free T4 index, and T4/thyroxine binding globulin is the abnormally enhanced binding of thyroid hormone by albumin, or by an anomalous protein migrating with a mobility similar to albumin as determined in paper electrophoretic systems. The abnormal T4 protein binding was also seen in several members of the patient's family indicating that the condition was familial. A new type of serum T4 protein binding abnormality that results in hyperthyroxinemia may falsely indicate thyrotoxicosis in clinically euthyroid subjects.

The formation of macrophage-lymphocyte rosettes was studied in lymphocyte cultures from patients with Graves' disease, Hashimoto's thyroiditis, other thyroid diseases and control subjects; the cultures were incubated with normal human thyroid and other non-specific antigens. At the end of incubation, the cell pellets were smeared on slides, stained with Wright's stain and the number of rosettes determined under the microscope. The membrane immunofluorescence technique was employed to identify whether the surrounding lymphocytes were T- or B-lymphocytes. In Graves' disease and Hashimoto's thyroiditis, the mean percentages of rosette formation with crude thyroid antigen were 0.98 ± 0.22 % (mean ± sem), and 1.15 ± 0.25 %, respectively. These values were significantly higher than those of control lymphocytes (0.03 ± 0.02 %). Lymphocytes from other thyroid diseases also gave higher values than controls. Kidney antigen, used as a control antigen, gave negative results in Graves' disease and other thyroid diseases, but in Hashimoto's thyroiditis, the mean percentage was of borderline significance. In the direct immunofluorescent staining study using fluorescein-conjugated goat anti-human Ig determinants, including the Fab fraction of anti-human IgG, it appeared that both B- and T-lymphocytes were involved in the rosettes, although B-lymphocytes were more numerous. These results indicate that in patients with Graves' disease and Hashimoto's thyroiditis, a probable immune reaction with thyroid antigen can be demonstrated by macrophage-lymphocyte rosette formation.

Thyroid stimulating substances other than TSH have been found in certain disease states associated with hyperthyroidism. The thyroid stimulator associated with the thyrotoxicosis of trophoblastic disease is uncertain; however, recent evidence suggests a role for hCG. To explore the thyroid stimulating properties of hCG further, we examined the ability of hCG to displace [1252]TSH from receptors on human thyroid membrane and to generate cyclic-AMP (c-AMP) from human thyroid slices. Human chorionic gonadotropin at a concentration of 40 IU/ml displaced labeled TSH from human thyroid membranes and, at a concentration of 69 IU/ml, hCG caused the generation of c-AMP in thyroid slices. These results suggest that hCG can bind to the TSH receptor on thyroid cells and can stimulate them to produce c-AMP at concentrations of hCG within the range that is found in trophoblastic disease.

A study of nocturnal growth hormone secretion in nine depressed adolescents and nine matched controls showed significantly greater secretory amplitudes at 2400 and 0100 hours in the depressed group. These differences were not related to sleep latency, total amount of slow wave sleep before the first REM period, nocturnal cortisol, or nocturnal free T4 levels. These findings suggest disturbed CNS regulation of nocturnal growth hormone in adolescent depressives.

It is a truism that developments in one discipline often unexpectedly illuminate a second area. Thus, recent illuminating advances in immunology have led to new understandings of the pathogenetic mechanisms of many hitherto obscure endocrine disorders. When an endocrine organ is the target of an immune assault, the dysfunction usually manifests itself as gland failure; however, in at least one disorder, Graves’ disease, the aberration in immune function is expressed as hyperfunction of the target endocrine gland. In the following discussion, we will detail the evidence that favors an immune basis for certain disorders affecting the thyroid gland, the adrenal cortex, the endocrine pancreas, the gonads, the parathyroid glands, and even the pituitary gland.

Excerpt Currently, Graves' disease is considered to have an immune basis (1). Numerous disturbances in cellular and humoral immunity have been documented in patients with Graves' disease; some such...