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Purpose To assess reported rates of gastrointestinal (GI) symptoms and their association with autoimmune diseases and microvascular complications in adults and children with type 1 diabetes. Methods The Gastrointestinal Symptom Scale was used to assess GI symptom type and severity in 2370 patients with type 1 diabetes aged 8 to 45 years evaluated as part of a clinical trial screening for celiac disease (CD). The presence and severity of GI symptoms and relationships with demographic, clinical, and other diabetes-related factors were evaluated. Results Overall, 1368 adults (57.7%) aged 19 to 45 years and 1002 (42.3%) pediatric patients aged 8 to 18 years were studied. At least 1 GI symptom was reported in 34.1% of adults as compared with 21.7% of children (P Main Conclusions These results highlight that GI symptoms are an important clinical morbidity and are associated with increasing age, duration of type 1 diabetes, HbA1c, and microvascular complications but not with autoimmune comorbidities including CD.

OBJECTIVE To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS Asymptomatic patients (8–45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA1c and continuous glucose monitoring over 12 months. RESULTS Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9–8.2%, N = 1,298] vs. 4.7% [95% CI 3.4–5.9%, N = 1,089], P = 0.035) with lower rates of prior CD screening (6.9% vs. 44.2%, P < 0.0001). Fifty-one participants were randomized to a GFD (N = 27) or GCD (N = 24). No HbA1c differences were seen between the groups (+0.14%, 1.5 mmol/mol; 95% CI −0.79 to 1.08; P = 0.76), although greater postprandial glucose increases (4-h +1.5 mmol/L; 95% CI 0.4–2.7; P = 0.014) emerged with a GFD. CONCLUSIONS CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Objectives A structured, reflection-based electronic portfolio program (ePortfolio), with novel faculty development initiative, involving ‘shadow coaches’, was shared with the newly formed Ottawa-Shanghai Joint School of Medicine (OSJSM). OSJSM is a partnership between Shanghai Jiao Tong University and the University of Ottawa. As the world’s first Sino-Canadian Joint Medical School, OSJSM introduced North American undergraduate medical curriculum to China. ‘Shadow coaching’ involved trans-Pacific pairing of coaches, supplemented by local faculty development. Framework (a) Pre-implementation: The well-established online ePortfolio platform at the University of Ottawa was mirrored at OSJSM. University of Ottawa ePortfolio coaches were recruited to serve as shadow coaches to their OSJSM counterparts. Shadow coaches provided mentoring and resources while maintaining awareness of cross-cultural issues. Faculty development consisted of face-to-face faculty development in Shanghai, several online synchronous sessions, and familiarization of University of Ottawa coaches with the Chinese medical education system. (b) Description/Components: This intervention, introduced in 2016–2017, involved five University of Ottawa shadow coaches paired with five OSJSM ePortfolio coaches. Student reflection encourages open frank discussion which is a new paradigm for Chinese students and faculty. Shadow coaches were encouraged to challenge new OSJSM coaches to widely explore physician roles and competencies. Results Initial results indicate that the experience served to effectively develop OSJSM coaches’ skills as evidenced by shadow coaches’ review of anonymized OSJSM student reflective writing. Conclusions Our project describes a novel tool using shadow coaching for faculty development for a cross-cultural partnership. Similar approaches can be utilized for culturally-sensitive long-distance faculty development.

IN BRIEF Painful diabetic peripheral neuropathy (PDPN) has a large negative impact on patients’ physical and mental functioning, and pharmacological therapies rarely provide more than partial relief. Mindfulness-based stress reduction (MBSR) is a group psychosocial intervention that was developed for patients with chronic illness who were not responding to existing medical treatments. This study tested the effects of community-based MBSR courses for patients with PDPN. Among patients whose PDPN pharmacotherapy had been optimized in a chronic pain clinic, those randomly assigned to treatment with MBSR experienced improved function, better health-related quality of life, and reduced pain intensity, pain catastrophizing, and depression compared to those receiving usual care.

Background: The effects of changes to resident physician duty hours need to be measureable. This time-motion study was done to record internal medicine residents’ workflow while on duty and to determine the feasibility of capturing detailed data using a mobile electronic tool.Methods: Junior and senior residents were shadowed by a single observer during six-hour blocks of time, covering all seven days. Activities were recorded in real-time. Eighty-nine activities grouped into nine categories were determined a priori.Results: A total of 17,714 events were recorded, encompassing 516 hours of observation. Time was apportioned in the following categories: Direct Patient Care (22%), Communication (19%), Personal tasks (15%), Documentation (14%), Education (13%), Indirect care (11%), Transit (6%), Administration (0.6%), and Non-physician tasks (0.4%). Nineteen percent of the education time was spent in self-directed learning activities. Only 9% of the total on duty time was spent in the presence of patients. Sixty-five percent of communication time was devoted to information transfer. A total of 968 interruptions were recorded which took on average 93.5 seconds each to service.Conclusion: Detailed recording of residents’ workflow is feasible and can now lead to the measurement of the effects of future changes to residency training. Education activities accounted for 13% of on-duty time.

Background: SGLT-2 inhibitors (SGLT-2i) have been associated with decreased all-cause mortality and cardiovascular (CV) morbidity in patients with type 2 diabetes (T2DM) and established CV disease in randomized trials. The objective of this study was to evaluate exposure time to SGLT-2i and other diabetic therapies on all-cause mortality and cardiovascular outcomes in elderly patients with newly diagnosed T2DM. Methods: We conducted a retrospective analysis of patients > 67 years of age who were started on a glucose lowering drug (GLD) between August 1, 2015 and January 1, 2017 using population-based health administrative data. The primary outcome was time to death from any cause. Exposure to all drugs was captured as time-dependent covariates. Secondary outcomes included time to admission to hospital for a cardiovascular outcome. Results: During the study, 36,021 individuals started an GLD. The prevalence of MI and CHF at baseline were low (6.4% vs 9.2% respectively). SGLT-2i were first-line treatment in 3.5% of patients and 7.1% of patients were exposed at any time during the study period. The SGLT-2i group was younger (71.9+/-4.6 yrs vs 74.7+/- 6.2 yrs) with a higher prevalence of MI at baseline. In contrast to other GLDs, death risk decreased as the proportion of observation exposed to SGLT-2i and biguanides increased. The association between individual drug exposures and cardiovascular outcomes was similar. Discussion: In contrast to previous cohort studies, this study examined the independent influence of both SGLT-2i and all other possible GLD individually on mortality and CV risk and based on exposure time. This study suggests that SGLT-2i and biguanides are associated with a decreased risk of all-cause mortality and CV outcomes in patients newly diagnosed with T2DM. Further research is needed to elucidate the mechanism by which SGLT-2i improves mortality and CV outcomes. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. Abstracts presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Objective: To clarify the selection of medical therapy following transsphenoidal surgery in patients with acromegaly, based on growth hormone (GH)/insulin-like growth factor 1 (IGF-1) response and glucometabolic control. Methods: We carried out a systematic literature review on three of the best studied and most practical predictive markers of the response to somatostatin analogues (SSAs): somatostatin receptor (SSTR) expression, tumor morphologic classification, and T2-weighted magnetic resonance imaging (MRI) signal intensity. Additional analyses focused on glucose metabolism in treated patients. Results: The literature survey confirmed significant associations of all three factors with SSA responsiveness. SSTR expression appears necessary for the SSA response; however, it is not sufficient, as approximately half of SSTR2-positive tumors failed to respond clinically to first-generation SSAs. MRI findings (T2-hypo-intensity) and a densely granulated phenotype also correlate with SSA efficacy, and are advantageous as predictive markers relative to SSTR expression alone. Glucometabolic control declines with SSA monotherapy, whereas GH receptor antagonist (GHRA) monotherapy may restore normoglycemia. Conclusion: We propose a decision tree to guide selection among SSAs, dopamine agonists (DAs), and GHRA for medical treatment of acromegaly in the postsurgical setting. This decision tree employs three validated predictive markers and other clinical considerations, to determine whether SSAs are appropriate first-line medical therapy in the postsurgical setting. DA treatment is favored in patients with modest IGF-1 elevation. GHRA treatment should be considered for patients with T2-hyperintense tumors with a sparsely granulated phenotype and/or low SSTR2 staining, and may also be favored for individuals with diabetes. Prospective analyses are required to test the utility of this therapeutic paradigm. Abbreviations: DA = dopamine agonist; DG = densely granulated; GH = growth hormone; GHRA = growth hormone receptor antagonist; HbA1c = glycated hemoglobin; IGF-1 = insulin-like growth factor-1; MRI = magnetic resonance imaging; SG = sparsely granulated; SSA = somatostatin analogue; SSTR = somatostatin receptor.

Papillary thyroid cancer is the most common type of differentiated thyroid cancer (DTC) and in most cases, disease is localized to the neck and remission of disease is common. Though distant metastasis of DTC is unusual; involved sites are more often the lungs and bones, while less common sites include the liver and kidney. No case of metastasis to both intraocular choroid and the pituitary gland has previously been reported. We describe a case of a 58-year-old man who presented with multifocal papillary thyroid carcinoma (PTC) with cervical node metastasis. According to risk stratifications in DTC, the patient stratified as low risk of recurrence. Five years after initial presentation, he was found to have mediastinal lymph node metastasis. Fifteen years post diagnosis, his PTC metastasized to his liver, bone, lung, pituitary gland, orbital choroid and choroid plexus. Remarkably, the only symptom the patient developed as a result of this metastasis was alteration in his vision, which was treated with bevacizumab. Despite initial improvement, he developed ptosis and third nerve symptoms. His pituitary metastasis was treated with Cyber-Knife Surgery and his systemic metastasis was treated with the tyrosine kinase inhibitor (TKI) lenvantinib, resulting in new improvement of his vision. Lenvantinib treatment led to a very marked decrease in the size of his intraocular and choroid plexus lesions and stabilization of his pituitary mass size. The patient developed central hypoadrenalism that required treatment with glucocorticoid replacement. A review of literature for the past 5 decades revealed that metastasis of DTC to the orbital choroid and the pituitary gland have been reported in 17 and 16 cases, respectively. This report is unique as it presents the first case of metastatic PTC to both the intraocular choroid and the pituitary gland. Furthermore, no prior study reported simultaneous DTC metastasis to intraocular choroid and the ventricular choroid. This case highlights that despite their rarity, intraocular and pituitary metastasis of DTC should be considered as potential causes of atypical symptoms such as visual changes or hypopituitarism. Finally, use of TKI therapy for DTC with metastasis to the intraocular choroid and pituitary gland can improve the disease course.

When recombinant human (rh) thyroid-stimulating hormone (TSH) is administered to thyroid cancer survivors, an acute extra-thyroidal effect raises pro-inflammatory cytokines and activates platelets. Thymic stromal lymphopoietin (TSLP) is a cytokine recently implicated in platelet activation. Our aim was to measure platelet microparticle levels after rhTSH stimulation in vivo, and to investigate TSLP expression in TSH-stimulated human adipocytes in culture. Blood samples for total and platelet microparticle analysis were obtained from thyroid cancer survivors before (day 1) and after rhTSH administration (day 5). Adipocytes, differentiated from stromal preadipocytes isolated from adipose tissue from surgical patients, were stimulated with TSH. TSLP mRNA expression, protein expression, and protein release into the adipocyte medium were measured. The level of platelet microparticles in thyroid cancer patients rose 5-fold after rhTSH stimulation. TSH upregulated TSLP mRNA expression in adipocytes in culture through a pathway that was inhibited by 66% by H89, a protein kinase A inhibitor. TSLP protein expression rose in response to TSH, and TSH-stimulated TSLP release into the medium was completely blocked by dexamethasone. In conclusion, TSLP is a novel TSH-responsive adipokine. Future studies will be needed to address the potential role of adipocyte-derived TSLP and whether it is linked to TSH-dependent platelet activation.

Ipilimumab is a monoclonal antibody directed against CTLA4 T-lymphocyte antigen used as cancer therapy. Immune-related adverse events are common side effects and may include hypophysitis-related hypopituitarism. The clinical features of six patients with ipilimumab-induced hypophysitis (IH) are described. The clinical features of IH reported in clinical trials, including the incidence of IH by gender and the likelihood of adrenal axis recovery, are summarized. Following the development of IH, most patients remain on glucocorticoid replacement despite efforts to withdraw therapy. Analysis of gender information in published clinical trials suggests that men are more prone to developing IH than women, and few patients fully recover the pituitary-adrenal axis function. Ipilimumab and other drugs within its class are likely to be used to treat many forms of cancer. Endocrinologists should anticipate a significant increase in the incidence of autoimmune hypophysitis. Strategies for early detection of IH and long-term management should be considered.

Introduction Individualizing glycemic targets to goals of care and time to benefit in persons with type 2 diabetes is good practice, particularly in populations at risk of hypoglycemia and adverse outcomes relating to the use of antihyperglycemics. Guidelines acknowledge the need for relaxed targets in frail older adults, but there is little guidance on how to safely deprescribe (i.e. stop, reduce or substitute) antihyperglycemics. Methods The purpose of this study was to synthesize evidence from all studies evaluating the effects of deprescribing versus continuing antihyperglycemics in older adults with type 2 diabetes. To this end, we searched MEDLINE, EMBASE, and Cochrane Library (July 2015) for controlled studies evaluating the effects of deprescribing antihyperglycemics in adults with type 2 diabetes. All such studies were eligible for inclusion in our study, and two independent reviewers screened titles, abstracts and full-text articles, extracted data, and evaluated risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment and a narrative summary were completed. Results We identified two controlled before-and-after studies, both of very low quality. One study found that an educational intervention decreased glyburide use while not compromising glucose control. The other reported that cessation of antihyperglycemics in elderly nursing home patients resulted in a non-significant increase in glycated hemoglobin (HbA1C). No significant change in hypoglycemia rate was found in the only study with this outcome measure. Conclusions There is limited evidence available regarding deprescribing antihyperglycemic medications. Adequately powered, high-quality studies, particularly in the elderly and with clinically important outcomes, are required to support evidence-based decision-making. Protocol registration number CRD42015017748. Electronic supplementary material The online version of this article (doi:10.1007/s13300-016-0220-9) contains supplementary material, which is available to authorized users.

BACKGROUND Given their essential role in developing professional identity, academic institutions now require formal assessment of the learning environment (LE). We describe the experience of introducing a novel and practical tool in postgraduate programmes. The Learning Environment for Professionalism (LEP) survey, validated in the undergraduate setting, is relatively short, with 11 questions balanced for positive and negative professionalism behaviours. LEP is anonymous and focused on rotation setting, not an individual, and can be used on an iterative basis. We describe how we implemented the LEP, preliminary results, challenges encountered and suggestions for future application. Academic institutions now require formal assessment of the learning environment METHODS: The study was designed to test the feasibility of introducing the LEP in the postgraduate setting, and to establish the validity and the reliability of the survey. Residents in four programmes completed 187 ratings using LEP at the end of one of 11 rotations. RESULTS The resident response rate was 87 per cent. Programme and rotation ratings were similar but not identical. All items rated positively (favourably), but displays of altruism tended to have lower ratings (meaning less desirable behaviour was witnessed), as were ratings for derogatory comments (again meaning that less desirable behaviour was witnessed). DISCUSSION We have shown that the LEP is a feasible and valid tool that can be implemented on an iterative basis to examine the LE. Two LEP questions in particular, regarding derogatory remarks and demonstrating altruism, recorded the lowest scores, and these areas deserve attention at our institution. Implementation in diverse programmes is planned at our teaching hospitals to further assess reliability. This work may influence other postgraduate programmes to introduce this assessment tool.

Thyroid-stimulating hormone (TSH) acts in an extra-thyroidal fashion and induces a pro-inflammatory, pro-coagulant state. Blood monocytes can be activated by vascular stress, but it is not known if this occurs upon TSH administration. Our aim was to determine if recombinant human (rh) TSH, administered acutely to patients being screened for thyroid cancer recurrence, alters blood monocyte gene expression.Patients (14 women, 1 man) had a mean (±SD) age of 48±10 years, a body mass index of 26±6 kg/m2, a history of total thyroidectomy and radioablation for thyroid cancer, and were on L-thyroxine therapy at a university teaching hospital. They received 2 intramuscular doses of rhTSH (0.9 mg), administered on days 1 and 2. Blood samples were obtained at baseline on day1, and on days 3 and 5.Monocyte MCP-1 mRNA (mean±SE) increased significantly by 1.7±0.3 fold on day 5 following rhTSH stimulation (p=0.03, n=15). IL-1β and CD36 mRNA expression also increased on day 5 (1.9±0.4 fold, p=0.07, n=14) and 2.5±0.4 fold, p=0.1, n=10), respectively, although did not quite reach statistical significance. Significant correlations were detected between the BMI of patients and their TSH-stimulated monocyte mRNA responses at day 5 for CD11a, (r=0.66, n=14, p=0.01); CD14 (r=0.638, n=13, p=0.019), and CD16, r=0.84, n=13, p=0.0003).TSH administration increases pro-atherogenic monocyte gene expression.

Background Since the mid-1980s, medical residents’ long duty hours have been under scrutiny as a factor affecting patient safety and the work environment for the residents. After several mandated changes in duty hours, it is important to understand how residents spend their time before proposing and implementing future changes. Time-motion methodology may provide reliable information on what residents do while on duty. Purpose The purpose of this study is to review all available literature pertaining to time-motion studies of internal medicine residents while on a medicine service and to understand how much of their time is apportioned to various categories of tasks, and also to determine the effects of the Accreditation Council for Graduate Medical Education (ACGME)-mandated duty hour changes on resident workflow in North America. Methods Electronic bibliographic databases were searched for articles in English between 1941 and April 2013 reporting time-motion studies of internal medicine residents rotating through a general medicine service. Results Eight articles were included. Residents spent 41.8% of time in patient care activities, 18.1% communicating, 13.8% in educational activities, 19.7% in personal/other, and 6.6% in transit. North American data showed the following changes after the implementation of the ACGME 2003 duty hours standard: patient care activities from 41.8% to 40.8%, communication activities from 19.0% to 22.3%, educational activities from 17.7% to 11.6%, and personal/other activities from 21.5% to 17.1%. Conclusion There was a paucity of time-motion data. There was great variability in the operational definitions of task categories reported in the studies. Implementation of the ACGME duty hour standards did not have a significant effect on the percentage of time spent in particular tasks. There are conflicting reports on how duty hour changes have affected patient safety. A low proportion of time spent in educational activities deserves further study and may point to a review of the educational models used., Video abstract

Background and aims Approximately 174 pregnancies in acromegaly have been reported. Our objectives were to identify the key challenges of preconception counselling in this population. Methods Case series of three acromegalic women with desire for pregnancy. Issues were identified from chart review and discussion with attending physicians. Literature review of acromegaly and pregnancy was conducted. Results Important issues identified included: impact of acromegaly on fertility, management of acromegaly in the peripartum period, screening for associated conditions, risk of progression of acromegaly/tumour growth during pregnancy, impact of acromegaly on pregnancy outcomes, surveillance during pregnancy, method of delivery and impact on neonatal outcomes and breastfeeding. Conclusions Pregnancy can be safely achieved in patients with acromegaly. There is little evidence to guide recommendations around conception and pregnancy surveillance. Patients can be reassured that in most situations, pregnancy proceeds without complication and that medical treatment can be used during pregnancy if necessary.

Objective To report the successful 10-year management of a gonadotroph macroadenoma with bromocriptine and review the management of gonadotroph adenomas with bromocriptine. Methods We present a case and review the pertinent literature. The effectiveness of bromocriptine in the management of gonadotroph adenomas is evaluated. Results A 62-year-old man was found to have a pituitary tumor after seeking medical assistance because of a 6-month history of headaches and blurred vision. He had decreased visual acuity and bitemporal field defects. Serum follicle-stimulating hormone (FSH) levels were increased, whereas serum luteinizing hormone and total testosterone levels were normal. Treatment with bromocriptine resulted in a decrease in serum FSH levels, complete resolution of his symptoms, and considerable improvement in his visual acuity and visual field defects. Treatment with only bromocriptine for 10 years resulted in maintenance of normal serum FSH levels and no recurrence of symptoms. Conclusion In the management of a gonadotroph adenoma, we recommend consideration of a therapeutic trial of bromocriptine. In cases that are refractory to this therapy, surgical treatment or external pituitary irradiation could then be used. (Endocr Pract. 1998;4:274-278)

Prolactin receptors (PRLR) have been identified in a number of human tissues and cell lines, although little is known about the human receptor protein. The cloning of the human PRLR cDNA has enabled further characterization of the receptor protein in transfected cells. Since the human cDNA is expressed at lower levels than the rat cDNA, we have constructed a hybrid cDNA (pECE r5'hPRLR) containing nucleotides of the 5' untranslated region and signal peptide of the rat PRLR and the protein coding and 3' untranslated portion of the human receptor. Expression of the hybrid receptor was increased more than two-fold compared to the human receptor as detected by specific binding of 125I-human growth hormone (GH) to transfected COS-7 cells. The relative molecular mass of the receptor was 93,000 Da, as determined by chemical cross-linking studies. Transcriptional assays were used to show the human PRLR was able to activate two milk protein genes; ovine beta-lactoglobulin and rat beta-casein. Transfected cells expressing the human PRLR receptor, treated with human GH or prolactin (PRL), induced a dose-dependent increase in transcriptional activation of the beta-casein/luciferase fusion gene. Glycosylated, and non-glycosylated human PRL, and ovine PRL were equally effective in activating the beta-casein promoter. Human placental lactogen and bovine PRL could also induce a greater than 10-fold induction, whereas insulin did not significantly stimulate the beta-casein promoter. The results show that the human PRLR can activate both beta-lactoglobulin and beta-casein milk gene promoters and that these reporter genes can be used to evaluate the functional activity of agonists and antagonists of the human PRLR.

Prolactin (PRL) and growth hormone (GH) receptors are members of a superfamily that include receptors for a number of cytokines. GH and its receptor form an unusual homodimer consisting of one molecule of GH and two molecules of receptor. A similar homodimer of the PRL receptor is probably required for biological effects to be seen. Using specific assays to measure the functional activity of PRL and GH receptors, a 25 amino acid juxtamembrane region has been identified as essential but not sufficient for normal action. More detailed studies have limited the region to eight amino acids, rich in prolines, that is highly conserved in many members of the receptor superfamily. Finally, GH and PRL have been shown to induce the rapid tyrosine phosphorylation of an associated kinase, Janus kinase 2, and of the receptor itself. 28 refs., 1 fig.

Thyroid-stimulating hormone (TSH) stimulates adipocyte lipolysis, but signal transduction pathways activated by TSH for this response have not been directly studied. Using differentiated 3T3-L1 adipocytes as well as primary human adipocytes, we characterized the lipolytic action of TSH with dose-response and time-course studies, and compared it with isoproterenol. Thyroid-stimulating hormone stimulated phosphorylation of perilipin and hormone-sensitive lipase (HSL). Inhibition of protein kinase A with H89 blocked TSH-stimulated lipolysis as well as phosphorylation of perilipin and HSL. Thyroid-stimulating hormone stimulated lipolysis in vivo, as indicated by an elevation in serum free fatty acid (FFA) levels after recombinant human TSH administration to thyroidectomized patients (42% increase, n = 19, P < .05). For patients with a body mass index less than 30 kg/m(2), the TSH-induced increase in serum FFA levels was 53% (n = 11, P < .05), whereas levels in patients with a body mass index of at least 30 kg/m(2) (n = 8) did not change after TSH treatment. In summary, TSH stimulates lipolysis and phosphorylation of perilipin and HSL in a protein kinase A-dependent manner in differentiated adipocytes in culture and raises serum FFA levels in vivo.

To assess the role of the adrenal glands in the development of hirsutism, levels of 11 β -hydroxy-androstenedione (11 β -OHA), 17α:-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (∆ 4 A), and free and total testosterone (T) were measured in 63 hirsute females and 30 control patients. Six of the hirsute patients had basal levels of 11 β -OHA and 17-OHP and responses to adrenocorticotropic hormone that were significantly greater than these values in controls and the other hirsute women. These women were designated as having an adrenal source for their hirsutism. Women with polycystic ovarian syndrome and idiopathic hirsutism had normal values of 11 β -OHA and 17-OHP. Levels of total and free T, DHEAS and ∆ 4 A were significantly higher than control values in all of the hirsute women. This study demonstrates that 11 β -OHA can be used as a marker to assess the adrenal contribution to hirsutism.

Background: It is now recognized that TSH can act on targets other than the thyroid, including the liver. Elevated serum TSH levels in euthyroid subjects were recently reported to correlate with high values of serum proprotein convertase subtilisin/kexin type 9 (PCSK9). This protein, expressed and secreted by hepatocytes, promotes higher LDL-cholesterol levels. We tested whether an acute increase of TSH levels following administration of TSH in vivo would raise PCSK9 levels in patients who had previously undergone total thyroidectomy and radioablation for thyroid cancer. Findings: TSH levels rose from 0.64 ± 1.02 mU/L on day 1 to 98.66 ± 4.83 mU/L on day 3, following injections of recombinant human TSH (on days 1 and 2). PCSK9 levels were 330 ± 99 ng/ml on day 1, and did not change on days 3 or 5 in response to TSH stimulation. Conclusions: Although a positive correlation between TSH and PCSK9 in euthyroid subjects has raised the possibility that TSH might act on the liver to raise PCSK9 values, our data show that PCSK9 levels are not affected by acute elevations of TSH levels. Whether chronic elevations of TSH are needed to upregulate PCSK9 remains to be determined.

Objective “The pseudomalabsorption of thyroxine” has been used to describe patients with hypothyroidism who fail to comply with their treatment. We describe a unique case of a 32-year-old with hypothyroidism who developed pituitary hyperplasia and hyperprolactinemia secondary to the pseudomalabsorption of thyroxine. Investigations and treatment After baseline thyroid-function tests were performed, the patient was administered levothyroxine 0.5 mg under the supervision of a registered nurse. Thyroid function testing was repeated at 30, 60, 120, and 180 minutes. Arrangements were made for further daily supervised loading of levothyroxine 0.1 mg. Results With the administration of 0.5 mg levothyroxine, free thyroxine levels increased by 120 minutes, and with daily supervised dosing of 0.1 mg there was normalization of the thyroid hormone levels and a reduction of thyroid-stimulating hormone levels. Maintenance of thyroid-stimulating hormone < 15 mU/L for 2 weeks led to a reduction in prolactin levels and regression in the size of the pituitary on magnetic resonance imaging. Conclusion If left untreated, these patients face significant morbidity and are at risk of developing pituitary hyperplasia, complications from an increase in pituitary size, hyperprolactinemia, and potentially myxedema coma. Recognizing pituitary hyperplasia and hyperprolactinemia as a complication from the pseudomalabsorption of levothyroxine may prevent the potential of a misdiagnosis of a prolactinoma leading to unnecessary investigations and inappropriate treatment. Patient awareness of this serious complication and the rapid, demonstrable resolution with adequate thyroid hormone replacement may provide motivation to comply with supervised dosing of levothyroxine. It has also been suggested that supervised treatment enables the individual to maintain their patient status, which may be in part the motivation behind this disorder.

Background Residency training takes place primarily on inpatient wards. In the absence of a resident continuity clinic, internal medicine residents rely on block rotations to learn about continuity of care. Alternate methods to introduce continuity of care are needed. Methods A web-based tool, Continuity of Care Online Simulations (COCOS), was designed for use in a one-month, postgraduate clinical rotation in endocrinology. It is an interactive tool that simulates the continuing care of any patient with a chronic endocrine disease. Twenty-three residents in internal medicine participated in a study to investigate the effects of using COCOS during a clinical rotation in endocrinology on pre-post knowledge test scores and self-assessment of confidence. Results Compared to residents who did the rotation alone, residents who used COCOS during the rotation had significantly higher improvements in test scores (% increase in pre-post test scores +21.6 [standard deviation, SD, 8.0] vs. +5.9 [SD 6.8]; p < .001). Test score improvements were most pronounced for less commonly seen conditions. There were no significant differences in changes in confidence. Residents rated COCOS very highly, recommending its use as a standard part of the rotation and throughout residency. Conclusion A stand-alone web-based tool can be incorporated into an existing clinical rotation to help residents learn about continuity of care. It has the most potential to teach residents about topics that are less commonly seen during a clinical rotation. The adaptable, web-based format allows the creation of cases for most chronic medical conditions.

Purpose: Fetuin-A is a hepatokine that is linked to lipid metabolism, obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Elevated thyroid-stimulating hormone (TSH) levels are associated with metabolic and cardiovascular disturbances. Our aim was to determine if TSH can regulate fetuin-A levels. Methods: Fetuin-A serum levels were examined in 26 subjects (19 women; previous thyroidectomy and radioactive iodine ablation) undergoing recombinant human TSH (rhTSH) stimulation to screen for thyroid cancer recurrence. Their age was 49±10 years, and body mass index (BMI) was 28±6 (both expressed as mean±SD). The patients received two doses of rhTSH (0.9 mg), administered 24 hours apart on days 1 and 2, without discontinuation of ongoing L-thyroxine therapy. Morning blood samples were obtained on days 1 (prior to the first dose of rhTSH), 3 and 5. Results: The baseline value of fetuin-A (mean±SD) for all participants was 527±186 mg/L. Values of fetuin-A did not change in response to rhTSH administration. The lack of response was not dependent on gender, age, baseline free thyroxine level or BMI. Conclusion: Fetuin-A has been implicated in metabolic and inflammatory conditions, but there have been no reports on whether fetuin-A is influenced by TSH. Within the context of rhTSH administration for surveillance of thyroid cancer recurrence, there was no effect on serum levels of fetuin-A.

Background Accrediting bodies now recognize the importance of developing the professionalism competency, by setting standards that require medical schools to identify where professionalism is addressed and how it is evaluated within the formal curriculum. The objective of this study was to compare how professionalism competency is formally addressed in the curricula of Canadian medical schools, and to better understand the Canadian approach to reporting and remediation of lapses. Methods A literature review was performed and with the input of the AFMC(Association of Faculties of Medicine of Canada) Professionalism group, questionnaires were generated. An electronic survey was circulated to key leaders across the country at all the medical schools. In-depth telephone interviews were used to further explore themes, and a subsequent focus group was held to discuss challenges, particularly related to reporting and remediation. Results The preponderance of formal professionalism teaching remains in the form of lectures and small group sessions in the preclinical years. Formal teaching declines significantly in the clerkship/clinical years. Evaluation is usually performed by a clinical supervisor, but OSCE, portfolio, and concern notes are increasingly used. Role modeling is heavily relied upon in clinical years, suggesting faculty training can help ensure clinical teachers recognize their influence on trainees. Formal remediation strategies are in place at most schools, and often involve essay writing, reflection exercises, or completion of learning modules about professionalism. Lack of clarity on what defines a lapse and fear of reprisal (for both trainees and faculty) limits reporting. Conclusions This study provides an overview of how professional identity formation is supported in the Canadian context, guided by the standards set out by CanMEDS. Despite a rich literature that describes the definition, program design and evaluation methods for professionalism, in some areas of the curriculum there is still an opportunity to ensure programs embrace the suggested framework. Examples of teaching and evaluation methods, deficiencies in the clinical years of study (clerkship) and challenges in addressing lapses and organizational structure are identified. The results help identify the gaps that need to be addressed and some solutions that can be modeled at other academic institutions.