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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.

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: 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 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)

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.

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.