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  • 11
    Online Resource
    Online Resource
    MDPI AG ; 2023
    In:  International Journal of Molecular Sciences Vol. 24, No. 3 ( 2023-01-29), p. 2550-
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 3 ( 2023-01-29), p. 2550-
    Abstract: Fibrous dysplasia (FD) is a rare, non-inherited bone disease occurring following a somatic gain-of-function R201 missense mutation of the guanine-nucleotide binding protein alpha subunit stimulating activity polypeptide 1 (GNAS) gene. The spectrum of the disease ranges from a single FD lesion to a combination with extraskeletal features; an amalgamation with café-au-lait skin hyperpigmentation, precocious puberty, and other endocrinopathies defines McCune–Albright Syndrome (MAS). Pain in FD/MAS represents one of the most prominent aspects of the disease and one of the most challenging to treat—an outcome driven by (i) the heterogeneous nature of FD/MAS, (ii) the variable presentation of pain phenotypes (i.e., craniofacial vs. musculoskeletal pain), (iii) a lack of studies probing pain mechanisms, and (iv) a lack of rigorously validated analgesic strategies in FD/MAS. At present, a range of pharmacotherapies are prescribed to patients with FD/MAS to mitigate skeletal disease activity, as well as pain. We analyze evidence guiding the current use of bisphosphonates, denosumab, and other therapies in FD/MAS, and also discuss the potential underlying pharmacological mechanisms by which pain relief may be achieved. Furthermore, we highlight the range of presentation of pain in individual cases of FD/MAS to further describe the difficulties associated with employing effective pain treatment in FD/MAS. Potential next steps toward identifying and validating effective pain treatments in FD/MAS are discussed, such as employing randomized control trials and probing new pain pathways in this rare bone disease.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
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  • 12
    In: Diabetes, American Diabetes Association, Vol. 70, No. Supplement_1 ( 2021-06-01)
    Abstract: Background: Women with gestational diabetes (GDM) have an increased risk of adverse perinatal outcomes and future type 2 diabetes (T2D). Gestational glucose intolerance (GGI, abnormal initial GDM screen) without GDM has been linked to adverse perinatal outcomes but is not a recognized T2D risk factor. We tested whether GGI without GDM is associated with incident T2D. Methods: Using clinical data from women seen at our US medical center for prenatal and primary care (1998-2018), we assessed risk of T2D (defined using validated laboratory and outpatient diagnoses) according to GGI/GDM status during pregnancy. We defined GGI as 1-hr glucose loading test (GLT) ≥ 140 mg/dl at ≥ 24 weeks gestation. We subcategorized GGI by 3-hr oral glucose tolerance test (OGTT) result. We used Cox proportional-hazard models with time-varying exposures/covariates to assess T2D risk after delivery, adjusting for age, race/ethnicity, parity, insurance type, marital status, BMI, and blood pressure. Women were followed from 1st delivery until diagnosed with T2D or censored at time of last primary care visit. Results: Among 13988 women, 17109 pregnancies had normal glucose tolerance (NGT, GLT & lt; 140mg/dL). Among 3619 GGI pregnancies (GLT ≥ 140 mg/dl), 2076 had a normal OGTT, 699 had 1 abnormal OGTT value, and 844 had GDM (≥ 2 abnormal OGTT values). Over a median of 8.3 years of follow-up, 2.2% (N=304 women) developed T2D. In our primary comparison, women with GGI without GDM (16% of pregnancies) had increased T2D risk compared to women with NGT (HR 2.1 [1.5-2.9], p & lt;0.001). Among women with GGI, T2D risk increased with the number of abnormal OGTT values (normal OGTT: HR 1.8; 1 abnormal OGTT value: HR 2.8; GDM: HR 11.7; p≤0.01 for all compared to NGT). Conclusions: Pregnant women with GGI without GDM have a two-fold increased risk of future T2D compared to those with NGT. Clinical data universally available during pregnancy identifies a large, previously unrecognized group of women who may benefit from T2D screening and prevention. Disclosure D. J. Selen: None. T. Thaweethai: None. S. Hsu: None. K. James: None. A. Kaimal: None. J. B. Meigs: Consultant; Self; Quest Diagnostics. C. E. Powe: None. Funding National Institutes of Health (2T32DK007028-46, K23DK113218); Robert Wood Johnson Foundation; Massachusetts General Hospital
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2021
    detail.hit.zdb_id: 1501252-9
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  • 13
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  Journal of the Endocrine Society Vol. 5, No. Supplement_1 ( 2021-05-03), p. A434-A434
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A434-A434
    Abstract: Background: Women with gestational diabetes mellitus (GDM) and gestational glucose intolerance (GGI, abnormal initial GDM screening test) and their infants have an increased risk of adverse perinatal outcomes including large for gestational age birth weight (LGA), pregnancy-related hypertension, neonatal intensive care unit (NICU) admission, and cesarean delivery. We expanded a prior analysis defining physiologic subtypes of GGI categorized by insulin resistance, insulin deficiency, or mixed pathophysiology. We aimed to determine if GGI subtypes are at differential risk for adverse outcomes. Methods: We applied homeostasis model assessment (HOMA2) to fasting glucose and insulin levels at 16–20 weeks’ gestation to assess insulin resistance and deficiency, defined using the 50th percentile in 220 women with a normal glucose loading test (GLT) at 24–30 weeks’ gestation. We defined GGI as GLT 1-hr glucose ≥140 mg/dL (n=245) and normal glucose tolerance (NGT) as GLT 1-hr glucose & lt;140 mg/dL (n=1538). We classified women with GGI into subtypes according to the presence of insulin resistance and/or deficiency. We compared odds of adverse outcomes in each subtype to odds in women with NGT using logistic regression with adjustment for age, race/ethnicity, marital status, and 1st trimester BMI, plus infant sex in LGA models. Results: Of women with GGI, 49.0% had the insulin resistant subtype (IR, n=120), 30.6% had the insulin deficient subtype (ID, n=75), 15.9% had mixed pathophysiology (MP, n=39), and 4.5% had no evidence of IR or ID (n=11). GLT results and GDM diagnosis were similar among GGI subtypes. We found increased odds of LGA (primary outcome) in women with IR compared to women with NGT (OR 1.97 [1.17–3.32] , p=0.01) in an unadjusted model; this was attenuated in an adjusted model with BMI (adjusted OR 1.43 [0.82–2.49], p=0.21). There was a trend toward increased odds of LGA in women with ID (adjusted OR 1.87 [0.92–3.80] , p=0.09) and no increased odds in women with MP (adjusted OR 1.33 [0.50–3.57], p=0.57) compared to NGT. The odds of pregnancy-related hypertension in the IR subtype were increased (adjusted OR 1.68 [1.02–2.77] , p=0.04) compared to women with NGT; women with ID (adjusted OR 0.91 [0.44–1.88], p=0.79) or MP (adjusted OR 1.13 [0.48–2.67] , p=0.78) did not have increased odds. Neither infants of women with IR nor ID had increased odds of NICU admission overall, yet among women with BMI & lt;25, infants of those with IR had increased odds of NICU admission compared to those of women with NGT (adjusted OR 3.37 [1.04–10.96], p=0.02); odds of NICU admission were not increased in infants of women with ID and BMI & lt;25 (adjusted OR 0.50 [0.07–3.83], p=0.50). There was no difference in cesarean delivery across subtypes. Conclusion: Insulin resistant GGI is a high-risk subtype for adverse perinatal outcomes. Using HOMA2 to delineate subtypes may provide opportunities for a personalized approach to GGI/GDM.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 14
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    Online Resource
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: D. Mendez: None. M.G. Fernandez: None. D.J. Selen: None. Background: Endogenous Cushing syndrome may result from an ectopic non-pituitary tumor. Severe hypercortisolism has high mortality, so prompt medical management to acutely decrease cortisol levels is necessary when no surgical options are available. Clinical Case: A 67-year-old male presented to the hospital with four weeks of fatigue and was found to have a right hilar mass with unsuppressed cortisol levels for which an ectopic tumor was suspected. On initial evaluation, the patient presented with hypokalemia, acute kidney injury, and metabolic alkalosis. In addition, a CT of the chest and abdomen with contrast revealed a right hilar mass with multiple liver lesions concerning for metastasis. These findings prompted workup for hypercortisolism, including 1mg and 8 mg dexamethasone suppression tests. Both tests demonstrated unsuppressed cortisol levels above 150 (reference range [RR] 5.5-20 ug/dl and assay maximum & gt;150) and elevated 24-hour urinary cortisol of 8125 (RR & lt;60 ug/dl), suspicious for an ACTH-secreting tumor. Subsequently, he underwent a liver biopsy to characterize the tumor further and was started on Bactrim for Pneumocystis pneumonia prophylaxis. Metyrapone and osilodrostat were considered for treatment but not available at our facility such that treatment was initiated with ketoconazole 200 mg orally twice daily with subsequent dose titration. He had a mild elevation of AST 52 (RR 7-42 IU/L) and ALT 52 (RR 10-45); therefore, his liver profile was monitored daily due to his elevated risk for hepatotoxicity. With the initiation of ketoconazole, cortisol serum levels decreased to 145 ug/dl after two days of treatment. The pathology report revealed small lung cell carcinoma as the etiology for ectopic Cushing’s syndrome, for which the oncology team-initiated etoposide and carboplatin. Unfortunately, on day 6 of the initiation of treatment, the patient rapidly deteriorated and passed away from pneumonia and septic shock. Conclusion: Severe hypercortisolism leads to an immunosuppressed state resulting in high mortality. Therapeutic options depend significantly on the accessibility of first-line treatment options and prompt initiation of medical treatment. When no other agents are available, ketoconazole should be started at high doses despite the mild elevation of liver enzymes with close monitoring of LFTs. While it is unclear if the patient’s deterioration was due to his cancer burden, chemotherapy, severe hypercortisolism, or a combination, given that osilodrostat and metyrapone are first-line treatment options, standardized systems should be reviewed in hospitals for faster acquisition of these medications to avoid delays in treatment initiation. In addition, the decision to transfer patients to the intensive care unit for etomidate infusion while awaiting the acquisition of the above medications should be considered promptly. Presentation: Friday, June 16, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
    detail.hit.zdb_id: 2881023-5
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  • 15
    Online Resource
    Online Resource
    The Endocrine Society ; 2023
    In:  Journal of the Endocrine Society Vol. 7, No. Supplement_1 ( 2023-10-05)
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 7, No. Supplement_1 ( 2023-10-05)
    Abstract: Disclosure: M.G. Fernandez: None. D.J. Selen: None. Background: Nonislet cell tumor hypoglycemia is an uncommon but severe complication of cancer. It results from tumoral overproduction of insulin-like growth factor 2 (IGF-2), which inhibits hepatic glycogenolysis and the release of glucagon and growth hormone (GH). These three mechanisms can result in severe and refractory hypoglycemia. Clinical Case: We present a case of a 57-year-old female newly diagnosed with metastatic cholangiocarcinoma who was admitted to the hospital after an episode of syncope at home in the setting of hypoglycemia with a serum blood glucose of 17 mg/dL (N & gt;60 mg/dL). During the hospital admission, evaluation of hypoglycemia included a normal TSH of 1.170 (reference range [RR] 0.3-5.5 mIU/ml), fasting morning cortisol of 23.3 (RR & gt;14-15 μg/dL), and a negative sulfonylurea screen. In addition, the patient had an undetectable level of Insulin & lt;3.0 (RR 3-25 mU/L), Beta-hydroxybutyrate & lt;0.10 (RR 0.02-0.27 mMol/L), C-peptide & lt;0.1 (RR 0.5-3.3 ng/ml), and Pro-insulin & lt;1.6 (RR 3-20 pmol/L). CT of the abdomen revealed disease progression with innumerable bilateral enhanced hypoattenuating masses in the liver. Management for refractory hypoglycemia required nutrition optimization, nausea control, close glucose monitoring, IV dextrose infusion, and intermittent intravenous glucagon for episodes of severe hypoglycemia ( & lt;40 mg/dL). During the hospitalization, the patient received the first cycle of chemotherapy with gemcitabine, cisplatin, and dexamethasone. On day 10 of admission, the IGF-2 resulted at 120 ng/ml (RR 180-580ng/ml) and IGF-1 & lt;10 (RR 50-317 ng/ml) with an IGF-2/IGF-1 ratio greater than 100 (cut off & gt;10), diagnostic of a large nonislet cell tumor as the most likely cause of her severe hypoglycemia. Artificial nutrition did not align with this patient’s goals of care, so she was discharged from the hospital with a FreeStyle Libre 2 for continuous glucose monitoring. However, two weeks later, she returned to the emergency department with hypoglycemia ( & lt;40 mg/dL), ultimately choosing to pursue hospice. Conclusion: Patients with large liver tumor burden can experience hypoglycemia due to low glycogen content in the liver. In addition, these patients can have decreased oral intake and weight loss, which confounds the clinical scenario and can delay diagnostic workup. Patients with refractory hypoglycemia and nonislet cell tumors require further evaluation for IGF-2 production, and alternative temporary nutritional options should be discussed with the patient immediately. Therapeutic options depend on the ability to treat underlying cancer. Palliative chemotherapy, surgery, or radiation can be considered to control the tumor and improve hypoglycemia for quality of life when the cancer is otherwise untreatable. Presentation: Thursday, June 15, 2023
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2023
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  • 16
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2019
    In:  International Journal of Obesity Vol. 43, No. 3 ( 2019-3), p. 633-637
    In: International Journal of Obesity, Springer Science and Business Media LLC, Vol. 43, No. 3 ( 2019-3), p. 633-637
    Type of Medium: Online Resource
    ISSN: 0307-0565 , 1476-5497
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2101927-7
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  • 17
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Background: Gestational glucose intolerance (GGI, abnormal initial gestational diabetes [GDM] screen) conveys an increased risk of future diabetes (DM) , even when GDM criteria is not met. We previously defined subtypes of GGI/GDM according to the underlying mechanism leading to hyperglycemia (insulin resistance vs. deficiency) . We aimed to determine if GGI subtypes are at differential risk for future prediabetes/DM; we hypothesized increased risk with insulin deficient subtypes. Methods: We defined GGI as glucose loading test 1-hr glucose ≥ 140 mg/dL at & gt; 22 weeks’ gestation. We applied homeostasis model assessment (HOMA) to fasting glucose and insulin at 16-20 weeks’ gestation and classified pregnancies with GGI without GDM into subtypes according to the presence of insulin resistance and/or deficiency. We used Cox proportional-hazards models with time-varying exposures to assess risk of preDM/DM (HbA1c ≥ 5.7% at ≥ 3 months after delivery) in each GGI subtype compared to pregnancies with normal glucose tolerance after adjustment for age, race/ethnicity, health insurance, and first trimester BMI. Women were censored at the time of last HbA1c or GDM diagnosis. Results: Of 671 women with a median 9.9 years of follow-up, 29% (n=196) developed preDM/DM. Among pregnancies in 113 women with GGI, 54% had the insulin resistant subtype (IR) , 25% had the insulin deficient subtype (ID) , and 16% had the mixed pathophysiology subtype (MP) . Subtypes with insulin deficiency (ID + MP) and insulin resistance (IR) were both associated with increased risk of preDM/DM (ID + MP hazard ratio [HR]=1.8 [1.1-2.9] , p=0.02 and IR HR=1.7 [1.1-2.6], p=0.01) . Each insulin deficient subtype also appeared to carry increased risk: ID HR=1.7 (0.9-3.1, p=0.12) and MP HR=2.1 (1.0-4.2, p=0.048) . Conclusions: GGI confers an increased risk of future prediabetes/DM, regardless of the mechanism leading to glucose intolerance. A combination of insulin resistance and deficiency may convey the highest risk of future prediabetes/DM. Disclosure D.J. Selen: None. T. Thaweethai: None. K. James: None. J.L. Ecker: None. J.B. Meigs: Consultant; Quest Diagnostics. C.E. Powe: None. Funding National Institutes of Health (T32DK007028) , Massachusetts General Hospital (Physician Scientist Development Award and Claflin Distinguished Scholar’s Award)
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 18
    In: Obstetrics & Gynecology, Ovid Technologies (Wolters Kluwer Health), Vol. 142, No. 3 ( 2023-09), p. 594-602
    Abstract: To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight–related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. METHODS: In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight–related adverse pregnancy outcomes. RESULTS: Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23–1.49, P 〈 .001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08–1.35, P 〈 .001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52–2.08, P 〈 .001). The odds of birth weight–related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. CONCLUSION: Gestational glucose intolerance in pregnancy is associated with birth weight–related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.
    Type of Medium: Online Resource
    ISSN: 0029-7844
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2012791-1
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  • 19
    In: Diabetes, American Diabetes Association, Vol. 67, No. Supplement_1 ( 2018-07-01)
    Abstract: Hyperglycemia is a common complication in hospitalized patients with type 2 diabetes mellitus (T2DM) on continuous enteral nutrition therapy (ENT). The purpose of this study was to identify an insulin regimen for this patient population that provided adequate coverage for hyperglycemia without significant hypoglycemia. A retrospective chart review was conducted at the University of Vermont Medical Center for noncritically ill patients admitted between 07/01/2012 and 09/01/2015 who had T2DM and received continuous ENT for ≥72 hours—209 patients met the inclusion criteria; 117 had received aspart sliding scale only and 92 had received aspart with long-acting glargine. Our results revealed no evidence of severe hypoglycemia (blood glucose & lt;40mg/dL) in either group, and the occurrence of hypoglycemia (blood glucose & lt;70mg/dL) was similar in both groups (p=0.54). However, there was a difference in the percentage of blood glucose values within the optimal range (100 to 180mg/dL): the aspart-only group had 60.3%±27.2% of values within this range compared to 36.6%±24.4% in the aspart+glargine group (p & lt;0.001). The aspart+glargine group had blood glucose levels & gt;180 mg/dL 58.8%±26.9% of the time compared to 33.1%±28.6% in the aspart-only group (p & lt;0.0001). In conclusion, both insulin regimens resulted in similar efficacy in noncritically ill, hospitalized patients with T2DM receiving continuous ENT without significant hypoglycemia. However, neither regimen resulted in blood glucose values in the optimal range for a sufficient percentage of the 72-hour period. A basal and bolus insulin regimen, rather than sliding scale only, is likely needed to improve overall glycemic control in these patients while preventing hypoglycemia. Further prospective studies are needed in this area to identify the most appropriate insulin program to treat hyperglycemia in hospitalized patients on ENT. Disclosure D.J. Selen: Employee; Spouse/Partner; CVS/Caremark. A.B. Howard: None. M.P. Gilbert: Consultant; Self; Sanofi US, Novo Nordisk A/S.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2018
    detail.hit.zdb_id: 1501252-9
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  • 20
    Online Resource
    Online Resource
    Elsevier BV ; 2018
    In:  Endocrine Practice Vol. 24, No. 10 ( 2018-10), p. 900-906
    In: Endocrine Practice, Elsevier BV, Vol. 24, No. 10 ( 2018-10), p. 900-906
    Type of Medium: Online Resource
    ISSN: 1530-891X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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