bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-166 Primary Adrenal Insufficiency Caused by Underlying Tuberculosis
Authors: Jamal Umara Zahir
Published: May 2020

Introduction

Primary adrenal insufficiency (AI) is a rare endocrine disorder affecting 1 in 100,000 people. Primary AI is a gradual destruction of the adrenal cortex. Etiology includes autoimmune, tuberculosis, histoplasmosis, blastomycosis, adrenal metastases, primary adrenal tumors, and opportunistic infections of HIV. Since aggressive treatment of TB, the incidence of TB adrenalitis has significantly declined, now accounting for 20% of reported cases where as autoimmune causes of AI account for 70%. Most common symptoms are non-specific, and diagnosis is often delayed, with patient initially presenting with a life-threatening adrenal crisis.

Case

Patient is an incarcerated 65 y/o African American male with PMHx of hypothyroidism who was admitted to the hospital for AMS after being found unresponsive in his prison cell. On admission, patient was febrile, hypotensive and tachycardic. He looked disheveled, confused, and lethargic. Other exam findings were negative.

Lab results revealed WBC 11.7/μL, serum sodium 116 mmol/L, serum potassium 5.2 mmol/L, serum glucose 68 mg/dL, serum osmolality 237mOsm/kg, TSH 26.3mIU/L, and random cortisol 1.6ug/dL. ACTH stimulation test revealed pre-challenge cortisol levels 5.1ug/dL, 30-minute 4.9ug/dL and 60-minute 4.5ug/dL. ACTH 1271 pg/mL (normal range 7.2-63.3pg/mL). A normal response is a stimulated cortisol level > 18ug/dl. Chest x-ray revealed left lower lobe pneumonia.

Clinical signs/symptoms and labs were consistent with primary AI. Adrenal crisis was most likely precipitated by underlying pneumonia. Workup was negative for 21-Hydrolase Antibodies, HIV, CMV, and histoplasmosis. However, QuantiFERON-TB Gold Test was positive. Abdominal CT revealed bilateral enlarged non-enhancing adrenal nodules with coarse calcifications. Biopsy of right adrenal gland revealed necrotizing caseating granulomatous inflammation. Biopsy was negative for isolated aerobic, anerobic, fungal organisms, AFB, and mycobacterium PCR.

Due to current findings and high suspicion of TB adrenalitis, patient is currently being treated as culture-negative tuberculosis along with PO hydrocortisone for underlying AI.

Discussion

Adrenal tuberculosis is a rare cause of primary adrenal insufficiency in developed countries. There should be high suspicion for AI when a patient presents with hypotension, hyponatremia, hyperkalemia and/or hypoglycemia. In this case, although patient did not have a positive AFB culture, he did have a positive QuantiFERON-TB Gold Test along with consistent findings on CT and biopsy. Thus, case was concluded to have high suspicion of primary AI secondary to underlying untreated tuberculosis. Prompt treatment with antituberculosis medication, appropriate steroid therapy, along with monitoring of adrenal function, underlying adrenal insufficiency may be reversible if detected in early stages and decrease mortality.
MON-117 Reducing Unnecessary Repeat Vitamin D Testing at a Large Ambulatory Hospital: A Quality Improvement Initiative
Authors: Koshkina Olexandra , Boggild Miranda , Tai Felicia , Mukerji Geetha
Published: May 2020

Background:

With the increasing interest in the importance and potential benefits of vitamin D, there has been a significant rise in unnecessary vitamin D testing.

The aim of the project was to reduce unnecessary repeat vitamin D testing at Women’s College Hospital by 50% by May 30th 2020.

Methods:

The Model for Improvement framework was used in the design of the quality improvement project to reduce unnecessary repeat vitamin D testing. Problem characterization was conducted to design the intervention to address root causes and iterative Plan-do-Study-Act cycles were used to develop an intervention that incorporated a best practice advisory (BPA). The primary outcome measure was unnecessary vitamin D testing. Unnecessary repeat testing was defined as: repeat 25-hydroxyvitamin D testing within 3 months or repeat 25-hydroxyvitamin D testing after a normal result (>75 mmol/L) in the preceding 12 months.

Secondary outcomes which included BPAs generated, as well as the number of BPAs that resulted in no test being ordered were tracked. Paper-based orders were also tracked as a balancing measure.

Results:

It was identified that 12.7% of vitamin D testing (n= 289/2276) between July 2017 and July 2018 was related to unnecessary repeat testing. Following our cause and effect analysis and problem characterization, it was noted that providers ordered repeat vitamin D testing due to being unaware of prior normal results, as well as due to a knowledge gap of current testing recommendations. If the 25-hydroxyvitamin D order was identified as unnecessary at the time of order entry, a BPA was generated at the point of care. The BPA was implemented on February 4th, 2019. As of August 31st, 2019 based on the analysis of the number of BPAs generated and the number of tests not ordered as a result, there has been a 26% reduction in the number of inappropriate repeat vitamin D orders.

Conclusions:

Based on the preliminary data, a best practice advisory alert for vitamin D testing can be an appropriate QI intervention to reduce unnecessary vitamin D testing. Ongoing data analysis will be conducted to assess the long-term impact and sustainability of this intervention. Next steps include consideration of implementation of force function to reduce inappropriate repeat vitamin D testing.
SAT-503 Levothyroxine Absorption Testing in Three Patients with Severe Hypothyroidism on Adequate Replacement
Authors: Martinez Eduardo Andres Lopez , Carlson Scott , Force Bahar Kapoor , Kanji Aleem , Jiang Bryan , Ram Nalini
Published: May 2020

Background: Levothyroxine (L-T4) absorption is a concern in patients who report appropriate self-administration but remain clinically and biochemically hypothyroid. However, there are no established guidelines for L-T4 absorption testing.

Clinical Cases: Two women (A and B) with a history of Graves’ disease and radioactive iodine ablation (RAI) on weight-based L-T4 replacement presented to the hospital with severe fatigue and bilateral leg swelling. A third woman (C) with a history of papillary thyroid carcinoma, total thyroidectomy and RAI, on suppressive doses of L-T4 presented to the clinic with fatigue, constipation and weight gain. All patients reported compliance with taking L-T4 with appropriate technique. They had no known medical problems contributing to a malabsorptive state, and were not taking any medications known to interfere with L-T4 absorption.

Initial testing of thyroid function revealed TSH (0.57-3.5 μIU/mL)/Free T4 (0.61-1.18 ng/dL) levels of 10.12/0.249, 45.95/<0.2 and 142/<0.2 in patients A, B and C respectively. Patients A and B tested negative for Helicobacter pylori infection, celiac disease and lactose intolerance. Patient C had been successfully treated for H. pylori infection in the past. Celiac testing was negative, but the patient tested positive for anti-parietal cell antibodies and vitamin B12 deficiency. She was referred to Hematology & GI specialists. None of the patients had clinical evidence of heart failure and had normal echocardiograms.

In order to evaluate for poor absorption, all patients underwent L-T4 absorption testing. Based on published data, baseline TSH and Free T4 levels were obtained followed by administration of 1000 mcg of L-T4. Next, free T4 levels were obtained at 2 hours for all patients and at 4, 8 and 24 hours for patient A & B. Patients A and B underwent testing in the inpatient setting, while Patient C was tested in the outpatient clinic.

In all cases, a > 50% rise in free T4 levels was observed at 2 hours, suggesting non-adherence or “pseudo-malabsorption”. Patients were counseled extensively regarding proper technique and compliance with L-T4. Patients A and B demonstrated rapid clinical improvement in the hospital, and Patient C reported to her next clinic visit with clinical and biochemical improvement.

Conclusions: Though guidelines have not been established for L-T4 absorption testing, case reports exist exhibiting the safety and efficacy of L-T4 absorption challenge with a weekly weight-based dose or 1000 mcg of LT4. Our case series show the success of the latter with meaningful results in as little as 2 hours. Case C demonstrates that this test can be done safely and cost-effectively as an outpatient. Standardization of L-T4 absorption test will be of great utility in the management of this common problem encountered by endocrinologists.
SAT-470 When The Heart Can’t Clap To The Thyroid’s Beat
Authors: Thakkar Aditi , Trejo-Parades Maria Camila , Madgula Anantha Sriharsha , Stevenson Margaret
Published: May 2020

Hyperthyroidism is associated with multiple cardiac pathologies including dilated cardiomyopathy, isolated right ventricular heart failure, and atrial fibrillation (AF). Long standing untreated hyperthyroidism in conjunction with AF can cause severe dilated cardiomyopathy with reduced ejection fraction that is completely reversible with treatment. We present the case of a previously healthy male who presented with florid congestive heart failure (CHF) as an initial presentation for hyperthyroidism. A 37-year-old male presented to the emergency department with progressively worsening dyspnea on exertion and lower extremity edema for one month. His heart rate was noted to be 172 bpm and an EKG was done that showed AF. He was clinically noted to be in heart failure and was admitted for further management. He was started on metoprolol with good heart rate control and was started on furosemide for diuresis. A transthoracic echocardiogram was done and showed severe global hypokinesis with left ventricular ejection fraction reduced to 20% along with bi-atrial enlargement and dilated left ventricular cavity. Ischemic cardiomyopathy was ruled out with left heart catheterization. A TSH level was checked as a part of workup for non-ischemic cardiomyopathy and atrial fibrillation and was markedly reduced to <0.01mIU/L with free T4 of 1.49ng/dL and free T3 of 6.7ng/dL. A diagnosis of hyperthyroid cardiomyopathy with concomitant tachycardia induced cardiomyopathy was made. Autoimmune workup was negative for anti-thyroid-peroxidase and anti-thyroid-stimulating antibodies. Ultrasound of his thyroid gland revealed multiple thyroid nodules concerning for toxic multinodular goiter. He was started on methimazole and discharged after volume optimization with diuresis to closely follow up with endocrinology and cardiology for further management. CHF can be the primary presentation in about 6% of patients with hyperthyroidism. T3 is the main thyroid hormone that binds to cardiomyocytes. It increases the expression of beta-adrenergic receptors on cardiomyocytes and subsequently increases heart rate and contractility. T3 can also cause atrial arrhythmias such as AF by decreasing the parasympathetic tone. Concomitant AF and hyperthyroidism can cause reduced ejection fraction due to tachycardia induced cardiomyopathy and dilated cardiomyopathy. Treatment mainly is with beta-blockers that slow down the heart as well decrease serum T3 levels by blocking 5-monodeiodinase which converts T4 to T3. Our patient was started on beta-blocker and methimazole with good reduction in heart rate and improvement of symptoms. Recovery of cardiac function will be assessed with longitudinal follow up. As hyperthyroidism is one of the few causes of CHF that is completely reversible, clinicians must maintain low degree of suspicion in patients with new onset heart failure especially when associated with AF.
OR13-06 Implementation of a High-Risk Fracture Program in an Integrated Healthcare Delivery System
Authors: Hamann Kendal L , Chandra Malini , Hui Rita L , Lee Catherine , Khan Mehreen M , Fulchino Lisa , Lo Joan Chia-Mei
Published: May 2020

BACKGROUND: Fracture events in older adults are important opportunities for secondary prevention. In response to national (HEDIS) quality metrics in 2008, our medical group implemented a fracture prevention program, identifying women age ≥65y who experienced a fracture and targeting them for osteoporosis screening or treatment within six months. In 2015, we added an outreach program for “high-risk secondary fracture prevention” targeting women age 60-85y and men age 70-85y for osteoporosis therapy within 6 months after a hip, pelvic, humerus, wrist or vertebral fracture. This study examines whether targeting “high-risk fracture” in women and men results in higher treatment rates following a non-vertebral major osteoporotic fracture.

METHODS: This retrospective study was conducted using data from women age 60-85y and men age 70-85y who experienced a fracture of the hip, humerus, and wrist in 2013-2014 (Cohort 1, the era of our HEDIS-only program) or 2015-2016 (Cohort 2, the era of our added “high-risk secondary fracture prevention” program). We excluded patients with primary bone disorders or metastatic cancer and those with osteoporosis treatment in the year prior to fracture. Osteoporosis drug therapy (oral/IV bisphosphonates, denosumab, raloxifene or teriparatide) initiated within six months after the fracture date was assessed. Differences between groups were compared using the chi-squared test, and multivariable logistic regression was used to examine predictors of treatment.

RESULTS: There were 5727 (Cohort 1) and 6469 (Cohort 2) adults identified with hip, humerus, or wrist fracture (high risk fracture). Wrist fracture was the most prevalent fracture in women and hip fracture the most prevalent in men. Osteoporosis treatment initiation within 6 months of the fracture date was achieved for 38% of women and 13% of men in Cohort 1 and 37% of women and 25% of men in Cohort 2. Among women age 60-64, treatment increased from 14% (Cohort 1) to 25% (Cohort 2). Overall, fracture in the later era (2015-2016) was associated with a slightly lower odds of post fracture treatment initiation (adjusted odds ratio OR 0.8, 95% confidence interval (CI) 0.7-0.9) in women 65-85y; however, a much higher odds of treatment was seen (OR 2.3, 95% CI 1.9-2.9) for men 70-85y. Older age, hip fracture, and past osteoporosis therapy were also associated with greater odds of treatment within 6 months.

CONCLUSION: Targeted high-risk fracture intervention resulted in a 2-fold increase in osteoporosis treatment after major non-vertebral osteoporotic fracture in men 70-85y and women 60-64y, the demographic subgroups not previously targeted by HEDIS-based intervention. However, treatment of fractures in women already targeted by HEDIS-based intervention did not increase. Future studies should address potential barriers to treatment and assess the impact of added high-risk fracture outreach on adherence to therapy.
MON-631 Quality of Life in a Pragmatic Trial of a Type 1 Diabetes Adolescent Transition Program
Authors: Leung Joseph M W S , Al-Yahyawi Naseem Y , Choi Heywood S , Stewart Laura L , Tang Tricia S , Amed Shazhan
Published: May 2020

Introduction: Adolescents with type 1 diabetes (T1D) experience ongoing deterioration in their glycemic control as they transition to young adulthood.1 Several trials have evaluated possible transition interventions to ameliorate the care gap between pediatric and adult services in T1D care, although it remains unclear which are the most appropriate.2,3 In this pragmatic study, we sought to determine whether the change in quality of life pre- and post-transition was different between adolescents with T1D accessing a transition program versus those who did not.

Methods: Between 2016-2018, we recruited 68 adolescents with T1D at their last pediatric diabetes clinic visit from a tertiary diabetes center without a structured transition program (control group) and 33 from a community-based outreach clinic with a transition program (intervention group) consisting of a transition coordinator, joint transition clinics, and pediatric and adult clinics located in the same building. At the time of transition and at one-year post-transition, we conducted chart reviews and administered surveys, including the SF-8 quality of life questionnaire. Analysis included descriptive statistics and linear regression models.

Results: The control and intervention groups had the following characteristics, respectively: age at transition 18.4 years vs. 20.5 years (p<0.001); female 47% vs. 55% (p=0.49); average A1C at the time of transition 8.2% vs. 9.1% (p=0.0053). There was no statistically significant difference in the change in SF-8 scores for each of the eight domains (general health, physical functioning, role physical, bodily pain, vitality, social functioning, mental health, and role emotional) between the two groups. However, older age at transition was associated with an improvement in SF-8 vitality domain scores between the pre- and post-transition timepoints (p=0.034). Female sex was associated with a worsening in SF-8 vitality domain (p=0.004) and social functioning domain (p=0.015) scores between the pre- and post-transition timepoints. Finally, higher average A1C in the year prior to transition was associated with a worsening in SF-8 role physical domain scores between the pre- and post-transition timepoints (p=0.002).

Conclusions: Quality of life scores in the vitality domain improved in the first year post-transition amongst young adults with T1D who transitioned at an older age, suggesting that a later transition may benefit adolescents with T1D. Additionally, worsening quality of life scores amongst young women and in those with higher pre-transition A1Cs suggest that these populations may require more specialized care at the time of transition.

References: 1. Foster et al. Diabetes Technol Ther. 2019;21(2):66-72.

2. White et al. Lancet Child Adolesc Health. 2017;1(4):274-83.

3. Spaic et al. Diabetes Care. 2019;42(6):1018-26.
OR13-02 Treatment with Zoledronic Acid Subsequent to Denosumab Cannot Fully Prevent Bone Loss
Authors: Sølling Anne Sophie K , Harsløf Torben , Langdahl Bente Lomholt
Published: May 2020

Purpose: Treatment with denosumab (DMAB) decreases bone resorption and fracture risk. Following discontinuation, bone resorption increases, bone mass is lost and fractures have been reported. The aim of the study was to investigate if an infusion of zoledronic acid (ZOL) can prevent increases in bone turnover and bone loss in patients previously treated with DMAB and if the timing of the ZOL infusion is important. Methods: The study was a 2-year randomized, open label, interventional study in patients with osteopenia after DMAB treatment for an average of 4.6 years. ZOL was administrated 6 months (6M group, n=20) or 9 months (9M group, n=20) after the last DMAB injection or when bone turnover was increased (OBS group, n=20). Patients in the OBS and the 9M groups were monitored closely and if p-carboxy-terminal collagen crosslinks (CTX) increased > 1.26 ug/l (50% above the range for postmenopausal women and elderly men), if BMD decreased > 5% at the lumbar spine or total hip, or if a patient suffered a low energy vertebral or hip fracture, ZOL was administered. In the OBS group, ZOL was administered no later than month 6. The patients were monitored with DXA 6, 12 and 24 months after treatment. ZOL was re-administered if BMD decreased > 5% at the lumbar spine or total hip or if CTX increased above 1.26 ug/l. We report the outcome 12 months after the initial ZOL infusion. The study is ongoing. Results: A total of 60 postmenopausal women and men with a mean age of 67.7 (range 51-85) years were enrolled in the study. In the OBS group 1, 2, 6, 1 and 0 patients fulfilled the CTX or BMD criteria for treatment 1, 2, 3, 4 and 5 months after baseline. The remaining 10 patients were treated at month 6. In the 9M group 2 patients fulfilled the CTX criteria for ZOL treatment at month 2. A total of 10, 5 and 5 patients in the 6M, 9M and OBS groups, respectively were re-retreated. In the 6M group CTX decreased initially, but increased rapidly thereafter, and 6 months after ZOL, CTX was 0.60±0.08 g/L (mean±SEM). CTX increased rapidly in the 9M and OBS Groups before ZOL, was suppressed by ZOL but increased again thereafter; CTX was 0.47±0.05 μg/L and 0.47±0.05 μg/L 6 months after ZOL in the 9M and the OBS groups, respectively. Mean CTX was within the premenopausal reference range 12 months after ZOL in all 3 groups. From study baseline to twelve months after ZOL BMD at the lumbar spine had decreased by 4.8±0.7%, 4.1±1.1%, and 4.7±1.2% in the 6M, 9M and OBS groups, respectively (p≤0.002 for all without differences between groups) and at the total hip by 2.6±0.5%, 3.2±0.8%, and 3.6±0.8% in the 6M, 9M and OBS groups, respectively (p≤0.001 for all without differences between groups). The decline in BMD was more pronounced in the months before ZOL in the 9M and OBS groups whereas the decline was steadier in the 6M group. Conclusion: Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia.
SUN-021 Age-Specific Multiples of the Median Level of Serum Anti-Mullerian Hormone Is a Potential Marker for Diagnosis of Polycystic Ovary Syndrome
Authors: Raymond Li Hang Wun , He Yi-Lei , Li Rong , Wong Ching Yin Grace , Sy Barre , Lam Ching Wan , S L Lam Karen , Peng Hong Mei , Mu Sha , Schooling Mary , Yeung William Shu Biu , Ho Pak Chung , Ng Ernest Hung Yu
Published: May 2020

Serum anti-Mullerian hormone (AMH) levels are significantly higher in women with polycystic ovary syndrome (PCOS) than in normal ovulatory women. Different diagnostic cut-off values of AMH for discriminating women with PCOS from normal controls have been proposed. This is attributed partly to the different assay methods used with different calibration, as well as the age-related changes in serum AMH levels. We propose that it may be more appropriate to use age-specific multiples of the median (MoM) of AMH value instead of a “one for all ages” cut-off as a diagnostic threshold. Hence, we conducted a retrospective study to validate the performance of age-specific MoM of AMH value in the diagnosis of PCOS. We studied on a cohort of 751 women presented to the clinic for menstrual disorders or fertility treatment, including 473 women diagnosed with polycystic ovary syndrome by the Rotterdam criteria and 278 normal ovulatory controls. Their archived serum samples, collected at the early follicular phase, were retrieved and assayed for AMH by the automated Access AMH assay. The MOM AMH of each subject was calculated based on the age-specific reference ranges recently established by our group. Our results showed that MOM AMH was significantly higher in women with PCOS compared to controls (p<0.0001). When stratified into five-yearly age groups, there was no significant difference in MOM AMH (p>0.05) among women with PCOS aged 21-25, 26-30 and 31-35 years, but those aged 36-40 years had significantly higher MOM AMH (p<0.05) compared to the other younger age groups. Among the ovulatory controls, no significant difference was observed in MOM AMH among all the age groups (p>0.05). The area under the receiver-operator characteristic curve was 0.852 (95% CI 0.825-0.877) (p<0.0001) for discriminating women with PCOS from ovulatory controls by MOM AMH. The best cut-off value of MOM AMH was 1.44, and the corresponding sensitivity and specificity were 76% and 79% respectively. At the fixed specificity of 80% and the corresponding sensitivity of 73% (with positive and negative likelihood ratios of 3.8 and 0.33 respectively), the cut-off value of MOM AMH was 1.5. In conclusion, age-specific MOM AMH is a promising surrogate of antral follicle count in the diagnosis of PCOS.
MON-024 Steroid Cell Tumor, Not Otherwise Specified; A Rare Case of Hyperandrogenism
Authors: folawewo kehinde Matilda , Shanaz Fazeena , Hodge MaKenzie , Osman Nada , Zenebe Anteneh Woldetensay , Ganta Vijaya A , Odonkor Wolali Akua-Sabia , Nunlee-Bland Gail Louise
Published: May 2020

BACKGROUND:

Steroid cell tumor is a rare sex cord stromal tumor. There are 3 types including steroid cell tumor not otherwise specified (NOS), stromal luteoma and leydig cell tumors.

Steroid cell tumor (NOS) is the most common of all the subtypes. About 75% of the steroid cell tumor (NOS) are secretory. They can secrete androgens and estrogens. In a few cases, cortisol and renin secretion have been reported. The patient’s clinical features depend on the hormone secreted.

CASE PRESENTATION

Here, we report a case of a 22-year-old woman who was seen at an outpatient clinic for hirsutism, irregular menstrual bleeding, and progressive weight gain. Examination revealed androgenic facial hair growth, clitoromegaly and obesity.

Initial differentials on presentation were PCOS, ovarian or adrenal pathology. Initial LH, FSH values were normal. Lab investigation showed elevated testosterone, DHEAS and 17-OH progesterone levels. Baseline labs showed Androstenedione of 3345 ng/dl (41-262 ng/dl), DHEAS of 595.5 ug/dl (110- 431.7 ug/dl), 17-OH progesterone was 2394 ng/dl (follicular: 15-70 ng/dl, Luteal: 35-290 ng/dl), total and free testosterone was 558 ng/dl (premenopausal; 10-55ng/dl) and 33.0 pg/ml, (0.8-1.4pg/ml), respectively. Patient subsequently had an ACTH stimulation test which showed an increase in 17-OH progesterone from 384 ng/dl to 657 ng/dl and a repeat showed an elevation from 204 to 322 ng/dl, ruling out a late onset CAH. She was then sent for pelvic sonogram which showed the presence of a left ovarian mass 4.9x 4.8x 4.8 cm and a pelvic CT scan confirmed a left ovarian mass measuring 6.8x5.5x 5.5 cm and an unremarkable right ovary. She underwent a laparoscopic unilateral salpino-oophorectomy and histology confirmed the diagnosis of an ovarian steroid cell tumor (NOS). Post-surgery, the androgen levels returned to normal. The patient is now being followed for recurrence.

CONCLUSION

Women who present with virilism should be evaluated adequately with comprehensive history taking and physical examination along with appropriate biochemical tests and imaging studies to confirm tumor location and plan for surgery.
MON-719 The Cellular and Molecular Landscape of Hypothalamic Patterning and Differentiation
Authors: Kim Thomas
Published: May 2020

The hypothalamus is a central regulator of physiological homeostasis. During development, multiple transcription factors coordinate the patterning and specification of hypothalamic nuclei. However, the molecular mechanisms controlling hypothalamic patterning and cell fate specification are poorly understood. To identify genes that control these processes, we have used single-cell RNA sequencing (scRNA-Seq) to profile mouse hypothalamic gene expression across multiple developmental time points. We have further utilised scRNA-Seq to phenotype mutations in genes that play major roles in early hypothalamic patterning. To first understand hypothalamic development, hypothalami were collected at both embryonic (E10-E16, E18) and postnatal (PN4, PN8, PN14, PN45) time points. At early stages, when the bulk of hypothalamic patterning occurs (E11-E13), we observe a clear separation between mitotic progenitors and postmitotic neural precursor cells. We likewise observed clean segregation among cells expressing regional hypothalamic markers identified in previous large-scale analysis of hypothalamic development. This analysis reveals new region-specific markers and identifies candidate genes for selectively regulating patterning and cell fate specification in individual hypothalamic regions. With our rich dataset of developing mouse hypothalamus, we integrated our dataset with the Allen Brain Atlas in situ data, publicly available adult hypothalamic scRNA-Seq dataset to understand hierarchy of hypothalamic cell differentiation, as well as re-defining cell types of the hypothalamus.

We next used scRNA-Seq to phenotype multiple mutant lines, including a line that has been extensively characterised as a proof of concept (Ctnnb1 overexpression), and lines that have not been characterised (Nkx2.1, Nkx2.2, Dlx1/2 deletion). We show that this approach can rapidly and comprehensively characterize mutants that have altered hypothalamic patterning, and in doing so, have identified multiple genes that simultaneously repress posterior hypothalamic identity while promoting prethalamic identity. This result supports a modified columnar model of organization for the diencephalon, where prethalamus and hypothalamus are situated in adjacent dorsal and ventral domains of the anterior diencephalon. These data serve as a resource for further studies of hypothalamic development and dysfunction, and able to delineate transcriptional regulatory networks of hypothalamic formation.

Lastly, using our mouse hypothalamus as a guideline, we are comparing dataset of developing chicken, zebrafish and human hypothalamus, to identify evolutionarily conserved and divergent region-specific gene regulatory networks. We aim to use this knowledge and information of key molecular pathways of human hypothalamic development and produce human hypothalamus organoids.
MON-707 Improving Screening for Diabetic Retinopathy in a Resident Based Clinic
Authors: Tofil Kathrin Sandra , Jayawardena Nishanie , Khan Noor , Escobar Francisco Bonilla
Published: May 2020

Introduction Diabetic retinopathy is the leading cause of blindness in US Adults. In order to improve screening rates, we partnered with the Division of Ophthalmology and installed an onsite retinal camera at our primary care clinic. This led to an improvement in EMR reported screening rates from 20.5% to 44% over the first 3 months. We noticed that any fundus photo, whether gradable or not, led to an automatic annotation in EMR (EPIC) health Maintenance that screening had been completed. Abnormal or ungradable (quality too poor to interpret) retinal photos must be followed up with a complete ophthalmologic evaluation. We designed a chart audit to investigate further whether ungradable retinal photos were being followed up appropriately. Methods A retinal camera was installed in the clinic, and patients obtained DR screening during their routine visits from May through October 2018. The nursing staff received training on using the camera and ensuring image quality. These images were then sent to an Ophthalmologist and resulted within the work week. Patients with an abnormal or poor-quality retinal photo were contacted by their resident PCP. We did a retrospective chart review of patients with ungradable photos evaluating whether patients were contacted and whether they followed up with Ophthalmology in the 3 month period after the initial intervention. Results Of the 131 patients who received fundus photos in the study period, 29 (22%) had ungradable photos. Twenty-four of these patients were contacted and ophthalmology consults were placed for 22 patients. Eleven (38%) of these patients went on to complete screening with Ophthalmology within 3 months of the ungradable photo. Eighteen patients, or 62% of ungradeable photos, remained incorrectly identified as having completed retinopathy screening by EMR. Discussion Over reliance on EMR reporting features can lead to incorrect assumptions about DR screening. Based on this analysis, we need to design better interventions for following up on ungradable photos and ensuring appropriate follow up. One such intervention may be changing how EMR reports ungradable photos. EPIC is a widely used EMR in outpatient settings and other practices may be facing similar issues.
OR01-05 Long-Term Efficacy of T3 Analogue Triac in MCT8 Deficiency
Authors: Geest Ferdy S van , Groeneweg Stefan , Toor Hans van , Wal Ronald van der , Waart Monique de , van den Berg Sjoerd Adrianus Antonius , Peeters Robin Patrick , Visser W Edward
Published: May 2020

Background: MCT8 deficiency is a severe disorder caused by mutations in the thyroid hormone transporter MCT8. MCT8 deficiency is characterized by severe intellectual and motor disability and high serum T3 concentrations that result in thyrotoxic symptoms in peripheral tissues. This predisposes to substantial morbidity and mortality. Preclinical studies showed that the T3 analogue Triac can bypass defective MCT8 at the cellular level. Recently, we reported the results of an international multicenter trial, in which biochemical and clinical outcomes improved in patients with MCT8 deficiency who were treated with Triac for 12 months (1). However, long-term follow-up data of patients with MCT8 deficiency treated with Triac are lacking, particularly in young children. Therefore, we aimed to investigate the long-term efficacy of Triac therapy in a worldwide cohort of patients with MCT8 deficiency.

Methods: We investigated the efficacy of oral Triac treatment in pediatric (n=78) and adult (n=5) patients with MCT8 deficiency in 20 countries. Triac dose was titrated according a predefined dose-escalation scheme aiming to normalize serum T3 concentrations (target 1.4-2.5 nmol/L). Thyroid function tests and biochemical markers of thyroid hormone action in peripheral tissues (SHBG, creatine kinase, creatinine) were measured at baseline and during control visits.

Findings: In total, 83 patients with a median baseline age of 5 years (range 6 months – 66 years) were treated, including 24 patients aged 0-2.5 years and 17 patients aged 2.5-5 years. They were treated with Triac during 144 patient years, of whom the follow-up time was >5 years in 9 patients and 2-5 years in 22 patients. Mean dose was 45 µg/kg/day (range 11-107 µg/kg/day). Once a stable dose was achieved, no further dose adjustments were needed.

Mean serum T3 concentrations decreased from 5.02 to 1.94 nmol/L (normal 1.4 – 2.5 nmol/L). SHBG concentrations improved from 238 to 204 nmol/L (normal 40-140 nmol/L). Mean creatine kinase and creatinine concentrations improved from 113 to 140 U/L (normal <230 U/L) and from 32 to 38 µmol/L (normal 31-68 μmol/L), respectively. No drug-related severe adverse events were reported.

Interpretation: Triac is a safe treatment that results in sustainable improvements of the severe thyrotoxic state in pediatric and adult patients with MCT8 deficiency.

References: 1. Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D, et al. Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial. Lancet Diabetes Endocrinol. 2019;7(9):695-706.
MON-488 Technologies of Diffuse Optics in the Diagnosis of Thyroid Cancer
Authors: Velazquez Gloria Beatriz Aranda , Presti Giuseppe Lo , Cortese Lorenzo , Contini Davide , Mora Alberto Dalla , Halperin Irene , Hanzu Felicia Alexandra , Pifferi Antonio , Squarcia Mattia , Tosi Alberto , Durduran Turgut , Porta Mireia Mora
Published: May 2020

BACKGROUND:

The most common tool to test malignancy in the study of thyroid nodules (NT) is ultrasound and fine needle aspiration biopsy (FNAB). However, the sensitivity and specificity of the method and the effectiveness in thyroid cancer are limited; therefore new methods to study thyroid nodules are required. In this way our goal is to introduce hybrid diffuse optical instruments that are capable to measure and discriminate altered microvascular blood flow, blood volume and tissue scattering coefficients of TN. Near-infrared diffuse optical technologies aim to overcome the shortcomings of present techniques while screening for malignant thyroid nodules for early and fast diagnosis of cancer. This idea was based on the previous experience in breast cancers with diffuse optical techniques.

METHODS:

We have developed a device based on near-infrared diffuse correlation spectroscopy (DCS), which is a technology aimed at retrieving the microvascular flow of a certain region of tissue by mean of low power near-infrared laser light, and used in combination with a commercial ultrasound system (US). In order to combine these devices, we have developed a probe enabling multimodal data acquisition and subsequently we have analyzed the optical properties and the blood flow index in the thyroid lobes of eleven subjects who presented a thyroid nodule.

RESULTS:

Four subjects have required FNAB: P4 and P7 were reported as being malignant (Bethesda VI and IV respectively) while P6 and P8 were evaluated as being benign (Bethesda II). Surgical removal confirmed papillary thyroid carcinoma in P4, while denied the result of FNAB for P7 (Multinodular thyroid hyperplasia). We have considered the contralateral lobe as intra-subject reference to validate the feasibility of the DCS system in a very absorbing tissue as thyroid is. The difference between the blood flow index of the nodule and the contralateral lobe is maximum for subject P4, while the difference in benign subjects is lower. T-test showed no significant difference between benign nodules and contralateral lobes. Subject P7 showed a small difference as for other benign subjects despite the FNAB results indicating presence of malignancy.

CONCLUSION:

Apparently diffuse optics technologies would be able to differentiate malignant thyroid nodules from benign thyroid nodules, but more measurements require confirming our preliminary results as that diffuse optical technology can complement the current techniques such as US and FNAB.

A new measurement campaign is being scheduled with a completed, fully integrated device that was developed within the LUCA project (http://www.luca-project.eu).
MON-168 Peri-Operative Glucocorticoids in Patients Having Total Joint Replacements: Help or Harm?
Authors: Chukir Tariq , Goodman Susan , Tornberg Haley , Do Huong , Thomas Charlene , Sigmund Alana , Russell Linda , Stein Emily Margaret
Published: May 2020

Introduction: There is limited evidence to guide peri-operative steroid regimen in patients receiving chronic glucocorticoid (GC) therapy. Many patients who undergo minor surgical procedures receive stress-dose steroids. While hemodynamic instability and hypotension are well-recognized risks of inadequate peri-operative GCs, there may be harms associated with using doses higher than necessary. Whether surgical outcomes differ according to peri-operative steroid dose is not known. We hypothesized that patients who had greater GC exposure have less hypotension, but higher rates of hyperglycemia and post-operative complications.

Methods: This retrospective study investigated the relationships between peri-operative GC use and post-operative complications following total hip/knee joint replacement (arthroplasty) in patients with rheumatoid arthritis (RA). All GCs were converted to prednisone equivalents; GC exposure was assessed by number of doses and total cumulative dose during the hospitalization. Complications (infection, thromboembolism and cardiovascular events) were determined by chart review.

Results: Of 432 patients with RA included, half (54%) underwent knee arthroplasty. Mean age was 64±12 years, 78% were women. Thirty percent of patients were on home GCs (mean dose 7±4mg/day). Median cumulative GC dose during hospitalization was 37mg [IQR 27, 57]. Compared to patients who only received one peri-operative dose of steroids, those who received multiple doses had a greater risk of post-operative complications (OR 3.319 (95% CI 1.03, 12.62; p<0.05] and hyperglycemia, glucose >180 mg/dl, [OR 1.812(0.99, 3.32; p<0.05]. They did not have an increase in hypotension or need for pressors. Among patients who received steroids while in the hospital (90%), there was a small but significant dose response relationship with hyperglycemia (r=0.16; p<0.01). Higher cumulative dose was also associated with higher risk of complications; for every 10 mg increase in cumulative dose, the risk of complications increased by 15% (p<0.01).

Conclusions: Among RA patients undergoing arthroplasty, we did not find that lower doses of GCs were related to more hypotension. However, patients with higher GC exposure were more likely to have hyperglycemia and post-operative complications. Our results suggest that use of peri-operative GC is not without risk, and the lowest doses possible should be considered. Further studies are needed to confirm these findings and to define the optimal dosing strategies for patients receiving peri-operative GCs.
SUN-637 The Impact of Hyperandrogenemia and Western-Style Diet on Post-Pregnancy Metabolism in Nonhuman Primates
Authors: Takahashi Diana Lynn , Mishler Emily , Slayden Ov Daniel , Hennebold Jon D , Roberts Charles T , True Cadence
Published: May 2020

Polycystic ovary syndrome (PCOS) often is associated with hyperandrogenemia and an increased incidence of obesity and type 2 diabetes. To understand the separate and combined effects of androgens and obesity on reproductive and metabolic parameters, our group established a nonhuman primate model consisting of animals receiving either testosterone (T, mean value of 1.4 ng/mL), an obesogenic western-style diet (WSD, 36% of calories from fat compared to 16% in normal monkey chow), or a combination of T+WSD. T+WSD increased insulin resistance compared to WSD alone after three years of treatment and reduced fertility. Those T+WSD animals that became pregnant had a mild worsening of glucose homeostasis during pregnancy. The current study sought to determine how T+WSD affected post-pregnancy metabolic health and whether T+WSD led to the worsening of insulin resistance after pregnancy. Intravenous glucose tolerance tests (ivGTT) were performed 1) before pregnancy, 2) approximately 3-4 months after C-section, which occurred between gestational day 130-135 (3rd trimester), and 3) one year post C-section. All animal groups tended to show increases in weight, BMI, and body fat percentage after pregnancy. Both WSD groups (WSD and T+WSD) had higher overall weights, BMI, and body fat percentages. Measures of insulin sensitivity such as fasting insulin, glucose, and insulin area under the curves during an ivGTT and homeostatic model of insulin resistance (HOMA-IR) all increased over time, but there were no differences between groups. The lack of treatment effect on measures of insulin resistance may be due to the fact that animals that did not become pregnant had significantly higher indices of insulin resistance. Experimental animals underwent a second round of fertility trials thereby allowing for a comparison of glucose homeostasis for those animals that became pregnant in both the 1st and 2nd trial. The WSD group demonstrated increased fasting glucose and glucose AUC during an early third trimester ivGTT in the second pregnancy compared to the first. The control, T, and T+WSD groups did not show significant differences in glucose homeostasis between the first and second pregnancy. These findings indicate that WSD consumption may increase the risk of worsened glucose homeostasis after pregnancy and during subsequent pregnancies. Testosterone, either in isolation or in combination with WSD, did not appear to have a significant impact on post-pregnancy metabolism or worsen metabolic outcomes in a second pregnancy.
MON-695 Multiple Recurrent Lipomatoses with Thiazolidinedione Therapy in Familial Partial Lipodystrophy, Dunnigan Variety (FPLD2)
Authors: Patni Nivedita , Garg Abhimanyu
Published: May 2020

Background: FPLD2, a rare autosomal dominant disorder due to heterozygous missense mutations in LMNA, is characterized by gradual loss of subcutaneous (sc) fat from the limbs starting during late childhood and predisposition to metabolic complications, such as diabetes, dyslipidemia and hepatic steatosis. Some patients, especially females, accumulate excess sc fat in the chin, neck, supraclavicular and perineal regions. We report disfiguring and disabling lipomatoses in unusual locations with thiazolidinedione therapy in two women with FPLD2.

Clinical Cases: A 57-year-old white female with FPLD2, due to heterozygous p.R482Q LMNA mutation, developed recurrent large lipomatoses in the axillae at age 33 years, and later in the posterior neck (buffalo hump), mons pubis and above sacrum. She developed diabetes at age 30 and was started on pioglitazone 45 mg daily, which was switched to rosiglitazone 8 mg daily at age 43 years. Supra-sacral lipomatoses were approximately 40 cm X 20 cm bilaterally and continued to grow despite lipectomy and multiple liposuctions. Rosiglitazone was stopped at age 56 years, and she reported no further increase in the size of lipomatoses. Her other medications included colesevelam, atorvastatin, metformin, glimepiride, lisinopril, losartan, hydrochlorothiazide, aspirin, insulin and dulaglutide. Her 54-year-old younger sister with FPLD2 (heterozygous p.R482Q LMNA mutation) was treated with lisinopril, metoprolol, atorvastatin, liraglutide, and insulin glargine and aspart, but no history of taking thiazolidinediones, and she never developed any lipomatoses. Another 43-year-old white female with FPLD2, due to heterozygous p.S583L LMNA mutation, was noticed to have lipomatous deposits in the axillae, medial gluteal region, labia and perineal regions. She developed diabetes mellitus at age 36 years and took metformin for 6 years and pioglitazone 30 mg daily for one year before she noticed the lipomatoses. Her other medications included atorvastatin, aldactone and vitamin D3. Pioglitazone was stopped and after one year, she reported reduction in the size of lipomatoses.

Conclusion: Thiazolidinediones are selective peroxisomal proliferator-activated receptor-γ agonists and induce weight gain by increasing fat mass, especially subcutaneous depots. Our cases suggest that thiazolidinediones can cause undesired growth of non-lipodystrophic adipose tissue in patients with FPLD2 and thus should be avoided.
MON-253 A Rare Case of Pituitary Aspergillosis Diagnosed by CSF PCR in an Immunocompetent Patient with Headaches and Photophobia
Authors: Popli Rakesh , Nikoomanesh Tina , Jackson Gavin
Published: May 2020

Background: Pituitary aspergillosis is a rare infection usually found in the immunocompromised population. It is oftentimes mistaken for a pituitary adenoma based on similar clinical presentation and characteristic findings on MRI. Most cases require removal of the pituitary mass in order to make a diagnosis. Here we present the case of an immunocompetent patient with headaches and photophobia diagnosed with pituitary aspergillosis by CSF PCR and treated medically with voriconazole.

Clinical Case: A 40-year-old woman with a questionable history of Brucellosis presented with a 3 month history of headaches along with 2 days of nausea and vomiting. Vital signs were notable for intermittent hypotension but were otherwise within normal limits. Physical exam was notable for tenderness at the left temporal region, diaphoresis and photophobia. Patient was otherwise alert and oriented and had no visual field deficits or extraocular muscle dysfunction.

Patient was found to have central adrenal insufficiency with undetectable AM cortisol (<0.5 mcg/dL, n 3.7-19.4 mcg/dL), inappropriately normal ACTH (7 pg/mL, n 6-58 pg/mL) and central hypothyroidism with low TSH (0.057 mcIU/mL, n 0.358-3.8 mcIU/mL) and low free T4 (0.48 ng/dL, n 0.76-1.46 ng/dL). Patient initially presented with hyponatremia (Na 119 mmol/L, n 137-145 mmol/L) likely secondary to central adrenal insufficiency and central hypothyroidism. Gadolinium-enhanced pituitary MRI showed a heterogeneous 1.8 cm pituitary mass with rim enhancement concerning for hypophysitis.

Patient was started on stress-dose steroids with IV hydrocortisone 100 mg IV q8h, levothyroxine 50 mcg PO daily and empiric antibiotic therapy with ceftriaxone, doxycycline and rifampin due to suspicion for neurobrucellosis. Lumbar puncture was obtained showing low glucose (39 mg/dL, n 40-70 mg/dL), normal protein (47 mg/dL, n 12-60 mg/dL) and an elevated white count (WBC 9/mcL, n 0-5/mcL) with lymphocyte predominance (97% lymphocytes, n 40-80%). Blood and CSF cultures showed no growth at 2 weeks. CSF was sent for multiplex PCR which came back positive for Aspergillus.

Patient was discharged with voriconazole 300 mg PO BID for 1 year, levothyroxine 75 mcg PO daily and hydrocortisone 10 mg PO Qam and 5 mg PO Qpm. Three months later, repeat MRI showed resolution of the pituitary mass and patient felt well without headaches, nausea or vomiting.

Conclusion: This case demonstrates an atypical example of pituitary aspergillosis diagnosed without pituitary mass biopsy and treated medically with voriconazole. It demonstrates the possible role of CSF PCR to diagnose the condition and guide antifungal treatment.