bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-173 A Gigantic Uterine Leiomyoma and Big Bilateral Adrenal Myelolipomas as a Result of Untreated Congenital Adrenal Hyperplasia
Authors: La Betty , Nguyen Ha , Tung Celestine , Choi Eugene
Published: May 2020

Introduction

Patients with untreated congenital adrenal hyperplasia (CAH) can present early with severe symptoms of salt wasting, adrenal insufficiency and hyperandrogenism. Late consequences as a result of long term untreated CAH are rarely seen nowadays. We present a patient who presented with a massive uterine leiomyoma and bilateral adrenal myelolipomas due to longstanding treatment noncompliance.

Clinical Case

A female was born with ambiguous genitalia and diagnosed with CAH at birth. She was raised as a female and received steroids until age 29 when she stopped taking steroids on her own with the intention of identifying as a male. At age 37, he presented with abdominal distension, vomiting, and hypotension. Physical exam was notable for hypotension, significantly distended abdomen, hirsutism, gynecomastia and clitoromegaly. Labs revealed sodium 126 meq/L (136–145) cortisol 78.5 ug/dL (3.7–19.4), ACTH 166 pg/mL (6–50), 17-hydroxyprogesterone 4356 ng/dL (≤285), androstenedione 7188 ng/dL (35–250), total testosterone 737 ng/dL (2–45), estradiol 142 pg/mL (48–440), aldosterone <1 ng/dL (3–16), renin 0.45 ng/mL/hr (0.25–5.82), metanephrines 56 pg/mL (≤205), normetanephrines 56 pg/mL (≤148). CT abdomen and pelvis revealed a large 31 x 35 x 31 cm pelvic mass, a 5.9 x 2.4 cm right adrenal mass and an 11.8 x 8.8 cm left adrenal mass. The patient underwent total abdominal hysterectomy and bilateral adrenalectomy. Pathology of the pelvic mass was consistent with uterine leiomyoma (gross tumor was 12.4 kg) and pathology of the bilateral adrenal masses were consistent with bilateral adrenal myelolipomas.

Discussion

Glucocorticoids and mineralocorticoids are the mainstays of treatment in CAH, with the goal of providing adequate replacement while reducing levels of ACTH and adrenal androgens. Persistently elevated levels of ACTH and androgens can lead to many serious sequela, even outside of adrenal insufficiency and virilization. Due to the conversion of androgens to estrogens, untreated females with CAH have significantly elevated levels of both hormones. These high levels of androgens and estrogen can then stimulate growth of estrogen-dependent organs as exemplified by our patient. Chronic ACTH stimulation can cause adrenal hyperplasia, but has also been associated with the development of other adrenal masses including adrenal myelolipomas. Adrenal myelolipomas can become hormonally functional or cause mass effect, hemorrhage, necrosis when reaching a large enough size.

Conclusion

This case demonstrates the importance of CAH treatment compliance as there are many serious sequela outside of the expected adrenal insufficiency and virilization. Even when the desired effect is virilization with physical male features, other means of hormonal therapy should be considered as there remains the risks of abnormal growth of certain organs sensitive to the excessive hormones.
SAT-556 Use of ACTH-Stimulated Lateralization Indices Underestimates Surgically Curable Primary Aldosteronism
Authors: Yozamp Nicholas , Sacks Barry , Underhill Jonathan , Fudim Tali , Vaidya Anand
Published: May 2020

Introduction: Adrenal venous sampling (AVS) is recommended to assess laterality in primary aldosteronism to determine whether a patient has unilateral, or surgically curable, disease. Institutional practices differ in whether ACTH stimulation is used or not and if so, whether values are obtained after a single injection of ACTH or during an ACTH infusion. Studies have demonstrated appreciable discordance between lateralization based on unstimulated versus stimulated AVS.

Objective: To assess the influence of ACTH-stimulation on lateralization indices.

Methods: We performed a retrospective cross-sectional analysis of 140 patients who underwent AVS between 2012–2019. We then validated these findings in a separate cohort of 233 patients who underwent AVS between 2008–2016. AVS was performed using simultaneous, unstimulated, and triplicate sampling from the inferior vena cava (IVC) and bilateral adrenal veins, followed by repeated sampling in duplicate or triplicate from each site following a bolus of 250 ug of ACTH (cosyntropin). The lateralization index (LI) was defined as the quotient of the aldosterone-to-cortisol ratios from each adrenal vein, and the categorical definition of lateralization was defined as a LI ≥ 2 (unstimulated) and LI ≥ 4 post-ACTH.

Results: The median unstimulated LI was 8.7 compared to 8.9 post-ACTH. Seventy-one of 140 patients (51%) had a decrease in LI following the ACTH bolus. Overall lateralization discordance was 21.4%, with the majority of this discordance (90%) attributed to situations where there was an unstimulated LI ≥ 2 that became a post-ACTH LI < 4, thereby transforming a unilateral interpretation into one of bilateral disease. Comparing the group that had an increase in LI after ACTH to the group that had a decrease in LI, the latter had significantly higher rates of lateralization pre-ACTH (89% vs 74%, p=0.02) and significantly lower rates of lateralization post-ACTH (50% vs 78%, p=0.001). All of these general findings were validated in the separate cohort of 233 patients. The discordance rate between pre-ACTH lateralization and available imaging data was 32%; the same discordance rate was found when comparing post-ACTH lateralization to imaging.

Conclusions: The administration of ACTH during AVS causes an increase in LI in half of patients and a decrease in LI in the other half. Using conventional cut-offs, pre-ACTH and post-ACTH lateralization indices disagree on laterality more than 20% of the time and almost always involve pre-ACTH unilateral disease that is classified as bilateral disease post-ACTH. These findings underscore that while ACTH stimulation may be useful for confirming adrenal vein selectivity, the decrease in post-ACTH LI may result in misclassification of surgically curable primary aldosteronism in a substantial proportion of patients.
SAT-263 A Vicious Cycle of Hypercortisolism - Cyclical Cushing’s Syndrome
Authors: Force Bahar Kapoor , Yoshor Daniel , Sebastian Sherly , Takashima Mas , Samson Susan Leanne
Published: May 2020

Background: Cyclical Cushing’s syndrome (CS) is described as periods of excess cortisol secretion interspersed with low or normal cortisol. The generally acceptable criteria for diagnosis is demonstration of 3 peaks and 2 troughs in cortisol secretion but, in practice, patterns and duration of cycles are unpredictable and can present a significant diagnostic challenge. Here, we present a case series of three patients who did not meet the published criteria but had pathological confirmation of ACTH-dependent CS.

Clinical Case: Two women (A: 30 year-old, B: 40 year-old), and one man (C: 30 year-old) presented to the Pituitary Center for second/third opinions regarding CS. All patients had significant central weight gain. Patient A described cycles of rapid weight gain and loss, fluctuating facial and leg swelling, anxiety and darkening of stretch marks or scars punctuated with episodes of fatigue, lightheadedness and nausea. Patients B and C reported cyclical leg swelling, facial redness and acne. These patients had additional clinical signs of Cushingoid facies, dorsocervical and supraclavicular fat pads. Patient C had violaceous striae.

Multiple tests for CS were performed: 1 mg overnight dexamethasone suppression test, two midnight salivary cortisols, and 24h urine free cortisol (UFC). All testing was normal, with a few exceptions. Patient A had an isolated midnight salivary cortisol elevated to 0.426 (<0.112 ug/dL). Patient C had two mildly elevated 24h UFC collections of 1.4 times upper limit of normal corresponding with his cycles of peripheral edema and acne. Patient B had completely negative testing. In all 3 patients, ACTH levels were not suppressed but also not elevated. Random serum DHEA-S levels were elevated in patients A and B.

Patients A and C were found to have possible pituitary microadenomas on MRI with dynamic contrast. Patient B’s MRI was negative but inferior petrosal sinus sampling revealed a markedly elevated tumoral level of ACTH of >62,500 pg/mL with CRH stimulation. All 3 patients underwent endoscopic transsphenoidal resection by an expert pituitary surgeon with no post-operative complications in patients A & B, but development of partial diabetes insipidus in patient C. In patients A & C, pathology revealed corticotroph hyperplasia while patient B was found to have a corticotroph adenoma. Patients A & B persisted to have symptoms of hypercortisolism, opted to undergo bilateral adrenalectomy and pathology showed diffuse adrenocortical hyperplasia for both.

Conclusion: Cyclical CS is likely underdiagnosed because of difficulty in obtaining biochemical confirmation even with strong clinical suspicion of CS. DHEA-S has a long half-life as well as minimal diurnal variation, and could be an additional clue in patients with suspected pituitary source of cyclical hypercortisolism. Ultimately, clinical concern should drive further diagnostic imaging and management.
SUN-698 Management of Hyperglycemia in an Adult Patient with Glycogen Storage Disease Type 1b
Authors: Mikhael Alexandra , Zimmerman Robert S
Published: May 2020

Background: Glycogen storage disease type 1b (GSD1b) is caused by a deficiency of glucose 6 phosphatase leading to glycogen deposition. The hallmark findings of GSD1b are hypoglycemia and lactic acidosis. GSD1b can be associated with hepatomegaly, hypertriglyceridemia, hematologic abnormalities, hypothyroidism, inflammatory bowel disease, proteinuria, and hypoglycemic seizures. Main stay of therapy is to avoid fasting and to ingest frequent feeds high in complex CHO. Raw cornstarch (CS) has been used for the treatment of hypoglycemia in GSD1b since the early 1980s. CS is digested slowly, providing a steady release of glucose allowing for more stable glucose levels over a longer period of time as compared with other sources of CHO. Adults may require more CS to maintain BG >70 mg/dL and lactate <2mmol/L during the night. We report a case of an adult patient with GSD1b admitted with inability to tolerate oral intake and found to have persistent hyperglycemia on admission requiring insulin therapy.

Clinical Case: A 31 year old female with a history of GSD1b complicated by hypoglycemia, Crohn’s disease, chronic pancreatitis and neutropenia was admitted for abdominal pain, emesis and inability to tolerate CS. She was made NPO and was started on a dextrose drip to avoid hypoglycemia and hyperlactatemia. The rate of dextrose infusion was adjusted to maintain lactate levels <2 mmol/L. She developed persistent hyperglycemia with glucose values of 250–350 mg/dL. Laboratory evaluation revealed an HbA1c of 7.6% (reference [ref] 4.3–5.6%), C-peptide of 1.3 ng/mL (ref 0.8–3.9 ng/mL), lactate of 2.3–3.1 mmol/L (ref 0.5–2.2 mmol/L). BHB levels were normal (WNL). Anti-GAD, insulin and islet cell antibodies were negative. The main goal was to avoid hypoglycemia while keeping ketone and lactate levels WNL. The decision was made to start a regular insulin infusion at a constant rate of 1 u/hr to keep BG <180 mg/dL while on the dextrose infusion with close monitoring of lactate and BHB. Insulin and dextrose drip rates were adjusted based on BG. The ultimate goal was to determine total daily insulin requirements while ingesting her home CS doses and to transition to long acting insulin. Short acting insulin boluses were not used given risk of hypoglycemia. The patient’s unpredictable tolerance to CS made determining a fixed insulin dose challenging. She eventually managed to tolerate CS and was transitioned to 10 units of insulin Detemir twice daily. She was discharged with plans to get a CGM and a ketone meter. BG readings at home were between 140–170 mg/dL.

Conclusion: We report a rare case of GSD1b and diabetes. The pathogenesis may be related to effects of chronic pancreatitis or metabolic syndrome. Treatment of hyperglycemia in patients with GSD1b is challenging given the heightened risk of fasting hypoglycemia. Treatment options are limited, and there are no data regarding the safe use of insulin in this patient population.
SUN-409 Subclinical Hypothyroidism in Hospitalized Patients with Chronic Heart-Failure or Chronic Renal-Failure Is Most Probably Not Due to Thyroid Disease
Authors: Bashkin Amir , Saleh Wagde Abu , Ronen Ohad
Published: May 2020

Introduction: Subclinical hypothyroidism is common in chronic diseases such as heart failure and advanced chronic renal failure. It is unclear whether this is a thyroid disease or an isolated TSH elevation. The goal of this study was to investigate the prevalence of worsening thyroid function in these patients with recurrent admissions. Methods: We performed a retrospective review of medical records of hospitalized patients in non-surgical wards from 2013–2016. First, all patients with TSH levels above the normal range (4.95 mIU/L) and up to 12 mIU/L with FT4 levels in the normal range were identified. We then investigated which of these patients were re-hospitalized at least once within at least six months. According to data from the re-hospitalization, an increase in TSH level above 12 mIU/L or initiation of levothyroxine treatment was defined as worsening of thyroid function. Patients treated with a drug affecting thyroid function or with a known thyroid disease prior to first hospitalization were excluded from the study. Chronic heart failure and chronic renal failure were determined according to reported diagnosis and drug treatment. Chronic renal failure patients were included if the glomerular filtration rate (GFR) in the first hospitalization was below 30 ml/min/1.72 square meter. Results: Overall, 90,199 TSH tests were sent from the non-surgical wards, most of them as part of the admissions profile. Of these, 2,116 hospitalizations met the inclusion criteria of the first hospitalization. In the final analysis, 126 inpatients with at least one re-hospitalization were included, of whom 43 (34.1%) had chronic heart failure and 22 (17.5%) had chronic renal failure. According to the most recent re-hospitalization, thyroid function was worse in 11(8.7%), 4 (9.3%) and 2 (9.1%) patients of the total, heart failure and renal failure groups respectively. The TSH level was found to be normal in re-hospitalization in 81.4% of those with heart failure and 86.4% of those with renal-failure. No association between heart failure or renal-failure and thyroid function worsening was found (p = 1.00 for both). Of 34 patients with chronic heart failure re-hospitalized after 1/2-1 year, in 29 (85.3%) the repeated TSH was normal, in 3 (8.8%) it was unchanged and in 2 (5.9%) it was worse. In most re-hospitalization the worsening was due to initiation of Levothyroxin treatment and because of the retrospective nature of the study we cannot be sure whether the initiation was justified; therefore, it is likely that the worsening percentage is even lower. Conclusions: An isolated TSH elevation in hospitalized patients with past medical history of chronic heart-failure or chronic renal failure does not indicate thyroid disease, in most cases.
MON-620 Ademolus Hypoglycemic Index
Authors: Ademolu Adegbenga Bolanle
Published: May 2020

This article proposes ADEMOLUS HYPOGLYCEMIC INDEX (AHI) which is a mathematical representation of hypoglycemic episode (HE) in a patient with recurrent hypoglycemia over a consecutive three months period. It also apply it to clinical practice using diabetic patients in order to demonstrate and emphasize its relevance in present day medical practice worldwide.

This is a retrospective study of 65 HE occurring in 6 randomly selected diabetes mellitus patients from 86 case files studied who had attended the endocrinology unit. The data was analyzed by using Ademolus Classification of hypoglycemia (ACH) and the 2018 ADA/EASD Classification of hypoglycemia to define hypoglycemia. AHI was calculated from the HE using the proposed mathematical formula. SPSS version 23 was used for data analysis. All six patients had a series of hypoglycemic episodes occurring in three consecutive months. Patient 1 had an AHI of 0.53 using both ACH and 2018 ADA/EASD classification.By using the Pearson correlation statistics, AHI using ACH correlated well with AHI using 2018 ADA/EASD classification of hypoglycemia with a value of 0.993.Similarly the findings of AHI derived using ACH is significant with values derived using ADA/EASD 2018 classification of hypoglycemia with a p-value of 0.000 (correlation is significant at values of 0.01). One of the clinical implication of AHI is that the risk of developing reversible or irreversible neurological damage can be reduced clinically as patient with mild to moderate form of chronic hypoglycemia yet to develop irreversible neurological damage or neurological sequelae can be prevented early enough from progressing since a reduced AHI value out of a series will be a pointer towards progression to neurological damage if it has not occurred! In patient 1 her AHI was not in the severe range. In patient 3, in the last quarter of 2016, her AHI was 0.60, in the first quarter of 2017, her AHI was zero, then between June, July and August 2017 her AHI was 0.64. At this juncture in this patient management, it will be good to evaluate the etiological factors in this chronic kidney disease diabetic patient who once again has started having recurrent hypoglycemia as it was some 6 months earlier. Patient 6 had two consecutive reading of AHI for two consecutive quarters of a year.The result reveals that she is chronically deteriorating gradually and tending towards more severity in her development of HE as her AHI fell from 0.52 in the preceding quarter to 0.46., this connotes worsening chronic hypoglycemic state over time and a poorer prognosis. The lower the AHI, the poorer the prognosis.AHI is relevant for monitoring of chronic or long term recurrent HE in susceptible individuals whether diabetic or not.

References: 1. Fonseca VA, Kirkman MS, Darsow T, Ratner RE (2012) The American Diabetes Association Diabetes Research Perspective. Diabetes Care 35(6): 1380–1387.
SAT-345 Etanercept Induced Hypercalcemia
Authors: Chaker Bayan , Alim Hussam , El-Zein Louna S
Published: May 2020

Non-PTH mediated hypercalcemia has multiple etiologies including medications. There are some case reports showing TNF-alpha inhibitors causing sarcoidosis or sarcoidosis type presentation involving lungs, skin, lymph nodes, and kidneys.

We report here a 69-year-old male with a past medical history of prostate cancer status post prostatectomy (in remission), CKD stage 3, and seronegative rheumatoid arthritis who was sent to the ED from clinic due to hypercalcemia. On admission, patient had a calcium level of 14.2 (8.7–10.4 mg/dL), albumin 4.1 (3.4–4.8 g/dL), magnesium 2.0 (1.3–2.7 mg/dL), creatinine 2.5 (0.7–1.3 mg/dL), iPTH <2 (14–88 pg/mL), PSA 0.13 (0–4 ng/mL), 25-OH vitamin D 45.3 (30–100 ng/mL), 1,25-OH vitamin D 144 (19.9–79.3 pg/mL), alkaline phosphatase 46 (46–116 U/L) along with generalized weakness, nausea, vomiting, poor appetite, decreased oral intake, dizziness, and slight epigastric pain. Patient was given IV fluids and a dose of Reclast 3.3 mg IV was given 2 days after admission. At home for at least the past year before admission, patient was on etanercept for seronegative rheumatoid arthritis which was held on admission. CT thorax was done which showed geographic ground glass worst in the bilateral upper lobes where there is interlobular septal thickening and interstitial consolidation highly suspicious for interstitial pneumonitis and reactive appearing mediastinal lymphadenopathy. During the admission PTH-rP was 2.5 (0–2.3 pmol/L) and angiotensin converting enzyme was 36 (9–67 U/L). Based on previous case reports, etanercept was held. Upon discharge 6 days later, calcium had improved to 10.0 mg/dL, albumin 3.3 g/dL, and creatinine to 1.5 mg/dL. Upon follow up, etanercept was continued to be held. One month later, calcium level improved to 9.2 mg/dL, albumin 4.0 g/dL, iPTH 187 pg/mL, PTH-rP 3.0 pmol/L, and 1,25 OH vitamin D 50.7 pg/mL. Patient’s calcium levels remained within normal range for over one year after admission and 1,25-OH vitamin D remained normal. Moreover, patient had nuclear medicine parathyroid scan which showed no evidence parathyroid adenoma. An ultrasound thyroid was done which was negative for any thyroid/parathyroid mass or nodule. Whole body bone scan was done which showed no evidence of osseous metastatic disease. Given up trending PTH-rP levels, patient was evaluated by oncology and was found to be up to date on age recommended cancer screening and no evidence of current malignancy. Repeat CT thorax done over one year later showed stable to mildly improved bilateral ill-defined centrilobular ground glass nodules in both lungs, greater on the left side, may represent improving infectious/inflammatory process. In conclusion, when in doubt, a good medication review is essential in the evaluation of hypercalcemia because TNF-alpha inhibitors like etanercept may cause a sarcoidosis like presentation.
SAT-518 Progression of Graves Disease to Hashimoto’s Thyroiditis Following Alemtuzumab Therapy for Multiple Sclerosis
Authors: Rapier Brandon , Gargasz Frank , Zmeili Omar Suheil
Published: May 2020

Introduction: Alemtuzumab, an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis is most commonly associated with Graves disease, but autoimmune hypothyroidism may also be seen. We present an unusual case where both were present in the same patient and progression from hyperthyroidism to hypothyroidism was seen within only a few months.

Clinical Case: A 33-year-old female referred to Endocrinology clinic for evaluation of hyperthyroidism. She was complaining of palpitations, tremors, increased sweating, heat intolerance, and unintentional weight loss for 3 months. She received 2 cycles of alemtuzumab treatments over the last 21 months for her multiple sclerosis. Last treatment was 8 months before she developed hyperthyroid symptoms. Patient had no prior history of thyroid disorder. Thyroid stimulating hormone (TSH) level was within normal range before alemtuzumab was administered. TSH was monitored periodically and was normal till 8 months after receiving alemtuzumab therapy. Physical exam was remarkable for diffuse enlarged thyroid, not tender, without palpated thyroid nodules but with thyroid bruit. No proptosis was present.

Thyroid function tests obtained by her primary care physician were consistent with hyperthyroidism. Patient found to have suppressed TSH <0.015 IU/mL [0.465 - 4.680IU/mL], elevated total T3 372ng/dL [97-169ng/dL], and elevated total T4 >24.9 ug/dL [5.5 - 11.0 ug/dL].

Further workup revealed elevated Free T3, 10.90 [2.77 - 5.27 pg/mL] and elevated free T4 > 6.99 ng/dL [0.78 - 2.19 ng/dL]. Thyrotropin receptor antibody (TR Ab) was elevated as well at 3.43 IU/L [<1.75 IU/L]. Pregnancy test was negative. Thyroid ultrasound demonstrated goiter with no focal thyroid nodules seen. She was started on methimazole 10 mg daily.

One month later, TSH was elevated at 31.58 though she only took methimazole for one week and then discontinued due to rash and pruritus. At that time, she reported severe fatigue and 25 lbs weight gain. Repeated labs one month later showed elevated TSH, 60.978 IU/ML, low free T4 0.08 pg/mL and low free T3 0.72 ng/dL. Thyroid peroxidase Antibody (TPO Ab) was obtained and was 5308.8 IU/mL [0.0 - 5.5 IU/mL]. She was started on levothyroxine 100 mcg daily. Two months later, levothyroxine dose was increased to 112 mcg daily due persistent TSH elevated. At subsequent visit, patient was euthyroid with normal TSH 3.191IU/mL and normal free T4 1.48 ug/dL.

Conclusion: This case was unique in that the patient developed both TR Ab and TPO Ab after alemtuzumab therapy which resulted in Grave’s disease followed by Hashimoto’s thyroiditis. The case highlights the importance of continuous monitoring of thyroid function in patients treated with alemtuzumab given the unpredictable autoimmune phenomena which may occur.
OR04-03 Calcitonin Receptor Expressing Neurons in the PVH Regulate Feeding Behavior
Authors: Gonzalez Ian Enrique , Cheng Wenwen , Pan Warren , Lu Chunxia , Ramirez-Matias Julliana , Pei Hongjuan , Adams Jessica , Zhu Allen , Faulkner Latrice Doreen , Myers Martin Grosvenor , Olson David P
Published: May 2020

The paraventricular nucleus of the hypothalamus (PVH) is a brain region crucial for energy homeostasis. Abnormal PVH development or damage leads to hyperphagic obesity and energy expenditure deficits underscoring the importance of PVH neuronal activity in energy balance control. Application of salmon calcitonin (sCT) to the PVH suppresses feeding and calcitonin receptor (CalcR) is highly expressed in the PVH of rodents suggesting that CalcR-expressing PVH neurons contribute to energy homeostasis. In situ hybridization reveals that many CalcRPVH neurons express melanocortin-4 receptor (MC4R), a receptor required for normal feeding behavior. To investigate the physiologic roles of CalcRPVH neurons, we generated CalcR-2a-Cre knock-in mice to manipulate CalcR-expressing cells. Deletion of MC4R from CalcR expressing cells using Cre-loxP technology resulted in profound obesity in both male and female mice by 16 weeks of age. This weight gain was attributable to hyperphagia, as cumulative food intake of the MC4R deleted mice was significantly greater than the controls and energy expenditure measurements acquired through CLAMS analysis were not significantly different. To determine the brain regions engaged by CalcRPVH neurons, we used anterograde Cre-dependent viral tracing reagents injected into the PVH of CalcR-Cre mice, and found that CalcRPVH neurons project to brain regions implicated in energy balance control, including the nucleus of the solitary tract and the parabrachial nucleus. To assess the acute effects of activating CalcRPVH neurons, we used DREADD technology to chemogenetically activate CalcRPVH neurons. CalcRPVH neuron activation suppressed feeding but had no significant effect on energy expenditure. To determine if the activity of CalcRPVH neurons is required for energy homeostasis, we silenced them using Cre-dependent tetanus toxin virus. Male mice with tetanus toxin silenced CalcRPVH neurons were obese 7 weeks following injection in part due to greater cumulative food intake; CLAMS analysis revealed no differences in energy expenditure. Mice with silenced CalcRPVH neurons as well as mice with CalcR deleted from the PVH had normal anorectic responses to sCT, suggesting sCT-induced anorexia does not require CalcRPVH neurons or CalcR expression in the PVH. Taken together, these findings suggest CalcRPVH neurons are an essential component of feeding and energy homeostatic circuitry.
OR30-02 Efficacy and Safety Comparison Between U100 Regular Human Insulin and U100 Rapid Acting Insulin When Delivered by a 24 Hour Wearable Insulin Delivery Device in Type 2 Diabetes
Authors: Mora Pablo , Sutton David R , Gore Ashwini , Baliga Bantwal S , Goldfaden, PharmD Rebecca , Nikkel Carla , Sink II John , Adams-Huet Beverley
Published: May 2020

Introduction: Increasing insulin prices have led to a renewed debate to determine if Rapid Acting Insulin (RAI) analogs offer an advantage over less expensive Regular Human Insulins (RHI). The steep increase in the cost of RAI has led to rationing of insulin or the total discontinuance of therapy by many patients due to cost. For many, RHI provides a more affordable option for insulin therapy when compared to RAI, especially if the limitations of the insulin profile can be overcome by delivering RHI through continuous subcutaneous insulin infusion (CSII) using a wearable insulin delivery device. To our knowledge, no data exists in a type 2 diabetes (T2D) population comparing RAI to RHI when delivered via CSII. Methods: This 14 week multi-center prospective, randomized parallel, non-inferiority study in a T2D population compared the efficacy and safety of RAI versus RHI when delivered by V-Go®, a 24-hr wearable patch-like insulin delivery device that provides a preset continuous basal rate of insulin and on-demand bolus dosing. This study was conducted in a real-world practice setting under usual standard of care. Glucose lowering agents were to remain stable unless removal warranted due to documented clinically significant hypoglycemia and the only specific guidance for insulin titration was to down-titrate if blood glucose levels were consistently lower than target range. Patients administering RAI with V-Go were randomized 1:1 to continue RAI or to switch to RHI. Primary endpoint assessed non-inferiority for the between group net difference in HbA1c derived from a mixed model analysis. Between group differences from baseline for insulin total daily dose (TDD) and hypoglycemia (based on 7 point glucose profiles) were evaluated as secondary endpoints. Results: One hundred thirteen patients (59 RHI and 54 RAI) were evaluated. Baseline characteristics were similar between cohorts. The mean change in HbA1c with RHI was -0.60% from a baseline of 8.41% vs -0.38% from a baseline of 8.33% with RAI (estimated treatment difference [ETD]: -0.22%; 95% confidence interval [CI] -0.67% to 0.22%; non-inferiority margin<0.4% and p=0.007). The mean change in TDD with RHI was 0.8 U/day from a baseline of 61.0 U/day vs 1.8 U/day from a baseline of 61.3 U/day with RAI (ETD: -1.04 U/day; 95% CI: -3.18 U/day to 1.11 U/day; p=0.92). The absolute change in percent of patients reporting hypoglycemia (≤ 70 mg/dL) from pre-randomization to post-randomization was +5.08% with RHI vs + 5.56% with RAI (ETD: -0.48%; 95% CI: -10.6% to 9.1%; p=0.91). Severe hypoglycemia was not reported in either cohort. Conclusion: Patients with T2D administering RAI with V-Go can safely switch to RHI maintaining similar glycemic control.
SAT-037 Effect of Weight on Serum Testosterone with Subcutaneous Testosterone Enanthate in Men with Testosterone Deficiency
Authors: Bhattacharya Rajib , Tursi James P , Jaffe Jonathan S
Published: May 2020

BACKGROUND: In men, obesity is often associated with low testosterone (T) levels, but information is limited as to how body weight affects the pharmacokinetic profile or dosing of testosterone therapy (TTh) in men with T deficiency. Historically, men with body mass index (BMI) >32.4 kg/m2 required higher doses of T 2% gel to achieve physiological T levels than men with BMI ≤29.1 or 29.2–32.4 kg/m2.(1) In a phase 3 trial (N=150) of subcutaneous (SC) testosterone enanthate (TE) administered weekly, concentration-guided dosing raised T levels to within physiological range in 92.7% of patients.(2) Here, we report a post hoc analysis evaluating the association between body weight and serum T levels attained with SC TE. Methods: SC TE was evaluated in an open-label, single-arm, dose-blinded, 52-week phase 3 trial (NCT02159469). Patients self-administered 75 mg SC TE weekly during the titration phase; blinded dose-adjustments in 25 mg increments occurred at pre-defined time points beyond the sixth dose. The primary endpoint of this study was the percentage of patients achieving an average serum T concentration (Cavg0-168h) of 300 to 1,100 ng/dL at week 12. For this post hoc analysis, a linear regression model with weight and dose as independent variables was used to assess differences in mean minimum T concentration (Cmin) and Cavg0-168h at week 12. Results: For this analysis, 137 patients were included. Doses were 50 mg (n=25), 75 mg (n=93), and 100 mg (n=19). The mean weight was 84.4 kg, 102.2 kg, and 112.0 kg for the 50 mg, 75 mg, and 100 mg dose groups, respectively (range, 49.9–146.5 kg). The dose-normalized T Cmin was 9.2 ng/dL, 5.7 ng/dL, and 4.3 ng/dL per 1 mg of SC TE for the 50 mg, 75 mg, and 100 mg groups, respectively. The dose-normalized T Cavg0-168h was 12.0 ng/dL, 7.2 ng/dL, and 5.7 ng/dL per 1 mg of SC TE. In an overall linear regression model, 48.2% (P<0.0001) and 55.0% (P<0.0001) of the total variance in Cmin and Cavg0-168h, respectively, can be predicted from the independent weight and dose variables. Conclusion: Our results show an inverse relationship between body weight and T exposure. Men with higher mean body weights required higher doses of SC TE to achieve physiologic T levels compared with men with lower mean body weights. The available doses provide effective options to reach target exposures. These findings highlight the impact of weight and dose selection on SC TE exposure. References: (1) Dobs et al., J Sex Med 2014;11:857–864; (2) Kaminetsky et al., J Urol. 2019;201:587–94.
SUN-265 Reduced Locomotive Behaviour and Increased Arcuate Nucleus Inflammation Are Observed in KISS1R KO Male Mice
Authors: Patel Raj , Maloney Shane K , Smith Jeremy Troy
Published: May 2020

The neuropeptide kisspeptin, encoded by the Kiss1 gene, binds the G- protein-coupled receptor Kiss1r (also known as GPR54) and is a novel player in the delicate balance of energy intake and expenditure. Mice that have a dysfunctional gene for Kiss1r develop an obese and diabetic phenotype. To further study how kisspeptin signalling impacts on energy balance, we investigated the relationship between absent kisspeptin signalling and locomotor behaviour in Kiss1rKO and wild type mice. Mice had free access to running wheels, and we examined the characteristics of wheel running over three weeks, and its flow-on effects on body mass. We subsequently examined dopaminergic neurons (via tyrosine hydroxylase (TH) staining) and hypothalamic inflammation (via Iba1 stained microglia). These studies also were performed following gonadectomy (GDX), to control for gonadal steroids. In intact males, the knockout (KO) mice covered only 10% of the distance travelled by wild-type (WT) per 24h (WT, 6363±643m; KO, 652±219m; P<0.0001). Moreover, in the WT there was a clear circadian pattern to the wheel-running activity, with most activity during lights off, while in the KO the running appeared randomly distributed across the 24h. After GDX, KO males continued to run significantly less than their WT counterparts (WT, 1652±474m; KO, 998±219m). In intact females, the KO mice covered only 23% of the distance travelled by WT per 24h (WT, 6030±747m; KO, 1379±364m; P<0.004). In OVX females, there was no difference between WT and KO mice (WT, 4150±1367m; KO, 3117±830m). Bodyweight analysis showed that access to running wheels prevented obesity usually seen in the Kiss1rKO mouse. In fact, in GDX males and females (at days 21 and 22 of wheel running) the KO mice were significantly lighter than WTs (at day 22: males, WT 28.67g; KO, 23.70g; P<0.05; females, WT, 27.38g; KO, 23.30g; P<0.05). Examination of TH revealed no significant difference in expression in the different genotypes in both sexes, in all areas examined. Investigation of Iba1 revealed significant higher counts in the male KO compared to the WT in the arcuate nucleus, but no difference in any other regions. We show that the locomotor activity in male and female Kiss1r KO mice is heavily dependent on the status of gonadal sex steroids. However, the lower running activity in male KO compared to WT remained after GDX, and this was paired with an elevated inflammation marker in the arcuate nucleus. Whether absent kisspeptin signalling acts as a significant regulator of voluntary activity is debatable, but patterns of locomotion behaviour could be disrupted, potentially involving circadian rhythm, this is under further investigation.
OR04-06 G Protein GSα in Muscle Is Essential for Survival During Cold Adaptation in the Absence of Thermogenesis of Brown Adipose Tissue
Authors: Chen Min , Sun Hui , Weinstein Lee Scott
Published: May 2020

Adaptive thermogenesis is important for the control of body temperature (Tb) and maintenance of body weight, and it is primarily regulated by sympathetically-driven brown adipose tissue (BAT). Studies indicate that muscle is also involved in thermogenic regulation. Gsα couples to ligands and receptors, including β-adrenergic receptors, to increase intracellular cAMP. Our previous studies have showed that mice with adipose-specific Gsα deficiency had inactive BAT and impaired cold tolerance. To determine whether Gsα/cAMP signaling in skeletal muscle compensates for loss of BAT thermogenesis, we generated mice with Gsα deficiency in adipocyte tissue alone (AdipGsKO), in skeletal muscle alone (SkMGsKO) or in both (AdipSkMGsKO). Compared to control mice, AdipGsKO and SkMGsKO mice had normal body weight, while AdipSkMGsKO showed reduced body weight with normal food intake and energy expenditure. Both AdipGsKO and AdipSkMGsKO mice had elevated fasting glucose levels, but similar glucose tolerance to control or SkMGsKO mice. SkMGsKO mice displayed reduced insulin sensitivity. When acutely exposed to 6oC for 3 hours, AdipGsKO and AdipSkMGsKO mice rapidly decreased their Tb, indicating that they are sensitive to acute cold exposure, consistent with their inactive BAT. To assess adaptation to chronic cold, mice were exposed to gradually declining ambient temperature from 22oC to 6oC with a daily decrease of 2oC and were then kept at 6oC for 5 days. As expected, both AdipGsKO and AdipSkMGsKO mice failed to stimulate BAT UCP1 by cold adaptation. Unexpectedly, AdipGsKO mice maintained normal Tb similar to control and SkMGsKO mice. However, AdipSkMGsKO mice started to rapidly drop their Tb when ambient temperature declined to 14oC and 85% of SkMGsKO mice (11/13) died before the end of experiment. These results suggest that when there is a lack of BAT function, Gsα/cAMP signaling in muscle plays an essential role for mice to survive in response to chronic cold challenge.
SUN-285 Too Big to Be True, Too Young to Stroke!
Authors: Jalil Fatima , De La Portilla Lori , Lorenzo Joseph Anthony , Mirza Faryal Sardar
Published: May 2020

BACKGROUND: Lactotroph adenomas are the most common type of pituitary adenomas and can cause infertility and menstrual irregularities in women; hypogonadism and gynecomastia in men.1 Giant prolactinomas are an unusual subset of pituitary macroadenomas with limited literature available on their management.2 We describe an unusual case of giant prolactinoma in a young man who presented with symptoms of stroke, that reversed with treatment with cabergoline. Clinical Case: 25-year old man presented with gradually progressing upper extremity weakness for evaluation of stroke. He reported stumbling into things when walking. There was a question of left sided facial droop and Bell’s palsy in recent past. He reported recent weight gain and erectile dysfunction. He was noted to have left homonymous hemianopsia on exam in addition to left upper and lower extremity weakness. MRI Brain showed an enormous mass that filled the sella turcica, invaded the sphenoid sinus and right side of the skull base, invaginating deep into the base of the right cerebral hemisphere with mass effect on the pons, right-sided midbrain, right temporal lobe and right basal nuclei, measuring 6.3 X 5.5 x 7.5 cm. Pituitary hormonal evaluation showed elevated prolactin (PRL) level with dilution at 13,580 ng/mL, with low testosterone (T) level (total T 42 ng/dL, free T 10 pg/mL, SHBG 15 nmol/L). Thyroid and adrenal axes were intact with normal IGF-1 level. In view of very high PRL level, he was started on cabergoline 0.5 mg daily initially and decreased to every other day after 2 weeks as PRL level began to decline. In 8 months, PRL levels decreased to 1293.07 ng/dl (90% reduction) and prolactinoma decreased to 6.0 x 3.7 x 4.7 cm (56% volume reduction). Total and free T improved to 134 ng/dL and 31 pg/dL respectively. He experienced marked improvement in left hemianopsia, with resolution of weakness and slurred speech. Energy level and erectile dysfunction improved. Currently he is being maintained on 0.5 mg cabergoline every other day Conclusion: Giant prolactinomas are uncommon and can present with compressive symptoms, that can be mistaken as stroke. Treatment with anticoagulation may cause hemorrhage and apoplexy with worsening of symptoms.1,2 There is limited data available regarding first line therapy for giant prolactinomas with 2 case reports where giant prolactinomas have been treated effectively with cabergoline.3,4 It is important to recognize the cause of such symptoms, and treated where possible with effective medical therapy to prevent morbidity. References: 1. Moraes A et al., Giant prolactinomas: the therapeutic approach. Clin Endo (Oxf). 2013 Oct;79(4):447-56 2. Acharya SV et al., Giant prolactinoma and effectiveness of medical management. Endocr Pract. 2010 Feb;16(1):42-6 3. Ahmed, M, et al., Large Prolactinoma. NEJM 2010; 363:177 4. Masoud, R et al., Giant prolactinoma: case report. J Diabetes Metab Disord. 2013; 12: 3
SUN-098 Low-Dose Infigratinib Treatment Does Not Lead to Changes in Phosphorous Preclinically in Mice
Authors: Reyes Maribel , Sinha Uma , Li Gary , Martin David
Published: May 2020

BACKGROUND: Infigratinib (BGJ398) is a potent and selective FGFR1-3 inhibitor under evaluation for the treatment of achondroplasia, the most common form of disproportionate short stature. Low doses of infigratinib were shown to be effective in improving skeletal abnormalities in a mouse model of achondroplasia [Demuynck et al. 2019; Komla-Ebri et al. 2016]. At higher doses in adult patients (e.g. 10-100-fold the dose shown to have efficacy in preclinical models of achondroplasia) infigratinib appears to be associated with elevation in phosphorus, an effect known to be associated with FGFR1 inhibition. Specifically, FGFR1 inhibition leads to decreases in FGF23, which, in turn, leads to decreased excretion of phosphate by the kidneys. We sought to understand the relationship between lower doses of infigratinib and changes in phosphorus in preclinical animal models. Methods: Changes in phosphorus were tested at multiple doses in three different species - mouse, rat, and dog - across five different studies. Infigratinib was given orally at doses ranging from 0.03 mg/kg to 30 mg/kg. Both PK and PD (i.e., phosphorus) data was available in all species. Measurement days ranged from day 10 to week 12, although PK/PD measurements occurred within 1 day of each other. All animals were treated in accordance with AVMA guidelines. Results: No significant dose-phosphorus relationship was observed in rats and mice treated with doses of infigratinib ranging from 0.03 mg/kg to 5 mg/kg. A dose-phosphorus and exposure (AUC0-24)-phosphorus relationship was observed at doses of infigratinib ≥10 mg/kg across transgenic mouse, rat, and dog studies. At low doses, the exposure (AUC0-24)-phosphorus relationship showed a shallow slope with linear regression analysis in rats and mice. Conclusions: These findings from five studies in three different species indicate that the exposure-phosphorus relationship is consistent. Importantly, no relationship was observed between dose and phosphorus levels in rats and mice treated with infigratinib at or below 5 mg/kg. Despite the fact that infigratinib is a FGFR1, 2 and 3 inhibitor, low doses of infigratinib shown previously to exert a significant effect in improving skeletal abnormalities in an achondroplasia mouse model, do not seem to result in meaningful changes in phosphorus. These experiments demonstrate that at doses of infigratinib much lower than used in oncology - like those being considered for use in clinical studies of achondroplasia - infigratinib is less likely to cause hyperphosphatemia. Infigratinib will be evaluated in global clinical studies in children with achondroplasia in 2020.
SAT-517 A Rare Case of Lithium-Induced Thyroiditis
Authors: Lokshin Vladimir , Soni Lina , Shrestha Sujata , Guber Helena Abby
Published: May 2020

BACKGROUND: Lithium is known to cause both hypo- and rarely hyper- thyroidism. It inhibits release of thyroid hormone and reduces the intrathyroidal iodothyronine/iodothyrosine ratio. Due to direct toxic or immunostimulatory effect, lithium can also cause thyroiditis. Lithium-induced thyroiditis is a rare entity with an incidence rate of about 1.3 cases per 1000 person-years. Given its generally painless and transient nature, symptoms of thyrotoxicosis may erroneously be attributed to an exacerbation of mania.

Clinical Case: We report the case of a 29 y/o man with bipolar disorder on lithium therapy who presented with a 2 week history of intermittent palpitations, increased irritability, racing thoughts, insomnia, tremors, increased bowel movement frequency, and 8 lbs weight loss despite an excellent appetite. He denied ocular symptoms, and did not have any recent illness, or new stressors. He had been on a stable dose of lithium for four years.

The physical exam was notable for: pulse 78 bpm and regular, exophthalmos, and a palpable, non-tender, non-nodular, thyroid. Labs: TSH 0.008 uIU/ml [0.350 - 5.50], FT3 6.5 pg/ml [2.0 - 4.4], T3 2.08 ng/mL [0.6–1.94] and FT4 1.96 ng/dl [0.8 - 2.7]. TPO, TSI and anti-thyroglobulin antibodies were negative. The lithium level was in the therapeutic range. Thyroid Uptake Scan showed decreased uptake of 2.6 % [normal 10–35%]. He was started on methimazole 20mg daily and atenolol, lithium was changed to risperidone by Psychiatry.

After 2 months, hyperthyroid symptoms had resolved, and he was biochemically hypothyroid (FT4 0.85 ng/dl, TSH 20uIU/ml). Methimazole and atenolol were discontinued, with sustained euthyroid state. Conclusion: Hyperthyroidism may develop after several years of lithium therapy. It may be mistaken for aggravation of mania, or for Grave’s disease, especially since lithium and Graves’ are both associated with exophthalmos. Key issues for management are whether to continue lithium and deciding if the incorporation of antithyroid medications is necessary. Of utmost importance is regular monitoring of thyroid function tests to ensure resolution of thyroiditis and to avoid the development of overt hypothyroidism.
SUN-058 Endocrine and Metabolic Complications in 16 Taiwanese Patients with Thalassaemia Major
Authors: Lo Fu-Sung
Published: May 2020

Backgrounds: Endocrine and metabolic abnormalities are quite common in patients with thalassaemia major, attributable, at least in part, to chronic iron overload. Endocrine and metabolic abnormalities are quite common in patients with thalassaemia major. Determining the prevalence of endocrine complications is difficult because of differences in the age of first exposure to chelation therapy, and the continuing improvement in survival in well-chelated patients.Patients and Methods: We performed a retrospective study of endocrine and metabolic data of 16 Taiwanese children (10 females and 6 males, 21.42±4.82 years) who attended in our patient clinics from Oct 2002 to Jan 2012. We analyzed height, weight, BMI, serum fasting glucose, thyroid function, growth hormone, adrenal, and gonadal functions. Results:These patients had very high serum ferritin levels with 4737.79±4572.03 ng/ml (482.8-12639). Auxological data show growth retardation (height SDS -1.05±1.34, weight SDS -0.67±0.52, BMI -0.37±0.49). Endocrine data reveal hypogonadism (n = 11, 69%), hypothyroidism (n=8, 50%), growth hormone deficiency (n=3, 19%), and adrenal insufficiency (n=3, 19%). Metabolic data show impaired fasting glucose (n=4, 25%) and diabetes (n=6, 37%). Conclusions: Patients with thalassemia major are at risk for a number of endocrine (growth hormone deficiency, hypothyroidism, adrenal insufficiency and hypogonadism) and metabolic problems (impaired fasting glucose and diabetes). It is necessary for endocrinologists to become skilled in these complications and provide long-term comprehensive care through the life of these patients.