bluuebunny/crossref_metadata_2025 huggingface dataset:
OR28-06 Assessment of Long Term Quality of Life According to Treatment Options in Low Risk Papillary Thyroid Microcarcinoma Patients - Active Surveillance or Immediate Surgery, (A Follow up Interim Analysis of Maestro)
Authors: Shin Soo Myoung , Kong Sung Hye , Ryu Junsun , Kim Min Joo , Cho Sun Wook , Song Young Shin , Yi Ka Hee , Park Do Joon , Hwangbo Yul , Lee You Jin , Lee Kyu Eun , Kim Su-jin , Jeong Woo-Jin , Chung Eun-Jae , Hah Jeong Hun , Choi June Young , Ryu Chang Hwan , Jung Yuh-Seog , Lee Eun Kyung , Park Young Joo , Moon Jae Hoon
Published: May 2020

Background: The Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) started in June 2016. As a follow-up study of comparing the quality of life (QoL) of the active surveillance (AS) and immediate surgery (OP) groups at 8 months (9.3±4.8 and 7.1±4.2 months, respectively), here we aimed to compare the QoL between the AS and OP groups after 18 months (22.8±4.0 and 22.3±4.3 months, respectively) of follow-up.

Methods: QoL of 108 participants who chose AS, 101 who underwent OP, twelve who changed from AS to OP was evaluated using a thyroid-specific QoL questionnaire at diagnosis and during follow-up (median 23 months).

Results: The mean ages of the participants in the AS and OP groups were 47.7±11.0 and 45.1±10.0 years (p=0.075), respectively. At baseline, better physical (8.2±1.4 vs. 7.6±1.8, p=0.032), psychological (7.4±1.2 vs. 6.7±1.6, p=0.010), and total health (7.4±1.0 vs. 6.7±1.3, p=0.005) were observed in the AS group than in the OP group. After a mean follow up of 22.7±4.2 months, better physical (8.1±1.5 vs. 7.4±1.7, p=0.008), psychological (7.7±1.3 vs. 7.0±1.5, p=0.002), and total health (7.5±1.2 vs. 6.8±1.3, p=0.001) were observed in the AS group than in the OP group, whereas spiritual health was comparable between the two groups: compared with the AS group, the OP group experienced more alterations in appetite, sleep, menstrual cycle, voice, motor skill, weight, appearance, cold or heat tolerance, and body swelling. Furthermore, better QOL scores were observed in the AS group in self-concept, personal relationships, sexual life, work motivation, productivity and quality of work, feeling of isolation, driving, doing household chores, preparing meals and doing leisure activities after long term follow up.

Conclusion: Patients who underwent AS had better QOL even after long term follow up. Low risk papillary thyroid microcarcinomas do not influence survival, however surgery related deterioration of QOL lasted long and did not improve even in late post-operative stages when patients were fully recovered from surgery.

Keywords: Quality of life; papillary thyroid microcarcinoma; active surveillance; immediate surgery
SAT-LB52 A Case of Cushing’s Syndrome in a Patient With Addison’s Disease
Authors: Mungo Nicolas A
Published: May 2020

This is a case of a 56-year-old female with history of Addison’s disease, T1DM, hypothyroidism and Asthma. She was diagnosed with Addison’s disease after multiple hospital visits consistent with adrenal crises (Fatigue, weakness, salt craving, abdominal pain, hypotension, hyperpigmentation and hyponatremia). Multiple abdominal images including CT abdomen did not reveal any pathology. A random cortisol and ACTH were found to be abnormal at 0.5 and 3362, respectively. She was started on Hydrocortisone 10mg in the morning and 5mg in the evening. Her physical exam revealed diffuse hyperpigmentation including palmar creases and oral mucosa. There was no facial plethora or striae. She had no history of proximal myopathy, easy bruising, hypertension or osteoporosis. Upon follow up, exam revealed progressive worsening of her diffuse hyperpigmentation. A random cortisol and ACTH, without holding her Hydrocortisone, revealed 64.3 and >2000, respectively. Concern arose for the possibility for a pituitary corticotrophin adenoma or ectopic secretion of ACTH driving her hyperpigmentation. MRI showed the pituitary gland had normal appearances. As there is a positive correlation between basal plasma ACTH values and the size of the pituitary adenoma in patients with Cushing’s disease the differential of a pituitary corticotrophin adenoma was originally thought to be dropped lower on the list of differentials. Further workup was pursued with an 8mg Dexamethasone suppression test to take advantage of the fact that ACTH secretion by the pituitary adenomas in Cushing’s disease are only relatively resistant to negative feedback regulation by glucocorticoids while most ectopic ACTH production from non-pituitary tumors are completely resistant to feedback inhibition. ACTH levels went from >2000 down to 29 post 8mg Dexamethasone, which led to decreasing suspicion of an ectopic source of ACTH and further concern for a pituitary corticotrophin adenoma in addition to Addison’s disease. ACTH measurements are not widely used in documenting the adequacy of treatment of primary adrenocortical disease. The hormone is released in pulses, particularly in the early hours of the morning, and measurement of isolated samples is of limited value. Inappropriately normal to slightly elevated ACTH levels despite adequate glucocorticoid replacement in patient with adrenal insufficiency could be related to an altered pituitary sensitivity to cortisol suppression. Extremely elevated ACTH levels despite supra-physiological glucocorticoid replacement in a patient with Addison’s raises the question as to what is the source of ACTH?
SAT-LB77 Thyroid Radiofrequency Ablation: A New Office Based Procedure for Endocrinologists
Authors: Guttler Richard B
Published: May 2020

Recent FDA approval of thyroid RF has made it possible for endocrinologists in the USA to finally treat their own patients after obtaining training. I have 5 years experience working with these systems and have trained many endocrinologists in my practice. In 2019 I began a preliminary study of 12 patients with negative biopsies to see the feasibility of doing thyroid RF in my ultrasound room in my office without going to imaging centers or the hospital. The fee for office based RF is 3-6 times less expensive. RF system by RF Medical Korea was used in all cases. The results are promising. Skin and thyroid capsule local injection was all that was needed for pain control. Vital signs were monitored by my roving nurse. The maximal watts used was 20-40. There were no major complications and only one bruise in the neck area. No vocal symptoms. All 12 tolerated the procedure and after 30 minutes observation left with only a small band aid over the injection site. Two flew out of state that night.Conclusion: A preliminary assessment of in office thyroid RF without general of conscience sedation by trained endocrinologists suggests larger study with 80-100 cases is the next step.
MON-LB043 A Case of Renovascular Hypertension With Cortisol-Producing Adrenal Masses
Authors: Higashitani Takuya , Aono Daisuke , Kometani Mitsuhiro , Karashima Shigehiro , Demura Masashi , Yoneda Takashi , Takeda Yoshiyu
Published: May 2020

Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and subclinical Cushing’s syndrome. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg; pulse rate, 132 beats/min; and plasma glucose level, 712 mg/dl. Abdominal computed tomography scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. Bilateral adrenal masses were immunohistologically identified as potential sites for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy.
MON-LB112 Socioeconomic Status, Literacy, and Sex Differences in the Progression of Retinopathy in Patients With Type 2 Diabetes in Tokyo, Japan
Authors: Emoto Naoya , Soga Akimi , Fukuda Izumi , Tanimura-Inagaki Kyoko , Harada Taro , Sugihara Hitoshi , Goto Rei
Published: May 2020

Socioeconomic status has profound effects on glycemic control and diabetic complications in patients with type 2 diabetes. Sex differences are one of the most important factors in socioeconomic status and may vary among countries or areas. The study aim was to determine if sex differences are associated with glycemic control and diabetic complications in Tokyo, Japan, one of the most educated countries in the world. This study initially enrolled 3307 patients treated from 2017 to 2019 at the medical school hospital located in Tokyo. All enrolled patients were asked to complete behavioral and socioeconomic surveys. A total of 276 type 2 diabetic patients (175 males, age 64.1 ± 0.88 y, disease duration 15.2 ± 0.78 y, mean ± SE y; 101 females, age 64.0 ± 1.1 y, disease duration 15.6 ± 1.01 y) agreed to participate in the study. The survey questionnaire has been previously reported in detail (Patient Preference and Adherence, 10:2151-2162, 2016). The questionnaire attempted to determine estimations of risk preference regarding things like lottery gambling and accident insurance. After reviewing the patients’ answers, however, it became clear that some were illogical, which suggested that these patients did not understand the context of the questions, the hypothetical economical situations, or even the instructions, probably because of lower literacy skills. Thus, we labeled these patients as the unreasonable (UR) group (n = 81), and the patients who provided appropriate answers, even if extremely risk averse or risk loving, were labeled as the reasonable (R) group (n = 195). The prevalence of UR answers generally increased with age (<50 y, 16%; 50-64 y, 10%; 65-74 y, 37%; ≥75 y, 64%) (p < 0.0001). After age adjustment, there was a significant correlation between the UR answers and educational attainment in both sexes. The prevalence of UR answers was significantly higher in females (38.6%) than in males (24%) (p < 0.01), which may be partly because the average number of educational years was lower for females than for males (males, 13.8 y; females, 12.9 y; p < 0.05), but both averages are very high among all countries. The prevalence of retinopathy was significantly higher in the UR than the R group in males (p < 0.05), but not in females. Job and economic status were not associated with prevalence of retinopathy. These results suggest that effects of literacy skills on progression of diabetic retinopathy may be sex dependent. Although the mechanism underlying this finding is unknown, sex may be an important biological factor beyond socioeconomic status in highly educated high-income countries.
SAT-LB304 A Rare Case of Atypical Teratoid/Rhabdoid Tumor of Sellar Region in an Adult
Authors: Madhavan Parvathy , Schwartz Paul , Kantorovich Vitaly
Published: May 2020

Introduction:

Atypical teratoid/rhabdoid tumor(ATRT) is an aggressive tumor of the central nervous system mostly seen in the pediatric age group. It is rare for these tumors to occur in adults, especially in the sellar region. Here we describe a case of ATRT of sellar region with rapidly progressive confusion and panhypopituitarism.

Case report: 58-year-old Caucasian woman presented with complaints of headache, generalized weakness, nausea and anorexia. Patient was also noted to be confused throughout her presentation and unable to provide detailed history. She also complained of blurring of vision and was noted to have visual field loss by her ophthalmologist. CT head without contrast revealed a sellar mass with suprasellar extension which is 2.5 x 2.4 x 3.5 cm with mass-effect on the base of anterior third ventricle. Blood work showed an A.M cortisol of 0.2 mcg/dL(6.2-19.4), prolactin of 62.6 ng/mL(4.8-22.3), TSH of 2 mIU/L(0.27-4.20) and free T4 of 0.36 ng/dL [0.80-1.90]. Cosyntropin stimulation test showed a 30-minute cortisol of 2.8 mcg/dL and a 60-minute cortisol of 4 mcg/dL. She was also noted to have hypernatremia with serum sodium upto 151 mmol/L(136-145). She was started on levothyroxine 88 mcg, DDAVP 0.1 mg PO twice daily and stress dose steroids which was weaned down to prednisone 7.5 mg daily eventually. MRI revealed 2.1 cm sellar mass with 3.1 cm suprasellar extension and rapidly progressive increase in size over several weeks period. Patient initially underwent left frontal midline craniotomy via transcallosal approach for resection of third ventricular and supra sellar tumor. For the residual tumor removal, she also underwent endoscopic resection of ATRT of brain via extended transnasal craniotomy with extensive nasoseptal flap repair of the skull base. Pathology revealed atypical teratoid/rhabdoid tumor of sellar region, WHO grade IV. The neoplastic cells characteristically show loss of INI-1 (SMARCB1), retained BRG1 (SMARCA4), focal weak positivity for EMA, Vimentin, Neurofilament (NF), CD56 and Cytokeratin AE1/AE3 is strongly positive. There is patchy non-specific immunoreactivity to PAX5 and PAX8. Hospital course was complicated by respiratory failure, NSTEMI, encephalopathy and patient is currently receiving supportive care for the same. Patient will be receiving radiotherapy and chemotherapy for further management of ATRT.

Conclusion:This case represents a rare occurrence of ATRT and suggests the need for suspicion in case of rapidly growing pituitary mass with progressive panhypopititarism.
SAT-LB44 WNT2B Regulates Adrenocortical Progenitor Cell Fate And Zona Glomerulosa Identity In Vivo
Authors: Little Donald W , Basham Kaitlin J , Hammer Gary D
Published: May 2020

Dysregulation of normal adrenal structure and function contributes to a spectrum of diseases from hypoplasia to cancer. Peripheral adrenocortical progenitor cells in the zona glomerulosa (zG) centripetally migrate and differentiate to replenish steroidogenic cells of the zG and the inner cortex over time (1). Both the fate of progenitor cells and aldosterone production by steroidogenic cells in the zG are regulated by Wnt signaling (2,3), but the cell-specific effects of individual Wnt ligands in the adrenal are not fully understood. To further characterize Wnt signaling components crucial for progenitor cell maintenance and zG identity, we analyzed mouse adrenals using single molecule in situ hybridization (smISH), which revealed the previously unknown expression of Wnt2b exclusively in the adrenal capsule. Wnt2b is co-expressed with the Wnt signaling potentiator Rspo3, the loss of which causes zG depletion and reduced adrenal size in mice (4). Therefore, we hypothesized that capsular WNT2B activates Wnt signaling in the underlying cortex to maintain the undifferentiated state of progenitor cells. To define the role of WNT2B in these processes, we generated Wnt2b conditional knockout (cKO) mice by crossing a capsule-specific Gli1-CreERT2 driver (5) and a floxed Wnt2b allele (6). We administered tamoxifen to 6-week-old male mice and assessed the effects of Wnt2b loss 4 weeks later. Gli1-CreERT2 activation significantly decreased Wnt2b expression (P<0.001) and resulted in a lower adrenal to body weight ratio in Wnt2b cKOs compared to controls (P<0.05). Adrenocortical proliferation (Ki67) was significantly decreased in Wnt2b cKO mice (P<0.0001), suggesting that WNT2B may mediate progenitor cell self-renewal. To characterize the effect of WNT2B loss on Wnt signaling, we assessed activation of the primary Wnt effector β-catenin. High β-catenin activity in the zG observed in wild-type mice was disrupted in Wnt2b cKO mice, together with markedly reduced expression of adrenocortical Wnt target genes Axin2 and Wnt4. In addition, Wnt2b loss resulted in downregulation of steroidogenic genes Cyp11b2 (P=0.0139) and Hsd3b6 (P=0.0679). Together, these data suggest that capsule-derived WNT2B activates cortical Wnt signaling to maintain the identity of both undifferentiated progenitor cells and differentiated steroidogenic cells of the zG, which has important implications for adrenal homeostasis and disease, including both primary adrenal failure and neoplasia.

References: (1) King et al., PNAS, 2009 Dec 15;106(50):21185-90. (2) Berthon et al., Hum Mol Genet., 2010 Apr 15;19(8):1561-76. (3) Heikkila et al., Endocrinol., 2002 Nov;143(11):4358-65. (4) Vidal et al., Genes & Dev., 2016 Jun 15;30(12):1389-94. (5) Ahn & Joyner, Cell, 2004 Aug 20;118(4):505-16. (6) Tsukiyama & Yamaguchi, Neurosci Lett., 2012 Mar 14;512(1):48-52.
MON-LB039 Acute Paraneoplastic Cushing’s Syndrome in a Patient With Small Cell Lung Cancer and Co-Incidental Adrenal Adenoma: A Case Report
Authors: Gerhardt Louisa Maria Sophie , Sabath Lisa , Borm Katrin , Capraro Joel , Müller Beat
Published: May 2020

Background: Paraneoplastic Cushing’s syndrome is a rare cause of hypercortisolism associated with high morbidity, especially in patients with small cell lung cancer. Therefore, early diagnosis and treatment are critical.

Clinical Case: Herein we present the case of a 58-year-old man who was referred to the endocrinology department, because of refractory hypokalemia (potassium 2.4 mmol/l; RI: 3.4 - 4.5 mmol/l) despite high potassium supplements and spironolactone therapy. History was remarkable for a metabolic syndrome with newly aggravated hypertension and a 60-pack-year smoking history. The patient reported a 20 kg weight gain in 6 weeks and proximal muscle weakness. On examination, he was overweight (BMI 44.8 kg/m²) with bilateral pitting edema. Other features of hypercortisolism such as striae rubrae, facial plethora or ecchymoses, respectively, were not apparent. Initial biochemical tests showed severe hypokalemia and metabolic alkalosis. Night-time salivary cortisol (205 nmol/l; RI: < 2.5 nmol/l), 24-hour urinary free cortisol (> 4357 nmol/24h; RI: 99 - 378 nmol/24h) and serum ACTH (158 ng/l; RI: < 61 ng/l) were markedly elevated. While the MRI of the head demonstrated no pituitary pathology, the CT of thorax and abdomen revealed a pulmonary mass as well as an incidental right adrenal mass. Bronchoscopic biopsy of the pulmonary mass confirmed the suspected diagnosis of ACTH-producing small cell lung cancer. The dignity of the right adrenal mass remained unclear, since the radiologic features per se could not differentiate between adrenal adenoma and metastasis. Chemotherapy with cisplatin/etoposide and inhibition of steroidogenesis with ketoconazole were initiated, which largely controlled the hypercortisolism. Imaging studies after completion of two cycles of chemotherapy showed a tumor response with regression of the pulmonary mass. The right adrenal mass remained stationary under chemotherapy. Thus, an adrenal metastasis could be excluded as potential cause of the adrenal mass, suggesting an incidental adrenal adenoma as the most likely diagnosis.

Conclusion: Paraneoplastic Cushing’s syndrome requires high clinical suspicion for early diagnosis, since many of the classical clinical features of hypercortisolism may still be absent, even if the underlying cancer is already advanced. In patients suspected to have Cushing’s syndrome a three-step diagnostic approach is recommended: (1) biochemical confirmation of hypercortisolism, (2) differentiation between ACTH-dependant and -independant hypercortisolism and (3) identification of its source. This approach helps avoiding misdiagnosis in patients who have both an ACTH-producing cancer and an adrenal adenoma [1].

References: [1] Lacroix et al. Cushing’s syndrome. Lancet 2015; 386: 913-927.
SAT-LB313 A Unicorn With Double Horns - Metastatic Paraganglioma in a Patient With Beckwith-Wiedemann Syndrome and Hereditary Paraganglioma Syndrome Iv
Authors: Narayanan Anand , Soe Myat , Wheeler Amber L , Fitzgerald Paul A
Published: May 2020

Introduction: Beckwith-Wiedemann syndrome (BWS), a multisystem genomic imprinting disorder in chromosome 11p15.5 region, is an overgrowth syndrome often presenting with macroglossia, abdominal wall defects, hemihyperplasia, enlarged abdominal organs and an increased risk of tumors including neuroblastoma, rhabdomyosarcoma, unilateral Wilm’s tumor, hepatoblastoma, adrenal cortical carcinoma and pheochromocytoma. Six cases of benign bilateral pheochromocytomas and one case of pheochromocytoma with lymph node metastasis in BWS have been described in the literature. We describe the first case of BWS with distant metastatic paraganglioma harboring an SDHB (succinate dehydrogenase subunit B) mutation.

Presentation: A 28-year-old male with BWS whose history included an omphalocele and diaphragmatic hernia in infancy, neuroblastoma resected at age 2, and left carotid paraganglioma (PGL) resected at age 22 presented with abdominal pain. CT A/P with contrast revealed a 3.3 x 4.4 cm hypervascular mass and multiple bone metastases. Workup revealed normal plasma/urine metanephrines, elevated plasma dopamine of 178 pg/ml (normal <20) and elevated chromogranin A of 190 ng/ml (normal <90). 68Ga-dotatate PET CT showed hypermetabolic 4.4 cm mass (SUV 83), right hypopharynx mass (SUV 49), and many dota avid areas throughout the skeleton. The abdominal mass was resected and pathology was consistent with PGL. Due to unusual presentation, patient underwent hereditary cancer genetic testing (67 gene panel) and pathogenic mutation (c.713delT) in the SDHB gene was identified, consistent with hereditary PGL syndrome IV.

Conclusion: While pheochromocytomas and other tumors are commonly found in association with BWS, PGLs are not. This is the first documented case of a patient with BWS having distant metastatic PGL. Malignant transformation of hereditary and sporadic pheochromocytomas and paraganglioma (PPGLs) is more common in SDHx associated PPGLs (>40% of metastatic PPGLs are related to an SDHB mutation). Hereditary PGL syndromes should be suspected in the case of PGLs that are recurrent, early onset (<45 years), extra-adrenal and/or metastatic. With additional genetic testing, our patient with an already rare growth disorder was found to have hereditary PGL syndrome IV caused by a pathogenic mutation in the SDHB gene. This unique case highlights the rationale and importance of systematic genetic cancer screening in the diagnostic evaluation of PPGLs.
SAT-LB310 A Mysterious Multiple Endocrine Neoplasia (MEN) Like Syndrome
Authors: Soe Myat Han , cheng cheng , Liu Chienying
Published: May 2020

Multiple endocrine neoplasia (MEN) is characterized by the occurrence of tumors involving two or more endocrine glands in a single patient. Among the four MEN syndromes, MEN4 due to CDKN1B mutation is characterized by parathyroid and anterior pituitary tumors in possible association with tumors of the adrenals, kidneys, and reproductive organs. We presented a patient with MEN 4 like syndrome without CDKN1B, menin or RET mutations.

74 year old male was diagnosed with acromegaly and primary hyperparathyroidism at age 63. Genetic testing revealed no mutations in menin and RET genes. At age 68, he was diagnosed with renal cell carcinoma (RCC) and at age 70, 2cm left adrenal mass was identified on surveillance computerized tomography (CT). No biochemical workup was pursued. Four years later, he developed hypertensive crisis during spine surgery at our institution. Workup revealed elevated plasma metanephrine (490 pg/ml, normal <57) and normetanephrine (1333 pg/ml, normal <148). CT showed the left adrenal mass increased in size to 4.5 cm. Family history is negative for any endocrine tumors. He underwent repeat genetic testing. Analyses of 133 gene panel reported no germline mutations in menin, RET, CDKN1B, NF12, VHL, SDH and other genes tested but there were variants of uncertain significance (VUS) identified in CHEK2 c.14C>T (p.Ser5Leu) and PTCH2 c.2812G>A (p.Gly938Ser). Patient successfully underwent left adrenalectomy after alpha blockage. Paired tumor-normal sequencing of the resected tumor detected a pathogenic deletion frameshift mutation in NF1 with loss of heterozygosity (LOH) along with copy number alterations with losses in 1p34.1-p11.2, 11p11.2-15.4, 11q14.1-q25 and 17q11.2 (including NF1). VUSs were also detected including CDKN1A C117Y variant, and CHD2P80L. Since germline and tumor testing failed to reveal any known pathogenic variants, whole exome sequencing (pending) will be pursued.

The presentation with RCC, pheochromocytoma, pituitary adenoma and parathyroid adenoma is consistent with a MEN syndrome in this patient despite no known pathogenic MEN mutations detected. Somatic mutation in NF1 is a common finding in pheochromocytoma. The biochemical phenotype of pheochromocytoma (elevated metanephrines) is consistent with cluster 2 tumors of kinase signaling pathway as seen in tumors of MEN syndrome and neurofibromatosis. We hope to gain more insight via whole exome sequencing to evaluate for potential novel gene mutation(s).
SUN-LB72 The Relationship Between Estrogen Exposure and Bone Health in Women With Cystic Fibrosis
Authors: Arora Neha , Wu Malinda , Tangpricha Vin
Published: May 2020

Patients with cystic fibrosis (CF) are at risk for cystic fibrosis-related bone disease (CFBD) characterized by low bone mineral density and fractures. Nutritional status, cystic fibrosis-related diabetes (CFRD), lung health, and sex hormone insufficiency affect CFBD. CF Foundation guidelines recommend exogenous estrogen treatment for women with CFBD and sex hormone deficiency. There is a lack of data regarding effects of exogenous estrogen supplementation on the bone health of CF women. This Emory IRB approved case-control study examined the association of estrogen on bone health in CF women. Data included demographics, sex hormone treatments, CFBD modifiers, and bone mineral density. 35 estrogen exposed subjects were matched 1:2 to 70 estrogen unexposed subjects for age, BMI, and transplant status. Statistical tests analyzed differences in bone health outcomes between the estrogen and non-estrogen exposed groups. At baseline, age, BMI, transplant status, and CFRD were not statistically different (p>0.05) between the two groups. The unexposed group had higher rates of pancreatic insufficiency (p=0.02). The exposed and unexposed subjects did not have statistically significant differences in areal bone mineral density at lumbar spine, femoral neck, or total hip (p>0.05). Our study demonstrates that there are no differences in bone mineral density at 3 different sites between estrogen exposed versus estrogen unexposed women. One limitation is that factors that may also influence bone density including vitamin D status, family history, and severity of CF mutation were not corrected for. Future longitudinal studies should determine if estrogen treatment can increase bone density over time in CF women.
SAT-583 Assessment of Thermoregulatory Pathways Induced in Male and Female Mice Lacking Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) in Response to Cold Acclimation
Authors: Filatov Ekaterina , Short Landon I , Forster Maeghan A M , Harris Simon S , Schien Erik N , Hughes Malcolm C , Cline Daemon L , Appleby Colin J , Gray Sarah L
Published: May 2020

Pituitary Adenylate Cyclase Activating Polypetptide (PACAP) is a peptide hormone known to regulate energy homeostasis1. Mice lacking PACAP are cold sensitive and have impaired adrenergic-induced thermogenesis2-4. Interestingly, Pacap null mice can survive cold housing if acclimated slowly, similar to what was observed in UCP1 deficient mice4,5. We hypothesized that Pacap-/- mice employ alternate thermogenic pathways to compensate for impaired adaptive thermogenesis and assessed shivering thermogenesis and UCP1-dependent and UCP1-independent adaptive thermogenesis in male and female Pacap-/- and Pacap+/+ with cold acclimation (4°C). Assessment of oxidative fibres in skeletal muscles and behavioural observations did not show evidence of prolonged shivering in male or female Pacap-/- mice during cold acclimation compared to Pacap+/+ mice. We did however observe morphological and molecular differences in adipose tissues of Pacap-/- mice compared to Pacap+/+ mice that were distinct in males and females. Cold-acclimated, female Pacap-/- mice had decreased induction of UCP1 protein in intrascapular brown fat (iBAT), yet had a significantly higher beiging and UCP1 immunoreactivity (ir) in gonadal white fat (gWAT) compared to female Pacap+/+ mice. Furthermore, beiging was observed in inguinal white fat (ingWAT) and gWAT of female Pacap-/- mice housed at thermoneutrality (30°C), a finding not observed in Pacap+/+ control mice. Unlike female mice, we did not observe impaired UCP1 induction in iBAT of male Pacap-/- mice compared to Pacap+/+ mice, and this was associated with negligible UCP1-ir in male gWAT similar to wildtype controls. Despite previous work that has established impaired adaptive thermogenesis in Pacap-/- mice4, we show here that UCP1 protein can be induced in adipose tissues of Pacap-/- mice during cold acclimation, although to a lesser degree or in a different pattern compared to Pacap+/+ control mice. Taken together, this work suggests that while PACAP is clearly involved in regulating thermoregulation, it is not required for cold-induced UCP1 expression. In addition, this work highlights sexual dimorphism in adipose tissue remodeling and induction of thermogenesis with cold acclimation. References: (1) Rudecki AP, et al. Trends Endocrinol Metab. 2016;27(9), 620–632. (2) Gray SL, et al. J Mol Endocrinol. 2001;15(10), 1739–1747. (3) Gray SL, et al. J Endocrinol. 2002;143(10), 3946–3954. (4) Diané A, et al. J Endocrinol. 2014;222, 327–339. (5) Golozoubova V, et al. FASEB J. 2001;15, 2048–2050.
SAT-LB105 A Transcribed Ultraconserved Noncoding RNA, Uc.336-As, Promotes White to Brown Conversion in 3T3-L1 Cells
Authors: He Xiaoying , Xiang Tao , Guan Hongyu , Li Yanbing
Published: May 2020

Brown adipose tissue (BAT) has gained its popularity since it shows great potential in counteracting obesity and metabolic diseases development. Transcribed ultraconserved regions (T-UCRs), a novel class of long non-coding RNA (lncRNAs), have been implicated in regulating diverse biological processes, including the process of white fat browning. However, the functional and mechanistic details of T-UCRs in the browning process are poorly understood. Here, we identified that a T-UCR, uc.336-as, played an important role during the browning process. Uc.336-as was significantly elevated during browning process induced by glucagon-like peptide-1 receptor agonist (exendin-4) or β3-adrenergic agonist (CL316,243). Overexpression of uc.336-as reduces the differentiation of 3T3-L1 preadipocytes into white adipocytes (inhibited lipid accumulation and decreased the expression of several adipogenesis markers) and induces brown characteristics during differentiation of 3T3-L1 preadipocytes (spurred browning adipocytes phenotypes and increased the expression of the browning associated genes). Moreover, we found that uc.336-as inhibited adipogenesis and promoted browning process via influencing the serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) axis, an essential signal pathway in adipocyte metabolism. Taken together, our data show that uc.336-as acts as a negative regulator in white adipocyte differentiation and promotes the browning process, suggesting a potential therapeutic role for uc.336-as in controlling obesity.
SUN-LB117 Faster Acting Insulin Aspart in Patients With Gestational Diabetes Mellitus - an Early Experience From India
Authors: Bhattacharyya Supratik
Published: May 2020

Aims: This study was undertaken to assess the effectiveness and safety of faster acting insulin aspart in patients with gestational diabetes. Though faster acting insulin aspart is approved to be used in pregnancy by regulatory bodies like USFDA, EMA and DCGI (India), no data is published till date on its usage in pregnancy. Settings and Design: An open-label, nonrandomized, and observational study conducted at single centre at Kolkata, India. Subjects and Methods: A total of 37 patients with gestational diabetes mellitus (GDM) were included in the analysis. Patients were started on insulin therapy (faster acting insulin aspart ± basal insulin) once medical nutrition therapy for 2 weeks failed to achieve control, that is., fasting plasma glucose ≥90 mg/dL and/or 1.0 h postprandial plasma glucose ≥130 mg/dL. Basal insulin dose was titrated to achieve a fasting of 90-100 and the Faster aspart was titrated to achieve a post-meal of 120 and not exceeding 130. Patients were followed once every 4 weeks until the 28th week, then once every 2 weeks until 32nd week, then once every week until delivery, and the final visit was on 30 ± 7 days after delivery of the child. Results: Out of 37 full term deliveries, only two had macrosomia. No congenital defects were noted in the anomaly scan and at births. There were no episodes of neonatal hypoglycemia reported. Only one episode of post-meal symptomatic maternal hypoglycemia was reported. Mean number of FiASP injections per day was 2.88 ± 0.39. Mean daily dose of FiASP used was 22.7 ± 6 international units. A total of 89% of the patients received faster aspart thrice daily and remaining received it twice daily. Conclusions: Faster acting insulin aspart was found safe in pregnancy, however, more studies with double-blind, standard controlled studies are required to confirm the findings of this study.
MON-LB86 The Sensitivity and Specificity of Various Thyroid Nodule Ultrasound Characteristics and the Diagnostic Accuracy of the ATA Guidelines and ACR TI-RADS for Predicting Thyroid Cancer at an Urban Endocrinology Clinic
Authors: Dacuycuy Leonierose , Gurung Purnima , Bao Ginny W , Chen Tony , Sudat Sylvia , Yin Anthony York Yul
Published: May 2020

Introduction: Several current guidelines assess sonographic features to guide management of thyroid nodules. The ACR uses an additive point system to assign the level of risk to various sonographic features, whereas the ATA groups sonographic features together to determine the level of risk. The purpose of this study is to compare the performance of the ATA guidelines and ACR TI-RADS at an urban endocrinology clinic in risk stratifying thyroid nodules by their specific sonographic features.

Methods: This retrospective, chart-review study includes adult patients who met sonographic criteria for fine needle aspiration (FNA) biopsy based on ATA or ACR TI-RADS at an outpatient endocrinology practice in San Francisco, CA between December 2011 and August 2019. Patients with a prior history of thyroid malignancy (anaplastic and medullary thyroid carcinoma or thyroid lymphoma) were excluded. The reference standard for the diagnosis of malignancy was surgical pathology or FNA cytology Bethesda category V or VI when surgical pathology was unavailable. Analysis of guideline performances and specific sonographic features included: sensitivities (Sn), specificities (Sp), positive predictive values (PPV), negative predictive values (NPV), and area-under-the-curve (AUC) using Fisher’s exact test.

Results: Two hundred seventy-five nodules among 195 adults (86.2% were women) were included in the analysis. Twelve nodules were malignant, with an associated malignancy rate of 4.4%. TI-RADS had higher accuracy based on AUC of 0.710 compared to 0.623 using ATA guidelines. TI-RADS also had a higher PPV of 21.4% among nodules with 9 points, versus 5.8% among nodules in the ATA “high suspicion” category. Ultrasound characteristics with the highest Sp, relative PPV and NPV were: microcalcifications (84.5%, 4.3%, 96.0%, respectively), taller-than-wide (81.7%, 7.1%, 96.7%), irregular margins (77.7%, 6.0%, 96.5%); the characteristic with the highest Sn was hypoechogenicity (83.3%), however this had relatively low Sp (25.4%) and PPV (4.5%).

Conclusions: TI-RADS performed better with higher overall accuracy and PPV when applied to nodules classified as having the highest malignancy risk. Taller-than-wide shape, irregular margins, and microcalcifications were the characteristics most useful for malignancy risk stratification. Limitations of this study include: interobserver bias, small sample size, referred patient population (which may differ from other institutions), and inability in some cases to confirm malignant FNA cytology with surgical pathology.
SUN-LB88 Thyrotoxic Periodic Paralysis in Hispanic Patients
Authors: Sarwar Tahira , Martinez Jose , Kirupakaran Johnathan , Rodriguez Giovanna , Bahtiyar Gül
Published: May 2020

BACKGROUND: Thyrotoxic periodic paralysis (TPP) presents as acute intermittent attacks of weakness related to hypokalemia, commonly reported in Asians and rare in Hispanics(1). Patients with TPP will have triiodothyronine (T3) triggered increased Na+/K+ ATPase pump activity and transcription of the KCNJ18 gene that encodes for the Kir2.6 channel(2). This permits insulin, catecholamines, stress and alcohol(3) to increase cellular intake of potassium, which causes depolarization and leads to weakness and paralysis. We report a case of TPP in a young Hispanic man who presented with lower extremity weakness and falls. CASE PRESENTATION: A 34-year-old Hispanic man with Graves’ disease, non-adherent to medications presented with generalized weakness, more pronounced in legs, and recurrent falls. Physical examination was unremarkable except for mild enlargement of thyroid gland and abnormal gait due to weakness. Laboratory data showed hypokalemia of 1.8 mmol/L (3.7-5.1 mmol/L) and a TSH level of <0.004 mIU/L (0.34-5.6 mIU/L). Free T4 3.74 ng/dL (0.6-1.6 ng/dL), free T3 597 pg/dL (230-420 Pg/dL), thyroid stimulating Ig 148 (<130). Electrocardiogram did not show U waves. Radio iodine 123 scan of thyroid revealed diffusely increased 24-hour radioactive uptake of 66.5% (10-30%). The patient was diagnosed with TPP and supplemented with three doses of potassium 40 mEq IV infusion. Methimazole and metoprolol were started. He made a good clinical recovery within days. After discharge, he was treated with I-131 (13 mci) and developed postablative hypothyroidism on long term. He was euthyroid on levothyroxine. He did not have any recurrence of weakness at 7-year follow-up. CONCLUSION: TPP is uncommonly seen in Hispanics patients as opposed to Asians(3). Physicians should consider TPP as part of the differential diagnosis in young hyperthyroid Hispanic men presenting with weakness or paralysis, as early recognition and treatment can reduce recovery time and potentially prevent tachyarrhythmia or death. REFERENCES: 1. Matta A, Koppala J, Gossman W. Thyrotoxic hypokalaemic periodic paralysis: a rare presentation of Graves’ disease in a Hispanic patient. BMJ Case Rep. 2014;2014. 2. Ryan DP, Ptacek LJ. Mutations in Potassium Channel Kir2.6 Cause Susceptibility to Thyrotoxic Hypokalemic Periodic Paralysis. Cell, 140(1), pp.88-98. 3. Amblee, A. and Gulati, S. (2016). Thyrotoxic Periodic Paralysis: Eight Cases in Males of Hispanic Origin from a Single Hospital. AACE Clinical Case Reports, 2(1), pp.e58-e64.
MON-073 Hyperinsulinemic Hypoglycemia Responsive to Diazoxide Due to a Previously Unknown ABCC8 Dominant Mutation
Authors: Figueredo Veronica M , Diaz Alejandro , Banchs Pedro Pagan
Published: May 2020

Background: Hyperinsulinism is the most common cause of persistent hypoglycemia. It results from different genetic defects, the most common being recessive and dominant mutations in the ABCC8/KCNJ11 genes. The majority of recessive mutations have a poor response to Diazoxide, while dominant mutations are highly variable in both clinical presentation and response to treatment. Prompt recognition and management is critical to avoid irreversible brain damage. Clinical case: A 38-week gestation male, born via emergent c-section due to decreased fetal movement, presented with neonatal hypoglycemia. Pregnancy was uncomplicated and mother had a normal OGTT. Patient had a history of suspected sepsis, seizures, pulmonary hypertension and respiratory distress requiring intubation. Blood glucose was undetectable at birth and required multiple dextrose 10% boluses. A critical sample with a glucose of 47 mg/dL showed an elevated insulin at 30.3 m IU/mL with undetectable ketone levels. Lactic acid, ammonia, cortisol, GH, plasma amino acids, acylcarnitine profile and uric organic acids where all normal for a hypoglycemic state. He required intravenous glucose infusion with GIR up to 17 mg/kg/min to maintain normoglycemia. A brain MRI at 11 days of life showed findings of white matter injury. Subsequent genetic testing identified a heterozygous c.4051G>A (p.Val1351Met) variant in ABCC8, classified as “of uncertain significance”. However, an entry in the ClinVar database (RCV000714711.1) exists from a research lab and was classified as likely pathogenic. Analysis of parental samples showed that the mother was heterozygous for the same genetic variant. She did not have a history of hypoglycemia. Patient was started on diazoxide (8 mg/kg/day) and chlorothiazide with resolution of hypoglycemia. At a follow up visit at 5 months of age, there was no history of hypoglycemia, and no need for adjustments of the diazoxide dose by weight (dose at that time of 7.4 mg/kg/day). Conclusion: The ABCC8 reported here is a dominant mutation causing hyperinsulinemic hypoglycemia responsive to diazoxide with a milder phenotype later in infancy. Longitudinal follow up of the case is warranted to understand the long term progress in patients with this particular mutation. Reference: Adam MP, Ardinger HH, Pagon RA, Wallace SE, et al. None. 1993. Familial hyperinsulinism.
SAT-222 Aggressive Phenotype Pheochromocytoma Associated with NF-1 and BRCA Mutation
Authors: Chaidarun Tanyawan , MacLeod Sara Rose , Chaidarun Sushela
Published: May 2020

Introduction

Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla that occur sporadically or with familial association. Familial predilection occurs in those with multiple endocrine neoplasia type 2, von Hippel-Lindau disease, and neurofibromatosis Type 1 (NF-1). To date, more than 21 gene mutations have been identified that are involved in the development of pheochromocytomas. However, co-existence of two different mutations such as NF-1 and BRCA gene mutations with pheochromocytoma has not been well described.

Clinical Case

A 40 year-old woman with NF-1 and recently diagnosed left breast invasive ductal carcinoma, estrogen positive, progesterone positive, HER-2 negative BRCA2 positive breast cancer and right breast lobular carcinoma in situ underwent staging CT scan. A 2.7 cm left adrenal incidentaloma with heterogeneous texture and 69–100 HU was discovered. Symptom review revealed chronic headaches and increasing frequency of anxiousness and irritability. She had no personal or family history of hypertension. Laboratory analysis showed elevated catecholamine levels included plasma normetanephrine of 2.8 nmol/L (normal <0.9), metanephrine of 0.9 nmol/L (normal <0.5), 24 hour urine metanephrine 498 mcg/24 hr (normal <180) and 24 hour urine normetanephrine of 1,152 mcg/24 hr (normal <451). Findings were consistent with adrenal pheochromocytoma.

She was immediately started on phenoxybenzamine and encouraged to increase fluid intake to expand intravascular volume before surgery. She underwent laparoscopic left partial adrenalectomy fourteen days later. Surgical pathology revealed a 3.0 cm pheochromocytoma in a background of nodular hyperplasia of the medulla, described as an aggressive tumor phenotype based on morphological features.

Conclusions

It has been estimated that 1.5–14% of adrenal incidentalomas are pheochromocytomas. While only 3% of NF-1 patients have pheochromocytomas, 20–50% of NF-1 patients with concurrent hypertension have underlying chromaffin tumors. This association is significant when compared to the pheochromocytoma incidence of 0.1% in all hypertensive individuals. Interestingly, germline mutations of BRCA-1 associated protein-1 gene have been reported in patients with paragangliomas, therefore it may be plausible to consider interactions between NF-1 and breast cancer BRCA-2 gene mutations, resulting in an unusual and more aggressive pheochromocytoma phenotype, even when detected at an early stage, as in this case. It is also important to recognize and adequately treat pheochromocytoma prior to having surgery to avoid possible intraoperative hypertensive crisis, a concept that was underscored in this particular case when the patient was relatively asymptomatic and entirely normotensive preoperatively.
SAT-LB126 Metformin Attenuates Sodium Retention and Blood Pressure in Hypertensive Diabetic Mice by Reducing the Phosphorylation of Renal NCC and Its Association With the Actin Cytoskeleton
Authors: Gholam Mohammed F , Waleed Alina , Tuna Kubra M , Carson-Marino Morgan , Chacko Kevin M , Malik Zeeshan S , Schramm Whitney C , Lopez Juliana V Pena , Alli Abdel A
Published: May 2020

Metformin is the first-line drug in the treatment of type 2 diabetes mellitus. The aim of this work was to evaluate the efficacy of metformin treatment in reducing blood pressure and investigate the molecular mechanism using a preclinical animal model. Adult male and female diabetic db/db mice with a blood glucose of greater than 300 mg/dl were salt-loaded (8% NaCl) for 10 days to induce hypertension. The mice were subject to metabolic cage studies for 24 hour urine collections in order to measure urinary electrolytes, albumin, and creatinine. Blood pressure was measured weekly by the tail-cuff method to assess the effect of metformin or vehicle given by oral gavage (dose of 60 mg/kg of body weight per day). At the end of the study the mice was euthanized and the left kidney was formalin-fixed and paraffin-embedded for immunohistochemistry while the right kidney was homogenized for Western blotting. Western blotting showed attenuation of total NCC and phospho-NCC in diabetic db/db mice given an oral gavage of metformin (Pearson correlation coefficient: 0.9470 +/- 2.52e-3) compared to vehicle (Pearson correlation coefficient: 0.9800 +/- 2.86e-3). Immunohistochemical analysis showed less co-localization of the actin cytoskeleton protein filamin and phosphorylated NCC in the metformin treated group compared to the control group. Taken together, we show metformin decreases sodium retention and blood pressure by reducing the density of renal NCC at the luminal membrane and the association between NCC and the actin cytoskeleton.