bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-536 SPOCK1 Promotes the Progression of Papillary Thyroid Cancer ViaPI3K/Akt Signaling Activation
Authors: Li Hai , Choy Manting , Guang Hongyu , Li Yanbing
Published: May 2020

With the increasing incidence, thyroid cancer as one of the most common malignancy, has got widespread attention during the past few years. Papillary thyroid cancer (PTC) is the most common thyroid cancer type. Understanding the underlining molecular mechanisms of PTC is of great interest. The oncogenic role of SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) has been demonstrated in several cancers, however, the clinical and functional significance of SPOCK1 in PTC are largely unknown. Here, we found that the expression of SPOCK1 was upregulated in PTC tissues when comparing with the adjacent normal thyroid tissues. The overexpression of SPOCK1 was associated with the clinicopathological characteristics of the patients with PTC. We demonstrated that the proliferation of PTC cells was significantly promoted and the apoptosis of PTC cells was significantly inhibited in cells with overexpression of SPOCK1. Furthermore, we showed that knockdown of SPOCK1 arrested the cell cycle in G0/G1 phase and promoted the apoptosis in PTC cell lines. Importantly, our data suggested that SPOCK1 promoted the progression of PTC cell via regulating the PI3K/Akt signaling pathway. Taking together, our findings demonstrate that SPOCK1 enhances the activation of PI3K/Akt signaling pathway, thereby promoting the proliferation and inhibiting the apoptosis of PTC cells.
SUN-918 A Brain Metastasis in Malignant Paraganglioma Treated with Multidisciplinary Strategy
Authors: Tanabe Akiyo , Miyahara Makiko , Hashimoto Makiko , Kajio Hiroshi
Published: May 2020

Introduction: The most common sites of metastatic pheochromocytoma/paraganglioma (PPGL) are regional lymph nodes, bone, liver, and lung. Metastatic PPGL to the brain is very rare. Herein we describe a case of malignant paraganglioma (PGL) with a brain metastasis in the 27th year of his clinical history. Clinical Case: A 57-year-old Japanese man presented with sudden onset of headaches, speech disturbance, and mild cognitive impairment. His medical history was significant for surgery to resect a left peri-adrenal PGL at 30 years of age. At 35 years of age small lung metastases were treated with 5 cycles of chemotherapy without demonstrable response. Hypertension was diagnosed at age 44 years and diabetes mellitus at 49 years of age. The some lung metastases gradually increased in size and he underwent video-assisted thoracic surgery (VATS) at age 50 years. Plasma norepinephrine (pNE) and urine normetanephrine (uNM) levels, which were 3-fold elevated above the upper limit of the reference ranges, normalized after VATS. Subsequently, hypertension was well controlled and pNE and uNM levels remained within the reference ranges. Then, at 57-years of age, he developed central nervous symptoms and a mass with broad peritumoral edema was found in his left parietal lobe on head MRI. The 1.6 cm mass was hypervascular and isointense on T1-weighted imaging and was an inhomogeneous high-intensity in T2-weighted imaging. Both 123-I-MIBG SPECT and 18F-FDG-PET/CT imaging showed strong uptake in the brain metastasis. Although pNE and uNM levels were within their respective reference ranges, the 123-I-MIBG was diagnostic of metastatic PGL. Dexamethasone (DEX) was started to improve the brain edema. The brain metastasis was treated with linear accelerator stereotactic radiosurgery (LINAC-SRS) which was tolerated well without any adverse effects. However, the tumor volume and peritumoral edema area had not decreased one year after LINAC-SRS. Because high dose of DEX needed to continue, and his drug-induced psychiatric symptoms had worsened, we decided to move to surgical option. A craniotomy and total tumor removal was performed without any perioperative event. His condition rapidly improved and the DEX treatment was discontinued after surgery. Although he had slight hemiplegia and aphasia, and small lung metastases, he maintained a stable disease three years after surgery. Conclusion: Because PPGLs are slow growing neoplasms, multidisciplinary treatment should be considered even though there are multiple metastases. SRS has been used to treat skull base and neck PGLs with local control rates >90%. However, although SRS could suppress tumor growth, dramatic tumor volume reduction is not expected. Therefore surgical approach should be considered for brain metastasis as the next strategy for intracranial decompression.
SAT-260 Resolution of a Cystic Macroprolactinoma with Dopamine Agonist Therapy
Authors: Ansari Mohammad Jamal Uddin , Abdelkarim Jumana , Baral Shailesh , Parveen Sanober , Mariam Murtaza Ali , Jabri Hadoun , Rehman Anis , Jakoby Michael G
Published: May 2020

Background. Prolactinomas with cystic regions occupying ≥ 50% of tumor volume are classified as cystic prolactinomas. They appear to arise from tumor necrosis or hemorrhage. Though Pituitary Society guidelines recommend surgery as first-line treatment for cystic prolactinomas, there is evidence that cystic prolactinomas are hormonally and anatomically responsive to treatment with dopamine agonists (DA). We present a case of a cystic macroprolactinoma fully responding to treatment with cabergoline. Case. A 31 year old male was referred for evaluation of gynecomastia, diminished libido, and erectile dysfunction that occurred over the course of eight months. Bilateral glandular breast tissue with a slight right asymmetry was present. Testes were 15–20 mL, soft, and without masses. Phallus and pubic hair were unremarkable. Morning (8 AM) testosterone, estradiol, and LH levels were 92 ng/dL (348–1197), 13.4 pg/mL (7.6–42.6), and 2.0 mIU/mL (1.7–8.6), respectively. Prolactin level was 331 ng/mL (4–15), and MRI with pituitary protocol revealed a 1.4 x 1.0 x 1.5 cm cystic mass with peripheral rim enhancement and extension into the suprasellar cistern. No mass effect on the optic chiasm was observed. Somatotroph, thyrotroph, and corticotroph axes were unaffected. Cystic macroprolactinoma causing hyponadotropic hypogonadism complicated by gynecomastia was diagnosed. The patient chose initial management with cabergoline 0.25 mg twice weekly. Three months after starting treatment, libido and erectile function had recovered to baseline, 8 AM testosterone was 607 ng/dL, and hyperprolactinemia was well controlled (4.2 ng/mL). At six months, anatomic resolution of the cystic macroprolactinoma was demonstrated on repeat pituitary MRI. Plastic surgery was required for management of gynecomastia. Conclusions. Surgery is recommended for management of cystic prolactinomas due to concern that a lack of dopamine receptors in the cystic components of tumors will make DA ineffective reducing tumor size. However, this case joins a growing body of evidence that DA can treat hyperprolactinemia and induce regression of cystic macroprolactinomas. For example, in a retrospective case review of patients with cystic macroprolactinomas at Massachusetts General Hospital, persistent cyst reduction occurred in 20 of 22 patients treated initially with DA, and median reduction in cyst volume exceeded 80 percent. Median time to documented cyst reduction was approximately six months, and there was no difference in degree of cyst reduction for patients treated with bromocriptine or cabergoline. The response of cystic prolactinomas to DA is similar to solid prolactinomas, and DA are reasonable initial treatment for cystic macroprolactinomas without clear indications for surgery.
MON-027 Activation of Endoplasmic Reticulum Stress Mediates Oxidative Stress-Induced Apoptosis of Granulosa Cells in Ovaries Affected by Endometrioma
Authors: Kunitomi Chisato , Harada Miyuki , Azahry Jerilee Mariam Khong
Published: May 2020

Endometriosis exerts detrimental effects on ovarian physiology and compromises follicular health. Granulosa cells of endometriosis patients are characterized by increased apoptosis, as well as high oxidative stress. Among several pathophysiologic factors associated with endometriosis, it is expected that oxidative stress contributes to the induction of apoptosis in granulosa cells, although the underlying mechanism remains unclear. Endoplasmic reticulum (ER) stress, a local factor closely associated with oxidative stress, has emerged as a critical regulator of ovarian function. We hypothesized that ER stress is activated by high oxidative stress in granulosa cells in ovaries with endometrioma and mediates oxidative stress-induced apoptosis. Ovaries from patients with endometrioma and control were collected to determine apoptosis, oxidative stress and ER stress by TUNEL, immunohistochemical staining of 8-OHdG and ER stress sensors, respectively. Human granulosa-lutein cells (GLCs) obtained from IVF patients were cultured with H2O2 (an oxidative stress inducer) or tauroursodeoxycholic acid (TUDCA, an ER stress inhibitor in clinical use) to assess apoptosis and ER stress by quantitative PCR and FACS. Activity of pro-apoptotic factors was determined by caspase-8 activity assay and western blotting for cleaved caspase-3. Human GLCs from patients with endometrioma expressed up to two times higher level of mRNAs associated with the unfolded protein response (UPR), including ATF4, ATF6, the spliced form of XBP1, HSPA5, and CHOP. In addition, the levels of phosphorylated ER stress sensor proteins, IRE1 and PERK, were elevated. Given that ER stress results in phosphorylation of ER stress sensor proteins and induces UPR factors, these findings indicate that these cells were under ER stress. H2O2 increased expression of UPR-associated mRNAs in cultured human GLCs, and this effect was abrogated by pre-treatment with TUDCA. Treatment with H2O2 increased apoptosis and the activity of pro-apoptotic factors caspase-8 and caspase-3, both of which were attenuated by TUDCA. Our findings suggest that activated ER stress induced by high oxidative stress in granulosa cells in ovaries with endometrioma mediates apoptosis of these cells, leading to ovarian dysfunction in endometriosis patients. Targeting ER stress with currently clinically available ER stress inhibitors, or with these agents in combination with antioxidants, may serve as a novel strategy for rescuing endometriosis-associated ovarian dysfunction.
MON-091 The Clinical and Endocrinologic Manifestations of Craniopharyngioma in Taiwanese Pediatric Population: One Medical Center Experience
Authors: Huang Ching-Chih , Lo Fu-Sung
Published: May 2020

Introduction: Craniopharyngioma is a rare tumor located in the suprasellar region. Due to the unique tumor location, hypothalamic-pituitary axis dysfunction is usually presented in these patients. The major symptoms are headache, visual impairment, increased intracranial pressure, and endocrinologic abnormalities. However, diagnosis is often delayed because of slow growth of the tumor and subtle symptoms. Our aims are to describe the clinical and endocrinologic manifestations before the surgical resection of craniopharyngioma in Taiwanese pediatric population. Method: We retrospectively reviewed 42 pediatric patients of craniopharyngioma in a tertiary medical center between 1996 to 2019. The clinical parameter including the initial presentation, age at diagnosis, height, weight, pituitary gland function, tumor location, time to diagnosis, and pathology reports are collected and analyzed. Results: A total of 42 patients (24 boys and 18 girls) were included in the study. The mean age at diagnosis was 8.6 years, ranging from 1 to 16-year-old. The average time to diagnosis was 7.7 months and 15.9 months for the patients with and without neurological signs, respectively. The most common initial presentation is headache (25/42, 60%), followed by visual impairment (20/42, 48%) and short stature (13/38, 34%). If short stature was the only initial presentation, 4 (4/7, 57%) of them were diagnosed of craniopharyngioma because they developed subsequent neurological deficits during clinic follow-up. Pituitary function tests showed that10 patients (10/25, 40%) had TSH deficiency and 8 patients (8/16, 50%) had central adrenal insufficiency. Image studies reported 26 patients with hypothalamic involvement and 4 patients without. All of 8 patients (8/37, 22%) with obesity had a tumor involving the hypothalamus. Pathology reports revealed 31 adamantinomatous type and only 1 papillary type. Conclusion: The study showed most (71 percent) of Taiwanese pediatric patients with craniopharyngioma presented with at least one endocrine dysfunction. Therefore, comprehensive pituitary evaluation for all patients with craniopharyngioma should be warranted. Furthermore, neurological signs and pituitary functions should both be monitored during the clinic follow-up for children with short stature or obesity in order to early diagnosis of craniopharyngioma.
MON-204 Pheochromocytoma and Paraganglioma: An Emerging Cause of Secondary Osteoporosis
Authors: Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Fukumoto Tazuru , Matsuda Yayoi , Nagata Hiromi , Ogata Masatoshi , Kawate Hisaya , Miyazawa Takashi , Sakamoto Ryuichi , Ogawa Yoshihiro
Published: May 2020

Context: Many endocrine diseases are known to cause secondary osteoporosis, which is potentially reversible by treatment of the underlying disease itself. Pheochromocytoma (PHEO) and paraganglioma (PGL) (PHEO and PGL: PPGLs) are the rare catecholamine-producing neuroendocrine tumors, which are associated with low bone mineral density (BMD). However, PPGLs have not been recognized as a cause of secondary osteoporosis. Indeed, even the prevalence of osteoporotic fracture in patients with PPGLs is currently unknown. Furthermore, whether surgical resection contributes to the improvement of BMD has never been addressed. Objective: This study was designed to evaluate 1) whether PPGLs increase the risk of vertebral fracture (VF), which is the most common type of osteoporotic fracture and 2) whether surgical resection of PPGLs contributes to the improvement of BMD. Design and Settings: A retrospective cross-sectional study in a single referral center. Participants: Among 443 patients with adrenal tumor (AT), we included 62 patients with histologically confirmed PPGLs and 61 patients with non-functional AT. Intervention: The prevalence of VF was examined in 49 out of 62 patients with PPGLs and 61 patients with non-functional AT. In 23 out of 62 patients with PPGLs, BMD was evaluated at baseline and after surgery. Results: PPGLs had a higher prevalence of VF (43% [21/49]) than non-functional AT (16% [10/61]; p = 0.002). PPGLs were an independent risk factor for VF after adjusting for age and sex (odds ratio, 4.47; 95% confidence interval, 1.76–11.3; p = 0.001). In PPGLs, BMD expressed as Z score at the lumbar spine was significantly improved at follow-up (before -0.5±1.0, after -0.2±0.9; p = 0.005). Conclusion: This study demonstrates that PPGLs are an independent risk factor for VF and that their surgical resection contributes to the improvement of BMD in the trabecular bone. These observations support the notion that PPGLs are an emerging cause of secondary osteoporosis.
SUN-293 Acute and Long Term Evaluation of Pituitary Functions in Patients with Advanced Heart Block Requiring Pacemaker Implantation: A Pilot Study
Authors: Viswanath Arun
Published: May 2020

Background: Neuronal hypoxia and neuro-inflammation accompanying conditions like traumatic brain injury, stroke, cerebrovascular accidents and sub-arachnoid haemorrhage has been associated with hypopituitarism. Neuronal insults of similar magnitude and hypopituitarism [Growth Hormone (GH), gonadotropin and TSH deficiency in 27.2%, 9.0% and 2.2% patients respectively] has also been noted in a single study till date conducted in patients of ventricular arrhythmias requiring cardio-pulmonary resuscitation1. Patients with heart block, a more frequent form of cardiac arrhythmia usually presents with haemodynamic compromise and may be predisposed for developing either acute or delayed hypopituitarism which has never been studied before.

Aims and objective: Our study was aimed at exploring whether pituitary dysfunction occurs in patients presenting with heart block and requiring pacemaker implantation. We analysed anterior pituitary functions in these cohort of patients during acute hospitalization and later during follow.

Study design: Cross sectional prospective study

Materials and Methods: Fifty-one patients were included in the study (mean age-65.98±10.9years; 34 men & 17 women). Pituitary hormonal profile was done within 48 hours of presentation and after a mean follow up of 12.52 ± 2.2 months. Total T3, total T4, free T4, TSH, FSH, LH, Testosterone (in men), Estradiol (in women), Prolactin, and random Cortisol were measured in all participants at baseline and in follow-up. Fixed dose Glucagon (weight<90kg-1mg; ≥90kg-1.5mg) stimulation test was done in follow-up to assess GH and cortisol axes.

Results: Among 30 (out of 50) patients who turned up for follow-up, GH, cortisol and TSH deficiency was noted in 50% (n-15), 13.3% (n-4) and 3.2% (n-1) of subjects, respectively. Pan-hypopituitarism characterised by deficiency of at least two hormonal axes was seen in 16.7% (n-5) patients.

Conclusion: Significant delayed hypopituitarism especially GH deficiency was seen among patients of heart block.

Implications: This novel finding if reproduced in subsequent studies will result in unearthing of a significant etiology of hypopituitarism which could potentially become the most common cause of acquired adult onset hypopituitarism considering the huge burden of patients with heart block. Heightened cardiovascular risk due to hypopituitarism in these patients may be reversed by active screening and replacement of deficient hormones. References: (1) Simsek, Kaya, Tanriverdi et al. (2014) Evaluation of long-term pituitary functions in patients with severe ventricular arrhythmia: a pilot study. J Endocrinol Invest 37:1057-1064Keywords: Cortisol, GH deficiency, Heart block, Hypopituitarism, Pituitary Disclosure: Authors have nothing to disclose
SAT-219 Allgrove Syndrome: How to Suspect a Problem?
Authors: Volkova Natalia , Davidenko Ilia , Dzherieva Irina , Zibarev Alexander , Ganenko Lilia , Reshetnikov Igor , Sorokina Julia , Brovkina Snezhana
Published: May 2020

Background: Allgrove syndrome (triple A syndrome) is a rare autosomal recessive multisystem disease characterized by adrenal insufficiency, alacrimia and achalasia. It is caused by a mutation in the AAAS gene (12q13) encoding the protein ALADIN (1). This syndrome is often associated with neurological dysfunction disorders, amyotrophy, in such cases, it is named 4A and 5A syndrome, but sometimes there is also 2A syndrome. Prevalence:<1/1000000. The first description was in 1978. Clinical case: A 18-year patient A. complained of fatigue, weakness, darkening of the skin. From anamnesis of life: born from the first pregnancy without complications, weight 3200g. Parents often turned to the pediatrician with complaints: lethargy, frequent regurgitation, ARVI up to 6–7 times a year. Slow weight gain, dyspeptic syndrome (nausea, vomiting) was noted objectively. At the age of 3, the boy entered the surgical department with acute abdomen, fever, vomiting. Achalasia was revealed, reconstructive surgery was carried out. In the diagnostic search for the causes of body weight loss he was directed to the endocrinologist. There were an increase in ACTH 470 pg/ml (0,0-46 pg/ml), cortisol 0.05 µg/DL. Diagnosis: primary chronic adrenal insufficiency; the dose of hydrocortisone 10 mg/day did not change with age. An in-depth anamnesis found: the patient never cried with tears. Objectively: asthenic body type, BMI 16.5 kg/m2, hyperpigmentation of the palms, armpits; weakness in the proximal muscles of the limbs. Laboratory studies: ACTH 95 PG/ml, cortisol 0.1 µg/DL (3.7–19.4 µg/DL). The secretion of mineralocorticoids was evaluated: plasma aldosterone and renin levels were within the reference values. Ophthalmologist: injected conjunctiva, sclera. Schirmer’s test: mild alacrimia. It allowed to make the diagnosis: “Primary chronic adrenal insufficiency. Condition after surgery for achalasia (1997). Alacrimia. Allgrove Syndrome.” The dose of hydrocortisone was increased to 17.5 mg/day. In 2019, the patient complained of a sharp deterioration of health, darkening of the skin. The dose of hydrocortisone was increased to 25 mg/day (15 mg at 8.00, 10 mg in the afternoon). The ophthalmologist noted an increase in the severity of alacrimia, artificial tear drops was recommended. The diagnosis was confirmed by pathogenic mutation c.43C>T of the AAAS gene. Discussion: Despite the full clinical picture, the right diagnosis was made only after 14 years. We shown the difficulty of diagnosis is due to the lack of awareness of clinicians about the disease, the importance of interdisciplinary interaction, as well as the need for follow-up of such patients. Reference: (1) Handschug K, Sperling S, Yoon SJ, et al. Triple A syndrome is caused by mutations in AAAS, a new WD-repeat protein gene. Human Molecular Genetics. 2001;10:283–290.
SAT-658 Associations of Serum and CSF Kisspeptin Levels with Metabolic and Reproductive Parameters in Men
Authors: Mutirangura Pornthira , Sitticharoon Chantacha , Chinachoti Thitima , Iamaroon Arissara , Triyasunant Namtip , Churintaraphan Malika , Keadkraichaiwat Issarawan , Maikaew Pailin
Published: May 2020

Action of kisspeptin in the central nervous system (CNS) is well known on reproductive regulation; however, its peripheral action is not well understood. Recent studies have shown that peripheral kisspeptin might be related to obesity and/or metabolic parameters in humans [1]; however, these associations are still inconclusive. This study aimed to 1) compare serum or cerebrospinal fluid (CSF) kisspeptin levels between different body mass index (BMI) groups 2) compare levels of kisspeptin between serum and CSF, and 3) determine correlations between serum or CSF kisspeptin levels with clinical, metabolic, and reproductive parameters. There were 40 male subjects who underwent an operation with lumbar puncture anesthesia. Subgroup analysis was performed to compare between the lean-normal group (n=13) which included lean and normal weight subjects, the overweight group (n=10), and the obese group (n=17) according to BMI. Blood samples were collected after at least 8-hour fasting before intravenous cannulation prior to the operation while CSF samples were obtained by lumbar puncture before administration of the spinal anesthesia. Serum kisspeptin and leptin levels were significantly higher in the obese group when compared to the lean-normal and overweight groups even after adjusted to age while CSF kisspeptin levels were comparable between different BMI groups (p<0.05 all). Serum kisspeptin levels were significantly higher than CSF kisspeptin levels (p<0.001). Serum kisspeptin was significantly positively correlated with body weight (R= 0.351), BMI (R=0.549), plasma insulin (R=0.393), and serum leptin (R=0.45) (p<0.05 all), and tended to have a positive correlation with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (R=0.29, p=0.77) but was significantly negatively correlated with plasma LH (R=-0.37) (p<0.05). CSF kisspeptin was significantly positively correlated with plasma LH (R=0.452, p<0.05). These results suggest that serum kisspeptin levels were related to increased obesity, leptin, insulin, and insulin resistance while CSF kisspeptin levels were related to reproductive parameters. In summary, central kisspeptin might have a role on reproductive regulation while peripheral kisspeptin might have a role on metabolic regulation. Reference: (1) Izzi-Engbeaya, C., et al., The effects of kisspeptin on beta-cell function, serum metabolites and appetite in humans. Diabetes Obes Metab, 2018. 20(12): p. 2800–2810.
SUN-060 Steroid Hormone Profile Differentiates Gynecomastia and Pseudo- Gynecomastia in Pubertal Boys
Authors: Reinehr Thomas , Kulle Alexandra , Barth Andre , Lass Nina , Holterhus Paul-Martin
Published: May 2020

Background: Gynecomastia (defined by breast tissue) and pseudogynecomastia (defined by adipose tissue) is frequent in pubertal boys. However, the underlying pathomechanisms are not fully understood so far. An association to growth hormone axis- IGF-1 axis and sex hormones has been discussed. Methods: We analyzed serum steroid hormones (progesterone, estradiol [E2], estriol, estrone, cortisol, cortisone, testosterone [T], dihydrotestosterone [DHT]) by liquid chromatography-tandem mass spectrometry, as well as gonadotropins, prolactin, IGF-1 and IGFBP-3 in 124 pubertal boys with breast swelling (mean age 14 +/-2 years). The steroid hormones were compared to those of 84 healthy pubertal boys (mean age 14 +/-2 years) without breast swelling. The differential diagnosis of either gynecomastia or pseudogynecomastia was determined by ultrasound. Puberty was defined by testes volumes > 3ml on each side. Results: A total of 86 boys suffered from gynecomastia and 38 from pseudogynecomastia. In boys with gynecomastia the ratio E2/T (median 22, interquartile range [IQR] 8–75) was significantly (p<0.05) higher compared to boys with pseudogynecomastia (median 12 IQR 5–21) or healthy boys without breast swelling (median 18 IQR 6–44). DHT concentrations were significantly (p<0.001) lower in boys with gynecomastia (median 0.13 IQR 0.02–0.38 nM/L) or pseudogynecomastia (median 0.18 IQR 0.05–0.32 nM/L) compared to healthy boys (median 0.41 IQR 0.22–0.66 nM/L). T concentrations were significantly (p<0.05) lower in boys with gynecomastia (median 1.8 IQR 0.7–4.2 nM/L) compared to boys with pseudogynecomastia (median 4.3 IQR 1.4–6.9 nM/L) or healthy boys without breast swelling (median 3.1 IQR 0.6–7.6 nM/L). The ratio DHT/T was significantly (p<0.001) lower in boys with gynecomastia (median 0.09 IQR 0.02–0.17) or pseudogynecomastia (median 0.04 IQR 0.02–0.16) compared to healthy Boys without breast swelling (median 0.13 IQR 0.05–0.28). Boys with gynecomastia did not differ from boys with pseudogynecomastia according to the other steroid hormones, prolactin, IGF-1, or IGFBP-3 concentrations. Conclusions: Gynecomastia is characterized by a higher E2 to T ratio compared to healthy boys without breast swelling due to a relative T deficiency in the presence of similar E2 levels. The lower DHT/T ratio in gynecomastia and pseudogynecomastia compared to healthy boys without breast swelling points towards a functional 5 alpha reductase deficiency.
MON-127 Gaps in Knowledge of Social Determinants of Health in an Endocrinology Fellowship
Authors: Malek Rana , Lamos Elizabeth
Published: May 2020

Background: In June 2018, the Accreditation Council for Graduate Medical Education (ACGME) revised the common program requirements and identified a core requirement “to understand the social determinants of health (SDH) of the populations they serve and incorporate them in the design and implementation of the program curriculum, with the ultimate goal of addressing these needs and health disparities.1” Trainees must “demonstrate an awareness of and responsiveness to the larger context and system of health care, including the SDH, as well as the ability to call effectively on other resources to provide optimal health care.” While Association of American Medical Colleges (AAMC) teaching hospitals comprise 5% of the total US hospitals, they provide 40% of charity care in the US. In this setting, trainees need to be aware of the challenges faced by the communities they serve. SDH are increasingly recognized for their importance in the care of patients with diabetes and explain the health disparities in diabetes that exist throughout the US. Endocrinology fellows and the faculty teaching them must therefore demonstrate knowledge of SDH and health disparities.

Methods: We investigated the knowledge gaps in SDH in an urban academic endocrinology fellowship. All fellows and faculty members completed a 10-question survey that assessed knowledge, confidence, and motivation to learn about SDH. Six fellows and 10 faculty members completed the survey.

Results: While 60% of faculty and 83% fellows reported having an understanding of SDH, no fellows or faculty could correctly identify all 6 SDH. When asked about their confidence level in identifying SDH, 20% of faculty had low confidence, 70% were confident, and 10% were very confident. For fellows, 50% reported low confidence, 33% were confident, and 17% were very confident. There was lower confidence level in fellows and faculty when addressing SDH—with half the faculty feeling not confident or only somewhat confident. Fellows had lower confidence levels with addressing SDH, with 83% reporting low confidence. However, motivation was high amongst fellows and faculty to learn more about SDH—83% of fellows and 70% of faculty were very motivated to learn more about SDH.

Conclusion: The ACGME has made knowledge of SDH a common program requirement of all training programs. A needs assessment of SDH in an urban endocrinology fellowship program identified knowledge and confidence gaps about SDH, but a high motivation to learn by both fellows and faculty. While trainees and faculty often learn “on the job” about SDH and health disparities, this study reveals that formal curricular activities must be incorporated into endocrinology fellowship programs to meet the ACGME common program requirements.

1.

ACGME “Common Program Requirements.” https://www.acgme.org/What-We-Do/Accreditation/Common-Program-Requirements.
MON-015 Pregnancy Adapts Circadian Rhythms in the Reproductive Axis: Impact on Labor Regulating Drug Efficacy
Authors: Hoffmann Hanne Mette , Duong Thu V , Nguyen Duong , Muhammed Asad , Yaw Alexandra M
Published: May 2020

Molecular and behavioral timekeeping is regulated by the circadian system represented on the cellular level by clock transcription factors, including Period2 (PER2), Bmal1, Clock and Cry. These transcription factors drive a daily ~24h rhythm in gene expression leading to tissue specific receptor expression optimizing sensitivity to hormones and drugs dependent on the time of day. To synchronize circadian rhythms in the body to the time of day, the brain’s suprachiasmatic nucleus (SCN) translates environmental light information into neuronal and endocrine signals allowing circadian rhythm synchrony. Despite the critical role of circadian rhythms in fertility, it remains unknown how circadian rhythms change within reproductive tissues during pregnancy, and how these adaptations might impact drug efficacy. Monitoring wheel-running patterns in circadian PER2::luciferase (PER2::LUC) reporter mice, we confirmed that pregnancy is associated with reductions of activity and identified a correlation between delayed onset of behavioral activity during late pregnancy and ex vivo SCN PER2::LUC period, whereas no correlation between arcuate nucleus PER2::LUC rhythms was identified. The time of day of peak PER2::LUC expression provides a time-stamp as to the circadian phase of a tissue. Pregnancy impacted circadian synchrony in the reproductive axis, with the most dramatic change within the uterus. To understand how circadian rhythms responded to input during pregnancy, we performed a pharmacology study and found that circadian rhythm generation in the uterus responded differentially to hormones regulating pregnancy and labor depending on gestational age and the time of day of drug administration. To test for functional changes in uterine contraction capacity, we recorded ex vivo uterine contractions. Our preliminary data reveal a circadian change in uterine function in the mouse, which impacted labor regulating drug efficacy depending on the time of day. Together our data show that pregnancy is associated with behavioral changes in locomotor activity patterns, as well as adaptations in phase-relationships in reproductive tissues. Our chrono-pharmacology study indicates that a better understanding of labor-regulating drug efficacy can potentially allow increased efficacy of currently used drugs in the clinic to both induce labor as well as halt preterm labor.
MON-128 Improving Medication Adherence in Pediatric Patients
Authors: Diramerian Linda Garabet , Ejaz Sehar
Published: May 2020

Introduction Caring for chronic pediatric endocrine disorders commonly require long-term use of pharmacotherapy. Although these medications are effective in combating disease, their real benefits are often not achieved because of non-adherence. Health care professionals must be aware to the high prevalence of noncompliance which contributes to increased morbidity and medical complications, poorer quality of life and an overuse of the health care system and increase health care costs. Methods In order to better understand the factors contributing to noncompliance in our patient population, we performed a cross -sectional study along with medical chart review. We randomly selected 30 endocrine charts with chronic disorders and reviewed documentation of the need for medications, type of the visit, dose, duration, plan, patient compliance and refill follow up. Special attention was made if the physicians documented discussing the possible side-effects of the medication. An anonymous survey was handed to the parents at the end of visit and form was dropped in a locked box. No personal information or identification was collected. Parents were inquired about their understanding of the need for medication, side effects, compliance and the reason for poor compliance if they met the criteria. The chart reviewed showed that 47% of the patients reported poor compliance to physician during visit but when asked during the survey only 22 % reported poor compliance. 58% of the patients reported not knowing the possible side-effects of the medications. Reasons for non-compliance given by patients were 58% concerned about side effects of medication, refill not provided 4.8%, forgetting to take medication 2.4%, cost 2.4%, and language barrier 2.4%. Other 30% didn’t provide a specific reason for poor compliance. Conclusion Rates of medication adherence in pediatric patient with chronic medical illness range from 11% to 93%, with an estimated average of around 50%. Our population compliance correlates with the national average for pediatric population compliance. Our study also highlighted the importance of discussing possible side-effects with patients. Reviewing it periodically during clinic visits may decrease the risk of non-compliance. 58% of our patients reported lack of knowledge of proper side-effects of the treatment and impact of non -compliance to disease progression. Based on these results, we provided additional resources to physicians to better screen for factors that may affect compliance in each visit. Certain hard stops were added in medical documents and modifications were done in EMR. Information about common endocrine conditions and medication was added in EMR in English and Spanish. Physicians were encouraged to given written information about the proper use and side-effects. We are planning to do a follow up survey in 3–4 months to evaluate the improvement.
SUN-035 A Role for GNRH-II in the Control of Puberty?
Authors: Urbanski Henryk F
Published: May 2020

Hypothalamic gonadotropin-releasing hormone (GnRH) neurons represent the primary neuroendocrine link between the brain and the reproductive system. Although they play a key role in stimulating the release of FSH and LH from the anterior pituitary gland, the underlying mechanism by which they trigger the onset of puberty is unclear. To address this issue, RT-PCR, in situ hybridization histochemistry, and Affymetrix gene arrays were used to profile hypothalamic GnRH gene expression in prepubertal and adult rhesus macaques (Macaca mulatta). Like humans, these nonhuman primates express two molecular forms of GnRH (GnRH-I and GnRH-II), both of which are highly effective at stimulating gonadotropin release via the same GnRHR1 receptor. However, only GnRH-II shows increased hypothalamic expression in the presence of elevated estrogen concentrations (i.e., positive feedback), whereas GnRH-I expression either remains the same or decreases (i.e., negative feedback). In the present study, the hypothalamic expression levels of GnRH-I and GnRHR1 were found to be no different between prepubertal and adult animals, despite marked differences in circulating sex-steroid hormone levels, whereas the hypothalamic expression level of GnRH-II was significantly higher in the adults than in the juveniles. Therefore, although the traditional GnRH-I neurons are likely to play a fundamental role in initiating FSH and LH release during the early stages of pubertal development, GnRH-II neurons may play an important role in maintaining elevated gonadotropin release during the final stages (i.e., at a time when the GnRH-I neurons are subjected to increasing negative sex-steroid feedback from the maturing gonads). Taken together, the data suggest that sexual maturation in primates is likely to be orchestrated by the concerted action of two distinct GnRH neuronal subtypes that respond differentially to sex-steroid feedback.
SAT-363 Renal Papillary Necrosis Associated with Normocalcemic Hyperparathyroidism
Authors: Shakir Mohamed K M , Kiran Vijay , Bloomer Zachary , Shin Terry , Mai Vinh Q , Hoang Thanh Duc
Published: May 2020

IntroductionHypercalciuria is generally considered to be the most common identifiable metabolic risk factor for calcium nephrolithiasis. Important renal manifestations of primary hyperparathyroidism (PHPT) include asymptomatic nephrolithiasis, hypercalciuria, nephrocalcinosis, and chronic renal insufficiency. However renal papillary necrosis (RPN) occurring in PHPT has not been reported previously. We report a 50-year-old woman who manifested RPN associated with hypercalciuria and normocalcemic PHPT. Case ReportA 50-year-old Caucasian woman was evaluated in 2006 for hypercalcemia. She had no history of nephrolithiasis, fractures, or symptoms of hypercalcemia. Laboratory: serum calcium 11.8 mg/dL, ionized calcium 6.3 mg/dL, phosphorus 1.8 mg/dL, intact PTH 98 pg/mL (ref 15–65), urine calcium 543 mg/24 hrs (ref <235). Renal ultrasound showed no evidence of nephrocalcinosis or nephrolithiasis. A parathyroid scan was consistent with a left superior parathyroid adenoma. Patient underwent parathyroidectomy and became normocalcemic with normal serum PTH levels postoperatively. One year later she was diagnosed with a left sided bronchial carcinoid tumor. Surveillance Gallium-68 PET/CT scan done 2 years later was negative for any metastases. Twelve years later she reported to our clinic for follow up. She had no symptoms of hypercalcemia, fractures, nephrolithiasis, history of pyelonephritis, diabetes mellitus, analgesic use, or hypertension. Serum calcium was 9.1 mg/dL, serum phosphorous 3.8mg/dL, PTH 82 pg/mL, 25-OH vitamin D 34 ng/mL, 1,25-vitamin D 38 pg/mL, and a urorisk panel was normal except for a 24-hour urine calcium of 410 mg. However renal ultrasound showed bilateral RPN and this diagnosis was also confirmed by a CT scan. A urinalysis showed only microalbuminuria with no red cells. She had no history of any analgesic drug abuse, pyelonephritis, sickle cell disease, or diabetes mellitus. A glucose tolerance test was completely normal. Discussion RPN is characterized by coagulative necrosis of the renal medullary pyramids and papillae brought on by several associated disorders and toxins that exhibit synergism toward the development of ischemia. Although the initial kidney US was normal, a repeat US done 12 years later showed evidence of RPN. This finding along with hypercalciuria and a diagnosis of normocalcemic PHPT suggests that RPN may be associated with hypercalciuria and normocalcemic PHPT. Furthermore she had no other risk factors for RPN. Additional studies with large number of patients are needed to confirm the association between these 2 disorders.
SAT-349 Cinacalcet Resistant Tertiary Hyperparathyroidism with One Large Parathyroid Gland
Authors: Chaker Bayan , Alim Hussam , Taha Wael
Published: May 2020

Tertiary hyperparathyroidism is thought to develop after long term secondary hyperparathyroidism, such as CKD on dialysis. In This case, all parathyroid glands are significantly enlarged.

We report a case of an 84-year-old female with a past medical history of ESRD on HD and recurrent nephrolithiasis who was found to have an enlarged multinodular goiter with the dominant mass in the lower pole of the right gland measuring about 4.7 cm on thyroid ultrasound. Blood work was done which showed elevated intact PTH levels at 2720 pg/mL (12–88). Her calcium level was normal at that time at 10.5 mg/dL (8.6–10.8) with an albumin of 4.2 g/dL (3.5–5.7), and a phosphorus of 5.7 mg/dL (2.5–4.5). Patient had a DEXA scan which showed severe osteoporosis in the lumbar spine, left hip, and right forearm. Patient had increased PTH levels despite being on Cinacalcet. She had a nuclear medicine parathyroid scan with SPECT CT which showed increased uptake along the right inferior thyroid concerning for a large right lower parathyroid adenoma or functional thyroid nodule. FNA of the nodule was done and showed colloid nodule but PTH wash showed elevated PTH at 7634 pg/mL. She was referred for right lower parathyroidectomy and Cinacalcet was discontinued prior to surgery. She had right and left inferior parathyroidectomy and 4 gland exploration. Pathology showed the right inferior parathyroid gland to be markedly hyper-cellular, weighing 36 grams consistent with hyperplasia and the left inferior parathyroid gland to be slightly hyper-cellular parathyroid gland consistent with hyperplasia. No evidence of malignancy was noted on pathology. Prior to surgery her calcium level of 10.6 mg/dL which went down to 9.6 mg/dL post-operatively. Patient then developed severe hypocalcemia and hungry bone syndrome following the surgery requiring a calcium drip for 3 days post-operatively. Was changed to oral calcium but required large amounts of calcium gluconate and calcitriol supplementation and an extended hospital stay of 13 days. However, throughout the hospital stay, PTH levels continued trending back up to 239 which may represent either increased activity from remaining parathyroid glands or residual parathyroid adenoma with incomplete resection. Post-operative US neck showed Post-surgical collection in the lower pole of the right gland measuring 4.8 cm compatible with recent resection.

In conclusion, tertiary hyperparathyroidism can develop due to one enlarged parathyroid gland or an adenoma, which can be resistant to cinacalcet.
MON-465 Novel Thyroid Hormone β Mutation L266s Causes Atrial Fibrillation & Cerebral Infarction
Authors: Ono Wataru , Kameda Hiraku , Iesaka Hiroshi , Izumihara Satomi , Oe Yuki , Kamigaki Risa , Chiba Koki , Kameda Rena , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , hayashi Yoshitaka , Hideaki Miyoshi , Atsumi Tatsuya
Published: May 2020

Background: Resistance against thyroid hormone β (RTHβ) is characterized by reduced tissue sensitivity to thyroid hormone. Patients with RTHβ resistance typically demonstrate increases in FT3 and FT4 accompanied by inappropriately elevated TSH. Mutations in the TRβ gene are the most common genetic disorder in thyroid hormone resistance and result in impaired thyroid receptor functions due to a dominant negative effect. Here, we describe a case with a novel TRβ mutation, presenting atrial fibrillation and cerebral infarction.

Clinical case: A 55-year-old man presented chronic atrial fibrillation and tachycardia as the onset of cerebral infarction. Because blood tests revealed 5.6 pg/ml FT3 (reference range: 2.36–4.06), 3.39 ng/ml FT4 (0.71–1.5), 0.98 TSH μIU/ml (0.541–4.261), and negative TRAb, suggesting inappropriate secretion of TSH (SITSH). He was referred to our department for further investigation. All three test kits, including LUMIPULSE, ECLusys, and TOSOH, showed an unsuppressed TSH value despite hyperthyroxinemia, demonstrating genuine SITSH. His family history was unclear, but his father had died of heart disease. A pituitary MRI suggested microadenoma, but TSH-secreting pituitary adenoma was excluded because of a negative α subunit and responsiveness to a TRH stimulation test. The TRβ gene was analyzed with informed consent from the patient, and a novel mutation replacing the 266th amino acid serine (TCG) with leucine (TTG) in the 8th exon was found, confirming the diagnosis of RTHβ. Tachycardia and atrial fibrillation were considered to be caused by thyrotoxicosis in heart, which dominantly expresses TRα rather than TRβ. Therefore, β-blockers and anticoagulants, were continued.

Conclusion: This is the first report of a case of RTHβ with the TRβ L266S mutation. This novel mutation is located in the thyroid hormone-binding area of the TRβ gene, suggesting that reduced hormone binding may cause thyroid hormone resistance.
SAT-674 Anti PD1 Induced Type 1 Diabetes
Authors: Naranjo Maria Belen , Rosenthal David S , Kumar Salini Chellappan , Shariff Amal
Published: May 2020

Introduction: Pembrolizumab t is used to treat various cancers. It is associated with immune related adverse events (IRAEs) that can be life threatening [1,4]. We describe a patient who presented autoimmune Diabetes after the use of Pembrolizumab. Case: 64 y/o African American female PMHX of lung non-small cell lung cancer diagnosed in 2017 Clinical stage IV with gluteal metastasis, and dementia. Pt was referred by Oncology. The patient had a family history of Type 1 DM. and complained of dizziness, and unintentional weight loss (30 pounds) over a year. She had received 2 cycles of Pembrolizumab. The last cycle given 5 weeks before presentation to Endocrinology.Physical examination revealed cachectic female (weight 35 kg, height 147cm), dry mouth, BP 135/82, Plasma glucose 383mg%, A1c 7, negative Islet cell antibodies, positive anti-GAD, undetectableserum C-peptide. Cortisol 27, Acth 21 at 8 am and TSH 2.3. Discussion: In a systematic literature review, the early pattern of Diabetes onset with the use of checkpoint inhibitors was evaluated and on average after 4.5 treatment cycles [4].The incidence of immune checkpoint inhibitor-induced Type 1 Diabetes is estimated at 1% [3].This appeared to be earlier for the combination of anti-cytotoxic T-Lymphocyte associated antigen 4 monoclonal antibody and PD-1 therapy. The onset of β cell inflammation is often fulminant, suggested by the relatively low glycated hemoglobin levels, while C-peptide levels are usually low or undetectable at diagnosis and mostly positive GAD antibodies [5]. This side effect is predominantly found in patients exposed to blockade of the PD-1/PD-Ligand pathway. The IRAEs are primarily managed by immunosuppression with corticosteroids and discontinuation of immunotherapy except in autoimmune Diabetes which is irreversible. Physicians should be aware of and patients educated about the important multiorgan side effects since a growing number of patients are treated with checkpoint blockade.Azoury SC, Straughan DM, Shukla V. Immune checkpoint inhibitors for cancer therapy: clinical efficacy and safety. Curr Cancer Drug Targets 2015;15: 452-462Weber JS, Postow M, Lao CD, et al. Management of adverse events following treatment with anti-programmed death-1 agents. Oncologist 2016;21:1230-40Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H,Weiss SA et al Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes 2018;67(8):1471-1480de Filette JMK, Pen JJ, Decoster L, et al. Immune checkpoint inhibitors and Type 1 Diabetes mellitus: a case report and systematic review. Eur J Endocrinol. 2019;181(3):363–374.Akturk HK, Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced Type 1 Diabetes: a systematic review and meta-analysis. Diabet Med. 2019;36(9):1075–1081.