bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI297 Hemoglobin Decline As A Signal For Hyperprolactinemia Onset Prior To Prolactinoma Diagnosis In Hypogonadal Men
Authors: Rudman Yaron , Duskin-Bitan Hadar , Richter Ilan , Tsvetov Gloria , Masri-Iraqi Hiba , Akirov Amit , Shimon Ilan
Published: October 2023

Disclosure: Y. Rudman: None. H. Duskin-Bitan: None. I. Richter: None. G. Tsvetov: None. H. Masri-Iraqi: None. A. Akirov: None. I. Shimon: None.

Background: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and non-specific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. Methods: We retrospectively evaluated the pre-diagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. Results: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dl at diagnosis. We identified 25 patients with “informative” HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/ml; median follow-up, 14.0 years), demonstrating an obvious pre-diagnosis HB decrease (greater than 1.0 g/dl), from a pre-diagnosis baseline HB of 14.4±0.3 g/dl to 12.9±0.5 g/dl at diagnosis. The median “low-HB duration” (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between “low-HB duration” and patient-reported sexual dysfunction duration (n=17, R=0.502, p=0.04). The “low-HB duration” was significantly longer than the reported sexual dysfunction duration (7.0±4.5 vs 2.9±2.5 years, p=0.01). Conclusions: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.

Presentation: Friday, June 16, 2023
FRI300 Prolactinoma And Pregnancy: A Systematic Review And Meta-analysis
Authors: Bandeira Diego Barata , Alves Letícia Santana , Glezer Andrea , Boguszewski Cesar Luiz , Nunes-Nogueira Vania Santos
Published: October 2023

Disclosure: D.B. Bandeira: None. L.S. Alves: None. A. Glezer: None. C.L. Boguszewski: None. V.S. Nunes-Nogueira: None.

Introduction: Prolactinomas are the most common pituitary tumors, being an important cause of irregular menses and infertility. However, fertility can be restored, making pregnancy possible, especially for women who have achieved disease control, mainly on dopamine agonist (DA) treatment. Although literature data demonstrate safety in maternal and fetal outcomes, the evidence has not been systematically synthesized. Purpose: To perform a systematic review evaluating disease control and fetal and maternal outcomes in pregnancy of women with prolactinoma. Methods: We conducted a systematic review according to the Joanna Briggs Institute methodology for systematic reviews of etiology and risk. We included observational studies that evaluated pregnant women with prolactinoma. The outcomes of interest were spontaneous miscarriage, preterm birth, worsening of preexisting diabetes/development of gestational diabetes, tumor growth during pregnancy, headache, visual impairment, perinatal mortality, low birth weight, congenital malformations. Embase, Medline, LILACS, and CENTRAL were our source databases. To perform proportional meta-analyses, we used Stata Statistical Software 17. Results: Fifty-one studies were included encompassing a total of 2513 pregnancies in 1903 women with prolactinoma. The overall frequency of the pregnant women on DA at conception was 97% (from 49 studies of 2493 pregnancies; 95% confidence interval (CI), 93–99%); there were 9% of spontaneous miscarriage (from 38 studies of 2073 pregnancies; 95% CI, 7–12%), 3% of prematurity (from 38 studies of 1584 pregnancies; 95% CI, 3–2%), 9% of symptomatic tumor growth during pregnancy (from 38 studies of 1584 pregnancies; 95% CI, 5–15%), 4% of visual impairment (from 33 studies of 1480 pregnancies; 95% CI, 2–7%), 6% of headache (from 31 studies of 1385 pregnancies; 95% CI, 3–11%) and 4% of worsening of preexisting diabetes/development of gestational diabetes (from 9 studies of 666 pregnancies; 95% CI, 3–7%). The overall frequency of congenital malformations was 2% (from 23 studies of 1212 newborns; 95% CI, 1–4%), 2% of perinatal mortality (from 18 studies of 1123 newborns; 95% CI, 1–3%) and 6% of low birth weight (from 17 studies of 843 newborns; 95% CI, 3–9%). Conclusion: Pregnancy in women with prolactinoma is frequently safe in relation to fetal and maternal outcomes, presenting low frequency of spontaneous miscarriage, prematurity, tumor growth, visual impairment, headache, congenital malformations, perinatal mortality and of low birth weight.

Presentation: Friday, June 16, 2023
FRI319 Diagnostic And Management Challenges In A Patient With A Giant Pituitary Lactosomatotroph Adenoma
Authors: Peixe Carolina Ribeiro , López-Presa Dolores , Bugalho Maria João , Marques Pedro
Published: October 2023

Disclosure: C.R. Peixe: None. D. López-Presa: None. M. Bugalho: None. P. Marques: None.

Introduction: Giant prolactinomas are rare, accounting for only 2–3% of all prolactinomas. Although benign, several challenges may emerge at diagnosis and during their management. Case: A 38-yr man was incidentally diagnosed with a large skull base tumor on CT-scan undertaken due to head trauma. MRI showed a 55x33mm skull base mass, involving the clivus and sellar/parasellar regions, with bilateral cavernous sinus invasion. A chordoma was suspected leading to a transnasal biopsy, which revealed a PIT1+-plurihormonal pituitary adenoma. His serum prolactin levels were then assessed, which were markedly elevated at 50,414ng/mL (NR:4-15), with concomitant raised IGF-1 at 323ng/mL (NR:101-221). He was then referred to our Endocrine department. Retrospectively, there was a 3-yr history of erectile dysfunction, decreased libido, and infertility, although his testosterone levels were within reference range (307ng/dL; NR:240-830), and sperm analysis parameters were normal. He commenced on low dose cabergoline (0.5mg/week) and two months later clinical improvement was noted, accompanied by a marked reduction of prolactin (830ng/mL) and tumor shrinkage. He remains on cabergoline for ten months, and his latest prolactin and IGF-1 levels were, respectively, 496 and 224ng/mL. In the light of patient’s normal spermogram and restored sexual function, the couple has been referred to the Fertility clinic. Conclusions: The differential diagnosis of large skull base tumors, particularly those affecting sellar/clival regions, must always include prolactinoma, hence serum prolactin should be measured keeping in mind the possible occurrence of hook effect. Most giant prolactinomas respond to dopamine agonists, which should be considered as a first-line therapy, with marked reductions in both prolactin and tumor size often seen within the first weeks of treatment. GH-cosecretion may also ameliorate/normalize with dopamine agonists. In prolactinoma patients, infertility may or may not be directly related with hyperprolactinemia, hence a careful assessment is required, and its management may imply assisted reproductive techniques.

Presentation: Friday, June 16, 2023
FRI332 Check Point Inhibitor Induced Hypophysitis/Hypopituitarism
Authors: Chandpuri Ranjit Singh
Published: October 2023

Disclosure: R.S. Chandpuri: None.

Introduction: A case of Renal cell cancer with metastasis to contralateral kidney, which was treated with nivolumab/ Ipilimumab leading to hypophysitis/hypopituitarism. Case: 42-year-old female with past medical history of Left renal mass who underwent left radical nephrectomy. On surveillance imaging she was found to have evidence of new paraspinal mass suspicious for metastatic spread involving retroperitoneal lymph nodes and contralateral kidney. She would be referred to her oncologist for observation versus chemotherapy. Her oncologist ordered nivolumab and ipilimumab. Patient tolerated chemotherapy well. A surveillance brain MRI was ordered to check for any metastatic involvement and it showed enlargement of the pituitary gland with focal hypo-enhancing area concerning for immune check point inhibitor therapy induced hypophysitis. Labs showed- cortisol-0.8, ACTH <5, TSH-0.6, Free T4-0.60, Prolactin-57.9, FSH-3.7, LH-5.0. Clinically she would complain of fatigue, generalized weakness, hypotension and amenorrhea. The patient was reluctant to start thyroid hormone replacement therapy, and she appeared clinically euthyroid. A dedicated Pituitary MRI showed partially empty sella turcica, sella measuring approximately 0.2 cm in maximal height. There was no abnormal thickening or nodular enhancement of the pituitary stalk. No suprasellar mass effect or chiasmatic compression. She was placed on Prednisone/ Hydrocortisone with improvement in her fatigue and blood pressure. Conclusion: Immune checkpoint inhibitors are a new form of immunotherapy used in the treatment of various cancers (melanoma, RCC, colorectal). These agents can cause immune-mediated pituitary lesions (hypopituitarism/hypothyroidism). These drugs can cause a spectrum of issues ranging from single hormone deficiency to pan-hypopituitarism. Due to the new advances in chemo/immune therapy, providers need to be aware of such conditions to quickly recognize and treat them. Symptoms of this condition can be masked and can be attributed to other diseases processes ie(depression, anxiety, chronic fatigue syndrome). It would be best to come up with a screening process/order set for such patients with close communication between primary care, endocrinologists, oncologists in order to identify and treat the patients.

Presentation: Friday, June 16, 2023
FRI337 Progressive Suprasellar Chordoid Glioma Presenting With Panhypopituitarism, Diabetes Insipidus And Encephalopathy
Authors: Gatillo Jan Louie D , Maningat-Goco Maria Patricia Deanna D , Co Faith Abigail K
Published: October 2023

Disclosure: J.D. Gatillo: None. M.D. Maningat-Goco: None. F.K. Co: None.

Chordoid glioma is a rare central nervous system neoplasm of uncertain origin, with most cases seen at anterior wall or roof of the third ventricle. It is described as a perplexing lesion as it tends to mimic benign lesions at the onset but eventually some develop with threatening complications. We present a case of a 39 year old Filipino, female, who initially presented with a 1- year history of memory lapses, behavioral changes, and blurring of vision. MRI showed 4.3 x 3 x 4.2 cm heterogeneously enhancing suprasellar mass and was initially worked-up as pituitary macroadenoma. The imaging also showed heterogeneously enhancing extra-axial lesion along the right anteromedial temporal convexity. She underwent pterional craniotomy and sub temporal craniectomy with excision biopsy of tumor. Histopathology confirmed the diagnosis of chordoid glioma WHO Grade 2. However, only a few days after the surgery, she began to experience emotional lability and more behavioral changes. She then received oral Temozolomide for 4 cycles and whole brain radiotherapy for 32 cycles. Approximately 10 months since diagnosis was made, patient eventually developed seizures and manifested progressive drowsiness and generalized weakness. Patient was diagnosed and clinically presented with Panhypopituitarism and Diabetes Insipidus. She was maintained on levothyroxine, prednisone and desmopressin. A repeat MRI was done which showed apparent progression in the size (4.6 x 3.7 x 4.1 cm) of the heterogeneously enhancing suprasellar mass with signs of tumor infiltration and extension in the left lateral ventricle. Further, patient was treated with Bevacizumab and Nimotuzumab. Repeat MRI showed regression in size of the known suprasellar mass and improvement of symptoms. Little is still known about chordoid gliomas especially in the Asian population - their initial presentation as well as the best diagnostic approach and treatment strategy for this elusive disease. There is no formally recognized treatment protocol for chordoid glioma, and postoperative mortality and morbidity is high. More case reports are needed in order to ascertain the best diagnostic and treatment strategy for patients with chordoid glioma and its endocrine complications.

Presentation: Friday, June 16, 2023
FRI342 Hypophysitis Mimicking As Pituitary Adenoma
Authors: Chao Alex , Dhaliwal Athena , Yu Kaylee , Polis Sarah Najwa , Vernetti Nicholas John , Nakhle Samer
Published: October 2023

Disclosure: A. Chao: None. A. Dhaliwal: None. K. Yu, MD: None. S.N. Polis: None. N.J. Vernetti: None. S. Nakhle: None.

Background: Hypophysitis is defined as inflammation of the pituitary gland and causes include lymphocytic, granulomatous, xanthomatous, and IgG4 related hypophysitis. Hypophysitis can sometimes mimic a pituitary mass. It is more common in the female and associated with pregnancy. Lymphocytic hypophysitis may present with symptoms related to expansion of the pituitary gland and hormone deficiency. Expansion of the gland often causes headaches. Compression of the optic chiasm results in a decrease in the visual field, color perception, and in rare cases, diplopia due to lateral expansion of the pituitary gland.It also affects hypothalamic-pituitary axis and commonly impairs hormone production from corticotrophs, gonadotrophs and thyrotrophs. Patients treated with glucocorticoids can have hormonal recovery and resolutions of imaging findings. Clinical Case: Patient is a 30-year-old, previously healthy, female who initially presented to the emergency department with a worsening headache over the preceding three months. Brain MRI demonstrated a 1.8 cm enhancing mass and the radiologist interpreted the findings as a pituitary macroadenoma. The patient was seen by neurosurgery and was started on high doses of dexamethasone at 4 mg twice a day for three months duration.

After treatment, the patient’s headache improved although she reported an 80-pound weight gain. CT of the head three months later reported a prominent pituitary gland in size compatible with history of pituitary adenoma but decreased in size to 0.9 cm. Repeated brain MRI six months after treatment showed resolution of the mass. The patient also noted a cessation of her menstrual cycle around the onset of headache and laboratory evaluation consistent with hypogonadotropic hypogonadism (FSH 5.5 mIU/mL, LH 2.8 mIU/mL and estradiol 22 pg/mL). Regular menstrual cycles returned seven months after glucocorticoid treatment. Almost two years after the onset of her headaches, the patient was referred to the endocrine clinic for further evaluation of fatigue, low libido, and persistent weight gain. Repeat anterior pituitary function tests were unremarkable and showed FSH 5.6 mIU/mL, LH 3.3 mIU/mL, Estradiol 34 pg/mL, Sodium 139 mmol/L, IGF-1 129 ng/mL (-0.4 standard deviation), Ferritin 20 ng/mL, Prolactin 15.6 ng/mL, TSH 4.38 mIU/L, T4 free 1.1 ng/dL, Cortisol AM 10.9 mcg/dL, and Testosterone 13 ng/dL. Conclusion: We present a case of hypophysitis mistaken for a non-functioning macroadenoma with mild mass effect on the undersurface of the optic chiasm, headache and hypogonadotropic hypogonadism. The patient did not have risk factors such as pregnancy or other autoimmune conditions. After glucocorticoid treatment, recovery of hypogonadotropic hypogonadism and resolution of headache, and radiographic findings.

Presentation: Friday, June 16, 2023
FRI346 Can We Miss Panhypopituitarism After Transsphenoidal Surgery?
Authors: Makawi Alladdin , Huynh James , Elshimy Ghada
Published: October 2023

Disclosure: A. Makawi: None. J. Huynh: None. G. Elshimy: None.

Introduction: Disorders of water and osmolality due to aberrant ADH secretion and posterior pituitary function are common causes of morbidity among patients who undergo transsphenoidal hypophysectomy surgery (TSS). Postoperatively, central diabetes insipidus (DI) may present as a complication in up to 30% of cases. Moreover, hypopituitarism is an important complication of TSS, and can manifest as adrenal crises if missed by clinicians. We present a patient who underwent TSS for pituitary adenoma with postoperative course complicated by hypogonadism that was misdiagnosed for 10 years. Additionally he developed DI, secondary adrenal insufficiency (AI), and central hypothyroidism after resolution of his central hypogonadism. Case Description: 64-year-old male with medical history significant for chronic hypogonadism on hormonal replacement therapy and diabetes, presented for sleep disturbance and deviated septum with incidental finding of a large sphenoidal mass on CT imaging. MRI of brain confirmed a 4 cm macroadenoma invading from the inferior sella into the bilateral cavernous sinuses, clivus, and sphenoid sinus. Patient was then referred to neurosurgery for transsphenoidal resection. Patient underwent surgery and perioperative course complicated by a small CSF leak. He stayed in the neuro-ICU after the surgery and was monitored by the surgical team without endocrine consultation. He was discharged without proper postoperative evaluation of the HPA axis or education on symptoms of pan-hypopituitarism. Shortly after, he experienced significant symptoms consistent with adrenal insufficiency which prompted a visit to the emergency room. Thereafter, he finally presented to the neuroendocrine clinic for follow-up. Labs were notable for cortisol 1.2 mcg/dl, TSH 0.018 mcIU/ml, FT4 0.2ng/dl, and Na 130 mEq/ml, normal testosterone 551 ng/dl, mildly persistently elevated Na 147 mEq/ml with positive water deprivation test confirming central DI. He was treated with hydrocortisone and Synthroid for adrenal insufficiency and hypothyroidism respectively and was started on desmopressin for central DI. Discussion: Pan-hypopituitarism frequently occur after neurosurgical interventions and failure to involve endocrinology in the management of these cases may lead to missed diagnoses, unnecessary morbidity and mortality. This report serves as an excellent illustration of the importance of both surgical and medical management to prevent life-threatening complication such as adrenal crises as a result from pan-hypopituitarism.

Presentation: Friday, June 16, 2023
FRI365 A Patient With A Bronchial Carcinoid Presents With Cushingoid Symptoms Due To A Potentially Dangerous Supplement
Authors: Morales Tomas , Samarasinghe Shanika
Published: October 2023

Disclosure: T. Morales: None. S. Samarasinghe: None.

Introduction: Well-differentiated bronchial neuroendocrine neoplasms often follow a clinically indolent course and rarely cause Ectopic ACTH syndrome. Iatrogenic corticosteroid use is the most common cause of Cushing syndrome and should be considered in all patients regardless of clinical background. Clinical Case: A 59-year-old woman with an 11-year history of a 1.5 cm well differentiated bronchial carcinoid, presented with Cushingoid features. Hormonal activation of her known bronchial carcinoid was considered. Testing resulted in a normal 24-hour urine 5-HIAA (6 mg/d, n<15 mg/dL), elevated chromogranin A (201 ng/mL, n<103 ng/mL), normal histamine (<1.5 ng/mL, n <1.7 ng/mL), low-normal 7 AM serum cortisol (5.1 ug/dL, n 3.6-19.3 ug/dL), normal 7 AM ACTH (17 pg/mL, n<46 pg/mL) and a surprisingly low 24-hr urinary free cortisol (1.8 mcg/hr, n 4.0-50.0 mcg/hr). A late night saliva cortisol was 0.03 mcg/dL (n 3.4-16.8 mcg/dL). Echocardiography showed no evidence of carcinoid heart disease. A Dotatate PET-CT scan to assess for neuroendocrine tumor progression showed a stable right upper lobe pulmonary nodule with no evidence of metastatic disease. Ectopic Cushing syndrome was excluded given the low cortisol levels, and exogenous steroids were suspected, however the patient denied the use of oral, inhaled, or injected steroids. A cosyntropin stimulation test yielded a pre-stimulation cortisol of 6.2 ug/dL with an adequate post-stimulation cortisol of 23.5 ug/dL (n <46 pg/mL). At this stage of evaluation, the patient received an FDA alert regarding a glucosamine supplement she had started 4 months prior for joint pain. The notification advised of hidden drug ingredients including dexamethasone, diclofenac, and methocarbamol contained within Artri King glucosamine supplements not listed on the product label, but verified by FDA lab analysis. The FDA had received several adverse event reports including liver toxicity and death associated with such products. The patient’s symptoms gradually improved after discontinuation of the supplement. Conclusion: Ectopic ACTH production is reported in less than 5% of patients with squamous cell lung cancer and 3% of patients with lung or pancreatic (non-MEN1) neuroendocrine tumors. Factitious corticoid exposure is rare and can be evaluated with synthetic corticosteroid serum testing. Cushing syndrome due to supplements containing unreported corticosteroid doses should be considered in patients with typical Cushingoid features and contradictory hormonal testing.

References: Hayes, AR, Grossman, AB. Distinguishing Cushing's disease from the ectopic ACTH syndrome: Needles in a haystack or hiding in plain sight? J Neuroendocrinol. 2022; 34 (8):e13137; www.fda.gov/drugs/medication-health-fraud/public-notification-artri-king-contains-hidden-drug-ingredients

Presentation: Friday, June 16, 2023
FRI367 An Unusual Presentation Of A Thyroid Nodule: A Thyroid Paraganglioma
Authors: Owrangi Mohammad-Ehsan , Hasan Farhad
Published: October 2023

Disclosure: M. Owrangi: None. F. Hasan: None.

Introduction: Thyroid paraganglioma (PGL) is a rare thyroid tumor that originates from inferior laryngeal paraganglia. We present a case of a patient initially believed to have a thyroid nodule which turned out to be a PGL. Case Presentation: A 49 year-old white female with history of GERD and mild dysphagia who was found to have a left parathyroid adenoma vs. a left exophytic thyroid nodule. Previous ultrasounds had all showed slow but progressive enlargement of the lesion. Her labs had showed iPTH, Ca, TSH, and free T4 all within reference range and she was clinically euthyroid. She had 2 fine needle aspirations (FNA) which were both non diagnostic. She ultimately underwent surgical excision of the mass. The pathological examination showed cells that were positive for synaptophysin, chromogranin, GATA-3, S100, and neuron-specific enolase. They were negative for Ki-67, PTH, thyroglobulin, TTF-1, CK AE1/AE3, and CD 138. The overall findings were consistent with thyroid PGL. Discussion: In this case Thyroid PGL was diagnosed after pathological examination, including immunohistochemistry, was performed on a surgically excised sample, after 2 FNAs were non-diagnostic. Thyroid PGLs are elusive tumors. One study suggested that since they were first described in 1964, until 2015, there have only been 54 reported cases of thyroid PGLs, with a strong female predominance (88.9%). They often present as asymptomatic thyroid nodules and their diagnosis can be difficult by FNA alone as they can morphologically mimic medullary thyroid carcinoma, intrathyroidal parathyroid proliferation, metastatic neuroendocrine tumor, or calcitonin-negative neuroendocrine tumor of the thyroid gland (CNNETT). Thyroid PGLs are often benign, slow growing tumors and account for only 0.012% of all head and neck tumors with a malignancy rate of 4-16%. They usually present as single nodules averaging 3.5 cm and are often diagnosed with routine ultrasound assessment of the neck. Since they are associated with the parasympathetic nervous system, signs and symptoms including tachycardia, palpitations, and weight loss due to hormonal activity are classically absent from thyroid PGLs. In about 30% of cases, thyroid PGLs have a genetic predisposition and are more than one and associate with other tumors such as pheochromocytoma. Major hereditary disorders associated with paraganglioma include von Hippel-Lindau disease, multiple endocrine neoplasia, familial paraganglioma syndromes 1 to 4, and neurofibromatosis. Therefore, it is highly recommended that patients with a diagnosis of thyroid PGL undergo additional investigations with imaging, hormonal activity assessment, and genetic testing. Given the difference in management of thyroid PGLs compared to its cytology mimics, and their association with some familial cancer syndromes, use of immunohistochemical staining is crucial in making the correct diagnosis.

Presentation: Friday, June 16, 2023
FRI369 SDHB Hereditary Pheochromocytoma Paraganglioma Syndrome With Biochemically Silent Pheochromocytoma
Authors: Skariah Annie M , Zacharia Christine C
Published: October 2023

Disclosure: A.M. Skariah: None. C.C. Zacharia: None.

Background: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal autonomic paraganglia. Majority of cases are sporadic but 30-50% are associated with genetic mutations. Patients with SDHB mutations can present with pheochromocytoma, paragangliomas or both. Lesions are usually extra-adrenal and typically secrete norepinephrine and occasionally dopamine. These cases are often associated with higher malignancy rates (up to 79%) compared to other SDH-x associated mutation cases. Clinical Case: Our patient is a 64-year-old female with history of secondary adrenal insufficiency, hypothyroidism, osteoporosis, GAD who presented in 2005 with left occipital headache and dysphagia. Workup was notable for a glomus tumor. She underwent tumor embolization, resection, radical neck dissection and radiation therapy. Genetic testing was not performed at the time of diagnosis. Routine biochemical surveillance was done postoperatively. In 2018, the patient was found to have a mild elevation of normetanephrine 248 pg/ml (<148 pg/ml) and total metanephrine 297 pg/ml (<205 pg/ml) levels. Subsequent plasma, urinary metanephrine/catecholamine studies were negative. In 2021, her brother was diagnosed with pheochromocytoma. Genetic testing was then pursued in the patient, and she was found to have a pathogenic mutation c.724C>A (p.R242S) in the SDHB gene. In June 2022, CT chest, abdomen and pelvis with contrast was ordered, and she was found to have a homogeneously enhancing 1.3 x 1.1x 1.4 cm left adrenal nodule with indeterminate imaging characteristics. Following this CT, DOTATATE PET CT scan was done and demonstrated somatostatin avidity in the region of previously resected left glomus jugular tumor, right adrenal gland nodule and left inferior pubic ramus sclerotic lesion. Repeat biochemical testing remained negative for catecholamine excess. Despite being asymptomatic, there was concern for a biochemically silent pheochromocytoma. Alpha blockade was completed prior to right adrenalectomy in November 2022 and surgical pathology confirmed pheochromocytoma. The patient remains clinically stable, and she is now undergoing radiation therapy of her left pubic ramus lesion. Conclusion: It is important to have genetic evaluation early in the workup for a newly diagnosed PPGL. Additionally, suspicion for biochemically silent pheochromocytoma should be present even in the setting of negative biochemical workup and positive SDHB mutation.

Presentation: Friday, June 16, 2023
SAT187 A Case Of CDC73 Mutation Related Primary Hyperparathyroidism With Ectopic Parathyroid Hyperplasia
Authors: Wu Tao , Dhir Nikita , Bollineni Mohini
Published: October 2023

Disclosure: T. Wu: None. N. Dhir: None. M. Bollineni: None.

Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia, and most cases are sporadic. However, in 5-10% cases, it may occur as a syndromic and hereditary disease, like Multiple endocrine neoplasia type 1, type 2A, type 4, or CDC73 mutation related hereditary benign or malignant hyperparathyroidism. In patients with severe or early onset primary hyperparathyroidism, screening for genetic etiology should be considered. Case Presentation: A 35-year-old woman with a medical history of hypertension, kidney stones, and post-operative hypothyroidism presented to the endocrinology clinic due to recurrent hyperparathyroidism. She initially had a parathyroidectomy in 2008 and her calcium corrected at that time. She was again diagnosed with hypercalcemia due to primary hyperparathyroidism in 2021. She underwent re-exploration and had a right thyroid lobectomy with removal of three parathyroid glands. Her PTH was still 309 pg/mL (9-77 pg/mL) and calcium was 11.2 mg/dL (8.6-10.5 mg/dL), and she was started on Cinacalcet. The patient continued to have elevated calcium, bone pain, fatigue, and constipation. A 4D CT scan was ordered, which localized activity to a 1.5 cm arterial enhancing nodule in the anterior mediastinum, with intrathymic location. She underwent right video-assisted thoracoscopic total thymectomy with en bloc and the nodule was found to be ectopic parathyroid tissue. Post-operatively, her calcium normalized to 8.6 mg/dL and PTH was undetectable. She underwent genetic testing due to her recurrent hyperparathyroidism, which showed a CDC73 mutation. She is currently on calcitriol and calcium supplements, and serum calcium has been maintained in the low-normal range. Discussion: The CDC73 gene encodes a protein called parafibromin, which acts as a tumor suppressor, prohibiting cells from proliferating. Mutations in this gene are linked to jaw-tumor syndrome, familial isolated primary hyperparathyroidism (FIHP), and parathyroid carcinoma. These three CDC73-related disorders are clinically overlapping and inherited in an autosomal dominant manner. Biallelic mutations of the CDC73 gene are associated with a high risk of parathyroid cancer since the parafibromin protein is usually absent in parathyroid carcinoma and occasionally in atypical adenomas. FIHP tends to have a more severe clinical presentation with earlier onset (younger than 45 years). Additionally, patients with CDC73 related disorders are more prone to developing ossifying fibroma(s) of the jaw, uterine tumors, and various renal lesions. In summary, this case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed second surgery. Genetic testing is vital for early detection, surveillance, and familial genetic counseling in patients with CDC73 related disorders.

Presentation: Saturday, June 17, 2023
SAT607 Targeted Modulation Of Kisspeptin Neurons Improves Hyperandrogenism And Hyperactive LH Secretion In A Pre-clinical PCOS-like Mouse Model: Implications For Novel Therapeutics In PCOS Women
Authors: Coutinho Eulalia , Esparza Lourdes A , Kauffman Alexander S
Published: October 2023

Disclosure: E. Coutinho: Employee; Self; Crinetics. L.A. Esparza: None. A.S. Kauffman: Consulting Fee; Self; Crinetics.

Polycystic ovary syndrome (PCOS), a common reproductive disorder in women, is characterized by hyperandrogenemia, chronic anovulation, and/or cystic ovarian follicles. Another common hallmark of PCOS is LH hyper-pulsatility, believed to be driven by hyperactive GnRH neurons, but the reason for the increased GnRH secretion still remains unclear. We previously developed a PCOS-like mouse model using chronic letrozole (LET; aromatase inhibitor) and reported that LET females demonstrated multiple PCOS-like phenotypes, including polycystic ovaries, anovulation, hyperandrogenemia, enlarged ovaries, and hyperactive LH pulse secretion. Given the proposed role of hypothalamic arcuate kisspeptin neurons as the GnRH pulse generator, we determined that LET females have markedly elevated Kiss1 and Tac2 expression and increased Kiss1 neuronal activation in the arcuate nucleus, correlating with their hyper-pulsatile LH secretion. Thus, in the LET PCOS-like condition, and perhaps in PCOS women, increased hypothalamic kisspeptin and NKB neuron activity may be fundamental contributors to the hyperactive LH secretion and downstream hyperandrogenemia. We next tested this possibility using chemogenetics in transgenic PCOS-like mice to acutely and chronically suppress kisspeptin neuron activity. Acute inhibition of kisspeptin neurons successfully lowered abnormally high, rapid in vivo LH pulse secretion in PCOS-like females. Likewise, chronic in vivo suppression of endogenous kisspeptin neuron activity for several weeks dramatically lowered both circulating LH and T levels, and reduced ovarian weights, in females previously displaying a PCOS-like phenotype, with a trend towards improvement of overweight phenotype. These data support the hypothesis that overactive kisspeptin neurons may be one possible driver of neuroendocrine PCOS-like phenotypes. Importantly, these findings suggest that modulation of kisspeptin neurons may be a viable, novel therapeutic target to treat hyperandrogenism and hyperactive LH pulsatility in PCOS women. Indeed, although identical studies have not yet been done in humans, our findings complement recent clinical investigations using NKB receptor antagonists or dynorphin analogs to lower LH pulse secretion in PCOS women and other PCOS-like animal models.

Presentation: Saturday, June 17, 2023
SAT610 Multiple Endocrine Neoplasia Type 1 - The First Reported Case In An Indigenous Australian
Authors: Mignone Edward , Neal Kirsten
Published: October 2023

Disclosure: E. Mignone: None. K. Neal: None.

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare and under recognised syndrome. It has not been previously reported in Indigenous Australians for this reason. Clinical Case: A 48-year-old Indigenous Australian female was consulted on by an inpatient endocrine team in March 2020 for persistent hypercalcaemia on a background of a parathyroidectomy in 2011 for primary hyperparathyroidism (PHPTH). She was admitted to a remote Australian hospital for investigation and management of acute on chronic abdominal pain. Relevant medical history included a parathyroidectomy at age 40, multiple PE/DVT, MI, AF, CTEPH, right heart failure, HTLV-1 and recurrent abdominal pain presumed secondary to GORD. Gastroscopy from 2013 revealed chronic gastritis with hundreds of gastric polyps discovered on subsequent gastroscopy in 2015. The young age of PHPTH combined with her chronic gastritis and polyps prompted neuroendocrine tumour (NET) screening, including MEN1. At time of consult in 2020, laboratory studies were consistent with recurrence of PHPTH with a corrected calcium of 2.9 mmol/L (2.15-2.57mmol/L), serum PTH level 31.5 pmol/L (1-7pmol/L), vitamin D level 30 nmol/L, 24-hour urinary calcium variable between low and high. NET markers were markedly elevated with a gastrin level of 14042 ng/L (<100 ng/L), pancreatic polypeptide 2905 pmol/L (<55 pmol/L), urine 5HIAA ratio 8 mmol/L (<4 mmol/L), vasoactive intestinal peptide and glucagon levels normal. Pituitary studies, serum calcitonin, plasma metanephrines and PTH related protein levels were within normal limits. A CT of the abdomen showed thickened gastric folds, and persistent liver and IVC lesions from 2018. A diagnosis of Zollinger Ellison Syndrome (ZES) was made. Eventually, genetic testing was positive for a rare heterozygous variant of c.207dupC in exon 2 of MEN1 gene. A 68-gallium-DOTATATE PET/CT showed multiple avid pancreatic, gastric, nodal and liver lesions with high somatostatin receptor expression, suggestive of a neuroendocrine malignancy. Treatment was based largely on symptom control due to poor overall prognosis from underlying cardiorespiratory comorbidities. Abdominal pain from ZES was managed with a high dose PPI, H2 receptor antagonist and subcutaneous somatostatin analogue were trialled. Hypercalcaemia was treated with IV bisphosphonate therapy. Calcimimetic analogues were considered however patient declined. Genetic counselling was attempted however many cultural and logistical barriers were identified and family declined further testing. Unfortunately, our patient died in 2021 from presumed multifactorial respiratory failure. Conclusion: High index of suspicion is required to diagnose MEN1. This is particularly true within the Indigenous Australian population, with no prior documented cases reported.

Presentation: Saturday, June 17, 2023
SAT613 A Novel NF1 Mutation As The Underlying Cause Of Dysmorphic Features And Acromegaly In An Atypical Case Of Neurofibromatosis Type 1
Authors: Alsagheir Osamah , Alobaid Lulu Abdulaziz , Alswailem Meshael , Al-Hindi Hindi , Alzahrani Ali Saeed
Published: October 2023

Disclosure: O. Alsagheir: None. L.A. Alobaid: None. M. Alswailem: None. H. Al-Hindi: None. A.S. Alzahrani: None.

Introduction: Neurofibromatosis type 1 is an autosomal dominant disease with an estimated incidence of about 1:2000 cases. It is caused by genetic alterations in the gene NF1 encoding the tumor suppressor gene, neurofibromin. Patients with neurofibromatosis 1 are at an increased risk of a number of benign and malignant tumors including optic nerve gliomas, CNS tumors, malignant peripheral nerve sheath tumors, pheochromocytomas and many others. However, pituitary adenomas have been rarely described in neurofibromatosis type 1 and NF1 mutations have been found rarely in patients without manifestations of neurofibromatosis. In this report, we describe a patient with acromegaly who had some dysmorphic features but no clear skin or other manifestations of neurofibromatosis. He was found to have a deletion mutation in NF1 suggesting that his dysmorphic features and acromegaly are atypical manifestations of a previously undiagnosed neurofibromatosis type 1. Case Description: A 26-year-old-man presented at 18 years of age for evaluation of possible ventricular septal defect, which was ruled out by echocardiography, but he was found to have a subaortic membrane with moderate aortic regurgitation. He was also noticed to have coarse facial and body features which raised the possibility of acromegaly. He didn’t notice any facial changes, change in the size of hands and feet, headache or visual disturbances. In the family history, he reported that a number of his siblings are tall with large body habitus; none of them was evaluated or known to have medical illness. Physical examination: height 184 cm, weight 87 Kg, BMI 25, and BP 117/77 mmHg. He has frontal bossing, large supraorbital ridges, macrognathia, and hoarse deep voice but no skin tags, café au let spots, skin fibromas or freckling. Eye examination was unremarkable. Investigations: IGF-1 415 ng/ml (188-400), random GH 1.09 ng.ml (0.1-1.2). An oral glucose tolerance test showed baseline GH 0.99 increased to 8.05 ng/ml. An MRI of the pituitary gland showed a lobulated sellar and suprasellar heterogeneously enhancing pituitary adenoma. A Gallium 68 PET-CT scan showed an intense focus of uptake at the same location. Whole exome sequencing revealed a heterozygous NF1 mutation (NM_001128147.3: c.1782_*2del). This variant is likely pathogenic according to ACMG criteria. Conclusion: This case illustrates the value of whole exome sequencing for genetic testing in diagnosing atypical dysmorphia and other conditions when the diagnosis is not clear on clinical evaluation or conventional investigations. It also describes a rare association of acromegaly with neurofibromatosis.

Presentation: Saturday, June 17, 2023
THU133 Inpatient Hypoglycemia Management: Error Rates In Pediatric Diabetes Care
Authors: Odutayo Daniella A , Rizzi Elise M , Allen Natalie
Published: October 2023

Disclosure: D.A. Odutayo: None. E.M. Rizzi: None. N. Allen: None.

Hypoglycemia is a known side effect of exogenous insulin. During severe hypoglycemia, children with diabetes treated with insulin risk neurodevelopmental sequelae as protective glycolysis and ketogenesis are suppressed. Rapid treatment of hypoglycemia is crucial to prevent deleterious effects on neurocognition. There is a paucity of data elucidating inpatient hypoglycemia incidence and adherence to treatment standards in hospital care. The goal of this study is to assess the rate of hypoglycemia in children and adolescents with diabetes in the inpatient setting, and to assess adherence to American Diabetes Association (ADA) standards of care in treatment of hypoglycemia. Hypoglycemia is defined as blood glucose ≤ 70 mg/dL in children ≥5 years old, and ≤ 80 mg/dL in children<5 years old. ADA guidelines advise treatment with 15 grams of fast acting carbohydrates and glucose recheck in 15 minutes. The study includes a retrospective chart review with patients 18 years of age and under with a diagnosis of either Type 1 or Type 2 diabetes, with inpatient admission to a tertiary care pediatric hospital in a 2-year period beginning January 1, 2020. Point-of-care blood glucose (BG) results were analyzed, as well as appropriate documentation of events and treatment. Time to repeat BG (TTR) was also analyzed and used as a measure of rapid treatment and assurance of resolution; acceptable time to repeat BG is 15 +/-5 minutes. The number of hypoglycemic events was also analyzed. Emergency room visits and venous glucose estimations were excluded. There were 422 hypoglycemic events in children <5 years old, and 482 hypoglycemia events in children ≥5 years old. The median time to recheck was 41 min and 32.50 min with interquartile range of 12 to 65 min and 15 to 62.25 min respectively for children <5 years and children ≥5 years. 4.62% of all reported blood glucose checks showed hypoglycemia. The percentage of rechecks occurring after 20 min were 24% and 65% for children <5 years and children ≥5 years, respectively. Importantly, in the setting of severe hypoglycemia, defined as glucose <55 mg/dL, the median time to recheck was 21 min with interquartile range 7.75 to 34 minutes. Based on the results of the study, ADA guidelines were not met, with the average glucose recheck times being over 15 +/-5 minutes in both groups of children. In the setting of severe hypoglycemia, recheck times were closer to ADA guidelines. Additionally, there was a correlation between increased recheck times and increased rates of hypoglycemia. The next proposed steps are to develop and implement a hypoglycemia algorithm for pediatric diabetes patients during hospitalization.

Presentation: Thursday, June 15, 2023
THU141 Clinical Characteristics Of Korean Youth-onset Type 2 Diabetes Patients With Remission
Authors: Shin Sohyun , Kim Hwa Young , Kim Se Young , Kim Jaehyun
Published: October 2023

Disclosure: S. Shin: None. H. Kim: None. S. Kim: None. J. Kim: None.

Backgrounds: Improvement of beta cell function can occur in some patients with type 2 diabetes mellitus (T2DM). However, studies on remission of youth-onset T2DM with pharmacotherapy are sparse. We aimed to identify the clinical characteristics of pediatric patients experiencing remission. Methods: Medical records of pediatric patients with T2DM who were followed up for at least 1 year at Seoul National Bundang Hospital (2015-2022) were retrospectively reviewed. Remission of T2DM was defined as a return of HbA1c to <6.5% that persists for at least 3 months after discontinuation of glucose-lowering pharmacotherapy. Clinical characteristics between the remission and non-remission groups were compared at three time points (at diagnosis, 3 months after diagnosis, and remission). Results: Among 66 patients with T2DM (46 males, 69.7%), the mean age at diagnosis was 14.6±0.5 years, and the mean follow-up duration was 3.0±0.5 years. One (1.5%) patient underwent lifestyle modification only, 13 (19.7%) were treated with oral hypoglycemic agents only, and 52 (78.8%) were combined with insulin therapy at diagnosis. Twelve patients (18.2%) attained remission after a mean of 1.4±0.4 years from the time of diagnosis (at a mean age of 16.1±1.1 years). The remission group showed a higher proportion of males (100.0% vs. 63.0%, P = 0.012). At diagnosis of T2DM, urinary microalbumin-to-creatinine ratio (ACR) was lower in the remission group than in the non-remission group (2.0±1.6 mg/g vs. 11.2±2.9 mg/g, P = 0.010). There were no significant differences between the groups in the presence of initial diabetic ketoacidosis, HbA1c levels at diagnosis, and type of initial treatment. At the time of remission, HbA1c levels were significantly decreased (from 11.8% to 5.4%), while high-density lipoprotein cholesterol levels were increased (from 40.1 mg/dL to 45.7 mg/dL) than those at the time of diagnosis (both P <0.05). Recurrence occurred in three of 12 (25.0%) patients after a mean of 1.9±1.7 years from the time of remission. Conclusion: In Korean youth with T2DM, remission was observed in 18.2% after a mean of 1.4 years of intervention with lifestyle and pharmacotherapy. Youth with T2DM remission showed male predominance, and lower ACR at the time of diagnosis. Further studies about underlying pathophysiology and long-term outcomes after remission are warranted.

Presentation: Thursday, June 15, 2023
THU142 One-year Change In Bile Acids And Its Association With Changes In Metabolic Profile After Sleeve Gastrectomy In Youth
Authors: Tuli Shubhangi , Kaur Snimarjot , Bredella Miriam , Misra Madhusmita , Singhal Vibha
Published: October 2023

Disclosure: S. Tuli: None. S. Kaur: None. M. Bredella: None. M. Misra: None. V. Singhal: None.

Introduction: Bile acids (BAs) are hydroxylated steroid acids. Primary (10) BAs (cholic acid (CA) and chenodeoxycholic acid (CDCA) are synthesized by the liver. Secondary (20) BAs (deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) are formed from 10 BAs by the action of intestinal flora. Preclinical studies indicate a role of BAs in weight loss and metabolic improvements after metabolic and bariatric surgery (MBS). Data are inconsistent regarding changes in BAs after sleeve gastrectomy (SG), the most common MBS. Further, how BA changes contribute to metabolic improvements after SG is unclear. Objective: Evaluate changes in serum BAs 1 year after SG in youth with obesity and associations with changes in metabolic parameters. Methods: 16 adolescents (75% females) 13-22 years old with severe obesity were followed for one-year post-SG with assessments at baseline and during a mixed meal tolerance test (MMTT). We measured fasting BAs, glucose, insulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipids. Blood was drawn at 15, 30, 60, 90, and 120 minutes for glucose and insulin and at 0, 15, 60, and 120 minutes for BAs. Data are reported as changes over 15 minutes [t15–t0 of MMTT (Δ15)], area under the curve (AUC), and % change. Results: BMI decreased by 25.7% (p<0.0001). For 10 BAs: fasting CA levels decreased (33.3%, p=0.005), while Δ15 CA, CDCA and, total 10 BAs (113.3%, 188.9%, 152.9%, p<0.005), and AUC for CDCA and total 10 BAs (34.2%, p=0.004; 30.3%, p=0.015) increased one-year post-SG. For 20 BA: Δ15 DCA and total 20 BAs (212.5%, p≤0.011; 195.2%, p=0.004), and AUC DCA and total 20 BAs (95.0%, p=0.031; 59.4%, p=0.035) increased. Δ15 and AUC total BA also increased (100%, p=0.002; 1060.9%, p≤0.0001). Insulin resistance (HOMA-IR) (58.6%), low-density lipoprotein (LDL) (11.2%), triglyceride (14.6%), and ALT (26.9%) decreased (p<0.05), while high-density lipoprotein (HDL) levels (10.2%, p=0.04) increased. Decreases in AUC insulin were associated with increases in AUC 20/10 BA (ρ=-0.687, p=0.009). HBA1C decreases were associated with increases in AUC total BAs (ρ=-0.531, p=0.034). Increases in the insulinogenic index (Δ30 Insulin/ Δ30 glucose) correlated positively with fasting DCA (ρ=0.567, p=0.028). Increases in HDL were associated with increases in fasting CA (ρ=0.580, p=0.018) and UDCA (ρ=0.592, p=0.016). Conclusion: Total, 10, and 20 bile acids increase after SG in youth associated with improvements in metabolic profile.

Presentation: Thursday, June 15, 2023