bluuebunny/crossref_metadata_2025 huggingface dataset:
THU074 Plasma Spexin In Metabolic Syndrome Related To Adult Growth Hormone Deficiency: A Cross-sectional Study
Authors: Vergani Edoardo , Oliva Alessandro , Bruno Carmine , Currò Diego , Mancini Antonio
Published: October 2023

Disclosure: E. Vergani: None. A. Oliva: None. C. Bruno: None. D. Currò: None. A. Mancini: None.

Adult growth hormone deficiency (aGHD) shares with metabolic syndrome some clinical features such as higher fat mass percentage, increased total cholesterol, LDL, triglycerides, reduced HDL, and higher risk of developing type 2 diabetes mellitus and cardiovascular complications. Spexin, also known as neuropeptide Q, is a 14-aminoacid polypeptide, related to the galanin-kisspeptin family, produced in several human tissues. It is also secreted along with insulin by pancreatic beta cells; via paracrine effects they blunted reciprocal secretion. In type 2 diabetes mellitus spexin is closely correlated to fasting and post prandial glucose, glycosylated hemoglobin and HOMA index. Moreover, spexin infusion seems to ameliorate ALT and AST levels in non-alcoholic fatty liver disease. Given its controversial role in condition of metabolic impairment, we aimed to evaluate spexin plasmatic levels in aGHD. Thirty-eight subjects were included in the study, 18 aGHD patients (7 females and 11 males) and 20 healthy controls (12 females and 8 males). aGHD was diagnosed by a GHRH plus arginine test. Etiologies of GHD were as follows: 7 empty sellas, 5 post-surgical hypopituitarism, and 6 idiopathic with negative MRI scans. GHRH plus arginine stimulation tests were repeated twice in idiopathic aGHD to confirm the diagnosis. They were evaluated for glucose and insulin, HOMA and QUICKI index, total/LDL/HDL cholesterol, triglycerides, uric acid and IGF-1. Spexin was measured by ELISA, according to manufacturers’ protocols. Fat mass percentage was evaluated by DXA. Mean±SEM age of aGHD group was 59.7±2.7 years, while BMI was 30.2±2.2 kg/m2; control group aged 47.1±2.5 years, while BMI was 24.5±0.9 kg/m2. As expected, aGHD patients showed higher HOMA index, triglycerides and lower HDL than controls. Furthermore mean±SEM fat mass percentage was significantly higher in aGHD than controls (44.41±3.15 vs 32.2±3.64). Spexin levels were similar in the two groups (aGHD 1.17±0.21 vs controls 1.25±0.10 ng/ml). significant correlations were found in both populations. These results, although preliminary, seem to exclude a possible role of spexin in aGHD; however, spexin could represent another possible element of differentiation between aGHD and metabolic syndrome. Such controversial topic requires further evaluations.

Presentation: Thursday, June 15, 2023
FRI279 Submaximal Loss Of KNDy Neurons Accelerates And Amplifies Pulsatile LH Secretion In Female Rats
Authors: Campideli-Santana Ana C , da Costa Silva Kaoma S , Araújo-Lopes Roberta , Antunes Luma M , Szawka Raphael E
Published: October 2023

Disclosure: A.C. Campideli-Santana: None. K.S. da Costa Silva: None. R. Araújo-Lopes: None. L.M. Antunes: None. R.E. Szawka: None.

Kisspeptin is a powerful stimulator neuropeptide in the hypothalamus-pituitary-gonadal axis and is essential for fertility. Neurons in the arcuate nucleus (ARC) of the hypothalamus that coexpress kisspeptin, neurokinin B, and dynorphin (KNDy) play a crucial role in the control of luteinizing hormone (LH) secretion, but the neuroendocrine mechanisms involved in this regulation are not fully understood. Our previous study demonstrated that the moderate loss of KNDy neurons amplifies the LH surge induced by estradiol in ovariectomized rats (1). The current study aimed to perform a longitudinal evaluation of female rats in which KNDy neurons were ablated to determine the integrated role of this neuronal population in the control of pulsatile LH secretion. Adult female rats underwent a neurochemical ablation of KNDy neurons via intra-ARC stereotaxic injections of neurokinin-3 receptor agonist conjugated with saporin (NK3-SAP), while control animals received blank-saporin (Control). Estrous cyclicity was monitored over 21 days before and after the stereotaxic surgery. Three weeks after surgery, blood samples (10 µL) were withdrawn from the tail tip at 6-minute intervals for 180 minutes on the day of diestrus. Rats were then ovariectomized and the ovaries were processed for histological analysis. Whole blood LH levels were measured by ELISA and brains were immunohistochemically labeled for neurokinin B in the ARC. NK3-SAP rats bearing a submaximal loss of KNDy neurons (between 55-95%; n = 8) displayed irregular estrous cycles. The ovarian weight and the number of corpora lutea and atretic follicles were unaltered, whereas the number of healthy early antral follicles decreased in NK3-SAP rats. The frequency of LH pulses was increased and both pulse amplitude and mean LH levels were higher in NK3-SAP compared with Control rats. Thus, the submaximal loss of KNDy neurons affects the regularity of estrous cyclicity but does not preclude ovulation, while seems to stimulate the maturation of early antral follicles. Notably, KNDy neuron loss accelerates and amplifies LH pulsatile secretion during the rat estrous cycle. These results suggest a new role for KNDy neurons in restraining the frequency and amplitude of LH pulses in ovary-intact animals, with possible implications in the rate of recruitment of early antral follicles.

Reference: Campideli-Santana et al., J Neuroendocrinol. 2022 Nov;34(11):e13204. Support: FAPEMIG, CNPq, CAPES, and Pro-reitoria de Pesquisa-UFMG.

Presentation: Friday, June 16, 2023
FRI353 Diabetes Insipidus - Pituitary Apoplexy Or Placental Vasopressinase?
Authors: Rodrigues Nimmy M , Palacios Merchan Juan Diego , Twahirwa Marcel B
Published: October 2023

Disclosure: N.M. Rodrigues: None. J. Palacios Merchan: None. M.B. Twahirwa: None.

Background: Pituitary apoplexy is rare in pregnancy. Diabetes insipidus is rare at apoplexy onset, present in about 5% of patients presenting with apoplexy. Gestational DI can occur due to placental vasopressinase though this is more common in twin pregnancies and pre-eclampsia. Clinical Case: 28-year-old Hispanic woman was admitted at 34-weeks' gestation for 1 week of headache, visual symptoms, elevated blood pressure and polyuria. Her thirst was intact. She had a known history of 8 mm prolactinoma, which was diagnosed 2 years prior to admission. She was treated with Cabergoline 0.5 mg twice weekly, which was stopped once pregnancy was confirmed. A 24-hour urine collection was performed as part of her pre-eclampsia workup. Total volume was 11,250 mL, osmolality 97 mOsm/kg and sodium of 25 mmol/L. Serum sodium was 136 mmol/L. MRI of the brain showed pituitary apoplexy with large suprasellar area hemorrhage, compressing the pituitary gland and infundibulum, resulting in anterior displacement. The optic chiasm was also compressed and displaced superiorly. Her BP remained normal throughout admission and pre-eclampsia workup was negative. Lab work did not show significant hypopituitarism with TSH of 1.3 microIU/mL, Free T4 0.53 ng/dL, random Cortisol of 11.5 mcg/dL, IGF-1 167 ng/mL, Copeptin 3.8 pmol/L. Considering this was the third trimester of pregnancy as well as the chronicity of the bleed, thought to be 5-7 days, neurosurgery suggested conservative management. She continued to maintain normal serum sodium levels throughout admission. She was delivered at 35 weeks by Caesarean section. She received Hydrocortisone 100 mg IV before the surgery. She also received DDAVP 1 mcg IV before delivery since her sodium level increased to 145 mmol/L from a baseline of 133-136 mmol/L. The delivery was uneventful, and she had a healthy baby. After delivery, her urine output decreased to 180 cc/hour with significant improvement in thirst. Her serum sodium remained normal. This raises the question of whether DI was due to apoplexy or placental effect. Conclusion: Even though pregnancy causes hypertrophy of the lactotrophs, pituitary apoplexy is less common in microadenomas. Apoplexy in pregnancy is very rare, occurring only in 1 in 10,000 gestations. The clinical presentation in this case suggests a low threshold to order pituitary imaging in cases presenting with concerning sign symptoms of increase intracranial pressure. Guidelines are limited in the management of pituitary apoplexy in pregnancy. There are case reports and case series where patients with apoplexy were delivered with C- section at 34 weeks. In addition, the element of pregnancy induced DI makes this presentation unique.

Presentation: Friday, June 16, 2023
FRI354 Therapeutic Potential Of Oxcarbazepine In Central Diabetes Insipidus
Authors: Pittampalli Shanti , Pattan Vishwanath , Das Dhriti , Munasinghe Uthpala
Published: October 2023

Disclosure: S. Pittampalli: None. V. Pattan: None. D. Das: None. U. Munasinghe: None.

Introduction: Postoperative central Diabetes insipidus is usually transient but can be persistent. Persistent central Diabetes insipidus is prone to dose fluctuations in clinically unstable patients, especially when concomitant medications influence sodium and water homeostasis. Clinical Case: A 24-year-old female with headache and confusion had sellar and suprasellar mass of 6 cm x 4 cm with moderate to severe hydrocephalus and underwent Right craniotomy with debulking of the mass and pathology showed pilocytic astrocytoma. Postoperative course was complicated by short-term memory loss, right-sided weakness, adrenal insufficiency, and visual impairment. Repeat imaging showed increased size of suprasellar mass consequently requiring a transnasal transphenoidal resection. Post-operative neurological worsening was noted along with diffuse subarachnoid/ intraventricular hemorrhage with intraparenchymal hematoma in the right frontal lobe on CTA head. Hospital course included tracheostomy with mechanical ventilation. She had panhypopituitarism including CDI. CDI was initially managed by DDAVP 10mcg intranasal nightly and free water flushes. She had central adrenal insufficiency and central hypothyroidism treated by hydrocortisone and levothyroxine respectively. Hospital stay lasted for several months with multiple adjustments to the DDAVP dosage and free water flushes due to fluctuating serum sodium levels. She was started on levetiracetam 750 mg twice daily and oxcarbazepine 300 mg twice daily for seizure like activity. After two months, the oxcarbazepine dose was increased to 450 mg twice daily and later to 600 mg twice daily for breakthrough seizures. DDAVP was then discontinued as she developed hyponatremia. The dose of oxcarbazepine was reduced to 450 mg twice daily and she was subsequently discharged to a facility off DDAVP. Discussion: Postoperative CDI managed by DDAVP was complicated with oxcarbazepine-induced hyponatremia. CDI and sodium levels were controlled with oxcarbazepine after DDAVP discontinuation. Thus, oxcarbazepine has therapeutic potential as an antidiuretic agent as it can stimulate collecting tubule V2 receptor - G protein complex independent of ADH.

Presentation: Friday, June 16, 2023
FRI356 SIADH In Acromegaly And Cerebrovascular Accident
Authors: Simrampreet Gill , Guatemala Funes Irving Alexis , Gomez Danelly , Siddiqui Samrah , Zahedi Tooraj , Zhang Fan
Published: October 2023

Disclosure: S. Siddiqui: None. I.A. Guatemala Funes: None. G. Simranpreet: None. T. Zahedi: None. F. Zhang: None.

Introduction: Acromegaly is characterized by excess growth hormone secretion with distinctive features of acral overgrowth, soft tissue swelling, arthralgia, jaw prognostication, hyperglycemia, hyperhidrosis, and frontal bone bossing. Hypotonic hyponatremia may occur in patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH), hypothyroidism, hypocortisolism, polydipsia, medications, heart failure, liver disease, or renal dysfunction. We reported a rare case of a patient with acromegaly treated with octreotide (somatostatin analogue) who was admitted for cerebrovascular accident and developed hyponatremia due to SIADH. Case Report: Patient is an 81 year old female with typical clinical features of acromegaly who presented with expressive aphasia and left sided facial droop. MRI and CT head revealed a 26 x 14 x 29 mm densely calcified/ossified extra-axial mass in the posterior fossa, displacing the brainstem and small vessel ischemia. Patient was treated with monthly intramuscular injection of octreotide for more than 20 years before she was switched to oral octreotide formula two weeks ago. Patient had nausea, vomiting, and altered mental status. Labs showed hyponatremia with serum Na 118 mmol/L, low serum osmolality 247 mOsm/kg, high urine osmolality 437 mOsm/kg, and urine Na 104 mmol/L. Serum Na further dropped to 115 mmol/L after IV normal saline which may be related to the desalination phenomenon of SIADH. Tolvaptan and hypertonic saline were initiated followed by treatment with salt tablets and furosemide. After several days, her serum Na level slowly trending up back to normal 135 mmol/L and patient recovered with no focal neurological deficits. Discussion: Treatment for acromegaly involves multiple approaches, such as somatostatin receptor ligands, GH antagonism, surgery, radiotherapy, and dopamine receptor agonists. Life-treating endocrine disorder may result from pituitary infarction or hemorrhage in patient with acromegaly. Although gastrointestinal sodium loss may precipitate hyponatremia in our patient, her elevated urine sodium and urine osmolality were consistent with SIADH. Clinicians should be cautious of the sudden onset of hyponatremia due to SIADH in acromegaly patients and prompt treatment is warranted.

Presentation: Friday, June 16, 2023
THU176 Identification Of IGF1R Gene Variants In Short Children Born Small For Gestational Age
Authors: Kwon Eun Byul , Kang Min Jae , Hwang Il Tae
Published: October 2023

Disclosure: E. Kwon: None. M. Kang: None. I. Hwang: None.

Introduction: In short stature children born small for gestational age (SGA-SS), IGF1R gene is one of important candidate genes in catch-up failure. Various deletions and single nucleotide variants of IGF1R have been reported. In this study, we aimed to find the prevalence of IGF1R gene mutation and to analyze their clinical characteristics. Method: Short stature children who met the following criteria were included: 1) Birth weight ≤ 10 percentile, and 2) Height at initial visit ≤ 3 percentile, and 3) IGF-1 SDS > 0 or Height z-score < -2.5. Calculations of IGF-1 SDS and birth weight SDS were based on previous reports (Clin chem 2012;45:16-21 and Ann Pediatr Endocrinol Metab 2014;19:146-153, respectively). Deletions were detected using SALSA MLPA probemix kit P217-B2 IGF1R (MRC Holland, Amsterdam, the Netherlands) and single nucleotide variants were analyzed by sanger sequencing of whole exon (#21) and exon-intron boundaries. Results: Mean age, birth weight SDS, height z-score, and BMI z-score of total 65 subjects were 8.0 years, -1.88, -2.83, and -0.52, respectively. Number of subjects whose birth weight ≤ 3 percentile was 25. Maximal value of IGF-1 SDS was 1.45. Family history of parental short stature (≤ 3 percentile) was found in 18 subjects. Growth hormone stimulation test was undergone in 64 subjects. Peak GH level was 1.35-41.74 ng/mL and 25 subjects had peak GH level < 10 ng/mL. A heterozygous deletion in 15q26.2q26.3 was found in one subject. She was 6.6 years old and her height z-score, BMI z-score, and birth weight SDS were -4.22, 2.36, and -3.23, respectively. She had no family history of parental short stature and her serum levels of peak GH was 3.72 ng/mL and IGF-1 SDS was -0.66. Conclusion: In this study, the prevalence of IGF1R mutation was 1.5% (1/65 subjects). Although clinical characteristics of SGA-SS subjects are various and heterogenous, IGF1-IGF1R axis is an important mechanism in SGA-SS, therefore, further investigation is needed.

Presentation: Thursday, June 15, 2023
THU177 Brain Magnetic Resonance Imaging Abnormalities And Effect On Growth Response In Children With Growth Hormone Deficiency
Authors: Choe Jaewon , Lee Jieun , Kim Jae Hyun
Published: October 2023

Disclosure: J. Choe: None. J. Lee: None. J. Kim: None.

Purpose: There have been several studies on the association between structural abnormalities of the pituitary gland and its function. However, no studies have yet been conducted on children with idiopathic growth hormone deficiency (GHD) in Korea. We investigated clinical and laboratory findings of Korean children of idiopathic GHD by the presence or absence of pathologies in the pituitary gland. Material/Methods: A total of 479 patients were included from the LG growth study database. Participants had idiopathic GHD with available pituitary magnetic resonance imaging (MRI) and were treated with GH for at least 1 year between Feb, 2001 and Feb, 2020. Clinical characteristics were retrieved from the LG growth study database. Patients were divided into 3 groups according to pituitary MRI findings: (1) pathological findings in the pituitary gland; (2) pathological findings outside the pituitary gland; (3) without pathological findings with MRI. Results: Of the 479 patients, 297 (62.0%) were male and 198 (83.5%) were prepubertal. Their mean age was 7.56±2.95 years (2-16 years) and mean age of GH treatment was 7.56±2.96 years. Pituitary MR images of 354 (73.9%) patients were normal. Of the patients with detected pathologies (26.1%), 77 (61.6%) had pituitary hypoplasia, 15 (12.0%) had Rathke’s cleft cyst, 6 (0.05%) had partial empty sella, 6 (0.05%) had an arachnoid cyst, 3 (0.02%) had ectopic neurohypophysis, and 3 (0.02%) had a pineal cyst. There was no statistically significant difference in the height velocity after one year of GH treatment between groups with or without pituitary pathology (height SDS 0.71±0.34 with pituitary pathology and 0.66±0.35 with pituitary pathology; p=0.09). Conclusions: Among Korean children with GHD, approximately one-quarter of patients had abnormal pituitary MRI findings. There were no significant differences in predicting GH treatment response regardless of pituitary MRI abnormalities. Further long-term studies are needed.

Presentation: Thursday, June 15, 2023
THU179 Lifestyle Practices Elicited Different Responses To Growth Velocity Among Adolescents Depending On Different Levels Of Genetic Risk Score
Authors: Nguyen Nhat Nam , Fan Hsien-Yu , Chen Yang-Ching
Published: October 2023

Disclosure: N. Nguyen: None. H. Fan: None. Y. Chen: None.

Context: The evidence regarding effects of different lifestyle pratices, such as sun bathing, exercising, rope jumping, sleep duration, and milk intake, on growth velocity remain controversial and the influence of genetically determined characteristics on this association is less studied. Objective: To assess the impacts of different lifestyle pratices on annualized growth velocity and evaluate the role of several combined height-related alleles, mirrorred by the genetic risk score, on the association between lifestyle practices and growth among adolescents. Design: Prospective cohort study (mean follow-up duration: 2 years) Setting: Primary Care Participants: The Taiwan Puberty Longitudinal Study cohort, including male and female adolescent aged 6-17 (N = 1036) who were examined at both baseline and follow-up clinic visits. Main Outcome Measures: The effects of regular lifestyle practices (sun soaking, exercise habit, jumping rope, milk intake and sleep duration) on changes in height measurements. Participants will be stratified by either low or high genetic risk score. Results: Among lifestyle practices, sleep duration was significantly associated with growth velocity. Sleeping hours ranging between 7-8 hours per night were linked with a greatest growth. This relation was mainly driven by differences in males and was more obvious during Tanner’s stage II-III. The positive association between sleep duration and growth velocity was driven by significance in participants with low genetic risk score but not in those with high genetic risk score. Meanwhile, milk intake of greater than or equal to one cup per day had a modest effect on height velocity in male during Tanner’s stage I. Conclusions: Sleep duration was associated with growth velocity, in which 7-8 hours per night was optimal. The benefit of adequate sleep was greater in individuals having low genetic risk score. Milk intake may have modest effect on growth velocity.

Presentation: Thursday, June 15, 2023
FRI599 Quality Of Life In Girls With Turner Syndrome Using The Quality Of Life In Short Stature Youth Questionnaire (QoLISSY) - A Cross-sectional Study
Authors: Vijayakanthi Nandini , Marcus David J , Fritz Sobha P , Xiang Yijin , Fadoju Doris Olukemi
Published: October 2023

Disclosure: N. Vijayakanthi: None. D.J. Marcus: None. S.P. Fritz: None. Y. Xiang: None. D.O. Fadoju: None.

Background: Short Stature is a common finding in girls with Turner syndrome (TS). Its impact on Quality of life (QoL) in adolescents/adults with TS have been studied using generic QoL questionnaires. Short stature specific QoL questionnaires have not been used to study the impact of short stature and GH therapy in TS in previous studies. Methods: In this cross-sectional study, we aimed to evaluate QoL and the association between GH therapy and height on QoL of adolescents using the short stature specific questionnaire -Quality of Life in Short Stature Youth (QoLISSY). QoLISSY was designed specifically to assess QoL in short stature children with scales for both parents and children which assesses 3 core QOL dimensions: physical, social, emotional and 3 predictors of quality of life: Coping, Beliefs and Treatment (GH therapy). It has not been previously used in TS. Results: Of the 41 eligible patients, 37 patients were enrolled in the study. The mean age of our cohort was 16.3 ±1.3 years and the average final adult height was 145.03 ± 7.3 cm. About 70% of the patients received GH therapy and 80% received estrogen therapy. Compared to the reference short stature mean values, our TS cohort had comparable scores in all QoL subscales and total scores in both parent and patient reports apart from the parental report treatment subscale which was significantly lower than their respective reference short stature means [Mean ± SD: 47.43±27.13 vs 58.82±16.75; p=0.03]. Girls with height >-3SD had significantly lower score in the coping subscale, compared to the <-2SD height group [Mean ± SD: 42.14 ± 19.04 vs 62.25 ± 16.60; p= 0.024; multivariate analysis: p=0.012. In the parent report, the social subscale was significantly lower in the > -3SD height group compared to the <-2SD height group [Mean ± SD: 57.59 ± 22.25 vs 80.94 ± 11.26; p=0.022; multivariate analysis: p=0.024]. There was no statistically significant difference in the QOL between the GH vs no GH groups. Conclusion: We conclude that the QoL in girls with TS was comparable to the reference short stature population. GH therapy did not improve the QoL in girls with TS in our cohort. Height does not appear correlate with the overall QoL in girls with TS though they have some coping and social difficulties. We recommend psychological counseling and support for girls with TS especially to address their coping and social difficulties.

Presentation: Friday, June 16, 2023
FRI400 A Rare Case Of Acute Sheehan's Syndrome In An Antepartum Patient
Authors: Jalal Erica , Baldwin Chelsey
Published: October 2023

Disclosure: E. Jalal: None. C. Baldwin: None.

Sheehan’s syndrome (SS) is a known complication of postpartum hemorrhage. It is typically diagnosed several years after birth given slow symptom onset related to hypopituitarism. We report a rare case of life-threatening antepartum pituitary ischemia secondary to hypotension, representing an acute presentation of SS. A 19-year-old primigravid woman at 31 weeks of gestation was admitted to the intensive care unit for septic shock secondary to Klebsiella pneumoniae pyelonephritis. Despite appropriate treatment, persistent hypotension prevented weaning of vasopressor support. Due to concurrent mild hyponatremia, the following studies were obtained: morning cortisol (2.46 mcg/dL [4.5-23 mcg/dL]), thyroid stimulating hormone (TSH) (0.379 IU/L [0.47-4.7 IU/L]), free triiodothyronine (2.1 pg/mL [2.8-5.3 pg/mL]), and free thyroxine (0.77 ng/dL [0.7-1.8 ng/dL]). Endocrinology was consulted for evaluation of adrenal insufficiency and abnormal thyroid function tests. Her prolactin was measured at 10.3 ng/mL, far below the expected range in a 3rd trimester pregnancy (35-600 ng/mL). Her remaining anterior pituitary hormone panel was unremarkable. MRI brain without contrast showed no evidence of an acute stroke or hemorrhage and commented that the prominence of the pituitary gland was likely related to current pregnancy. Stress dose hydrocortisone 100mg thrice daily and levothyroxine 50 mcg daily were initiated, allowing for weaning of vasopressor support. By discharge, she was titrated to levothyroxine 75mcg daily and hydrocortisone 20mg in the morning and 5mg in the afternoon. Repeat outpatient pituitary function testing found increase of prolactin to 397 ng/mL (35-600 ng/mL) and of IGF-1 to 486 ng/mL (113-408 ng/mL) as well as normalization of TSH to 3.210 (0.45-4.5IU/L), indicating likely recovery of pituitary axis. When readmitted at 38 weeks gestation for scheduled induction, she was given stress dose hydrocortisone 100mcg for labor. On discharge, she was tapered to prednisone 10mg daily and levothyroxine 50mcg daily. Appropriate hormone replacement and stress dose hydrocortisone resulted in an uncomplicated delivery and signs of clinical pituitary recovery postpartum as she was able to breastfeed without need for supplementation and maintain normotension after self-discontinuing prednisone and levothyroxine. The leading diagnosis to explain this patient’s hypopituitarism is acute SS, which is defined as symptom onset within 6 weeks postpartum. In our case, septic shock caused an abrupt onset of persistent hypotension leading to hormone levels suggestive of panhypopituitarism while the patient was pregnant at 31 weeks of gestation, which has not been reported in prior literature. While known as a chronic diagnosis in the postpartum population, further research should explore possible stunning effect of acute hypotension manifesting as acute SS in peripartum patients.

Presentation: Friday, June 16, 2023
FRI452 A Rare Case of Klinefelter Syndrome, 48XXYY
Authors: Kachhadia Palak , Khan Shaza , Aldasouqi Saleh , Limon Ahmad Abu
Published: October 2023

Disclosure: P. Kachhadia: None. S. Khan: None. S. Aldasouqi: None. A. Abu Limon: None.

Introduction: Klinefelter Syndrome (KS), 47XXY, is the most commonly seen chromosomal abnormality causing infertility, or primary hypogonadism. Other chromosomal variants are rare. We present a very rare case of nondisjunction of the sex chromosome resulting in a 48XXYY KS variant. Case Presentation: The patient is a 45-year-old male was referred to our clinic for evaluation of early onset osteoporosis. The patient was accompanied by his sister, given his cognitive delay. On initial physical exam, there was a concern about acromegaly with signs of frontal bossing, increased hand size, increased ring size and increased shoe size. More recent pictures of the patient showed significant changes in his facial appearance from few years prior. Other symptoms included night sweats. Physical exam revealed decreased testicular volume (less than 3mL bilaterally). Pituitary labs showed elevated prolactin, elevated LH, FSH and low free and total testosterone. GH, IGF-1 levels were within normal range. Chromosomal analysis showed an unexpected pattern of 48XXYY. In addition, MRI of the pituitary was done which showed increased infundibular stalk and increase in size of the pituitary gland which was thought to be secondary to pituitary microadenoma. DEXA scan confirmed osteoporosis. Patient was treated with testosterone injections and alendronate. The rationale for alendronate therapy was considered as a bridge to prevent fractures while the bone density would expectedly improve with androgen therapy, over time. Discussion: Although KS is commonly seen at a frequency of 1:500-1:1000 males, less common and variable phenotypical presentations can occur and can lead to a delayed diagnosis. The reason for the delay of diagnosis in these rare KS variants is the cognitive impairment which leads to delayed evaluation of fertility or hypogonadism, as contrasted to patients with the common variant, KS 47XXY. Additionally, unlike the classic KS variant, these rare variants are often associated with learning disabilities and gross bony features. Conclusion: Clinicians should be familiar with different clinical presentations of the less common KS genetic variants, in contrast to classical KS variants. Patients with classical KS typically present early in view of recognizable complaints of infertility, while patients with the less common KS variants may not present early on due to cognitive delay. Thus, familiarity with the additional manifestations of the less common KS variants (e.g., gross bony features) can help clinicians to suspect the possibility of these variants, prompting chromosomal analysis for further evaluation in such patients.

Presentation Date: Friday, June 16, 2023
SAT010 Role Of Glucocorticoids In Induction Of Autophagy During Fetal Lung Development
Authors: Mishra Ritu , Mendelson Carole R
Published: October 2023

Disclosure: R. Mishra: None.

Development of the fetal lung and production of pulmonary surfactant is a complex process that involves crosstalk between the mesenchyme and epithelium, branching morphogenesis, thinning of the bronchi alveolar ducts and alveolar septa, differentiation of alveolar type II cells, increased synthesis of surfactant lipids and proteins and their trafficking to lamellar bodies (LBs). The regulation of these processes is incompletely understood. Autophagy has recently been shown to be critical for lung morphogenesis and lamellar body biogenesis. In studies of global and lung epithelial cell-specific knockout of a number of autophagy-related genes in mice, there was found to be neonatal respiratory distress and lethality at birth. Interestingly, the lung phenotype of mice with an epithelial cell-specific knockout of the autophagy gene, Beclin 1 (Becn1), was very similar to that of mice with a targeted deletion of the glucocorticoid receptor (GR) gene (GRKO). Moreover, this phenotype was also observed in mice double-deficient in steroid receptor coactivators (Src)-1 and 2 (Src-1/-2dKO), which serve an essential role in GR transcriptional activity in fetal lung. Therefore we were interested to determine whether GCs acting through the GR regulate autophagy gene expression in fetal lung. In preliminary studies, we made the exciting discovery that nuclear levels of phospho (p)-GRS220 increased markedly in mouse fetal lung (MFL) at 16.5 dpc (compared to 15.5 dpc) and continued to increase toward term (18.5 dpc). Importantly, nuclear levels of total GR remained unchanged from 15.5 -18.5 dpc. Moreover, we observed that treatment of cultured MFL epithelial cells with the synthetic glucocorticoid, dexamethasone (Dex), upregulated expression of the autophagy genes, Becn1, Atg7 and Lc3b. Dex Induction of autophagy genes was prevented by co-incubation with the potent small-molecule inhibitor, SI-2, which selectively reduces cellular protein levels of the SRC family of GR coactivators. The importance of SRC-1 and SRC-2 in the regulation of autophagy gene expression is further emphasized by our finding that Becn1 and Atg7 expression was significantly reduced in lungs of Src-1/-2 dKO fetal mice at term. Previously, we found that glucocorticoids increase expression of transcription factor, C/EBPβ in an SRC-1/SRC-2-dependent manner which further upregulates C/EBPα in MFL epithelial cells. In ChIP-qPCR studies, we observed an increased binding of p- GRS220 and C/EBPα to the promoter regions of autophagy genes in MFL with advancing gestation. We also observed that siRNA-mediated knockdown of C/EBPα prevented Dex induction of autophagy gene expression. These exciting collective findings suggest that glucocorticoids together with SRC-1 and SRC-2 enhance autophagic flux in fetal lung via the C/EBP signaling pathway.

Presentation: Saturday, June 17, 2023
FRI505 A Rare Case Of Methimazole Induced Grave Agranulocytosis
Authors: Barua Nabonita , Idriss Setana , Panta Raju , Jamal Issra , Hodge Jordesha
Published: October 2023

Disclosure: N. Barua: None. S. Idriss: None. R. Panta: None. I. Jamal: None. J. Hodge: None.

Introduction: Agranulocytosis is a rare side effect of methimazole that usually occurs in a dose-dependent fashion within the first 3 to 6 months of initiation. It occurs in 0.2 - 0.5% of patients with Graves' disease who receive treatment with antithyroid drugs (ATD). We describe a rare case of agranulocytosis in a 36-year-old female treated with methimazole for hyperthyroidism. Case: A 36-year-old female, who was diagnosed with Graves' disease 2 months prior, presented to the Emergency Department for evaluation of worsening sore throat, odynophagia, dysphagia, and fever for 12 days after failed outpatient treatment with amoxicillin. Pre-admission labs showed free T4 > 7.77ng/dl, TSH <0.01 mIU/L, thyrotropin receptor antibody elevated at 28.30. She was initially treated with methimazole 10mg TID then reduced to BID few weeks prior to hospitalization. On arrival, her temperature was 102.8 F, heart rate 120 bpm, and blood pressure 116/65 mmHg. On physical exam, she had thyromegaly and discomfort on palpation of the neck. Labs showed WBC of 0.6k/mm3, absolute neutrophil count (ANC) of 0, Hgb 11.1 g/dl, TSH <0.01 mIU/L, Free T4 3.11 ng/dL and free T3 6.7 pg/ml. CT neck with contrast revealed tonsillitis and epiglottitis with associated tonsillar and peritonsillar abscess. She was started on Vancomycin, Cefepime and Acyclovir for 7 days; and Fluconazole 14 days for epiglottitis, tonsillitis, HSV, and oral candidiasis. Methimazole was discontinued, and she was started on cholestyramine 4 gm 6 hourly, dexamethasone 2 mg IV 8 hourly and propranolol 20 mg 8 hourly with improvement of her free T4 from 3.11-2.93. Her free T3 worsened from 8.1 to 11.1, potassium iodide 50 mg 6 hourly was added to the regimen. After 10 days of treatment, her thyroid blood tests and ANC improved, and she was discharged. She underwent total thyroidectomy 2 weeks after discharge and was placed on levothyroxine 75 mcg daily. Conclusion: Agranulocytosis from ATDs has a remarkably high mortality rate of about 21.5%. The mechanism behind is both immune-mediated toxicity and direct toxicity from oxidative process mediated by myeloperoxidase and cytochrome P450 enzymes. Agranulocytosis caused by ATD is usually dose dependent and mostly present with significant hyperthyroid state. Alternative ways of treatment should be promptly initiated as cross-reaction between methimazole and propylthiouracil occurs in about 15.2% of cases. Patient education about this dreadful side effect and awareness about seeking immediate medical attention at symptom onset is key in successful remediation of this condition.

Presentation: Friday, June 16, 2023
FRI512 Thyrotoxic Periodic Paralysis With Extreme Hypokalemia Precipitated By Acute Alcohol Intoxication In A Patient With Graves’ Disease
Authors: Batra Jaskaran , Reddy Ankireddypalli Anvitha , Kaur Jasleen
Published: October 2023

Disclosure: J. Batra: None. A.R. Ankireddypalli: None. J. Kaur: None.

Introduction: Thyrotoxic periodic paralysis (TPP) is a muscle and electrolyte disorder, mostly seen in the setting of hyperthyroidism. It is characterized by reversible painless muscle weakness and hypokalemia. Prevalence is highest in East Asian populations, approximately 2%, and 0.1-0.2% in other populations. Males are much more likely to be affected. Common provoking factors include exercise, fasting, and changes in diet. Clinical case: A 29-year-old male of East Asian ethnicity presented to the hospital with the complaint of multiple bouts of inability to lift his extremities for 1 day. He also complained of generalized weakness. He did not have any changes in his mental status and was fully oriented at the time of the presentation. No breathing difficulty was reported. He had been drinking the night before with his friends and drank 1 L of vodka. His past medical history was significant for hyperthyroidism secondary to Graves’ disease, which was diagnosed a year ago. He had been prescribed methimazole but had not been adherent to the medication. The basic metabolic panel revealed undetectable serum potassium of <1.5 (3.4 to 5.3 mmol/L). The rest of the electrolytes and renal function were unremarkable. TSH was suppressed at <0.01 (0.3 to 4.20 uIU/L) and free T4 levels were significantly elevated at 7.77 (0.9 to 1.70 ng/dL). The thyrotropin receptor antibody was 33 (0.00 to 1.75 IU/L). EKG showed sinus tachycardia with nonspecific T-wave abnormalities. Thyroid ultrasound showed diffusely heterogenous parenchyma with diffusely increased blood flow throughout the thyroid on doppler. Echocardiogram showed a normal ejection fraction of 55-60% with mild concentric left ventricular wall thickening consistent with left ventricular hypertrophy. He was initially treated with intravenous potassium replacement and high doses of propylthiouracil, hydrocortisone, and propranolol, leading to the resolution of his symptoms. He was discharged on methimazole and propranolol therapies. Learning points: • Patients with Graves’ disease are routinely counseled against tobacco use to avoid worsening of orbitopathy. Hyperthyroid patients should also be counseled regarding avoidance or moderation of alcohol intake to avoid this rare but potentially life-threatening complication of thyrotoxic periodic paralysis. • The incidence of TPP is significantly higher in the East Asian populations, especially among males (8.7-13%). Counseling regarding provoking factors, the importance of adherence to medications, and the maintenance of euthyroidism to avoid TPP is essential.

Presentation: Friday, June 16, 2023
FRI561 The Thyroid Trifecta
Authors: Kachhadia Palak , Khan Shaza , Abu Limon Ahmad , Aldasouqi Saleh
Published: October 2023

Disclosure: P. Kachhadia: None. S. Khan: None. A. Abu Limon: None. S. Aldasouqi: None.

Introduction: Autoimmune Hashimoto’s Thyroiditis (HT) and Graves’ Disease (GD) may co-exist or may occur alternatingly, known in many case reports as Graves’s Alternans. Hyperfunctioning (Toxic, hot) thyroid nodules (TN) may also co-exist with GD, a rare condition called Marine-Lenhart syndrome. However, the co-existence of HT, GD and TN is perceivably rarer. Case Presentation: The patient is a 45 year old female with a prior history of HT for 20 years, who presented to the clinic with symptoms of minimal eye pain, tremors, fatigue, diarrhea and anxiety. She was not on thyroid replacement, with normal thyroid function tests (TFTs). Physical exam showed bilateral proptosis, a moderate goiter, hand tremors, mild anxiety and tachycardia. Labs showed high TPO (3995.0 IU/mL, n <18 IU/mL), Thyrotropin receptor antibody (5.25 IU/L, n<1.75 IU/L), and Thyroid-stimulating immunoglobulins (1.8 TSI index, n<1.3 TSI index) with low-normal TSH of 0.42 uIU/mL (0.35-4.01 uIU/mL) , mid-range free triiodothyronine (FT3) at 3.6 pg/mL (2.8-4.4 pg/mL) and normal free thyroxine (FT4) at 0.80 NG/dL (0.61-1.37 NG/dL). Thyroid US showed a 2.4 cm left lobe inferior nodule classified as TI-RADS 3. Fine needle aspiration of this nodule was benign. Radioactive Iodine-123 Uptake Scan showed a hot nodule in the left inferior lobe and with visible uptake in the rest of the gland (uptake was mid-normal). She was started on methimazole 5mg once daily and propranolol 10mg BID with improvement in her symptoms. Subsequent TFTs showed stable T4 and T3 and normalization of TSH to 1.78 uIU/mL (0.35-4.01 uIU/mL). Discussion: Marine-Lenhart syndrome was described in 1911 by surgeons David Marine and Carl Lenhart. Graves’ Alternans has been described in the literature, with variable time separation. Though thyroid nodules occur in up to 35% of those with GD, only 1-4.1% are deemed functional nodules. Nuclear medicine imaging via Tc-99m pertechnetate or I-123 iodine at diagnosis of GD generally shows such nodules as cold nodules lacking uptake, while the rest of the gland has diffuse uptake. However, with normalization of TSH through treatment, these cold nodules may alternate uptake and present as hot nodules. Conclusion: In conclusion, this case presents the co-existence of HT, GD and HN, a term we are calling “Thyroid Trifecta”. It is imperative that HNs should be identified if RAI treatment is planned in such patients. Literature review portrays cases in which if thyrotoxicosis persists post RAI treatment for GD, careful examination and repeat RAIU may show a hot nodule consistent with Marine-Lenhart Syndrome. These patients may benefit instead from thyroidectomy. In the case of our patient, definitive treatment options have been discussed and she has been referred for thyroidectomy due to the presence of the TN. RAI ablation will be avoided in view of mild but active thyroid eye disease.

Presentation: Friday, June 16, 2023
SAT549 False Alarm: Profoundly High Thyroglobulin Level Without Evidence Of Thyroid Malignancy
Authors: Thelmo Franklin L , Watari Jessica , Miller Jeffrey L
Published: October 2023

Disclosure: F.L. Thelmo: None. J. Watari: None. J.L. Miller: None.

Thyroglobulin (TG) remains a clinical mainstay for monitoring of disease burden and recurrence in patients with differentiated thyroid cancer. TG levels are expected to be low to undetectable in patients who undergo total thyroidectomy and less than 30 ng/mL in patients who undergo thyroid lobectomy. We describe a case of a 52-year-old patient who underwent thyroid lobectomy for a 16 mm minimally invasive follicular thyroid carcinoma (single vessel angioinvasion) who was later found to have a TG level in excess of 2,000 despite no signs of metastatic disease. A 52-year-old male with past medical history of prediabetes and minimally invasive follicular thyroid cancer presented for follow-up after right lobectomy five years prior. The patient was lost to follow-up after his lobectomy. During work-up of paresthesias, a cervical spine MRI incidentally noted a 41 mm enhancing mass in the left thyroid lobe. The patient had a TSH of 1.1 mIU/L. A dedicated thyroid ultrasound was performed which found a left 2.9 cm TI-RADS 3 nodule which was biopsied and found to be benign (Bethesda II). TG level was obtained and found to be significantly elevated at 2,479.9 ng/mL with negative thyroglobulin antibodies. This was repeated twice with subsequent levels being 1,857.5 ng/mL and 2,555.1 ng/mL. TG antibodies remained undetectable throughout the clinical course. The patient had a CT chest, abdomen, and pelvis exam for which no signs of metastatic disease were detected. A skeletal survey was performed which showed no evidence of metastatic disease. The patient elected for a completion thyroidectomy to ensure there was no undetected malignancy. The patient underwent successful completion thyroidectomy. Surgical pathology showed benign nodular hyperplasia. The patient was started on replacement levothyroxine and one month later the TG level became undetectable. We would like to draw attention to this patient’s profoundly high TG levels which are normally associated with recurrence of thyroid malignancy or large goiter. After comprehensive evaluation this patient was found to have no underlying disease recurrence. A completion thyroidectomy showed no malignancy within remnant thyroid tissue or adjacent lymph nodes and repeat TG level was undetectable after completion showing that native thyroid tissue had significantly high TG production without underlying disease. We believe his remaining relatively normal thyroid lobe was a super producer of thyroglobulin. Despite TG being a sensitive marker for residual thyroid tissue and disease, the standard cut-off for lobectomy must be used with caution and may not apply to every patient.

Presentation Date: Saturday, June 17, 2023
SAT557 Unexpected Whole Body Scan Finding
Authors: Gastelum Alheli Arce , Liu Catherine Y , McCowen Karen
Published: October 2023

Disclosure: A. Arce Gastelum: None. C.Y. Liu: None. K. McCowen: None.

A 41-year-old man presented with a neck mass. Following total thyroidectomy with central and bilateral lateral neck node dissection, he received a diagnosis of stage I T2N1bMx multifocal papillary thyroid cancer with extensive extrathyroidal extension, angioinvasion and 14/65 positive lymph nodes. Surgery was complicated by temporary post operative hypoparathyroidism. Lab testing one week post thyroidectomy, before radioiodine ablation showed a serum TSH 23 uIU/mL, thyroglobulin: 34.1 ng/mL, with thyroglobulin antibody: <0.9 [IU]/mL.Post RAIA Whole Body Scan revealed increased uptake in the right orbit, concerning for metastatic disease. Confirmatory MRI of the brain showed a right superior intraorbital cystic lesion. Although orbital metastases are infrequent, a metastatic lesion was suspected due to the aggressiveness of his thyroid cancer. The patient was referred to ophthalmology several months after surgery and underwent right orbitotomy with excision and biopsy of the mass. The pathology was consistent with a multilocular cystic tumor lined by bland cuboidal epithelium, containing proteinaceous concretions and entirely negative for metastasis. Extensive thyroid cancer is treated with surgery followed by radioactive iodine (I-131) in case of tissue remnants or extra nodal metastases. Although unusual, false-positive scans exhibiting the presence of 131I uptake in the absence of residual thyroid tissue can occur.Fibrotic lung conditions, pleural effusions and bronchiectatic lesions have been reported to concentrate iodine in the absence of thyroid cancer metastasis. One prior report of a conjunctival inclusion cyst also resulted in radioiodine uptake in the orbit. Unless identified as a false positive, radioiodine uptake may result in a diagnostic fallacy. The correlation of clinical signs and serum thyroglobulin trends with imaging techniques should be emphasized to prevent unnecessary additional therapy.

Presentation Date: Saturday, June 17, 2023