Endocrine Abnormalities Research Articles

Effect of Bushen Huoxue recipe on serum metabolomics in polycystic ovary syndrome rats

Objective To investigate the effect of Bushen Huoxue Recipe (BSHXR) on serum metabolomics in polycystic ovary syndrome rat (PCOSR). Methods In our study, twenty-four 6-week-old Sprague-Dawley (SD) female rats were randomly divided into three groups: treatment group, model group and blank group. The blank group and other groups were gavaged in different ways each morning, and the rats were treated with normal saline or BSHXR containing liquid each afternoon. Liquid chromatography-mass spectrometry (LC-MS) was employed to study serum metabolites in the treatment group after the study as well as in the model and blank groups. Results There was a tendency to normalize the histomorphology of ovarian pathology and the abnormal sex hormone level of PCOSR was significantly improved after BSHXR treatment. The level of serum metabolites was greatly changed in PCOSR treated with the BSHXR. We identified 32 metabolic targets of BSHXR in PCOSR using LC-MS, and further revealed BSHXR targeted five major metabolic pathway: retrograde endocannabinoid signaling, taurine and hypotaurine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis, arginine and proline metabolism. Conclusion: Our study found that BSHXR plays a role in the treatment of PCOS by regulating key metabolic pathways in the PCOSR.

Short Stature and Distinct Growth Characteristics in Angelman Syndrome

Introduction: Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition, and motor skills accompanied by unique behaviors, distinct facial features, and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history, and endocrine abnormalities. Methods: Data were collected from patients’ medical files in AS National Clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak height velocity, and final height. Results: The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual produced 280 data points. Final height SDS was significantly lower compared to general population (−1.23 ± 1.26, p < 0.001), and in deletion group versus non-deletion (−1.67 ± 1.3 vs. −0.65 ± 0.96, p = 0.03). Final height SDS was significantly lower compared to height SDS in preschool period (−1.32 vs. −0.47, p = 0.007). Patient’s final height SDS was significantly lower than the parents’ (∆final-height SDS = 0.94 ± 0.99, p = 0.002). IGF1-SDS was significantly decreased compared to general population (−0.55 ± 1.61, p = 0.04), with lower values among deletion group (−0.70 ± 1.44, p = 0.01). Conclusions: AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence, resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.

The Prevalence and Patterns of Toxicity With Immune Checkpoint Inhibitors in Solid Tumors: A Real-World Experience From a Tertiary Care Center in Oman.

Introduction Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple cancers over the last decade. They work by employing the immune system and exhibiting activity over T cells resulting in immune upregulation. Despite their widespread use, they produce side effects that can limit their use. The immune-related adverse events (irAEs) can be sometimes significant. The irAEs caused by ICIs may occur at any time during the treatment and can vary in grade (G). We sought to study the prevalence and toxicity patterns of ICIs in Oman. Methods One hundred forty-one adult patients (≥18 years) who received at least one dose of nivolumab, pembrolizumab, atezolizumab, or durvalumab between 2016 and 2022 were included. The data were analyzed retrospectively using univariable and multiple-variable logistic regressions. The Wilcoxon rank-sum test and Cochran-Armitage trend test were also used to summarize the continuous and ordinal data. Results Out of the 141 patients, 80 patients (56.7%) received pembrolizumab, and 48 (34%) received nivolumab. Common irAEs included endocrine abnormalities, pneumonitis, and colitis. Thirty patients (21.3%) experienced varying irAE grade toxicity. Out of the 30, 23 patients (82%) developed grade 2 and 3 irAEs. Discussion Predictive analysis showed that male sex and lower hemoglobin (Hb) and bilirubin levels were all significant predictors (p < 0.05) when associated with irAE occurrence. The prevalence of irAEs was similar compared to other reports, literature reviews, or meta-analyses. Female sex has been mentioned previously also to be a predictive factor for endocrine-related toxicities.

Pediatric craniopharyngioma: a 20-year study on epidemiological features, clinical presentation, and survival outcomes in a tertiary care center from LMIC.

Craniopharyngioma constitutes approximately 10% of primary brain tumors in children. It can cause considerable morbidity and mortality due to the local aggressiveness of the tumor itself or its management affecting the hypothalamus-pituitary axis and optic pathway involvement. There is very scarce data available from LMIC which makes the management controversial where multidisciplinary teams are already not available in most of the centers. This is a single-center cross-sectional retrospective review of 20-year record of 49 patients with craniopharyngioma treated between 2001 and 2020 at Aga Khan University Hospital, a tertiary care center in Karachi, Pakistan. We have assessed the epidemiological data of children presenting with the diagnosis of craniopharyngioma, treatment modalities used, and neurological, endocrine, and hypothalamic complications in these patients. The assessment involved a retrospective review of medical records and medical follow-up. Out of a total of 49 patients, 26 (53%) were male, and 23 (46.9%) were female. The mean age was 9.5years (SD ± 4.5years). Most common symptoms at initial presentation were headache 41 (83.6%), visual deficit 40 (81.6%), nausea and vomiting 26 (53%), and endocrine abnormalities 16 (32%). Treatment modalities used at our center include gross total resection 11 (22%) and subtotal resection 38 (77%) out of total, while 6 (12.2%) patients received intracystic interferon. Histopathologic findings of the majority of patients (40 (81%)) revealed an adamantinomatous type of tumor. Only 23 (46.9%) children followed in clinic post-op. Median follow-up after craniopharyngioma presentation was 5years (± 2.1 SD, range: 2-10years). Pituitary hormone deficiencies (98%) and visual disturbances (75%) were the most common long-term health conditions observed. Since pituitary hormone deficiencies and visual disturbance were the most common long-term health conditions observed in our study, these patients require a multidisciplinary team follow-up to improve their quality of life.

Ambiguous Effects of Obesity on Cancer Prognosis and Treatment Response: A Narrative Review

Obesity is a lifestyle disease that is a proven predisposing factor for many illnesses and is often associated with a poor prognosis. Here, the author tries to associate the relationship between the incidence of obesity in patients with cancer and the prognosis of the same. The present medical literature suggests an ambiguous and conflicting relationship. This study presents an extensive literature review of the mechanisms that may govern the survival outcomes of patients with cancer presenting with obesity. Medical literature databases, namely PubMed, Google Scholar, and BioMed Central databases, were searched. Out of 335 relevant results, 75 met the inclusion criteria. The results were varying in nature, with some papers showing poor prognosis due to the association of obesity with metabolic and endocrine abnormalities, which promote tumour growth, while others suggest that excess adiposity may promote a greater expression of programmed cell death protein-1 in effector CD8+ T lymphocytes, promoting a better response to immune checkpoint blockade therapies. Some even argue against the existence of the so-called ‘obesity paradox’, considering it a by-product of statistical misinterpretation and biases. In conclusion, the phenomenon is definitely intriguing but needs further investigation and research regarding other processes that may all in all affect cancer prognosis.

Environmental stress during adolescence promotes depression-like behavior and endocrine abnormalities in rats

ObjectiveTo assess the ability of environmental stress (ES) during adolescence on depression-like behaviors and endocrinology in rats. MethodsMale and female Sprague-Dawley rats before or during puberty were divided into three groups: control group (CON), low-frequency ES group (LF), and high-frequency ES group (HF). ES included water/food deprivation and reversal of day and night. After 4 weeks of ES, the behavioral tests were performed. Plasma concentrations of hormones and peptides were determined by enzyme-linked immunosorbent assay (ELISA). ResultsES induced a significant decrease in sucrose preference value in female adolescent rats but not males. In prepubertal rats, the reductions in sucrose preference upon ES were observed without a sex-specific effect. Compared with the CON group, female adolescent rats showed a significant increase, while male adolescent rats showed a significant decrease in plasma corticosterone (CORT) after ES. Also, ES significantly increased plasma leptin in female and male adolescent rats. Moreover, ES significantly increased plasma cholecystokinin (CCK), neuropeptide Y (NPY), and testosterone (TS) levels in adolescent female rats but not in males. No significant differences were found in plasma progesterone and E2 among adolescent rats. The prepubertal male rats showed significant plasma E2 and TS increase after ES, while there were no significant differences between groups in plasma CORT, leptin, CCK, NPY, and progesterone. ConclusionsES may cause depression-like behaviors in adolescent female rats. Our findings supplement the scientific basis for formulating strategies to treat and prevent adolescent depression.

Early short-term effects on catecholamine levels and pituitary function in patients with pheochromocytoma or paraganglioma treated with [177Lu]Lu-DOTA-TATE therapy.

While there are reports of treatment-related endocrine disruptions and catecholamine surges in pheochromocytoma/paraganglioma (PPGL) patients treated with [177Lu]Lu-DOTA-TATE therapy, the spectrum of these abnormalities in the immediate post-treatment period (within 48 hours) has not been previously evaluated and is likely underestimated. The study population included patients (≥18 years) enrolled in a phase 2 trial for treatment of somatostatin receptor (SSTR)-2+ inoperable/metastatic pheochromocytoma/paraganglioma with [177Lu]Lu-DOTA-TATE (7.4 GBq per cycle for 1 - 4 cycles). Hormonal measurements [adrenocorticotropic hormone (ACTH), cortisol, thyroid stimulating hormone (TSH), free thyroxine (FT4), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, growth hormone, prolactin], catecholamines, and metanephrines were obtained on days-1, 2, 3, 30, and 60 per cycle as per trial protocol, and were retrospectively analyzed. Among the 27 patients (age: 54 ± 12.7 years, 48.1% females) who underwent hormonal evaluation, hypoprolactinemia (14.1%), elevated FSH (13.1%), and elevated LH (12.5%) were the most frequent hormonal abnormalities across all 4 cycles combined. On longitudinal follow-up, significant reductions were noted in i. ACTH without corresponding changes in cortisol, ii. TSH, and FT4, and iii. prolactin at or before day-30 of [177Lu]Lu-DOTA-TATE. No significant changes were observed in the gonadotropic axis and GH levels. Levels of all hormones on day-60 were not significantly different from day-1 values, suggesting the transient nature of these changes. However, two patients developed clinical, persistent endocrinopathies (primary hypothyroidism: n=1 male; early menopause: n=1 female). Compared to day-1, a significant % increase in norepinephrine, dopamine, and normetanephrine levels were noted at 24 hours following [177Lu]Lu-DOTA-TATE dose and peaked within 48 hours. [177Lu]Lu-DOTA-TATE therapy is associated with alterations in endocrine function likely from radiation exposure to SSTR2+ endocrine tissues. However, these changes may sometimes manifest as clinically significant endocrinopathies. It is therefore important to periodically assess endocrine function during [177Lu]Lu-DOTA-TATE therapy, especially among symptomatic patients. https://clinicaltrials.gov/ct2/show/NCT03206060?term=NCT03206060&draw=2&rank=1, identifier NCT03206060.

Adrenocortical function in patients with Single Large Scale Mitochondrial DNA Deletions: a retrospective single centre cohort study.

Single Large Scale Mitochondrial DNA Deletions (SLSMDs), Pearson Syndrome (PS) and Kearns-Sayre Syndrome (KSS), are systemic diseases with multiple endocrine abnormalities. The adrenocortical function has not been systematically investigated with a few anecdotal reports of overt adrenal insufficiency (AI). The study aimed to assess the adrenocortical function in a large cohort of SLSMDs. A retrospective monocentric longitudinal study involved a cohort of 18 SLSMDs patients. Adrenocortical function was evaluated by baseline adrenocorticotrophic hormone (ACTH) and cortisol measurements and by high- (HDT) and low-dose (LDT) ACTH stimulation tests and compared with 92 healthy controls (HC). Baseline adrenocortical function was impaired in 39% of patients and by the end of the study, 66% of PS and 25% of KSS showed an insufficient increase after ACTH stimulation, with cortisol deficiency due to primary AI in most PS and subclinical AI in KSS. Symptomatic AI was recorded in 44% of patients. Peak cortisol levels after ACTH stimulation tests were significantly lower in patients than in HC (P < .0001), with a more reduced response to LDT vs HDT (P < .05). Our study highlights that cortisol deficiency due to primary AI represents a relevant part of the clinical spectrum in SLSMDs, with more severe impairment in PS than in KSS. Basal and after-stimulus assessment of adrenocortical axis should be early and regularly investigated to identify any degree of adrenocortical dysfunction. The study allowed the elaboration of a diagnostic process designed for the diagnosis, treatment, and follow-up of adrenocortical abnormalities in SLSMDs.

Pediatric adrenocortical carcinoma: clinical features and application of neoadjuvant chemotherapy

ObjectiveTo summarize the clinical characteristics of children with adrenocortical carcinoma (ACC) and preliminarily explore the indications for and efficacy of neoadjuvant chemotherapy in certain patients.MethodsThe data of 49 children with adrenocortical tumors (ACT) in the past 15 years were retrospectively analyzed, and after pathology assessment using Weiss system grading, 40 children diagnosed with ACC were included. Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and three-dimensional (3D) reconstruction of contrast-enhanced computed tomography data were used to evaluate the response to neoadjuvant chemotherapy.ResultsForty patients (17 males, 23 females) with ACC were enrolled. Abnormal hormone levels were common in children with ACC (n = 31), and in terms of clinical presentation, sexual precocity was the most common (n = 14, 35.0%), followed by Cushing’s syndrome (n = 12, 30.0%). Seven of 40 children received neoadjuvant chemotherapy due to a maximum lesion diameter greater than 10 cm (n = 4), invasion of surrounding tissues (n = 2), intravenous tumor thrombus (n = 2), and/or distant metastasis (n = 2); 2 patients achieved partial response, and 5 had stable disease according to the RECIST 1.1 standard. Furthermore, 3D tumor volume reconstruction was performed in 5 children before and after neoadjuvant chemotherapy. Tumor volumes were significantly reduced in all 5 children, with a median volume reduction of 270 (interquartile range, IQR 83, 293) (range: 49–413) ml. After surgery with/without chemotherapy, the 5-year overall survival rate for all children was 90.0% (95% CI-confidence interval 80.0–100.0%), and the 5-year event-free survival rate was 81.5% (95% CI 68.0–97.7%).ConclusionIn the diagnosis and treatment of pediatric ACC, a comprehensive endocrine evaluation is necessary to facilitate early diagnosis. Surgery and chemotherapy are important components of ACC treatment, and neoadjuvant chemotherapy should be considered for children with ACC who meet certain criteria, such as a large tumor, distant metastases, or poor general condition.

Recent advancement in targeted therapy and role of emerging technologies to treat cancer.

Cancer is a complex disease that causes abnormal cell growth and spread. DNA mutations, chemical or environmental exposure, viral infections, chronic inflammation, hormone abnormalities, etc., are underlying factors that can cause cancer. Drug resistance and toxicity complicate cancer treatment. Additionally, the variability of cancer makes it difficult to establish universal treatment guidelines. Next-generation sequencing has made genetic testing inexpensive. This uncovers genetic mutations that can be treated with specialty drugs. AI (artificial intelligence), machine learning, biopsy, next-generation sequencing, and digital pathology provide personalized cancer treatment. This allows for patient-specific biological targets and cancer treatment. Monoclonal antibodies, CAR-T, and cancer vaccines are promising cancer treatments. Recent trial data incorporating these therapies have shown superiority in clinical outcomes and drug tolerability over conventional chemotherapies. Combinations of these therapies with new technology can change cancer treatment and help many. This review discusses the development and challenges of targeted therapies like monoclonal antibodies (mAbs), bispecific antibodies (BsAbs), bispecific T cell engagers (BiTEs), dual variable domain (DVD) antibodies, CAR-T therapy, cancer vaccines, oncolytic viruses, lipid nanoparticle-based mRNA cancer vaccines, and their clinical outcomes in various cancers. We will also study how artificial intelligence and machine learning help find new cancer treatment targets.

SAT192 Non-syndromal Primary Hyperparathyroidism Presenting As Asymptomatic Hypercalcemia In A Teenage Patient.

Abstract Disclosure: S. Humayon: None. M. Shah: None. P.N. Kabir: None. C.A. Penaherrera: None. Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia in the general population, and is often discovered incidentally. The condition rarely presents in patients under age 18, particularly when it is not associated with genetic syndromes such as MEN 1. Case presentation: A previously healthy 17-year-old female was referred to Endocrinology clinic for evaluation of positive thyroid peroxidase antibodies with normal TSH and free T4. Review of laboratory results from 6 months prior, revealed an elevated total calcium level of 12.3 mg/dl. Patient at the time denied any symptoms of hypercalcemia. Repeat testing revealed a calcium level of 13.1 mg/dl, PTH level of 183 pg/ml, alkaline phosphatase 232 IU/L. Her vitamin D level was 28 ng/ml, with elevated calcitriol level of 362 ng/ml. The patient denied a history of kidney stones or other endocrine abnormalities in the past. She did mention a family history of hypercalcemia in her father requiring neck surgery. Patient was admitted to the hospital for management of hypercalcemia with intravenous fluid hydration. Subsequent work-up included a sestamibi parathyroid scan which revealed an asymmetric area of delayed uptake in the left thyroid gland, suggestive of a single parathyroid adenoma. The patient underwent single-gland parathyroidectomy, during which PTH levels decreased from 134 pg/ml to 15 pg/ml. She recovered uneventfully from the procedure and was started on oral calcium supplementation, which was tapered two months after surgery since there was no evidence of post-operative hypoparathyroidism. Conclusion: Primary hyperparathyroidism, when presenting prior to the age of 30, is most commonly associated with genetic syndromes such as MEN1 and typically presents as multi-glandular hyperplasia. Isolated primary hyperparathyroidism, secondary to a single parathyroid adenoma is seen less frequently in this younger subset of patients. This can be found in the absence of other endocrine abnormalities, with or without the presence of a family history. Prompt identification of hypercalcemia followed by evaluation of the same, may prevent delays in diagnosis and subsequent management of primary hyperparathyroidism. This can help prevent morbidity associated with hypercalcemia. Presentation: Saturday, June 17, 2023

SAT627 Is Cyberknife Stereotactic Radiosurgery Effective For Treating Cushing’s Disease?

Abstract Disclosure: G. Wintermyer: None. E. Villanueva: None. Patients with pituitary adenoma can often present with endocrine abnormalities. Transsphenoidal surgery(TSS) is the “gold standard” treatment. In patients with recurrent or post-surgery remaining adenoma, stereotactic radiosurgery with CyberKnife (CKRS) has demonstrated to be a good adjuvant therapy. Occasionally patients develop hypopituitarism and adrenal insufficiency (AI) post CKRS. Here is a patient with ACTH-secreting pituitary adenoma with Cushing’s disease who developed remission afterCKRS:52-year-old-male with PMHx of T2DM, hypothyroidism, HTN presented to hospital complaining of fatigue, ataxia, 40-lbs weight loss over four months and mood changes. Due to ataxia, CT of the head was done which revealed an Empty Sella. During the workup, ACTH and cortisol were detected 131 pg/mL and 37.5 ug/dL respectively. After ruling out life-threatening medical conditions, he was discharged with endocrinology referral for Empty Sella syndrome (ESS) and elevated ACTH. During endocrinology evaluation, patient was sent for testosterone, LH, FSH, ACTH, AM cortisol, prolactin and DHEAS tests. Results were as follows: elevated ACTH (91 pg/mL) and Cortisol (33.5ug/dL), elevated DHEAS (401 ug/dL) and prolactin (15 NG/dL), low testosterone (72 NG/dL), within appropriately low LH and FSH. Later, PM Salivary cortisol level, Dexamethasone suppression test(DST), and urine free cortisol (UFC) level were tested. He had pituitary MRI concurrently. Salivary cortisol and UFC were high. There was no suppression of cortisol level after DST. Pituitary MRI demonstrated pituitary tumor. He was diagnosed with Cushing’s disease and was referred to neurosurgery for pituitary tumor TSS. Patient was started on Ketoconazole prior to surgery. Pathology confirmed ACTH-secreting pituitary adenoma. After surgery, Cortisol level normalized, and the patient regained his energy. Post-surgery MRI showed complete resection of adenoma. Ketoconazole was discontinued post-operatively. Two years later, during routine workup, there were elevations in 24-hour and PM salivary cortisol levels. The patient was asymptomatic. He failed his DST. Repeat pituitary MRI showed small hypo enhancement at the bottom of Sella suspicious for pituitary adenoma recurrence. The patient underwent CKRS. Cortisol level and pituitary axis activity remained normal since CKRS. No change was noted in the six-month and one-year surveillance MRI. Even though TSS is a “gold standard” treatment for pituitary adenoma, the likelihood of remaining residues or recurrence of the tumor is high. Frequent pituitary hormone checks can detect recurrence of adenoma before emerging symptoms. CKRS should be considered as a therapeutic option for recurrent adenoma. Clinicians should frequently check patients for hypopituitarism and AI post-CKRS. Clinicians should also recognize that ESS may contribute to MRI-negative Cushing’s disease. Presentation: Saturday, June 17, 2023

FRI288 Single-Cell Transcriptomics Identifies Pituitary Gland Cell Type Population Changes In Diet Induced Obesity

Abstract Disclosure: R.E. Ruggiero-Ruff: None. B. Le: None. N. Lainez: None. D. Coss: None. Obesity is a worldwide growing public health concern, with a current prevalence of 43% in the United States and projected future increase. Obesity is associated with type 2 diabetes, cardiovascular disease, stroke, and endocrine abnormalities. The pituitary gland is the master gland that responds to metabolic perturbations and regulates homeostasis via hormone secretion. Thyrotrophic, gonadotropic, somatotropic, lactotropic and corticotropic dysfunctions may occur as a consequence of obesity and perpetuate pathophysiologic conditions since pituitary hormones regulate metabolic function in return. Previous work from our lab determined that mice fed high fat diet have reduced levels of gonadotropin hormones, indicating that diet-induced obesity may play a role in pituitary hormone production. We postulate that diet-induced obesity alters the pituitary transcriptome and/or select population changes. To determine the effect of diet-induced obesity on pituitary gland population plasticity, we performed single-cell RNA-sequencing (scRNA-seq) of pituitary glands from control and high-fat diet-fed mice and characterized population changes and gene expression changes in each population. While gonadotrope population changes levels of gene expression that results in the lower gonadotropin levels, somatotrope and lactotrope populations, on the other hand, change at the population level with alterations in the cell numbers that result in altered levels of growth hormone and prolactin in the circulation. In summary, we defined diet-induced changes in pituitary hormone production and population shifts that may play a role in altered hormone production in obese patients and consequently dysregulation of homeostasis. Presentation: Friday, June 16, 2023

SAT230 A Case Of Pseudohypoparathyroidism Without Any Hereditary Features

Abstract Disclosure: I. Haque: None. L.A. Robles: None. Background: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders characterized by resistance to parathyroid hormone. PHP type Ib is characterized clinically by isolated renal PTH resistance manifesting as hypocalcemia, hyperphosphatemia, and increased serum PTH. About 60-70% of patients also present with elevated TSH levels due to TSH resistance. We present a unique case of adult onset PHP. Clinical Case: A 30-year-old woman admitted to the hospital for recent onset recurrent hypocalcemia with symptoms of weakness, muscle spasm and cramps. Until recently she was in a normal state of health. Admission labs revealed ionized calcium 0.78 (1.15 - 1.30 MM/L) , serum Ca 6.2 (Albumin 4.3). PTH elevated to 364. Creatinine 0.54 mg/dl, GFR 131 ml/min. Vit D level 35, Bone ALP 49.3 (premenopausal female :4.5-16.9 UG/L), Mag 1.9 , Ph 6.6. A 24-hour urine collection for Ca showed a value of 14 mg/24hr (50 - 400 MG/24H). Additionally, she was found to have a TSH &amp;lt;0.01 and Free T4 1.1. These labs confirmed PTH-resistant hypocalcemia and hyperphosphatemia with concurrent hyperthyroidism. Thyroid Ultrasound demonstrated a possible parathyroid adenoma on the left measuring 0.8x0.4x0.7 cm, which we suspect was a result of hyperplasia from PTH hypersecretion secondary to PTH resistance. TSI and TRAB antibodies were later found to be positive confirming grave’s hyperthyroidism. She had a similar presentation about 3 months earlier with symptomatic hypocalcemia and was discharged on Calcitriol, Ca CO3, and Cholecalciferol. Prior to this including through childhood, patient denies symptoms or lab abnormalities. Patients’ physical exam shows a height of 5ft 4-inch, weight 78kg, BMI 29.7. She had no abnormal facial features or skeletal/digit abnormalities. Patient reached all physical and cognitive milestones at expected times through childhood. Her calcium supplementation was adjusted to calcium carbonate 2000 mg every 8 hours, calcitriol 1 mcg twice daily, cholecalciferol 1000 units daily. Her total calcium improved to 7.4, ionized calcium improved to 0.93, phosphorus remained elevated at 6.1. Patient was discharged at her will due to personal social commitment. She was also started on Methimazole 5mg daily on discharge. Follow up labs showed Ca remained stable and eventually normalized on the above Ca supplementation 6 months after discharge. Conclusion: Unlike PHP Ia, patients with PHP Ib usually lack the physical characteristics of Albright hereditary osteodystrophy (round facies, short stature, short metacarpal bones (especially III-V), obesity, subcutaneous calcifications, and developmental delay), and typically show no other endocrine abnormalities, although our patient presented with subclinical hyperthyroidism. Typically, PTH-resistance disorders present as symptomatic hypocalcemia in childhood, however our patient presented in adulthood. Presentation: Saturday, June 17, 2023

SAT346 Empty Sella Syndrome And Hypopituitarism In A Childhood Cancer Survivor

Abstract Disclosure: W. Akhter: None. J.L. Gilden: None. Introduction: It has been reported that 50% of childhood cancer survivors develop an endocrinopathy and require life-long monitoring. Hypopituitarism is common in patients who have been treated with radiotherapy and is progressive and irreversible. We present the case of a young cancer survivor, referred for evaluation of secondary amenorrhea and hyperprolactinemia., who was diagnosed with empty sella syndrome and hypopituitarism. Clinical Case: A 29-year-old female with past history of right maxillary rhabdomyosarcoma at age 15, treated with chemotherapy and radiation, was referred to the endocrinology clinic for evaluation of secondary amenorrhea and hyperprolactinemia. Menarche was at age 13, and stopped when starting chemotherapy and radiation. She had not been treated with hormone replacements or dopamine agonists. Upon evaluation, she had fatigue, lethargy, generalized muscle weakness, but denied headaches, fractures, abdominal pain, galactorrhea, and vaginal dryness. Laboratory revealed hypopituitarism with low estradiol &amp;lt;15 (nl=30-400 pg/ml premenopausal women, &amp;lt;10 pg/ml postmenopausal women) with inappropriately low FSH 0.82 (nl=1.5-12.4 mIU/ml), and low LH 0.22 (nl=5-25 IU/L premenopausal female), high prolactin 41.3 (nl=non-pregnant female &amp;lt;25 ng/mL, pregnant female 80-400 ng/mL), negative HCG, low cortisol 3.4 (nl=5-25 mcg/dL), low ACTH 9.7 (nl= 10-60 pg/mL), normal TSH 2.446 (nl=0.27-4.20 uIU/mL) and Free T4 0.54 (nl=0.5-1.6 ng/dL), negative thyroglobulin &amp;lt;1 (nl=0-4 IU/mL) and thyroid peroxidase AB 0.46(n=0-9 IU/mL), normal HbA1C 5.2(nl&amp;lt;5.7 %). MRI pituitary with contrast done 11 yrs. earlier showed a 1.5 mm focus of relative delayed and nonenhancement between anterior and posterior pituitary gland, as well as an overall volume of the pituitary smaller than expected for age. However, recent repeat MRI of brain and sella revealed a partially empty sella without evidence of macro or microadenoma. Conclusion: Patients with childhood malignancies have a greater chance of survival, as observed in the past 30 years. It is now recognized that disorders of the hypothalamic-pituitary axis can occur at any time in patients who have undergone radiation therapy. We should be aware that empty sella syndrome, which can be caused by radiation, can also be associated with hormonal abnormalities. Studies have reported that 50 % of patients with empty sella syndrome had endocrine dysfunction, with the most common endocrine abnormality being hyperprolactinemia. Therefore, amenorrhea in our patient could be from hypopituitarism caused by radiation and empty sella, as opposed to hyperprolactinemia. When evaluating amenorrhea our focus should not be entirely on hyperprolactinemia, but a diagnosis of empty sella syndrome can be missed, thus delaying appropriate hormonal replacement therapy. Presentation: Saturday, June 17, 2023

SAT498 A Challenging Case of Hypothyroidism Requiring Frequent Primary Care Visits to Achieve Euthyroidism

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: We report a patient with persistent primary hypothyroidism despite multiple adjustments in thyroid medication. Clinical Case: A 67-year-old white man with multinodular goiter underwent total thyroidectomy in 2016 for abnormal thyroid nodule biopsy. Surgical pathology revealed papillary thyroid cancer with lymph node metastasis. He subsequently received radioactive iodine ablation treatment. His plasma thyroid stimulating hormone (TSH) level was noted to be 0.275 uIU/mL (normal range 0.35-4.00 uIU/mL) in January 2017 on levothyroxine 224 micrograms daily. Subsequently, his plasma TSH level continued to remain elevated with variable levels despite multiple titrations of his levothyroxine dosage, counseling, and multiple follow-up visits. Plasma TSH level went up as high as 108.140 uIU/mL (normal range changed to 0.55-4.78 uIU/mL). In January 2022, plasma TSH level normalized to 3.125 uIU/mL with high plasma free thyroxine level of 2.45 ng/dL (normal range 0.89-1.76 ng/dL), but plasma TSH level increased again to 5.190 uIU/mL in April 2022. Home care nurse was involved in monitoring of the patient taking thyroid medication daily and correctly but was unsuccessful. The patient and his son reported taking thyroid medicine daily and correctly. There was no concern for malabsorption or interference with any of his medications. The patient was subsequently asked to come to primary care clinic every week for six weeks with all his medications. He was unable to come to endocrinology clinic due to travel time being more than one hour. His repeat plasma TSH normalized to 1.010 uIU/mL. The etiology of previously high plasma TSH level was suspected due to non-compliance with taking his thyroid medication. Non-compliance was discussed in detail with the patient and his son, including life-threatening consequences of hypothyroidism. The patient verbalized understanding and was willing to comply with the recommendations. The patient was then asked to stop coming weekly to primary care clinic. Repeat plasma TSH level in October 2022 was again noted to be high at 80.723 uIU/mL. He again claimed compliance, but weekly visits to primary care clinic were resumed. In December 2022, he was noted to have low plasma TSH level of 0.232 uIU/mL. Conclusion: Once weekly visits seem impractical but might be required in a certain group of patients with persistent abnormal thyroid hormone levels where no etiology can be found. Presentation Date: Saturday, June 17, 2023

SAT467 Monitoring TSH Over Time May Not Be Necessary in Patients With Thyroid Nodules

Abstract Disclosure: S. Kaul: None. A. Gupta: None. Introduction: A substantial number of patients with thyroid nodules receive monitoring of blood thyroid stimulating hormone (TSH) levels after the initial diagnosis. There is not enough literature supporting long-term monitoring of blood TSH levels in these patients with thyroid nodules. The objective of this study was to evaluate the change in blood TSH level in patients with known thyroid nodules over time and to determine if repeat blood TSH testing is required in these patients. We hypothesized that monitoring of blood TSH level is not warranted in patients with thyroid nodules in the absence of a history of medical conditions or medications that are known to affect thyroid hormone levels. Methods: We studied 100 patients aged 18 to 99 years at the Dayton VA Medical Center with at least one thyroid nodule on imaging studies from January 2010 to December 2016 with normal blood TSH level at time of the diagnosis of the thyroid nodule. Subjects with abnormal thyroid hormone level, history of hot thyroid nodule, autoimmune thyroid disease (on imaging or blood work), thyroid or pituitary surgery, radioactive iodine treatment, neck irradiation, or usage of thyroxine or any other medications known to affect thyroid hormone levels were excluded. Blood TSH level at the time of diagnosis of thyroid nodule and after were retrospectively studied and analyzed for 100 subjects. Normal blood TSH level range at time of diagnosis was noted to be 0.35-5.50 uIU/mL or 0.35-4.00 uIU/mL depending on the assay method used. Normal repeat blood TSH level range was noted to be 0.35-5.50 uIU/mL, 0.35-4.00 uIU/mL, or 0.55-4.78 uIU/mL depending on the assay method used. Results: 100 subjects with normal blood TSH at the time of diagnosis of their thyroid nodule had blood TSH level monitoring for an average time period of 5.74 years. Out of the 100, six subjects (6%, 95% CI [2.52%, 12.73%]) developed an abnormal blood TSH level in a mean time period of 6.94 years. One subject’s initial blood TSH level increased from 3.38 uIU/mL to 7.76 uIU/mL after 8.52 years. This subject did not receive treatment with thyroxine. In the other five subjects, blood TSH level decreased to below normal range in a mean time period of 6.63 years and ranged from 0.25-0.52 uIU/mL. Blood TSH level remained within normal range for 94 subjects in a mean time period of 5.67 years. Conclusion: Monitoring of blood TSH level over time may not be required in most patients with thyroid nodules in the absence of symptoms, medical conditions, or medications that are known to affect thyroid hormone levels. Presentation Date: Saturday, June 17, 2023

FRI253 Concurrent Adrenal Insufficiency And Hyperthyroidism In A Breast Cancer Patient Treated With Pembrolizumab Therapy

Abstract Disclosure: A.U. Kulkarni: None. D.T. Patel: None. E.B. Ruby: None. Anti-programmed cell death-1 (Anti-PD1) antibodies (e.g., Pembrolizumab) are immune checkpoint inhibitors that are widely in use for the treatment of many advanced malignancies. This has resulted in various side effects known as irAEs (immune-related adverse events). Endocrine irAEs include hypophysitis, adrenal insufficiency (AI), hypothyroidism, and hyperthyroidism. A 40-yo female with a history of recently diagnosed triple-negative breast cancer, status post chemotherapy, and immunotherapy with Pembrolizumab (last treatment a month prior to presentation) came in with fatigue, weight loss, and persistent vomiting for two weeks. Her initial BP was noted to be 80/50 mmHg, with HR 108bpm. She appeared weak and tired with no other abnormalities on physical exam. The thyroid was normal with no enlargement. Significant labs were creatinine 1.4mg/dL (0.4-1.3mg/dL), corrected calcium 12.8mg/dL, TSH of &amp;lt;0.01mUI/L and fT4 of 4.47ng/dL (0.61-1.12ng/dL) (thyroid tests were previously normal). The patient was admitted to the ICU for hypovolemic shock refractory to IV fluids and endocrinology was consulted for multiple hormonal abnormalities. AKI and hypercalcemia were likely from dehydration as they subsequently resolved with IV fluids. AM cortisol level was low at 0.7ug/dL(3-16ug/dL). The cosyntropin test was positive, confirming AI. ACTH level was &amp;lt;5pg/mL (normal&amp;lt;46pg/mL) indicating a diagnosis of secondary AI, likely from immunotherapy. She was initiated on IV hydrocortisone. MRI brain was obtained to evaluate for hypophysitis which was unremarkable. Further thyroid testing was pursued which showed negative Thyroid peroxidase and anti-thyroglobulin antibodies. Thyroid scan showed a focal hot nodule in the left lobe suspicious for an autonomous nodule. She was started on beta blockers and methimazole with the goal of optimizing her thyroid function prior to her elective mastectomy. Pembrolizumab was discontinued with the plan to re-challenge after surgery. BP stabilized and she was discharged home on hydrocortisone with close outpatient follow-up with Endocrinology and Oncology. The clinical manifestations of Anti-PD1-associated AI are very non-specific and difficult to diagnose as they can be confused with the cancer-related illness itself or chemotherapy. Multiple endocrine abnormalities on initial labs with recent Pembrolizumab therapy in our patient raised suspicion for irAEs. Even though the occurrence of AI from anti-PD1 drugs is extremely rare, being &amp;lt;1%, it can be life-threatening. Very few cases of Anti-PD1-induced thyroid dysfunction have been reported, however further testing in our patient confirmed hyperthyroidism from a toxic thyroid nodule. With the increasing popularity of these drugs, endocrinological complications are on the rise, and we as clinicians need to be vigilant and intervene at an early stage to prevent irreversible and fatal outcomes. Presentation: Friday, June 16, 2023

SAT438 Nivolumab Induced Endocrinopathies- Outcomes And Learning

Abstract Disclosure: K. Kethireddi: None. S. Jhetam: None. S.B. Parthasarathy: None. Background: Nivolumab is an anti PD-1 mAB (Programmed Cell Death protein) used in the treatment of melanoma, renal, head &amp; neck and other cancers. Use of Nivolumab either as a single therapy or in combination with other immune check point inhibitors (CPI) like Ipilimumab, Pembrolizumab often results in immune mediated endocrinopathies. Existing literature on Nivolumab indicates median time to the onset of hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, and hypophysitis as 1.5 months, 2.9 months, 4.4 months and 4.9 months respectively. Our objective is to add to the existing body of knowledge, compare local data on presentation and other variables of these endocrinopathies with recommendations to improve diagnosis and access to treatment of these endocrinopathies. Design: It is a retrospective analysis of the patients who received Nivolumab (single or combination therapy) between 2019 and 2022 in our hospital. Methodology: A total of 83 patients were treated either with single therapy Nivolumab (n=44) or combination therapy (n=39) and were screened for immune endocrine toxicities. Data was collected mainly from hospital based clinical software for routine use. Data was also collected on prior endocrine tests such as Hba1c and Thyroid function, if done prior to commencement of immunotherapy. Major results: Nineteen patients (23%) developed immune related endocrinopathies which included Thyroiditis/hypothyroidism (n= 12) followed by adrenalitis (n= 6), Type 1 Diabetes (n=1) and hypophysitis (n=3). Onset of thyroid dysfunction occurred between 4 to 8 weeks, adrenalitis between 8 to 32 weeks, hypophysitis between 4 weeks to 12 weeks and 24 weeks for type 1 diabetes mellitus. All patients were appropriately counselled and were provided with Patient Information leaflet. Regular screening bloods (Hba1c, Glucose, Cortisol and Thyroid function tests) were requested in most patients. Emergency presentations of Diabetic ketoacidosis (n=1) and Adrenal insufficiency (n=2) were noted with no mortality. Conclusion: 23% of the patients on Nivolumab had immune mediated endocrinopathy with Thyroiditis/Hypothyroidism being the commonest and the earliest endocrine abnormality. A Standard Operating Procedure for acute endocrine emergencies post Immunotherapy based on Society for Endocrinology guidance, needs to be implemented with education to create greater awareness given the expected high prevalence of these endocrinopathies post Immune CPI therapies. We recommend oral steroid (prednisolone/hydrocortisone) rescue pack and patient education on SMBG (Self-monitoring of blood glucose) as a part of sick day rule management in these patients and we believe this to be lifesaving and resource saving measure given the critical nature of these endocrine emergencies post immune CPI therapies. Presentation: Saturday, June 17, 2023

FRI306 Natural History Of Untreated Prolactinoma

Abstract Disclosure: M. Sadek: None. N. Sandila: None. D.B. Clarke: None. S.A. Imran: None. BACKGROUND Prolactinomas (PRLomas) are the most common functioning pituitary tumors, and the majority are microPRLomas (&amp;lt;10 mm in size). Current guidelines do not support treating asymptomatic or minimally symptomatic microPRLomas based on older studies utilizing insensitive imaging and assay techniques, whereas only limited information is available about the natural history of microPRLomas based on new generation assay and advanced imaging modalities. OBJECTIVES This study aims to assess the natural history of medically untreated microPRLomas with regards to long-term trends of serum PRL, tumor growth, clinical symptoms, and their effect on other pituitary function. METHODS We conducted a retrospective review of all patients diagnosed with microPRLoma since 2005 from our comprehensive provincial pituitary registry in Nova Scotia, Canada. Secondary causes of hyperprolactinemia were excluded. Outcomes were extracted at diagnosis and each follow-up visit. PRL, % above upper limit of normal (AULN) and tumor size (mm) were modelled using linear mixed effects models and clinical symptoms were analyzed with McNemar’s Test. Increase in PRL was modeled with exact logistic regression with change in tumor size and symptoms as predictors. RESULTS A total of 28 patients were identified; median age at diagnosis was 37 yrs (IQR 27.5 - 47.5) and median follow-up was 70 months (IQR 41.5 - 123.5). No patient had additional pituitary hormonal abnormality except gonadal dysfunction. Median tumour size at diagnosis was 3 mm (IQR 2 - 4), and median PRL (AULN) was 50% (IQR 15.2 - 113.3). Twenty four (85.7%) had symptoms at diagnosis including: galactorrhea, oligomenorrhea and amenorrhea. At last follow-up, those without symptoms at diagnosis remained asymptomatic and the majority (80%) with symptoms at presentation had complete resolution of symptoms (p&amp;lt;0.01). Only 20% had persistent symptoms, commonest being galactorrhea, but none had worsening of symptoms. There was no evidence of any association between elevated serum prolactin and persistent symptoms. Overall, mean change in tumor size (mm) was -0.9286 (p-value = 0.0138), of which, 2 patients (7%) had an increase since diagnosis (mean increase = 2.5 mm) while the rest (93%) had either no change or a decrease in tumor size. Serum PRL (AULN) when adjusted for change over time (month) over during the entire follow-up period decreased in 20 (71.4%) patients by a median of -0.00793 (IQR -0.01556 - -0.00597) and increased in 8 (28.6%) by a median of 0.00321 (IQR 0.00181 - 0.01549).CONCLUSIONS Although limited by sample size, these findings suggest that when left untreated, the majority of microPRLomas remain stable both in terms of size and PRL values and clinical symptoms resolve in most patients over time. Presentation: Friday, June 16, 2023