bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON94 Collision tumor with Rathke cleft cyst and co existing Cushing's disease
Authors: Mittal Ashima , Jaiswal Gayatri 
Published: November 2022

Abstract

Introduction
- Collision tumors, i.e., co-occurring distinct histopathological lesions are rare. We present a case of a 48-year-old female present with co-existing Rathke cleft cyst (RCC) and pituitary adenoma with Cushing disease.

Case
- 48-year-old female presented for evaluation of an incidental sellar mass with enlarged pituitary noted on MRI brain. The patient complained of symptoms of mental fogginess, confusion, intermittent dizziness for the last 1 year. The patient had complained of easy bruising with no reported weight gain, change in facial appearance, proximal muscle weakness. MRI brain showed mildly enlarged pituitary measuring 13 mm with RCC.Past medical history was significant for recent-onset Type 2 Diabetes and Hypertension. The examination was unremarkable with no signs of Cushing's syndrome. Lab work showed elevated ACTH of 51 pg/ml (10-48) with AM cortisol level of 14.7 mcg/dl (6- 18.4). IGF-1 levels elevated at 307 ng/ml (77- 220). LH, FSH, FT4, prolactin levels were normal. Given elevated ACTH levels, further testing showed elevated midnight salivary cortisol at 0.22 and 0.239 mcg/dl (0.010-0.090), elevated 24-hour urine cortisol 141 ug/ 24 hrs. (6- 44), absence of suppression with 1 mg dexamethasone with cortisol 12.4 mcg/dl (&lt; 1.8), ACTH 123 pg/ml (10-48) with dexamethasone levels 432 ng/dl (140- 295). Lab work was consistent with ACTH-dependent hypercortisolism. MRI pituitary showed 7.5×7.8 mm RCC.8 mg dexamethasone suppression test and CT chest, abdomen, and pelvis were performed to differentiate between ectopic Cushing's and Cushing's disease. Cortisol levels suppressed greater than 50% after 8 mg dexamethasone from baseline cortisol – 17.7 mcg/dl and ACTH 67 pg/ml to cortisol 3.4 mcg/dl and ACTH – 34 pg/ml with dexamethasone levels of 3120 ng/dl (1600–2850). CT chest abdomen, pelvis showed no evidence of bronchial carcinoid or other potential lesions. With neuroimaging findings and biochemical confirmation of Cushing's disease, the patient underwent transsphenoidal resection.

Discussion
– The association between RCC and pituitary adenoma was found in 0.5–1.9% cases per literature review1, co-occurrence with ACTH producing pituitary adenoma being rarer. The diagnosis of collision tumors can be challenging as the most common presentation on imaging is a cystic mass. Appropriate biochemical testing is indicated based on clinical presentation, initial laboratory testing, and level of suspicion. Elevated ACTH levels along with diabetes and hypertension led to a diagnosis of Cushing's disease in our patient with the initial presentation of an incidental RCC. The knowledge about collision tumors is important, especially in unusual presentations as in our case.

References
Sagan KP et al. Cushing's Syndrome in a patient with Rathke's cleft cyst and ACTH cell hyperplasia detected by 11C-Methionine PET Imaging-A Case Presentation. Front Endocrinol (Lausanne). 2020; 11: 460. Published 2020 Jul 22.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
OR08-5 Associations Between Signal Transducer and Activator of Transcription (STAT) Mutations and Galactorrhea
Authors: Al-Naqeeb Ghadah , Cypess Aaron , Zenno Anna , Jumani Sanjay 
Published: November 2022

Abstract

Background
Prolactin (PRL) is responsible for the development of mammary glands and milk production. STAT1 and STAT3 are genes that express transcription factors that mediate PRL's intracellular signaling, but an association between their function and galactorrhea has not yet been identified. Here we describe three patients with somatic STAT mutations and galactorrhea.
A 27-year-old woman with hyper-IgE syndrome (Job's Syndrome) due to a STAT3 deletion mutation (p.Val463del) associated with recurrent infections reported thin, white, bilateral discharge with breast manipulation beginning in adolescence. She did not have spontaneous leakage or pain. At presentation, PRL was slightly elevated to 27.9 (ref. 2.0-25.0 mcg/L) with otherwise normal levels of anterior pituitary hormones. She was not on any drugs known to cause hyperprolactinemia. MRI showed a 5×4 mm microadenoma without any mass effect.
A 32-year-old woman also with Job's syndrome due to a heterozygous loss-of-function STAT3 mutation (p.R382Q) associated with recurrent infections and papillary thyroid cancer described unilateral, chronic, thin, white nipple discharge with light touch of her right breast for "as long as she could remember." She had a history of breast abscesses, but at presentation there was no evidence of abscess or infection. PRL was 15.1 mcg/L, and other anterior pituitary hormones were normal. MRI showed a structurally normal pituitary.
A 22-year-old woman with a STAT1 activating mutation (p.E235A) associated with recurrent infections, autoimmune hypothyroidism, T1DM, and hypogonadotropic hypogonadism requiring pubertal induction at age 12y reported bilateral galactorrhea starting at age 18y. A white, milky discharge could be expressed with light manipulation, but no discharge was produced spontaneously. PRL was 16.2 mcg/L with serial dilution and has consistently been in the reference range. Anterior pituitary evaluation was normal except for elevated TSH of 12.5 (ref. 0.27-4.2) consistent with autoimmune hypothyroidism. MRI revealed a diffusely enlarged pituitary gland (12mm in the cranio-caudal dimension) without focal hypo-enhancement.

Conclusions
It is known that PRL signaling involves the JAK/STAT pathway, and an analysis of human milk cells showed upregulated STAT3 and downregulated STAT1 during lactation (PMID 26909879). These three cases provide clinical evidence for a mechanistic connection between STAT signaling and galactorrhea and suggest that STAT3 and STAT1 function in opposite directions to regulate lactation. In our cases, increased STAT1 or decreased STAT3 activity are associated with normal-PRL, inducible galactorrhea. Beyond understanding the specific intracellular signaling pathways leading to galactorrhea, these observations may be utilized for developing therapies for those with impaired lactation.
Presentation: Saturday, June 11, 2022 12:30 p.m. - 12:45 p.m.
ODP042 Hereditary Pheochromocytoma with a Novel Mutation in the Succinate Dehydrogenase Subunit A gene
Authors: Karuppasamy Gowri , Farooqi Amer , Sajid Sadia , Elouzi Elhadi 
Published: November 2022

Abstract
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumorswith a diverse clinical presentation. Pathogenic variants in the genes encoding different subunits of the succinate dehydrogenaseenzyme complex that plays a central role in energy metabolism,have been linked to hereditary PPGL syndromes. Here wereport a rare case of hereditary pheochromocytoma with a novel mutation in the succinate dehydrogenase subunit A (SDHA) gene. A middle aged woman presented with left sided abdominal pain and was incidentally found to have bilateral adrenal lesions on abdominal imaging. She denied any symptoms of catecholamine excess but her plasma metanephrines level was elevated. Family history was significant for breast cancer in her motherand sister. Computed tomography (CT) scan of the abdomen showed bilateralbulky adrenal glands with a lesion in theleft adrenal gland. Magnetic resonance imaging (MRI) abdomen was performed for further characterization, the lesion measured approximately 2.8×2.6 cm with imaging characteristics suggestive of pheochromocytoma. Iodine-131 Metaiodobenzylguanidine (MIBG) whole body scan showed abnormal focal radiotracer uptake at the left adrenal gland, and she then underwentleft sided robotic adrenalectomy. Following surgery, the patient had symptomatic relief. Histopathology confirmed the diagnosis of pheochromocytoma measuring 2×2×1.5 cm with PASS (Pheochromocytoma of the Adrenal gland Scaled Score) score of 1/10, due to cellular monotony. Genetic testing revealed that she was positive for a pathogenic mutation in the SDHA gene consistent with the diagnosis of hereditary PPGL syndrome. Genetic testing was performed for the patient due to her presentation with bilateral adrenal masses and family history of cancers. Guidelines recommend genetic testing for patients with features that indicate a high likelihood of a hereditary cause for PPGL, including positive family history, syndromic features, and multifocal, bilateral, or metastatic disease. SDHA mutated PPGLs have diverse phenotypes and may be at high risk of metastasis. They are also associated with extra-adrenal tumors, include gastrointestinal stromal tumours (GIST), pituitary adenomas, papillary thyroid carcinoma, renal carcinoma and breast carcinoma. The detection of susceptibility genes for hereditary PPGL syndromes has key implications, for surveillance to detectextra-adrenal disease and recurrent tumors, as well as for consideration of genetic testing forfamily members.
Presentation: No date and time listed
PMON181 RGS4 Is Essential For The Sympathetic Regulation of The Short-chain Fatty Acid Receptor FFAR3 In The Heart
Authors: Carbone Alexandra , Cora Natalie , Desimine Victoria , Ghandour Jennifer , Goldberger Jeffrey , Iacobellis Gianluca , Suster Malka , Valiente Rachel , Wang Gaofeng , Lymperopoulos Anastasios 
Published: November 2022

Abstract

Background
Free fatty acids (FFAs) are essential cell nutrients but also important signaling molecules regulating various cellular processes. Short-chain fatty acids (SCFAs), like propionate and butyrate, activate two different types of G protein-coupled receptors (GPCRs), FFAR2 and FFAR3. FFAR3 (also known as GPR41) couples to Gi/o proteins lowering cyclic 3', 5'-adenosine monophosphate (cAMP) levels and activating mitogen-activated protein kinases (MAPKs). In addition to adipose tissue, FFAR3 is highly expressed in peripheral sympathetic ganglia augmenting sympathetic nervous system (SNS) outflow. Regulator of G protein Signaling (RGS)-4 belongs to the RGS superfamily of proteins and inactivates (terminates) both Gi/o- and Gq-protein signaling. Cardiac RGS4 has been implicated in atrial fibrillation (AFib) prevention via calcium signaling attenuation. Finally, β-adrenergic receptors (ARs), the major mediators of catecholaminergic and SNS actions in cardiac myocytes, stimulate cAMP synthesis and activate protein kinase A (PKA), which is known to activate RGS4 via phosphorylation.

Objective
We examined whether RGS4 regulates cardiac FFAR3 signaling.

Methods
We used H9c2 cardiomyocytes transfected to express the human FFAR3. After treatment with catecholaminergic agonists and/or propionic acid plus various pharmacological inhibitors and siRNA to deplete RGS4, we performed signaling assays (western blotting, cAMP accumulation, GTP binding, ELISA) to delineate the precise involvement of RGS4 in the cardiac βAR-FFAR3 signaling crosstalk.

Results
RGS4 is essential for the dampening of propionate/FFAR3-dependent signaling in H9c2 cardiomyocytes since siRNA-mediated RGS4 depletion significantly enhances the effect of propionic acid on cAMP lowering, Gi/o activation, and p38 MAPK activation. Notably, concomitant isoproterenol or salbutamol treatment blocks propionic acid-induced signaling via the FFAR3 in H9c2 cardiomyocytes, indicating negative regulation of FFAR3 by catecholamines via the β2AR. Mechanistically, this is mediated by RGS4, since neither isoproterenol, nor salbutamol can inhibit propionate signaling upon siRNA-mediated RGS4 depletion. Finally, β2AR inhibition of FFAR3 signaling via RGS4 is dependent on β2AR-activated PKA, because pre-treatment with the PKA inhibitor H89 abrogates the catecholaminergic inhibition of FFAR3 signaling in H9c2 cardiomyocytes, as measured by cAMP lowering, downstream p38 MAPK activation, and interleukin (IL)-6 production.

Conclusion
Catecholamine-activated RGS4 abrogates SCFA/FFAR3 signaling and function in cardiac myocytes. This may represent part of the mechanism via which RGS4 protects against both AFib pathogenesis and FFAR3-promoted SNS hyperactivity and inflammation in the myocardium.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP372 A Rare Case Of Cornelia de Lange Syndrome With Hyperinsulinism And Hypopituitarism
Authors: Greve Katherynne , Chang Eric 
Published: November 2022

Abstract

Background
Cornelia de Lange syndrome (CdLS) is characterized by slow growth with short stature, intellectual disability with developmental delays, distinctive facial features, and limb defects. Various genetic mutations have been associated with CdLS, with approximately 60% of cases having a mutation in the NIPBL gene. There are few published reports of endocrine disorders in individuals affected by CdLS.

Clinical Case
A four month old female was admitted for hypoglycemic seizures. She had previously undergone workup for CHARGE syndrome. Physical exam was remarkable for acrocephaly, malar hypoplasia, hypertelorism with downslanting eyes, hirsutism, and bradydactyly. During her hospitalization, she remained persistently hypoglycemic despite repeated dextrose boluses, prompting a scheduled fasting test. Results indicated severe hypoglycemia (37 mg/dL) with inappropriate suppression of beta-hydroxybutyrate (0. 08 mmol/L) and negative urine ketones. Her glucagon stimulation test result showed an exaggerated increase of the glucose greater than 30 mg/dL after glucagon administration (glucose was 31 mg/dL at the start of the test; peak glucose was 77 mg/dL after receiving 0. 03 mg/kg of glucagon), indicating excessive glycogen stores. These findings were consistent with hyperinsulinism. Furthermore, she was found to have an undetectable cortisol (&lt;1. 0 ug/dL) with hypoglycemia, prompting a low dose ACTH stimulation test with results consistent with central adrenal insufficiency (baseline ACTH: &lt;5 pg/mL, baseline cortisol: &lt;1. 0 ug/dL, peak cortisol after receiving 10 micrograms of cosyntropin was 1.1 ug/dL). Additional evaluation revealed a low free T4 (0.5 ng/dL). Interestingly, the initial TSH was 6.46 uIU/mL, which later became undetectable (&lt;0. 05 uIU/mL), consistent with central hypothyroidism. Ultimately, a brain MRI showed sella turcica hypoplasia with absence of the dorsum sella as well as corpus callosum hypoplasia and a thin pituitary infundibulum. The child was treated with diazoxide, hydrocortisone, and levothyroxine with improvement in clinical course. Genetic testing eventually confirmed CdLS, showing a heterozygous variant mutation (c.8077_8079dupGAC: p. D2693dup) in exon 47 of NIPBL gene, classified as autosomal dominant.

Conclusion
There are very few clinical reports that mention either hyperinsulinism or hypopituitarism in an individual affected by CdLS. This patient is a rare documented case of CdLS presenting with both hyperinsulinism and hypopituitarism. Further understanding of the different genetic mutations seen with CdLS could help identify atypical forms of CdLS associated with endocrinopathies and more clearly direct unifying treatment.
Presentation: No date and time listed
ODP378 Biliary Sludge in a Neonate with Congenital Hypothyroidism
Authors: Dorado Juan Pablo Hayes , ALACA Fortunato Amachuy , Vargas Gerben Justiniano , Ortiz Alexis Bellot , Ayala Marco Antonio Calla , Tapia Emilene Coca 
Published: November 2022

Abstract

Background
Most cases of congenital hypothyroidism are asymptomatic. When signs are evident, they are nonspecific. Characteristic clinical findings, including prolonged jaundice are seen in less than 5% of affected neonates.

Clinical Case
Female newborn, full term, appropriate weight for gestational age, five days old, Kramer zone 3 jaundice. The laboratory ruled out hemolysis, blood group incompatibility and TORCH infections. Hepatobiliary ultrasound showed biliary sludge. The screening for congenital hypothyroidism reported a TSH value of 38 mlU/L; the free T4 value was analyzed and was low. With the diagnosis of congenital hypothyroidism, levothyroxine therapy was started. The biliary sludge disappeared two weeks after initiation of hormone therapy.

Conclusion
It is important to exclude other causes of biliary sludge formation, such as sepsis, parenteral nutrition, hemolytic disease, metabolic diseases, some drugs and pyloric stenosis. Congenital hypothyroidism may be associated with biliary sludge formation; thyroid hormones have an inhibitory effect on the contractility of the sphincter of Oddi.
Presentation: No date and time listed
ODP383 Clinical Presentation and Management of Diabetes Mellitus in Youth with Prader-Willi Syndrome
Authors: Paprocki Emily , Eickhoff Paige , Sweeney Brooke , Halpin Kelsee 
Published: November 2022

Abstract

Background
Diabetes mellitus (DM) is reported in 7–24% of adults with PWS. It is thought that abnormal glucose metabolism develops as a consequence of severe obesity and/or insulin resistance. Given obesity and insulin resistance often develop in childhood in children with PWS, DM occurs in youth as well. There are limited data detailing the clinical presentation of DM, diabetes complications, and therapies used in pediatric patients with PWS.

Methods
A retrospective chart review of patients less than 21 years of age with genetically confirmed PWS seen July 2014 through July 2021 was performed. Patients were included if they also had a diagnosis of DM based on a single value meeting American Diabetes Association criteria: fasting blood glucose of ≥ 126 mg/dL, HbA1c ≥ 6.5%, 2-hour blood glucose of ≥ 200 mg/dL on oral glucose tolerance test, or random blood glucose of ≥ 200 mg/dL with symptoms of hyperglycemia.

Results
Of the 88 patients identified with PWS, nine (10%) were found to have DM. Means and range sat diabetes diagnosis were age 11.4 years (7–16), HbA1c8.2% (6.6– 12.4), BMI 38.7 kg/m2 (23.1–73.6),and BMI z-score2.4 (1.3–3.1). Five patients were female. Six patients were non-Hispanic white, two non-Hispanic black, and one Hispanic. Of these nine patients with DM, six had at least three diabetes autoantibodies assessed. All antibodies were negative in three patients, two patients had a weakly positive islet cell antibody only, and one patient had all four autoantibodies positive. Most patients were identified incidentally on screening laboratory evaluation in clinic, two patients had polyuria, and one patient was admitted with vomiting and mixed diabetic ketoacidosis/hyperosmolar hyperglycemic syndrome (DKA/HHS). Diabetes treatment methods included one patient on metformin only; four on metformin and insulin; three on metformin, insulin, and GLP1 receptor agonist; and one patient on insulin only. Of the six patients on insulin, only two were using short acting insulin with meals. No patients were treated using insulin pumps or continuous glucose monitors. No patients underwent bariatric surgery. Only one patient had hypertension requiring treatment with medication. No patients had nephropathy, dyslipidemia, neuropathy, or retinopathy.

Conclusions
DM is seen in children with PWS and often diagnosed incidentally. Regular screening is important as development of DKA/HHS is possible if diabetes goes unrecognized. While type 2 diabetes is more common than type 1 diabetes, diabetes antibodies should be measured. Standards of care for treatment are lacking resulting in variability in therapeutic regimens. Fortunately, despite markedly elevated BMI at DM diagnosis, diabetes comorbidities are not commonly seen.
Presentation: No date and time listed
OR18-6 Tracking the Diagnosis and Progression of Madelung Deformity in Pediatric Turner Syndrome Patients
Authors: Backeljauw Philippe F , Gutmark-Little Iris , Little Kevin , Huron Alex 
Published: November 2022

Abstract

Background
Turner syndrome (TS) is a chromosomal anomaly occurring in females which presents with numerous medical and developmental manifestations including skeletal deformities. A specific developmental skeletal dyplasia seen in TS patients is Madelung deformity (MD), characterized by a growth deficiency of the distal radial physis that causes excessive radial inclination and volar tilt, with resultant ulnocarpal impaction. Surgical intervention, particularly in early stages, can halt progression of or reverse MD. Despite a considerable body of literature highlighting the presence of MD in TS, it is often underdiagnosed, in part due to a lack of data documenting the epidemiology and natural history.

Objective
Analyze the frequency of diagnosis of MD in patients meeting key radiographic threshold criteria and document the time course of the deformity in these patients using these parameters.

Methods
From a database of 264 patients with a confirmed diagnosis of TS, bone age radiographs for 187 (71%) were retrospectively measured against generally accepted cutoffs for MD using two parameters: ulnar tilt = UT and lunate subsidence = LS. For patients meeting general inclusion criteria of UT &gt; 33° or LS &lt; 0 mm, historical measurements of UT and LS were obtained using past bone ages and patients’ charts were reviewed to determine if a clinical diagnosis of MD was made.

Results
7 patients (7/187 = 3.7%) met overall inclusion criteria and had radiographs consistent with Madelung Deformity. Of these 7, only one clinical diagnosis (14%) of MD was made; this patient underwent subsequent surgical intervention. The 6 undiagnosed patients had an average UT and LS of 40.5 degrees and -4.4 mm at the time of most recent bone age (∼16.3 years old). The time-courses for 4 (UT) and 3 (LS) of the 6 non-surgical patients were plotted over time from 7.2–18.9 years of age. Patients crossed threshold at an average age of 15.3 and 13.6 years for UT and LS, respectively. Average maximum read-to-read growth rates of 5.3 degrees and 3.5 mm occurred at an average age of 15.3 (UT) and 14.2 years (LS).

Conclusion
Our results suggest MD is significantly underdiagnosed in patients with TS, highlighting the need for better screening tools to make this diagnosis. This would include physical examination looking for the characteristic wrist deformity and careful analysis of bone age radiographs at an earlier age, when corrective surgery is more likely to succeed. We recommend careful scrutiny of yearly bone age radiographs from 10-15 years of age to ensure that the diagnosis of MD is not missed, and obtaining bilateral wrist radiographs (PA and Lateral views) for verification. Future research should focus on documenting disease progression using radiographic trends, as well as assessing how onset and progression are affected by therapeutic interventions such as growth hormone.
Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.