bluuebunny/crossref_metadata_2025 huggingface dataset:
6665 A Case of Exogenous Cushing Syndrome and Acute Adrenal Insufficiency from Usage and Subsequent Withdrawal of Unregulated Glucocorticoid Supplement Ardosons
Authors: Rao Angela , Faidat Ishola Adeola , Desai Dimpi , Sellmeyer Deborah E
Published: October 2024

Disclosure: A. Rao: None. A.F. Ishola: None. D. Desai: None. D.E. Sellmeyer: None.

Introduction: Exogenous Cushing’s syndrome is a frequent complication of therapeutic glucocorticoids. Rare cases of exogenous hypercortisolism from supplements have been reported. We report the first case of exogenous Cushing’s syndrome due to an unregulated anti-inflammatory supplement called Ardosons. Clinical Case: A 47-year-old male with medical history of ankylosing spondylitis, obstructive sleep apnea, and hypertension presented to the hospital with several weeks of generalized weakness. Five weeks prior to his admission, he was evaluated by Rheumatology and started on adalimumab for ankylosing spondylitis, and all previous medications were stopped.His medication history was notable for Ardosons, an unregulated supplement he obtained in Mexico for ankylosing spondylitis that contains 25 mg of indomethacin, 0.75 mg of oral betamethasone, and 215 mg of methocarbamol. He had been taking two tablets of Ardosons daily for the past ten years, and throughout this time had noted 160 lb weight gain, worsening hypertension, and development of obstructive sleep apnea.His symptoms on hospital presentation since stopping Ardosons included weakness, nausea, vomiting, and hypotension. Clinically, he appeared Cushingoid with violaceous striae, abdominal adiposity, prominent dorsoclavicular and supraclavicular fat pads, and scattered ecchymoses. Due to these exam findings, the medical team obtained a 1 mg dexamethasone suppression test which showed morning cortisol of 1.1 ug/dL [reference range post-suppression <1.8 ug/dL]. Endocrinology was consulted and due to clinical features of acute adrenal insufficiency, in the setting of abrupt withdrawal from systemic glucocorticoids, he was started on physiologic hydrocortisone with symptomatic improvement. At his subsequent endocrinology clinic visit five weeks later, he had lost 20 lbs, and striae were less prominent. His hypothalamic-pituitary-adrenal axis has been serially reassessed and shows continued impaired adrenal function, most recently with morning cortisol of 2.9 ug/dL [reference range 6-18 ug/dL], and ACTH of 49.9 [reference range 7-63 pg/mL]. Clinical Lesson: This is the first case of exogenous Cushing syndrome resulting from usage of a medication called Ardosons, which contains a potent glucocorticoid. Abrupt withdrawal of agents like these can cause acute adrenal insufficiency and can present as a diagnostic challenge, as physical findings may paradoxically show evidence of cortisol excess. Thorough medication reconciliation and supplementation history is essential to identify potential hidden corticosteroids which can have severe and lasting systemic effects.

Presentation: 6/2/2024
6552 A soft case of Pheochromocytoma
Authors: Lai William , Delsignore Valentina , Steven Scott
Published: October 2024

Disclosure: W. Lai: None. V. Delsignore: None. S. Steven: None.

Introduction: Pheochromocytoma is a rare condition estimated to occur in less than 0.2% of patients with hypertension [1]. Symptomatology is critical in prompting suspicion for testing for pheochromocytoma with patients going undiagnosed up to 50% of the time based on one post mortem study [2]. The following is an atypical case of pheochromocytoma in which the initial presenting symptom was erectile dysfunction. Case: The patient is a 37 year old male who had been complaining of difficulty obtaining and maintaining erections as well as fatigue over the past year prior to presentation. He subsequently began experiencing frequent episodes of nausea, vomiting, headaches, sweating, palpitations, and pallor which resulted in several visits to local emergency departments. Despite having no known prior history of tachycardia or hypertension, he was found to be both tachycardic and hypertensive. Abdominal computed tomography (CT) demonstrated a septated right adrenal mass measuring 8.0x7.7x7.4cm. The lesion measured 44 Hounsfield units (HU) on pre-contrast imaging, 57 HU one minute following contrast administration, and 58 HU ten minutes following contrast administration on dedicated adrenal CT. Laboratory studies revealed serum metanephrines of 3,919pg/mL and serum normetanephrines of 3,184pg/mL as well as 24 hour urinary metanephrines of 22,154ug and 24 hour urinary normetanephrines of 8,702ug. His symptomatic episodes resolved after starting a low dose of doxazosin. He underwent laparoscopic resection of the adrenal mass with surgical pathology revealing pheochromocytoma with a Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) of 8. Serum metanephrine and normetanephrine levels and 24 hour urinary metanephrine and normetanephrine levels became undetectable following surgical intervention. His erectile dysfunction and other symptoms completely resolved. Conclusion: Pheochromocytomas can pose a diagnostic challenge and therefore require a high level of clinical suspicion based on symptoms. The classic triad for pheochromocytoma which includes headaches, sweating, and tachycardia is relatively uncommon with paroxysmal findings occurring more often. There has been only one other documented case in which the initial presenting symptom of pheochromocytoma was erectile dysfunction, but this case illustrates that erectile dysfunction should certainly be considered as one of the possible symptoms that raises suspicion for pheochromocytomas [3].

Presentation: 6/3/2024
7321 A Mixture Of PCBs Induces Sex-Specific Disruptions To Cognitive And Neuromolecular Endpoints In Grandchildren Of Exposed Rats
Authors: Hilz E N , Morales-Ledesma E , Deka J , Bhamidipati S , Thompson L , Wiley D C , Gore A C
Published: October 2024

Disclosure: E.N. Hilz: None. E. Morales-Ledesma: None. J. Deka: None. S. Bhamidipati: None. L. Thompson: None. D.C. Wiley: None. A.C. Gore: None.

Polychlorinated biphenyls (PCBs) are a weakly estrogenic class of ubiquitous environmental endocrine-disrupting chemicals that affect a range of sex-specific neuroendocrine and reproductive outcomes. Furthermore, these effects can extend intergenerationally via epigenetic changes carried down the germline. In humans, PCBs are associated with sexually dimorphic and hormone sensitive neurobehavioral disorders including attention deficit hyperactivity disorder (ADHD) and depression; however, little preclinical work has modeled these cognitive changes in rats and none has determined if they extend intergenerationally via endocrine-mediated changes to the brain. In the current work, pregnant and nursing Sprague-Dawley rats were exposed to the PCB mixture Aroclor 1221 (A1221). Male and female grandchildren of these rats, exposed preconceptionally to A1221 via the germline, underwent a battery of behavioral tasks to assess attentional phenotype, cognitive flexibility, and reward preference followed by targeted 3’ RNA sequencing (TAGseq) to assess neuromolecular changes in brain regions that support these behaviors. Results revealed that A1221 exposure had sex-specific effects. In germline-exposed females, A1221 decreased conditioned orienting suggestive of a hyporesponsive attentional phenotype and impaired attentional set-shifting suggestive of reduced cognitive flexibility; in both males and females, germline exposure to A1221 increased preference for sucrose solution indicating potential hypersensitivity to rewarding substances. From these animals, dopamine (DA) cell numbers in the midbrain significantly and negatively correlated with behavioral changes. TAGseq in regions of the brain DA system (including the prelimbic region of the prefrontal cortex, core of the nucleus accumbens, and substantia nigra and ventral tegmental area of the midbrain), revealed that molecular disruptions of A1221 were most apparent along the male germline: in the core of the nucleus accumbens, A1221 downregulated genes involved in myelination and upregulated genes involved in synaptic signaling compared to controls. Using gene ontology (GO), it was determined that GO sets involved in these processes were differentially affected throughout regions of the DA system of exposed animals in both males and females. These data show that the PCB mixture A1221 impairs different aspects of cognitive behavior between the sexes in a manner that emerges over generations, and may be mediated by both structural and molecular changes in the brain DA system. Supported by 1F32-ES034257-01A1 and R01 ES028464.

Presentation: 6/3/2024
8214 Adrenocortical Oncocytic Neoplasm Presenting As Cushing's Syndrome: A Case Report
Authors: Chu Lee Ainee Krystelle , ROSARIO M I C H A E L D
Published: October 2024

Disclosure: A.C. Lee: None. M.D. Rosario: None.

Adrenocortical oncocytoma is often non-functioning and detected incidentally. We report a case of a functioning adrenal oncocytic neoplasm referred for adrenal incidentaloma. She is a 33-year-old female hypertensive and diabetic, had 10-kilogram weight gain in a span of one year, with easy bruisability, and irregular menses for the last 10 months. Physical examination showed moon facies, buffalo hump, purple-colored violaceous striae measuring 1.2-1.4 cm in diameter, thin skin and hirsutism. There was an incidental finding of a left adrenal mass measuring 3.0 x 2.9 x 3.0 cm on CT scan. Work-up done: 1-mg dexamethasone suppression test (DST) with unsuppressed 8am cortisol at 948 nmol/L (reference range (RR) 172- 303), ACTH <1.00 pg/ml (RR 3.0 – 30.0); Total 24-hour urine metanephrine 136 mcg/24 hours (RR 115-695); Normal Plasma Aldosterone Concentration 169pg/ml (RR 57-335), and Plasma Renin Activity 21.4pg/mL (RR 5.4-34.5). She was referred for further evaluation and definitive management. CT scan with adrenal protocol showed an enhancing isodense mass in the lateral limb of the left adrenal (3.2 x 3.1 x 2.9 cm). Plain, venous and delayed Hounsfield Unit respectively as follows: +47, +84, +72 with absolute and relative wash out at 32.4 % and 14.3% respectively, worrisome for neoplasm versus metastasis. The right adrenal is unremarkable. Repeat work up showed unsuppressed 1-mg DST at 17.90 ug/dL (RR <1.8) with low 4pm ACTH 2.14 pg/ml (RR: 3.00 - 30.00). Dehydroepiandrosterone Sulfate low 3.40 ug/dL (RR: 95.80 - 511.70) with normal plasma free metanephrine 10.31pg/ml (RR: <65pg/ml). She was assessed to have ACTH-independent Cushing syndrome secondary to adrenal mass to consider malignancy and underwent left laparoscopic adrenalectomy. Pre-operatively, hydrocortisone 50 mg intravenously was given and continued every 6 hours intra-operatively. Histopathology revealed ﻿﻿adrenal cortical adenoma with oncocytic features , tumor size 3.3 cm in widest dimension, with low mitotic tumor grade (<20 mitoses per 10 millimeter square). Lymphatic and vascular invasion was not identified and all surgical margins were negative for tumor. Postoperatively, hydrocortisone was shifted to prednisone and tapered. Six months post operatively, 8 am serum cortisol (24-hour post steroid discontinuation) was adequate at 20 ug/dL with gradual improvement in the patients Cushing’s features. Nine months post-adrenalectomy, there was resumption of her regular menses and twelve months thereafter total weight loss was at 13 kilograms. Physical examination showed a remarkedly lighter violaceous striae with decreased hirsutism. Whole abdominal CT scan twelve months post operation was unremarkable. Recurrence and metastases have been described in patients with an adrenal oncocytic carcinoma post-surgery hence our patient will be closely followed-up to check for any recurrence or metastases.

Presentation: 6/1/2024
6983 Pembrolizimab Induced Hypophysitis: Uncommon Side Effect Leading To Late Diagnosis
Authors: Chaudhary Taibah , Syed Omar , Shridar Archana , Kaur Ravleen , Chaudhary Omaima , Zubair Muhammad Saad
Published: October 2024

Disclosure: T. Chaudhary: None. O. Syed: None. A. Shridar: None. R. Kaur: None. O. Chaudhary: None. M.S. Zubair: None.

Background: Pembrolizumab, an immune checkpoint inhibitor, has shown efficacy inducing remission in various malignancies. Associated immune-related adverse effects (irAEs) have been recorded but cases of concomitant hypophysitis and thyroiditis are rare. Clinical case: The patient is a 41-year-old male with a past medical history significant for metastatic melanoma of the left calf, status post sentinel lymph node biopsy and left inguinal lymph node dissection, treated with pembrolizumab for one year. He initially presented with a severe headache that was preceded by two months of fatigue and impaired concentration. CT and MRI head were both unremarkable while lab work was significant for cortisol 0.2 ug/dL and adrenocorticotropic hormone (ACTH) 1.1 pmol/L. A full hormone panel was ordered which showed normal insulin-like growth factor-1 (IGF-1), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Free testosterone was at the lower end of normal. Prolactin was elevated at 27.3 ng/mL. The thyroid function tests showed primary hypothyroidism with elevated thyroid stimulating hormone (TSH) at 109 uIU/mL, low T4 at 1.5 ug/dL, and low free T4 at 0.4 ng/dL. There were no signs or symptoms of posterior pituitary dysfunction. The patient was diagnosed with hypophysitis and started on hydrocortisone 20 mg once daily along with levothyroxine 175 mcg once daily. DEXA scan showed normal bone mineral density. Subsequently, the patient presented to our care and reported symptom improvement after taking the prescribed medication however he continued to develop fatigue by the end of the day. Therefore, hydrocortisone prescription was switched to 15 mg in the morning and 10 mg at noon. A repeat thyroid function panel, sex hormone binding globulin, and LH were ordered, to be followed up at the patient's next visit. The patient was also advised to wear a medical alert bracelet at all times moving forward. Conclusion: Due to non-specific symptoms at onset, hypophysitis can be undiagnosed or misdiagnosed therefore it is important to have a high clinical suspicion with patients on PD-1 inhibitors presenting with such symptoms. It is also imperative to order a full set of hormones as this patient had concomitant primary hypothyroidism.

Presentation: 6/1/2024
8513 Toxic Metals Are Associated With Increased Diabetes And Obesity Through Gut Microbiota Changes In Five African-Origin Populations
Authors: Jorgensen Julianne , Choo-Kang Candice , Issa Lina , Gilbert Jack A , Ecklu-Mensah Gertrude , Luke Amy , Bedu-Addo Kweku , Forrester Terrence , Bovet Pascal , Lambert Estelle V , Rae Dale , Argos Maria , Dai Yang , Sargis Robert Michael , Dugas Lara R , Layden Brian T
Published: October 2024

Disclosure: J. Jorgensen: None. C. Choo-Kang: None. L. Issa: None. J.A. Gilbert: None. G. Ecklu-Mensah: None. A. Luke: None. K. Bedu-Addo: None. T. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. M. Argos: None. Y. Dai: None. R.M. Sargis: None. L.R. Dugas: None. B.T. Layden: None.

Obesity is associated with an increased risk for cardiometabolic diseases, such as type 2 diabetes mellitus (T2D). Prior research has shown an association between toxic metals/metalloid (hereafter, “metals”) exposures, including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), and increased T2D risk. Importantly, metal exposure has been suggested to impact the gut microbiome. Gut microbiome composition and metabolism are key to the development and progression of obesity and diabetes, thus we propose a potential novel interaction via the gut microbiota between metals and T2D, although the exact pathway remains unclear. We studied a large African-origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US (n=188, 51% female, mean age=43.0±6.5 yr). Analyzing 16S rRNA Amplicon sequencing, anthropometrics, and creatinine-adjusted urinary metal levels, we observed metal levels were significantly associated with country of origin and in most countries were significantly associated with decreased microbial diversity. Metal levels were highest in Ghana and lowest in the US, and were significantly different between Ghana and the US for As and Pb (p-value < 2.2e-16). Individually, Pb levels were significantly associated with fasting blood glucose and BMI, As levels were associated with T2D diagnosis, and Hg levels were associated with obesity diagnosis. Pb levels were significantly associated with a lower proportion of potential acetate- and butyrate-producing microbial strains. Similarly, As levels were associated with decreased proportion of potential butyrate-producing genera. Microbial strains in individuals with high Pb levels showed significant association with obesity and T2D risk and strains in individuals with significant high As levels were associated with only T2D risk. Hg and Cd were not significantly associated with microbes and clinical status. These taxa are significantly associated with increased heme metabolism. With this study, we aimed to begin to describe the effect of metals and the risks for obesity and diabetes through its action within the gut microbiome. We demonstrate that toxic metal exposures were associated with differences in the gut microbiome and predicted metabolism that may also be associated with increased obesity and T2D risk.

Presentation: 6/1/2024
6479 Acute Estradiol and Progesterone Therapy In Hospitalized Adults With Moderate COVID-19: A Randomized Control Trial
Authors: Lovre Dragana , Bateman Kristin M , Saltzman Leia Y , Fahd Qadir Mirza Muhammad , Mauvais-Jarvis Franck
Published: October 2024

Disclosure: D. Lovre: Research Investigator; Self; Novo Nordisk, Corcept Therapeutics. K.M. Bateman: None. L.Y. Saltzman,: None. M. Qadir: None. F. Mauvais-Jarvis: None.

Background and Objective: COVID-19 outcomes are less severe in women vs men. Experimental studies show that estradiol (E2) and progesterone (P4) produce anti-inflammatory immune responses and immune tolerance and enhance antibody production. The effect of E2 and P4 combination on COVID-19 severity is unknown. The aim of the study was to evaluate the efficacy of a short systemic E2/P4 combination in mitigating COVID-19 severity in hospitalized men and women. Methods: Phase 2, double blind, placebo-equivalent controlled, single center trial of ten participants (men and women) who were hospitalized for COVID-19, with scores 3 to 5 on the 9-point World Health Organization (WHO) ordinal scale for clinical improvement. Participants were randomized into two arms and treated for five days: 1) E2 Cypionate (5 mg IM once) and micronized P4 (200mg, PO daily); and 2) Placebo-equivalent (normal saline (1ml, IM once) and folate (400mcgs, PO daily), in addition to standard of care (SOC). The primary outcome was the proportion of patients improving to scores 1 or 2 on the WHO scale on the day of discharge. Secondary outcomes included length of hospital stay (LOS), days on oxygen therapy (DOT), readmission rates (RR), adverse events (AEs) and change in inflammatory biomarkers assessed by untargeted proteomics. Findings: There were no significant differences between the treatment groups in COVID-19 severity by WHO score, LOS, DOT, RR or AEs. Patients in the E2/P4 arm exhibited a decrease in inflammatory biomarkers of respiratory and gastrointestinal disease (GI) and significant change in immune and inflammatory responses. Conclusions: Use of short-term systemic E2/P4 is associated with decrease in biomarkers of respiratory and GI disease inflammation and change in biomarkers of immune and inflammatory response.

Presentation: 6/3/2024
6790 High IGF-1: What Else Could It Be?
Authors: Pinson-Hilkemeyer Amber , Ghalib Luma
Published: October 2024

Disclosure: A. Pinson-Hilkemeyer: None. L. Ghalib: None.

A 28-year-old transgender male was referred to the pituitary clinic to evaluate an incidentally found small pituitary cyst. The initial MRI was ordered as part of a workup of recurrent headaches and possible Multiple Sclerosis (MS). He has been on a stable dose of testosterone cypionate 120mg every two weeks since 2020. The pituitary endocrine workup showed an elevated insulin like growth factor-1 (IGF-1) at 385.1 ng/ml (Reference range 96 – 262 ng/ml), however further hormonal workup was unremarkable with the most recent testosterone level of 309 ng/mL. He did not have any acromegalic features on examination. He underwent growth hormone suppression testing with an oral glucose tolerance test and GH suppressed to 0.12 ng/mL in 120 min, which was not consistent with the diagnosis of acromegaly. He has continued to have an elevated IGF-1 on repeat testing for 18 months.There are not many cases reporting elevated IGF-1 in the setting of hormonal therapy in the trans community. But it has been reported that administration of testosterone to hypogonadal and non-hypogonadal men can lead to increased levels of IGF-1. It has also been reported that cross-sex hormone treatment (HT) in the transgender population with either testosterone for a transgender male or estradiol for a transgender female has been related to increased levels of IGF-1 after starting treatment. It is well documented in patients with acromegaly, there are increased risk of cardiovascular and musculoskeletal disease, systemic inflammation, and insulin resistance. However, it is not well studied in the transgender population. More research is needed to determine the incidence and clinical significance of the isolated elevation in IGF-1 in this population. Also, if there is any benefit to screening transgender individuals who are on HT for elevated IGF-1 and if they are considered to be at increased risk for developing other potential side effects?

Presentation: 6/3/2024
6600 Hyperkalemia Shortly After Surgical Treatment For Primary Hyperaldosteronism
Authors: Hernandez Hernandez M , Colon Castellano J
Published: October 2024

Disclosure: M. Hernandez Hernandez: None. J. Colon Castellano: None.

Primary hyperaldosteronism was thought to be a rare cause of secondary hypertension in the United States. However, recent epidemiologic data estimates that approximately 5-15% of patients with a diagnosis of hypertension are due to hyperaldosteronism. This number may be higher due to patients being widely underdiagnosed. Most of these patients can be cured with a surgical approach. Patients who undergo adrenalectomy for primary hyperaldosteronism need to be closely monitored for electrolyte disturbances. Post-adrenalectomy hyperkalemia in hyperaldosteronism is thought to be secondary to resultant hypoaldosteronism caused by suppression of the juxtaglomerular apparatus on the contralateral adrenal gland secondary to the volume-expanded state before unilateral adrenalectomy. It has been reported in a subset of patients and it is a known cause of increased morbidity and mortality as patients may present with severe hyperkalemia. We present the case of a 63-year-old male patient with medical history of hypertension who was diagnosed with primary hyperaldosteronism when he presented with hypokalemia in routine laboratories performed after an elective laparoscopic cholecystectomy. The patient’s laboratories were remarkable for potassium levels at <2mEq/L, normal sodium levels, and further workup obtained which was remarkable for plasma aldosterone concentration: plasma renin activity (PAC/PRA) at 216. The medication regimen at home included Lisinopril 40mg p.o. daily, Nifedipine 60mg p.o. daily, and oral potassium replacement. The patient was consulted to the Endocrinology service which recommended further imaging studies. Abdomino-pelvic CT scan was remarkable for a right adrenal adenoma measuring 1.5 cm with 24 Hounsfield units. The patient was initially managed with aldosterone antagonists and then a right adrenalectomy was performed successfully after adrenal vein sampling. Approximately two weeks after the adrenalectomy, the patient was called back to the Emergency Room (ER) due to hyperkalemia 6.5mEq/L. Upon arrival at the ER, there were no EKG changes associated with hyperkalemia, and he was given appropriate treatment for potassium levels. The patient was started on Fludrocortisone with excellent clinical response and is currently being followed at Endocrinology clinics. The etiology of this patient’s hyperkalemia soon after adrenalectomy demonstrates the effect of relative hypoaldosteronism from chronic suppression of the left adrenal gland due to aldosterone excess produced by the right adrenal adenoma. Fludrocortisone is a synthetic mineralocorticoid and it has potent effects in reducing potassium levels mediated by sodium reabsorption and potassium excretion at the distal renal tubules. Early treatment in these patients is crucial to prevent the development of electrolyte disturbances that may ultimately lead to life-threatening arrhythmias.

Presentation: 6/2/2024
7932 A Case of Acromegaly with Recurrence After Spontaneous Transient Resolution
Authors: Tadisina Shourya , Mohammed Sobrina Sarah , Patel Vaishali Bhavin
Published: October 2024

Disclosure: S. Tadisina: None. S.S. Mohammed: None. V.B. Patel: None.

Introduction: Pituitary apoplexy occurs from hemorrhage or infarction of the pituitary gland; a rare complication of pituitary adenomas. Pituitary apoplexy is a life-threatening endocrine emergency but can occasionally be asymptomatic. When occurs in a functional adenoma it can cause resolution of hormonal hypersecretion and remission. We describe a case of Acromegaly with transient spontaneous resolution likely from possible infarction of the pituitary adenoma which later developed recurrence with increasing Insulin like growth factor (ILGF-1) levels and size of the pituitary adenoma. Case Presentation: A 56-year-old male with history of multinodular goiter, prostate cancer on androgen deprivation therapy (ADT) presented for his thyroid but was found to have coarse facial features with widely spaced teeth on exam. He reported that he noticed these symptoms for about 2-3 years along with significant weight gain, increase in shoe size and ring size. Work up revealed evidence of acromegaly with elevated ILGF-1- 607 ng/ml (50-317ng/ml) and an oral glucose tolerance test that did not suppress growth hormone (GH) to <1 ng/dl. Rest of the anterior pituitary hormonal work up was normal except for a low testosterone level due to ADT. Initial MRI Pituitary showed a small pituitary gland with decreased enhancement in the inferior Sella slightly more eccentric to the left. This could be a collapsed cyst; no mass effect as expected with an adenoma. Radiology and Neurosurgery reviewed imaging and confirmed a 3mm pituitary microadenoma. Serial hormonal work up revealed a downtrend in the ILGF-1 levels with normal values at 182 ng/ml at 8 months from initial evaluation. A multidisciplinary pituitary conference was held and the case was diagnosed as Acromegaly with spontaneous partial resolution. This case has a unique presentation as the imaging findings were not consistent with the biochemical and clinical findings making this a diagnostic challenge. A plausible explanation is that a spontaneous bleed or infarction of the adenoma could have caused it to shrink in size and biochemical improvement. He was closely monitored with serial imaging, biochemical and clinical evaluation. The follow up ILGF-1 levels done at 4 months from resolution showed increase to 407 ng/dl and a follow up MRI done at 10 months from the initial MRI showed a hypo enhancing pituitary adenoma 0.7x0.7x0.8 cm. Neurosurgery recommended surgical resection due to the increase in size and the ILGF-1 levels. This recurrence was thought to be likely from only partial infarction/bleed of the adenoma causing regrowth from the residual cells. Conclusion: Pituitary apoplexy causing complete/partial resolution of acromegaly can be a diagnostic and therapeutic challenge. There are few cases reported in literature with spontaneous resolution of acromegaly and only one case with recurrence after 18 years of apparent cure.

Presentation: 6/2/2024
6462 A Case of Presumed IgG4 Related Hypopituitarism
Authors: Lai William , Turtz Alan , Traisak Pamela , Morgan Farah Hena
Published: October 2024

Disclosure: W. Lai: None. A. Turtz: None. P. Traisak: None. F.H. Morgan: None.

Introduction: Hypopituitarism is a rare disorder of decreased hormone secretion with a prevalence of 0.05% [1]. It is exceedingly rare to be caused by pituitary inflammation such as IgG4 mediated plasmacytic cell invasion hypophysitis which accounts for 4% of all hypopituitarism cases [2]. We present a challenging case of presumed IgG4 hypophysitis using Leporti criteria. Case: A 79 year old male with a medical history of hypertension, hypothyroidism, and mitral valve repair presented to the hospital for syncope, fatigue, and hypotension. Blood work done was significant for a low cortisol of 0.8 µg/dL (5-25 µg/dL), ACTH of 5 pg/mL (10-60 pg/mL), TSH of 0.120IU/mL (0.5-5IU/mL), and FT4 of 0.89ng/dL(0.7-1.9ng/dL). Prolactin and IGF1 were unremarkable. He was started on hydrocortisone 10 mg in the morning and 5 mg in the evening with improvement in symptoms. On follow up with Endocrinology, an MRI revealed an intrasellar/ suprasellar mass measuring 18 mm craniocaudal, sellar component of 11x9 mm, and suprasellar component 13x9mm with effacement and superior displacement of the optic chiasm raising the question of hypophysitis, and an incidental finding of a parotid mass. IgG4 testing was sent with results elevated at 377 mg/dL. PET scan showed uptake in the pituitary gland, right parotid gland, as well as mediastinal and hilar lymphadenopathy. Biopsy of the right parotid lesion showed pleomorphic adenoma. Patient deferred biopsy of hilar lymph nodes.The patient’s steroids were changed to prednisone to treat likely IgG4 mediated hypophysitis and repeat MRI after 4 weeks of treatment showed a reduction in the size of the pituitary lesion. He was subsequently referred to rheumatology for further evaluation of systemic disease. Additional work up including SPEP, Cryoglobulins, ANA IFA, ANCA, C3, C4, SSA, SSB, ACE, and immunoglobulin levels were negative. Conclusion: IgG4 related hypopituitarism is a rare diagnosis that is difficult to diagnose. In this case a definitive diagnosis with histological sampling was not obtained but a working diagnosis of IgG4 related hypophysitis was made based on clinical presentation, MRI findings, an elevated IgG4 > 140, and response to treatment. He ultimately fulfilled the diagnostic criteria proposed from Leporti et al [3]: MRI with sellar mass, IgG4 > 140mg, and steroid responsive decrease in size of the pituitary lesion, with concomitant improvement of symptoms. This case highlights the difficulty in diagnosis of IgG4 hypophysitis and the benefit of using non histological diagnostic criteria.

Presentation: 6/1/2024
12352 A Case Of Sellar Pituitary Cyst With Elevated Prolactin In A 74-Year-Old Woman
Authors: Tkach Marko S , Pinero-Pilona Antonio
Published: October 2024

Disclosure: M.S. Tkach: None. A. Pinero-Pilona: None.

A 74-year-old woman diagnosed with a pituitary mass, described as a prolactinoma, presented for follow-up care with elevated prolactin (“PL”). Initial diagnosis of a prolactinoma was 46 years prior to presentation. Prior imaging was not available. She received bromocriptine for 31 years; as PL increased to 90 on a drug holiday, bromocriptine was resumed for over a decade. After that time, PL decreased to 23, 11 years later. She was switched to cabergoline after reporting a “stuffy nose”. With PL up to 37.8 two years later, cabergoline was increased to 0.5 mg one tablet twice a week. PL subsequently dropped to 8.2 over the next two years. Upon presentation, she reported no brain imaging for “over 30 years”. She denied galactorrhea, headache, sweating, nausea, weight change, severe hypertension, hypotension, diabetes, hirsutism, fatigue, or muscle weakness. She denied visual field changes, or any formal visual field testing for over 20 years. Exam on initial presentation was unremarkable except for a diffuse goiter. Initially ordered labs were unremarkable, though A1c was 6.2%. Undiluted PL was 6.0 (confirmed on 1:100 dilution). Another PL was measured at 4.6 total and 3.8 monomeric. TSH was 1.47. Thyroglobulin antibodies and TPO were undetectable. On pituitary MRI, "the pituitary gland shows a partially empty sella turcica which is asymmetrically slightly outwardly convex on the right, possibly representing an occult arachnoid cyst versus cystic adenoma. There is a midline pituitary stalk. No parasellar abnormalities.” Scalloping of the right sellar portion was noted. Cystic changes in the pituitary in this case may be related to cystic prolactinoma, arachnoid cysts, or cystic degeneration of a prolactinoma after long-term treatment with a dopamine agonist. Cystic prolactinomas have been termed “transitional cell tumors of the pituitary” as they possess both Rathke cleft cyst and prolactinoma features. Reduced efficacy of response to medical as compared to surgical therapy in these patients has been observed. They also tend to lead to lower PL levels than solid prolactinomas, complicating diagnosis. Arachnoid cysts (“AC”) are collections of CSF within the arachnoid membrane: present in about 1.7% of the population, they account for about 1% of intracranial masses. Although an uncommon location, sellar AC have been previously described and are estimated to comprise about 3% of AC. Nonfunctioning pituitary masses or AC with stalk compression can cause elevated PL; these respond to dopamine agonist therapy, though it is not considered definitive therapy in the case of a nonfunctioning adenoma. This case represents the difficulties in management and transition of long-term care and treatment of prolactinomas as well as assessing pituitary radiological findings.

Presentation: 6/1/2024
7229 A Rare Case of Igg4 Hypophysitis Presenting as Hypogonadotropic Hypogonadism
Authors: Dimech Christina , Jaiswal Gayatri
Published: October 2024

Disclosure: C. Dimech: None. G. Jaiswal: None.

Hypophysitis is a rare pituitary disorder including a broad range of inflammatory processes which affect the pituitary gland and infundibulum. Previously reported as 1 per 9 million individuals, the true incidence of hypophysitis per year is largely unknown due to the increase of novel etiologies such as immunoglobulin G4 (IgG4)- related disease. IgG4-related hypophysitis (IgG4-RH) was first clinically described in 2004 and later biopsy proven in 2007. The main clinical features are elevated serum IgG4 level and IgG4-positive lymphocyte infiltration of tissues on histopathology. IgG4-RH is reported to account for 1.3% of primary hypophysitis with 3.2:1 incidence ratio of men to women, in the 6th decade of life. Here we present a case of a 68-year-old Caucasian male who presented for evaluation of hypogonadotropic hypogonadism. As fasting morning testosterone levels were significantly low, MRI pituitary was completed which revealed a homogenously enhancing pituitary gland with thickened, nodular enhancement of the pituitary infundibulum. Subsequent lab work-up revealed normal function of remaining anterior pituitary without evidence of central vasopressin deficiency. Evaluation of underlying etiologies was unremarkable except for significantly elevated IgG4 levels (472mg/dL). Based on the significantly elevated IgG-4 levels (>135 mg/dl) and the radiographic findings of the pituitary infundibulum, the diagnosis of possible IgG4-RH was made. The patient was initiated on treatment with rituximab and glucocorticoid therapy with prednisone. Following 3 months of medical therapy, MRI pituitary showed resolution of stalk inflammation, confirming diagnosis of IgG4- RH.

Presentation: 6/1/2024
6591 Effects of Levoketoconazole on 24-hour Mean UFC (mUFC) in the SONICS Study: Relation to Baseline mUFC in Adults with Cushing’s Syndrome: a Post-hoc Analysis
Authors: Huang Robbie , Harper Dawn , Meyer James , Cohen Fredric M
Published: October 2024

Disclosure: R. Huang: Employee; Self; Xeris Pharmaceuticals. D. Harper: Employee; Self; Xeris Pharmaceuticals. J. Meyer: Employee; Self; Xeris Pharmaceuticals. F.M. Cohen: Consulting Fee; Self; Xeris Pharmaceuticals.

Background: Prior exploratory analyses of the open-label, non-randomized, single-arm Phase 3 SONICS study of levoketoconazole suggested that the mUFC response rate at 6 months varied by baseline mUFC stratum. That exploration focused on the subset of the study population that had completed Dose-Titration phase and advanced into the 6-month Maintenance phase. We now expand this exploration to include all enrolled patients in SONICS who were treated and had a postbaseline mUFC, aiming to further elucidate relationships between baseline biochemical disease severity, drug dose, and intermediate-term mUFC response. Methods: 94 adults with confirmed Cushing’s syndrome were enrolled to receive levoketoconazole treatment at a starting dose of 150 mg BID, titrated as needed at 150 mg intervals until a maximum dose of 600 mg BID or an adequate response was achieved in the investigator’s judgment. Following Dose-Titration phase, eligible patients immediately entered a Maintenance phase of approximately 6 months, during which the dose could be changed only to regain biochemical control or for safety reasons. The primary endpoint was the proportion of patients in the ITT population with mUFC normalization at end of the 6-month Maintenance phase, without a dose increase during maintenance. For the current analyses, 92 patients treated with levoketoconazole and with baseline mUFC measurement (modified ITT) were stratified into 3 baseline mUFC subgroups—Group 1: 1.5x to ≤2.5x upper limit of normal (ULN); Group 2: >2.5x to ≤5x ULN; Group 3: >5x ULN and analyzed with respect to mUFC response, average daily dose, and adverse events following 6 months of Maintenance therapy. Results: Group 2 had the highest apparent mUFC response rate (12/33 [36.4%]); 95% CI 0.20, 0.54) as compared with Group 1 (12/38 [31.6%]; 95% CI 0.16, 0.47) or Group 3 (5/21 [23.8%]; 95% CI 0.01, 0.55); Group 3 having a notably lower response. Daily doses of levoketoconazole were related to baseline mUFC. Thus, Group 3 used a nominally higher average daily dose during Maintenance therapy and at the end of the 6-month Maintenance phase (680 mg and 741 mg) than Group 1 (508 mg and 566 mg) or Group 2 (617 mg and 611 mg). Group 3 had more liver-related adverse events of special interest than Group 1 or 2 (14% vs 7.9% or 3.0%) and more AEs leading to discontinuation (24% vs 12% or 16%). Conclusion: In this post-hoc analysis, lower mUFC at baseline predicted the likelihood of achieving mUFC normalization following 6 months of levoketoconazole Maintenance therapy and was associated with lower Maintenance dose requirements and lower rates of potentially clinically important liver-related AEs.

Presentation: 6/1/2024
7900 Growth Hormone Secretion Disruption Leads to Sex Dimorphic Effects on Mices Reproduction
Authors: Alves Guilherme Andrade , Frazao Renata
Published: October 2024

Disclosure: G.A. Alves: None. R. Frazao: None.

Growth hormone (GH) is required for sexual maturation and sex steroid mediation of the ovulatory cycle. In humans and animal models, late puberty onset and infertility can be seen in cases of GH secretion disruption. Hypothalamic nuclei containing either kisspeptin or leptin receptor-expressing neurons, required for puberty onset and fertility, are GH-responsive. The selectively induced ablation of GH receptors from Kiss1-expressing cells in female mice is not required for puberty onset despite the downregulation of Kiss1 and Gnrh1 hypothalamic expression in pubertal animals. In contrast, the lack of GH signaling in leptin receptor-expressing cells leads to late sexual maturation but no modulation of Kiss1 or Gnrh1 hypothalamic levels in female mice. The impact of disrupted GH secretion throughout the development on hypothalamic areas associated with reproductive function remains unclear. To determine whether GH secretion disruption differentially affects female and male mice reproduction, we selected mice that hypersecrete GH (here denominate as bGH) or with spontaneous GH deficiency (Ghrhrlit/lit), as well as their littermates (control) for the experiments. We recorded mice’s body weight gain and sexual maturation during development, as well as body length and hypothalamic mRNA expression at the adult stage. We further assess the estrous cycle length of female mice and the fertility rate of male and female animals. As predicted, male and female bGH mice showed increased body weight gain during development and increased nasoanal length compared to control mice. The Ghrhrlit/lit male and female mice showed decreased body weight gain and lower nasoanal length than control mice. bGH and Ghrhrlit/lit female mice showed similar puberty timing to control mice, whereas bGH and Ghrhrlit/lit male mice exhibited a late puberty onset. Interestingly, bGH female mice exhibited disrupted estrous cycles and were infertile, whereas Ghrhrlit/lit female mice showed no differences in estrous cycle length compared to control animals and were fertile. While it is known that Ghrhrlit/lit male mice are subfertile, bGH male mice exhibited no fertility deficit. In contrast to control mice, bGH mice showed upregulated AgRP mRNA expression levels, whereas Pomc expression levels were downregulated, despite no differences in Kiss1, Gnrh1, Esr1, and Tac3 mRNA expression. AgRP and Pomc levels were downregulated in Ghrhrlit/lit females, whereas Tac3 and Ghrh mRNA expression were upregulated compared to control animals. Our findings suggest a GH-induced sexually dimorphic modulation of the HPG axis. Adequate GH signaling seems required for puberty transition in male mice, while GH hypersecretion impairs female mice's fertility despite not affecting puberty onset. Whether changes in metabolism or a specific class of neurons contribute to the observed effects needs further investigation.

Presentation: 6/3/2024
8793 Bilateral Pheochromocytoma Related To Multiple Endocrine Neoplasia Syndrome 2
Authors: Compas Frantzcess , Samir Desai Neesha , Moalem Jacob , Harbuz-Miller Inga
Published: October 2024

Disclosure: F. Compas: None.

Background: Pheochromocytomas are rare catecholamine secreting neuroendocrine tumors of the adrenal medulla that overproduce metanephrines. These tumors may occur sporadically or arise from several genetic disorders including Multiple Endocrine Neoplasia Type 2 (MEN 2). Symptoms of a pheochromocytoma are hypertension, palpitations, anxiety, headache, diaphoresis, and tremors. Bilateral pheochromocytomas are exceedingly rarer compared to unilateral cases. Clinical Case: A 30-year-old male without significant past medical history initially presented to his primary care physician at the age of 18 with episodic palpitations that occurred at least once a week during exercise. Over the years the palpitations progressed and were accompanied by intermittent chest pain. Family history included a mother with thyroid nodules who died from multiple organ failure. Extensive cardiac evaluation revealed hypertension, leading to beta-blocker initiation. He underwent further testing for causes of secondary hypertension. Shortly after he presented to the emergency room with sudden onset aphasia, confusion, and combativeness. CT scan was performed which revealed posterior reversible encephalopathy syndrome. Abdominal imaging from secondary hypertension workup revealed bilateral adrenal masses. Urine metanephrines revealed a metanephrine of 67,950 mcg/24 hr and urine normetanephrine of 27,150 mcg/24 hr. He was admitted to the hospital. In preparation for bilateral adrenalectomy alpha blockade was initiated followed by beta blockade. He underwent a bilateral adrenalectomy. Pathology from adrenalectomy revealed that bilateral masses consistent with a bilateral pheochromocytoma. Shortly afterwards he was diagnosed with medullary thyroid cancer. Genetic testing revealed that this patient had MEN 2a syndrome. Discussion Bilateral pheochromocytomas from MEN 2a syndrome are exceptionally rare, accounting for a small percentage of all cases. They present more severe and cause fluctuating hypertension due to the simultaneous release of catecholamines from both adrenal glands. This case highlights the importance of considering rare causes of hypertension and the implications of delayed diagnosis and treatment. Conclusion: This is an exceedingly rare case of a bilateral pheochromocytoma implicated by MEN 2a that went undetected for years and presented with life threatening complications.

Presentation: 6/2/2024
7411 Hypothalamic Estrogenic Signal Regulates Prolactin Homeostasis and Reproduction in Female
Authors: Yu Meng , Wang Chunmei , Xu Yong
Published: October 2024

Disclosure: M. Yu: None. C. Wang: None.

Both 17β-estradiol (E2) and prolactin (PRL) are important reproductive hormones. It has been well established that E2 can act on estrogen receptor-α (ERα) in the lactotroph cells in the pituitary to upregulate PRL level. This mechanism may explain the high PRL and high E2 during proestrus phase or pregnancy, however, it could not explain high PRL but low E2 singling during lactation. We found that central supplement of E2 reduced PRL level in lactating dams, suggesting a novel inhibitory role of E2 on lactational hyperprolactinemia. To explore the mechanism and the relationship with reproductive regulation, firstly we compared the activity of ERα-expressing neurons in the hypothalamus during virgin and lactation. We found that ERα neurons in the ventrolateral subdivision of the ventromedial hypothalamus (ERαvlVMH) were inhibited during lactation. Further, we specifically deleted ERα from vlVMH in virgin females. These mice with deletion of ERαvlVMH showed dramatic changes: 1) lactation-like hyperprolactinemia and prolactinoma, 2) developed mammary gland and amenorrhea, and 3) disrupted reproduction including enlarged uterus and reduced fertility. Consistently, we specifically activated ERαvlVMH neurons in lactating mice and found that these lactating mice showed attenuated lactational hyperprolactinemia and impaired maternal cares. Together, we revealed a novel neuroendocrine mechanism that hypothalamic E2-ERα signaling regulate PRL homeostasis, which is important to maintain reproduction in females. Our study also supports that lactational suppression of hypothalamic E2-ERα signaling is required to maintain normal lactation which may contribute to reduced fertility during lactation.

Presentation: 6/1/2024