bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP026 An Incidental Giant Normotensive Pheochromcytoma with Elevated Metanephrines demonstrated no evidence of hypertensive crisis during a major surgery
Authors: Camacho Yudi , Jamal Yusra , Brutsaert Erica , Goswami Gayotri
Published: November 2022

A 48-year-old Caucasian male with no known past medical history admitted to our hospital following MVA resulting in acute severely comminuted displaced fracture of the left femur and tibia. On admission, the patient was in severe pain. His vitals were significant for elevated blood pressure (BP) of 137/100 and pulse rate of 161 per minute, which resolved soon after pain medications and splint placement. On review of systems, he denied episodic spells of headaches, palpitations, pallor, tremors, anxiety, abdominal pain, or diaphoresis. He denied any family history of endocrine disorders. Physical exam was unremarkable, except for the left femur traction splint. He had multiple CT imaging performed for evaluation of his injuries. On CT scan of the abdomen, he was found to have a 7.2cm adrenal incidentaloma with imaging characteristics consistent with pheochromocytoma. He was admitted to the intensive care unit for one day for closer monitoring where he remained hemodynamically stable without any BP lowering medications. Laboratory work up for a pheochromocytoma was pending. However, due to concern of compartment syndrome of left lower extremity, patient underwent two emergent procedures of open reduction and internal fixation of left femur and tibial fracture repair. Robust monitoring of hemodynamics was performed during both surgeries but patient did not require any antihypertensive medications during the procedures. Eventually, serum total metanephrines drawn on admission day two, resulted as 7848 pg/ml (normal <205pg/ml), normetanephrines 3626 pg/ml (normal <148pg/ml), and metanephrines 4224 pg/ml (normal<57pg/ml). Serum cortisol, aldosterone, renin, dehydroepiandrosterone sulfate, and glucose were within normal limits. On day 3 of admission, repeated serum metanephrines were persistently elevated in 4000s. 24-hour (hr) urine studies showed total metanephrines 7353 mg/24hr (normal <832 mg/24hr), metanephrines 4934 mg/24hr (normal <315 mg/24hr), normetanephrines 2419 mg/24hr (normal <676 mg/24hr) and creatinine2.3g/24 hr (normal <2. 0g/24hr) . MRI abdomen confirmed pheochromocytoma abutting the pancreas and left upper pole of kidney. Interestingly, patient remained hemodynamically stable with highest BP measurement of 120/90 throughout the hospital course. He was eventually discharged on Prazosin 1 mg twice daily which was gradually increased to 5 mg daily in divided doses; increase fluid intake and high salt diet. Beta-blocker was not added due to borderline blood pressure. The patient underwent robotic left radical adrenalectomy without any intraoperative hemodynamic instability. Pathology was consistent with pheochromocytoma, confined to the adrenal gland without no capsular invasion. The patient refused genetic testing.

Presentation: No date and time listed
PMON106 Persistent Prolactin Levels in a Patient with Pituitary Adenoma
Authors: Kadakia Natasha , Sadiq Sobia
Published: November 2022

We present a peculiar case of persistently elevated prolactin levels with significant residual tumor in the setting of dopamine agonist therapy.This is a 45 year old male with no known medical history who presented with a seizure. Work up was significant for a large homogeneously extra-axial mass (57×35×44 mm) arising from the left clinoid extending anteriorly, inferiorly, and posteriorly to the planum sphenoidale, the sphenoid sinus, and the suprasellar cistern, respectively. The mass extended superiorly to compress the hypothalamus, and medially to the right cavernous sinus. This mass was causing elevation of the optic chiasm and encasement of the left optic nerve and the left internal carotid artery with displacement of the pituitary infundibulum to the right. Biochemical workup revealed hyperprolactinemia with a prolactin level greater than 2000, and secondary hypogonadism; free testosterone level of 27.1. He was started on therapy with a dopamine agonist, cabergoline at 0.5 mg. This dose was up titrated to a max dose of 12 mg weekly over 6 months. Subsequently, prolactin levels trended down from initial levels of >2000 to 1142 to 1115 to 1045 to 710 with corresponding increases in cabergoline. He began to experience CSF rhinorrhea. Neurosurgery recommended medical therapy given the high risk anatomical location of the prolactinoma. In our interdisciplinary conference, discussion was had regarding other therapeutic agents. Patient was started on anastrozole and metformin. He subsequently started somatostatin, as well. Patient underwent a repeat MRI Sella on 9/2021 with a 50% decrease in size. Most recently, the patient has had a repeat seizure and is scheduled for a repeat MRI with possible consideration of surgical resection despite the high risk surgery.Current guidelines suggest symptomatic patients that do not achieve normal prolactin levels or show significant reduction in tumor size on standard doses of a dopamine agonist should be increased to maximal tolerable doses before referring for surgery There is literature regarding alternative treatment options in the setting of elevated prolactin levels with a discordant response to first line therapy. Options include switching to another dopamine agonist, radiotherapy, or alternative options. One of these options include aromatase inhibitors, with inhibitory effects on prolactin gene transcription. There are studies that outline use of Temzolamide for aggressive pituitary tumors and carcinomas, however, there is not enough data regarding its use in resistant Prolactinomas. Lastly, somatostatin analogues have been shown to reduce prolactin levels due to the presence of somatostatin receptors in prolactinomas. A published case series (Sosa-Eroza et al.) showed 5 patients with DA resistance with two cases with reduction in tumor volume and prolactin level. Our patient has had a response to sandostatin with most recent prolactin levels 111.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON117 IGF-1 Testing: Diagnostic Pitfalls
Authors: Perez-Martinez Sebastian
Published: November 2022

Introduction

Acromegaly is a rare endocrine disorder, with an incidence of 5.3/million/year, that results from persistent hypersecretion of growth hormone (GH), which stimulates hepatic secretion of insulin-like growth factor-1 (IGF-1). The best single test for the diagnosis of acromegaly is measurement of serum IGF-1; however, the result must be interpreted with caution, with understanding of potential pitfalls. Here we present a case of falsely elevated IGF-1 levels.

Case Description

A 43-year-old female with medical history of prediabetes, sleep apnea, and headaches was referred to endocrine clinic for evaluation of possible acromegaly. Patient had been evaluated by her primary care physician for frequent headaches, unintentional weight gain, and bilateral leg and hand swelling. Patient endorsed being unable to wear her wedding ring for a few years.

Initial laboratory evaluation by primary care physician 3 months prior revealed normal thyroid function, prolactin, FSH, LH, random cortisol, but elevated IGF-1 of 310 ng/mL (normal 71-258 ng/mL), with negative pregnancy test. Brain MRI at that time revealed a pineal gland cyst but no pituitary abnormality.

During her initial endocrine visit, IGF-1 was repeated, which was again elevated but improved to 283 ng/mL (normal 71-258 ng/mL). Other pertinent labs included a normal random ACTH of 18 pg/mL (normal <47 pg/mL), and pm cortisol of 2.4 mcg/dL (normal 2.9-17.3 mcg/dL). Physical examination was notable for a few light purple striae on abdomen, acanthosis nigricans, and mild limb edema, but no macrognathia, enlarged hands or feet. Given patient's lack of typical features of acromegaly, normal pituitary imaging, and spontaneous IGF-1 improvement, it was decided to postpone GH measurements with oral glucose tolerance test but repeat IGF-1 in 6 months.

Patient was able to follow up 11 months after initial visit at which patient denied any worsening symptoms. At that time, repeat laboratory study showed normal IGF-1 of 231. Given spontaneous normalization of IGF-1 levels, no further laboratory testing or imaging studies were recommended, and patient was instructed to follow up in 11-12 months.

Discussion

Prompt diagnosis of acromegaly is crucial. However, it is important to note IGF-1 could be falsely elevated. A retrospective review by Erickson et. al of 2747 unique patients with IGF-1 elevation, 117 (4%) were found to have false-positive results following a review of the clinical data. In addition to acromegaly, other causes of elevated IGF-1 levels include high protein and high glycemic-index diet, pregnancy, hyperthyroidism, IGF-1 assay problems, and some rare tumors (carcinoids) secreting IGF-1. Discovery of "falsely" elevated IGF-1 may lead to unnecessary testing and physician visits. Therefore, clinicians should consider retesting patients after some time interval if spurious IGF-1 is suspected, before aggressively pursuing more extensive investigations.

Presentation: No date and time listed
PMON122 Unveiling the Kraken- An Incidentally Found Silent Corticotroph Adenoma of the Pituitary Gland
Authors: Shteyman Sara , Azmath Misbah , Kantorovich Vitaly
Published: November 2022

Introduction

Silent corticotroph adenomas (SCA) are an unusual and rare variant of non- functioning pituitary adenomas (NFA) that do not produce biochemical hypercortisolism or clinical Cushing's disease (CD), yet stain strongly for ACTH on immunohistochemistry. They represent 3-19% of non-functioning adenomas and 20% of corticotroph producing adenomas. SCAs are distinguished by their late presentation, frequent cavernous sinus involvement and earlier recurrence requiring multimodal management.

Case

We present a case of a 70 year old female with a remote history of breast cancer (2002) and uterine cancer (2016) in remission who was found to have an incidental soft tissue mass in the sella turcica on CT head after a fall in 2021. An MRI brain confirmed the mass as a 1.8×2.0×1.5 cm pituitary lesion with expansion to the sella. Patient had no symptoms related to pituitary hyperfunction or mass effect. Biochemical workup including IGF-1, prolactin, LH, FSH, and AM Cortisol level were all within normal limits. Ophthalmologic evaluation was normal. Repeat pituitary MRI 2 months later showed increasing homogeneously enhancing lesion on the left petrous ridge measuring 2.8×2.8×1.3 cm. There was extension into the cavernous sinus with involvement and encasement of the carotid artery. After multi-disciplinary evaluation including neurosurgery and ENT, patient elected to undergo transnasal endoscopic resection of pituitary tumor. The tumor was only partially resected due to its close association with the carotid artery. Final pathology was significant for monotonous proliferation of tumor cells with small round nuclei and amphophilic cytoplasm, characteristic of a pituitary adenoma. The tumor cells stained strongly positive for ACTH, and negative for all other hormone receptors. Further endocrine workup showed normal morning cortisol and ACTH and marginally elevated 24 hour urine cortisol measuring 47.6 mcg/g creatinine (ULN 42.3). Her clinical presentation was consistent with a SCA. A Dotatate PET/CT was ordered to be performed 3 months postoperatively to assess for SSTR receptors for potential targeted therapy against the residual tumor.

Discussion

We present the case of an elderly female who was incidentally found to have an invasive SCA precluding its complete resection. There are multiple theories regarding the lack of biological activity of SCAs including lack of enzyme in the tumor to cleve the active ACTH from the prohormone state, dysfunctional lysosomal activity leading to destruction of ACTH before secretion, origin from POMC positive pars intermedia cells instead of true corticotropic cells. These tumors have an increased rate of tumor invasion and recurrence making them difficult to treat. A potential targeted treatment may be somatostatin receptor ligands which will be seen on the dotatate PET/CT.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON125 A Case of Hypothalamic Lipoma Causing Hyperprolactinemia in a Patient With Family History of Birt-Hogg-Dubé Syndrome
Authors: Branis Natalia , Thota Geethika
Published: November 2022

A 41year old female with a medical history significant for depression presented for evaluation of bilateral nipple discharge for 5 months. The patient reported that for the last 5 months she started noticing expressible nipple discharge. She reported no associated headaches, vision changes. She denied the use of vitamins, supplements, herbal remedies. No associated fatigue, changes in the shoe/ring size, heat/cold intolerance, tremors, recent weight changes. She denied neck enlargement, neck pain, dysphagia. The patient reported her menstrual cycles had always been heavy and irregular (every 33-50 days). She has never been pregnant. She has been on Sertraline for the last 4 years with no recent dose changes. Family history was significant for Birt-Hogg-Dubé (BHD) syndrome in father, brother, and sister. The patient has not been tested yet. Initial blood test revealed TSH 1.180 uiu/ml (0.45-4.5 uiu/ml), free T4 1.15 ng/dl (0.82- 1.77 ng/dl), T3 91ng/dl (71-180 ng/dl), FSH 3.8 mIU/ml, LH 3.7 mIU/ml, IGF-1 83 ng/ml (74-239 ng/ml), prolactin 107 ng/ml (4.79-23.3 ng/ml), monomeric prolactin 75.7 ng/ml, macroprolactin 23%, estradiol 16 pg/ml, AM Cortisol 6.5 ug/dl (6.2-19.4ug/dl). The urine pregnancy test was negative. Given low normal AM cortisol, a Cosyntropin stimulation test was done, which was normal. MRI Pituitary with contrast showed flattening of pituitary contour compatible with a partially empty sella turcica and an 8 mm fat intensity in hypothalamic region compatible with a lipoma, stable since last 4 years. The patient was referred to Neurosurgery for further evaluation. The patient remained asymptomatic and medical therapy was not indicated. Genetic testing for BHD was discussed. The patient will be followed in the clinic with a follow-up of prolactin levels and imaging as needed.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON129 Pituitary Adenoma Co-Secreting GH, Prolactin and ACTH
Authors: Wilson Sarah , Tucci Marissa , Lovre Dragana , Galagan Robert
Published: November 2022

Background

Pituitary adenomas co-secreting GH, Prolactin and ACTH are rare.

Clinical Case

A 38-year-old male with a past medical history of depression and type 2 diabetes mellitus was seen in the endocrinology clinic for an evaluation of acromegaly. In the preceding four years, the patient had experienced an enlargement of his hands and feet, hyperhidrosis, development of an underbite, snoring, daytime somnolence, erectile dysfunction, headaches, and blurry vision. His visual fields were normal.

Physical exam: BP 137/85, BMI 39 kg/m2. He had coarse facial features, acral changes of his hands and feet, and wide spacing of his teeth. There was a notable absence of facial plethora, abdominal obesity with thin extremities, proximal muscle weakness, purple abdominal striae, and galactorrhea.

Initial laboratory results: GH 16.9 ng/mL (0.05-3 ng/ml), IGF-1 1,109 ng/mL (82-242 ng/mL), Prolactin (PRL) 96.9 ng/ml (5-20 ng/ml), testosterone 34 ng/dL (200-1000 ng/dL), LH 2.3 miu/ml (1.4–12 miu/ml), FSH 4.8 miu/ml (1.5-12 miu /ml), ACTH 197.6 pg/mL (7.2- 63.3 pg/mL), 0800 cortisol 16.2 ug/dL (5-29 ug/dL), 24-hour urine free cortisol 56.84 mcg (3.5-40 mcg), HS salivary cortisol 0.242 (<0.359 ug/dL), overnight 1 mg Dexamethasone suppression test cortisol 6.9 mcg/dL (< 1.8 mcg/dL), normal Free T4 and TSH, and A1c 9.7%.

A pituitary MRI revealed a 3.9 cm lobulated, intra and supra-sellar mass with mass effect on the optic chiasm and 75% encasement of the left supra-clinoid internal carotid artery.

Neurosurgery performed an endoscopic, endonasal partial resection of the pituitary tumor. The histology was diagnostic of an adenoma, and immunohistochemical staining was positive for GH and PRL, but not ACTH.

Post-op lab results: GH 1.07 ng/ml, IGF-1 353 ng/ml, PRL 9.6 ng/ml, testosterone 41 ng/dL, ACTH 68.2 pg/ml, cortisol 4.5 ug/dL, 24-hr urine free cortisol 8 mcg, HbA1c 5.7%.

Discussion

The intent of this case presentation is to report the rare finding of a pituitary tumor co-secreting GH, ACTH, and Prolactin. The diagnosis of acromegaly was confirmed by significant elevations of GH and IGF-1. The diagnosis of subclinical Cushing's disease was confirmed by elevated ACTH level, 24-hr urine free cortisol, and failed dexamethasone suppression test. The elevated PRL may have been due to tumor PRL secretion or stalk effect. The reduction of these parameters after surgery corroborated the presence of pleurihormonal secretion. This patient's findings support screening for co-secretion of multiple pituitary hormones in patients with acromegaly.

Reference

Pleurihormonal ACTH-GH Adenoma: Case Report and Systematic Literature Review World Neurosurg 2018 114: 158-164

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON132 Biochemical and Radiologic Discordance in the Post-operative Surveillance of a Filipino Patient With Acromegaly
Authors: Enverga Mariel C , Isidro Jocelyn C , Po Rainer Wandrew Y , Sarigumba Marion B
Published: November 2022

Background

Trans-sphenoidal surgery is the recommended initial therapy in patients with acromegaly. Early cure rate is 80-90% for microadenomas and <50% for macroadenomas. The goal is a serum IGF-1 that is normal for age and gender with GH <1mcg/L by immunoradiometric or chemiluminescent assays.

Clinical Case

A 71-year old male who consulted for diabetes management was eventually worked up for acromegaly He presented with coarsened facial features, hoarse voice, frontal bossing and enlarged hands and feet. Medical history includes hypertension, hepatosplenomegaly, colonic polyposis, obstructive sleep apnea and nasal septal deviation post-repair.

Laboratory tests showed elevated IGF-1 (566.15, n: 91-282 ng/ml) and non suppressed GH after 75g OGTT (50.1, n<2.47 ng/mL). Pituitary hormonal profile showed normal prolactin (98.13, n: 86-324 mIU/L), TSH (1.63, n: 0.27-4.2 uIU/ml), FT4 (17.78, n: 12-22 pmol/L), ACTH (35, n: 7.2-63.3 pg/mL), Cortisol (387.4, n: 172-497 nmol/L), LH (4.56, n: 1.7-8.6 mIU/mL) and FSH (15.4, n: 1.5-12.4 mIU/mL). Contrast-enhanced pituitary MRI revealed a 1.5×2.0×1.9 cm pituitary macroadenoma with compression of the optic chiasm.

Patient underwent trans-phenoidal surgery and excision of the tumor. Histopathology revealed a homogenous cells in sheets, acidophilic, densely granular and consistent with sommatotrophs, mammotrophs and sommatomammotrophs.

Post-procedure GH was normal (2.731 ng/mL). Two months post-operatively, there was a significant decrease in both GH (1.84 ng/mL) and IGF-1 levels (258.59 ng/mL) while other pituitary hormones all within reference range. Contrast-enhanced pituitary MRI at 2 months showed interval surgical removal of the mass, with decompression of the optic chiasm. Clinically, there was softening of facial features and improvement in his voice. His cranial did not show pituitary mass. However, repeat GH after 75g OGTT (0.37 ng/mL, 2.3 ng/mL) and IGF-1 (361 ng/mL, 523,6 ng/mL) at 9 and 12 months post-surgery, respectively, were found above the reference range.

Conclusion

Discordance between anatomic and biochemical testing must be investigated thoroughly considering pulsatile hormone secretion, comorbidities and possible microscopic residual disease. Testing with the same assay is important to avoid inter-assay variability. Post-operative monitoring should be done at 12 weeks as it may take time for IGF-1 to normalize. If IGF-1 remains elevated, medical, surgical, radiotherapy, or combination may be considered especially in the presence of an identifiable focus.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON161 Decreased serum Wnt antagonist levels in patients with active acromegaly
Authors: Chen Huan , Huang Hong , Wang Yijie , Zhang Yan , Liu Mengsi , Yuan Lou , Zhang ZiWei , Zhu Dalong , Li Ping
Published: November 2022

Objectives

The Wnt signalling pathway is an important modulator of bone metabolism. This study aims to clarify the changes in Wnt antagonists in active and biochemically controlled acromegalic patients.

Methods

We recruited 77 patients newly diagnosed with acromegaly. Of those, 41 patients with complete follow-up data were included. Thirty healthy patients matched for age, sex, and body mass index served as controls. Wnt antagonists [sclerostin (SOST), dickkopf-related protein 1 (DKK-1), and Wnt inhibitory factor 1 (WIF-1)], bone turnover markers [osteocalcin, procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX)] and the bone remodelling index were investigated at baseline and posttreatment.

Results

Acromegalic patients had higher serum osteocalcin, P1NP, and CTX and a higher bone remodelling index than controls (all P < 0.01). Serum SOST, DKK-1 and WIF-1 levels were significantly decreased in acromegalic patients compared to controls (all P < 0.01). Serum SOST and WIF-1 levels correlated negatively with growth hormone levels; SOST levels were positively correlated with WIF-1. Posttreatment, serum bone turnover markers and the bone remodelling index decreased, while SOST and WIF-1 significantly increased (P < 0.05). DKK-1 levels did not change compared to baseline (P > 0.05). In biochemically controlled patients, SOST, WIF-1 and bone turnover markers almost reached normal levels (all P > 0.05).

Conclusion

Patients with active acromegaly exhibited significantly decreased Wnt antagonist levels. The reduction in Wnt antagonists might be involved in the compensatory mechanism of increased bone fragility in active acromegaly.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON182 PACAP Receptor Expression in Sympathetic Ganglia of the Autonomic Nervous System
Authors: Pandher Parleen , Rahim Yamna , Duong Katrina , Gray Sarah
Published: November 2022

In obesity, energy intake exceeds energy expenditure and concomitantly increases risk of chronic diseases, including metabolic diseases such as diabetes. Therapeutics to correct dysregulations in energy balance are needed and one notable neuropeptide being studied is pituitary adenylate cyclase-activating polypeptide (PACAP), an overarching regulator of the stress response1,2. In the context of metabolism, PACAP has been shown to regulate adaptive thermogenesis, an energy burning process regulated by the sympathetic nervous system (SNS) in response to cold stress and overfeeding. While research suggests PACAP acts centrally at the level of the hypothalamus to regulate energy balance3-5, PACAP is also known to be expressed in the SNS. In preganglionic neurons innervating the adrenal medulla6, PACAP is co-localized with acetylcholine and regulates catecholamine synthesis and release. Recent neuronal tracing studies have shown that postganglionic fibres of the stellate ganglia innervate intrascapular brown adipose tissue (BAT), the main thermogenic tissue in mammals7. However, PACAP's role within the sympathetic nerves innervating and regulating energy metabolism in adipose tissues is not known. As such, our group is interested in characterizing PACAP and PACAP receptor expression in sympathetic nerves innervating and regulating energy metabolism in BAT (via the stellate ganglia) in response to metabolic stressors, such as cold stress. We hypothesize that PACAP is released from preganglionic nerves which binds PACAP receptors (PAC1, VPAC1, VPAC2) expressed in postganglionic nerves of the stellate ganglia. Here we report, for the first time, PAC1 and VPAC1 expression in the stellate ganglia with sex-specific differential gene expression based on housing temperature. Analysis of PAC1 splice variant expression identified at least two variants in tissues of the SNS (adrenal gland, superior cervical ganglia and the stellate ganglia). These results will support future functional studies characterizing PACAP regulation of catecholamine production in peripheral ganglia which will contribute to assessing G-protein coupled receptors (GPCRs) as potential therapeutic targets for obesity and metabolic disease.

References

1. Gray SL, Cline DL. 2019. Fink G, Ed. Elsevier: London UK. p.279-91. 2. Mustafa T. 2013. Adv Pharmacol. San Diego, Calif. p.445-57. 3. Banki E, Pakai E, Gaszner B, et al. 2014. J Mol Neurosci 54(3): 543-54. 4. Contreras C, Gonzalez F, Fernø J et al. 2015. Ann Med. 47(2): 150-68. 5. Resch JM, Maunze B, Gerhardt AK, et al. 2013. Am J Physiol-Endoc M. 305(12): E1452-E1463. 6. Eiden LE, Emery AC, Zhang L, et al. 2018. Pflügers Arch. 470(1): 79-88. 7.François M, Torres H, Huesing C, et al. 2019. Ann N T Acad Sci. 1454(1): 3-13.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON37 Diabetes and Hypopituitarism Secondary to Iron Overload in a Patient with Pure Red Cell Aplasia
Authors: Jo Inha , Mora Guido , Robinson Sylvia , Minutti Carla
Published: November 2022

Background

Pure red cell aplasia is a rare bone marrow disorder that results in decline in red blood cell production by the bone marrow. Treatment involves multiple blood transfusions to keep up the red blood cell count, which can lead to iron overload. Hypopituitarism is a condition, where two or more pituitary hormones are deficient. Here we present a case of diabetes and hypopituitarism secondary to iron overload from blood transfusions.

Clinical Case

A 19 year male with pure red cell aplasia was admitted for anemia and was noted to have short stature with growth percentile at 0.36% with predicted MPH estimated to be 180.5 cm. He was Tanner stage 2 on exam and work-up showed IGF1 128 (n 281-510 ng/mL), Testosterone of <1 (n 250-1100 ng/dL), LH 1.1 (n 1-10 mIU/mL), FSH 1.5 (n 1-10 mIU/mL), delayed bone age of 15 years consistent with delayed puberty and hypogonadotropic hypogonadism so he was initiated on 50 mg IM Testosterone monthly. After 1 month, he presented to the hospital again for mild DKA secondary to high dose steroids as part of treatment for his underlying medical condition and also pancreatic dysfunction given history of regular transfusions and iron overload. Initial Fructosamine level was 438 equivalent to HgbA1c of ∼10-11%. He was started on SQ insulin regimen with both long- and short-acting insulin and 50 mcg Levothyroxine as thyroid levels checked during admission showed hypothyroid state, thus, meeting diagnostic criteria for hypopituitarism. Brain MRI was obtained which was negative for mass or lesions, however abdominal MRI showed very high level iron overload on liver, spleen and pancreas. Steroids were weaned and insulin regimen was adjusted on a regular interval according to his blood glucose levels, however, he was not able to wean off insulin even after steroids were discontinued and was transitioned to 70/30 regimen for ease of management with normalization of Fructosamine levels. His testosterone was eventually increased up to 200 mg and was transitioned to daily topical Androgel and currently increasing dose gradually. His most recent testosterone level was 38 ng/dL with goal range of 400-600 ng/dL. His thyroid levels continued to be stable on current dose. He had passed the ACTH stimulation test ∼4-6 weeks after discontinuation of steroids and decided not to pursue growth hormone therapy.

Conclusion

Patients who receive regular blood transfusions are at risk of iron overload, which can affect multiple organs including the pancreas and pituitary gland. This can subsequently lead to insulin-dependent diabetes and hypopituitarism, which should bring awareness of regular assessment of diabetes and pituitary function starting early in life.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP034 Circulating Protein Biomarkers for Discriminating Malignant from Benign Adrenal Tumors Using Mass Spectrometry-Based Proteomic Analysis
Authors: Park Seung Shin , Moon Sun Joon , Jang Han N , Han Dohyun , Kim Jung Hee
Published: November 2022

Backgrounds

Adrenal cortical carcinoma (ACC) is a rare malignant tumor derived from the adrenal gland with a poor prognosis. Since there is no effective medical treatment, early diagnosis and surgical resection are the only way to cure ACC completely. However, early diagnosis of ACC is sometimes tricky because there are no useful diagnostic biomarkers to differentiate ACC from benign adrenal tumors. Therefore, we aimed to identify circulating protein biomarkers to distinguish malignant from benign adrenal tumors using mass spectrometry-based proteomic analysis.

Methods

Plasma samples were obtained from 27 patients with ACC and 69 age- and sex-matched patients with adrenal adenoma. We performed the liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a data-independent acquisition (DIA) method in plasma samples. Among the quantified 381 proteins, differentially expressed proteins (DEPs) were selected using Student's t-tests for pairwise comparison with a false discovery rate < 0. 05 and |fold-change|> 1.5. In addition, we performed machine learning algorithms such as random forest and XGBoost to select featured DEPs to discriminate ACC.

Results

The mean age of patients was 52 years, and 38 (39.6%) patients were male. Among 19 DEPs, 8 proteins were overexpressed and 11 were underexpressed in ACC patients. In a further analysis using machine learning algorithms, random forest identified 4 proteins as important features for establishing the classifier. The panels with these four proteins showed a good discrimination performance with an area under the curve (AUC) of 0.94 and an accuracy of 0.96. Eight proteins were identified in the XGBoost algorithm. Four proteins in plasma samples were common DEPs from the traditional methods and machine learning algorithms.

Conclusions

High plasma levels of two proteins (One is involved in the migration, attachment and organization of cells into tissues. The other is V region of the variable domain of immunoglobulin light chains), and low plasma levels of two proteins (One is involved in cell-cell adhesion and recognition. The other is V region of the variable domain of immunoglobulin heavy chain) might be circulating protein biomarkers of ACCs compared with benign adrenal adenomas.

Presentation: No date and time listed
PMON49 Checkpoint Inhibitor Induced Hypophysitis with Growth Hormone Deficiency and Implications for the Treatment of ACTH Deficiency
Authors: DeCherney Stephen , Favoreto Natalia , Fiacco Nicholas , Ishizawar Rumey , Saxena-Beem Shruti
Published: November 2022

Background/Purpose

Hypophysitis is a known complication of immune checkpoint inhibitor (ICI) therapies used in the treatment of malignant cancers. In general, central adrenal insufficiency (AI) and hypothyroidism are the most recognized deficiencies following a diagnosis of ICI induced hypophysitis. As a result, other hypothalamic-pituitary axes (HPAs) are either incompletely evaluated or are disregarded from a therapeutic standpoint. Of particular importance is the growth hormone axis which is well established to affect tissue level metabolism of cortisol and cortisone through its effect on 11 beta hydroxysteroid dehydrogenase in target tissues. Our hypothesis is that growth hormone deficiency is also present in ICI induced hypophysitis.

Methods

We queried current and legacy electronic medical records of patients who received ICI for clinical notes mentioning adrenal insufficiency and concern for hypophysitis using the EMERSE tool. Patients with ICI exposure were included if they had 2 of the following 3 criteria; new onset central AI as defined by a low ACTH and cortisol, pituitary imaging suggestive of hypophysitis, or clinical presentation concerning hypophysitis. Patients were excludedfrom the analysis if there was a history of brain irradiation or in whom the diagnosis was not clear due to high dose steroid exposure prior to biochemical evaluation.

Results

Twenty-nine patients met inclusion criteria. Out of 29 patients, 16 underwent testing of the growth hormone axis with IGF-1 (11) and/or random growth hormone level (5). Seventeen patients (59%) had biochemical evidence of deficiency of 3 or more HPAs. Twenty-six patients (90%) had biochemical evidence of 2 or more PHAs. Two patients only underwent evaluation of 2 pituitary axes so it is unknown if they indeed suffered from panhypopituitarism. Most patients (28/29) were prescribed hydrocortisone for AI with an average dose of 20 mg per day.

Conclusions

Our findings are suggestive that growth hormone deficiency may be present in ICI induced hypophysitis. This finding holds implications for cortisol replacement therapy for coexisting AI. When one considers the average adrenal cortisol production is 5.7–7.4 mg/m2/day or 9.5–9.9 mg/day, 20 mg of daily cortisol replacementmay be too high in the face of concomitant growth hormone deficiency. Practice changes may include lower doses ofhydrocortisone replacement or adjustment to cortisone acetate which has been shown to have more favorable effectson tissue level metabolic effects.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON69 Effective Suppression of Gonadotropins and Gonadal Steroids Following Oral Administration of Leuprolide
Authors: Shangold Gary , Rubin Arkady , Daggs Thomas , Vrettos John , Rasums Andrejs , Consalvo Angelo , Skeet Nicola , Shields Paul
Published: November 2022

A platform designed to enable systemic delivery of peptides via the oral-GI route was employed to deliver low doses of leuprolide --- 4 mg qd (Treatment A, n=9), 4 mg bid (Treatment B, n=9), and 10 mg bid (Treatment D, n=12) --- daily for 28 days to regularly-menstruating, healthy female volunteers. Pharmacodynamic (PD) effects on LH, FSH, estradiol, and progesterone, along with leuprolide drug levels, were assessed weekly and compared to those following a single intramuscular injection of leuprolide acetate 3.75 mg (Treatment C, n=5) in a parallel-group design. The primary PD endpoint was the subject incidence of E2 suppression to ≤40 pg/mL on Treatment Day 29; additional endpoints --- E2 suppression rates on Treatment Days 8, 15 and 22, incidence of 'ovulation' defined as progesterone level ≥3 ng/mL, and suppression of LH and FSH levels --- were assessed on Treatment Days 8, 15, 22, and 29. Safety and tolerability of the test drugs was also assessed. Dose-dependent suppression of E2 was seen, with 66.7%, 87.5%, 100% and 100% of subjects in Treatments A, B, C and D, respectively, achieving E2 ≤40 pg/mL. Median E2 levels on days 15, 22, and 29 were <40 pg/mL after 4 mg bid po, and <20 pg/mL after both 10 mg bid po and the 3.75 mg injection. 'Ovulation rates’ on days 22 and 29 were 0% after both 10 mg bid po and 3.75 mg im. Because of the initial burst following injection of the monthly depot, leuprolide Cmax was greater in Treatment C (17.5 ±2.7 ng/mL) on Dosing Day 1 than for oral leuprolide (3.7 ±3.2 ng/mL for 4 mg qd, 4.1 ±5.1 ng/mL for 4 mg bid), though by Day 29, Css in Treatment C (1.7 ±1.2 ng/mL) was lower than that day's Cmax for oral leuprolide (2.7 ±3.6 ng/mL for 4 mg qd, 4.8 ±6.2 ng/mL for 4 mg bid). Cmax and AUC0-24h were dose-dependent but not strictly dose-proportional. Leuprolide "trough" levels prior to oral dosing were frequently below LLQ (25 pg/mL) in subjects treated with 4 mg qd; this occurred in only 6% of samples on 10 mg bid, and 0% on 4 mg bid, thus confirming reliability of oral delivery of leuprolide. There were no Serious or severe Adverse Events, nor changes in laboratory values of concern. One subject discontinued the study due to a transient episode of nausea, vomiting, and headache during her initial dose of 4 mg po. A total of 80 AEs were treatment-emergent, generally mild in intensity, and spread relatively evenly across all 4 treatment groups. This investigation confirms effective suppression of gonadal steroids via oral administration of leuprolide, comparable to that of injectable leuprolide, and to some marketed doses of GnRH antagonists (historical data).

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON73 Lipid profile in patients with Cushing's syndrome and the impact of surgical treatment
Authors: Varghese Ron , McGlotten Raven , Shamburek Robert , Nieman Lynnette
Published: November 2022

Introduction

Cushing syndrome (CS) patients have an increased mortality rate, primarily due to increased cardiovascular and cerebrovascular disease. We postulated that lipoprotein or lipid profiles might underlie this risk.

Methods

We measured traditional lipid panels (Cholesterol, TC; calculated low density lipoprotein, LDL; triglycerides, TG; high density lipoprotein, HDL) by Abbot enzymatic assay and lipoprotein particles (particle size and number for HDL, LDL and VLDL) by nuclear magnetic resonance spectroscopy in CS patients before and after surgical remission. Values are shown as median (IQR or range).

Results

After initial evaluation, 41 subjects (median age 53 (IQR 39-63) years; 27 female) had presumed Cushing's disease (CD, n=23), ectopic ACTH secretion (EAS, n=17), or adrenal adenoma (AA, n=1). Fourteen were on chronic statin therapy. All median lipid values were normal except HDL, at 55mg/dl (range 27 - 59mg/dl, normal (RR) <60). Twenty-six patients had decreased HDL; of these, other abnormal values included TC and LDL (n=4), TG (n=4), TC, LDL, TG (n=2), LDL and TG (n=2) or LDL only (n=2). Other elevated LDL levels occurred alone (n=1) or with TC (n=2). Three patients had only an increase in TC, LDL, or TG. Median LDL particle number was increased at 1015 (IQR 809-1353; RR <1000), with normal particle size. Eighteen patients had increased LDL particle number (1005 - 2989); 7/18 had increased TC and/or LDL. The median particle size and number for HDL and VLDL were normal in all patients except for one with an increased VLDL particle number of 199.7 (RR 6.8 - 126.1; TGs 302mg/dl, LDL 61 mg/dl, HDL 36 mg/dl, Chol 158 mg/dl). Sixteen subjects with CD (n=10), EAS (n=5) or AA (n=1) (13 females, median age 53 (IQR 40-58) years) had data at last study visit (LSV) after surgical remission. At LSV (median 13 months, range 3-26 months) abnormal preoperative LDL particle size persisted in 5/10, with new abnormalities (to 1450nm) in 3 patients. Initially high LDL and TC normalized in 3/6 and 4/5 patients. Abnormal HDL values were new in 2 patients and persisted in 7/8 from baseline. HDL particle number was low in two of these patients, while one with an HDL of 90mg/dl had increased particle size (10.6nm). TG and VLDL particle number and size remained normal except for one patient with low values. A statistically significant decrease (p=0.03) of median VLDL particle size from 49.5 nm (IQR 47.8-52.5) to 45.5nm (IQR 43.3–49.6), was noted at LSV.

Conclusions

While the numbers are small, these data suggest that the moderate cardiovascular risk conferred by elevated LDL particle size and low HDL persisted for up to 26 months of remission. Improved initiation and modification of treatment for these abnormalities might improve outcomes.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP036 Cortisol Values During the Standard-Dose Cosyntropin Stimulation Test: Personal Experience with Elecsys Cortisol II Assay
Authors: Hamrahian Amir , Dinparastisaleh Roshan , Husni Hasan , Abusamaan Mohammed , Sokoll Lori , Salvatori Roberto
Published: November 2022

Background

There has been debate regarding the appropriate cortisol cutoffs during the cosyntropin stimulation test (CST) when the newer cortisol assays are used. Recent studies have recommended cortisol cutoffs lower than previously recommended. We aimed to evaluate the cortisol levels during the standard dose CST in patients evaluated for adrenal insufficiency and found to have a normal HPA axis using the Elecsys ® Cortisol II (Roche Diagnostics)assay. METHODS: This was a retrospective chart review study of adult patients who had the CST performed within an academic ambulatory setting from January 2018 to December 2020. They had ICD-10 codes of pituitary gland disorders in their problem list or diagnoses at the time of data extraction. Only patients with a normal HPA axis were included in the analysis, which was defined based on evaluation by an endocrinologist, restrictive exclusion criteria, and a lack of glucocorticoid administration for at least 6 months after CST. Exclusion criteria included oral glucocorticoid use within 6 months before the CST or 3 months for other routes, albumin < 2.5 g/dL, liver disease, pituitary insult within 6 weeks before the CST, estrogen and opioid use within 3 months before the CST, and pregnancy. The results are reported in the median (range).

Results

Out of 305 patients, 63 (20.6) met the study criteria. The median age was 54.7 (27.6-89.1) years; 32 (51%) were females, and 27 (43%) were white. The duration of follow-up after the CST was 13.9 (6.3-43.9) months. Cortisol values at 30- and 60-minutes post-CST were available for 43 (68.2%), and 61 patients (96.8%), respectively. The cortisol levels at 30- and 60-minutes after the CST were 21.7 (15.7-29.1) µg/dL and 24.4 (17.9-35.8) µg/dL, respectively. The lowest cortisol levels at 30 and 60 minutes after the CST for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the entire cohort.

Conclusion

Our study supports using a lower cortisol cutoff value at 30 minutes after the CST using the Roche Elecsys ® Cortisol II assay. The lowest cortisol level in our cohort was 15.7 ug/dL. However, the same pass criteria cannot be used at 60 minutes. Therefore, it is essential to consider the time of cortisol draw after the CST.

Presentation: No date and time listed
PMON84 A Unique Case of Diabetes Insipidus Revealing Hodgkin's lymphoma
Authors: Akcan Tugce , Patel Hiral , Pathak Ram
Published: November 2022

Introduction

While diabetes insipidus rarely presents as a symptom of non-Hodgkin's lymphoma, it is very rarely a revealing symptom of Hodgkin's lymphoma. We present a case of this unique association.

Case presentation

We report a case of a 25-year-old previously healthy male with no significant past medical history who presented with complaints of polydipsia, polyuria, and nocturia. A water deprivation test confirmed central diabetes insipidus. He started therapy with oral desmopressin and had clinical improvement. Magnetic resonance imaging (MRI) of his head showed thickened infundibulum and a lack of posterior pituitary bright spot, consistent with infundibulo-neurohypophysitis. There were no obvious masses within the anterior or posterior lobe, nor were suprasellar soft tissue masses noted. Diabetes mellitus (DM), autoimmune diseases, and infectious diseases were excluded. A chest x-ray revealed a superior mediastinal mass and a CT scan confirmed multiple mediastinal lymphadenopathies. A biopsy of pre-tracheal lymph node revealed nodular sclerosing Hodgkin's lymphoma. The patient received six cycles of chemotherapy with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) and achieved a complete remission. A follow up MRI head scan showed a decreasing in the thickness of infundibulum along with non-visualization of the posterior pituitary bright spot. Finally, his symptoms resolved with DDAVP therapy.

Conclusions

Diabetes insipidus involving the pituitary gland of Hodgkin's lymphoma is an extremely rare presentation of endocrine deficiency and malignancy. The literature describes only a few such cases. Clinicians should be aware diabetes insipidus might rarely present as a symptom of Hodgkin's lymphoma without obvious metastatic involvement of the neurohypophysial system. Continuing to report anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians who handle patients with a similar presentation.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP038 Efficacy of Medical Treatment Compared to Unilateral Adrenalectomy in a Cohort of Patients with Primary Aldosteronism Treated at the Centre Hospitalier Universitaire de Sherbrooke – CHUS
Authors: Boily Pascale , St-Jean Matthieu
Published: November 2022

Background

Primary aldosteronism (PA) is associated with a high burden of cardiometabolic complications such as coronary heart disease, atrial fibrillation, left ventricular hypertrophy, stroke and chronic kidney disease. It is therefore essential to screen, confirm the diagnosis and then implement a targeted treatment, to lower the rate of these complications. According to the latest Endocrine Society guidelines for the management of PA, unilateral adrenalectomy is recommended when the secretion of aldosterone is mostly coming from one adrenal. If the secretion is bilateral or if the patient refuse surgery, medical treatment with mineralocorticoid receptor antagonist is indicated. Nevertheless, there are limited data comparing these two treatments on their impact on the number and dosage of anti-hypertensive drugs needed to control the disease.

Objective

The objective was to compare the impact of medical or surgical treatment on the antihypertensive defined daily dose (DDD) after 6 months of treatment in our cohort of PA patients followed at the CHUS. We've also evaluated the kalemia, blood pressure and renin after 6 and 12 months of treatment. Long term blood pressure control has also been evaluated.

Methodology

To answer this question, we conducted a single-center retrospective cohort study. Adults followed at CHUS between 2000 and 2021, with a confirmed diagnosis of PA and a follow-up of at least 6 months were included. Pregnancy was the only exclusion criteria. The primary outcome was the variation in the antihypertensiveDDD in patients medically treated compared to those surgically treated after 6 months.

Results

A total of 46 patients were included in our cohort, from which 28 were medically treated. Patients in the surgical group were younger, had a higher diastolic blood pressure and aldosterone/renin ratio. Among the 18 patients who underwent unilateral adrenalectomy, only 6 of them had a clearly lateralized secretion confirmed by adrenal veins sampling. At 6 months, the antihypertensive DDD variation was statistically significantly higher in the surgical group, with a decrease of 1.7 compared to a decrease of 0.6 in the medical group. Even after age, diastolic blood pressure and aldosterone/renin ratio adjustments, the difference between the 2 groups remains statistically significant, with a p value of 0. 033.

Conclusion

These results indicate that the surgical treatment of patient with primary aldosteronism leads to a greater DDD decrease at 6 months, even after adjusting for disease severity and despite the fact that the surgical group is not exclusively unilateral. However, the impact of disease control on long-term outcomes could not be assessed due to missing data.

Presentation: No date and time listed