bluuebunny/crossref_metadata_2025 huggingface dataset:
12426 Performance Of Dehydroepiandrosterone-Sulphate In Diagnosing Mild Autonomous Cortisol Secretion: A Systematic Review And Meta-Analysis
Authors: Saini Jasmine , Salama Bahaa , Renate Chacko Shireen , Yu Kai , Bancos Irina
Published: October 2024

Disclosure: J. Saini: None. B. Salama: None. S.R. Chacko: None. K. Yu: None. I. Bancos: None.

Objective: Measurement of baseline dehydroepiandrosterone sulfate (DHEAS) is suggested by the guidelines in support of diagnosing mild autonomous cortisol secretion (MACS). However, evidence on the diagnostic accuracy of DHEAS in MACS is difficult to interpret due to differences in the diagnostic cutoffs, small sample size, and heterogeneous reference standards. We aimed to conduct a systematic review and meta-analysis of published literature to assess the performance of DHEAS in diagnosing MACS, as defined in the 2023 guidelines. Methods: A comprehensive search was conducted using several databases from each database’s inception to January 8th, 2024. Databases include Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Databases of Systematic Reviews, and Scopus. Only original studies of at least 20 participants were included. MACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. QUADAS-2 was used to assess the risk of bias. Bivariate and random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results: The initial search yielded 285 articles, and only 7 studies met the inclusion criteria. In 7 studies (1 from North America, 3 from Asia, and 3 from Europe), a total of 574 patients with MACS and 830 referent subjects (patients with adrenal tumors without MACS) were included. The mean age was specified only in 5 studies and was similar in patients with MACS (55.5 years) and referent group (53.3 years). Patients with MACS had a higher number of women (323/472, 68.4%) as compared to the referent group (352/658, 53.4%). DHEAS cutoffs studied included: lower cutoff of age-and sex-specific ranges (3 studies), 40 mcg/dL (3 studies), 60 mcg/dL (1 study), and 67.5 mcg/dL (1 study). With increasing DHEAS cutoff, sensitivity for MACS diagnosis increased, and specificity decreased. Most studies (4 studies) used the chemiluminescent immunoassay to measure DHEAS. A meta-analysis of studies using DHEAS cut-off between 40-70 mcg/dL was performed, with a pooled sensitivity of 68% (95% CI: 51-81) and a pooled specificity of 85% (78-89). The positive likelihood ratio was 4 (95% CI: 3-6; I2=36.94, P=0.175) and the negative likelihood ratio was 0.4 (0.3-0.6; I2=49.97, P=0.092). Most studies were at a high risk of bias for selection of patients, index, or reference standard. Conclusion: Based on limited heterogeneous evidence, measurement of DHEAS provides additional value in diagnosing MACS. Further larger diagnostic accuracy studies should explore various DHEAS cutoffs and consider assay variability.

Presentation: 6/3/2024
5142 Pheochromocytoma In The ICU- Hiding In Plain Sight
Authors: Chandrashekar N , Arafah B
Published: October 2024

Disclosure: N. Chandrashekar: None. B. Arafah: None.

Introduction: Pheochromocytomas are catecholamine-secreting tumors that are rare but dangerous and occur in <0.2% of patients with hypertension. Case: A 28 year old female with a 10 year history of hypertension and invasive stage 2b cervical cancer s/p chemoradiation presented to the hospital with circulatory shock from Takutsubo cardiomyopathy requiring intubation, vasopressors, CVVH, and ECMO. The endocrinology service was consulted due to a highly vascular, 3.6 cm, ∼23 Hounsfield units right adrenal mass evidenced on CT abdomen done months prior to admission. There were elevations in plasma normetanephrine to 15 nmol/L (ref <0.90 nmol/L), plasma metanephrine to 1.5 nmol/L (ref <0.50 nmol/L), urinary metanephrine to 565 ug/24-hours (ref 36 - 209 ug/24-hr), and urinary normetanephrine to 2580 ug/24-hr (ref 95 - 449 ug/24-hr). With her acute illness and recent use of vasopressors and quetiapine, these labs could not be accurately interpreted, and outpatient follow up was recommended. She was discharged home on metoprolol and hydralazine for hypertension management by her primary team. She was re-admitted to the CICU 2 days later for hypertensive emergency with flash pulmonary edema. With further questioning, she endorsed longstanding hypertension with episodes of headaches, palpitations, and vomiting. Her cancer therapy related menopause caused frequent nighttime hot flashes while inpatient. These episodes precipitated witnessed symptoms of catecholamine release with severe hypertension and palpitations. It was noted during her hospitalization that her symptoms were controlled during the day with frequent escape during the night despite continuous alpha and subsequent beta blockade every 6 hrs. Estrogen therapy would have been beneficial, however given a recent DVT, this was avoided and instead megestrol acetate and venlafaxine were used. With these additions, her adrenergic spells completely resolved. She then underwent a right adrenalectomy and had no significant fluctuations in her BP intraoperatively with complete resolutions of symptoms postoperatively. The pathology revealed a right 2.7 cm pheochromocytoma with no local invasion or distant metastasis. Conclusion: This is a case of pheochromocytoma crisis with cardiogenic shock followed by subsequent hypertensive emergency in the setting of inappropriate beta-blocker use. Confounders like vasopressors (increases catecholamines), intrinsic stress of critical illness (increases catecholamines), and quetiapine use (can increase normetanephrine levels) make it difficult to analyze labs. In these cases, a thorough history and imaging are key to establishing a diagnosis and initiating life-saving treatment. Another unique feature of this case is the control of the patient’s triggering menopausal hot flashes with megace and venlafaxine to preempt adrenergic spells during her admission.

Presentation: 6/2/2024
6794 Primary Adrenal Insufficiency Following Bilateral Adrenal Hemorrhage Secondary To Antiphospholipid Syndrome
Authors: Alameri Majid , Mohamed Alnuaimi Abdulla , Alabrach Yousef , Abbas Aymen , Baroud Sarah , El Khazendar Mohammed
Published: October 2024

Disclosure: M. Alameri: None. A.M. Alnuaimi: None. Y. Alabrach: None. A. Abbas: None. S. Baroud: None. M. El Khazendar: None.

Introduction: Adrenal insufficiency (AI) is a rare life-threatening complication of antiphospholipid antibody syndrome (APS) accounting for 0.4% to 0.5% of Al cases. Case report: A 26-year-old female with background history of primary antiphospholipid syndrome (PAPS) presented with 3 weeks history of dull abdominal pain and fatigue. Examination revealed dehydration, orthostatic hypotension and hyperpigmented skin. Biochemistry assessment was consistent with primary adrenal insufficiency (hyponatremia 125 mol/L, hyperkalaemia 6.8 mmol/L, low random cortisol 142 mol/L, high ATCH 440 pmol/L [N 1.6-13.9], low aldosterone <1.05 ng/dL and high renin 128 ng/L [N 4-23.7]). She received 100mg hydrocortisone followed by regular IV hydrocortisone q6hrs. CT abdomen revealed bilaterally enlarged hyperdense adrenal glands suggestive of haemorrhage. Adrenal MRI confirmed subacute bilateral adrenal haemorrhage (BAH) replacing whole adrenal glands with hemosiderin depositions and calcifications without evidence of underlying tumor. Anti-21-hydroxylase antibody came back negative. She was discharged on hydrocortisone, fludrocortisone and hydroxychloroquine. Education was given for sick days rule and hydrocortisone emergency kit was provided for adrenal crisis. Discussion and conclusion: We describe a patient with APS, who developed Al due to bilateral subacute adrenal haemorrhages. Adrenal haemorrhage is rare but life-threatening complication of APS. High clinical vigilance is important to consider adrenal haemorrhage in differential diagnosis of Al, specifically in patients with known antiphospholipid antibody syndrome (APS).

Presentation: 6/3/2024
7446 Primary Adrenal Mature Teratoma Initially Diagnosed As An Adrenal Myelolipoma
Authors: White-Cotsmire A , Kodali B , Avram A M , Shah S S
Published: October 2024

Disclosure: A. White-Cotsmire: None. B. Kodali: None. A.M. Avram: None. S.S. Shah: None.

Background: Teratomas are a type of germ cell tumor containing different types of tissue (e.g., hair, teeth, bone adipose, muscle). Most teratomas are benign (i.e., mature), but they may also be malignant (i.e., immature). Both immature and mature teratomas contain derivatives of ectoderm, endoderm, and mesoderm; however, immature teratomas are differentiated by the presence of embryonic, usually neuroectodermal, tissue. Mature teratomas have the potential for malignant transformation (1–2% of cases), usually squamous cell carcinoma within the teratoma. Extra-gonadal teratomas are rare (only 1–5%); reported locations include sacrococcygeal, head and neck, retroperitoneum, mediastinum, brain and spine, liver, and rarely adrenal glands. (1) Only 18 cases of adult primary adrenal teratomas have been reported since 1952. (2)Clinical Case: A 48-year-old woman with 4 days of worsening abdominal pain underwent CT imaging, which demonstrated a 6cm complex left adrenal mass containing peripheral and scattered internal-coarse calcifications with internal soft tissue and fat components, suggestive of adrenal myelolipoma with probable sequela of previous hemorrhage. Subsequent endocrine follow-up ruled out a cortisol secreting tumor with a negative dexamethasone suppression test and pheochromocytoma with normal serum free metanephrines and normetanephrines. Dedicated adrenal protocol CT scan further characterized the mass as a mature adrenal teratoma containing a rudimentary mandible and two teeth within the soft tissue associated with internal microscopic fat. The left renal vein was anteriorly displaced by this left adrenal mass and severely narrowed by the large adrenal mass, with development of left retroperitoneal collateral venous drainage from the left kidney into the lumbar venous system. The patient opted for conservative management with active clinical surveillance. Conclusion: This is a rare case of adrenal mature teratoma in an adult, originally diagnosed as an adrenal myelolipoma. This case highlights the use of more dedicated adrenal imaging for the characterization of adrenal tumors and the broad differential of benign non-functional adrenal tumors, including myelolipomas, lipomas, angiomyolipomas, and nonfunctional adenomas. However, a definitive diagnosis can only be confirmed by surgical removal of the tumor, usually through a laparoscopic approach, with histopathologic evaluation. References: (1) O’Donovan EJ, Thway K, Moskovic EC. Extragonadal teratomas of the adult abdomen and pelvis: a pictorial review. Br J Radiol. 2014;87(1041):20140116. doi:10.1259/bjr.20140116(2) Zhou L, Pan X, He T, et al. Primary adrenal teratoma: A case series and review of the literature. Mol Clin Oncol. 2018;9(4):437-442. doi:10.3892/mco.2018.1687

Presentation: 6/1/2024
8104 Rare Case Of Ectopic Cushing’s Syndrome Secondary To Metastatic Parotid Pleomorphic Adenocarcinoma
Authors: Sean Neutel Bradley , Manroa Pooja
Published: October 2024

Disclosure: B.S. Neutel: None. P. Manroa: None.

Background: Pleomorphic adenocarcinoma of the parotid gland is a rare malignancy and ectopic ACTH secretion from these tumors is very rarely described. We report a case of ectopic Cushing’s syndrome (CS) in such a patient and describe the clinical course. Clinical Case: A 69-year-old female with left parotid pleomorphic adenocarcinoma status post surgery and adjuvant radiotherapy presented to her local hospital approximately 7 months after initial treatment with proximal muscle weakness and near-syncope. Workup revealed profound hypokalemia at 1.6 mmol/L (n 3.5-5.3 mmol/L) along with new-onset hypertension (BP 175/110 mm Hg) and hyperglycemia with a HbA1c 6.5 % (n <5.7%), as well as metabolic alkalosis with a bicarbonate level of >40 mmol/L (n 22-32 mmol/L). A CT scan showed multiple liver metastases and a biopsy confirmed metastatic parotid pleomorphic adenocarcinoma. She was then transferred to our comprehensive cancer center for further management. She reported muscle weakness, easy bruising, and facial edema. She denied acne, hirsutism, or abdominal striae. Endocrine workup revealed a random cortisol of 56 mcg/dL (n 3-18 mcg/dL) and ACTH of 378 pg/mL (n 7.2-63.3 pg/mL). Her AM cortisol level remained unsuppressed at 79.2 and 59.4 mcg/dL (n< 1.8 mcg/dL) after 1 mg and 8 mg overnight dexamethasone suppression tests respectively. Late-night salivary cortisol was 7.9 mcg/dL (n <0.112 mcg/dL). An MRI of the sella was negative for any pituitary lesions. After stabilizing her clinical condition and correcting electrolyte abnormalities, she was started on chemotherapy with paclitaxel and carboplatin by the oncologist. Based on clinical suspicion of ectopic CS, ketoconazole was started and titrated upwards with rapid improvement of blood pressure, hypokalemia, and hyperglycemia. She was discharged home and antihypertensives were tapered off. ACTH staining on the liver biopsy was unable to be performed due to paucity of the specimen. A Ga-68-DOTATATE PET CT revealed increased radiotracer uptake in the liver lesion suggestive of SSTR 2 receptor positivity. Despite initial clinical improvement, her disease progressed with widespread liver, lymph node, and osseous metastases within 3 months necessitating escalating doses of ketoconazole, spironolactone, and potassium supplementation. The patient elected to pursue hospice care due to intolerance to chemotherapy and passed away shortly afterward. Conclusion: Although ectopic CS caused by parotid pleomorphic adenocarcinoma is rare, prompt recognition and treatment is necessary because ectopic ACTH production is associated with poor prognosis in these patients.

Presentation: 6/3/2024
8180 Rare Variants Of Adrenocortical Carcinoma: A Retrospective Cohort Study
Authors: Villavicencio Torres Camila A , Bancos Irina
Published: October 2024

Disclosure: C.A. Villavicencio Torres: None. I. Bancos: None.

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an estimated annual incidence of 0.7-2 cases per million per year. Scarce data are available on rare histological variants of ACC. Objective: To describe the clinical presentation and outcomes of patients diagnosed with oncocytic, sarcomatoid and myxoid ACC variants. Methods: Retrospective single center cohort study, 1992-2021 of patients with rare histological ACC variant. Results: A total of 20 patients were diagnosed with oncocytic (17, 85%), sarcomatoid (2, 10%), or myxoid (1, 5%) ACC. Median age of diagnosis was 47 years (range 17-80), and 14 (70%) were women. All patients had unilateral ACC (12, 60% left) with a median tumor size of 11 cm (range 4-29). Adrenal hormone excess was documented in 10 (50%) patients, mostly with either glucocorticoid or androgen excess. ENSAT stage I, II, III, and IV was documented in 2 (10%), 10 (50%), 6 (30%), and 2 (10%) patients, respectively. All patients were treated with adrenalectomy (laparoscopic in 5 and open in 15). In addition, patients were treated with mitotane (10, 50%), radiation (7, 35%), and chemotherapy (5,25%). Mitotane was administered for a median of 12 months (range 4-31) and was discontinued mainly due to side effects in 9 (90%) patients. Patients were followed for a median follow up of 6.5 years (range 0.4-12). In addition to 2 patients who presented with ENSAT stage IV metastatic disease, metastatic disease developed in additional 6 (30%) patients who initially presented with localized ACC (3 stage 2, 3 stage 3, 5 oncocytic, 1 sarcomatoid). Metastatic sites included lung (n=2), omentum (n=1), duodenum (n=1), liver (n=4), and bones (n=1). At the end of follow up, 11 (55%) patients remained disease free (53% oncocytic, 50% sarcomatoid, 100% myxoid), 5 (25%) patients were alive with metastatic ACC (23% oncocytic, 50% sarcomatoid), and 4 patients died of ACC (median time to death 21 months (range 10-50) post-adrenalectomy). Conclusions: Patients with oncocytic, sarcomatoid, and myxoid ACC may have a better prognosis than in reported literature. Larger multicenter studies are needed to identify patient and tumor-specific factors that guide management to assure improved outcomes in these very rare patients.

Presentation: 6/2/2024
7432 Secondary Adrenal Insufficiency Caused By Concurrent Treatment With Budesonide And Itraconazole
Authors: Anjum F , Jakoby M G
Published: October 2024

Disclosure: F. Anjum: None. M.G. Jakoby: None.

Introduction: Inhaled corticosteroids (ICS) are unlikely to affect corticotroph axis function even at high doses due to low systemic absorption. However, co-treatment with drugs that reduce hepatic clearance of ICS may predispose patients to secondary adrenal insufficiency (AI). We report a case of secondary AI that occurred during concurrent treatment with budesonide and itraconazole. Case presentation: A 42-year-old female with longstanding asthma managed with inhaled budesonide (160 μg twice daily) was started on itraconazole (200 mg twice daily) for management of pulmonary histoplasmosis. Over the next three months, she experienced severe fatigue, and laboratory evaluation was notable for an undetectable (< 0.4 μg/dL) 8 AM cortisol level. Serum sodium (140 mM, 136-145) and potassium (4.6 mM, 3.5-5.1) were unremarkable, and a diagnosis of drug induced secondary AI was made. Treatment with hydrocortisone (15 mg in the morning, 5 mg in the evening) was started, and the patient’s infectious disease specialist stopped itraconazole, substituting posaconazole (300 mg daily) for an additional six months. Her pulmonologist substituted fluticasone (250 μg twice daily) for budesonide. After an approximate two-month hydrocortisone taper, 8 AM ACTH level was easily detectable (37.2 pg/mL, 7.2-63.3), though 30 min stimulated cortisol level was subnormal (11.1 μg/dL, expected > 18). Hydrocortisone was successfully tapered off over an additional two-months (30 min stimulated cortisol 23.4 μg/dL). Discussion: The literature on ICS induced secondary AI is generally case reports and series, and the incidence is very low (1.1/10,000 patient-years at risk). Limited oral bioavailability, high deposition in lungs, extensive protein binding, and robust hepatic clearance are factors that minimize the effects of ICS on corticotroph axis function. However, concurrent treatment with potent CYP3A4 inhibitors like itraconazole can significantly reduce hepatic clearance of ICS and predispose to systemic effects, including Cushing syndrome when high dose ICS are prescribed or secondary AI at lower doses. In a series of 25 cystic fibrosis patients co-treated with itraconazole and budesonide, 11/25 (44%) developed secondary AI. Our patient likely developed secondary AI but not Cushing syndrome due to treatment with low dose budesonide. This case illustrates the importance that endocrinologists recognize CY3A4 inhibiting drugs as a risk factor for secondary AI in patient treated with ICS.

Presentation: 6/3/2024
7213 Severe IGF-2 Mediated Hypoglycemia In A Patient With Adrenocortical Carcinoma: A Case Report
Authors: Pereira M Camelo , Itersky P , Sternlieb S , Manuel N , Dendy J
Published: October 2024

Disclosure: M. Camelo Pereira: None. P. Itersky: None. S. Sternlieb: None. N. Manuel: None. J. Dendy: None.

Background: Hypoglycemia has been rarely described as a complication of adrenocortical carcinoma (ACC). Tumor cells produce insulin-like growth factor II, causing a paraneoplastic syndrome with severe refractory hypoglycemia. We report the unusual case of a patient with known ACC presented with seizures and severe IGF-2 mediated hypoglycemia. Clinical case: A 21-year-old man presented to a regional hospital due to new onset seizures in September 2023. He had been diagnosed with ACC in July 2022, when he presented to the hospital with frank Cushing’s syndrome. CT scan of his chest and abdomen at that time revealed a large left suprarenal mass and multiple lung and liver masses; a biopsy from the liver lesion confirmed the diagnosis of ACC and he was started on treatment with mitotane, levoketoconazole and hydrocortisone. Oncology attempted treatment with 3 cycles of cisplatin and etoposide, with no significant response; subsequently, treatment with Keytruda initially decreased tumor size, but ultimately his CT scan showed progression of disease and mitotane was stopped in August 2023. When brought to the hospital in September 2023 due to seizures and altered mental status, the patient’s blood glucose (BG) was 25 mg/dL (70-110 mg/dL) on point of care testing, so he was started on IV 10% dextrose with improvement in BG and mental status. He underwent endotracheal intubation and was taken to the intensive care unit, showed improvement and was eventually transferred to the general medical floor, where the dextrose infusion was discontinued. However, the following day, he had another hypoglycemic episode complicated with a seizure and had to be reintubated, returning to intensive care. The patient was subsequently transferred to a large tertiary hospital. Evaluation showed undetectable point-of-care BG (< 5 mg/dL) as well as hypokalemia. Fasting labs showed undetectable BHB, undetectable insulin, C-peptide of 0.32 ng/mL (0.78 - 5.19 ng/mL), and negative insulin antibodies. IGF-2/IGF-1 ratio was elevated at 15.6, suggesting IGF-2 mediated hypoglycemia. He was started on IV glucose 20% and glucagon infusions. Mitotane was restarted aiming to decrease tumor burden and consequently IGF-2 levels. Given his hypokalemia, his levoketoconazole dose had to be increased; he was also treated with stress dose steroids. His BG levels improved, and he had partial neurologic recovery, however ultimately curative treatment was not possible given the extent of his disease, so he was transitioned to comfort-focused care. Conclusion: This case illustrates the importance of appropriate workup of IGF-2 mediated hypoglycemia, allowing for the best possible therapeutic approach. In our case, reducing tumor burden was not feasible since the patient had widely metastatic disease, leading to a poor outcome.

Presentation: 6/3/2024
7777 The Adrenal Tumor Volumes Help Predict Surgical Indications And Postoperative Recurrence Of PMAH
Authors: Suzuki Sawako , Ishiwata Kazuki , Ruike Yutaro , Igarashi Katsushi , Watanabe Suzuka , Sugo Masafumi , Fujimoto Masanori , Koide Hisashi , Yokote Koutaro
Published: October 2024

Disclosure: S. Suzuki: None. K. Ishiwata: None. Y. Ruike: None. K. Igarashi: None. S. Watanabe: None. M. Sugo: None. M. Fujimoto: None. H. Koide: None. K. Yokote: None.

Introduction: Primary macronodular adrenal hyperplasia (PMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing's syndrome (CS). Unilateral adrenalectomy of the largest gland has been proposed as a treatment for PMAH. However, there are cases of recurrence or persistence of hypercortisolism after unilateral adrenalectomy, and remaining tumor volumes might be associated. Objective: This study aimed to analyze whether tumor volume helps select treatment and predict postoperative recurrence. Patients and methods: We conducted a retrospective study of thirteen patients (five males and eight females, mean age 59 years) with CS due to PMAH in a single center. Eight patients with PMAH underwent unilateral adrenalectomy, but five PMAH were not. Long-term clinical and biochemical outcomes were analyzed in operated and non-operated patients (112±57 months after unilateral adrenalectomy and 144±49 months after initial diagnosis, respectively). Results: Eight PMAH patients who underwent unilateral adrenalectomy had total tumor volumes greater than 1500 mm2. After unilateral adrenalectomy, when the size of the remaining adrenal tumor was greater than 1000 mm2 (1053, 1268, and 1910, respectively), recurrence occurred along with enlargement of the residual adrenal tumor in two cases, and diabetes worsened in one case. However, when the size of the remaining adrenal tumor was less than 500 mm2 (18.2, 201, 214, 327, and 446, respectively), CS resolved. Among five PMAH patients who did not receive surgery, three PMAH patients with total tumor volume less than 1500 mm2 (856, 1038, and 1496, respectively) were biochemically controlled. However, in two PMAH patients with a total volume greater than 1500 mm2 (1610 and 1650), Cushing's signs, including buffalo hump and central obesity, appeared and worsened metabolic complications during follow-up. Conclusions: Our data suggest that adrenalectomy should be considered in PMAH with a total tumor volume greater than 1500 mm2. Unilateral adrenalectomy might have a risk of recurrence if the remaining adrenal tumor is over 1000 mm2. Further large-scale examination is required.

Presentation: 6/3/2024
6793 The Potential Of Melatonin As A Treatment Option For Cushing’s Syndrome In Humans Based On Observations In Cushingoid Dogs
Authors: Fecteau Kellie
Published: October 2024

Disclosure: K. Fecteau: None.

It is known that the secretion of cortisol and melatonin is circadian, with the former increasing during morning hours and the latter increasing during the dark hours of night. Studies investigating melatonin concentrations in patients with Cushing’s syndrome have reported differing results, with some having low melatonin concentrations, and others normal or high concentrations. Interestingly, adrenal glands have been shown to express melatonin receptors, and in vitro studies with human adrenal cells have shown a decrease in cortisol, as well as other adrenocortical steroids, when treated with melatonin. In human adrenal gland explants, melatonin reportedly inhibited ACTH stimulated circadian clock genes, as well as cortisol and progesterone production. Melatonin is often used as a first-line of treatment in dogs with atypical Cushing’s, where cortisol is normal, other adrenocortical steroids are elevated, and typical clinical signs of Cushing’s are present. Retrospective data collected in our diagnostic laboratory from dogs that had at least two submissions (before & during treatment), showed 34 percent of dogs on melatonin improved clinically. Of the 34 percent, 26.4 percent experienced either similar or more aberrant steroid concentrations, and 7.6 percent experienced lower steroid concentrations. Approximately 40 percent of dogs had significantly lower androstenedione when retested on melatonin. In humans, Cushing’s disease is a rare cause of androgen excess, with one study reporting occurrence of less than 4 percent in women. Adrenocortical carcinoma is also rare, however, women with this type of tumor may exhibit clinical signs of androgen excess due to adrenal androgen hypersecretion, and up to 25 percent of women with clinical signs had normal testosterone and elevated androstenedione. Therefore, based on the effectiveness of melatonin on lowering androstenedione concentrations and improving clinical signs associated with increased androgens and glucocorticoids in dogs, it may be an inexpensive and conservative option, especially for patients presenting with clinical signs but diagnostic testing is either negative of equivocal for Cushing’s.

Presentation: 6/2/2024
6571 Tracking Emotional Well-being And Hormonal Interactions In Adrenal Insufficiency Through Ecological Momentary Assessment
Authors: Miya Aika , Suga Ayami , Suzuki Yumiko , Nomoto Hiroshi , Kameda Hiraku , Nakamura Akinobu , Ohira Hideki , Nakamura Toru , Ozaki Yuka , Atsumi Tatsuya
Published: October 2024

Disclosure: A. Miya: None. A. Suga: None. Y. Suzuki: None. H. Nomoto: None. H. Kameda: None. A. Nakamura: None. H. Ohira: None. T. Nakamura: None. Y. Ozaki: None. T. Atsumi: None.

Background: For people undergoing glucocorticoid replacement, adrenal insufficiency underlies diminished physical function and emotional well-being. When psychological stress escalates, increasing the hormone replacement dosage is required for preventing adrenal failure, but the optimal timing for this adjustment is not clear. Using Ecological Momentary Assessment (EMA) that allows real-time evaluation of momentary emotional states, we investigated the relationship between the emotional states of people with adrenal insufficiency and cortisol levels to seek the early detection of symptoms of adrenal failure. Methods: We conducted surveys on 14 healthy adult males using the EMA smartphone application for two weeks. The surveys were conducted five times a day, including upon waking and before bedtime. The surveys targeted aspects including momentary fatigue, depressive mood, anxiety, positive emotions, and stress in daily life. Cortisol levels were measured from their saliva samples collected upon waking each day. Next, we conducted a pilot study with two adult males with adrenal insufficiency using the same system. Results: In healthy males (average age 53.3 years), 87.3% (856 out of 980) of EMA surveys were completed. Multilevel correlation analysis revealed a significant relationship within individuals between elevated salivary cortisol levels and increased fatigue (p < 0.01). Between individuals, heightened fatigue was significantly related to worsening of the depressive mood, as well as decreased positive emotions (p < 0.05). In a pilot analysis, Case 1, a 72-year-old male with ACTH deficiency, was using hydrocortisone at a dosage of 15mg per day. Case 2, a 68-year-old male with hypopituitarism, was taking hydrocortisone at a dosage of 20mg per day. In both cases, 87.1% (122 out of 140) of EMA surveys were completed. There was no significant correlation between elevated salivary cortisol levels and fatigue. However, the relationship of salivary cortisol levels to depressive mood, to anxiety, and to positive emotions varied among individuals and within each individual as well. Conclusion: Our findings suggest the relationships between fatigue, momentary emotional well-being and salivary cortisol levels appear to differ among people with and without adrenal insufficiency. EMA may be useful for gaining the understanding of daily emotional states, potentially offering a new personalized preventive approach for adrenal insufficiency.

Presentation: 6/2/2024
6713 Voriconazole Usage, An Atypical Cause Of Primary Adrenal Insufficiency
Authors: Turkiewicz J , Kanin M , Shmadi S
Published: October 2024

Disclosure: J. Turkiewicz: None. M. Kanin: None. S. Shmadi: None.

Introduction: Primary adrenal insufficiency (AI) is a rare, life-threatening clinical entity. AI can be the result of infection, autoimmune processes, genetic conditions, medication, or malignancy. The medications most associated with AI include anti-epileptics, azoles, steroids, monoclonal antibodies, beta-2 agonists, bisphosphonates, opioids, hormone therapies, and protein kinase inhibitors. We present a case of voriconazole induced primary AI. Case Description:A 67 year old man with unspecified psychosis, hypothyroidism, chronic pulmonary aspergillosis, and severe malnutrition presented for hypothermia and was found to have septic shock from a urinary track infection. On admission, history was limited, though he reported poor oral intake and nonspecific abdominal pain. He had a BMI of 18 and was tachycardic, hypotensive, and hypothermic to 35.5 C. He was started on antibiotics including empiric vorincazole therapy for chronic pulmonary aspergillosis, and empiric steroids x4 days with improvement in labs and clinical status. He was then transferred to the inpatient psychiatry unit for ongoing treatment of psychosis. 1 month later, a rapid response was called after the patient was found down. He was confused, lethargic, hypoglycemic and hypotensive. Acute laboratory revealed glucose of 25 mg/dL, sodium of 116 mmol/L, potassium of 3.7 mmol/L, and creatinine of 0.49 mg/dL. TSH level was 4.8 mclU/mL (range 0.3-4.7). Cortisol was 11 mcg/dL at 7:15 AM (range 8-25). He was started on hydrocortisone with improvement in vitals, labs and mentation. ACTH was 14 pg/mL (range 6-59) the following day, though after steroid administration. Weeks later, AM cortisol was 8 with an ACTH of 104 after holding the PM dose of hydrocortisone the night before. Cosyntropin stim test revealed peak cortisol of 13mcg/dL (<15). Voriconazole level: 2.99 ug/mL (range 1-5.5). Abdominal imaging demonstrated normal adrenal glands. CT head was without a sellar mass. The patient was discharged on hydrocortisone, though was lost to follow up. Discussion:AI due to voriconazole is rare, reported to occur <2% of time, with only a few cases in the literature. Ketoconazole and fluconazole are more often linked with AI, through inhibition of steroidogenic enzymes 11b-hydroxylase, 17a-hydroxylase and 18-hydroxylase. Voriconazole, a second-generation azole, is a potent CYP450 enzyme inhibitor, leading to decreased synthesis of steroidogenic enzymes, indirectly decreasing steroidogenesis. AI is typically seen after 3 months or more of use and is reversible with discontinuation. Our patient had been off and on voriconazole for 2 years with plan for chronic use, and had therapeutic range voriconazole levels after treatment for 3 weeks prior to the rapid response. This case demonstrates the risk of precipitating AI with second-generation azoles.

Presentation: 6/3/2024
6457 You Are Never Too Old For Pheo
Authors: Masumy M , McAdams B , Mikkilineni P
Published: October 2024

Disclosure: M. Masumy: None. B. McAdams: None. P. Mikkilineni: None.

Introduction: Pheochromocytomas (PCC) are a rare neuroendocrine tumor derived from chromaffin cells. The incidence is estimated at 8 in 1 million individuals with no sex or ethnic predilection. It is estimated that 0.05-0.2% of hypertensives may have PCC. Its incidence generally peaks between the third and fifth decades of life. The classic PCC symptoms are headaches, hypertension, palpitations, pallor and tachycardia. However, most patients may not present with these symptoms, and may go undiagnosed. Untreated PCC can have significant morbidity and mortality such as MI, CVA, and hypertensive crises. The current standard of evaluation for PCC includes obtaining serum metanephrines, then if significantly elevated, obtaining CT imaging. Oftentimes, surgical resection is the treatment of choice, but PCC may recur, thus regular follow up is needed. We present a case of PCC in an elderly patient who developed symptoms over a year. Case presentation: A 72-year-old Caucasian female with diabetes presented to the emergency department with palpitations, severe headache, flushing and hypertension. She began experiencing these spells several months earlier with increasingly difficult to manage hypertension. She also had a CVA and NSTEMI earlier in the year. Her blood pressure regimen included amlodipine 20 mg, valsartan 160 mg, and carvedilol 12.5 mg bid. Despite this her blood pressure was uncontrolled. She also had palpitations and unease up to an hour after taking valsartan. Due to her symptoms; PCC was suspected. Serum metanephrines were obtained with her normetanephrines measured at 3334.7 pg/ml and metanephrines were 475.6 pg/ml, these were significantly elevated and thus an abdominal CT scan was done. On CT, she was found to have a 4.9 cm x 4.4 cm left adrenal mass with a density of 31 Hounsfield units. Her symptoms, labs and imaging were strongly indicative of PCC and she was referred to surgery. Her previous blood pressure medications were discontinued, and doxazosin was titrated to a goal SBP of 120 mmHg. Then metoprolol was added to attain a goal heart rate below 70 bpm. She then underwent a successful laparoscopic left adrenalectomy. She is now on 5mg of amlodipine for her blood pressure and metformin for her diabetes. She will be having regular follow ups to monitor for pheochromocytoma recurrence. Conclusion: Though pheochromocytoma is a rare entity that affects individuals primarily in the third and fourth decade of life, it may also occur in elderly patients. In patients with difficult hypertension, screening with metanephrines may be indicated if these are significantly elevated CT imaging should be obtained. When obtaining CT imaging, Hounsfield units are important in characterizing PCC. Achieving adequate alpha blockade before beta blockade is also essential pre-surgery for the best outcome. Even after surgery, patients will require lifelong follow up to monitor for recurrence.

Presentation: 6/1/2024
7928 A "PTH-Mediated" Hypercalcemia Of Malignancy
Authors: Sekhon Navharsh , James Bingham Robert
Published: October 2024

Disclosure: N. Sekhon: None. R.J. Bingham: None.

Background: We present a challenging diagnostic case of a 73-year-old female with PTH-mediated hypercalcemia in the presence of new metastatic uterine cancer. Case: A 73-year-old female with a past medical history of hypertension and abdominal aortic aneurysm was seen in the hospital for hypercalcemia. She endorsed constipation, fatigue, and generalized weakness for the past few weeks. This was the second hospitalization related to hypercalcemia over the period of 10 days. During the previous hospitalization, her admission calcium was 17 mg/dL and was treated with IV fluids, calcitonin, and zoledronic acid. There was a history of intentional weight loss of about 30-40 lbs in the last 3 months by reducing carbohydrate intake. The patient had a 40-pack years of smoking history. There was no family history of calcium disorders or cancers. Home medications included amlodipine 10 mg QD, docusate sodium 100 mg BID, senna 1 tab QHS, and Vit D 5000 U QD. On physical examination, she was hemodynamically stable but appeared confused and lethargic. The rest of the examination was unremarkable. Laboratory results were remarkable for hypercalcemia (Ca: 13.3 mg/dL), hypophosphatemia (Phosphorus: 2.3 mg/dL), and elevated PTH of 418.3 pg/mL (Ref. Range: 18.4-80.1 pg/mL). CT abdomen/ pelvis revealed innumerable ill-defined hypodense lesions throughout the liver concerning metastatic disease and a 5 cm mass in the uterine fundus. The patient was worked up with the view of hypercalcemia related to malignancy. However, PTHrP (PTH-related peptide) came back normal, which was checked twice during both hospitalizations. Liver biopsy showed metastatic high-grade carcinoma highly suspicious for GYN malignancy with negative PTH staining. Imaging studies for localization including CT soft tissue neck and CT 4D parathyroid with and without contrast failed to show any parathyroid lesions. Endometrial biopsy obtained during subsequent hospitalization showed high-grade adenocarcinoma with focal squamous differentiation. Immunohistochemical staining identified scattered positivity for PTH. The patient was managed as per hypercalcemia of malignancy guidelines with IV fluids and denosumab. Discussion: Hypercalcemia of malignancy due to ectopic PTH secretion has been reported in < 1% of cases. Only two endometrial cancer cases with ectopic PTH have been reported in the literature. PTH-mediated hypercalcemia is seen in primary hyperparathyroidism, parathyroid cancers, or ectopic PTH. In all cases of hypercalcemia of malignancy, primary hyperparathyroidism should be ruled out in the presence of elevated PTH. Diagnosing ectopic PTH secretion by tumor can be challenging due to constant changes in cells with metastasis. Conclusion: This is a rare case of endometrial cancer with liver metastasis and ectopic PTH secretion by primary tumor leading to recurrent hospitalizations related to hypercalcemia.

Presentation: 6/2/2024
6463 A Case of Tumour-Induced Osteomalacia Which Remitted After Treatment of Metastatic Prostate Cancer
Authors: Chua J , Chuah M
Published: October 2024

Disclosure: J. Chua: None. M. Chuah: None.

A case Tumour-induced osteomalacia (TIO) which remitted after treatment of metastatic prostate cancer. Dr Chua Jia Min, Dr Matthew Chuah Bingfeng Abstract Case report: A 69-year-old gentleman with a known history of bladder cancer presented to the emergency department with fatigue, lower back pain and bilateral lower limb weakness worsening over the past one month. MRI and bone scan revealed extensive osteoblastic bone metastases across the skeletal system. This gentleman was referred to the Endocrinology service for the evaluation of high PTH. His corrected calcium was normal at 2.17mmol/L (2.09-2.46mmol/L) and iPTH was raised at 8.74pmol/L (1.60-6.90pmol/L). He was noted to have severe hypophosphatemia 0.34mmol/L (0.94-1.50mmol/L). Bicarbonate levels were normal, there was no glycosuria or proteinuria. There was no history of IV ferrous carboxymaltose use. Further investigations were consistent with urinary phosphate loss - TRP was 0.398 and TMP-GFR was 0.199. ALP was elevated at 282ug/L (39-99ug/L). 25-hydroxyvitamin D was low at 12 ug/L, which accounted for the high PTH levels (secondary hyperparathyroidism). FGF-23 levels returned high at 1293 RU/ml (<180 RU/ml). BMD showed osteoporosis with T-score of -2.6 at the left femoral neck. He was subsequently diagnosed with metastatic prostate adenocarcinoma, based on histology from a bone biopsy of an affected vertebrae. PSA was markedly raised at 606ug/L. A diagnosis of TIO secondary to metastatic prostate cancer was made. The patient was started on PO sodium-phosphate solution 4ml TDS (approximately 3mmol/kg/day of elemental phosphorus), calcitriol 0.25mcg BD and vitamin D was replaced. After phosphate was replete, the patient's weakness and fatigue improved. He was subsequently started on androgen deprivation therapy with leuprorelin acetate injection once every 3 months and apalutamide daily. SC denosumab 60mg Q6monthly was also commenced in view of extensive bone metastases. Repeat imaging showed response to treatment with decrease in the size of the prostate and bone lesions. His PSA levels are now undetectable and TMP-GFR has normalised. His oral phosphate and calcitriol doses were gradually reduced and subsequently stopped. His calcium and phosphate levels remain within normal limits on no supplementation, suggesting remission of his TIO. PTH levels normalised after vitamin D repletion. Learning points TIO is a rare paraneoplastic syndrome usually associated with mesenchymal tumours, and treatment involves resection of the causative tumour. Cases of TIO secondary to prostate cancer (an epithelial cancer) are exceedingly rare. Despite metastatic disease, this patient responded exceedingly well to his cancer therapy. Suppression of the tumour cells with androgen deprivation therapy resulted in the lack of phosphotonin production and remission of his TIO.

Presentation: 6/1/2024
6980 A Case Report Of Severe Hypercalcemia In Acute Decompensated Liver Cirrhosis
Authors: Mohamed Eid Mennaallah , Michael Sargis Robert
Published: October 2024

Disclosure: M.M. Eid: None. R.M. Sargis: None.

Introduction: Hypercalcemia in advanced liver disease in the absence of malignancy is a rare condition. Case: A 26 year old female with history of liver cirrhosis secondary to alcohol use disorder, presented with hematemesis and ascites. She was diagnosed with acute decompensated liver cell failure and transferred to our facility for liver transplantation. On Day 10 of her hospital course, she had an acute rise in serum calcium (Ca) to 10.8 mg/dl (N 8.7-10.5),albumin (Alb) 2.6 g/dl, corrected calcium (CCa) 11.9mg/dl. On day 13 Ca peaked to 13.5 mg/dl, CCa 14 mg/dl, ionized Ca 6.5mg/dl (N 4.2-5.4 mg/dl). Serum Ca was normal on day 9, Ca 8.7mg/dl, Alb 2.5 g/dl and CCa 9.9 mg/dl. She was not taking lithium, vitamin A or antacid. No personal or family history of bone disorder, fracture or kidney stone. On exam, blood pressure 85/45, heart rate 110 bpm, jaundiced with abdominal distension and respiratory distress. Labs: hemoglobin 8.1 g/dl, WBC 32.5K/Ul, platelet 136 K/Ul, serum creatinine 1.82 mg/dl, Na 133 mmol/l, K 3.5 mmol/l, Total/Direct bilirubin 29.9/18.1 mg/dl, alkaline phosphatase 166 U/L, AST/ALT 60/42U/l, Mag 2.3 mg/dl, Phos 5 mg/dl, INR 3, PTT 50 sec, parathyroid hormone (PTH) 12 pg/ml (N12-88), TSH 1.02 mciu/ml (N 0.34-4), 25 hydroxy vitamin D 17 ng/ml (N 20-80), parathyroid related peptide (PTHrP) 3.9 pmol/l (N<3.4), 1,25 di-hydroxy vitamin D 9.8 pg/ml (N 19.9-79.3), alpha fetoprotein 9.1 ng/ml (N <9). Normal anti smooth muscle and anti mitochondrial antibodies. Negative viral hepatitis serology. CT abdomen did not reveal hepatobiliary mass or tumor nor kidney stone. She was intubated and mechanically ventilated. Vasopressor support was initiated. One dose of calcitonin 4 units/kg and zoledronic acid 4 mg were given. Serum Ca decreased to 12 mg/dl, CCa 12.6 mg/dL then to 10.2 mg/dl, CCa 11mg/dl within hrs. Calcium normalized to 8.4mg/dl, CCa 9.2 mg/dl, ionized Ca 4.3 mg/dl within 24 hrs. Her condition deteriorated and withdrawal of care was decided. Conclusion: Our case demonstrates non PTH and non vitamin D mediated severe hypercalcemia in setting of acute decompensated cirrhosis and absence of malignancy. Previous literature has noted poor prognosis of hypercalcemia with acute decompensated cirrhosis. While hypercalcemia in cirrhosis may arise from paraneoplastic processes, in absence of malignancy it is speculated that acute hypercalcemia may arise from the inflammatory mediators inducing osteoclastic bone resorption as osteoclast activating factor, prostaglandin and immobilization. Some reports found an association between hypercalcemia and elevations in bilirubin and creatinine(1). Further research is needed to understand the pathophysiology and the management of hypercalcemia in acute decompensated cirrhosis. References: 1-Gerhardt A, Greenberg A, Reilly JJ Jr, Van Tiel DH. Hypercalcemia. A complication of advanced chronic liver disease. Arch Intern Med 147 274-277 1987.

Presentation: 6/2/2024