bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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 &lt; 0.01). Between individuals, heightened fatigue was significantly related to worsening of the depressive mood, as well as decreased positive emotions (p &lt; 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

Abstract
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 (&lt;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 &lt;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

Abstract
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

Abstract
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 &lt; 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

Abstract
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 (&lt;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

Abstract
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&lt;3.4), 1,25 di-hydroxy vitamin D 9.8 pg/ml (N 19.9-79.3), alpha fetoprotein 9.1 ng/ml (N &lt;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
12350 A Rare Case Of Giant Parathyroid Adenoma Managed Medically For 8 Months: A Case Report
Authors: Labram Saffi , Bilandzic Luka 
Published: October 2024

Abstract
Disclosure: S. Labram: None. L. Bilandzic: None.
Background: Single parathyroid adenoma is the most common cause of primary hyperparathyroidism, and is attributed to approximately 85% of cases[1]. However, those classified as giant (weighing over 3.5 g and having a size greater than 2cm2) are exceedingly rare. This reports a rare case of primary hyperparathyroidism caused by giant parathyroid adenoma and details biochemical response following medical and surgical management. Case Report: A 64 year old black female presented with severe abdominal pain, confusion and constipation. Investigations revealed severe hypercalcemia of 17.3 mg/dl with massively elevated parathyroid hormone of 1255 pg/mL. Ultrasound showed a large hypoechogenic lobulated mass inferior to the left thyroid lobe representing a giant parathyroid adenoma. Due to delayed surgery the patient was initially treated medically over the course of 8 months. Over these months she was admitted to hospital 3 times for symptomatic hypercalcemia and received a total of 3 zolendronic acid infusions. Despite this she was unable to achieve long term remission of hypercalcemia. Cinacalcet was added and tolerated at the dose of 30 mg daily. Hypercalcemia improved, but remained elevated at a range of 11-13 mg/dL and the symptoms of brain fog and constipation did not subside entirely. She was eventually able to undergo surgical resection, and a giant parathyroid adenoma weighing 8.9 g was excised. Intraoperative intact parathyroid hormone (IOiPTH) sampling showed &gt; 50% reduction (prior to removal 878pg/mL, 10 minutes after removal 132 pg/ml, 20 minutes after removal 96pg/mL). Pathological review showed an atypical parathyroid tumor. As the tumor lacked invasive growth it did not meet criteria for carcinoma. Conclusions: This is a rare case of primary hyperparathyroidism caused by a giant solitary parathyroid adenoma. The gold standard for management of primary hyperparathyroidism secondary to parathyroid adenoma is minimally invasive parathyroidectomy. However in our case, due to inability to access immediate surgery, challenging and prolonged medical treatment of severe hypercalcemia followed for 8 months. Ultimately, normalization of calcium level was achieved only by surgical intervention. IOiPTH measurements showed appropriate decrease confirmatory for the complete removal of the adenoma. References: 1. Dr Jacqueline Payne (2016). Hyperparathyroidism. [online] Patient.info. Available at: https://patient.info/doctor/hyperparathyroidism-pro#nav-2. 2. Rahim Mahmodlou, Amin Sedokani, Apameh Pezeshk and Bita Najafinejad (2022). Giant parathyroid adenoma: a case report. Journal of Medical Case Reports, 16(1). doi:https://doi.org/10.1186/s13256-022-03401-y.
Presentation: 6/2/2024