SAT-495 1-α-Hydroxylase Activity-Mediated Hypercalcemia Associated with Ovarian Dysgerminoma

Background: Humoral hypercalcemia of malignancy is classically associated with increased tumor production of parathyroid hormone-related peptide (PTHrP). While 1,25 dihydroxy vitamin D (1,25D) mediated hypercalcemia has been demonstrated with a range of granulomatous disorders and lymphomas, there have only been 11 cases reported in ovarian dysgerminomas, of which only 2 were in adults. Ovarian dysgerminoma is the most common ovarian malignancy in childhood but is much more infrequent in adults. We present a case of a rare ovarian malignancy in an adult woman with an even more rare presentation of 1,25D mediated hypercalcemia. Case: A 23 year old African American female with a history of intravenous drug abuse was admitted for dilation and curettage for suspected molar pregnancy. Her operative course was complicated by uterine perforation requiring diagnostic laparoscopy which revealed a large, firm, irregular left ovarian mass concerning for malignancy. Laboratory findings were pertinent for calcium 13.4mg/dl (8.5-10.5), albumin 3.5g/dl (3.5-5.0), creatinine 1.61mg/dl (0.6-1.2), phosphorus 4.0mg/dl (2.5-4.5), alkaline phosphatase elevated at 170 Units/L (25-125) and appropriately suppressed PTH of 4 pg/ml (10-65). Previous calcium levels were all normal. Additional work-up revealed normal PTHrP, 25-OH Vitamin D 14.2 mg/dl (20-50) and high-normal 1,25 dihydroxy vitamin D at 76pg/ml (19.9-79.3). Tumor markers β-hCG, LDH, α-fetoprotein, and CA 19-9 were all elevated. CT scan of the abdomen and pelvis characterized the lesion to be a heterogenous 16.5 x 10.0 x 18.3 cm pelvic mass. The patient was initially given intravenous isotonic fluids and 4mg of intravenous zoledronic acid which decreased calcium to 10mg/dl. Biopsy of the mass performed during initial laparoscopy confirmed the suspected diagnosis of ovarian dysgerminoma. A left salpingo-oophorectomy was performed and the patient developed mild hypocalcemia post-operatively to a nadir of 6.7mg/dl (adjusted for albumin: 7.7) requiring calcium supplementation. The 1,25D level on post-operative day 2 was low at 9.1 pg/ml. Surgical pathology demonstrated metastatic ovarian dysgerminoma with para-aortic lymph node involvement. Conclusion: Our case demonstrates an unusual case of humoral hypercalcemia of malignancy. Exogenous 1-α-hydroxylase expression has been reported exceedingly rarely in solid tumors other than lymphomas. While we were unable to stain the tumor for 1-α-hydroxylase, the abrupt drop in 1,25D and calcium levels post resection strongly support our diagnosis. To our knowledge, our patient is the second oldest patient reported in literature to have 1,25D mediated hypercalcemia associated with an ovarian dysgerminoma

Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome

Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis

Comparative evaluation of sequential and premixed administration of hyperbaric bupivacaine with fentanyl in subarachnoid block for lower limb surgeries – A randomized prospective study

Background: Subarachnoid block is the most commonly used anesthetic technique for lower limb surgeries. Fentanyl is very often combined with hyperbaric bupivacaine as an adjuvant. This study was conducted to compare the block characteristics by administrating bupivacaine and fentanyl in a sequential and premixed manner. Aims and Objectives: The primary objective was to compare the effects of hyperbaric bupivacaine and fentanyl administered either as a premixed solution or sequentially on block characteristics-onset of sensory and motor blockade, regression of block and duration of analgesia. The secondary objective was to study the hemodynamic changes and adverse effects. Materials and Methods: A total of 72 patients scheduled to undergo lower limb surgery were allocated to three groups. Patients in Group A received 15 mg of 0.5 % bupivacaine heavy (H), followed by 25 mcg of fentanyl intrathecally using different syringes. Group B received 25 mcg of fentanyl, followed by 15 mg of 0.5% bupivacaine H in a separate syringe. Group C received premixed 0.5 % bupivacaine H 15 mg and fentanyl 25 mcg in single syringe. The block characteristics-onset and regression of sensory and motor blockade, duration of analgesia, and adverse effects were studied. Results: The mean time (minutes) taken for onset of sensory block was 2.40±0.51 in group A, 4.80±0.53 in Group B and 6.70±0.50 in Group C. Mean time (minutes) taken for onset of motor block was 4.35±0.43 in Group A, while it was 5.64±0.65 and 7.32±0.64 in Groups B and C, respectively. Two segment regression and duration of motor blockade were found to be longer in Group A. Conclusion: Sequential intrathecal administration of bupivacaine followed by fentanyl has a faster onset and prolonged duration of block when compared to the premixed group

Multiple Acyl-Coenzyme A Dehydrogenase Deficiency Leading to Severe Metabolic Acidosis in a Young Adult

Background: Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder affecting fatty acid oxidation. Incidence at birth is estimated at 1:250 000, but type III presents in adults. It is characterized by nonspecific symptoms but if undiagnosed may cause ketoacidosis and rhabdomyolysis. A review of 350 patients found less than one third presented with metabolic crises. Our objective is to describe an adult with weakness after carbohydrate restriction that developed a pulmonary embolism and ketoacidosis, and was diagnosed with MADD type III. Case Report: A 27-year-old woman with obesity presented to the hospital with fatigue and weakness worsening over months causing falls and decreased intake. She presented earlier to clinic with milder symptoms starting months after initiating a low carbohydrate diet. Testing revealed mild hypothyroidism and she started Levothyroxine for presumed hypothyroid myopathy but progressed. Muscle biopsy suggested a lipid storage myopathy. Genetic testing revealed a mutation in the ETFDH (electron transfer flavoprotein dehydrogenase) gene likely pathogenic for MADD; however, before this was available she developed severe ketoacidosis and rhabdomyolysis. She empirically started a low-fat diet, carnitine, cyanocobalamin, and coenzyme Q10 supplementation with improvement. Over months her energy and strength normalized. Discussion: MADD may cause ketoacidosis and rhabdomyolysis but this is rare in adults. Diagnosis requires clinical suspicion followed by biochemical and genetic testing. It should be considered when patients present with weakness or fasting intolerance. Treatment includes high carbohydrate, low-fat diets, supplementation, and avoiding fasting. Conclusion: There should be greater awareness to consider MADD in adults presenting with neuromuscular symptoms, if untreated it may cause severe metabolic derangements