Browsing by Author "Subbu, Karthik"

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    Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome
    (Endocrine Society, 2021-05-03) Subbu, Karthik; Tariq, Zunera; Erickson, Dana Z.; Bancos, Irina; Donegan, Diane; Medicine, School of Medicine
    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.
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    SAT-495 1-α-Hydroxylase Activity-Mediated Hypercalcemia Associated with Ovarian Dysgerminoma
    (Oxford University Press, 2019-04-15) Subbu, Karthik; Saeed, Zeb; Mariash, Cary; Graduate Medical Education, IU School of Medicine
    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.