Browsing by Author "Mariash, Cary N."

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    Corrigendum: Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study
    (Frontiers Media, 2022-04-27) Pivonello, Rosario; Bancos, Irina; Feelders, Richard A.; Kargi, Atil Y.; Kerr, Janice M.; Gordon, Murray B.; Mariash, Cary N.; Terzolo, Massimo; Ellison, Noel; Moraitis, Andreas G.; Medicine, School of Medicine
    [This corrects the article DOI: 10.3389/fendo.2021.662865.].
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    Development of an objective tool for the diagnosis of myxedema coma
    (Elsevier, 2015-09) Chiong, Yien Vickie; Bammerlin, Elaine; Mariash, Cary N.; Department of Medicine, IU School of Medicine
    Myxedema coma, a rare entity, with a reported 25%–65% mortality had no objective criteria for making the diagnosis when we began our study. We developed an objective screening tool for myxedema coma to more easily identify patients and examine the best treatment method in future prospective studies to reduce the mortality of this entity. We conducted a retrospective chart review to find all patients aged ≥18 years admitted with myxedema coma from January 1, 2005 through June 13, 2010 at Indiana University Health Methodist Hospital. On the basis of both our retrospective chart review and on literature accounts, we identified 6 criteria to diagnose myxedema coma. We identified 10 patients initially diagnosed with myxedema coma and established a control group consisting of 13 patients identified with altered mental status and increased thyroid-stimulating hormone (TSH) levels. The 6 variables we created for the screening tool were heart rate, temperature, Glasgow coma scale, TSH, free thyroxine, and precipitating factors. The screening tool has a sensitivity and specificity of about 80%. We ran a logistic regression model using the 10 study patients and 13 controls with the 6 variables. No variables alone significantly contributed to the model. However, the overall model was highly significant (P = 0.012), providing strong support for a scoring system that uses these variables simultaneously. This screening tool enables physicians to rapidly diagnose myxedema coma to expedite treatment. A more refined diagnostic tool may be used in future clinical studies designed to determine the optimal treatment.
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    Hyperthyroidism in Pregnancy and Lactation: A Different Paradigm?
    (Oxford University Press, 2021-01-07) Rind, Jubran; Mariash, Cary N.; Medicine, School of Medicine
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    Hypothyroidism Prolongs Hospitalization Following Surgery
    (Scientific Research, 2019-12) Villavicencio, Raquel; Mariash, Cary N.; Medicine, School of Medicine
    Objective: Each year 45 million surgical procedures are performed in the United States, and a significant number of these are performed on hypothyroid patients. Little guidance is available to determine the postoperative risk to these subjects. We hypothesized that new surgical techniques and modern anesthesia would lead to no differences in outcome between hypothyroid patients and euthyroid controls. Methods: We queried surgical databases in our health system for patients who underwent an operative procedure between January 1, 2010 and December 31, 2015 with a TSH > 10 mcU/mL or a FT4 < 0.6 ng/dL. Identified patients were matched to euthyroid controls selected for age, sex, surgical procedure, and search interval. Predicted length of hospital stay (LOS) was determined using the American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator. Results: We identified 29 hypothyroid patients. The LOS was significantly longer for the hypothyroid patients compared to the predicted LOS (14.4 vs 6.7 days, P < 0.001). The LOS in the matched controls was not significantly different than their predicted LOS (9.6 vs 7.1 days, P = 0.11). Other complications were not different between the hypothyroid and control patients. Conclusions: In contrast to our initial hypothesis, hypothyroidism is associated with a 2-fold longer LOS following surgery. Hypothyroidism continues to place patients at increased surgical risk.
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    Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study
    (Frontiers Media, 2021-07) Pivonello, Rosario; Bancos, Irina; Feelders, Richard A.; Kargi, Atil Y.; Kerr, Janice M.; Gordon, Murray B.; Mariash, Cary N.; Terzolo, Massimo; Ellison, Noel; Moraitis, Andreas G.; Medicine, School of Medicine
    Introduction/purpose: Relacorilant is a selective glucocorticoid receptor modulator (SGRM) with no progesterone receptor activity. We evaluated the efficacy and safety of relacorilant in patients with endogenous Cushing syndrome (CS). Materials and methods: A single-arm, open-label, phase 2, dose-finding study with 2 dose groups (NCT02804750, https://clinicaltrials.gov/ct2/show/NCT02804750) was conducted at 19 sites in the U.S. and Europe. Low-dose relacorilant (100-200 mg/d; n = 17) was administered for 12 weeks or high-dose relacorilant (250-400 mg/d; n = 18) for 16 weeks; doses were up-titrated by 50 mg every 4 weeks. Outcome measures included proportion of patients with clinically meaningful changes in hypertension and/or hyperglycemia from baseline to last observed visit. For patients with hypertension, clinical response was defined as a ≥5-mmHg decrease in mean systolic or diastolic blood pressure, measured by a standardized and validated 24-h ABPM. For patients with hyperglycemia, clinical response was defined ad-hoc as ≥0.5% decrease in HbA1c, normalization or ≥50-mg/dL decrease in 2-h plasma glucose value on oral glucose tolerance test, or decrease in daily insulin (≥25%) or sulfonylurea dose (≥50%). Results: 35 adults with CS and hypertension and/or hyperglycemia (impaired glucose tolerance or type 2 diabetes mellitus) were enrolled, of which 34 (24 women/10 men) received treatment and had postbaseline data. In the low-dose group, 5/12 patients (41.7%) with hypertension and 2/13 patients (15.4%) with hyperglycemia achieved response. In the high-dose group, 7/11 patients (63.6%) with hypertension and 6/12 patients (50%) with hyperglycemia achieved response. Common (≥20%) adverse events included back pain, headache, peripheral edema, nausea, pain at extremities, diarrhea, and dizziness. No drug-induced vaginal bleeding or hypokalemia occurred. Conclusions: The SGRM relacorilant provided clinical benefit to patients with CS without undesirable antiprogesterone effects or drug-induced hypokalemia.
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    THU035 Impact Of Surgery Or Medical Treatment With The Selective Glucocorticoid Receptor Modulator Relacorilant On Hypercoagulopathy In Patients With Cushing Syndrome
    (The Endocrine Society, 2023-10-05) Simeoli, Chiara; Di Paola, Nicola; Stigliano, Antonio; Lardo, Pina; Kearney, Tara; Mezosi, Emese; Ghigo, Ezio; Giordano, Roberta; Mariash, Cary N.; Donegan, Diane; Feelders, Richard A.; Hand, Austin L.; Moraitis, Andreas G.; Pivonello, Rosario; Medicine, School of Medicine
    In patients with Cushing syndrome (CS), hypercoagulability represents a significant concern, leading to an elevated risk for thrombotic events. Hypercoagulability persists for several months (mos) after curative surgery, and current CS treatment guidelines recommend anticoagulation therapy for up to 3 mos after surgery. In patients with Cushing disease, hemostatic parameters may even worsen after surgery, independent of surgical outcome, with improvements beginning about 3 mos after successful surgery (Casonato et al. Blood Coagul Fibrinolysis 1999). This transient worsening may be due to increased inflammation as cortisol levels, and hence cortisol’s anti-inflammatory effects, are reduced after successful surgery, leading to increased activity in the coagulation cascade, which normalizes over time. Here, we evaluate the impact of surgery or treatment with the selective glucocorticoid receptor modulator relacorilant (RELA) on the coagulation state in patients with CS, reporting findings from a retrospective, longitudinal, monocentric, surgical cohort study and an open-label phase 2 study of RELA (NCT02804750). In the surgical study, coagulation markers were assessed in 30 patients before curative surgery and in remission. In the RELA study, patients received either RELA 100-200 mg for 12 weeks or RELA 250-400 mg for 16 weeks; coagulation markers were assessed in 34 patients throughout the study. In the surgical study, baseline (BL) mean 24-h urinary free cortisol (UFC) was 615.6 mcg/day (by immunoassay; 2.1x upper limit of normal [ULN]); mean and median time to hemostasis assessment after remission were 6.2 and 6 mos, respectively. Significant mean changes from BL were observed in activated partial thromboplastin time (aPTT; +2.0 sec, P=0.031), factor VIII (fVIII; -24.2%, P=0.044), and von Willebrand factor (vWF; -20.6%, P=0.018), whereas platelet count was unchanged. In the RELA study, BL mean UFC was 211.9 mcg/day (by tandem mass spectrometry; 4.2x ULN). Similar to the surgical study, significant mean changes from BL to last observed visit were reported in aPTT (+1.5 sec, P=0.046), fVIII (-18.9%, P=0.022), and platelet count (-68.8*109/L, P<0.0001), while vWF was unchanged. Significant improvements in other coagulation factors, eg, fIX and fX, were seen in patients with abnormal values at BL. These studies showed that coagulation markers in patients with CS improve 6 mos after curative surgery, and that treatment with RELA may have similar effects after 3-4 mos. The previously observed transient increase in fVIII immediately after surgery was absent with RELA, where negative mean changes from BL were seen throughout the study. This is presumably due to the less abrupt reduction of cortisol activity with RELA compared to surgery. RELA’s effects on hypercoagulopathy support further investigation of preoperative use and in patients with CS who are not eligible for surgery.