Metyrapone Reduced Urinary-Free Cortisol Levels in Cushing Syndrome

Metyrapone treatments helped patients with Cushing syndrome reach normal, urinary-free cortisol levels in the short-term and also had long-term benefits, according to a study published in Endocrine.

This observational, longitudinal study evaluated the effects of the 11β -hydroxylase inhibitor metyrapone on adult patients with Cushing syndrome. Urinary-free cortisol and late-night salivary cortisol levels were evaluated in 31 patients who were already treated with metyrapone to monitor cortisol normalization and rhythm.

The average length of metyrapone treatment was 9 months, and 6 patients had 24 months of treatment. After 1 month of treatment, the mean urinary-free cortisol was reduced from baseline by 67% and mean late-night salivary cortisol level decreased by 57%.

Analyzing only patients with severe hypercortisolism, after 1 month of treatment, the mean urinary-free cortisol decreased by 86% and the mean late-night salivary cortisol level decreased 80%. After 3 months, normalization of the mean urinary-free cortisol was established in 68% of patients. Mean late-night salivary cortisol levels took longer to decrease, especially in severe and very severe hypercortisolism, which could take 6 months to drop. Treatment was more successful at normalizing cortisol excretion (70%) than cortisol rhythm (37%). Nausea, abdominal pain, and dizziness were the most common adverse events, but no severe adverse event was reported.

Future research is needed to evaluate a larger cohort with randomized dosages and stricter inclusion criteria to evaluate metyrapone’s effects on cortisol further.

Study researchers conclude that metyrapone was successful and safe in lowering urinary-free cortisol after just 1 month of treatment and controlling long-term levels in patients with Cushing syndrome.

This study was supported by Novartis.

Reference

Ceccato F, Zilio M, Barbot M, et al. Metyrapone treatment in Cushing’s syndrome: a real-life study [published online July 16, 2018]. Endocrine. doi: 10.1007/s12020-018-1675-4

From https://www.endocrinologyadvisor.com/general-endocrinology/metyrapone-cushing-syndrome/article/786716/

Cushing’s Syndrome Eludes Treatment Paradigm or Standard Approach to Care

Results of two systematic reviews indicate that while surgery is the preferred treatment, many patients present with contraindications without an accepted management paradigm leaving clinicians to follow a patient-centric approach to care.

With commentary by Eliza B. Geer, MD

Cushing’s syndrome may arise from an endogenous glucocorticoid excess is either adrenocorticotropic hormone (ACTH)-dependent or ACTH-independent; each variation has numerous underlying causes, including pituitary tumor, adrenal tumor, or other unknown causes.

Although rare, ectopic Cushing’s syndrome results from a non-pituitary ACTH-producing source. Cushing’s disease, a type of Cushing’s syndrome, affects an estimated 1.2 to 2.4 million people each year, and is caused by an ACTH-secreting pituitary adenoma.1

While surgery is preferred for treatment of Cushing's syndrome many patients need a medical approach instead.

Gaining insights into treatment preferences and efficacy for Cushing’s syndrome were the focus of two separate systematic reviews and meta-analyses, both published in the journal, Pituitary: one regarding medical treatments for Cushing’s syndrome,2 and the other comparing endoscopic versus microscopic transsphenoidal surgery for Cushing’s disease.3

Assessing Medical Management of Cushing’s Syndrome

The meta-analysis examining medical care of individuals with Cushing’s syndrome encompassed 1520 total patients across 35 studies, most of whom had Cushing’s disease.2 However, only 2 of the 35 studies were randomized trials, highlighting the lack of and clear need for controlled clinical trials on medical therapies for Cushing’s syndrome.

Surgery is typically first-line treatment—whether transsphenoidal pituitary adenomectomy for Cushing’s disease,4 removal of the ACTH-producing tumor in ectopic Cushing’s syndrome or adrenalectomy in ACTH-independent Cushing’s syndrome.5

However, many patients require medical therapy owing to contraindications for surgery, for recurrent disease, or to control cortisol secretion prior to surgery or radiotherapy. Results of the meta-analysis reflected wide-ranging normalization of cortisol levels depending upon the agent used– from 35.7% for cabergoline to nearly 82% for mitotane in Cushing’s disease.2 Combination therapy (medications used either together or sequentially) was shown to increase effectiveness in normalizing cortisol levels.2

In an interview with EndocrineWeb, Eliza B. Geer, MD, medical director of the Multidisciplinary Pituitary and Skull Base Tumor Center at Memorial Sloan Kettering Cancer Center in New York City, noted that most medical therapies for Cushing’s syndrome are used off-label (in the US), and thus may lack clinical trial efficacy and safety data; consequently, this review provides useful information for treatment selection. However, Dr. Geer said there was substantial diversity of treatments reviewed in this paper – including tumor-directed therapies, cortisol synthesis inhibitors, an adrenolytic therapy, and a receptor blocker, used alone or in combination.

Further, treatments used in the studies addressed a range of Cushing’s etiologies and reflected heterogeneous study designs (for example follow-up ranged from 2 weeks to 11.5 years).2  As such, she said, “findings provided by this review should be viewed in the context of a broader clinical understanding of Cushing’s treatment.”

Specifically, Dr. Geer said, “Dr. Broersen’s analysis found that efficacy of medical therapy was improved by prior radiotherapy. But we know that radiotherapy is recommended on an individualized basis in only a fraction of Cushing’s patients, depending on tumor behavior and treatment history. Also, the fact that mitotane was shown here to have the highest efficacy of all therapies does not make this the appropriate treatment for all, or even most, Cushing’s patients; mitotane is adrenolytic and has a high rate of significant adverse effects.”

Too Many Questions Persist, Necessitating Focus on Attaining Management Paradigm

Dr. Geer also highlighted the need for answers to basic questions when investigating Cushing’s treatments: How do we define ‘successful’ treatment? What goals of care can patients expect? Which cortisol measurements and cut-offs can be used? How do we define clinical remission—resolution of which symptoms and comorbidities? She said Cushing’s syndrome is one of the most challenging endocrine diseases to treat because of the lack of an accepted, universal treatment or management paradigm.

Treatment is often multimodal and always multidisciplinary, with patient-specific decision trees that must consider many factors, including goals of care, treatment history, disease etiology and severity, tumor behavior, and individual responses to medical therapies, she told EndocrineWeb.

She concluded, “While Broersen et al’s study provides a useful review of available medical therapies, it reinforces something we already know about the treatment of Cushing’s: Expertise is required.”

Pituitary surgery is first-line treatment for Cushing’s disease. Currently, there are two main techniques for transsphenoidal pituitary surgery: microscopic and endoscopic. The operating microscope provides three-dimensional vision and may be advantageous in identifying small tumors; the broader field of vision afforded by the endoscope may be advantageous for complete resection of large tumors.3  Generally, despite an absence of studies directly comparing relative remission and complication rates between microscopic versus endoscopic approaches, most surgical centers choose to use one or the other; few have both.3

Examining the Surgical Options to Manage Cushing’s Disease

The second systematic review is the first to compare remission and recurrence rates, and mortality after microscopic versus endoscopic transsphenoidal pituitary surgery for Cushing’s disease.3 The review included 97 studies of 6695 patients: 5711 individuals having the microscopic procedure and 984 undergoing endoscopic surgery.

Results of the meta-analysis found no clear difference between the two techniques in overall remission (80%) or recurrence (10%).3 Short-term mortality for both techniques was < 0.5%. However, endoscopic surgery was associated with a greater occurrence of cerebrospinal fluid leak (12.9 vs 4.0%) but a lesser occurrence of transient diabetes insipidus (11.3 vs 21.7%).3

The authors reported a higher percentage of patients in remission (76.3 vs. 59.9%) and lower percentage recurrence rates (1.5 vs 17.0%) among patients undergoing endoscopic surgery for macroadenomas.3

When interviewed regarding the second meta-analysis,3 Dr. Geer said that the potential benefit of endoscopy over microscopy has been questioned for ACTH-secreting tumors specifically since most are microadenomas.

“With the caveat that few studies (four of the 97 reviewed) compared techniques directly, Broersen et al3 found that endoscopic surgery was associated with higher remission rates compared to microscopic surgery for large tumors, but the two techniques were comparable for small tumors,” said Dr. Geer, however, “one limitation of these data is the lack of standardized criteria to define diagnosis and remission of Cushing’s among the studies reviewed.”

Need for Consistency in Clinical Trials and Surgical Expertise

The study investigators concluded, “endoscopic surgery for patients with Cushing’s disease reaches comparable results for microadenomas, and probably better results for macroadenomas than microscopic surgery,” despite the greater learning curve associated with endoscopic surgery.3 As such, based on their findings, the authors concluded that “endoscopic surgery may thus be considered the current standard of care. Microscopic surgery can be used based on neurosurgeon’s preference.” They did not respond to EndocrineWeb for a request for comment.

As more neurosurgeons receiving training with the endoscope, the preferred technique for pituitary surgery is changing. Dr. Geer said, “Broersen’s review provides reassurance that the newer endoscopic technique is at least equal to the microscope for microadenomas and may be preferred for macroadenomas.”

“However, [conclusions based on the systematic review] do not change our role as endocrinologists treating Cushing’s disease, which is to refer, when indicated, to the available neurosurgeon with the most favorable outcomes and lowest rate of complications, both of which depend directly on level of experience with the procedure and the instrument being used, whether endoscope or microscope,” she said.

The authors had no financial conflicts to declare.

From https://www.endocrineweb.com/professional/cushings/cushings-syndrome-eludes-treatment-paradigm-standard-approach-care

Measuring TSH Levels Could Improve Diagnosis for Cushing’s Syndrome

Measuring the variation in thyroid stimulating hormone blood levels between midnight and morning may be better for diagnosing Cushing’s syndrome than current approaches, a study suggests. 

The study, “TSH ratio as a novel diagnostic method for Cushing’s syndrome,” was published in the Endocrine Journal

Cushing’s syndrome (CS) is a condition characterized by excess cortisol in the blood, which can lead to a variety of issues, including obesity, high blood pressure, abnormal lipid levels, osteoporosis, depression, and cognitive impairments.

In some cases, patients have high cortisol levels, but lack the typical physical features of Cushing’s syndrome. These patients are considered to have subclinical Cushing’s syndrome (SCS), and are at higher risk for cardiovascular disease.

Being able to properly diagnose CS and SCS is of utmost importance for proper intervention and treatment of these patients.

Current methods of diagnosis rely on dexamethasone suppressing tests or late-night salivary and blood cortisol tests, as well as measurements of cortisol in urine. However, because cortisol is a stress-hormone, it can be elevated in cases of mental or physical stress, leading to false positive results on these tests. 

Researchers in this study examined if another hormone, called the thyroid stimulating hormone (TSH), could be used to diagnose Cushing’s syndrome with better accuracy.

TSH is a hormone that stimulates the thyroid gland and whose secretion is affected by the body’s circadian rhythm. Its highest levels in the blood are usually seen in the late evening or early morning. However, patients with CS or SCS lack this nocturnal increase in TSH levels, which could be useful as a new diagnostic approach.

The study recruited 142 patients with suspected CS and SCS, and 21 patients with depression, being treated at the Osaka University Hospital in Japan.

Patients received the ordinal screening tests for Cushing’s syndrome, along with measurements of their midnight-to-morning TSH levels.

After taking the tests, only 20 patients were diagnosed as having Cushing’s, including 12 with over (normal) Cushing’s syndrome and 10 with subclinical Cushing’s syndrome.

Patients with Cushing’s had significantly lower midnight TSH levels than non-Cushing’s patients. No differences were seen in morning levels between the groups. Of note, TSH ratio was maintained in patients with depression, suggesting TSH levels could be used to diagnose Cushing’s in patients with depression.

Researchers observed that serum TSH ratio had powerful diagnostic accuracy. Among patients identified as having Cushing’s, 90% actually had the disease. And among patients excluded for Cushing’s, 95% did not have the condition. These sensitivity and specificity rates were better than with current diagnostic approaches.

However, when considering this test, patients with a severe TSH deficiency must be taken into account.

Overall, these results suggest that the midnight-to-morning serum TSH ratio is a potential new way to diagnose both CS and SCS with a higher specificity than the current diagnostic methods

“The strength of our current survey is its prospective design and the evaluation of not only overt CS but also SCS. The limitation is the relatively small number of CS group patients, especially overt CD,” the researchers wrote.

“New prospective studies will be needed with a larger number of patients in order to further clarify the optimal TSH ratio in the diagnosis of CS,” the study concluded. 

From https://cushingsdiseasenews.com/2018/06/28/measuring-tsh-levels-may-improve-cushings-syndrome-diagnosis-study/

Cushing’s syndrome caused by ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis: a case report

  • Wakako Fujiwara Email author View ORCID ID profile,
  • Tomohiro Haruki,
  • Yoshiteru Kidokoro,
  • Takashi Ohno,
  • Yohei Yurugi,
  • Ken Miwa,
  • Yuji Taniguchi and
  • Hiroshige Nakamura
Surgical Case Reports20184:55

https://doi.org/10.1186/s40792-018-0459-7

Received: 28 March 2018

Accepted: 31 May 2018

Published: 11 June 2018

Abstract

Background

Ectopic ACTH-producing thymic carcinoid tumors are rare, but often behave aggressively with local invasion and distant metastasis. We herein report a case of ACTH-producing thymic typical carcinoid tumor with lymph node metastasis treated by surgery and postoperative radiation therapy.

Case presentation

A 61-year-old woman was admitted to be evaluated for hypoglycemia and hypokalemia. Laboratory data revealed elevation of serum cortisol and ACTH levels. Overnight administration of 8 mg dexamethasone did not suppress plasma ACTH. Chest CT demonstrated a tumor of 30 mm in diameter and enlargement of the lymph node at the anterior mediastinum. Ectopic ACTH syndrome was suspected and total thymectomy and lymph node dissection were performed. The histopathological examination indicated typical carcinoid tumor and mediastinal lymph node metastasis, and immunohistochemical staining was positive for ACTH. The plasma ACTH level decreased immediately after surgery. She received postoperative radiation therapy of 60 Gy.

Conclusion

Ectopic ACTH-producing thymic typical carcinoid tumors are rare, and it is important to consider this disease and perform appropriate treatment.

Keywords

Thymic carcinoid ACTH Cushing’s syndrome Total thymectomy

Background

Among adrenocorticotrophic hormone (ACTH)-dependent Cushing’s syndrome, 10–20% is due to nonpituitary tumors termed ectopic ACTH syndrome (EAS). The most common cause of EAS is small cell lung cancer, followed by thymic carcinoids. Thymic carcinoids are very rare neuroendocrine tumors that often complicate endocrine disorders. Although previously assumed to be variants of bronchopulmonary carcinoid tumors, they are generally more aggressive and difficult to treat. It is widely accepted that surgical resection is the only curative treatment for localized lesions, and the efficacy of chemotherapy and radiotherapy has not been well established.

We herein report a case of EAS caused due to a thymic typical carcinoid tumor successfully treated by surgery followed by radiation.

Case presentation

A 61-year-old woman visited her primary care doctor because of general malaise, face edema, skin pigmentation, insomnia, and polyuria. Blood examination revealed marked hypokalemia and impaired glucose tolerance. Bilateral adrenal enlargement was observed on abdominal ultrasonography, and she was referred to our hospital for further examination. Endocrine examination showed both elevated plasma cortisol (107.7 pg/mL) and ACTH levels (1100 pg/mL), and increased urinary excretion of free cortisol (6650 mcg/day) and 17-ketogenic steroids (78.7 mg/day). Plasma cortisol and ACTH levels were elevated without any diurnal rhythm. Plasma cortisol was not suppressed by the overnight 8-mg dexamethasone suppression test. There was no response of plasma ACTH or cortisol to exogenous corticotropin-releasing hormone (CRH). Other hormones of the pituitary, thyroid, and adrenal medulla were all in normal ranges. Thus, ectopic ACTH syndrome was strongly suggested.

Chest computed tomography (CT) demonstrated a tumor of approximately 30 mm in diameter and enlargement of the lymph node in the anterior mediastinum (Fig. 1). High accumulation of 18-fluorodeoxyglucose in the anterior mediastinum tumor (maximum standardized uptake value [SUV] 2.48) but not in the lymph node was observed on positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy also revealed mild uptake in the tumor. Collectively, these data were consistent with a diagnosis of EAS caused by an anterior mediastinum tumor, possibly thymic carcinoid tumor. There was no abnormal finding indicating multiple endocrine neoplasia (MEN).

Figure 1
Fig. 1

Chest CT image. A tumor (30 × 30 × 14 mm) without invasion localized in the anterior mediastinum (a). Enlargement of lymph node (b)

Before the operation, we administered 500 mg/day of metyrapone, and both ACTH and cortisol levels decreased to 68.5 pg/mL and 3.02 mcg/mL respectively. After 2 months of medical treatment, her symptoms were relieved and bilateral adrenal enlargement decreased. Under open thoracotomy by median sternotomy, she underwent total thymectomy, pericardial partial resection, dissection of the anterior regional and the right paratracheal lymph nodes, and sampling of the subcarinal lymph node. Histopathologically, the tumor consisted of round to spindle-shaped cells with high nucleus/cytoplasm ratios containing finely granular chromatin. Necrosis was absent, and mitotic figures were infrequent, with less than two per ten high-power fields (HPF). Tumor cells were positive for chromogranin A, synaptophysin, CD-56, and ACTH on immunohistochemistry (Fig. 2). The tumor had invaded the pericardium, and mediastinal lymph nodes were positive for metastasis. The final diagnosis was stage IVA (pT2N1M0) ACTH-producing thymic typical carcinoid tumor. The plasma ACTH level decreased to 14.8 pg/mL, less than normal, immediately after surgery (Fig. 3). Hydrocortisone was administered during the perioperative period and was gradually tapered, and finished 4 months after surgery. She received postoperative radiation therapy of 60 Gy. At 8 months after surgery, she showed no sign of Cushing’s syndrome or recurrence of the tumor without any medications.

Figure 2
Fig. 2

HE staining (a) indicated typical carcinoid tumor. Tumor cells were positive for synaptophysin (b), CD-56 (c), and ACTH (d) on immunostaining

Figure 3
Fig. 3

Changes in plasma ACTH levels during the clinical course

Discussion

Ectopic ACTH-producing thymic carcinoid tumor is an extremely rare clinical condition, comprising 29% of all thymic carcinoids and 5–42% of all ectopic ACTH-producing syndrome [12]. It has been reported that radical surgical resection of the ACTH source is the only effective treatment [3]. Prior to surgery, medication therapy should be done to prevent perioperative complications and perform surgery when hormone values and symptoms are controlled. Furthermore, there is a risk of postoperative adrenal insufficiency; strict perioperative management is desirable.

Unlike pulmonary and other carcinoid tumors, thymic carcinoids often behave aggressively as an advanced disease with local invasion, lymph node metastasis, and distant metastasis because of the high proportion of atypical carcinoid tumors. Regarding ACTH-producing thymic tumors, Neary et al. reported three cases of well-differentiated ACTH-producing thymic neuroendocrine carcinomas, and the patients had no lymph node metastasis, recurrence, or death. On the other hand, nine cases of moderately differentiated ACTH-producing thymic neuroendocrine carcinomas almost had lymph node metastasis, and all patients had recurred [4]. However, our case was a typical carcinoid tumor with lymph node metastasis and local invasion.

As a surgical procedure, a median sternotomy approach is generally recommended because this enables excision of the entire thymus, perithymic fat, other affected mediastinal structure, and aggressive lymph node dissection. However, there is no standard for lymph node dissection in thymic epithelial tumors even though lymph node metastasis is an important prognostic factor. Hwang et al. recommended right paratracheal node dissection in addition to anterior regional lymph node dissection for TNM clinical stage II or higher diseases because they are crucial stations on the lymphatic pathway of thymic malignancies [5]. In the present case, we performed total thymectomy, followed by lymph node dissection of the anterior regional and right paratracheal nodes, and sampling of subcarinal lymph node via median sternotomy. The anterior mediastinal lymph nodes were positive for metastasis. Consequently, we considered the extent of lymph node dissection to be adequate, and radical resection was completed because the postoperative plasma ACTH level was successfully decreased. Although a good prognosis is expected by combined surgery and radiation, relatively high malignancy characteristics are observed compared with typical carcinoids, and strict follow-up is needed.

Conclusion

We report a rare case of ectopic ACTH-producing thymic typical carcinoid with local invasion and regional lymph node metastasis. Surgical resection was effective to control Cushing’s syndrome in this case, and nodal staging may help to guide adjuvant treatment, but systemic nodal dissection/sampling is yet to be standardized.

Abbreviations

ACTH: 

Adrenocorticotrophic hormone

CRH: 

Corticotropin-releasing hormone

CT: 

Computed tomography

SUV: 

Standardized uptake value

PET: 

Positron emission tomography

MEN: 

Multiple endocrine neoplasia

HPF: 

High-power fields

CD-56: 

Cluster of differentiation-56

Declarations

Acknowledgements

The authors thank Dr. Nosaka and Dr. Umekita for diagnostic assessment of this case.

Availability of data and materials

The dataset supporting the conclusions of this article is included within the article.

Authors’ contributions

WF and YT were the attending doctors for the patient. WF, YK, KM, YT, and HN performed the operation. WF, TH, and HN drafted this manuscript. All authors have read and approved the final manuscript.

Ethics approval and consent to participate

No applicable.

Consent for publication

This patient consented to the reporting of this case in a scientific publication.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

References

  1. Yoshikawa T, Noguchi Y, Matsukawa H, et al. Thymus carcinoid producing parathyroid hormone (PTH)-related protein: report of a case. Surg Today. 1994;24:544–7.View ArticlePubMedGoogle Scholar
  2. Alexandraki KI, Grossman AB. The ectopic ACTH syndrome. Rev Endocr Metab Disord. 2010;11:117–26.View ArticlePubMedGoogle Scholar
  3. Zhou X, Hnag J, Che J, et al. Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor. J Thorac Dis. 2016;8:888–93.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Neary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus—experience with 12 patients over 25 years. J Clin Endocrinol Metab. 2012;97:2223–30.View ArticlePubMedPubMed CentralGoogle Scholar
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Copyright

© The Author(s). 2018

Relacorilant Effectively Manages Cortisol Effects in Cushing’s Patients

Relacorilant, an investigational therapy developed by Corcept Therapeutics, may effectively manage the effects of excess cortisol in patients with Cushing’s syndrome, interim data from an ongoing Phase 2 trial show.

In particular, the treatment significantly improved sugar tolerance and the levels of osteocalcin, a bone growth biomarker  commonly suppressed by excess cortisol.

Corcept announced in a press release that the trial (NCT02804750) has completed patient enrollment. Results from the first patients will be presented during the upcoming 27th American Association of Clinical Endocrinologists (AACE) annual meeting, May 16-20 in Boston. Full data is expected by the third quarter of 2018.

Relacorilant, also known as CORT125134, was designed to prevent the effects of excess cortisol by blocking one of its receptors, the glucocorticoid receptor.

In a Phase 1 trial with healthy volunteers, multiple doses of relacorilant had a similar effect as Korlym (mifepristone) — an approved medicine for Cushing’s patients — without its known side effects.

In addition to the early efficacy data, the study showed that the treatment was generally safe and well-tolerated by the patients, with adverse events reportedly mild in severity.

These findings supported the launch of the Phase 2 trial in patients with Cushing’s syndrome. In the trial, roughly 30 patients are receiving escalating doses of relacorilant for a total of 12 weeks.

Patients were divided into two groups. The first group, which includes 17 patients, receives the lowest dose — 100 mg/day of relacorilant for four weeks, followed by 150 mg/day for four weeks, and then 200 mg/day for the last four weeks. The second group, called the high-dose cohort, is treated with a similar regimen but with a starting dose of 250 mg/day and a final dose of 350 mg/day.

Patients in the low-dose group had a significant improvement in their glucose tolerance and a 60% increase in blood osteocalcin.

In addition, the treatment reduced the blood pressure in 45% of patients with uncontrolled high blood pressure from cortisol excess. Importantly, the results after 12 weeks of relacorilant were similar to those seen after six months of Korlym treatment.

Safety data continues to show a positive profile, with no evidence of serious adverse effects and no affinity toward the progesterone receptor, which is a major drawback of Korlym.

“Relacorilant’s clinical results are striking because the doses these patients received were the study’s lowest. We did not expect patients to experience any meaningful clinical benefit, but they clearly did,” Robert S. Fishman, MD, chief medical officer of Corcept, said in the release. “We look forward to presenting data from these low-dose patients at the AACE meeting next week. With the trial’s final, high-dose cohort fully enrolled, we will have final data in the third quarter.”

Supported by these preliminary data, Corcept has accelerated the preparations for a Phase 3 trial on relacorilant in Cushing’s syndrome patients.

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