Postsurgical treatment often necessary in persistent, recurrent Cushing’s disease

Nearly half of adults with Cushing’s disease that persists or recurs after surgical treatment require second and sometimes third therapeutic interventions, including pituitary surgical reintervention, radiotherapy, pharmacotherapy or bilateral adrenalectomy, study data from Mexico show.

Moisés Mercado, MD, FRCPC, of the ABC Hospital Neurological and Cancer Centers in Mexico City, and colleagues evaluated 84 adults (median age, 34 years; 77 women) with Cushing’s disease to determine the long-term efficacy of secondary interventions for persistent and recurrent Cushing’s disease. Median follow-up was 6.3 years.

Overall, 81 participants were primarily treated with transsphenoidal surgery. More than half experienced long-lasting remission (61.7%); disease remained active in 16%, who were diagnosed with persistent Cushing’s disease; and 22% experienced relapse after remission and were diagnosed with recurrent Cushing’s disease.

After the initial procedure, 18 participants required pituitary surgical reintervention, including 10 with recurrent and eight with persistent disease. Radiation therapy was administered to 14 participants, including two as primary therapy and 12 after failed pituitary surgery. Pharmacologic treatment with ketoconazole was prescribed for 15 participants at one point during the course of disease. Bilateral adrenalectomy was performed in 12 participants.

Pituitary surgical reintervention was the most commonly used secondary treatment (22.2%), followed by pharmacologic therapy with ketoconazole (16%), radiotherapy (14.8%) and bilateral adrenalectomy (14.8%). More than half of participants experienced early remissions after a second operation (66.6%) and radiotherapy (58.3%), whereas long-lasting remission was reached in only 33.3% of participants who underwent a second surgery and 41.6% of participants who underwent radiotherapy. Half of participants who underwent bilateral adrenalectomy were diagnosed with Nelson’s syndrome.

Overall, 88% of participants achieved remission, and disease was biochemically controlled with pharmacologic treatment in 9.5% of participants after their initial, secondary and third-line treatments.

“The efficacy of treatment alternatives for recurrent or persistent [Cushing’s disease] vary among patients, and often, more than one of these interventions is required in order to achieve a long-lasting remission,” the researchers wrote. – by Amber Cox

Disclosure: The researchers report no relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/in-the-journals/%7B5519b312-5912-4c65-b2ed-2ece3f68e83f%7D/postsurgical-treatment-often-necessary-in-persistent-recurrent-cushings-disease

Bilateral testicular tumors resulting in recurrent Cushing’s syndrome after bilateral adrenalectomy

Corresponding author: Troy Puar, MRCP (UK), Department of Medicine, Div. of Endocrinology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. Phone: +31 243614599, Fax: +31 243618809, e-mail: Troy_puar@cgh.com.sg
Received: July 14, 2016
Accepted: November 29, 2016
First Published Online: November 30, 2016

Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing’s disease is extremely rare.

We present a rare case of a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing’s disease with complete clinical resolution. Cushingoid features recurred 12 years later, along with bilateral testicular enlargement. Hormonal tests confirmed ACTH-dependent Cushing’s. Surgical resection of the testicular tumors led to clinical and biochemical remission.

We report bilateral testicular tumors occurring in a patient with recurrent Cushing’s disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia. This suggests the presence of pluripotent cells even in patients without CAH.

– See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2016-2702#sthash.F4lfWg9j.dpuf

Elevated late-night salivary cortisol may indicate recurrent Cushing’s disease

Carroll TB, et al. Endocr Pract. 2016;doi:10.4158/EP161380.OR.

 

Elevated late-night salivary cortisol may serve as an early biochemical marker of recurrent Cushing’s disease, and prompt intervention may result in clinical benefits for people with Cushing’s disease, according to recent study findings.

According to the researchers, late-night salivary cortisol level is more sensitive for detecting Cushing’s disease recurrence compared with urinary free cortisol or a dexamethasone suppression test.

Ty B. Carroll, MD, assistant professor at the Medical College of Wisconsin Endocrinology Center and Clinics in Menomonee Falls, and colleagues evaluated 15 patients (14 women; mean age, 49.1 years) with postsurgical recurrent Cushing’s disease (mean time to recurrence, 3.3 years) after initial remission to determine the performance of urinary free cortisol and late-night salivary cortisol measurements for detecting recurrent Cushing’s disease.

Participants were identified as having Cushing’s disease between 2008 and 2013; there was no standard for follow-up, but after remission confirmation participants were followed at least every 6 months after surgery for 2 years and then annually thereafter. Late-night salivary cortisol was the primary biochemical test to screen for recurrence, and follow-up tests with a dexamethasone suppression test, urinary free cortisol or other tests were performed if late-night salivary results were abnormal or if suspicion of recurrence was high.

Of the cohort, 80% had normal urinary free cortisol (< 45 µg/24 hours) at recurrence. Primary transphenoidal adenoma resection was performed in all participants. Evidence of pituitary adenoma on MRI at the time of recurrence was present in seven of 12 participants with normal urinary free cortisol and two of three participants with abnormal urinary free cortisol. Normal renal function was present in all participants, and 14 underwent testing with late-night salivary cortisol, dexamethasone suppression test and urinary free cortisol.

Of participants with normal urinary free cortisol at recurrence, nine had an abnormal dexamethasone suppression test (cortisol 1.8 µg/dL), and all had at least one elevated late-night salivary cortisol measurement (> 4.3 nmol/L). Mean late-night salivary cortisol was 10.2 nmol/L, and mean urinary free cortisol was 19.9 µg/24 hours.

Therapy for recurrent Cushing’s disease was administered in 11 of the 12 participants with abnormal urinary free cortisol. Adrenocorticotropic hormone (ACTH)-staining pituitary adenoma was confirmed in three participants who underwent repeat transphenoidal adenoma resection. Pharmacotherapy was administered to seven participants with normal urinary free cortisol, and two additional participants underwent bilateral adrenalectomy.

Abnormal dexamethasone suppression test was found in two participants with elevated urinary free cortisol at the time of recurrence, and two participants had confirmed abnormal late-night salivary cortisol. All three participants with elevated urinary free cortisol at the time of recurrence underwent therapy.

“This study has shown potential clinical benefit of either surgical or medical therapy in recurrent [Cushing’s disease] patients with elevations of [late-night salivary cortisol] and normal [urinary free cortisol],” the researchers wrote. “We believe that the outcomes observed in this retrospective case series suggest that the risk/benefit ratio of early treatment needs to undergo a more rigorous prospective evaluation utilizing [late-night salivary cortisol] elevation as an early biochemical marker of recurrent [Cushing’s disease].” – by Amber Cox

Disclosure: Carroll reports being a consultant for Corcept Therapeutics. Please see the full study for a list of all other authors’ relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B9ea4e4ed-6428-49b8-9b2a-11462cb21349%7D/elevated-late-night-salivary-cortisol-may-indicate-recurrent-cushings-disease

Patients with ARMC5 mutations: The NIH clinical experience

Screenshot 2016-05-27 13.12.55

 

Adrenal Disorders

R Correa, M Zilbermint, A Demidowich, F Faucz, A Berthon, J Bertherat, M Lodish, C Stratakis

Summary: Researchers conducted this study to describe the different phenotypical characteristics of patients with armadillo repeat containing 5 (ARMC5) mutations, located in 16p11.2 and a likely tumor-suppressor gene. They determined that patients with bilateral adrenal enlargement, found on imaging tests, should be screened for ARMC5 mutations, which are associated with subclinical Cushing’s syndrome (CS) and primary hyperaldosteronism (PA).

Methods:

  • Researchers identified 20 patients with ARMC5 mutations (germline and/or somatic) who were enrolled in a National Institutes of Health (NIH) protocol.
  • They obtained sociodemographic, clinical, laboratory, and radiological data for all participants.

Results:

  • Three families (with a total of 8 patients) were identified with ARMC5 germline mutations; the rest of the patients (13/20) had sporadic mutations.
  • The male to female ratio was 1.2:1; mean age was 48 years and 60% of patients were African American.
  • Forty percent of patients were diagnosed with CS, 20% with subclinical CS, 30% with hyperaldosteronism, and 10% had no diagnosis.
  • The mean serum cortisol (8 am) and Urinary Free Cortisol were 13.1 mcg/dl and 77 mcg/24 hours, respectively.
  • Nearly all patients (95%) had bilateral adrenal enlargement found on CT or MRI.
  • Patients underwent the following treatments: Bilateral adrenalectomy (45%), unilateral adrenalectomy (25%), medical treatment (20%), and no treatment (10%).
  • ARMC5 mutations are associated with primary macronodular adrenal hyperplasia (PMAH) and are also seen in patients with PA, especially among African Americans.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57884/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

Cushing’s disease recurrence predictive factors: Outcome analysis of patients in VANCOUVER over 30 years

Screenshot 2016-05-27 13.12.55

 

Pituitary Disorders/Neuroendocrinology

R Chen, J Levi, M Almalki, S Yi, M Johnson, E Ur

Summary: The objective of this study was to describe the management and outcomes of patients with Cushing’s disease (CD) in the Vancouver region over a 30-year period and to investigate the predictive factors of CD recurrence. Researchers found CD recurrence in 45.8% of patients who received initial transsphenoidal surgery (TSS), and that a post-operative serum cortisol level > 140nmol/L may be a positive predictor of recurrence in these patients.

Methods:

  • Researchers retrospectively reviewed the clinical charts from endocrinologists in Vancouver who provided consent to participate in this study.
  • Included in this study were 48 patients diagnosed with CD since 1985.

Results:

  • All 48 patients received initial TSS; the mean follow-up time was 11.73 (±6.98) years.
  • More than half of the patients (n=26, 54.2%) remained in remission, and 22 patients (45.8%) received subsequent interventions due to CD recurrence.
  • Second-line therapies included repeat TSS (40.9%), stereotactic radiotherapy (18.2%), and bilateral adrenalectomy (36.4%).
  • Among patients with disease recurrence, the average post-operative serum cortisol level was significantly higher (489.0 nmol/L vs 114.7nmol/L; P=0.003).
  • The positive predictive value for recurrence with post-operative serum cortisol > 140nmol/L was 76.5% (P=0.049), while serum cortisol < 140nmol/L had an 80% predictive value for non-recurrence (P=0.035).

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ37C4C5D3BF1A4FAE9C479A696660535B/57894/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-AACE2016&nonus=0

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