scholarly journals High Prevalence of Adrenal Remnant Tissue in Patients Undergoing Bilateral Adrenalectomy for Cushing’s Disease

2020 ◽  
Author(s):  
Julian B. Wilson ◽  
Mohan Zopey ◽  
Jaimie Augustine ◽  
Randolph Schaffer ◽  
Manfred Chiang ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Signs And Symptoms ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Adrenal Tissue ◽  
Number Of Patients ◽  
Free Cortisol ◽  
Endogenous Cortisol

AbstractBilateral adrenalectomy (BLA) is a treatment option for patients with Cushing’s Disease (CD) if transsphenoidal pituitary surgery fails or is not a therapeutic option. For most patients, BLA eliminates endogenous glucocorticoid and mineralocorticoid production, but for a small number of patients, endogenous secretion of adrenal hormones from adrenal tissue continues or recurs, leading to signs and symptoms of hypercortisolism. If adrenal tissue is confined to the adrenal bed, it is considered adrenal remnant tissue, while if it is outside the adrenal bed, it is considered adrenal rest tissue. We retrospectively evaluated morning serum cortisol, nighttime serum cortisol, nighttime salivary cortisol, and 24-h urine free cortisol on at least three occasions in 10 patients suspected of having endogenous cortisol production. Imaging of adrenal remnant tissue was also reviewed. Ten of 51 patients who underwent BLA during this time period had adrenal remnant/rest tissue marked by detectable endogenous glucocorticoid production; 9 of the 10 patients had signs and symptoms of hypercortisolism. Localization and treatment proved difficult. We conclude that the incidence of adrenal remnant/rest tissue in those undergoing BLA following unsuccessful pituitary surgery was 12% although there may have been a selection bias affecting this prevalence. The first indication of remnant tissue occurrence is a reduction in glucocorticoid replacement with symptoms of hypercortisolism. If this occurs, endogenous cortisol production should be tested for by cortisol measurements using a highly specific cortisol assay while the patient is taking dexamethasone or no glucocorticoid replacement. Endocrinologists need to monitor the development of both adrenal remnant tissue and Nelson’s syndrome following BLA.

scholarly journals P34 Characteristics, diagnosis and management of Cushing’s disease - A systematic review and meta-analysis

BJS Open ◽  
2021 ◽  
Vol 5 (Supplement_1) ◽  
Author(s):  
Chan Hee Koh ◽  
Danyal Z Khan ◽  
Ronneil Digpal ◽  
Hugo Layard Horsfall ◽  
Hani J Marcus ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cushing’S Disease ◽  
Meta Analysis ◽  
A Priori ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Diagnosis And Management ◽  
Over Time

Abstract Introduction The clinical practice and research in the diagnosis and management of Cushing’s disease remains heterogeneous and challenging to this day. We sought to establish the characteristics of Cushing’s disease, and the trends in diagnosis, management and reporting in this field. Methods Searches of PubMed and Embase were conducted. Study protocol was registered a-priori. Random-effects analyses were conducted to establish numerical estimates. Results Our screening returned 159 papers. The average age of adult patients with Cushing’s disease was 39.3, and 13.6 for children. The male:female ratio was 1:3. 8% of patients had undergone previous transsphenoidal resection. The ratio of macroadenomas: microadenomas:imaging-undetectable adenomas was 18:53:29. The most commonly reported preoperative biochemical investigations were serum cortisol (average 26.4µg/dL) and ACTH (77.5pg/dL). Postoperative cortisol was most frequently used to define remission (74.8%), most commonly with threshold of 5µg/dL (44.8%). Average remission rates were 77.8% with recurrence rate of 13.9%. Median follow-up was 38 months. Majority of papers reported age (81.9%) and sex (79.4%). Only 56.6% reported whether their patients had previous pituitary surgery. 45.3% reported whether their adenomas were macroadenoma, microadenoma or undetectable. Only 24.1% reported preoperative cortisol, and this did not improve over time. 60.4% reported numerical thresholds for cortisol in defining remission, and this improved significantly over time (p = 0.004). Visual inspection of bubbleplots showed increasing preference for threshold of 5µg/dL. 70.4% reported the length of follow up. Conclusion We quantified the characteristics of Cushing’s disease, and analysed the trends in investigation and reporting. This review may help to inform future efforts in forming guidelines for research and clinical practice.

scholarly journals Spontaneous remission of hypercortisolism presumed due to asymptomatic tumor apoplexy in ACTH-producing pituitary macroadenoma

2013 ◽  
Vol 57 (6) ◽  
pp. 486-489 ◽  
Author(s):  
Marcio Carlos Machado ◽  
Patricia Sampaio Gadelha ◽  
Marcello Delano Bronstein ◽  
Maria Candida Barisson Vilares Fragoso
Keyword(s):  
Salivary Cortisol ◽  
Signs And Symptoms ◽  
Spontaneous Remission ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
High Plasma ◽  
Imaging Data ◽  
Cystic Component ◽  
Free Cortisol

Cushing's disease (CD) is usually caused by secretion of ACTH by a pituitary corticotroph microadenoma. Nevertheless, 7%-20% of patients present with ACTH-secreting macroadenomas. Our aim is to report a 36-year-old female patient with CD due to solid-cystic ACTH-macroadenoma followed up during 34 months. The patient presented spontaneous remission due to presumed asymptomatic tumor apoplexy. She showed typical signs and symptoms of Cushing's syndrome (CS). Initial tests were consistent with ACTH-dependent CS: elevated urinary free cortisol, abnormal serum cortisol after low dose dexamethasone suppression test, and elevated midnight salivary cortisol, associated with high plasma ACTH levels. Pituitary magnetic resonance imaging (MRI) showed a sellar mass of 1.2 x 0.8 x 0.8 cm of diameter with supra-sellar extension leading to slight chiasmatic impingement, and showing hyperintensity on T2-weighted imaging, suggesting a cystic component. She had no visual impairment. After two months, while waiting for pituitary surgery, she presented spontaneous resolution of CS. Tests were consistent with remission of hypercortisolism: normal 24-h total urinary cortisol and normal midnight salivary cortisol. Pituitary MRI showed shrinkage of the tumor with disappearance of the chiasmatic compression. She has been free from the disease for 28 months (without hypercortisolism or hypopituitarism). The hormonal and imaging data suggested that silent apoplexy of pituitary tumor led to spontaneous remission of CS. However, recurrence of CS was described in cases following pituitary apoplexy. Therefore, careful long-term follow-up is required.

scholarly journals Radiotherapy as a tool for the treatment of Cushing’s disease

2019 ◽  
Vol 180 (5) ◽  
pp. D9-D18 ◽  
Author(s):  
Frederic Castinetti ◽  
Thierry Brue ◽  
Oskar Ragnarsson
Keyword(s):  
Medical Treatment ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Limiting Factor ◽  
Pituitary Insufficiency ◽  
Line Treatment ◽  
Second Line ◽  
High Prevalence

Treatment of Cushing’s disease (CD) is one of the most challenging tasks in endocrinology. The first-line treatment, transsphenoidal pituitary surgery, is associated with a high failure rate and a high prevalence of recurrence. Re-operation is associated with an even higher rate of a failure and recurrence. There are three main second-line treatments for CD – pituitary radiation therapy (RT), bilateral adrenalectomy and chronic cortisol-lowering medical treatment. All these treatments have their limitations. While bilateral adrenalectomy provides permanent cure of the hypercortisolism in all patients, the unavoidable chronic adrenal insufficiency and the risk of development of Nelson syndrome are of concern. Chronic cortisol-lowering medical treatment is not efficient in all patients and side effects are often a limiting factor. RT is efficient for approximately two-thirds of all patients with CD. However, the high prevalence of pituitary insufficiency is of concern as well as potential optic nerve damage, development of cerebrovascular disease and secondary brain tumours. Thus, when it comes to decide appropriate treatment for patients with CD, who have either failed to achieve remission with pituitary surgery, or patients with recurrence, the pros and cons of all second-line treatment options must be considered.

scholarly journals Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment

Endocrine ◽  
2020 ◽  
Vol 70 (2) ◽  
pp. 218-231
Author(s):  
Leah T. Braun ◽  
German Rubinstein ◽  
Stephanie Zopp ◽  
Frederick Vogel ◽  
Christine Schmid-Tannwald ◽  
...  
Keyword(s):  
Medical Therapy ◽  
Cushing’S Disease ◽  
Small Sample Size ◽  
Case Reports ◽  
Treatment Options ◽  
Pituitary Surgery ◽  
Small Sample ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Success Rates

Abstract Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrenalectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy). All treatment options have specific advantages, limitations, and side effects. Therefore, treatment decisions have to be individualized according to the specific needs of the patient.

Osilodrostat: A Novel Steroidogenesis Inhibitor to Treat Cushing’s Disease

2020 ◽  
pp. 106002802096880
Author(s):  
John A. Dougherty ◽  
Divya Sanjaykumar Desai ◽  
Javier Barrios Herrera
Keyword(s):  
Cushing’S Disease ◽  
Qt Interval ◽  
Data Extraction ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Pivotal Phase ◽  
Qt Interval Prolongation ◽  
Free Cortisol ◽  
Significant Difference ◽  
Life Threatening

Objective: To review data on efficacy and safety of osilodrostat (Isturisa), a novel oral steroidogenesis inhibitor for treatment of Cushing’s disease (CD), a life-threatening endocrine disorder. Data Sources: A PubMed/CINAHL search from inception to September 25, 2020, was performed using the following keywords: osilodrostat, 11-beta hydroxylase, pituitary, ACTH hypersecretion, and Cushing’s disease. Study Selection and Data Extraction: Phase 2 and 3 clinical trials and supplementary documents investigating osilodrostat were obtained from a primary literature search, the manufacturer’s website, and the Food and Drug Administration website. These articles evaluated the clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions for osilodrostat. Data Synthesis: Osilodrostat was efficacious and safe in the treatment of CD in mostly middle-aged Caucasian women. A pivotal phase 3 study revealed a significant difference in 24-hour mean urinary free cortisol (primary end point) between osilodrostat and placebo (86% vs 29%; P < 0.001). Relevance to Patient Care and Clinical Practice: Osilodrostat provides a potent and consistent effect in reducing life-threatening supraphysiological levels of cortisol in patients with CD. Hypocortisolism adverse effects can be mitigated by slowly increasing osilodrostat’s dose at ≥2-week intervals. QT interval prolongation was noted; therefore, the QT interval must be monitored by the electrocardiogram. Increased levels of cortisol precursors during treatment with osilodrostat may increase the risk of hypokalemia, edema, and hypertension. Conclusions: Osilodrostat was efficacious in decreasing cortisol levels and safe in treating patients who have failed or are ineligible for pituitary surgery. Although risks exist, a pivotal clinical trial revealed efficacy in 86% of participants.

A critical evaluation of transsphenoidal pituitary surgery in the treatment of Cushing's disease: Prediction of outcome

1990 ◽  
Vol 123 (4) ◽  
pp. 423-430 ◽  
Author(s):  
Richard D Arnott ◽  
Richard G Pestell ◽  
Penelope A McKelvie ◽  
J Keith Henderson ◽  
Peter M McNeill ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Critical Evaluation ◽  
Pituitary Surgery ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Late Relapse ◽  
Free Cortisol ◽  
Transsphenoidal Pituitary Surgery ◽  
Cortisol Excretion

Abstract. Twenty-eight patients underwent transsphenoidal pituitary surgery for Cushing's disease. Selective surgical procedures were performed in 26. In 19 patients pituitary adenoma was confirmed histologically and 5 had clumps or clusters of ACTH-staining cells. At follow-up after 22.3 (range 5-56) months 21 (75%) patients remained in clinical and biochemical remission. The 24-h urinary free cortisol performed between 1 and 4 weeks postoperatively while patients took replacement doses of dexamethasone (0.5 to 0.75 mg per day) was found to predict outcome. All patients with suppressed urinary free cortisol excretion have remained in remission, 3 with levels in the normal range have suffered late relapse after initial remission, and 4 with elevated urinary free cortisol excretion were regarded as having failed to remit. Furthermore, all patients with unsuccessful outcomes had no pituitary adenoma and 3 had features consistent with corticotrope nodular hyperplasia at histological examination compared to only 2 and 1, respectively, of patients still in remission. We conclude that 24-h urinary free cortisol performed at 1 to 4 weeks postoperatively whilst on low-dose dexamethasone and the histological findings may predict outcome following transsphenoidal pituitary surgery in Cushing's disease.

scholarly journals Low immediate postoperative serum-cortisol nadir predicts the short-term, but not long-term, remission after pituitary surgery for Cushing’s disease

2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Jon Ramm-Pettersen ◽  
Helene Halvorsen ◽  
Johan Arild Evang ◽  
Pål Rønning ◽  
Per Kristian Hol ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Short Term ◽  
Postoperative Serum

scholarly journals Limited value of cabergoline in Cushing's disease: a prospective study of a 6-week treatment in 20 patients

2016 ◽  
Vol 174 (1) ◽  
pp. 17-24 ◽  
Author(s):  
Pia Burman ◽  
Britt Edén-Engström ◽  
Bertil Ekman ◽  
F Anders Karlsson ◽  
Erik Schwarcz ◽  
...  
Keyword(s):  
Prospective Study ◽  
Cushing’S Disease ◽  
Salivary Cortisol ◽  
Case Reports ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Morning Cortisol ◽  
Free Cortisol ◽  
A Prospective Study

Context and objectiveThe role of cabergoline in Cushing's disease (CD) remains controversial. The experience is limited to case reports and few open studies that report the effects determined after ≥1 month of treatment. In prolactinomas and dopamine-responsive GH-secreting tumours, effects of cabergoline are seen within days or weeks. Here, we searched for short-term effects of cabergoline in CD.DesignTwenty patients (19 naïve and one recurrent) were included in a prospective study. Cabergoline was administered in increasing doses of 0.5–5 mg/week over 6 weeks.MethodsUrinary free cortisol (UFC) 24 h, morning cortisol and ACTH, and salivary cortisol at 0800, 1600 and 2300 h were determined once weekly throughout. Diurnal curves (six samples) of serum cortisol were measured at start and end.ResultsAt study end, the median cabergoline dose was 5 mg, range 2.5–5 mg/week. The prolactin levels, markers of compliance, were suppressed in all patients. During the treatment, hypercortisolism varied, gradual and dose-dependent reductions were not seen. Five patients had a >50% decrease of UFC, three had a >50% rise of UFC. Salivary cortisol at 2300 h showed a congruent >50% change with UFC in two of the five cases with decreased UFC, and in one of the three cases with increased UFC. One patient with decreases in both UFC and 2300 h salivary cortisol also had a reduction in diurnal serum cortisol during the course of the study.ConclusionsCabergoline seems to be of little value in the management of CD. Only one patient had a response-like pattern. Given the known variability of disease activity in CD, this might represent a chance finding.

scholarly journals Prospective evaluation of transsphenoidal pituitary surgery in 108 patients with Cushing's disease

2007 ◽  
Vol 51 (8) ◽  
pp. 1355-1361 ◽  
Author(s):  
Guilherme Rollin ◽  
Nelson Pires Ferreira ◽  
Mauro A. Czepielewski
Keyword(s):  
Diabetes Insipidus ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Therapeutic Choice ◽  
Remission Rates ◽  
Transsphenoidal Pituitary Surgery ◽  
Suppression Test

Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for Cushing's disease (CD). Despite the widespread acceptance of this procedure as the first line treatment in CD, the indication of a second TSS in not cured or relapsed DC patients is not consensus. We report the results of TSS in 108 patients with CD (a total of 117 surgeries). The mean postoperative follow-up period was 6 years. Remission was defined as clinical and laboratorial signs of adrenal insufficiency, period of glucocorticoid dependence, serum cortisol suppression on oral 1-mg dexamethasone overnight suppression test and clinical remission of hypercortisolism. We evaluated 103 patients with CD by the time of the first TSS. Fourteen patients underwent second TSS (5 had already been operated in others centers; in 5 patients the first surgery was not curative; in 4 patients CD relapsed). Remission rates were 85.4% and 28.6% (p < 0.001) after first and second TSS, respectively. In microadenomas, remission rates were higher than macroadenomas (94.9% vs. 73.9%; p = 0.006). In patients with negative pituitary imaging remission rates were 71.4% (p = 0.003; vs. microadenomas). Postoperative complications were: transient diabetes insipidus, definitive diabetes insipidus, hypopituitarism, stroke and one death. Only hypopituitarism was more frequent after second TSS (p = 0.015). In conclusion, TSS for CD is an effective and safe treatment. The best remission rates were observed at the first surgery and in microadenomas. The low remission rates after a second TSS suggest that this approach could not be a good therapeutic choice when the first one was not curative.

scholarly journals Five years follow up of patients with Сushing’s disease with and without visualized pituitary adenoma on MRI, who underwent transsphenoidal adenomectomy

2017 ◽  
Vol 63 (5) ◽  
pp. 276-281
Author(s):  
Patimat M. Khandaeva ◽  
Zhanna E. Belaya ◽  
Lyudmila Ya. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
Andrey Yu. Grigoriev ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Surgery Complications ◽  
Free Cortisol ◽  
Transsphenoidal Adenomectomy

The remission rate of Cushing’s disease in patients after neurosurgery varies from 59 to 94%, while the recurrence rate is 3 to 46%. Aim — to evaluate the five-year outcome in neurosurgery patients with Cushing’s disease (CD), depending on preoperative MRI-based identification of pituitary adenoma. Material and methods. The study included 105 neurosurgery patients with histologically confirmed CD. CD remission was confirmed by the development of adrenal insufficiency and/or normalization of serum cortisol and 24-hour urinary free cortisol (24h UFC) levels, as well as by clinical remission. Results. Pituitary adenoma was not visualized by gadolinium MRI in 35 cases. The size of visualized pituitary adenoma varied from 0.3 to 29 mm. After first neurosurgery, remission was achieved in 87 (82.8%) patients. After second neurosurgery, remission occurred in 12 patients. Radiation therapy was conducted in 24 patients. Six patients had bilateral adrenalectomy. Two patients died during remission: one patient died from stroke two years after neurosurgery, and the other patient died due to surgery complications. During five-year follow-up after neurosurgery, remission continued in 76 (72.8%) patients, including 27 (77%) of 35 patients without MRI-detected adenoma and 49 (70%) of 70 patients with MRI-detected pituitary adenoma, p=0.15. Sixty-six patients developed recurrence, and 14 patients had active hypercortisolism. Conclusion. There was no correlation between the rate of preoperative MRI-based detection of pituitary adenoma and the rate of remission in neurosurgery patients with Cushing’s disease during the five year follow-up. The size of pituitary adenoma was a risk factor for adenoma recurrence.

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