scholarly journals Prognostic markers of remission of cushing's disease after transsphenoidal endoscopic adenomektomii.

2018 ◽  
Vol 95 (12) ◽  
pp. 1106-1111
Author(s):  
Natalia V. Gussaova ◽  
W. A. Choi ◽  
V. Yu. Cerebillo ◽  
A. A. Paltsev ◽  
A. V. Savello ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Threshold Value ◽  
Optimal Threshold ◽  
Cushing's Disease ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Free Cortisol ◽  
One Year ◽  
Cortisol Suppression

Aim. To study the role of prognostic oral high-dose dexamethasone suppression test (HDDST) and pituitary MRI in the prognosis of Cushing’s disease (CD). remission after transsphenoidal endoscopic surgery (TSS). Material and methods. 59 patients with Cushing’s disease (9 men, 50 women, mean age 40 years (15-72) underwent TSS were included. Before the TSS HDDST and pituitary MRI were performed in all cases. Postoperative examination was done one year after surgery. Remission criteria were: combination of normal midnight serum cortisol levels, normal 24 hour urine free cortisol (UFC) excretion and serum cortisol suppression less than 50 nmol/l in 1-mg dexamethasone test or secondary adrenal insufficiency (the need for glucocorticoid replacement). The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was calculated by ROC-analysis. Results. One year after surgery CD remission was confirmed in 39 patients, whereas in 20 patients hypercortisolism persisted. The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was 72%. Test’s sensitivity and specificity were 82% and 84%, respectively. The probability of wrong prediction was 17% (p=0,0001). In our study, the results of TSS did not correlate with MRI adenoma size.

scholarly journals Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

2022 ◽  
pp. 152-161
Author(s):  
N. V. Kuritsyna ◽  
U. A. Tsoy ◽  
V. Yu. Cherebillo ◽  
A. A. Paltsev ◽  
A. I. Tsiberkin ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Serum Cortisol Level ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Morning Serum Cortisol ◽  
Transsphenoidal Adenomectomy ◽  
Important Challenge ◽  
One Year

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

How early can one diagnose Cushing’s disease? An early diagnosis in a case of prepubertal Cushing’s disease

2014 ◽  
Vol 27 (11-12) ◽  
pp. 1043-1047 ◽  
Author(s):  
Julia Hoppmann ◽  
Isabel V. Wagner ◽  
Gudrun Junghans ◽  
Stefan A. Wudy ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Cushing’S Disease ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
High Dose ◽  
Thyroid Function Tests ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

Abstract Background: Cushing’s disease is very rare in children, and the diagnosis is frequently delayed by several years. Objective: We report a case of prepubertal Cushing’s disease with a medical history of only 9 months. This case illustrates the difficulties involved in diagnosing children at the early stage of the disease. Case presentation: An 8-year-old prepubertal boy presented with rapid weight gain accompanied by a decreasing growth velocity and hirsutism. Thyroid function tests and growth factor levels were normal, thus excluding hypothyroidism and growth hormone deficiency. Cushing’s syndrome was confirmed by elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels, and a lack of cortisol suppression in the low-dose dexamethasone suppression test. Further tests to investigate the source of the hypercortisolism showed the following results: Basal morning adrenocorticotropic hormone (ACTH) was normal. The high-dose dexamethasone suppression test led to a 51% decrease in cortisol level. In the corticotropin-releasing hormone (CRH) test, ACTH and cortisol increased only by 28%. Repeated magnetic resonance imaging (MRI) finally revealed a microadenoma in the anterior pituitary, thus establishng the diagnosis of Cushing’s disease. Upon diagnosis, the patient underwent transsphenoidal surgery. Histological analysis confirmed an ACTH-secreting pituitary adenoma. Conclusion: This case illustrates the difficulties associated with the clinical, biochemical, and radiological diagnoses of Cushing’s disease in children. Early diagnosis remains a challenge because test results often do not match standard diagnostic criteria.

scholarly journals Tumor shrinkage by metyrapone in Cushing's disease exhibiting glucocorticoid-induced positive feedback

2021 ◽  
Author(s):  
Yasutaka Tsujimoto ◽  
Hiroki Shichi ◽  
Hidenori Fukuoka ◽  
Masaaki Yamamoto ◽  
Itsuko Sato ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Positive Feedback ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
High Dose ◽  
Tumor Shrinkage ◽  
Feedback Systems ◽  
Cross Sectional

Abstract Context Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing’s disease (CD). Its pathophysiology and prevalence remain unclear. Case description A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma ACTH levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment. Ex vivo experiments The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3-D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (p <0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather 20–40% suppression (p <0.05). Clinical study A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low dose- (LD) and high dose- (HD) DST from 2014 to 2020 was performed. Eight cases (8.7 %) showed an increase in serum cortisol after both LDDST and HDDST. Conclusions This is the first report of a patient with GC-driven positive-feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive-feedback in CD and the therapeutic approach for these patients remain to be investigated.

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 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 Cavernous sinus sampling in patients with Cushing's disease

2015 ◽  
Vol 38 (2) ◽  
pp. E6 ◽  
Author(s):  
Till Burkhardt ◽  
Jörg Flitsch ◽  
Philine van Leyen ◽  
Nina Sauer ◽  
Jens Aberle ◽  
...  
Keyword(s):  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Correct Diagnosis ◽  
Cushing's Disease ◽  
High Dose ◽  
Consecutive Series ◽  
Test Results ◽  
High Dose Dexamethasone ◽  
Invasive Method

OBJECT Correct diagnosis and precise localization of adenomas in patients with Cushing's disease are essential for avoiding unsuccessful transsphenoidal pituitary exploration. In addition to the well-established inferior petrosal sinus sampling, preoperative cavernous sinus sampling (CSS) was introduced as a potentially improved way to predict adenoma lateralization. The authors present their results with CSS in a consecutive series of patients with Cushing's disease. METHODS During 1999–2014, transsphenoidal surgeries were consecutively performed in 510 patients with Cushing's disease. For most patients, suppression of cortisol in high-dose dexamethasone tests and stimulation of adrenocorticotropic hormone and cortisol after administration of corticotropin-releasing hormone were sufficient to prove the diagnosis of adrenocorticotropic hormone–dependent hypercortisolism. Of the 510 patients, 67 (13%) were referred to the department of neuroradiology for CSS according to the technique of Teramoto. The indications for CSS were unclear endocrine test results or negative MRI results. Data for all patients were retrospectively analyzed. RESULTS A central/peripheral gradient was found in 59 patients; lateralization to the left or right side was found in 51. For 8 patients with a central/peripheral gradient, no left/right gradient could be determined. For another 8 patients with equivocal test results, no central/peripheral gradient was found. No severe CSS-associated complications were encountered. Of the 51 patients who underwent transsphenoidal surgery, the predicted lateralization was proven correct for 42 (82%). CONCLUSIONS As MRI techniques have improved, the number of potential candidates for this invasive method has decreased in the past decade. However, because detecting minute adenomas remains problematic, CSS remains a useful diagnostic tool for patients with Cushing's disease.

scholarly journals Cushing’s disease: Does low-dose pasireotide offer a comparable efficacy and safety to high-dose?

2021 ◽  
Vol 2021 ◽  
Author(s):  
Mimi Wong ◽  
Usman H Malabu ◽  
Ipeson Korah ◽  
YongMong Tan
Keyword(s):  
Cushing’S Disease ◽  
Low Dose ◽  
Cushing's Disease ◽  
Comparable Efficacy ◽  
High Dose ◽  
List Type ◽  
Residual Tumour ◽  
Biochemical Effect ◽  
Free Cortisol

Summary Whilst literature is expanding on pasireotide use in the management of Cushing’s disease (CD), there is still currently much unknown about long-term and low-dose pasireotide use in CD. We present a 60-year-old female with residual CD after transphenoidal surgery (TSS), being successfully managed with S.C. pasireotide for over 10 years. For 6 years, her S.C. pasireotide was inadvertently administered at 360 µg twice daily (BID), almost half the recommended dose of 600 µg BID. Despite the low-dose, her urinary free cortisol (UFC) normalised within 6 months and Cushingoid features resolved. She remained in biochemical and clinical remission on the same low-dose for 6 years, before a medication audit discovered her mistaken dose and directed her to take 600 µg BID. With the higher dose 600 µg BID for the next 5 years, her glycaemia worsened without any changes in her UFC and residual tumour volume. Our case showed the continuing effectiveness and safety of treatment with S.C. pasireotide for more than 10 years, and that a low-dose regimen may be considered an option for responders by its safety profile. Learning points A lower dose of pasireotide may be effective in the initial treatment of CD than the recommended 600 µg BID dosage, though more studies are required to explore this. Low-dose pasireotide use has the benefit of minimising adverse effects. In the long-term, pasireotide has a sustained clinical and biochemical effect and is well tolerated.

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.

scholarly journals ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

2015 ◽  
Vol 173 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Katrin Ritzel ◽  
Felix Beuschlein ◽  
Christina Berr ◽  
Andrea Osswald ◽  
Nicole Reisch ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Predictive Value ◽  
Positive Likelihood Ratio ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
High Dose ◽  
Ectopic Cushing’S Syndrome ◽  
Cortisol Suppression ◽  
Dexamethasone Suppression

ObjectiveThe aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome.Subjects and methodsWe retrospectively analyzed cortisol and ACTH after the injection of 100 μg human CRH in confirmed Cushing's disease (CD, n=78) and confirmed ectopic Cushing's syndrome (ECS, n=18). Cortisol and ACTH increase (in percentage above basal (%B)) at each time point, maximal increase (Δmax %B), and area under the curve (AUC %B) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (%B) after 8 mg of dexamethasone was evaluated as a supplementary criterion.ResultsAn increase in ACTH of ≥43%B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases.ConclusionThe present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive.

Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery

1995 ◽  
Vol 132 (6) ◽  
pp. 722-726 ◽  
Author(s):  
RJM Ross ◽  
SL Chew ◽  
L Perry ◽  
K Erskine ◽  
S Medbak ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Transsphenoidal Surgery ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Successful Outcome ◽  
Small Female ◽  
Free Cortisol ◽  
Cortisol Levels ◽  
Biochemical Features ◽  
Mr Scanning

Ross RJM, Chew SL, Perry L, Erskine K, Medbak S, Afshar F. Diagnosis and selective cure of Cushing's disease during pregnancy by transsphenoidal surgery. Eur J Endocrinol 1995;132:722–6. ISSN 0804–4643 The diagnosis of Cushing's Disease during pregnancy is complex because the biochemical features are obscured by changes in the normal hypothalamo-pituitary-adrenal axis that occur during gestation. To date, treatment has not been successful and there is a high incidence of maternal and fetal complications. We report the case of a 24-year-old woman with Cushing's disease who presented during her 16th week of pregnancy. Diagnosis was confirmed by the finding of elevated serum and urinary free cortisol levels with loss of the normal circadian rhythm of serum cortisol. Cortisol levels failed to suppress after a low-dose dexamethasone test but suppressed after a high-dose test. There was an exaggerated serum cortisol and plasma adrenocorticotrophin (ACTH) response to corticotrophinreleasing hormone (CRH). Magnetic resonance (MR) scanning demonstrated a pituitary tumour and cure was effected by transsphenoidal surgery where tumour immunostaining for ACTH was removed. Postoperatively the patient made an uncomplicated recovery; serum cortisol and plasma ACTH levels were undetectable at 9 days following surgery and recovery of the hypothalamo-pituitary axis occurred at 99 days after surgery. Caesarean section was performed at 38 weeks of pregnancy and a healthy but small female infant was delivered. This case illustrates the biochemical features of Cushing's disease during pregnancy and is the first report of the use of CRH testing and MR scanning in this clinical situation. The cure by surgery and successful outcome for mother and infant, with preservation of normal anterior pituitary function, suggest that transsphenoidal surgery may be the treatment of choice. RJM Ross, Dept of Endocrinology, St Bartholomew's Hospital, London ECIA 7BE, UK

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