scholarly journals Endogenous ACTH Concentration-Cortisol Secretion Dose Analysis Unmasks Decreased ACTH Potency in Cushing's Disease with Restoration after Successful Pituitary Adenomectomy

2011 ◽  
Vol 96 (12) ◽  
pp. 3768-3774 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Daniel M. Keenan ◽  
Johannes D. Veldhuis
Keyword(s):  
Surgical Treatment ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Pulse Frequency ◽  
Cushing's Disease ◽  
P Value ◽  
Cortisol Secretion ◽  
Acth Concentration ◽  
Active Disease

Background: The relationship between circulating ACTH levels and cortisol secretion in Cushing's disease is not precisely known. Hypothesis: Chronic ACTH hyperstimulation leads to decreased adrenal potency and is restored after normalization of ACTH secretion. Subjects: Subjects included 20 patients with Cushing's disease, eight patients in long-term remission, and 36 healthy controls. Outcomes: ACTH and cortisol secretion rates and analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were evaluated. Results: Both basal and pulsatile secretion of ACTH and cortisol were increased in patients with active disease but normal in cured patients. ACTH, but not cortisol pulse frequency, was amplified in patients and restored after successful surgical treatment. ACTH EC50, an inverse measure of potency, was higher during pulse onset in Cushing's disease (59 ± 7.4 ng/liter) than in controls (20 ± 3.7 ng/liter) (P < 0.0001) and remitted patients after surgery [15 ± 3.2 ng/liter, P value not significant (NS) vs. controls] and during pulse recovery phases [128 ± 18 (P <0.0001), 70 ± 8.4, and 67 ± 17 ng/liter (NS vs. controls), respectively]. Efficacy was increased in active disease and normalized after surgical treatment [patients, 38 ± 8.3 nmol/liter · min, vs. controls, 21 ± 2.3 nmol/liter · min (P <0.0001), and cured patients, 15 ± 3.2 nmol/liter · min (NS vs. controls)]. Sensitivity to endogenous ACTH did not differ among the three groups. Conclusion: The adrenal gland in Cushing's disease exhibits decreased responsiveness to submaximal ACTH drive and amplified efficacy, with unchanged sensitivity. These target-gland abnormalities are reversible in long-term remission after pituitary surgery.

Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance

2005 ◽  
Vol 63 (5) ◽  
pp. 549-559 ◽  
Author(s):  
A. Brew Atkinson ◽  
Adele Kennedy ◽  
M. Ivan Wiggam ◽  
David R. McCance ◽  
Brian Sheridan
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Remission Rates

scholarly journals Significant GH deficiency after long-term cure by surgery in adult patients with Cushing’s disease

2007 ◽  
Vol 156 (2) ◽  
pp. 233-239 ◽  
Author(s):  
Francesca Pecori Giraldi ◽  
Massimiliano Andrioli ◽  
Laura De Marinis ◽  
Antonio Bianchi ◽  
Antonella Giampietro ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Pituitary Surgery ◽  
Male Gender ◽  
Cushing's Disease ◽  
Gh Secretion ◽  
Wide Variability ◽  
Acth Secreting

Objective: Impaired GH secretion usually accompanies Cushing’s syndrome and a variable proportion of patients reportedly fail to recover normal GH secretion after successful treatment. This wide variability is most probably due to differences in the treatment (i.e. surgery and/or radiotherapy), timing of patient re-evaluation after surgery and dynamic tests employed to challenge GH secretion, and hinders a precise assessment of risk of GH deficiency after cure. The aim of the present study is to evaluate GH secretory status after long-term cure of Cushing’s disease achieved by surgery alone. Design and methods: We studied 34 patients (27 females and 7 males, age range 21–68 years) formerly affected by Cushing’s disease. Patients were studied 2–20 years (median 3.3 years) following remission of hypercortisolism; all patients underwent transsphenoidal surgery with the removal of an ACTH-secreting adenoma; repeat pituitary surgery for relapse was performed in two patients while bilateral adrenalectomy was necessary in two patients. In all subjects, the GH response to GHRH+arginine stimulation was evaluated. At the time of testing, 13 patients were still on steroid replacement therapy. Results: In long-term surgical remission, 22 patients (65.0%) presented subnormal GH secretion; partial GH deficiency (GH peak <16.5 μg/l) was found in 11 patients and severe GH deficiency (GH peak <9 μg/l) in another 11. Male gender and length of hypercortisolism were risk factors for postsurgical GH deficiency. Conclusions: This study demonstrates the presence of GH deficiency in a high percentage of patients with Cushing’s disease after long-term remission of hypercortisolism obtained by surgery alone. Male gender and length of hypercortisolism are the most significant predictors of postsurgical GH deficiency. This finding is significant as it highlights that even the most favourable therapeutical course, i.e. remission achieved by surgery alone, is accompanied by impaired GH secretion. Assessment of GH secretion is therefore recommended for all patients cured from Cushing’s disease, even if not submitted to radiotherapy. Studies on the clinical impact of GH deficiency and the use of GH replacement therapy seem warranted in patients cured from Cushing’s disease.

Effect of primary empty sella syndrome on pituitary surgery for Cushing's disease

2014 ◽  
Vol 121 (3) ◽  
pp. 518-526 ◽  
Author(s):  
Gautam U. Mehta ◽  
Kamran D. Bakhtian ◽  
Edward H. Oldfield
Keyword(s):  
Pituitary Gland ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Empty Sella ◽  
Cushing's Disease ◽  
Csf Leak ◽  
Empty Sella Syndrome ◽  
Csf Leaks ◽  
Primary Empty Sella

Object Primary empty sella syndrome (ESS) results from herniation of arachnoid mater into the pituitary fossa. It has been suggested to have a negative effect on pituitary surgery; however, outcomes in this cohort have not been defined. This study was performed to determine the effect of ESS on immediate and long-term biochemical outcome after pituitary surgery for Cushing's disease (CD). Methods Using a matched cohort study design, the authors followed patients treated with pituitary surgery for CD with and without ESS. Complete ESS was defined as pituitary gland height ≤ 2 mm, whereas partial ESS was defined as pituitary gland height > 2 mm but less than three-quarters of the total sellar depth. The primary end points were immediate and long-term biochemical outcome. Cerebrospinal fluid leaks were recorded as a secondary end point. Results Seventy-eight patients with CD and primary ESS were identified and matched with 78 patients with CD without ESS. After surgical management, immediate biochemical remission was achieved in 69 patients (88%) with ESS and 75 controls (96%, p = 0.10). Long-term remission was achieved in most patients in both groups (5-year cure: 85% vs 92%, p = 0.10). Among patients with ESS, the presence of complete ESS predicted a worse long-term outcome (p = 0.04). Intraoperative CSF leaks were significantly more frequent with ESS (54% vs 24%, p < 0.001), and despite sellar floor repair, the rate of postoperative CSF leaks was also increased (6% vs 3%, p = 0.27). Conclusions Biochemical outcome after pituitary surgery for CD was worse in patients with complete ESS, and the risk of a CSF leak was increased with both partial and complete ESS. However, as outcome remains superior to those following alternative therapies and the biology of these tumors is unchanged in the setting of ESS, pituitary surgery should remain the initial treatment of choice.

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

Neuropsychological Functioning in Patients with Cushing’s Disease and Cushing’s Syndrome

2020 ◽  
Author(s):  
Sonja Siegel ◽  
Cedric Fabian Kirstein ◽  
Agnieszka Grzywotz ◽  
Bernd Otto Hütter ◽  
Karsten Henning Wrede ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Neuropsychological Functioning ◽  
Cushing's Syndrome ◽  
Neuropsychological Impairment ◽  
Cushing's Disease ◽  
Neuropsychological Function ◽  
Visuospatial Processing ◽  
Active Disease

Abstract Purpose To present a systematic review of the presence and severity of neuropsychological impairment in the six main neuropsychological domains (attention, executive function, language, visuospatial processing, intelligence, and memory) in patients with Cushing’s disease (CD) and/or Cushing’s Syndrome (CS) at various stages of the illness. The work aims to identify neuropsychological leverage points for focused diagnosis and rehabilitation in CS/CD patients. Methods A pubmed literature search was performed and augmented by searching the reference lists of review articles identified by this search strategy. After excluding irrelevant hits, we systematically extracted data from 27 studies for each main neuropsychological domain, differentiating between active disease, short- and long-term remission. Results The literature gives evidence for neuropsychological impairment in all domains in Cushing patients with active disease. The most consistent impairments concerned memory and visuo-spatial processing, whereas the data are discordant for all other domains. Significant improvement of neuropsychological function – although not returning to normal in all domains – is shown in short-term and long-term remission of the disease. However, the published literature is thin, suffering from repetitive subsample analyses publishing, methodological concerns as lack of control for confounders such as depression. Conclusions Memory is the most extensively investigated domain in CS/CD patients and impairment is most prominent in active disease. Patients should be counseled that neuropsychological function will improve with normalization of hypercortisolism and over time. More studies with more stringent methodological criteria, larger patient samples and controlling for confounders are required to enhance our understanding of neuropsychological function in patients with CS/CD.

scholarly journals Criteria of cure and remission in Cushing's disease: an update

2007 ◽  
Vol 51 (8) ◽  
pp. 1362-1372 ◽  
Author(s):  
Mauro A. Czepielewski ◽  
Guilherme A.F.S. Rollin ◽  
Alessandra Casagrande ◽  
Nelson P. Ferreira
Keyword(s):  
Cushing’S Disease ◽  
Previous Treatment ◽  
Pituitary Surgery ◽  
Serum Cortisol ◽  
Normal Subjects ◽  
Cushing's Disease ◽  
Biochemical Tests ◽  
Transsphenoidal Pituitary Surgery ◽  
Cortisol Levels

We review the clinical and biochemical criteria used for evaluation of the transsphenoidal pituitary surgery results in the treatment of Cushing's disease (CD). Firstly, we discuss the pathophysiology of the hypothalamic-pituitary-adrenal axis in normal subjects and patients with CD. Considering the series published in the last 25 years, we observed a significant variation in the remission or cure criteria, including the choice of biochemical tests, timing, threshold values to define remission, and the interference of glucocorticoid replacement or previous treatment. In this context we emphasize serum cortisol levels obtained early (from hours to 12 days) in the postoperative period without any glucocorticoid replacement or treatment. Our experience demonstrates that: (i) early cortisol < 5 to 7 µg/dl, (ii) a period of glucocorticoid dependence > 6 mo, (iii) absence of response of cortisol/ACTH to CRH or DDAVP, (iv) return of dexamethasone suppression, and circadian rhythm of cortisol are appropriate indices of remission of CD. In patients with undetectable cortisol levels early after surgery, recurrence seems to be low. Finally, although certain biochemical patterns are more suggestive of remission or surgical failure, none has been proven to be completely accurate, with recurrence observed in approximately 10 to 15% of the patients in long-term follow-up. We recommended that patients with CD should have long-term monitoring of the CRH-ACTH-cortisol axis and associated co-morbidities, especially hypopituitarism, diabetes mellitus, hypertension, cardiovascular disturbances, and osteoporosis.

scholarly journals Sequential hormonal changes in 21 patients with recurrent Cushing's disease after successful pituitary surgery

2011 ◽  
Vol 165 (5) ◽  
pp. 729-737 ◽  
Author(s):  
Roula Bou Khalil ◽  
Camille Baudry ◽  
Laurence Guignat ◽  
Carmen Carrasco ◽  
Jean Guibourdenche ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Positive Response ◽  
Pituitary Surgery ◽  
Cushing's Disease ◽  
Hormonal Changes ◽  
Long Term Follow Up ◽  
Mean Time ◽  
Midnight Cortisol

ObjectiveTo describe the sequence of hormonal changes during recurrence of Cushing's disease (CD) after successful transsphenoidal surgery (TSS).DesignRetrospective study in a single center.Patients and methodsWe studied 101 of the 127 patients treated by TSS for CD between 1996 and 2009, who had hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily defined ‘overt recurrence’, as presence of two classical parameters of excess cortisol (increased midnight – either serum or salivary – and 24 h urinary cortisol (UC)), leading to further specific therapeutic action, and ‘mild recurrence’, as presence of a single classical parameter, leading to simple surveillance.ResultsOf the 101 patients, 21 (20.8%) presented with recurrence, ‘mild’ or ‘overt’, during long-term follow-up (median 50.4 months, range 7–99). Recurrence occurred less frequently (16.8 vs 50%, P=0.02), and later (mean 44.7 months, median 43, range 7–94 vs mean 21.5 months, median 17, range 3–61, P=0.05), in patients with early post-TSS hypocortisolism compared with those with eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2 months, while UC elevation was observed at 50.6 months. Vasopressin analogs and CRH tests were eventually positive in 85 and 93% of all patients respectively; a positive response to one of the two dynamic tests preceded the increase in midnight cortisol or UC in 71 and 64% of the patients respectively.ConclusionA positive response to vasopressin analogs and/or CRH tests occurs early in recurrence, followed by an increase in midnight cortisol, while UC elevation is at a later stage.

scholarly journals Efficiency and tolerance of mitotane in Cushing's disease in 76 patients from a single center

2012 ◽  
Vol 167 (4) ◽  
pp. 473-481 ◽  
Author(s):  
Camille Baudry ◽  
Joël Coste ◽  
Roula Bou Khalil ◽  
Stéphane Silvera ◽  
Laurence Guignat ◽  
...  
Keyword(s):  
Median Time ◽  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Urinary Free Cortisol ◽  
Treatment Discontinuation ◽  
Cushing's Disease ◽  
Single Center ◽  
Free Cortisol ◽  
Transsphenoidal Pituitary Surgery ◽  
Acth Concentration

ContextAlternatives to transsphenoidal pituitary surgery may be required in Cushing's disease (CD) as a first- or second-line treatment. Mitotane is a potent anti-cortisolic drug but has been rarely investigated in the treatment of CD.ObjectiveEvaluation of the efficacy and tolerance of mitotane in CD patients.Design and settingRetrospective analysis of 76 patients treated with mitotane from 219 patients diagnosed with CD between 1993 and 2009 in a single center.Main outcome measureRemission was defined as normalization of 24-h urinary free cortisol (24-h-UFC).ResultsRemission was achieved in 48 (72%) of the 67 long-term treated patients, after a median time of 6.7 (5.2–8.2) months. Mean plasma mitotane concentration at the time of remission was 10.5±8.9 mg/l, with a mean daily dose of 2.6±1.1 g. A negative linear relationship was observed between plasma mitotane concentration and 24-h-UFC (P<0.0001). Seventeen of 24 (71%) patients with durable remission subsequently experienced recurrence, after a median time of 13.2 (5.0–67.9) months. At the time of treatment discontinuation, ACTH concentration was statistically associated with a lower recurrence probability (hazard ratios 0.57 (0.32–1.00), P=0.05). Intolerance leading to treatment discontinuation occurred in 19 patients (29%). A pituitary adenoma became identifiable during mitotane treatment in 12 (25%) of the 48 patients with initial negative pituitary imaging allowing subsequent transsphenoidal surgery.ConclusionMitotane is useful at different stages of CD. Mitotane dose adjustment based on plasma concentration monitoring and side effects could control hypercortisolism in the majority of CD patients.

Sinonasal Outcomes after Pituitary Surgery in Patient's with Cushing's Disease

2020 ◽  
Author(s):  
Nadeem R. Kolia ◽  
Paul A. Gardner ◽  
Carl H. Snyderman ◽  
Eric W. Wang
Keyword(s):  
Cushing’S Disease ◽  
Pituitary Surgery ◽  
Cushing's Disease
Sign in / Sign up

Export Citation Format

Share Document