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.

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 &lt; 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 &lt;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 &lt;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 Update on the management of recurrent Cushing's disease

2015 ◽  
Vol 38 (2) ◽  
pp. E16 ◽  
Author(s):  
Martin J. Rutkowski ◽  
Patrick M. Flanigan ◽  
Manish K. Aghi
Keyword(s):  
Patient Outcomes ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Bilateral Adrenalectomy ◽  
Cushing's Disease ◽  
Tumor Control ◽  
Repeat Resection ◽  
Risks And Benefits ◽  
Acth Secreting

After transsphenoidal surgery, Cushing's disease (CD) shows excellent long-term remission rates, but it may recur and pose a therapeutic challenge. Findings in recent published reports on the treatment of recurrent adrenocorticotropic hormone (ACTH)–secreting tumors suggest that repeat resection, radiation-based therapies such as Gamma Knife surgery and proton-beam radiosurgery, pharmacotherapy, and bilateral adrenalectomy all have important roles in the treatment of recurrent CD. Each of these interventions has inherent risks and benefits that should be presented to the patient during counseling on retreatment options. Radiation-based therapies increasingly appear to have efficacies similar to those of repeat resection in achieving biochemical remission and tumor control. In addition, an expanding retinue of medication-based therapies, several of which are currently being evaluated in clinical trials, has shown some promise as tertiary adjunctive therapies. Lastly, bilateral adrenalectomy may offer durable control of refractory recurrent CD. An increasing number of published studies with long-term patient outcomes highlight the evolving treatment patterns in the management of recurrent CD.

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

scholarly journals Long-term results of treatment in patients with ACTH-secreting pituitary macroadenomas

2003 ◽  
pp. 195-200 ◽  
Author(s):  
S Cannavo ◽  
B Almoto ◽  
C Dall'Asta ◽  
S Corsello ◽  
RM Lovicu ◽  
...  
Keyword(s):  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Long Term Results ◽  
Cushing's Disease ◽  
Tumor Diameter ◽  
Pituitary Macroadenoma ◽  
Second Surgery ◽  
Acth Secreting

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.

scholarly journals Successful long-term control of Cushing’s disease after partial resection of gigantic ACTH-secreting pituitary adenoma

2016 ◽  
Vol 2 (1) ◽  
pp. 88-93
Author(s):  
Vatroslav Čerina ◽  
◽  
Luigi Cavallo ◽  
Ivan Kruljac ◽  
Jelena Marinković Radošević ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Partial Resection ◽  
Cushing's Disease ◽  
Acth Secreting

scholarly journals Surgical Remission of Pituitary Adenomas Confined to the Neurohypophysis in Cushing’s Disease

2006 ◽  
Vol 91 (7) ◽  
pp. 2656-2664 ◽  
Author(s):  
Robert J. Weil ◽  
Alexander O. Vortmeyer ◽  
Lynnette K. Nieman ◽  
Hetty L. DeVroom ◽  
John Wanebo ◽  
...  
Keyword(s):  
Body Mass ◽  
Cushing’S Disease ◽  
Anterior Lobe ◽  
Cushing's Disease ◽  
Posterior Lobe ◽  
Repeat Surgery ◽  
Tertiary Referral Center ◽  
Acth Secreting

Abstract Context: Partial or total removal of the pituitary cures 60–80% of patients with Cushing’s disease (CD) in whom an adenoma cannot be identified at surgery. Many patients who fail complete or partial hypophysectomy are cured by sellar and parasellar irradiation. Design/Patients: As part of a series of prospective studies of CD, we identified 12 patients (34.5 ± 19.9 yr; 11 females; four children) with tumors located completely within the neurohypophysis among 730 patients undergoing surgery for CD. Setting: The study was conducted at a tertiary referral center at a clinical research hospital. Results: All 12 patients had clinical and biochemically defined CD. Tumor was visible at surgery in 11 patients; all 12 tumors were positive for ACTH by immunohistochemistry. Two tumors were excised at repeat surgery because of persistent hypercortisolism within 14 d of negative exploration of the adenohypophysis. There were no long-term complications. At follow-up of 71.9 ± 34.2 months (range, 30–138 months), all patients are in remission of CD. Adult patients have had significant improvement in weight and body mass indices, with restoration of normal menses in all women. In the four pediatric patients, height, weight, and body mass indices have been restored toward normal by surgical remission of CD. Hypopituitarism or long-term neurohypophysial dysfunction has not occurred. Conclusion: We report a new subset of patients with CD, ACTH-secreting adenomas that arise wholly within the posterior lobe of the pituitary gland. In cases of CD in which an adenoma is not identified in the adenohypophysis and in patients with persistent hypercortisolism after complete or partial excision of the anterior lobe, tumor within the neurohypophysis should be considered; selective adenomectomy of a neurohypophyseal, ACTH-secreting tumor can produce long-term remission.

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 Comorbidity and cardiovascular risk factors in adult GH deficiency following treatment for Cushing's disease or non-functioning pituitary adenomas during childhood

2012 ◽  
Vol 166 (4) ◽  
pp. 593-600 ◽  
Author(s):  
Oskar Ragnarsson ◽  
Charlotte Höybye ◽  
Peter J Jönsson ◽  
Ulla Feldt-Rasmussen ◽  
Gudmundur Johannsson ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Cushing’S Disease ◽  
Gh Deficiency ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pituitary Tumour ◽  
Cushing's Disease ◽  
Pituitary Hormone ◽  
Gh Treatment

ObjectiveCushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood.Design, patients and methodsThis was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry.ResultsThe median age at diagnosis of pituitary tumour was 14.0 years (range 10–17) in patients with CO-CD and 13.7 years (range 8–17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P<0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P=0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%,P=0.018). At 1 year on GH treatment, total- and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA.ConclusionAdult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature.

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