Evaluation and Follow-Up of Patients With Cushing Disease After Pituitary Surgery

Object Transsphenoidal pituitary surgery is the primary therapy for Cushing disease because of its potential to produce lasting remission without the need for long-term drug or hormone replacement therapy. The authors evaluated the current role of pure endoscopic endonasal pituitary surgery in the treatment of Cushing disease. Methods Twenty-five patients underwent pure endoscopic surgery for confirmed Cushing disease. Thirteen patients had microadenomas and seven had macroadenomas; magnetic resonance images obtained in five patients were only suspicious or nondiagnostic, and thus they underwent inferior petrosal sinus sampling. Two patients had evidence of cavernous sinus involvement. Final histological results were consistent with adrenocorticotropin hormone (ACTH)–secreting adenoma in 20 patients. Results Twenty patients (80%) had clinical remission and laboratory confirmation of hypocortisolemia (serum cortisol < 100 nmol/L requiring substitution therapy), suppression to low-dose dexamethasone, and normal 24-hour urinary free cortisol. The median follow-up period was 17 months (range 3–32 months). There was no recurrence at the time of the last follow-up. Three patients presented with new anterior pituitary deficiency, but no one had permanent diabetes insipidus. In one patient a cerebrospinal fluid leak developed but later resolved following lumbar drainage. Treatment failure was attributable to involvement of the cavernous sinus in two patients, incomplete tumor removal in one, negative exploration in one, and nodular corticotroph hyperplasia of the pituitary gland in one. Conclusions Early results indicated that endoscopic endonasal surgery is a safe and effective treatment for ACTH-producing adenomas. The rate of remission in this study is comparable to those in previous series, and the rate of major postoperative complications is extremely low. Further studies with a larger number of patients and longer follow-ups are required to determine whether this more minimally invasive pure endoscopic approach should become the standard of care for the surgical treatment of Cushing disease.

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Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease

Journal of Neurosurgery ◽

10.3171/2008.8.jns08339 ◽

2009 ◽

Vol 111 (3) ◽

pp. 531-539 ◽

Cited By ~ 89

Author(s):

Jay Jagannathan ◽

Rene Smith ◽

Hetty L. DeVroom ◽

Alexander O. Vortmeyer ◽

Constantine A. Stratakis ◽

...

Keyword(s):

Mr Imaging ◽

Remission Rate ◽

Pituitary Surgery ◽

Anterior Lobe ◽

Accurate Identification ◽

Cushing Disease ◽

Complete Excision ◽

Imaging Results ◽

Prospective Database

Object Many patients with Cushing disease still have active or recurrent disease after pituitary surgery. The histological pseudocapsule of a pituitary adenoma is a layer of compressed normal anterior lobe that surrounds the adenoma and can be used during surgery to identify and guide removal of the tumor. In this study the authors examined the results of using the pseudocapsule as a surgical capsule in the resection of adenomas in patients with Cushing disease. Methods The authors reviewed a prospective database of data obtained in patients with Cushing disease who underwent surgery. The analysis included all cases in which a lesion was identified during surgery and in which the lesion was believed to be confined to the pituitary gland in patients with Cushing disease between January 1990 and March 2007. Since the objective was to determine the success of using the pseudocapsule as a surgical capsule, patients with invasive tumors and patients in whom no lesion was identified during surgery—challenging cases for surgical success—were excluded from analysis. Results In 261 patients an encapsulated adenoma was identified at surgery. Tumor was visible on MR imaging in 135 patients (52%); in 126 patients (48%) MR imaging detected no tumor. The range of tumor size overlapped considerably in the groups with positive and negative MR imaging results, indicating that in addition to size other features of the adenoma influence the results of MR imaging. In 252 patients hypercortisolism resolved after the first operation, whereas in 9 patients (3 with positive MR imaging and 6 with negative MR imaging) early reoperation was required. Hypercortisolism resolved in all 261 patients (256 with hypocortisolism and 5 with eucortisolism) before hospital discharge. Forty-six patients (18%) had postoperative electrolyte abnormalities (30 with hyponatremia and 16 with diabetes insipidus), but only 2 patients required treatment at discharge. The mean clinical follow-up duration was 84 months (range 12–215 months). Six patients (2%) had recurrence of hypercortisolism, all of whom were treated successfully with reoperation. Conclusions Because of their small size, adenomas can be challenging to identify in patients with Cushing disease. Use of the histological pseudocapsule of an adenoma allows accurate identification of the tumor and helps guide its complete excision. With this approach the overall remission rate is high and the rate of complications is low.

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Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

Neuroendocrinology ◽

10.1159/000496846 ◽

2019 ◽

Vol 108 (3) ◽

pp. 211-218 ◽

Cited By ~ 1

Author(s):

Andreea Liliana Serban ◽

Elisa Sala ◽

Giulia Carosi ◽

Giulia Del Sindaco ◽

Claudia Giavoli ◽

...

Keyword(s):

Surgical Intervention ◽

Pituitary Surgery ◽

Disease Recurrence ◽

Adrenal Function ◽

Surgical Removal ◽

Cushing Disease ◽

Adult Age ◽

First Line Therapy ◽

Acth Secreting

Background: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). Objective: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. Patients and Methods: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. Results: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. Conclusion: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.

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Significance of Crooke's Hyaline Change in Nontumorous Corticotrophs of Patients With Cushing Disease

Frontiers in Endocrinology ◽

10.3389/fendo.2021.620005 ◽

2021 ◽

Vol 12 ◽

Author(s):

Amit Akirov ◽

Vincent Larouche ◽

Ilan Shimon ◽

Sylvia L. Asa ◽

Ozgur Mete ◽

...

Keyword(s):

Remission Rate ◽

Retrospective Chart Review ◽

Pituitary Surgery ◽

Serum Cortisol ◽

Outcome Data ◽

Cushing Disease ◽

Persistent Disease ◽

Feedback Suppression ◽

Biochemical Testing

BackgroundGlucocorticoid excess in Cushing disease (CD) leads to negative feedback suppression, resulting in Crooke's hyaline change (CC) of nontumorous pituitary corticotrophs. We aimed to determine the predictive value of CC of nontumorous corticotrophs in CD.MethodsThe retrospective chart review study included patients with clinical, biochemical, radiologic and outcome data and evaluable histopathology specimens from pituitary surgery for CD. The main outcome was remission of CD, defined by clinical features, biochemical testing, and corticosteroid dependency.ResultsOf 144 CD patients, 60 (50 women, mean age 43.6±14) had clinical follow-up, biochemical data and histopathology specimens that included evaluable nontumorous adenohypophysis. Specimens from 50 patients (83.3%) demonstrated CC in nontumorous corticotrophs, and 10 (16.7%) had no CC (including 3 with corticotroph hyperplasia). One patient with CC was lost to follow-up and one without CC had equivocal outcome results. During a mean (SD) follow-up period of 74.9 months (61.0), recurrent or persistent disease was documented in 18 patients (31.0%), while 40 (69.0%) were in remission. In patients with CC, the remission rate was 73.5% (95% CI, 59.7%-83.7%) (36/49), whereas it was 44.4% (95% CI, 18.9%-73.3%) (4/9) in patients with no CC. The combination of serum cortisol >138 nmol/L within a week of surgery coupled with absence of nontumorous CC greatly improved the prediction of recurrent or persistent disease.ConclusionsCC of nontumorous corticotrophs was observed in 83% of patients with CD, and most patients with CC experienced remission. Absence of CC in nontumorous corticotrophs may serve as a predictor of reduced remission in patients with CD.

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Dynamic testing after pituitary surgery: is follow-up re-testing useful?

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0028-1096359 ◽

2008 ◽

Vol 116 (09) ◽

Author(s):

C Berg ◽

T Meinel ◽

A Yüce ◽

H Lahner ◽

K Mann ◽

...

Keyword(s):

Dynamic Testing ◽

Pituitary Surgery

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Recovery of the adrenal function after pituitary surgery in patients with Cushing Disease: remission or recurrence?

Endocrine Abstracts ◽

10.1530/endoabs.56.p823 ◽

2018 ◽

Author(s):

Andreea Serban ◽

Elisa Verrua ◽

Elisa Sala ◽

Marco Locatelli ◽

Maura Arosio ◽

...

Keyword(s):

Pituitary Surgery ◽

Adrenal Function ◽

Cushing Disease ◽

Disease Remission

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Surgical outcomes in cushing disease: Endoscopic transsphenoidal pituitary surgery

Endocrine Abstracts ◽

10.1530/endoabs.63.p1087 ◽

2019 ◽

Author(s):

Pablo Remon-Ruiz ◽

Elena Dios-Fuentes ◽

Eva Venegas ◽

Miriam Cozar-Duenas ◽

Ariel Kaen ◽

...

Keyword(s):

Surgical Outcomes ◽

Pituitary Surgery ◽

Cushing Disease ◽

Transsphenoidal Pituitary Surgery

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

BJS Open ◽

10.1093/bjsopen/zrab032.033 ◽

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.

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Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience

Journal of Endocrinological Investigation ◽

10.1007/s40618-021-01562-z ◽

2021 ◽

Author(s):

E. Sala ◽

G. Carosi ◽

G. Del Sindaco ◽

R. Mungari ◽

A. Cremaschi ◽

...

Keyword(s):

Median Time ◽

Pituitary Surgery ◽

Somatostatin Analogues ◽

Exclusion Criterion ◽

Single Centre ◽

Disease Evolution ◽

Single Centre Experience ◽

Pituitary Irradiation

Abstract Purpose A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. Methods We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008–2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. Results In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24–84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3–12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66–150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. Conclusion A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

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Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

Acta Endocrinologica ◽

10.1530/eje-13-0325 ◽

2013 ◽

Vol 169 (3) ◽

pp. 329-337 ◽

Cited By ~ 48

Author(s):

M A E M Wagenmakers ◽

H D Boogaarts ◽

S H P P Roerink ◽

H J L M Timmers ◽

N M M L Stikkelbroeck ◽

...

Keyword(s):

Treatment Option ◽

Cushing’S Disease ◽

Remission Rate ◽

Pituitary Surgery ◽

Primary Treatment ◽

Endoscopic Technique ◽

Cushing's Disease ◽

Recurrence Rates ◽

Transsphenoidal Pituitary Surgery

ContextAlthough the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now.ObjectiveTo gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas.DesignRetrospective cohort study.Patients and methodsThe medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤50 nmol/l either basal or after 1 mg dexamethasone.ResultsThe remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71±39 months of follow-up (mean±s.d., range 10–165 months).ConclusionsEndoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.

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