Predictors of long-term remission after transsphenoidal surgery in Cushing's disease

OBJECTIVE: The aim of this study was to review the results of surgery for pediatric patients with Cushing's disease who were less than 18 years old and underwent transsphenoidal surgery in a specialized center during a 25-year period. SUBJECTS AND METHODS: Retrospective study, in which the medical records, histology and pituitary imaging of 15 consecutive pediatric patients with Cushing's disease (mean age: 13 years) were evaluated by the same team of endocrinologists and a neurosurgeon from 1982 to 2006. Patients were considered cured when there was clinical adrenal insufficiency and serum cortisol levels were below 1. 8 µg/dL or 50 nmol/L after one, two, three, or seven days following surgery; they therefore required cortisone replacement therapy. Follow-up was for a median time of 11.5 years (range: 2 to 25 years). RESULTS: Clinical and biochemical cure was achieved in 9/15 patients (60%) exclusively after transsphenoidal surgery. Hypopituitarism was observed in four patients; growth hormone deficiency, in two; permanent diabetes insipidus, in one case. CONCLUSIONS: Cushing's disease is rare in children and adolescents. Transsphenoidal surgery is an effective and safe treatment in most of these patients. Plasma cortisol level < 1. 8 µg/dL following surgery is the treatment goal and is a good predictive factor for long-term cure of Cushing's disease.

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Long term follow-up of transsphenoidal surgery for the treatment of Cushing's disease in childhood.

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.80.8.7629245 ◽

1995 ◽

Vol 80 (8) ◽

pp. 2475-2479 ◽

Cited By ~ 1

Author(s):

M C Leinung ◽

L A Kane ◽

B W Scheithauer ◽

P C Carpenter ◽

E R Laws ◽

...

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Cushing's Disease ◽

Long Term Follow Up

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Results of repeated transsphenoidal surgery in Cushing's disease. Long-term follow-up

Endocrinología y Nutrición ◽

10.1016/j.endonu.2013.10.008 ◽

2014 ◽

Vol 61 (4) ◽

pp. 176-183 ◽

Cited By ~ 18

Author(s):

Pablo Valderrábano ◽

Javier Aller ◽

Leopoldo García-Valdecasas ◽

José García-Uría ◽

Laura Martín ◽

...

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Cushing's Disease ◽

Long Term Follow Up

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Transsphenoidal surgery for Cushing's disease: a review of success rates, remission predictors, management of failed surgery, and Nelson's Syndrome

Neurosurgical FOCUS ◽

10.3171/foc.2007.23.3.7 ◽

2007 ◽

Vol 23 (3) ◽

pp. 1-6 ◽

Cited By ~ 67

Author(s):

Daniel F. Kelly

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Remission Rate ◽

Cushing's Disease ◽

Surgical Morbidity ◽

Nelson’S Syndrome ◽

Nelson's Syndrome ◽

Radio Therapy ◽

Transsphenoidal Adenomectomy

✓ Cushing's disease is a serious endocrinopathy that, if left untreated, is associated with significant morbidity and mortality rates. After diagnostic confirmation of Cushing's disease has been made, transsphenoidal adenomectomy is the treatment of choice. When a transsphenoidal adenomectomy is performed at experienced transsphenoidal surgery centers, long-term remission rates average 80% overall, surgical morbidity is low, and the mortality rate is typically less than 1%. In patients with well-defined noninvasive microadenomas, the long-term remission rate averages 90%. For patients in whom primary surgery fails, treatment options such as bilateral adrenalectomy, stereotactic radiotherapy or radiosurgery, total hypophysectomy, or adrenolytic medical therapy need to be carefully considered, ideally in a multidisciplinary setting. The management of Nelson's Syndrome often requires both transsphenoidal surgery and radio-therapy to gain disease control.

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Cushing’s disease: the desmopressin test as a compelling predictive marker of long-term remission after transsphenoidal surgery

Acta Endocrinologica ◽

10.1530/eje-20-0261 ◽

2020 ◽

Vol 182 (6) ◽

pp. C17-C19

Author(s):

D A Vassiliadi ◽

S Tsagarakis

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Predictive Marker ◽

Positive Test ◽

Cushing's Disease ◽

Recent Issue ◽

Recurrence Rates ◽

Existing Data

Transsphenoidal surgery (TSS) is the treatment of choice in Cushing’s disease. However, recurrence rates are substantial and currently there are no robust predictors of late prognosis. As accumulating evidence challenge the accuracy of the traditionally used early postoperative cortisol values, alternative tests are required. The study of Cambos et al., published in a recent issue of the European Journal of Endocrinology, adds to the existing data that support a role of the desmopressin test as an early and reliable predictive marker in successfully TSS-treated patients. However, despite these promising data, the use of this test is hampered by the fact that it can be applied only in patients with a documented preoperative positive test. Moreover, the lack of robust criteria to define positive postoperative responses represents another major limitation.

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Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease

Acta Endocrinologica ◽

10.1530/eje-07-0514 ◽

2008 ◽

Vol 158 (1) ◽

pp. 91-99 ◽

Cited By ~ 102

Author(s):

F Castinetti ◽

I Morange ◽

P Jaquet ◽

B Conte-Devolx ◽

T Brue

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Urinary Free Cortisol ◽

Postoperative Treatment ◽

Cushing's Disease ◽

Intention To Treat ◽

Free Cortisol ◽

In Series

ContextAlthough transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases. Adjunctive treatments each have specific drawbacks. Despite its inhibitory effects on steroidogenesis, the antifungal drug ketoconazole was only evaluated in series with few patients and/or short-term follow-up.ObjectiveAnalysis of long-term hormonal effects and tolerance of ketoconazole in CD.DesignA total of 38 patients were retrospectively studied with a mean follow-up of 23 months (6–72).SettingAll patients were treated at the same Department of Endocrinology in Marseille, France.PatientsThe 38 patients with CD, of whom 17 had previous transsphenoidal surgery.InterventionKetoconazole was begun at 200–400 mg/day and titrated up to 1200 mg/day until biochemical remission.Main outcome measuresPatients were considered controlled if 24-h urinary free cortisol was normalized.ResultsFive patients stopped ketoconazole during the first week because of clinical or biological intolerance. On an intention to treat basis, 45% of the patients were controlled as were 51% of those treated long term. Initial hormonal levels were not statistically different between patients controlled or uncontrolled. Ketoconazole was similarly efficacious as a primary or postoperative treatment. Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases. No adrenal insufficiency was observed. Adverse effects were rare in patients treated long term.ConclusionsKetoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.

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Usefulness of desmopressin testing to predict relapse during long-term follow-up in patients in remission from Cushing’s disease

Endocrine Connections ◽

10.1530/ec-17-0292 ◽

2017 ◽

Vol 6 (8) ◽

pp. 791-799 ◽

Cited By ~ 7

Author(s):

Alberto Giacinto Ambrogio ◽

Massimiliano Andrioli ◽

Martina De Martin ◽

Francesco Cavagnini ◽

Francesca Pecori Giraldi

Keyword(s):

Cushing’S Disease ◽

Transsphenoidal Surgery ◽

Response Pattern ◽

Disease Recurrence ◽

Cushing's Disease ◽

Close Monitoring ◽

Long Term Follow Up ◽

Over Time

Recurrence of Cushing’s disease after successful transsphenoidal surgery occurs in some 30% of the patients and the response to desmopressin shortly after surgery has been proposed as a marker for disease recurrence. The aim of the present study was to evaluate the response to desmopressin over time after surgery. We tested 56 patients with Cushing’s disease in remission after transsphenoidal surgery with desmopressin for up to 20 years after surgery. The ACTH and cortisol response to desmopressin over time was evaluated in patients on long-term remission or undergoing relapse; an increase by at least 27 pg/mL in ACTH levels identified responders. The vast majority of patients who underwent successful adenomectomy failed to respond to desmopressin after surgery and this response pattern was maintained over time in patients on long-term remission. Conversely, a response to desmopressin reappeared in patients who subsequently developed a recurrence of Cushing’s disease, even years prior to frank hypercortisolism. It appears therefore that a change in the response pattern to desmopressin proves predictive of recurrence of Cushing’s disease and may indicate which patients require close monitoring.

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