Effect of Perioperative Glucocorticoid Replacement on Prognosis of Surgical Patients With Sellar Lesions

Study Overview
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Brief Summary
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The purpose of this four-arm randomized controlled study is to determine whether eliminating glucocorticoids (GC) replacement in perioperative period in surgical patients with sellar lesion could result in similar or better outcomes comparing to traditional replacement therapy, regarding postoperative recovery of pituitary function and other postoperative complications (infection, pain, quality of life, recurrence). Surgical patients of our center with MRI-confirmed diagnosis of sellar lesion will be enrolled, insulin tolerance test (ITT) will be performed for assessment of the pituitary function at enrollment. Patients with normal pituitary function will be randomized into non-GC replacement group (group A) and low-dose GC replacement group (group B), while patients with impaired pituitary function will be randomized into low-dose GC replacement group (group C) and high-dose GC replacement group (group D). The primary outcome is the hypothalamic-pituitary-adrenal (HPA) -axis function of the patients, evaluated by plasma cortisol and adrenocorticotropic hormone (ACTH) levels. The secondary outcomes include the hypothalamic-pituitary-thyroid (HPT) axis function (TSH, thyroid-stimulating hormone, free T3, free T4), postoperative water-electrolyte balance, infection, recurrence and health-related quality of life.

Official Title
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Effect of Perioperative Glucocorticoid Replacement on Prognosis of Surgical Patients With Sellar Lesions

Conditions
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Pituitary Neoplasms, Craniopharyngiomas

Intervention / Treatment
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* Drug: Hydrocortisone
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 Surgical patients with MRI-confirmed diagnosis of sellar lesions (non-functioning pituitary adenoma or craniopharyngioma) Exclusion Criteria: Patients with pre-existing hyperthyroidism or Cushing's syndrome Patients with long-term glucocorticoids replacement history Patients with other co-morbidities that pose known influence upon the HPA-axis function (cardiovascular or cerebrovascular disease, metabolic disease or epilepsy) Patients with severe panhypopituitarism Patients with history of radiotherapy of the pituitary gland

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: A. Normal function, non-GC replacement<br>No glucocorticoid replacement will be given perioperatively. | |
| Active Comparator: B. Normal function, low-dose GC<br>Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1. 80mg hydrocortisone at day 2; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet at day 4 and day 5; 2.5mg at day 6; | Drug: Hydrocortisone<br>* used intravenously<br>Drug: Prednisone<br>* used as tablet form<br>|
| Active Comparator: C. Impaired function, low-dose GC<br>Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1. 80mg hydrocortisone at day 2; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet at day 4 and day 5; 2.5mg at day 6; | Drug: Hydrocortisone<br>* used intravenously<br>Drug: Prednisone<br>* used as tablet form<br>|
| Active Comparator: D. Impaired function, high-dose GC<br>Hydrocortisone 100mg i.v. before anesthesia induction, and postoperative day 1 and day 2. 60mg hydrocortisone at day 3; 60mg at day 3; 20mg at day 4; 5mg oral prednisone acetate tablet per day, since postoperative day 3. | Drug: Hydrocortisone<br>* used intravenously<br>Drug: Prednisone<br>* used as tablet form<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline plasma cortisol level | Plasma cortisol at 8:00, 16:00, 24:00 respectively | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Change from baseline plasma ACTH level | ACTH at 8:00; | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Change from baseline 24-hour urine free cortisol | 24-hour urine free cortisol | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Change from baseline insulin tolerance test result | insulin tolerance test result | 7, 30, 90 days post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline plasma TSH level | plasma TSH level | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Sodium, potassium concentration in the blood and urine | Concentration of sodium, potassium in the blood and urine | Daily post-op,for the duration of hospital stay, an expected average of 7 days | 
| Number of patients with postoperative infection | Routine blood test, body temperature fluctuation, cerebrospinal fluid test if necessary. | For the duration of hospital stay, an expected average of 7 days | 
| Change from baseline health-related quality of life | The 15-Dimensions measure of health-related quality of life | 7, 30, 90 days post-op | 
| Number of patients with recurred tumor | Enhanced MRI scan of the sellar region. | 3,6,12 months after surgery | 
| Change from baseline plasma free T3 level | plasma free T3 level | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Change from baseline plasma free T4 level | plasma free T4 level | 1, 3, 5, 7, 30, 90, 180, 360 days post-op | 
| Urine output | 24-hour urine output | Daily post-op,for the duration of hospital stay, an expected average of 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hydrocortisone, Pituitary adenomas, Replacement therapy