Hydrocortisone Use During Peri-operation for Pituitary Adenomas

Surgery Clinical Trial

Official title:

Withholding Hydrocortisone vs Routine Use of Hydrocortisone During Peri-operation in Pituitary Adenoma Patients With Intact Hypothalamus-Pituitary-Adrenal Axis: Randomized Controlled Trial to Assess Safety and Complications

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04621565
• Other study ID #: ZS-2608
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2020
• Est. completion date: July 2022

Study information

• Verified date: November 2020
• Source: Peking Union Medical College Hospital
• Contact: Bing Xing, MD
• Phone: +861069152530
• Email: xingbingemail[@]aliyun.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose hypothalamus pituitary adrenal axis are intact are safe.

Description:

Pituitary is the headquarters of the endocrine system of the body, secreting several hormones maintaining the normal function of the endocrine organs. After surgery, pituitary dysfunction is seen in a small proportion of patients, even in some patients resulting in severe consequence, i.e. adrenal insufficiency or pituitary crisis. Therefore, patients undergoing pituitary surgery have been usually given "stress dose" steroids whether their hypothalamus pituitary adrenal (HPA) axis are deficient or preserved. Results of several retrospective studies showed that there was no significantly increase in postoperative adrenal insufficiency in no supplementation (of hydrocortisone) group than in supplementation group. Given the considerable side effects of using steroids, whether hydrocortisone administration is necessary for all patients with pituitary adenomas during peri-operation needs to be discussed. For Chinese patients with pituitary adenomas except for those of Cushing's disease, hydrocortisone administration during the peri-operation is a routine practice. Peking Union Medical College Hospital is the China Pituitary Disease Registry Center. Here, the investigators aim to launch a single-center prospective randomized controlled trial to verify the hypothesis that withholding hydrocortisone during the peri-operation in patients with pituitary adenomas whose HPA axis are intact are safe.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 436
• Est. completion date: July 2022
• Est. primary completion date: July 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients with pituitary adenomas that need surgical resection of the tumor, whose hypothalamus-pituitary-adrenal axis are intact
• Patients of either gender aged from 18 years to 70 years

Exclusion Criteria:

• Patients with Cushing's disease
• Patients with pituitary adenomas who have already developed secondary adrenal insufficiency before surgery
• Patients with pituitary apoplexy or other acute pituitary conditions that need emergency surgery
• The postoperative pathology result indicates that the tumor is not a pituitary adenoma
• Patients that refuse to participate in the study or those who ask to quit after enrollment

Related Conditions & MeSH terms

• Adenoma
• Adrenal Insufficiency
• Pituitary Adenoma
• Pituitary Diseases
• Pituitary Neoplasms
• Surgery

Intervention

Drug:
• Normal saline
No hydrocortisone or other steroids are given before, during, and after the surgery, except that patients develop postoperative adrenal insufficiency. If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.
• Hydrocortisone
Hydrocortisone sodium succinate is given on the operation day (100mg at 0800 & 100mg at 2000), the postoperative day 1 (100mg at 0800 & 50mg at 2000), and the postoperative day 2 (25mg at 0800). Hydrocortisone (po.) is then given starting from the afternoon of postoperative day 2 (20mg at 1600 and 0800) to the end of the first postoperative week, and 20mg at 0800 during the second postoperative week. This is called the "hydrocortisone taper program". If a patient develops postoperative adrenal insufficiency, he/she needs to receive hydrocortisone treatment (20mg at 0800 and 20mg at 1600) for one month and then check the level of morning serum cortisol to decide if it is time to start the hydrocortisone taper program.

Locations

Country	Name	City	State
China	Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking Union Medical College Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

Lee HC, Yoon HK, Kim JH, Kim YH, Park HP. Comparison of intraoperative cortisol levels after preoperative hydrocortisone administration versus placebo in patients without adrenal insufficiency undergoing endoscopic transsphenoidal removal of nonfunctioning pituitary adenomas: a double-blind randomized trial. J Neurosurg. 2020 Jan 24:1-9. doi: 10.3171/2019.11.JNS192381. [Epub ahead of print] — View Citation

Sterl K, Thompson B, Goss CW, Dacey RG, Rich KM, Zipfel GJ, Chicoine MR, Kim AH, Silverstein JM. Withholding Perioperative Steroids in Patients Undergoing Transsphenoidal Resection for Pituitary Disease: Randomized Prospective Clinical Trial to Assess Safety. Neurosurgery. 2019 Aug 1;85(2):E226-E232. doi: 10.1093/neuros/nyy479. — View Citation

Tohti M, Li J, Zhou Y, Hu Y, Yu Z, Ma C. Is peri-operative steroid replacement therapy necessary for the pituitary adenomas treated with surgery? A systematic review and meta analysis. PLoS One. 2015 Mar 16;10(3):e0119621. doi: 10.1371/journal.pone.0119621. eCollection 2015. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Rate of newly-developed diabetes mellitus	A random reading of blood sugar level more than 200 mg/dL (11.1 mmol/L), or a reading after two hours (after OGTT) over 200 mg/dL (11.1 mmol/L) indicates diabetes mellitus.	During the first 3 postoperative months
Other	Rate of newly-developed diabetes insipidus	Urine volume > 300ml for more than 3h or > 6 liter per day, specific gravity of urine <1.003, and serum sodium levels > 145 mmol/L indicate diabetes insipidus.	During the first 3 postoperative months
Other	Concentration of blood electrolytes	The level of Na+, K+, and Ca++ in the blood	At the 3rd postoperative month
Other	Concentration of blood cells	Numbers of erythrocytes, leukocytes, neutrophils, lymphocytes, thrombocytes in the blood	At the 3rd postoperative month
Other	Percentage of blood cells	Percentage of neutrophils, monocytes, lymphocytes of the leukocytes	At the 3rd postoperative month
Other	Concentration of indexes of coagulation function #1	Prothrombin time, activated partial thromboplastin time, and thrombin time	At the 3rd postoperative month
Other	Level of international normalized ratio	Level of international normalized ratio	At the 3rd postoperative month
Other	Level of D-Dimer	Level of D-Dimer	At the 3rd postoperative month
Other	Rate of deep venous thrombosis	Deep venous thrombosis as detected by ultrasound	During the first 3 postoperative months
Other	Rate of other complications	Decreased bone density, osteoporosis, fracture, acne, and infections.	During the first 3 postoperative months
Primary	Rate of newly-onset adrenal insufficiency	Adrenal insufficiency: lower-than-normal serum cortisol level at 8 a.m., plus the following related symptoms, including serious fatigue, muscle weakness, decreased appetite, nausea, vomiting, diarrhea, low blood pressure, palpitation, and fever.	During the first 3 postoperative days
Secondary	Rate of newly-onset adrenal insufficiency	Adrenal insufficiency: lower-than-normal serum cortisol level at 8 a.m., plus the following related symptoms, including serious fatigue, muscle weakness, decreased appetite, nausea, vomiting, diarrhea, low blood pressure, palpitation, and fever.	From the 3rd postoperative day to the 3rd postoperative month