A nurse is caring for a client who is postoperative following a bilateral adrenalectomy

Indian J Endocrinol Metab. 2015 Nov-Dec; 19[6]: 834–840.

Abstract

Aim:

To assess the outcome of patients undergoing bilateral adrenalectomy for Cushing's syndrome [CS].

Methods:

All patients who underwent bilateral adrenalectomy for CS at the Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences hospital between 1991 and 2013 were included. Medical records were reviewed to obtain patient characteristics and follow-up data.

Results:

Twenty-seven patients were studied. Mean age was 28.74 ± 12.95 years [range 9–60], male:female ratio was 1.7:1. About half that is, 48.19% were of Cushing's disease [failed trans-sphenoidal surgery [TSS]], 37.04% were of ectopic CS [ECS], and 14.81% were of CS due to bilateral adrenal pathology. Median follow-up period was 80.5 months. Before surgery, 74.1% patients had body mass index > which after surgery declined to kg/m2 [mean BMI - 35.7[10] and 35.0[9]]. Clinical improvement was seen in most of the patients after bilateral adrenalectomy. Around 75% of our patients showed improvement in obesity and diabetic status and more than 90% patients showed improvement in blood pressure control, proximal myopathy, hirsutism, and psychiatric symptoms. Some symptoms of CS persist despite achieving biochemical normal cortisol levels after surgery. Although there is an improvement in symptoms and quality of life after bilateral adrenalectomy, yet it remains a little inferior when compared with the matched population.[9,11] Psychiatric disorders and chronic fatigue persist long after achieving biochemical normocortisolism.[8,12] The quality of life after bilateral adrenalectomy does not appear to be different in patients treated with laparoscopic when compared with an open approach.[11]

The adrenal crisis remains a dreaded sequelae of bilateral adrenalectomy and persists as an important cause of morbidity and sometimes mortality in these patients. In our series, 36.3% patients develop at least one episode of adrenal crisis during a median follow-up of 80.5 months, whereas it varied between 9% and 64% with a median rate of 28% in other series[13] [Table 4]. In a study almost 25% of patients treated by bilateral adrenalectomy had at least one episode of adrenal crisis requiring admission to the hospital and administration of intravenous saline with corticosteroids.[14] In a recently published review on the outcome of bilateral adrenalectomy, the incidence of the adrenal crisis was 9.3/100 patient-year, whereas it was somewhat higher in our patients [10.16/100 patient-year].[13] Patients experiencing the first attack are much more prone to die than those who have already experienced it but survived. Sadly 2 out of 5 of our patients who experienced the first attack of crisis died on the way to the hospital. However, all the 3 patients who experienced multiple attacks of adrenal crisis did survive. An adrenal crisis leading to mortality after bilateral adrenalectomy remains the most fearsome squeal among the minds of surgeons. As our data shows, a majority of patients do survive and can be expected to lead a near normal life. By adequate glucocorticoid substitution and education of patients after bilateral adrenalectomy, adrenal crisis can be managed and prevented.

Table 4

Comparison of outcome with other series

In our series, we found 41% of our patients develop NS and the incidence varies widely between 0% and 47%[13] [Table 4]. The diagnostic criteria of NS remain controversial, and a firm consensus is still lacking.

Following bilateral adrenalectomy,[15,16] the diagnosis of NS is based on:

• Growing residual pituitary adenoma

• ACTH levels > mg/dl

• Hyperpigmentation of the skin.

In 2010 in a review study on NS, Barber et al.,[17] laid down a new diagnostic criteria which is, “a patient of bilateral adrenalectomy for CD having at least one of the following two criteria:

• An expanding pituitary tumor in MRI brain

• An elevated level of ACTH to > ng/L from a single plasma sample collected at 8.00 AM prior to steroid administration or a rise of ACTH to >% on at least two consecutive occasions.”

A study demonstrated that NS is a frequent complication after bilateral adrenalectomy and developed in 28% of patients.[18] Several factors that can predict development of NS are high basal level of ACTH after adrenalectomy, young age at adrenalectomy, presence of pituitary tumor before adrenalectomy, prophylactic pituitary radiotherapy, subnormal steroid replacement, pre-treatment urinary cortisol level, and female gender. Of these, the high basal level of ACTH after adrenalectomy remains the best predictive factor.[11,19,20,21] Prophylactic pituitary radiotherapy is a protective factor against the development of NS.[11,22]

Surprisingly in 2 of our ECS patients, source remained unidentified initially but could be detected only during the follow-up. Once identified, these patients underwent surgery and the tumor was excised successfully. Based on these observations is it wise not to rush for bilateral adrenalectomy in these patients. Repeated imaging studies over a period of time may unveil the primary source, which then may become amenable to surgery at a later date. However, this approach remains controversial as a delay in surgery can lead to worsening of CS, and, therefore, poor quality of life. If survival is a problem and primary/ectopic is not identified, then bilateral adrenalectomy is to be strongly considered.

Overall mortality

Overall mortality in our series was 22% which is quite well-comparable to mortality in other series and varies from 0% to 88% [median 17%] at a median follow-up of 41 months[13] [Table 4]. Three patients died in the perioperative period including one patient at 3 months after surgery but during the same admission. All the 3 patients presented with severe muscle weakness preoperatively and despite successful and uneventful surgery could not be weaned off postoperatively from the ventilator due to the poor respiratory effort. They developed repeated chest infections and despite best ICU care succumbed to sepsis and multi-organ failure.

Mortality during follow-up

Overall, 13.6% patient died during the follow-up period. The mortality was the highest in patient of ECS due to the progression of their underlying disease process after bilateral adrenalectomy.[13] In our study also, the highest mortality [50%] was seen in the patients diagnosed to have ECS. Risk factors for mortality included:

• Male sex [5 males, 1 female]

• Diagnosis of ECS where the source remains undetected

• Prolonged ventilator dependence during the postoperative period.

Most of the deaths occurred in perioperative and in the early follow-up period. Causes include recurrent chest infections, hypercortisolism and immunosuppression causing increased susceptibility to infection, muscle weakness, and poor respiratory effort leading to recurrent lower respiratory tract infections. Mortality during long-term follow-up could be attributed to adrenal crisis.

CONCLUSIONS

Bilateral adrenalectomy is a valid treatment option for the management of manifestations of hypercortisolism in patients of CS. It provides good palliation in CD with failed TSS and unlocalized ECS while the procedure is curative for bilateral adrenal CS patients. The majority of patients experience good survival and a good quality of life. However, a higher morbidity and mortality do occur if co-morbidities are more severe during the preoperative period. Despite advances in medical sciences, the procedure carries higher morbidity and mortality but may still need to be done in some patients where other treatment options fail. Due to inherent complexities involved in diagnosis, management, postoperative care, and follow-up, the procedure should be performed only in well-equipped and experienced centers.23

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest

Acknowledgments

We are thankful to Dr. Prabhakar Mishra, Department of biostatistics, SGPGI Lucknow, for statistical analysis.

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