Introduction

Adrenal insufficiency is rare after unilateral adrenalectomy for non-functioning adrenal tumours(1). Incidental adrenal neoplasms, called incidentalomas mostly tend to be benign and

asymptomatic (2). Subclinical Cushing’s syndrome (SCS) with subtle cortisol elevations

and abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis without clinical signs

is more frequent than previously thought (2). The incidence of SCS is approximately 5-

10 % of the adrenal incidentalomas (2). Dynamic testing is recommended for evaluating

autonomous cortisol

production by an adrenal incidentaloma (3). The overnight 1 Mg dexamethasone

suppression test (ODST) is recommended as the initial screening test (3). In those

patients where surgery is done for adrenal incidentalomas based on size considerations

(>4Cms) or suspicion of malignancy then subclinical Cushing’s syndrome should be

considered and evaluated due to the risk of adrenal insufficiency perioperatively (3).

Glucocorticoid therapy in the perioperative period and post operative assessment of HPA

axis recovery are indicated in patients with SCS (3). We would like to present one such

case where the pre-operative cortisol levels were normal, but post operatively the

Cortisol levels were low with a subnormal Synacthen test confirming adrenal

insufficiency.

Case Presentation

A 43 years old female patient was referred to the Endocrinology department at



Al Zahra Hospital, Sharjah for a low cortisol level after she had the removal of a left

adrenal adenoma laparoscopically. On post-op day 2 the patient had an AM cortisol in the

hospital which was found to be low at 1.9 micrograms per dl (mcg/dl). She was

asymptomatic. Her serum sodium was found to be slightly low at 133 mmol/l (Normal

range 135-153), potassium was normal at 3.8 mmol/l (Normal range 3.5-5.3). She was in

no acute distress and her vital signs were normal. A Synacthen (Cosyntropin,

Tetracosactrin) test was ordered which confirmed a low baseline cortisol of 1.8 mcg/dl

half an hour after injecting Synacthen it was 10.2 mcg/dl and

1 hour post Synacthen was 15.8 mcg/dl, a subnormal response to

Synacthen.

An ACTH (intact) level done prior to giving Synacthen was low at 1.3

picograms/ml(pg/ml) (Normal

range 10-60 pg/ml). The patient denied receiving any steroids of any kind either

orally or parenterally or intranasally prior to surgery.

She did not have any stigmata of Cushing’s syndrome. The patient is known to have type

1 diabetes as well as primary hypothyroidism over several years with reasonable though

slightly suboptimal glycemic control ( Hba1C of 7.3). She has not noticed any increase in

insulin requirements over the past several years. She did not have any stigmata of

Cushing’s syndrome. She has no history of hypertension. She did not receive any

Etomidate by the anesthesiologist as well. Pre operative hormonal workup done by the

urologist showed a 11 AM cortisol level of 14.4 mcg/dl and plasma

catecholamines were normal. Serum electrolytes prior to surgery were normal.

Pre-operatively she had a CT scan of the abdomen which showed a well defined mass

lesion of the left adrenal gland 6.5 X 4.0 Cms without significant enhancement with

contrast.

A diagnosis of secondary/tertiary adrenal insufficiency due to subclinical Cushing’s

syndrome from the left adrenal tumor was made and she was started on hydrocortisone

25 mgs intravenously every 8 hours which was reduced over the next 48 hours and she

was switched to Hydrocortisone 10 mgs BID and she was discharged home in a stable

condition with proper instructions regarding stress dosing of hydrocortisone and was also

given hydrocortisone 100 mgs/ml vial to be taken intramuscularly in case of an

emergency.

Histopathology of the large adrenal mass (Figures 1,2,3,4&5) on the left side of 6.5 X 3.0

X 4.0 cms, showed a smooth encapsulated mass firm in consistency. Cut surface was

fleshy pale grayish in color. Microscopic examination showed a benign tumor lesion

made up of bundles of schwann cells including very few scattered and mature ganglion

cells. The pathological diagnosis was Ganglioneuroma.

Two weeks post discharge the patient came back for follow up feeling good without any

complaints. An 8 AM cortisol was done after holding the previous day’s evening dose as

well as the morning dose of hydrocortisone and it came back at 12.4

mcg/dl. Presuming that the HPA axis is beginning to recover a repeat Synacthen test was

done which showed a baseline cortisol of 10.7 mcg/dl and ACTH level of

33.3 pg/ml. Half an hour post Synacthen serum cortisol was 19.1 mcg/dl

and 1 hour post was 22.3 mcg/dl indicating a normal response to


Synacthen. The hydrocortisone dose was reduced to 10 Mgs OD. Two weeks later an 8

AM cortisol level was done after holding the AM dose of hydrocortisone and it was

normal 12.3 mcg/dl and her electrolytes were normal. She was advised to

completely discontinue the hydrocortisone and recommended stress doses of

hydrocortisone for any major procedures in the next 6 months.

Macroscopic Examination

Figure 1

Figure 1: Left adrenalectomy specimen made up of a large tomor mass measuring 6.5 x3 x 4 Cms, potato like, having smooth capsulated surface.

Figure 2

Figure 2: Cut surface is fleshy, pale brayish in color

Microscopic Examination

Figure 3

Figure 3: Benign tumor lesion made up of bundles of Schwann cells. Haematoxylin & Eosin stain (H&E). Magnification X 10 times.

Figure 4

Figure 4: Bundles of schwann cells. H&E stain. Magnification X 20 times.

Figure 5

Figure 5: Few scattered mature ganglion cells. H&E stain. Magnification X 40 times.

Case discussion

This interesting patient was found to have an incidental left adrenal mass when she was

worked up for left loin pains. Her pre-op hormonal workup for the adrenal mass revealed

normal cortisol levels as well as plasma catecholamine levels. On day 2 of the post

operative period she was found to have an AM cortisol level which was very low. A

subsequent Synacthen test showed a subnormal response to tetracosactrin as well as a

very low baseline ACTH (intact) level. She was asymptomatic. The only other laboratory

abnormality was a slightly low serum sodium level which goes in favor of secondary

adrenal insufficiency. She was treated with intravenous hydrocortisone without any

mineralocorticoids. She was stable on the treatment. Within several weeks her

Hypothalamic pituitary adrenal axis improved and she was withdrawn from the steroid

treatment.

In retrospect the explanation for the adrenal insufficiency was that she had

subclinical Cushing’s syndrome from the left adrenal mass which caused HPA axis

suppression. It is to be noted that her cortisol

level prior to surgery was normal, emphasizing the need for dynamic testing for


subclinical Cushing’s syndrome prior to surgery.

A literature review of reports of adrenal ganglioneuroma causing either pre-clinical or

overt Cushing’s syndrome was made. There was one report of virilizing adrenal

ganglioneuroma in a woman with subclinical Cushing’s syndrome by Diab et al(6) from

the Cleveland clinic. There were reports of Cushing’s syndrome with adrenal

neuroblastoma in an infant (Kenny et al)(7), Adrenocortical adenoma and

ganglioneuroblastoma in a child( Dahms et al)(8) and ectopic Cushing’s syndrome due to

an adrenal ganglioneuroma(Corcuff et al)(9). Adrenal ganglioneuroma is a rare cause of

subclinical Cushing’s syndrome.

Conclusion

Adrenal insufficiency is rare after unilateral adrenalectomy for non-functioning adrenal tumors. Subclinical Cushing’s syndrome although rare could have enormous clinical implications

to the patient if the diagnosis is missed as this could lead to catastrophic adrenal

insufficiency in the immediate post op period. Dynamic testing of autonomous cortisol

production for all adrenal masses is currently recommended pre-operatively. The current

recommendations from AACE include perioperative glucocorticoid therapy and post

operative assessment of HPA axis recovery in patients with SCS. Adrenal

ganglioneuroma is a rare cause of subclinical Cushing’s syndrome.