Adrenocorticotropic Hormone-Independent Hypercortisolism Managed by Bilateral Retroperitoneoscopic Adrenalectomy: Report of a Case and Review of Literature.

Bilateral adrenalectomy is the reference treatment for Cushing's syndrome related to adrenocorticotropic hormone-independent macronodular adrenal hyperplasia (AIMAH). We report a case of AIMAH managed by sequential retroperitoneoscopic adrenalectomy and review the literature of the same. Copyright:

INTRODUCTION

Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome (CS) in children. Bilateral adrenalectomy (BA) is the definitive treatment. We report a case of AIMAH managed by sequential retroperitoneoscopic adrenalectomy and review the literature of the same.

CASE REPORT

A 7-year-old boy presented with excessive weight gain for the past 1 year. On examination, he was obese, hyposthenic with a body mass index of 50 (weight 67 kg, height 117 cm) [Figure 1a]. He was hypertensive (blood pressure [BP] 130/90 mmHg). There was no family history of similar illness. His serum cortisol levels were elevated (28.3 mcg/dl). The epinephrine, norepinephrine, dopamine, and testosterone levels were within normal levels. The ACTH levels were very low (<1 pg/ml). The dehydroepiandrosterone sulfate levels were high (181.50 mcg/dl). Genetic studies were not done. On magnetic resonance imaging (MRI) of the abdomen, both adrenals were nodular (left > right) with no obvious focal lesion [Figure 2a]. MRI of the brain showed a normal pituitary gland. He had concentric left ventricular hypertrophy (secondary to systemic hypertension) on echocardiography. A diagnosis of AIMAH was reached. BP control needed four anti-hypertensives (enalapril, nifedipine, furosemide, and spironolactone). He underwent left retroperitoneoscopic adrenalectomy. As his BP and serum cortisol levels remained elevated (28.06 mcg/dl), a right retroperitoneoscopic adrenalectomy was performed 2 weeks later.

Figure 1

Clinical picture: (a) At presentation. (b) At 6 months of follow-up

Figure 2

Magnetic resonance image showing adrenal hyperplasia and intraoperative picture. (a) Adrenal gland. (b) Opening Gerota's fascia. (c) Inferior adrenal vein. (d) Adrenal gland being retrieved through the bag

Retroperitoneoscopic adrenalectomy

The procedure was performed with the patient in prone position with a 90° angle between the spine and the legs. It is vital to maximize the distance between the rib and the hip bone. A 1-cm skin incision was made at the tip of the 12th rib, and the retroperitoneal space was expanded by blunt finger dissection and camera port inserted. A 5-mm trocar was inserted just below the tip of 11th rib. The third trocar (5 mm) was placed, at the same level of the first one, at half distance between the spine and the first port. Retroperitoneoscopy was performed with a 10-mm 30° endoscope. The Gerota's fascia was opened [Figure 2b]. The upper pole of the kidney was identified. The peritoneum was identified laterally and the diaphragm superiorly. The adrenal gland is situated between these landmarks. The dissection was done from lateral to medial side, gently lifting the adrenal gland off the kidney and freeing it of its lateral attachments. Small vessels were controlled with diathermy. As they progressed medially, the adrenal vein is identified, isolated, and divided [Figure 2c]. The adrenal gland was extracted through the camera port with a retrieval bag system [Figure 2d].

Pathology suggested nodular adrenal hyperplasia. He was discharged on adrenal hormone replacement. At 6 months of follow-up, he showed a significant weight reduction [Figure 1b]. His cortisol levels have come down to normal levels.

DISCUSSION

AIMAH is a rare cause of ACTH-independent CS. It involves both adrenal glands that are massively enlarged and can reach 10–100 times their normal weight. Its etiology is unclear. Studies have demonstrated the expression of ectopic membrane receptors in the adrenal cortex, due to dedifferentiation of adrenocortical cells or mutations in promoter regions or transcription factors. Stimulation of these ectopic receptors is a possible mechanism of cell growth and proliferation.[1] AIMAH has a genetic origin, with mutation in ARMC5 gene accounting for more than 50% of cases.[2] These enlarged adrenals secrete cortisol independently of pituitary ACTH, which results in CS.

Different treatment strategies have been used in patients with AIMAH. BA is considered the standard treatment.[3] It completely resolves CS, but the patient is obliged to life-long primary adrenal insufficiency, to receive lifetime steroid replacement therapy, and is susceptible to adrenal insufficiency crisis. It also has a high risk of mortality.[4] Unilateral adrenalectomy (UA) has been reported only in few studies with limited postoperative data.[5] UA of the larger gland appears to be a reasonable alternative to BA in overt CS, as it normalizes the cortisol levels and improves CS, with a risk for adrenal insufficiency much lower than in BA. On the other hand, UA leaves the patient with an abnormal adrenal and may lead either to persistent CS or to a high risk of recurrence. UA has an advantage over BA which is if needed the other side can be operated while once BA is done, it is a permanent. Further prospective studies are needed to better evaluate the benefits of UA over BA.

Since its first description in 1993 by Gagner et al.,[6] minimally invasive adrenalectomy has become the preferred technique for the removal of adrenal tumors. Both transperitoneal adrenalectomy and retroperitoneoscopic adrenalectomy are feasible, safe, and effective and guarantee better short-term outcomes than open surgery for benign lesions. The retroperitoneal approach is useful in patients who may have scarring or adhesions from previous abdominal surgery and avoids bowel handling and the potential for injury to the intra-abdominal viscera. It could be advantageous in very obese patients and in bilateral lesions as this approach does not require changing the position of the patient on the operating table. No intraperitoneal insufflation is needed which is very useful in patients with potential cardiovascular or respiratory compromise. Disadvantages are the smaller maneuvering space and fewer anatomic landmarks, which cause a greater learning curve. Many studies indicate that posterior retroperitoneoscopic adrenalectomy is superior to laparoscopic one regarding operation time, pain score, blood loss, complications rate, and return to normal activity.[7] A meta-analysis suggested that retroperitoneoscopic adrenalectomy has equivalent outcome to laparoscopic surgery but is associated with shorter hospital stay.[8]

In our case, as the patient was very obese, we did retroperitoneal adrenalectomy. We initially operated on the left side (as it was the larger gland) with the intention of avoiding adrenal insufficiency. However, the free cortisol levels persisted to be high. Hence, we had to remove the right adrenal as well. This reinforces the fact that BA is the standard treatment for AIMAH.

CONCLUSION

AIMAH is a rare cause of ACTH-independent CS. Preoperative stabilization is important. BA is still the standard modality for its treatment. Retroperitoneoscopy is a safe and effective approach for adrenalectomy, especially for obese patients, patients with cardiopulmonary insufficiency, and in patients where BA is planned.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.