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Successful treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia with laparoscopic adrenalectomy: a case series
© Ito et al.; licensee BioMed Central Ltd. 2012
Received: 26 January 2012
Accepted: 2 August 2012
Published: 18 September 2012
Adrenocorticotropic hormone-independent macronodular adrenal hyperplasia, characterized by bilateral macronodular adrenal hypertrophy and autonomous cortisol production, is a rare cause of Cushing’s syndrome. Bilateral adrenalectomy is considered the standard treatment for adrenocorticotropic hormone-independent macronodular adrenal hyperplasia but obliges the patient to receive lifetime steroid replacement therapy subsequently, and may increase the patient’s risk of adrenal insufficiency. These circumstances require surgeons to carefully consider operative strategies on an individual basis.
We performed successful laparoscopic adrenalectomy on four patients with adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. Computed tomography scans showed bilateral adrenal enlargement in all patients. Case 1: a 56-year-old Japanese woman presented with obvious Cushing’s symptoms during treatment for diabetes mellitus and hypertension. Case 2: a 37-year-old Japanese man also presented with Cushing’s symptoms during treatment for diabetes mellitus and hypertension. These patients were diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia based on endocrinologic testing, and underwent bilateral laparoscopic adrenalectomy. Case 3: an 80-year-old Japanese woman was hospitalized due to unusual weight gain and heightened general fatigue, and was diagnosed as Cushing’s syndrome caused by adrenocorticotropic hormone-independent macronodular adrenal hyperplasia. She underwent unilateral laparoscopic adrenalectomy due to high operative risk. Case 4: a 66-year-old Japanese man was discovered to have bilateral adrenal tumors on medical examination. He did not have Cushing’s symptoms and was diagnosed as subclinical Cushing’s syndrome due to suppressed adrenocorticotropic hormone serum levels and loss of cortisol circadian rhythm without abnormal levels of serum cortisol. He underwent unilateral laparoscopic adrenalectomy. During follow-up, serum cortisol levels were within the normal range in all cases, and serum adrenocorticotropic hormone levels were not suppressed. Further, cases with Cushing’s syndrome experienced clinical improvement.
We were able to effectively treat adrenocorticotropic hormone-independent macronodular adrenal hyperplasia in patients with obvious Cushing’s symptoms by laparoscopic bilateral adrenalectomy, which promptly improved symptoms. Further, unilateral adrenalectomy was effective for treating an older patient at high operative risk and a patient with subclinical Cushing’s syndrome.
Adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH), an impairment demonstrated by bilateral macronodular adrenal hypertrophy and autonomous cortisol production, is a rare cause of Cushing’s syndrome. Although bilateral adrenalectomy is considered the standard treatment for AIMAH [1, 2], patients receiving this treatment are subsequently obliged to receive lifetime steroid replacement therapy and may be susceptible to adrenal insufficiency. Given these concerns, the operative strategy for treating AIMAH must be considered carefully for each individual case.
Here we report the surgical and clinical aspects of four cases of AIMAH that were treated by laparoscopic adrenalectomy, including two requiring bilateral adrenalectomy.
Clinical and biochemical findings
Body mass index (kg/m2)
Size of adrenal gland
Serum cortisol (μg/dL) (basal values: 5.3 to 11.0)
Plasma adrenocorticotropic hormone (pg/mL) (normal values: 7.2 to 63.3)
At 8 a.m.
At 11 p.m.
A 56-year-old Japanese woman presented with several symptoms characteristic of Cushing’s syndrome, including moon face and central obesity, during treatment for diabetes mellitus and hypertension. She was diagnosed as Cushing’s syndrome caused by AIMAH due to autonomous production of adrenal cortisol, which was accompanied by suppressed serum ACTH levels (<5.0pg/mL) and a loss of cortisol circadian rhythm. She underwent laparoscopic bilateral adrenalectomy because of her overt Cushing’s symptoms. The operative procedure in this case has been described by Shinbo et al. . Cortisol replacement therapy was started immediately upon completion of surgery.
An 80-year-old Japanese woman was hospitalized because of unusual weight gain (about 10kg over about two years) and general fatigue. Upon admission, she was diagnosed as Cushing’s syndrome. She underwent unilateral adrenalectomy due to high operative risk. We based our decision on the side to operate on based on which gland was larger according to CT scan findings.
A 66-year-old Japanese man was incidentally discovered to have bilateral adrenal tumors but no Cushing’s symptoms. The endocrinological data showed a normal level of cortisol (10.4μg/dL) with a suppressed serum ACTH level (<5.0pg/mL), which showed neither a cortisol circadian rhythm nor suppression by dexamethasone administration (9.1μg/dL after 1mg; 16.9μg/dL after 8mg). He underwent right laparoscopic adrenalectomy due to subclinical Cushing’s syndrome. In this case, the right adrenal gland was removed, because adrenal venous sampling revealed that cortisol production from the right gland was much greater than from the left (right: 38.9μg/dL; left: 20.3μg/dL).
Operative procedures and results
Site of adrenalectomy
Operation time (minutes)
Blood loss (g)
Weight of adrenal gland (L/R, g)
Discharge (post-operative day)
Dosage of hydrocortisone at discharge (mg/day)
Surgical site infection
Clinical course and outcomes
Follow-up duration (months)
Dosage of hydrocortisone (mg/day)
Body mass index (kg/m2)
Serum cortisol at 8 a.m. (μg/dL) (normal values: 5.3 to 11.0)
Plasma adrenocorticotropic hormone (pg/mL) (normal values: 7.2 to 63.3)
Bilateral adrenalectomy and steroid replacement therapy is considered the standard treatment for AIMAH [1, 2]. Several cases of successful laparoscopic bilateral adrenalectomy for AIMAH have been reported [3–6], and each involved little blood loss during surgery. Laparoscopic adrenalectomy is less invasive than open surgery for treating AIMAH and may prevent a number of post-operative complications due to impaired glucose tolerance and immunodeficiency. However, treatment of AIMAH requires considerable skill given the impressive size and fragility of adrenal tumors.
Although we opted for a bilateral approach here, several patients have been treated successfully after receiving only medical treatment or subtotal or unilateral adrenalectomy [7–9]. The rationale for implementing these treatments was to avoid impairing our patients’ quality of life due to the risk of critical adrenal insufficiency after bilateral adrenalectomy. Two recent reports note that unilateral adrenalectomy of the larger gland with AIMAH resulted in improvement in Cushing’s symptoms after a mean follow-up time of 53 or 78.8 months [10, 11]. However, the efficacy of unilateral adrenalectomy for AIMAH remains controversial because the mean patient age in these reports is 52.6 years, clearly insufficient for long-term assessment. We reasoned, therefore, that if a patient receives a second operation to remove the remaining gland when Cushing’s syndrome recurs during follow-up, unilateral adrenalectomy might also be effective in selected cases such as those reported here. In patients with subclinical AIMAH, the decision regarding therapy should take into account normalization of cortisol excess. Unilateral adrenalectomy is the treatment of choice, as well as medical treatment or subtotal or unilateral adrenalectomy, for normalization of cortisol excess. However, careful attention must be paid after unilateral adrenalectomy, as the criteria and long-term prognosis of this procedure in subclinical AIMAH have not been well established. If unilateral adrenalectomy is performed, determination of the surgical site should be based on asymmetrical adrenal enlargement or adrenal venous sampling analysis; the gland more strongly influencing the patient’s condition should be removed.
In our experience, laparoscopic bilateral adrenalectomy for AIMAH with obvious Cushing’s symptoms was effective in rapidly improving symptoms when performed by an experienced surgical team. Further, unilateral adrenalectomy can also be effective when the patient is older and subject to high operative risk or does not present with clinical symptoms. Because long-term prognosis associated with this surgical technique remains controversial, strategies for treating AIMAH must be carefully considered on a case-by-case basis.
Written informed consent was obtained from all patients for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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