Bilateral Macronodular Adrenal Hyperplasia

Cushing’s syndrome is the set of clinical manifestations secondary to a chronic excess of glucocorticoids. Bilateral macronodular adrenal hyperplasia with subclinical cortisol secretion is the most common, but its prevalence remains unknown. We describe a case of bilateral macronodular adrenal hyperplasia. This is a 36-year-old female patient who had been consulting for secondary amenorrhea and developing asthenia for 4 months. The clinical examination noted an overweight patient with high blood pressure, facio-trunk obesity, hirsutism and purple stretch marks in the abdomen and thighs. Biologically, hypokalemia at 2.9 meq/l (3.5 5.4), normal calcemia at 90 mg/l (85 104), fasting blood sugar was 0.84 g/l (0.7 1), the tests for minute, low and high dexamethasone suppression test revealed insufficient suppression of cortisol. The cortisoluria collected from the second day to the third day of the high dexamethasone suppression test was at 186 μg/24 h (<60), the ACTH (Pg/ml) was undetectable (6.4 49.8). The diagnosis of an independent adrenocorticotrophin (ACTH) Cushing syndrome was made and the adrenal CT scan revealed bilateral macronodular hyperplasia. A bilateral adrenalectomy was performed and a complete remission of Cushing syndrome was achieved. We prescribed to her, hydrocortisone 20 mg/day and alpha-fludrocortisone 25 to 50 μg/day, This medical observation showed that macro-nodular adrenal hyperplasia with overt Cushing syndrome can occur in the third decade of life. Bilateral adrenalectomy has resulted in a complete cure for Cushing’s syndrome, but may be fraught with complications.


Introduction
Cushing's syndrome is the set of clinical manifestations secondary to a chronic excess of glucocorticoids. Its origin may be dependent on the adrenocorticotropic hormone (ACTH) in 80% of cases or independent of adrenocorticotrophin ACTH, therefore adrenal in 20% of cases. The adrenal origin can be bilateral in less than 2% of cases and in this case it can be bilateral macronodular or micronodular hyperplasia of the adrenals [1] [2] [3] [4]. Bilateral macronodular hyperplasia (BMAH) with subclinical cortisol secretion is the most common, but its prevalence remains unknown [5] [6] [7]. We describe a case of bilateral macronodular adrenal hyperplasia.

Observation
A 36-year-old patient who has been consulting for secondary amenorrhea and asthenia evolving since four months.
At the clinical examination, we observe an apyretic and asthenic patient, a body mass index (BMI) at 26.44 kilos/m 2 , high blood pressure at 160/100 mmHg, pulse at 80 beats/minute, facio-truncal obesity with a lunar facies, the roots of the pelvic limbs are slender, a hirsutism in the chin and cheeks evaluated at 7/36 according to the score of Ferriman and Galway, purple stretch marks on the abdomen and thighs, thin and ecchymotic skin.
The diagnosis of an independent ACTH Cushing syndrome was retained and the adrenal CT scan revealed bilateral macronodular hyperplasia with adrenals that measured on average 8 cm in diameter and descended to the renal hilum. Iodocholesterol scintigraphy was not performed. Bone densitometry was not performed.
The medical preparation for surgery had consisted of the administration of nizoral (ketoconazole) 600 mg/day but stopped a week later before the occurrence of significant hepatic cytolysis with transaminases increased to more than four times the normal upper. She was then put on OP'DDD (mitotane) 3 g/day for a month later combined with orimetene (aminogluthetimide) 1000 mg/day for a week. The medical preparation was stopped two days before surgery. Bilateral laparoscopic adrenalectomy was retained but converted to laparotomy intraoperatively before rupture of the splenic pedicle complicated by profuse hemorrhage. This first intervention was limited to the left adrenalectomy and a caudal

Discussion
Our patient's age was lower than that described in the literature. Physiologically, ACTH by binding in the fasciculated zone on its receptor coupled to protein G (melanocortin type 2), induces an enzymatic cascade leading to the synthesis of cortisol.
In BMAH, the synthesis of cortisol is dependent on illegitimate receptors coupled to the protein G. These latter under the influence of several hormones such as the gastric inhibitory polypeptide (GIP), catecholamines, vasopressin, glucagon, serotonin, angiotensin 2, luteinizing Hormone (LH) or human chorionic gonadotrophin (HCG) stimulate cortisol synthesis [14]. In BMAH with Cushing's syndrome, 80% of patients have an illegitimate receptor and 55% of patients have several [9] [10] [15]. These illegitimate receptors are responsible for the formation of adrenal  [3]. Autocrine synthesis by the hyperplastic adrenals of ACTH, the regulation of which does not depend on the corticotropin releasing hormone (CRH), has also been described in recent studies [13].
In the molecular test, several genes are linked to the occurrence of BMAH.
As a prelude to surgery, steroidogenesis inhibitors such as ketoconazole, mi-  [4]. Bilateral adrenalectomy in all-cause Cushing syndrome is responsible for 17% mortality according to Ritzel et al. [18]. In our case, the conversion of laparoscopic adrenalectomy to laparotomy occurred after the rupture of the splenic pedicle, which testifies that this surgery is not without complications.
When cortisoluria is less than twice the normal value, a unilateral adrenalectomy of the largest adrenal gland or the one which has the most fixed marked iodocholesterol is indicated [10]. Sheikh Ahmad et al analyzed 71 cases of unilateral adrenalectomy performed for bilateral macronodular adrenal hyperplasia.

Conclusion
This medical observation has shown that macro-nodular adrenal hyperplasia with patent Cushing syndrome can occur in the third decade of life. Bilateral adrenalectomy has resulted in a complete cure for Cushing syndrome, but it can be punctuated by complications.