CUSHING'S SYNDROME CAUSED BY AN ADRENOCORTICAL CARCINOMA AFTER A BARIATRIC SURGERY: CASE REPORT

INTRODUCTION

Interest in the study of adrenocortical carcinoma has greatly increased in the last 12 years. In the last decade, more medical articles about this subject have been published than in the last 50 years¹. Adrenal carcinoma is a rare and aggressive neoplasia and the affected patients have less than a 50% chance of survival in five years. In the metastatic disease, the survival rate is less than 15%². It has an incidence of 0.7 to 0.2 per 1 million people each year with bimodal distribution and it is predominant in females². The incidence is shown to be higher in children from the South of Brazil due to environmental and genetic factors^3,4. It represents 3-6% of all carcinomas³.

The purpose of this report is to relate a patient with morbid obesity that underwent bariatric surgery and after that developed the Cushing's syndrome caused by an adrenocortical carcinoma.

CASE REPORT

A 54 years old patient was admitted to the endocrinology unit in February 2012. She had a 3-month history of acne, hirsutism, muscle weakness in her lower limbs, increasing levels of hypertension and diabetes mellitus imbalance. The physical exam revealed a rounded face, clavicular fatness, a fatty hump, BP= 200X100 mmHg, BMI=32.4 kg/m². She had a gastric bypass due to morbid obesity in 2009, with BMI=52,47 kg/m². Hormonal data were consistent with CS- ACTH independent (Table 1).

TABLE 1
- Laboratorial and weight evolution during the patient's follow-up

	February 2012	May 2012	August 2012	March 2013	References
ACTH	< 5.0	33.2	< 5.0	< 5.0	<46 pg/ml
DHEA-S	1410		248.6		19-205 u/dl
Androstenedione	>10	0.32	4.61	>10	0.40-3.0 ng/ml
17 -alpha-OH-progesterone	2.14		0.23	297ng/dl **	0.19 -1.0 ng/ml
SHBG	45.60	128.2	56.20		18-114 nmol/l
Free testosterone	6.78	0.05	0.48	23.75	0.19 - 2.06 ng/dl
Total testosterone	6.55		0.53		0.06-0.82 ng/ml
Urinary free cortisol	224.1	18.8	90.9		10-90 ug/24 h
LDDST* cortisol	31.87		9.75	15.23
LH	<0.1		19.2		1.7 - 8.6mUl/ml

• DHEA-S=plasma dehydroepiandrosterone sulfate; *LDDST=low dose dexamethasone suppression test; **change in the ng/dl method (VR: 59-344 ng/dl)

Abdominal computed tomography showed an expanding lesion in the left adrenal area of 13.0X9.0 cm, with irregular contour lines and heterogeneous caption of contrast (Figure 1).

She was submitted to a left adrenalectomy and partial nephrectomy in April 2012. Her anatomopathological exam result was 630 g, size 21X10X 5.0 cm (Figure 2).

The pathologic findings were: 15 mitosis in 50 high power fields and the nuclear pleomorphisms was present; it showed the presence of confluent necrosis and capsular invasion; Ki-67 index was 20% positive according to the immunohistochemical criteria ; TNM tumor stage was 3-0-0.

There was regression of clinical and laboratorial alterations related to the Cushing's syndrome. She had a follow-up as an outpatient and used mitotane 2 g per day. After seven months, abdominal and thoracic tomography showed recurrence of the tumor and metastasis in the lungs (Figure 3).

FIGURE 1
- Abdominal tomography showing adrenal tumor

FIGURE 2
- Resected adrenal tumor

FIGURE 3
- Adrenal mass

As there was no satisfactory response from mitotane, cisplatin and etoposide, her clinical situation worsened and she died 13 months after having had an adrenalectomy. The patient's daughter has agreed in writing to allow the publication of this study.

DISCUSSION

Brazil is the country with the second highest numbers of bariatric surgeries and it has the highest number of bariatric surgeons in the world⁵. Although Cushing syndrome is a rare cause of obesity, it is supposed that some of the patients that have had bariatric surgery have it. There are few studies about it in patients with morbid obesity². Cushing is a disease difficult to diagnose and many times its diagnosis happens too late⁶. When hypercortisolism appears, it can be an ACTH - dependent Cushing's syndrome (70 to 80%) or ACTH - independent caused by adrenocortical tumors or hyperplasia adrenal^7,8. It is more prevalent in high risk populations such as obese people with poorly controlled diabetes and its incidence ranges between 3.3 to 5.8% in published studies ⁸. Screening for Cushing before bariatric surgery has been suggested in order to avoid a procedure that could be lethal and irreversible as it has already been described^8,9. There are reports about it over 9.33% in obese patients¹⁰. Approximately 60% of adrenal carcinomas are functioning and 70% are manifested by Cushing syndrome, associated or not to virilization. Virilization and DHEA-S high levels are more associated to malign tumors¹¹. In those tumors, the symptoms associated to the glucocorticoids excess develop fast (from 3 to 6 months)². Patients with higher recurrence risk present a high rate of malignity in the histology (Ki67 staining of >10% of tumor cells, >20 mitotic figures per 50 high power fields) no matter what the tumor size and the vascular and capsular invasion¹². Ki67 is the most powerful detector of the located or advanced disease and it can guide the treatment¹. Adrenal carcinomas grow very fast and very often they present metastasis in the lungs and liver¹¹. This patient's adrenalectomy did not show evidence of metastasis. However, after seven months she had a recurrence of the disease and there was lung metastasis. This case highlights the fact that patients with morbid obesity should be investigated in regard to other endocrinal diseases. Future studies are needed to evaluate the true Cushing syndrome prevalence in this population¹⁰. It is believed that this is the first case reported in the literature that refers functioning adrenocortical carcinoma which was diagnosed after bariatric surgery. The authors emphasize the importance of having an endocrinologist in the surgical team, who also diagnoses and treats Cushing syndrome in morbidly obese patients.

REFERENCES

• ¹
  Fassnacht M, Kroiss M, Allolio B. Update in adrenocortical carcinoma. The Journal of clinical endocrinology and metabolism. 2013;98(12):4551-64.
• ²
  Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, et al. Combination chemotherapy in advanced adrenocortical carcinoma. The New England journal of medicine. 2012;366(23):2189-97.
• ³
  Ribeiro RC, Michalkiewicz EL, Figueiredo BC, DeLacerda L, Sandrini F, Pianovsky MD, et al. Adrenocortical tumors in children. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al]. 2000;33(10):1225-34.
• ⁴
  Sandrini R, Ribeiro RC, DeLacerda L. Childhood adrenocortical tumors. The Journal of clinical endocrinology and metabolism. 1997;82(7):2027-31.
• ⁵
  Buchwald HO, D.M. Metabolic/Bariatric Surgery Worldwide 2011. Obesity surgery. 2013;23:427-36.
• ⁶
  Aron D. Cushing's Syndrome: why is diagnosis so difficult? Rev Endocr Metab Disord. 2010:105-16.
• ⁷
  Stiles LE. Cushing syndrome and bariatric surgery: why, when, and how to evaluate preoperatively. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2009;5(1):119-21.
• ⁸
  Fleseriu M, Ludlam WH, Teh SH, Yedinak CG, Deveney C, Sheppard BC. Cushing's syndrome might be underappreciated in patients seeking bariatric surgery: a plea for screening. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2009;5(1):116-9.
• ⁹
  Savastano S, Pivonello R, Colao A. Bariatric surgery for obesity and hidden Cushing syndrome. Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2009;5(1):121-2.
• ¹⁰
  Tiryakioglu O, Ugurlu S, Yalin S, Yirmibescik S, Caglar E, Yetkin DO, et al. Screening for Cushing's syndrome in obese patients. Clinics. 2010;65(1):9-13.
• ¹¹
  Nag S, McCulloch A. Cushing's syndrome due to an adrenocortical carcinoma. Postgraduate medical journal. 2003;79(934):466.
• ¹²
  Berruti A, Fassnacht M, Haak H, Else T, Baudin E, Sperone P, et al. Prognostic Role of Overt Hypercortisolism in Completely Operated Patients with Adrenocortical Cancer. European urology. 2013.

Publication Dates

• Publication in this collection
  2015