Adrenocortical carcinoma: a diagnostic and treatment dilemma

Abstract

A 61-year-old woman was referred by her GP with a 12-month history of weight gain, facial puffiness, difficulty climbing stairs and the tendency to bruise easily. On clinical examination she had a moon face, bruising all over the body and a raised blood pressure of 170/100 mmHg. Routine haematological and biochemical tests were normal apart from a raised glucose level of 16 mmol/litre. 9 am cortisol was raised on three consecutive occasions: 698, 842 and 716 nmol/litre (normal range 119–618 nmol/litre). A simultaneous adrenocorticotropic hormone was undetectable at <5 ng/litre (normal range <50 ng/litre). 24-hour urine cortisol excretion was raised on three consecutive occasions 1643, 2130 and 1918 nmol/24 hours (normal range 33–286 nmol/24 hours). Computed tomography scan of the abdomen and chest revealed a 5 cm mass with heterogeneous enhancement in the right adrenal gland. The liver, both kidneys and spleen were normal and the lung fields were clear. The report stated that the size of the tumour and enhancement characteristics were more in keeping with a malignant rather than benign neoplasm. The patient was commenced on metyrapone and underwent right laparoscopic adrenalectomy. The tumour was removed intact and histopathology revealed features of adrenocortical adenoma with no convincing evidence of malignancy. She made a good clinical and biochemical recovery postoperatively and cortisol levels in the blood and urine returned to normal. Ten months later she developed swellings at the site of entrance of the laparoscope and at the site of the drain. On examination she had 2 cm diameter mobile subcutaneous nodules at three of the port sites. Computed tomography of the abdomen revealed a normal adrenal bed but three subcutaneous masses lying in the right upper quadrant, leading to suspicions of metastasis. The masses were excised and histology confirmed them to be cancerous and morphologically similar to the tumour excised from the adrenals. However, they had acquired more worrying histological features (higher mitotic and apoptotic rate, as well as focal necrosis) and were regarded as being of uncertain malignant potential. The patient made a good recovery from the operation and remained well for the next 2 years with no clinical or biochemical evidence of recurrence of the disease. However, she again developed a puffy face, difficulty going upstairs and her blood pressure became more difficult to control. Her 9am cortisol was raised (679 nmol/litre) with undetectable adrenocorticotropic hormone. 24-hour urine cortisol was raised (2704 nmol/litre), and a computed tomography of the abdomen revealed a 5.4 × 3.6 cm right para-aortic/infrahepatic mass – a 1.1 cm para-aortic lymph node was also noticed. She was commenced on metyrapone and mitotane and referred for debulking surgery. The patient was aware that the surgery would not be curative but would make her Cushing's easier to manage and improve her response to subsequent chemotherapy. She underwent debulking surgery for intra-abdominal metastasis. Part of her right kidney, lymph nodes and appendix were removed. She had hypoadrenalism following debulking surgery. Her mitotane and metyrapone was stopped and she was commenced on high-dose steroid replacement which was gradually tapered off. The patient responded very well to the surgery and her general health improved greatly. Six months after surgery a routine computed tomography scan of the abdomen showed a 2.4 × 2 cm hepatic metastasis. She was referred for surgical ablation but died of a massive cerebral haemorrhage.