Massive haemorrhagic adrenal metastases leading to sudden death: a case report

Abstract

Although adrenal glands are a common site of metastatic cancer, clinically significant haemorrhage into these is very uncommon with only a few cases having been previously published in the English literature. Here, a case of massive adrenal haemorrhage secondary to metastasis of lung cancer that led to the death of the patient is reported. To the best of our knowledge, such an acute death, without any prior medical attention or intervention, as a consequence of haemorrhagic adrenal metastasis has not been described before and is an important consideration in a person with lung cancer who dies unexpectedly.

BACKGROUND

Although adrenal metastases are fairly common in patients with lung cancer, symptomatic cases of haemorrhage into these are unusual. In particular, sudden unexpected death due to these has not been previously described to date. It is important for treating doctors and pathologists to know about this complication.

CASE PRESENTATION

A 68-year-old man initially presented to his doctor with a 6-week history of cough with haemoptysis. Following radiological investigations, bronchoscopy examination and biopsy, he was diagnosed to have a non-small cell carcinoma of the lung. He subsequently underwent a left upper lobectomy, which revealed a pleomorphic carcinoma, and he was TNM staged as T2N1M0 at the time, with no clinical or radiological evidence of metastatic carcinoma. The patient was very anxious about chemotherapy and its side effects and was therefore given radiotherapy for a period of 29 days. At the end of this period, all the biochemical and haematological investigations were normal. In particular, there were no abnormalities that would point towards any blood clotting problems or evidence of adrenal insufficiency. Thereafter he remained reasonably well and asymptomatic for the next 5 weeks. During this period he was living alone at home and had not complained about any alarming signs or symptoms to anyone. One day, however, he was unexpectedly found dead at his residence. He underwent an autopsy to establish the underlying cause of death.

On autopsy, the left lower lobe of the lung and the liver each showed a single metastatic deposit of tumour measuring 3 cm and 2 cm in maximum dimension, respectively. The right adrenal gland was markedly enlarged, weighing 1147 g and measuring 20 cm at its maximum dimension. On sectioning, it was completely replaced by necrotic tumour and showed extensive areas of haemorrhage associated with blood clots. The left adrenal gland was also enlarged, weighing 134 g and measuring 6 cm in maximum dimension. The cut surface showed appearances similar to the right adrenal gland. There was no bleeding into the peritoneal cavity or retroperitoneal space. The other organ systems were essentially within normal limits except for mild coronary artery atherosclerosis.

Histological sections from the adrenal glands showed necrotic metastatic deposits of pleomorphic carcinoma, the morphological appearances and immunohistochemical features being identical to those of the primary tumour. In addition, extensive areas of haemorrhage were confirmed microscopically (fig 1).

Figure 1.

Metastatic pleomorphic carcinoma in the adrenal. Tumour cells are separated by areas of haemorrhage and a small focus of necrosis (haematoxylin and eosin (H&E), magnification 200×).

DISCUSSION

The adrenal glands constitute a common site for metastatic deposits of malignant tumours. Lung carcinomas are one of the most common sources of primary tumour. Conversely, up to 40% of patients with non-small cell lung cancer develop unilateral or bilateral adrenal metastases as the carcinoma progresses.^1,2 Most of these adrenal metastases are asymptomatic. In a study of 464 patients with metastatic tumours of the adrenal gland spanning a 30-year period, only 4% of the adrenal lesions were symptomatic. The spectrum of clinical presentations secondary to adrenal metastases which have been described in the literature include pain in the lower chest, back or abdomen,³ a palpable abdominal mass¹ or symptoms and signs related to either adrenal insufficiency (Addison disease)^1,4–7 or adrenal haemorrhage.^1,2,8–12

Despite the high incidence of adrenal metastases in disseminated malignant tumours, primary adrenal insufficiency caused by this is relatively rare. This low incidence may be attributed to the fact that over 90% of the adrenal glands must be destroyed before there is functional cortical loss. In addition, the signs and symptoms of Addison disease may be masked or overlooked in patients with advanced malignancies.¹ However, it is important to identify adrenal insufficiency caused by adrenal metastases as replacement hormone therapy may dramatically ameliorate the symptoms and improve the quality of life of these patients.^4,6 The various clinical manifestations that may point towards adrenal insufficiency include unexplained nausea, vomiting, weight loss and weakness, postural hypotension and skin and mucosal hyperpigmentation.⁵ Blood tests often demonstrate hypoglycaemia, hyponatraemia and hyperkalaemia. Adrenal insufficiency can be confirmed in these patients by measuring serum cortisol levels after standardised adrenocorticotropic hormone (ACTH) stimulation (should be below 560 nmol/litre for diagnosis) or by an elevated plasma ACTH:cortisol ratio.⁷

Although primary adrenal neoplasms have often been reported to cause adrenal haemorrhage, clinically significant adrenal haemorrhage by metastasis is exceedingly rare. The clinical manifestations depend on whether one or both adrenal glands are involved, if their function is partially or completely destroyed, and the extent of protrusion/containment of the haemorrhage within the adrenal gland.¹³ The symptoms which have been reported as a result of adrenal haemorrhage are usually non-specific and include sudden pain in the abdomen, flank or back, nausea and vomiting, confusion, weakness and high fever. Thus in patients with lung cancer with sudden abdominal or back pain in association with hypotension and anaemia, adrenal haemorrhage secondary to metastatic carcinoma is an important consideration in the differential diagnosis. CT scan imaging helps in the diagnosis of the condition, which needs to be treated urgently by adrenalectomy.² Proper oncological resection may not, however, always be feasible, particularly if the adrenal gland with tumour is surrounded by a large retroperitoneal haematoma. In such cases, a possible treatment strategy is transarterial embolisation to control the active bleeding, followed by surgical resection at a later date once haemostasis has been completely achieved.^13,14

Sudden death due to massive haemorrhage in adrenals involved by metastatic cancer without any prior medical attention or intervention, to the best of our knowledge, has not been reported before. Our patient was found dead in his house and for 5 weeks before his death had not undergone any investigations or seen a doctor. It is likely that he did have some symptoms before he died. However, he must have gone on to develop hypovolaemic shock, which ultimately led to his death.

In conclusion, although symptomatic adrenal metastases are rare, they may present with clinical features secondary to adrenal insufficiency or haemorrhage in the adrenal gland. The possibility of intratumoural haemorrhage in the adrenal glands needs to be considered as a cause of death in a patient with lung cancer who dies suddenly and unexpectedly.

LEARNING POINTS

• Symptomatic cases of adrenal metastases with haemorrhage are rare.

• Sudden unexpected death due to massive haemorrhagic adrenal metastases is extremely unusual.

• Other manifestations of adrenal metastases include adrenal insufficiency, abdominal pain and a palpable mass.