Multiple drugs

Abstract

Adrenal haematoma and adrenal decompensations: case report An approximately 59-year-old man developed bilateral adrenal haematoma during treatment with bevacizumab, and adrenal decompensations during treatment with oxaliplatin, raltitrexed and tipiracil/trifluridine for metastatic colorectal cancer (mCRC) [not all routes stated; time to reaction onset not stated]. The man was diagnosed with stage IV metastatic colorectal cancer in 2016 at the age of 58 years. He had a significant history of hypertension, dyslipidaemia and appendectomy. He was active smoker (28 pack/year). He had received multiple chemotherapies until March 2017. However, after 4 months, he developed polymetastatic relapse. Therefore, from 27 August 2017, he started receiving palliative chemotherapy with bevacizumab 7.5 mg/kg along with IV raltitrexed and oxaliplatin concomitantly. After 4 cycles, at follow-up, a CT scan was performed which showed stable disease. On 7 November 2017, he presented to the emergency department with a 12 hours history of acute diffuse abdominal pain, nausea, no passing stool and gas. Subsequent physical examination showed diffuse abdominal tenderness. Laboratory examination revealed hypokalaemia (2.6 mmol/L), hypophosphataemia (0.56 mmol/L), slightly elevated lactate dehydrogenase and C-reactive protein level. Thereafter, a abdominal CT scan was performed which showed appearance of bilateral adrenal enlargement, indicating acute adrenal haematoma.He subsequently started receiving opioid and hydroelectrolytic supplementation. On 8 November 2017, he was admitted. Subsequent blood test showed decreased cortisol level (13 nmol/L) and highly elevated adrenocorticotropic hormone (ACTH) level, suggesting an adrenal insufficiency. Hence, ACTH stimulation test was performed which showed <11 nmol/L of cortisol at 30 min and 60 min. Based on this test, primary adrenal insufficiency was confirmed. After 24 hours of hospitalisation, he developed fever, hypotension and tachycardia, indicating septic shock. Hence, from 9 November 2017, he started receiving treatment with unspecified large spectrum antibiotics and IV fluids. His differential diagnosis included adrenal metastases, addison disease, adrenal primary tumour and other autoimmune diseases. After ruling out other differential diagnosis, it was concluded that, he had developed bevacizumab induced adrenal haematoma which complicated by adrenal insufficiency. The man subsequently started receiving treatment with hydrocortisone and fludrocortisone. Additionally, bevacizumab therapy was discontinued, but his raltitrexed and oxaliplatin was continued. Subsequent blood tests showed elevated procalcitonin and Creactive protein levels (193 mg/L), leukocytosis with neutrophilia and high creatinine level. Additionally, he was found to have low level of haemoglobin (16 g/L) and haematocrit (4.3%). His symptoms improved and no infection was found in blood and urine cultures. However, antibiotics and hydrocortisone supplementation were continued. On day 7, an adrenal MRI scan was performed which showed bilateral enlarged adrenal glands, hypointense signal intensity in T1 and T2 weighted images without contrast enhancing, in favour of a chronic bleeding. On 14 November 2017, he was transferred to the endocrinology Unit. Subsequent blood test showed low renin, aldosterone and ACTH levels. He received raltitrexed and oxaliplatin therapy till 6 December 2017. He received irinotecan monotherapy from 6 December 2017 to 6 February 2018. However, liver metastasis progression was observed. Hence, from 6 February 2018, he started receiving hepatic arterial infusion oxaliplatin 130 mg/m2 and IV raltitrexed 3 mg/m2 every 3 weeks following solitary pulmonary metastasis radiofrequency ablation. Follow-up CT scan showed peritoneal progression of disease. He received oxaliplatin and raltitrexed therapy till 5 October 2018. Due to disease progression, tipiracil/trifluridine [trifluridine /tipiracil] was initiated on 5 October 2018. During chemotherapy, he was hospitalised few times for reversible adrenal decompensation. It was concluded that, this chemotherapy was responsible for stress condition of adrenal decompensations. Therefore, hydrocortisone dose was doubled during the first week of each chemotherapy cycle with good tolerance and no need for further hospitalisation. At follow-up, a CT scan was performed which showed a partial regression of adrenal haematomas. After 8 months from diagnosis, his ACTH level was in normal range (45.8 ng/L). Eventually, he died due to progression of colorectal cancer metastatic in November 2018.