Dual pathology leading to hypercalcaemia: the issue with confirmation bias

HH Aung, N Lin, A Solomon, S Zac-Varghese, ENHIDE, East and North Herts NHS Trust

Abstract: Mr AM, a 69 year old Caucasian gentleman, presented with chronic fatigue, right knee pain and thigh pain. He was found to have hypercalcaemia (3.55 mmol/L) and was admitted in September 2020. He had a past medical history of hypertension and congenital bilateral retinal detachment causing total blindness in his right eye and 50 % vision loss in his left eye. He had a significant family history of acromegaly in his brother, treated with trans-sphenoidal surgery, and metastatic breast cancer in his mother. Initial investigations included PTH, elevated at 16.22 pmol/L, a myeloma screen which was negative, vitamin D, normal at 96.2 nmol/L and normal TFT. He was given a provisional diagnosis of primary hyperparathyroidism, treated with intravenous fluids, and discharged after two days with a calcium level 2.79 mmol/L. There was a plan for further biochemical testing, parathyroid imaging and outpatient endocrine follow up.

10 days later, Mr AM represented with backpain. He had noticed the development of a painless, hard, lump in the right lower back. The mass was visible on his chest x-ray, and the radiologist advised further characterisation by ultrasound. On this occasion, his calcium was elevated at 3.91 mmol/L. He was admitted to the endocrine ward and had further investigations. A repeat myeloma screen was negative, the urine calcium creatinine clearance ratio was 0.0348, serum ACE was < 10 U/L. Imaging was requested including an ultrasound and sestamibi parathyroid, USS renal and a DEXA. He had the sestamibi during the admission which showed a focus of retained tracer on the left upper lobe consistent with a parathyroid adenoma. He was treated with intravenous fluids and cinacalcet and discharged home with a plan for the USS chest and parathyroid as an outpatient and endocrine follow up.

He was readmitted after a further 10 days with nausea and vomiting and hypercalcaemia. On this occasion, a history of significant weight loss, 9 kg within 6-months, was noted by the admitting physician and a CT chest, abdomen and pelvis was organised. This revealed multiple necrotic liver lesions, multiple lytic axial lesions, deposit in T9 vertebra, destruction of L2 vertebra and right femoral lesser trochanteric destruction. A tissue biopsy noted neuroendocrine malignancy morphology with the presence of high positivity of synaptophysin and CD 56. Chromogranin, CK20, CD 45 and melanin A were negative. Further questioning revealed that he sometimes experienced episodes of palpitation, sweating and flushing. He also had an episode of loss of consciousness three years previously. He denied headache and diarrhoea. Urine metanephrines were sent (result awaited). Genetic testing is also awaited. He was referred to the Royal Free Hospital NET department and the MDT outcome was for platinum-based chemotherapy.

Discussion: This case report highlights the issues with confirmation bias. The diagnosis of primary hyperparathyroidism was presumed on the first visit and all subsequent investigations were in line with this. As a result, the significant history of weight loss, palpitation, flushing was not noted or investigated thoroughly. The hypercalcaemia in this case is possibly due to dual pathology, primary hyperparathyroidism and the clinically dominant NET with bone metastases.