An uncanny case of paraneoplastic calcitriol mediated hypercalcaemia.

Summary: A 77-year-old female patient with a history of treated breast cancer and a recently diagnosed laryngeal cancer presented with severe hypercalcaemia associated with suppressed parathyroid hormone (PTH) levels. Her initial investigations included 25-hydroxy vitamin D levels, short synacthen test, bone scan, myeloma screen and thyroid function tests which were within normality. A computerised tomography (CT) scan showed some right lung apical fibrotic changes. Her PTH-related peptide (PTHrP) was normal and sarcoidosis was also excluded. Her previous and current malignancies were thought to be unlikely behind her hypercalcaemia. Her 1,25-dihydroxy vitamin D (calcitriol) levels were found to be elevated. Her hypercalcaemia was initially managed with intravenous fluids and intermittent bisphosphonates infusions which would transiently reduce her calcium levels. Steroid treatment was initiated which improved her hypercalcaemia; however, the calcium levels rebounded on tapering the steroids down, a pre-requisite prior to a positron emission computerised tomography (PET-CT) scan to determine the source of the excess calcitriol production. This was cancelled following an emergency admission with marked hypercalcaemia and acute renal and liver injury. A contemporary CT scan showed a right apical lung mass with hepatic lesions suggestive of a disseminated lung primary. The histology obtained from a liver biopsy was compatible with metastatic small-cell lung carcinoma. Unfortunately, her clinical condition deteriorated further and she did not survive. To the best of our knowledge, this is the first report in the literature describing calcitriol-mediated hypercalcaemia due to a small-cell lung cancer. Learning points: Paraneoplastic hypercalcaemia may manifest even without overt detection of the primary cancer. The workup for paraneoplastic hypercalcaemia should be meticulous. Both bisphosphonates and steroids are useful in the initial management of calcitriol-mediated hypercalcaemia, but the definitive management is the treatment of the cause.

Refractory paraneoplastic hypercalcaemia responding to cinacalcet.

A woman in her late 70s presented with an increased frequency of micturition, suprapubic pain and weight loss. She was found to be having advanced cancer of the urinary bladder, coupled with bilateral hydronephrosis.Whilst undergoing surgical intervention for the latter, she was incidentally found to be having hypercalcaemia. This was found to be paraneoplastic in nature, possibly due to elevated parathyroid hormone related peptide with no evidence of bone metastasis. The histology of the resected tumour revealed squamous and sarcomatoid differentiation. Her hypercalcaemia initially responded to intravenous fluids, and later on zolendronate,but the problem recurred again, with the response to a repeat dose of zolendronate and even denosumab being unsatisfactory. As a last resort cinacalcet was started, and although there was a good response to it, our patient sadly died a few weeks later.We believe our case to be the first case of hypercalcaemia associated with isolated bladder cancer which showed a successful response to cinacalcet.

Idiopathic CD4 Lymphocytopenia Presenting as Cryptococcal Meningitis.

A 54-year-old male presented to our center with a 3-month history of headache, giddiness, and blurring of vision. Cerebrospinal fluid examination revealed him to be having cryptococcal meningitis. He was worked up for probable causes of immunosuppression including HIV and other infections and had an autoimmune profile as well as a bone marrow examination, none of which revealed any abnormality. Lymphocyte flow cytometry revealed low counts of CD4 T lymphocytes, likely secondary to idiopathic CD4 lymphocytopenia. He was treated for cryptococcal meningitis. Due to marked immunosuppression, the disease progressed rapidly with deterioration in neurological and hemodynamic status, leading to his demise.

New Onset Refractory Status Epilepticus as a Manifestation of Tuberculosis of the Central Nervous System.

A 28-year-old male presented to us with new onset refractory status epilepticus. Prior to his seizures, he had a history of fever, headache and blurring of vision, for which he was admitted elsewhere. No cause was found; he was treated symptomatically and was discharged as his symptoms had abated. Post-discharge, he started having multiple seizures. Neuro-imaging suggested encephalitis. He progressed to status epilepticus and was referred to our center. We intensified the anti-epileptic medications but owing to no response, he had to be put under coma with thiopental, yet the seizures persisted. Workup for the etiology of his seizures was negative except for CSF TB-PCR (Gene Xpert) being positive and hence anti-tuberculous therapy was initiated. By this time, he developed rhabdomyolysis, and thereafter renal failure with dyselectrolytemia, and thus there was a plan to initiate dialysis. But before this could be done, he succumbed to a cardiac arrest secondary to ventricular tachyarrhythmias. We believe this to be the first reported case of new onset refractory status epilepticus secondary to tuberculosis of the central nervous system.

Dysautonomia and hyponatraemia as harbingers of Guillain-Barre syndrome.

A 56-year-old woman with a medical history of hypertension presented to our hospital with back pain, abdominal pain, vomiting and elevated blood pressure. The laboratory parameters including evaluation for secondary hypertension were within normal ranges at the time of presentation. During her hospitalisation, fluctuations in her blood pressure and pulse were observed which were attributed to autonomic disturbances, the cause of which was unknown. On the seventh day after presentation to the hospital, the patient developed focal seizures and slurred speech which was believed to be secondary to hyponatraemia detected at that time. Hyponatraemia improved with hypertonic saline and she experienced no further seizures. On the eighth day of her admission, she developed acute flaccid paralysis of all her limbs and respiratory distress. We concluded this to be secondary to Guillain-Barre syndrome (GBS). She responded to plasmapheresis.The presence of dysautonomia and hyponatraemia before the onset of paralysis makes this a rare presentation of GBS.

Primary hepatic hemangioendothelioma in a patient with Budd-Chiari syndrome.

A 36-year-old woman was diagnosed with compensated cirrhosis of liver secondary to Budd-Chiari syndrome (BCS) and had undergone stenting of a thrombosed left hepatic vein. Eight months later, she presented with jaundice and right upper quadrant pain. CT revealed multiple focal lesions in the liver, which on biopsy proved to be hepatic hemangioendothelioma (HHE). Her liver disease and ascites progressively increased. Four months later, magnetic resonance cholangiopancreatography showed an advanced stage of HHE with infiltration of the common bile duct and vascular invasion with a blocked stent, with metastasis to the spleen and dorsolumbar vertebrae. We believe this is the first reported case of an HHE developing in the background of BCS.