Pituitary macroadenoma apoplexy as a rare complication of Bruton tyrosine kinase inhibitor in chronic lymphoid leukaemia.

BACKGROUND: Pituitary apoplexy is a neurosurgical emergency and is a known yet rare complication of pituitary macroadenoma. Patients typically present with visual field defects, headache and altered sensorium. There are multiple risk factors for this complication and a thorough drug history is essential to exclude iatrogenic causes of disease. We present an extremely rare case of newly diagnosed pituitary insufficiency unveiled by ibrutinib therapy (a Bruton tyrosine kinase inhibitor). Furthermore, after initial withdrawal of ibrutinib because of the erroneous diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH), its re-administration led to the development of classical pituitary apoplexy 4 months after treatment was restarted. CASE PRESENTATION: A male patient in his 60s with a background of chronic lymphocytic leukaemia (CLL) on ibrutinib and venetoclax presents with acute confusion and deranged electrolytes. He is found to be hyponatraemic and is diagnosed with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and treated with fluid restriction. He represents again 3 weeks later with hyponatraemia and further investigations reveal pituitary insufficiency and macroadenoma. He was restarted on ibrutinib and venetoclax at the time of discharge. Four months later, he presents with sudden retro-orbital headache associated with vomiting. Clinical findings include cranial nerve III, IV and XI palsy. Humphrey's visual field examination revealed a left visual field index (VFI) of only 1% while the right was 64% with temporal hemianopia. Both pupils were mid-dilated and poorly reactive to light. MRI pituitary with contrast showed features of pituitary apoplexy and optic nerve compression. He was urgently referred to the neurosurgical team and underwent an emergency trans-sphenoidal hypophysectomy with circumferential excision of the macroadenoma. Post-operative recovery was uneventful with marked improvement in vision bilaterally. The patient was restarted on ibrutinib and venetoclax 2 weeks post-operatively. Approximately 1 year post-treatment, he remains in radiological, clinical and biochemical remission from CLL and all medications have been withdrawn. CONCLUSIONS: This is a unique and rare case of pituitary macroadenoma apoplexy following the commencement of ibrutinib for CLL. Central nervous system haemorrhage is a rare side effect of ibrutinib due to its platelet dysfunction effects. A thorough assessment is required to assess the risks and benefits of using ibrutinib in patients with pituitary macroadenoma to avoid serious complications.

Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours.

Mutations in succinate dehydrogense-B (SDHB) and the von Hippel-Lindau (VHL) genes result in an increased risk of developing chromaffin tumours via a common aetiological pathway. The aim of the present retrospective study was to compare the clinical phenotypes of disease in subjects developing chromaffin tumours as a result of SDHB mutations or VHL disease. Thirty-one subjects with chromaffin tumours were assessed; 16 subjects had SDHB gene mutations and 15 subjects had a diagnosis of VHL. VHL-related tumours were predominantly adrenal phaeochromocytomas (22/26; 84.6%), while SDHB-related tumours were predominantly extra-adrenal paragangliomas (19/25; 76%). Median age at onset of the first chromaffin tumour was similar in the two cohorts. Tumour size was significantly larger in the SDHB cohort in comparison with the VHL cohort (P=0.002). Multifocal disease was present in 9/15 (60%) of the VHL cohort (bilateral phaeochromocytomas) and only 3/16 (19%) of the SDHB cohort, while metastatic disease was found in 5/16 (31%) of the SDHB cohort but not in the VHL cohort to date. The frequency of symptoms, hypertension and the magnitude of catecholamine secretion appeared to be greater in the SDHB cohort. Renal cell carcinomas were a feature in 5/15 (33%) of the VHL cohort and 1/16 (6%) of the SDHB cohort. These data indicate that SDHB-related tumours are predominantly extra-adrenal in location and associated with higher catecholamine secretion and more malignant disease, in subjects who appear more symptomatic. VHL-related tumours tend to be adrenal phaeochromocytomas, frequently bilateral and associated with a milder phenotype.

Clinical manifestations of familial paraganglioma and phaeochromocytomas in succinate dehydrogenase B (SDH-B) gene mutation carriers.

OBJECTIVE: Phaeochromocytomas and paragangliomas are familial in up to 25% of cases and can result from succinate dehydrogenase (SDH) gene mutations. The aim of this study was to describe the clinical manifestations of subjects with SDH-B gene mutations. DESIGN: Retrospective case-series. PATIENTS: Thirty-two subjects with SDH-B gene mutations followed up between 1975 and 2007. Mean follow-up of 5.8 years (SD 7.4, range 0-31). Patients seen at St Bartholomew's Hospital, London and other UK centres. MEASUREMENTS: Features of clinical presentation, genetic mutations, tumour location, catecholamine secretion, clinical course and management. RESULTS: Sixteen of 32 subjects (50%) were affected by disease. Two previously undescribed mutations in the SDH-B gene were noted. A family history of disease was apparent in only 18% of index subjects. Mean age at diagnosis was 34 years (SD 15.4, range 10-62). 50% of affected subjects had disease by the age of 26 years. 69% (11 of 16) were hypertensive and 80% (12 of 15) had elevated secretions of catecholamines/metabolites. 24% (6 of 25) of tumours were located in the adrenal and 76% (19 of 25) were extra-adrenal. 19% (3 of 16) had multifocal disease. Metastatic paragangliomas developed in 31% (5 of 16). One subject developed a metastatic type II papillary renal cell carcinoma. The cohort malignancy rate was 19% (6 of 32). Macrovascular disease was noted in two subjects without hypertension. CONCLUSION: SDH-B mutation carriers develop disease early and predominantly in extra-adrenal locations. Disease penetrance is incomplete. Metastatic disease is prominent but levels are less than previously reported. Clinical manifestations may include papillary renal cell carcinoma and macrovascular disease.

Unplanned readmission to hospital: a comparison of the views of general practitioners and hospital staff.

OBJECTIVE: to compare the views of general practitioners and hospital staff on the reasons for unplanned readmission of older people. METHODS: we studied 124 patients aged 65 years or over who were readmitted within 28 days of discharge. We determined the views of hospital staff and the patient's general practitioner on the reasons for readmission and compared them using McNemar's test. RESULTS: the crude readmission rate was 13.2%. The commonest agreed reason for readmission was a relapse or complication of the initial illness. Opinions differed most significantly when the reason was poor health or inadequate preparation on discharge. CONCLUSION: hospital discharge policies should take into account general practitioners' views on the causes of unplanned readmission.

Are we using percutaneous endoscopic gastrostomy appropriately in the elderly?

Many percutaneous endoscopic gastrostomy patients are very elderly and frail. Outcomes after percutaneous endoscopic gastrostomy have been disappointing in some instances: about a fifth of patients are dead within 30 days of the procedure and those that survive often have a severely impaired functional status. Many healthy elderly persons would not wish for tube feeding especially in the context of advanced dementia. Despite this the number of patients receiving percutaneous endoscopic gastrostomy continues to increase. The case mix, outcomes and ethical issues of percutaneous endoscopic gastrostomy feeding are reviewed. Guidance on selection of appropriate patients is given.