John Ayuk

The diagnosis and management of inpatient hyponatraemia and SIADH

Hyponatraemia is a very common medical condition that is associated with multiple poor clinical outcomes and is often managed suboptimally because of inadequate assessment and investigation. Previously published guidelines for its management are often complex and impractical to follow in a hospital environment, where patients may present to divergent specialists, as well as to generalists.

MANAGEMENT OF ENDOCRINE DISEASE: Acromegaly and cancer: an old debate revisited

Based on experimental and animal models, epidemiological data from non-acromegaly populations, and longitudinal and cross-sectional cohorts of patients with acromegaly, a potential association between acromegaly and cancer has long been hypothesized, in particular colorectal cancer, and, to a lesser extent, breast, thyroid and prostate cancers. The exact mechanisms underlying this potential association have not been fully elucidated. Results from studies examining cancer incidence and mortality in acromegaly have been inconsistent, with some demonstrating increased risk, whereas others show no increase. This article reviews the existing data relating to cancer risk and mortality in acromegaly, exploring the limitations of study designs and the impact of changes in disease control and patient outcomes over time.

A randomised, open-label, parallel group phase 2 study of antisense oligonucleotide therapy in acromegaly

Objective ATL1103 is a second-generation antisense oligomer targeting the human growth hormone (GH) receptor. This phase 2 randomised, open-label, parallel-group study assessed the potential of ATL1103 as a treatment for acromegaly. Design Twenty-six patients with active acromegaly (IGF-I >130% upper limit of normal) were randomised to subcutaneous ATL1103 200 mg either once or twice weekly for 13 weeks and monitored for a further 8-week washout period. Methods The primary efficacy measures were change in IGF-I at week 14, compared to baseline and between cohorts. For secondary endpoints (IGFBP3, acid labile subunit (ALS), GH, growth hormone-binding protein (GHBP)), comparison was between baseline and week 14. Safety was assessed by reported adverse events. Results and conclusions Baseline median IGF-I was 447 and 649 ng/mL in the once- and twice-weekly groups respectively. Compared to baseline, at week 14, twice-weekly ATL1103 resulted in a median fall in IGF-I of 27.8% (P = 0.0002). Between cohort comparison at week 14 demonstrated the median fall in IGF-I to be 25.8% (P = 0.0012) greater with twice-weekly dosing. In the twice-weekly cohort, IGF-I was still declining at week 14, and remained lower at week 21 than at baseline by a median of 18.7% (P = 0.0005). Compared to baseline, by week 14, IGFBP3 and ALS had declined by a median of 8.9% (P = 0.027) and 16.7% (P = 0.017) with twice-weekly ATL1103; GH had increased by a median of 46% at week 14 (P = 0.001). IGFBP3, ALS and GH did not change with weekly ATL1103. GHBP fell by a median of 23.6% and 48.8% in the once- and twice-weekly cohorts (P = 0.027 and P = 0.005) respectively. ATL1103 was well tolerated, although 84.6% of patients experienced mild-to-moderate injection-site reactions. This study provides proof of concept that ATL1103 is able to significantly lower IGF-I in patients with acromegaly.

Lesson of the month 2: Blunt abdominal trauma: atypical presentation of phaeochromocytoma

A 26-year-old man presented following blunt abdominal trauma to a regional major trauma centre for emergency embolisation of a retroperitoneal bleed from a presumed renal laceration. Imaging had also revealed a large right suprarenal mass. Embolisation resulted in a hypertensive crisis raising the suspicion of a metabolically active adrenal tumour. The course was further complicated by the development of ischaemic bowel requiring emergency laparotomy. Intraoperatively he became haemodynamically unstable from an actively haemorrhaging lesion. Emergency laparotomy and adrenalectomy was performed as a life-saving procedure. Histology confirmed a phaeochromocytoma. The patient made a gradual recovery and was discharged home with no sequelae. Definitive management of phaeochromocytoma is surgical resection which requires prolonged preoperative optimisation with alpha receptor blockers to adequately control blood pressure and prevent hypertensive crises. Parenteral alpha receptor blockers, such as phentolamine, are optimal treatment for intraoperative hypertensive emergencies, yet they are currently not available in the UK.

When Occam's razor fails: hemipontine infarct on a background of previous surgery and radiotherapy for craniopharyngioma.

A 68-year-old man presented with a 5-day history of left-sided hemiparesis, dysphasia and abnormal gait. His medical history included type 2 diabetes mellitus, hypertension and previous craniopharyngioma, treated with complex surgical debulking and subsequent radiotherapy 13 years earlier. As a result, the patient developed panhypopituitarism (gonadotrophin deficiency, growth hormone deficiency, adrenocorticotropic deficiency, thyrotropin deficiency and diabetes insipidus) and remained under the care of the endocrine team. His treatment included replacement testosterone, growth hormone, hydrocortisone, levothyroxine, desmopressin and metformin for type 2 diabetes mellitus. Clinical examination revealed left-sided hemiplegia with upper-motor-neurone signs and global dysphasia. Blood profile was normal. Given his history, it was initially felt this presentation was linked to his previous intracranial disease. However, an urgent CT of the …

Response to 'How we define hyponatremia?'.

P. Grant, J. Ayuk, P.-M. Bouloux, M. Cohen, I. Cranston, R.D. Murray, A. Rees, N. Thatcher and A. Grossman Royal Sussex County Hospital, Brighton, UK, Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital, Birmingham, UK, Diabetes and Endocrinology, Royal Free London NHS Foundation Trust, London, UK, Diabetes and Endocrinology, Portsmouth Hospitals NHS Trust, Queen Alexandra Hospital, Hampshire, UK, Department of Diabetes and Endocrinology, Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds, UK, Department of Endocrinology and Diabetes, Cardiff University School of Medicine, Cardiff, UK, DepartmentofMedicalOncology,ChristieHospital,NHSTrustManchester,Manchester,UK, Departmentof Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK