Search

Chest pain with elevated serum troponin is a common clinical presentation and is normally managed as suspected myocardial infarction or acute coronary syndrome (ACS). We report a 49 year old man who presented with central chest pain sweating and breathlessness. He had a significantly elevated serum troponin I level and a subsequent angiogram showed near normal coronary arteries. He was subsequently investigated for fever and found to have a 3cm right sided adrenal mass consistent with a pheochromocytoma. After confirmation and appropriate blockade laparoscopic adrenalectomy was performed. Pheochromocytoma may present as a mimic of acute coronary syndrome but this is often unrecognized and leaves the patient at risk of future pheo crisis events which may be fatal.

Editor – Faloon and colleagues describe a 26-year-old man who developed phaeochromocytoma crisis following blunt abdominal trauma and attempted embolisation.[1][1] The patient had a phase of sustained hypotension giving rise to multi-organ dysfunction. Ischaemia of the colon was treated with

Introduction: Multi-modal therapy for adrenocortical carcinoma (ACC) includes surgery, therapy with the adrenolytic agent mitotane and systemic chemotherapy. Achievement of therapeutic mitotane concentrations (≥14 mg/l) has been related to improved outcomes. Aim: To evaluate the effectiveness of a defined* high dose protocol mitotane therapy in patients with advanced ACC (stages III and IV). Methods: Review of patients presenting to KCH with stage III or IV ACC and the mitotane concentration achieved through the Lysosafe monitoring service. Results: N=57 patients were referred and first diagnosed with ACC (2008-17) of whom 44 patients had stage III or IV disease at diagnosis and were managed actively with surgery and/or mitotane therapy. 40/44 patients underwent surgical resection of the primary tumour;11/22 patients with stage IV disease subsequently received systemic chemotherapy [10 patients received a combination of etoposide, doxorubicin and cisplatin (EDP) and 1 patient received a combination of carboplatin and etoposide]. 38/44 patients were initiated on mitotane therapy. The median overall survival of patients with stage IV disease was 25.3 months. The median survival for stage III has not been reached. An additional 9 patients had prior management, including surgery, elsewhere and were referred for mitotane initiation. A total of 47 patients were therefore included in the mitotane pharmacokinetic analysis. Six patients were excluded: 3 patients died shortly after mitotane initiation, 1 patient withdrew due to a severe reaction and 2 patients had not completed 12 weeks therapy at the time of submission. Of the remaining 41 patients, 33 commenced the ‘high dose’ protocol and the remainder the ‘low dose’ protocol. For patients on the high dose protocol, 25/33 (76%) reached a mitotane concentration ≥14 mg/l within 12 weeks of initiation of therapy, compared to 3 patients from the low dose protocol group (P=0.084). In the high dose protocol group, 21 patients (84%) maintained therapeutic drug concentrations in ≥50% of the subsequent follow-up samples and 12 patients (48%) maintained therapeutic drug concentrations in ≥75% of subsequent samples. Conclusion: The use of high dose protocol mitotane therapy is a successful strategy to achieve and maintain therapeutic drug concentrations when treating patients with advanced ACC (stages III and IV). In combination with an assertive surgical approach and optimal chemotherapy, this has resulted in outcomes that compare favourably (median OS 25.5 months in stage IV disease) with previously published series which describe a median OS

Destructive communication is a problem within the NHS; however previous research has focused on bullying. Rude, dismissive and aggressive (RDA) communication between doctors is a more widespread problem and underinvestigated. We conducted a mixed method study combining a survey and focus groups to describe the extent of RDA communication between doctors, its context and subsequent impact. In total, 606 doctors were surveyed across three teaching hospitals in England. Two structured focus groups were held with doctors at one teaching hospital. 31% of doctors described being subject to RDA communication multiple times per week or more often, with junior and registrar doctors affected twice as often as consultants. Rudeness was more commonly experienced from specific specialties: radiology, general surgery, neurosurgery and cardiology. 40% of respondents described that RDA moderately or severely affected their working day. The context for RDA communication was described in five themes: workload, lack of support, patient safety, hierarchy and culture. Impact of RDA communication was described as personal, including emotional distress and substance abuse, and professional, including demotivation. RDA communication between doctors is a widespread and damaging behaviour, occurring in contexts common in healthcare. Recognition of the impact on doctors and potentially patients is key to change.

Summary We describe severe hypokalaemia and hypertension due to a mineralocorticoid effect in a patient with myelodysplastic syndrome taking posaconazole as antifungal prophylaxis. Two distinct mechanisms due to posaconazole are identified: inhibition of 11β hydroxylase leading to the accumulation of the mineralocorticoid hormone 11-deoxycorticosterone (DOC) and secondly, inhibition of 11β hydroxysteroid dehydrogenase type 2 (11βHSD2), as demonstrated by an elevated serum cortisol-to-cortisone ratio. The effects were ameliorated by spironolactone. We also suggest that posaconazole may cause cortisol insufficiency. Patients taking posaconazole should therefore be monitored for hypokalaemia, hypertension and symptoms of hypocortisolaemia, at the onset of treatment and on a monthly basis. Treatment with mineralocorticoid antagonists (spironolactone or eplerenone), supplementation of glucocorticoids (e.g. hydrocortisone) or dose reduction or cessation of posaconazole should all be considered as management strategies. Learning points: Combined hypertension and hypokalaemia are suggestive of mineralocorticoid excess; further investigation is appropriate. If serum aldosterone is suppressed, then further investigation to assess for an alternative mineralocorticoid is appropriate, potentially using urine steroid profiling and/or serum steroid panelling. Posaconazole can cause both hypokalaemia and hypertension, and we propose that this is due to two mechanisms – both 11β hydroxylase inhibition and 11β HSD2 inhibition. Posaconazole treatment may lead to cortisol insufficiency, which may require treatment; however, in this clinical case, the effect was mild. First-line treatment of this presentation would likely be use of a mineralocorticoid antagonist. Patients taking posaconazole should be monitored for hypertension and hypokalaemia on initiation and monthly thereafter.

Editor – The Royal College of Physicians (RCP) has produced a report on inpatient referrals from generalist to specialist teams describing the presentations and conditions specialists feel ought to be referred, and conversely those which do not require this.[1][1] Inpatient referral is a neglected

Phaeochromocytoma [corrected] crisis is an endocrine emergency associated with significant mortality. There is little published guidance on the management of phaeochromocytoma [corrected] crisis. This clinical practice update summarizes the relevant published literature, including a detailed review of cases published in the past 5 years, and a proposed classification system. We review the recommended management of phaeochromocytoma [corrected] crisis including the use of alpha-blockade, which is strongly associated with survival of a crisis. Mechanical circulatory supportive therapy (including intra-aortic balloon pump or extra-corporeal membrane oxygenation) is strongly recommended for patients with sustained hypotension. Surgical intervention should be deferred until medical stabilization is achieved.

Insulin overdose can cause harm due to hypoglycaemia, effects on electrolytes and acute hepatic injury. The established long-acting insulin analogue preparations (detemir and glargine) can present specific management problems because, in overdose, their effects are extremely prolonged, often lasting 48-96 hours. The primary treatment is continuous intravenous 10% or 20% glucose infusion with frequent capillary blood glucose monitoring. Surgical excision of the insulin injection site has been used successfully, even days after the overdose occurred. Once the effects of overdose have receded, diabetes treatment must be restarted with care, especially in patients with type 1 diabetes. Monitoring serum insulin concentration has been successfully used to predict when the effects of the overdose will cease.

Hypophysitis is a rare condition characterised by inflammation of the pituitary gland, usually resulting in hypopituitarism and pituitary enlargement. Pituitary inflammation can occur as a primary hypophysitis (most commonly lymphocytic, granulomatous or xanthomatous disease) or as secondary hypophysitis (as a result of systemic diseases, immunotherapy or alternative sella-based pathologies). Hypophysitis can be classified using anatomical, histopathological and aetiological criteria. Non-invasive diagnosis of hypophysitis remains elusive, and the use of currently available serum anti-pituitary antibodies are limited by low sensitivity and specificity. Newer serum markers such as anti-rabphilin 3A are yet to show consistent diagnostic value and are not yet commercially available. Traditionally considered a very rare condition, the recent recognition of IgG4-related disease and hypophysitis as a consequence of use of immune modulatory therapy has resulted in increased understanding of the pathophysiology of hypophysitis. Modern imaging techniques, histological classification and immune profiling are improving the accuracy of the diagnosis of the patient with hypophysitis. The objective of this review is to bring readers up-to-date with current understanding of conditions presenting as hypophysitis, focussing on recent advances and areas for future development. We describe the presenting features, investigation and diagnostic approach of the patient with likely hypophysitis, including existing conventional techniques and those in the research/development arena. Hypophysitis usually results in acute and persistent pituitary hormone deficiency requiring long-term replacement. Management of hypophysitis includes control of the inflammatory pituitary mass using a variety of treatment strategies including surgery and medical therapy. Glucocorticoids remain the mainstay of medical treatment but other immunosuppressive agents (e.g. azathioprine, rituximab) show benefit in some cases, but there is a need for controlled studies to inform practice.

Myocarditis is inflammation of the cardiac muscle. The symptoms, signs and basic investigation findings can mimic that of myocardial infarction. The most common cause is infection (most commonly viral). Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive diagnostic test for potential acute myocarditis as it allows assessment of myocardial oedema and scar. A man aged 25 years was admitted with chest pain, dizziness, headache, palpitations and sweating. His troponin was mildly positive. A CMR was performed which showed mild myocarditis and a right suprarenal mass which was confirmed to be a phaeochromocytoma based on biochemistry and a dedicated imaging workup. Phaeochromocytoma can lead to cardiac involvement in the form of left ventricular dysfunction, or catecholamine-induced myocarditis.

Background Referrals are an important and frequent part of a junior doctor’s work. Difficulty with making successful referrals is also very common. Despite this, training in referral skills is not routinely carried out in medical schools. Results We designed and delivered a 1-h interactive lecture to final year medical students to teach referral skills. The lecture was delivered on six occasions to up to 70 students at each session. 191 students attended and provided evaluation. 68 % of students had no previous training in referral skills and 99 % felt that referral skills should be included in the undergraduate curriculum. 90 % reported that the lecture had improved their understanding of referral techniques and 83 and 80 % felt that the lecture had improved their ability and confidence, respectively. Conclusions Referral skills can be successfully taught in a large group lecture setting. We recommend that the teaching of referral skills is incorporated into all medical schools’ curricula.

Summary Therapeutic shrinkage of prolactinomas with dopamine agonists achieves clinical benefit but can expose fistulae that have arisen as a result of bony erosion of the sella floor and anterior skull base by the invasive tumour, resulting in the potential development of cerebrospinal fluid (CSF) rhinorrhoea, meningitis, and rarely pneumocephalus. Onset of symptoms is typically within 4 months of commencing therapy. The management is typically surgical repair via an endoscopic transnasal transsphenoidal approach. A 23-year-old man presented to the Emergency Department with acute left limb weakness and intermittent headaches. Visual fields were full to confrontation. Immediate computed tomography and subsequent magnetic resonance imaging (MRI), demonstrated a 5 cm lobular/cystic mass invading the right cavernous sinus, displacing and compressing the midbrain, with destruction of the bony sella. He was referred to the regional pituitary multidisciplinary team (MDT). Serum prolactin was 159 455 mIU/l (7514.37 ng/ml) (normal ranges 100–410 mIU/l (4.72–19.34 ng/ml)). Cabergoline was commenced causing dramatic reduction in tumour size and resolution of neurological symptoms. Further dose titrations were required as the prolactin level plateaued and significant residual tumour remained. After 13 months of treatment, he developed continuous daily rhinorrhea, and on presenting to his general practitioner was referred to an otolaryngologist. When next seen in the routine regional pituitary clinic six-months later he was admitted for urgent surgical repair. Histology confirmed a prolactinoma with a low proliferation index of 2% (Ki-67 antibody). In view of partial cabergoline resistance he completed a course of conventional radiotherapy. Nine months after treatment the serum prolactin had fallen to 621 mIU/l, and 12 months after an MRI showed reduced tumour volume. Learning points CSF rhinorrhoea occurred 13 months after the initiation of cabergoline, suggesting a need for vigilance throughout therapy. Dedicated bony imaging should be reviewed early in the patient pathway to assess the potential risk of CSF rhinorrhoea after initiation of dopamine agonist therapy. There was a significant delay before this complication was brought to the attention of the regional pituitary MDT, with associated risk whilst left untreated. This demonstrates a need for patients and healthcare professionals to be educated about early recognition and management of this complication to facilitate timely and appropriate referral to the MDT for specialist advice and management. We changed our nurse-led patient education programme as a result of this case. Having developed partial cabergoline resistance and CSF rhinorrhoea, an excellent therapeutic response was achieved with conventional radiotherapy after limited surgery.

Non-islet cell tumour induced hypoglycaemia (NICTH) is a rare but potentially reversible cause of recurrent low blood glucose.

A 45 year old woman was being regularly reviewed in primary and secondary care because of a five year history of type 2 diabetes that had required early insulin treatment; refractory hypertension; and subsequent chronic kidney disease. She had previously described other symptoms, including weight gain, bruising, flushes, and low mood, all of which had been attributed to obesity and menopause. She was not taking any glucocorticoids. After presenting to her local emergency department with a Colles’ fracture after a low impact fall, she was referred to the endocrinology department for suspected Cushing’s syndrome; subsequent investigation confirmed the diagnosis. Cushing’s syndrome describes the clinical consequences of chronic exposure to excess glucocorticoid irrespective of the underlying cause. Endogenous causes of Cushing’s syndrome are rare and include a cortisol-producing adrenal tumour, which may be benign or malignant; excess secretion of adrenocorticotrophic hormone (ACTH) from a pituitary tumour (Cushing’s disease); or an ectopic ACTH-producing tumour (ectopic Cushing’s syndrome). More commonly, prolonged administration of supraphysiological glucocorticoid treatment (including tablets, inhalers, nasal sprays, and skin creams) can also cause the same clinical condition1 2 (also known as exogenous or iatrogenic Cushing’s). #### How common is Cushing’s syndrome?