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Open access

Mohammed Faraz Rafey, Arslan Butt, Barry Coffey, Lisa Reddington, Aiden Devitt, David Lappin and Francis M Finucane

Summary

We describe two cases of SGLT2i-induced euglycaemic diabetic ketoacidosis, which took longer than we anticipated to treat despite initiation of our DKA protocol. Both patients had an unequivocal diagnosis of type 2 diabetes, had poor glycaemic control with a history of metformin intolerance and presented with relatively vague symptoms post-operatively. Neither patient had stopped their SGLT2i pre-operatively, but ought to have by current treatment guidelines.

Learning points:

  • SGLT2i-induced EDKA is a more protracted and prolonged metabolic derangement and takes approximately twice as long to treat as hyperglycaemic ketoacidosis.
  • Surgical patients ought to stop SGLT2i medications routinely pre-operatively and only resume them after they have made a full recovery from the operation.
  • While the mechanistic basis for EDKA remains unclear, our observation of marked ketonuria in both patients suggests that impaired ketone excretion may not be the predominant metabolic lesion in every case.
  • Measurement of insulin, C-Peptide, blood and urine ketones as well as glucagon and renal function at the time of initial presentation with EDKA may help to establish why this problem occurs in specific patients.
Open access

Stephanie Wei Ping Wong, Yew Wen Yap, Ram Prakash Narayanan, Mohammad Al-Jubouri, Ashley Grossman, Christina Daousi and Yahya Mahgoub

Summary

We report our experience on managing a case of florid Cushing’s disease with Methicillin-resistant Staphylococcus aureus (MRSA) sepsis using intravenous etomidate in the intensive care unit of a UK district general hospital.

Learning points:

  • Severe Cushing’s syndrome is associated with high morbidity and mortality.
  • Etomidate is a safe and effective medical therapy to rapidly lower cortisol levels even in the context of severe sepsis and immunosuppression.
  • Etomidate should ideally be administered in an intensive care unit but is still feasible in a district general hospital.
  • During treatment with etomidate, accumulation of serum 11β-deoxycortisol (11DOC) levels can cross-react with laboratory cortisol measurement leading to falsely elevated serum cortisol levels. For this reason, serum cortisol measurement using a mass spectrometry assay should ideally be used to guide etomidate prescription.
Open access

Punith Kempegowda, Lauren Quinn, Lisa Shepherd, Samina Kauser, Briony Johnson, Alex Lawson and Andrew Bates

Summary

A 62-year-old Asian British female presented with increasing tiredness. She had multiple co-morbidities and was prescribed steroid inhalers for asthma. She had also received short courses of oral prednisolone for acute asthma exacerbations in the last 2 years. Unfortunately, the frequency and dose of steroids for asthma was unclear from history. Her type 2 diabetes mellitus (DM) control had deteriorated over a short period of time (HbA1c: 48–85 mmol/mol). Blood tests revealed undetectable cortisol and ACTH (<28 mmol/L, <5.0 ng/L). Renin, electrolytes and thyroid function were within normal limits. A diagnosis of secondary adrenal insufficiency, likely due to long-term steroid inhaler and recurrent short courses of oral steroids for asthma exacerbations was made. Patient was commenced on hydrocortisone 10 mg, 5 mg and 5 mg regimen. Steroid inhaler was discontinued following consultation with respiratory physicians. Despite discontinuation of inhaled steroids, patient continued not to mount a response to Synacthen®. Upon further detailed history, patient admitted taking a ‘herbal’ preparation for chronic osteoarthritic knee pain. Toxicology analysis showed presence of dexamethasone, ciprofloxacin, paracetamol, diclofenac, ibuprofen and cimetidine in the herbal medication. Patient was advised to discontinue her herbal preparation. We believe the cause of secondary adrenal insufficiency in our patient was the herbal remedy containing dexamethasone, explaining persistent adrenal suppression despite discontinuation of all prescribed steroids, further possibly contributing to obesity, hypertension and suboptimal control of DM. In conclusion, a comprehensive drug history including herbal and over-the-counter preparations should be elucidated. Investigation for the presence of steroids in these preparations should be considered when patients persist to have secondary adrenal insufficiency despite discontinuation of prescribed steroid medications.

Learning points:

  • The likelihood of complementary and alternative medicines (CAMs) in medication-induced secondary adrenal insufficiency should be considered in any patient presenting with potential symptoms of adrenal insufficiency.
  • If the contents of CAM preparation cannot be ascertained, toxicology screening should be considered.
  • Patients should be advised to stop taking CAM preparation when it contains steroids and hydrocortisone replacement therapy commenced, with periodic reassessment of adrenal function, and then if indicated weaned accordingly.
  • Patients should be informed about the contents of CAM therapies, so they can make a truly informed choice regarding the risks and benefits.
  • This case also highlights a need to increase regulatory processes over CAM therapies, given their propensity to contain a number of undisclosed medications and potent steroids.
Open access

G Leksic, A M Alduk, V Molnar, A Haxhiu, A Haxhiu, A Balasko, N Knezevic, T Dusek and D Kastelan

Summary

Primary aldosteronism (PA) is characterised by aldosterone hypersecretion and represents a common cause of secondary hypertension. During diagnostic evaluation, it is essential to determine the aetiology of PA since the treatment of unilateral and bilateral disease differs significantly. Adrenal vein sampling (AVS) has been implemented as a gold standard test for the diagnosis of PA subtype. However, due to the AVS complexity, costs and limited availability, many patients with PA are being treated based on the computed tomography (CT) findings. In this article, we present two patients with discrepant CT and AVS results, demonstrating that AVS is the only reliable method for localising the source of aldosterone excess.

Learning points:

  • CT is an unreliable method for distinguishing aldosterone-producing adenoma (APA) from bilateral adrenal hyperplasia (BAH).
  • CT can be misleading in defining lateralisation of the aldosterone excess in case of unilateral disease (APA).
  • AVS is the gold standard test for defining the PA subtype.
Open access

Michelle Maher, Mohammed Faraz Rafey, Helena Griffin, Katie Cunningham and Francis M Finucane

Summary

A 45-year-old man with poorly controlled type 2 diabetes (T2DM) (HbA1c 87 mmol/mol) despite 100 units of insulin per day and severe obesity (BMI 40.2 kg/m2) was referred for bariatric intervention. He declined bariatric surgery or GLP1 agonist therapy. Initially, his glycaemic control improved with dietary modification and better adherence to insulin therapy, but he gained weight. We started a low-energy liquid diet, with 2.2 L of semi-skimmed milk (equivalent to 1012 kcal) per day for 8 weeks (along with micronutrient, salt and fibre supplementation) followed by 16 weeks of phased reintroduction of a normal diet. His insulin was stopped within a week of starting this programme, and over 6 months, he lost 20.6 kg and his HbA1c normalised. However, 1 year later, despite further weight loss, his HbA1c deteriorated dramatically, requiring introduction of linagliptin and canagliflozin, with good response. Five years after initial presentation, his BMI remains elevated but improved at 35.5 kg/m2 and his glycaemic control is excellent with a HbA1c of 50 mmol/mol and he is off insulin therapy. Whether semi-skimmed milk is a safe, effective substrate for carefully selected patients with severe obesity complicated by T2DM remains to be determined. Such patients would need frequent monitoring by an experienced multidisciplinary team.

Learning points:

  • Meal replacement programmes are an emerging therapeutic strategy to allow severely obese type 2 diabetes patients to achieve clinically impactful weight loss.
  • Using semi-skimmed milk as a meal replacement substrate might be less costly than commercially available programmes, but is likely to require intensive multidisciplinary bariatric clinical follow-up.
  • For severely obese adults with poor diabetes control who decline bariatric surgery or GLP1 agonist therapy, a milk-based meal replacement programme may be an option.
  • Milk-based meal replacement in patients with insulin requiring type 2 diabetes causes rapid and profound reductions in insulin requirements, so rigorous monitoring of glucose levels by patients and their clinicians is necessary.
  • In carefully selected and adequately monitored patients, the response to oral antidiabetic medications may help to differentiate between absolute and relative insulin deficiency.
Open access

Michal Barabas, Isabel Huang-Doran, Debbie Pitfield, Hazel Philips, Manoj Goonewardene, Ruth T Casey and Benjamin G Challis

Summary

A 67-year-old woman presented with a generalised rash associated with weight loss and resting tachycardia. She had a recent diagnosis of diabetes mellitus. Biochemical evaluation revealed elevated levels of circulating glucagon and chromogranin B. Cross-sectional imaging demonstrated a pancreatic lesion and liver metastases, which were octreotide-avid. Biopsy of the liver lesion confirmed a diagnosis of well-differentiated grade 2 pancreatic neuroendocrine tumour, consistent with metastatic glucagonoma. Serial echocardiography commenced 4 years before this diagnosis demonstrated a progressive left ventricular dilatation and dysfunction in the absence of ischaemia, suggestive of glucagonoma-associated dilated cardiomyopathy. Given the severity of the cardiac impairment, surgical management was considered inappropriate and somatostatin analogue therapy was initiated, affecting clinical and biochemical improvement. Serial cross-sectional imaging demonstrated stable disease 2 years after diagnosis. Left ventricular dysfunction persisted, however, despite somatostatin analogue therapy and optimal medical management of cardiac failure. In contrast to previous reports, the case we describe demonstrates that chronic hyperglucagonaemia may lead to irreversible left ventricular compromise. Management of glucagonoma therefore requires careful and serial evaluation of cardiac status.

Learning points:

  • In rare cases, glucagonoma may present with cardiac failure as the dominant feature. Significant cardiac impairment may occur in the absence of other features of glucagonoma syndrome due to subclinical chronic hyperglucagonaemia.
  • A diagnosis of glucagonoma should be considered in patients with non-ischaemic cardiomyopathy, particularly those with other features of glucagonoma syndrome.
  • Cardiac impairment due to glucagonoma may not respond to somatostatin analogue therapy, even in the context of biochemical improvement.
  • All patients with a new diagnosis of glucagonoma should be assessed clinically for evidence of cardiac failure and, if present, a baseline transthoracic echocardiogram should be performed. In the presence of cardiac impairment these patients should be managed by an experienced cardiologist.
Open access

Charlotte Boughton, David Taylor, Lea Ghataore, Norman Taylor and Benjamin C Whitelaw

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.