Browse

You are looking at 1 - 7 of 7 items for :

  • Haemoglobin A1c x
Clear All
Open access

Miriam Hinaa Ahmad and Ismat Shafiq

Summary

We report a case of a 21-year-old African American female with history of pre-diabetes, and a diagnosis of a rare leukemia, blastic-plasmacytoid dendritic neoplasm (BPDCN), who developed diabetic ketoacidosis (DKA) after the third dose of PEG-asparaginase infusion. She was successfully treated with insulin. Asparaginase is a vital part of treatment protocols for acute lymphoblastic leukemia (ALL) in combination with other chemotherapeutic drugs. Asparaginase therapy has been reported to cause hyperglycemia especially when used in conjunction with glucocorticoids for the treatment of ALL in the pediatric population. Multiple mechanisms for hyperglycemia have been hypothesized which include decreased insulin secretion, impaired insulin receptor function and excess glucagon formation. Hyperglycemia is usually self-limiting but can deteriorate to diabetic ketoacidosis. DKA is a rare adverse effect with asparaginase therapy with an incidence rate of about 0.8%.

Learning points:

  • DKA is a rare finding following asparaginase therapy.

  • Hyperglycemia is most commonly seen with asparaginase treatment when used along with glucocorticoid.

  • Frequent blood glucose monitoring and prompt initiation of insulin treatment with hyperglycemia can prevent severe complications.

  • Patients and physician education on this complication can reduce morbidity due to DKA.

Open access

Senhong Lee, Aparna Morgan, Sonali Shah and Peter R Ebeling

Summary

We report a case of a 67-year-old man with type 2 diabetes presented with diabetic ketoacidosis, two weeks after his first dose of nivolumab therapy for non–small-cell lung carcinoma. He was started on empagliflozin two days prior in the setting of hyperglycaemia after the initiation of nivolumab therapy. Laboratory evaluation revealed an undetectable C-peptide and a positive anti-glutamic acid decarboxylase (GAD) antibody. He was treated with intravenous fluids and insulin infusion and was subsequently transitioned to subcutaneous insulin and discharged home. He subsequently has developed likely autoimmune thyroiditis and autoimmune encephalitis.

Learning points:

  • Glycemic surveillance in patients receiving immune checkpoint inhibitors is recommended.

  • Early glycemic surveillance after commencement of anti-programmed cell death-1 (PD-1) inhibitors may be indicated in selected populations, including patients with underlying type 2 diabetes mellitus and positive anti-glutamic acid decarboxylase (GAD) antibody.

  • Sodium-glucose co transporter-2 (SGLT2) inhibitors should be used with caution in patients on immunotherapy.

Open access

Ali A Zaied, Halis K Akturk, Richard W Joseph and Augustine S Lee

Summary

Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.

Learning points:

  • Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).

  • Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.

  • Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.

Open access

Ploutarchos Tzoulis, Richard W Corbett, Swarupini Ponnampalam, Elly Baker, Daniel Heaton, Triada Doulgeraki and Justin Stebbing

Summary

Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.

Learning points:

  • Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.

  • Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.

  • Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.

  • Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.

Open access

Florence Gunawan, Elizabeth George and Adam Roberts

Summary

Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0.02 mU/L (0.5–5.5 mU/L), fT4: 5.2 pmol/L (11–22 pmol/L), fT3: 4.0 pmol/L (3.2–6.4 pmol/L), cortisol (12:00 h): <9 nmol/L (74–286 nmol/L), FSH: 0.7 IU/L (1.5–9.7 IU/L), LH: <0.1 IU/L (1.8–9.2 IU/L), PRL: 1 mIU/L (90–400 mIU/L), SHBG: 34 nmol/L (19–764 nmol/L) and total testosterone: <0.4 nmol/L (9.9–27.8 nmol/L). High-dose dexamethasone (8 mg) was administered followed by hydrocortisone, thyroxine and topical testosterone replacement. Two weeks post administration of the third cycle, he became unwell with lethargy, weight loss and nocturia. Central diabetes insipidus was diagnosed on the basis of symptoms and sodium of 149 mmol/L (135–145 mmol/L). Desmopressin nasal spray was instituted with symptom resolution and normalization of serum sodium. Three weeks later, he presented again polyuric and polydipsic. His capillary glucose was 20.8 mmol/L (ketones of 2.4 mmol), low C-peptide 0.05 nmol/L (0.4–1.5 nmol/L) and HbA1c of 7.7%. T1DM was suspected, and he was commenced on an insulin infusion with rapid symptom resolution. Insulin antibodies glutamic acid decarboxylase (GAD), insulin antibody-2 (IA-2) and zinc transporter-8 (ZnT8) were negative. A follow-up MRI pituitary revealed findings consistent with recovering autoimmune hypophysitis. Immunotherapy was discontinued based on the extent of these autoimmune endocrinopathies.

Learning points:

  • The most effective regime for treatment of metastatic melanoma is combination immunotherapy with nivolumab and ipilumimab, and this therapy is associated with a high incidence of autoimmune endocrinopathies.

  • Given the high prevalence of immune-related adverse events, the threshold for functional testing should be low.

  • Traditional antibody testing may not be reliable to identify early-onset endocrinopathy.

  • Routine screening pathways have yet to be adequately validated through clinical trials.

Open access

E S Scott, G R Fulcher and R J Clifton-Bligh

Pancreatogenic diabetes is characterised by recurrent severe hypoglycaemia due to changes in both endocrine and exocrine functions. There are no guidelines to manage these individuals. Herein, we describe the post-operative management of two people who developed pancreatogenic diabetes following total pancreatectomy for neuroendocrine malignancy. In both individuals, diabetes was managed using sensor-augmented predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII). We demonstrate the benefit of sensor-augmented CSII in averting hypoglycaemia whilst optimising glycaemic control. Expected rates of severe hypoglycaemia in individuals with pancreatogenic diabetes can be averted with the use of continuous glucose monitoring (CGM) technology, optimising quality of life and reducing the risk of diabetes-related complications.

Learning points:

  • There are no clear guidelines to manage people with pancreatogenic diabetes.

  • We describe the use of CGM with predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII) in the management of two individuals post-pancreatectomy.

  • Predictive low-glucose suspend technology can achieve excellent glycaemic control whilst avoiding recurrent and severe hypoglycaemia in people with pancreatogenic diabetes.

  • Predictive low-glucose suspend CGM should be considered as an effective therapeutic option for the management of pancreatogenic diabetes.

Open access

Ayanthi A Wijewardene, Sarah J Glastras, Diana L Learoyd, Bruce G Robinson and Venessa H M Tsang

Summary

Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour that originates from the parafollicular cells of the thyroid gland. The most common presentation of MTC is with a single nodule; however, by the time of diagnosis, most have spread to the surrounding cervical lymph nodes. Cushing’s syndrome is a rare complication of MTC and is due to ectopic adrenocorticotrophic hormone (ACTH) secretion by tumour cells. Cushing’s syndrome presents a challenging diagnostic and management issue in patients with MTC. Tyrosine kinase inhibitors (TKI) previously used for the management of metastatic MTC have become an important therapeutic option for the management of ectopic ACTH in metastatic MTC. The article describes three cases of ectopic ACTH secretion in MTC and addresses the significant diagnostic and management challenges related to Cushing’s syndrome in metastatic MTC.

Learning points:

  • Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour.

  • Cushing’s syndrome is a rare complication of MTC that has a significant impact on patients’ morbidity and mortality.

  • Tyrosine kinase inhibitors (TKI) provide an important therapeutic option for the management of ectopic ACTH in metastatic MTC.