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.
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.
Luca CioccariDepartment of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland Australian and New Zealand Intensive Care Research Centre, School of Public Health and Preventive Medicine, Monash University, Prahran, Australia
The combination of hyperosmolar hyperglycaemic state and central diabetes insipidus is unusual and poses unique diagnostic and therapeutic challenges for clinicians. In a patient with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology that is considered, and achieving glycaemic control remains the first course of action. However, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and urine osmolality suggest concurrent symptomatic diabetes insipidus. We report a rare case of concurrent manifestation of hyperosmolar hyperglycaemic state and central diabetes insipidus in a patient with a history of craniopharyngioma.
In patients with diabetes mellitus presenting with polyuria and polydipsia, poor glycaemic control is usually the first aetiology to be considered.
However, a history of craniopharyngioma, severe hypernatraemia, hyperglycaemia and discordance between urine-specific gravity and osmolality provide evidence of concurrent diabetes insipidus.
Therefore, if a patient with diabetes mellitus presents with severe hypernatraemia, hyperglycaemia, a low or low normal urinary-specific gravity and worsening polyuria despite correction of hyperglycaemia, concurrent diabetes insipidus should be sought.
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.
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.
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.
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.
Bilateral adrenal hemorrhages rarely occur during the neonatal period and are often associated with traumatic vaginal deliveries. However, the adrenal gland has highly regenerative capabilities and adrenal insufficiency typically resolves over time. We evaluated a newborn female after experiencing fetal macrosomia and a traumatic vaginal delivery. She developed acidosis and acute renal injury. Large adrenal hemorrhages were noted bilaterally on ultrasound, and she was diagnosed with adrenal insufficiency based on characteristic electrolyte changes and a low cortisol (4.2 µg/dL). On follow-up testing, this patient was unable to be weaned off of hydrocortisone or fludrocortisone despite resolution of hemorrhages on ultrasound. Providers should consider bilateral adrenal hemorrhage when evaluating critically ill neonates after a traumatic delivery. In extreme cases, this may be a persistent process.
Risk factors for adrenal hemorrhage include fetal macrosomia, traumatic vaginal delivery and critical acidemia.
Signs of adrenal hemorrhage include jaundice, flank mass, skin discoloration or scrotal hematoma.
Adrenal insufficiency often is a transient process when related to adrenal hemorrhage.
Severe adrenal hemorrhages can occur in the absence of symptoms.
Though rare, persistent adrenal insufficiency may occur in extremely severe cases of bilateral adrenal hemorrhage.
Consider adrenal hemorrhage when evaluating a neonate for shock in the absence of an infectious etiology.
Metformin is recommended as the first-line agent for the treatment of type 2 diabetes. Although this drug has a generally good safety profile, rare but potentially serious adverse effects may occur. Metformin-associated lactic acidosis, although very uncommon, carries a significant risk of mortality. The relationship between metformin accumulation and lactic acidosis is complex and is affected by the presence of comorbid conditions such as renal and hepatic disease. Plasma metformin levels do not reliably correlate with the severity of lactic acidosis. We present a case of inadvertent metformin overdose in a patient with both renal failure and hepatic cirrhosis, leading to two episodes of lactic acidosis and hypoglycemia. The patient was successfully treated with hemodialysis both times and did not develop any further lactic acidosis or hypoglycemia, after the identification of metformin tablets accidentally mixed in with his supply of sevelamer tablets. Early initiation of renal replacement therapy is key in decreasing lactic acidosis-associated mortality.
When a toxic ingestion is suspected, direct visualization of the patient’s pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.
Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.
Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).
An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.
Ketoacidosis occurring during lactation has been described infrequently. The condition is incompletely understood, but it appears to be associated with a combination of increased metabolic demands during lactation, reduction in carbohydrate intake and acute illness. We present a case of a 27-year-old woman, 8 weeks post-partum, who was exclusively breastfeeding her child whilst following a low carbohydrate diet. She developed gastroenteritis and was unable to tolerate an oral diet for several days. She presented with severe metabolic acidosis on admission with a blood 3-hydroxybutyrate of 5.4 mmol/L. She was treated with intravenous dextrose and intravenous sodium bicarbonate, and given dietary advice to increase her carbohydrate intake. She made a rapid and full recovery. We provide a summary of the common causes of ketoacidosis and compare our case with other presentations of lactation ketoacidosis.
Ketoacidosis in the lactating woman is a rare cause of raised anion gap metabolic acidosis.
Low carbohydrate intake, starvation, intercurrent illness or a combination of these factors could put breastfeeding women at risk of ketoacidosis.
Ketoacidosis in the lactating woman has been shown to resolve rapidly with sufficient carbohydrate intake and intravenous dextrose.
Early diagnosis and prompt treatment are essential because the condition is reported to be reversible with a low chance of recurrence with appropriate dietary advice.
Udaya M KabadiVeteran Affairs Medical Center and Broadlawns Medical Center, Des Moines University of Osteopathic Medicine, Des Moines, Iowa, USA University of Iowa, Carver College of Medicine, Iowa City, Iowa, USA Medicine and Endocrinology, University of Iowa, Iowa City, Iowa, USA Des Moines University, Des Moines, Iowa, USA
Diabetic ketoacidosis (DKA) is commonly encountered in clinical practice. The current case is a unique and rare presentation of DKA as the initial manifestation of Cushing’s disease secondary to ACTH-secreting pituitary adenoma. Appropriate management as elaborated in the article led to total remission of diabetes as well as the Cushing’s disease.
DKA is a serious and potentially life-threatening metabolic complication of diabetes mellitus.
Some well-known precipitants of DKA include new-onset T1DM, insulin withdrawal and acute illness.
In a patient presenting with DKA, the presence of a mixed acid–base disorder warrants further evaluation for precipitants of DKA.
We present a rare case of DKA as an initial manifestation of Cushing’s disease secondary to ACTH-producing pituitary adenoma.