Endocrine Abstracts

Background: Hypoglycaemia is a common critical condition in paediatric emergencies, with diverse aetiologies including metabolic disorders and endocrine dysfunctions. Adrenal insufficiency is a life-threatening cause, that requires prompt diagnosis and intervention. This case study presents a rare incidence of hypoglycaemia secondary to adrenal failure in a paediatric patient with Kearns-Sayre Syndrome (KSS), a mitochondrial disorder affecting multiple systems.

Case Presentation: A 4-year-old boy, initially presented with significant and recurrent hypoglycaemia. A poor cortisol response(292 nmol/l) during hypoglycaemia was noted. Synacthen test confirmed adrenal insufficiency with cortisol levels of 267 nmol/l at 0 minutes, 234 nmol/l at 30 minutes, and 334 nmol/l-60 minutes as well as ACTH 375 ng/l, Renin >500 and low aldosterone. Hydrocortisone and fludrocortisone replacement was commenced.

Investigations: Urinary steroid profile was abnormal but not diagnostic - Elevated DHEA and unusual pregnenolone metabolites. Adrenal antibodies were negative and VLCFA, plasma amino acids, urinary organic acids and free carnitine were normal. Gross lactic aciduria and ketonuria were noted. MRI scans showed no abnormalities including normal adrenals. Lactate was persistently raised 5-8 mmol/l, which led to further investigation including mitochondrial DNA testing. This revealed a 2kb deletion consistent with Kearns-Sayre/Pearson spectrum disorder. Subsequently, the echocardiogram and nerve conduction studies were normal but he has developed significant liver dysfunction and failure to thrive and exocrine pancreatic insufficiency.

Kearns-Sayre Syndrome: KSS is a rare (estimated prevalence1/1,25,000) mitochondrial genetic disorder with multisystem involvement. Typically manifesting in childhood, its signs and symptoms vary based on multi-organ involvement- CNS, cardiac, skeletal muscle, and endocrine manifestations- adrenal insufficiency, pancreatic exocrine insufficiency, lactic acidosis, microalbuminuria, transaminitis, ongoing weight loss, and intolerance to Creon. Diagnosis modality for KSS is to identify deletion of mitochondrial DNA genome by Next-generation sequencing in peripheral blood leukocyte sample. Most patients could live for several decades.

Learning Points: This case is an example of inherited metabolic disorders, an important differential in adrenal insufficiency. Persistent raised lactate levels should prompt further investigation despite a normal initial “metabolic screen”. Understanding adrenal insufficiency within the broader context of rare metabolic conditions like Kearns-Sayre Syndrome is crucial for accurate diagnosis and effective management.