Hypoglycaemia in a Child Unmasks a Unique Association

Childhood hypoglycaemia results from impairment or defects in glucose homeostasis and has a blood glucose (BG) operational threshold of 60 mg/dL (<3.3 mmol/L) as below this level, neurological symptoms occur, and if the BG falls below 50 mg/dL (2.8 mmol/L), it is highly likely to cause long-term neurological consequences. A 38-month-old previously healthy boy presented with hypoglycaemic seizures (BG: 30 mg/dL [1.7 mmol/L]) after a brief period of being unwell. The sepsis screen was normal. Hypoglycaemia screen detected a low cortisol level (28 nmol/L [83–555]). This was also associated with a low thyroid-stimulating-hormone (0.768 mIU/mL [0.5–5.5]) and a low-normal T4 (5.57 μg/dL [5–12]). Hydrocortisone and levothyroxine replacement was started. Four weeks from the time of discharge, the short synacthen test (SST; generic name: tetracosactide acetate) for adrenal function revealed a low stimulated cortisol (2/1.51/1.52 nmol/L at 0, 30, and 60 min, respectively, post synacthen [normal range: 83–550; peak >420 μg/dL]) and low basal adrenocorticotropic hormone (4.6 pg/mL [10–60]). A rare diagnosis of isolated secondary adrenocortical insufficiency was made, and the neuroimaging demonstrated a reduced pituitary height (3 mm). Three months later, levothyroxine was tapered and omitted as the child was euthyroid, but the SST showed a similar flat response to the synacthen. The genetic testing demonstrated a pathogenic heterozygous mutation in the nuclear factor kappa B subunit 2 (NFKB2) gene responsive for common variable immunodeficiency (CVID), and this entity has been described as deficient anterior pituitary hormone with CVID syndrome (DAVID syndrome). The immunoglobulin profile showed a decrease in three types of immunoglobulin (IgM, IgG, and IgE), meeting the diagnostic criteria for CVID. Till date, less than 35 cases are reported worldwide, and of which, less than 5 of them presented with adrenal insufficiency prior to immunodeficiency, making this case rare and teaching us a lesson to think beyond the usual causes of hypoglycaemia.