Suspected Central Adrenal Insufficiency in a Patient with Phosphomannomutase 2-Congenital Disorder of Glycosylation

Phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG) is a hereditary defect causing hypoglycosylation of N-linked glycoproteins. It was recently suggested that patients with PMM2-CDG may have central adrenal insufficiency. We present an 18-year-old male with PMM2-CDG, whose initial screening suggested adrenal insufficiency. The patient displayed a morning plasma cortisol of 57 nmol/L (2.07 μg/dL) (reference range, 133-537 nmol/L [4.82-19.46 μg/dL]), a 30-minute ACTH-stimulated cortisol of 165 nmol/L (5.98 μg/dL), and a low-normal ACTH. The patient never experienced obvious symptoms of adrenal insufficiency nor clinical improvement after transient introduction of hydrocortisone. Additional assessment was therefore conducted, including cortisol binding globulin, which was markedly low (253 mmol/L (14.7 mg/L) (reference range, 750-2500 mmol/L [43.7-93.1 mg/L])). Subsequently, 8 Am salivary cortisol measured 24 hours after last hydrocortisone ingestion was normal-to-slightly elevated (38 nmol/L (1.38 μg/dL) (reference range, 2.48-29 nmol/L [0.09-1.05 μg/dL])). In conclusion, we present a patient with PMM2-CDG who, upon measurement of plasma cortisol, displayed "biochemical" adrenal insufficiency, although with low cortisol binding globulin and normal morning salivary free cortisol levels. This case illustrates the caveats of total cortisol for the diagnosis of adrenal insufficiency in patients with PMM2-CDG and highlights the potential impact of N-linked hypoglycosylation on endocrine evaluation.