The patient is an 18-year-old Han female admitted to Peking Union Medical College Hospital due to adrenal crisis triggered by pneumonia.
She has developed recurrent respiratory infections since age 5, and failed to respond to multiple hepatitis B virus (HBV) vaccinations.
Reduced serum cortisol and ACTH levels were discovered at 16 when glucocorticoid replacement was initiated.
In addition, hair loss started from age 4, and absence of pubic and axillary hair was noticed after development of regular menstruation.
Her history includes nephrotic syndrome, which was confirmed to be minimal change nephropathy by renal biopsy.
Physical examination at admission revealed alopecia totalis, oral candidiasis, hypohidrosis, and trachyonychia.
Facial or dental abnormalities was not noted.
She is the only child in her family.
Symptom and signs of the above disorders were not identified among her nonconsanguineous parents.
Initial immunologic tests revealed remarkable panhypogammaglobulinemia and reduced cell counts of B cells, T cells, and natural killer (NK) cells (Table ​(Table1).1).
CD4/CD8 ratio, as well as expression levels of various T-cell activation markers were in normal range, except increased proportion of CD8+/HLA-DR+ subset.
Antinuclear antibodies (ANA) and antineutrophil cytoplasmic antibodies (ANCA) were negative.
When regular hydrocortisone replacement was suspended, her 8:00 am serum cortisol was measured at 0.93 μg/dL, with ACTH <5.00 pg/mL.
Serum levels of other anterior pituitary hormones, as well as serum and urine osmolality were within reference range.
Both antiperoxidase antibody and antithyroglobulin antibody were negative.
She had positive antiprotein tyrosine phosphatase antibody, with fasting blood glucose at 5.9 mmol/L.
Magnetic resonance imaging with contrast suggested a normal pituitary.
She was diagnosed with CVID, isolated ACTH deficiency, and ectodermal dysplasia.
Symptoms of fever, cough, and vomiting cleared with antibiotics and stress-dose hydrocortisone treatment.
Intravenous immunoglobulin (IVIG) therapy was suggested but denied by the parents.
At follow-up 1 year after her discharge, she reported no infection events during the previous year as she stayed at home and avoided outdoor activities.
Her glucocorticoid replacement was withdrawn 4 months after discharge, and she has only received traditional Chinese medicine ever since.
Lymphocyte subsets test done at the follow-up documented increased levels of B cells and T cells, while NK cell count remained below normal limit.
To assess her NK-cell activity, a flow cytometric procedure was done following previously described method.[10,11] Effector to target cell ratio was set at 10:1.
Less apoptosis of target cell line (12.43%, reference range 15.11–26.91%) was observed when cocultured with patient's peripheral blood mononuclear cells (PBMC), indicating a deficient NK-cell cytotoxicity.