Pedro F S Freitas, Julia M Oliveira, Claudio E Kater
Hospital Militar de Área de
Brasília, Brasília, Brazil
(P F S Freitas MD); and Division
of Endocrinology, Department
of Medicine, Escola Paulista de
Medicina, Universidade Federal
de Sao Paulo, Sao Paulo, Brazil
(J M Oliveira MD, C E Kater PhD)
Correspondence to:
Dr Pedro F S Freitas, Hospital
Militar de Área de Brasília,
Brasília, DF 70630-000, Brazil
pedro.freitas05@gmail.com
A 19-year-old man presented with a 4-day history of
abdominal pain, nausea, vomiting, and fever. He had no
medical history. On examination his temperature was
38·8°C, he was dehydrated and tachycardic, and he had
postural hypotension: his blood pressure was 110/40 mm Hg
supine and 88/36 mm Hg standing. On palpation of
his abdomen, the patient reported widespread pain with
equivocal rebound tenderness. We also noted diffuse
darkening of the mucous membranes and skin, which the
patient said had gradually increased over the past 7 years.
The hyperpigmentation was more pronounced on the
skin over the patient’s joints, hands and feet nail beds,
gingivae, and the dorsum of the tongue (figure).
Laboratory tests showed a sodium concentration of
116 mmol/L, a potassium concentration of 5·3 mmol/L, a
low morning serum cortisol concentration of 63·4 nmol/L
(normal range 172–496), and a high plasma adrenocorticotropic
hormone concentration of 440 pmol/L (normal
range 1·5–13·9). We started the patient on an intravenous
saline drip and gave him a bolus of 100 mg of hydrocortisone
intravenously. After 24 h the patient’s symptoms
improved, and after 6 days his electrolytes normalised.
Further investigations found no HIV antibodies, no
antibodies against 21-hydroxylase, no antibodies to
Paracoccidioides brasiliensis (also known as South American
blastomycosis), and a negative tuberculin test. However,
the patient’s serum concentration of hexacosanoic acid—a
very long chain fatty acid (VLCFA)—was 2·82 μmol/L
(normal range 0·22–0·88).
Molecular sequencing found a missense mutation in
exon 6 of the ABCD1 gene—the R518Q mutation—in
both the patient and his mother confirming the diagnosis
of X-linked adrenoleukodystrophy. Additionally, when
we repeated a neurological examination, we found the
patient to have a previously unnoticed, slight left
hemiparesis with preserved deep tendon reflexes, muscle
tone, and normal sensation. After 9 days in the hospital,
the patient went home taking oral hydrocortisone and
fludrocortisone.
The characteristic mucocutaneous manifestations of
Addison’s disease (AD) are the crucial clue in diagnosing
this life-threatening condition: ideally, they should be
engrained into every clinician’s visual memory—the
other signs and symptoms of AD are non-specific.
X-linked adrenoleukodystrophy is a rare genetic disorder
characterised by intracellular accumulation of VLCFA.
Phenotypes range from a severe progressive cerebral form
in boys to a myelopathy form in adults. AD may occur
throughout the lifespan, independently of the neurological
presentations; it is seen as an isolated manifestation in up
to 10% of cases. X-linked adrenoleukodystrophy must be
considered as a differential diagnosis of AD in young
men—even if neurological symptoms are not obvious at
initial examination, as we found in our patient (video).
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31680-9/fulltext