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Hypotension results not only from hypovolemia but also
from deﬁciency of cortisol itself, which exhibits a variety of
genomic and nongenomic eﬀects on vascular tone (4). Hyponatremia results from renal salt wasting, volume depletion, and
resultant hypersecretion of antidiuretic hormone (ADH) caused
by aldosterone insuﬃciency. Additionally, cortisol exerts direct
and indirect negative feedback on ADH secretion; thus, its deﬁciency also leads to elevated ADH levels (5). Hyperkalemia is
attributable to the loss of aldosterone, which normally promotes
the urinary excretion of dietary potassium. In our patient, these
classic abnormalities were not observed. Her normal serum
sodium and low serum potassium levels may be explained by
zealous mineralocorticoid replacement in combination with
chronic gastrointestinal potassium and magnesium losses.
Common precipitants of AC include infection, surgical procedures, trauma, and abrupt withdrawal of glucocorticoid therapy
(2). AC occurs more frequently in patients with primary compared to secondary AI, likely reﬂecting residual glucocorticoid
secretion in the latter (1, 6). In a large German retrospective
cohort study, the incidence of AC was higher in patients with
APS-2 and highest in those with APS-2 and type 1 DM (6).
It is crucial that diagnostic testing not cause a delay in treatment. When AC is suspected, intravenous ﬂuids (1 L normal
saline in the ﬁrst hour followed by continuous administration)
and glucocorticoids (100 mg of hydrocortisone followed by
200 mg over 24 hours as a continuous infusion or in divided
doses every 6 hours) should be administered promptly with
concurrent testing of serum chemistries, cortisol, and adrenocorticotropic hormone (7). Long-term maintenance therapy
usually consists of oral hydrocortisone (15 to 25 mg/day) or cortisone acetate (20 to 35 mg/day) in two or three divided doses.
Most patients also require ﬂudrocortisone at a dose of 0.05 to
0.2 mg/day (7). It cannot be overemphasized that patients with
primary AI must never discontinue glucocorticoid replacement
for any reason. As the present case illustrates, discontinuation of
glucocorticoid therapy can have disastrous consequences despite
adequate mineralocorticoid replacement.
The autoimmune polyglandular syndromes are a group
of disorders characterized by endocrine and nonendocrine
immune-mediated dysfunction. Three main syndromes have
been described. Autoimmune polyglandular syndrome-1
(APS-1) is an autosomal recessive disorder caused by mutations in the autoimmune regulator (AIRE) gene, which results
in a loss of central tolerance, the process by which self-reactive
T cells are eliminated in the thymus during early diﬀerentiation.
It usually manifests during infancy with mucocutaneous

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candidiasis; primary AI and hypoparathyroidism occur later.
APS-1 is associated with other autoimmune diseases including type 1 DM, vitiligo, alopecia, hepatitis, pernicious anemia,
and primary hypothyroidism. The diagnosis is made by genetic
testing. Hormone replacement and aggressive treatment of
mucocutaneous candidiasis are the mainstays of treatment (8).
APS-2, also known as Schmidt syndrome, is the most common
autoimmune polyglandular syndrome. In contrast to APS-1,
APS-2 is a polygenic disorder associated with particular HLA
class II haplotypes in addition to mutations in several non-HLA
genes. Onset is during adulthood, and the individual endocrine
and nonendocrine components may develop years or decades
apart. Primary AI plus either autoimmune thyroid disease or
type 1 DM are the principal manifestations; associated diseases
include celiac disease, pernicious anemia, myasthenia gravis, vitiligo, and alopecia. Treatment focuses on the identiﬁcation and
management of the component autoimmune conditions (8).
The third form, immune dysregulation, polyendocrinopathy,
enteropathy, X-linked (IPEX) syndrome is a rare disorder caused
by mutations in the forkhead box P3 (FOXP3) gene resulting in
functional or quantitative deﬁciency of regulatory T cells. The
disease manifests in the ﬁrst days to months of life with severe
autoimmune enteropathy, dermatitis, and type 1 DM and may
be rapidly fatal if untreated. Immunosuppressive drugs can be
eﬀective in ameliorating autoimmune and allergic disease but
are associated with signiﬁcant toxicity. Restoration of regulatory
T-cell function via hematopoietic stem cell transplantation oﬀers
the potential for cure (8).
1.
2.
3.
4.
5.
6.

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Baylor University Medical Center Proceedings

Volume 30, Number 4

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