Autoimmune polyglandular syndrome

Autoimmune polyglandular syndrome type 1

• Pathophysiology: mutation in the AIRE gene (Autosomal Recessive, on chromosome

21q22.3), which leads to reduced immune tolerance. In the thymus the T cells that react
with this gene product either go through apoptosis or become T-Reg and helps in the
identification of other autoreactive T cells.
• Antibodies reactive to self → Adrenal and parathyroid glands with unknown reason for
target
• 1:100,000
• Usually detected in childhood

Signs and symptoms

1. Hypoparathyroidism: hypocalcemia and elevated phosphorus. Leads to muscle
cramping and seizures. Association with anti-parathyroid gland antibodies that are
directed against the calcium-sensing receptor
2. Primary adrenal insufficiency (Addison disease): low cortisol and aldosterone. They help
to maintain adequate blood pressure. Adrenal insufficiency usually develops later, at age
10 to 15 years. The antigen targets are adrenal enzymes including P450scc (side-chain
cleavage enzyme), P450c17 (17-alpha-hydroxylase), and P450c21 (21-hydroxylase). The
presence of adrenal autoantibodies has a high (92 percent) positive predictive value for
development of adrenal insufficiency
3. Chronic mucocutaneous candidiasis: infection with Candida on mouth, esophagus, and
genitalia
4. Ectodermal dystrophy: vitiligo, reduced dental enamel, alopecia
5. Liver, lungs, kidney, intestines, salivary glands, and spleen might also be affected
(hypogonadism, pernicious anemia, alopecia, vitiligo, hepatitis). Malabsorption and
other gastrointestinal disorders occur in about 25 percent of patients

Diagnosis:
• 2/3 of the bold signs and symptoms
• DNA testing for AIRE mutations
• Laboratory tests for autoantibodies against interferons

Treatment:
• Treat the manifestations present
• Use hormone replacement therapy (thyroxin, hydrocortisone, insulin)
• Immunosuppression for extra endocrine effects
• Calcium and Vitamin D in hypoparathyroidism
• Vitamin B12 when pernicious anemia
• Antifungals for chronic mucocutaneous Candidiasis
Autoimmune polyglandular syndrome type 2

• Pathophysiology: Associated with HLA DR3 and/or HLA DR4 haplotypes

• More common than 1, 2:100,000
• Onset usually in adulthood

Signs and symptoms

1. Primary adrenal insufficiency
2. Thyroid autoimmune disease (Hashimoto)
3. DM1
4. Less common: celiac disease, pernicious anemia, alopecia, vitiligo
5. Hypopituitarism due to autoimmune hypophysitis, preferentially causing ACTH
deficiency, can occur alone or in combination with thyrotropin or, rarely, growth
hormone deficiency
6. Hypoparathyroidism does not occur in this disorder, and alopecia and pernicious anemia
are much less frequent than in the type I syndrome.

Diagnostics
• Condition‑specific antibody tests (e.g., TPO antibodies in Hashimoto thyroiditis,
antiparietal cell antibodies in pernicious anemia)

Hypocalcemia by hypoparathyroidism
• Tetany may be mild (perioral numbness, paresthesias of the hands and feet, muscle
cramps) or severe (carpopedal spasm, laryngospasm, and focal or generalized seizures,
which must be distinguished from the generalized tonic muscle contractions that occur in
severe tetany). The classic physical findings in patients with neuromuscular irritability due
to latent tetany are Trousseau's and Chvostek's signs

• Other patients have less specific symptoms, such as fatigue, hyperirritability, anxiety, and
depression, and some patients, even with severe hypocalcemia, have no neuromuscular
 symptoms. Cardiac findings may include a prolonged QT interval, hypotension, heart
failure, and arrhythmia
• Chronic hypocalcemia might lead to basal ganglia calcifications, cataracts, dental
abnormalities, and ectodermal manifestations. Some patients also report poor quality of
life.
• Laboratory findings: hypocalcemia, low PTH, elevated phosphorus. Usually have normal
or low Vitamin D. Normal magnesium and creatinine levels

Treatment for chronic hypoparathyroidism

• IV calcium gluconate if acute sever symptoms
• Oral calcium and Vitamin D (use calcitriol as it does not require renal activation with
shorter onset) over recombinant PTH
• Oral calcium glubionate, calcium carbonate, or calcium citrate is administered (30 to 75
mg/kg elemental calcium daily) in four divided doses, along with calcitriol 0.02 to 0.06
mcg/kg/day in two equally divided doses (usual dose 1 mcg per day, maximum reported
dose 2 mcg per day). The dose of calcitriol may be adjusted at two- to four-week intervals
aiming to maintain the serum calcium concentrations within the low-normal range and to
avoid hypercalciuria (>4 mg/kg/24 hours)
• Monitoring: Monitoring of urinary and serum calcium and serum phosphate is required
weekly initially, until a stable serum calcium concentration (at the low end of the normal
range) is reached. Thereafter, monitoring serum calcium, creatinine, phosphorus, and 25-
hydroxyvitamin D (25[OH]D) every 6 to 12 months is sufficient
• Adverse effects of treatment: Nephrocalcinosis/nephrolithiasis and renal insufficiency
have been reported in 15 and 13 percent of patients, respectively.
• These findings suggest that PTH restores bone metabolism to levels more typical of
euparathyroid individuals; however, the clinical significance of this finding is not clear.

Dose calculation for our patient: