A 27 year old female with probable type II poly glandular autoimmune syndrome presents critically unwell with..
Normal anion gap, compensated metabolic acidosis
with hyperkalaemia, hyponatraemia (corrected for glucose = 131), elevated lactate, hyperglycaemia and renal impairment
due to exacerbation of her endocrine disease (Addison’s crisis) and septic shock (tachycardia, temperature elevation, hypotension, elevated lactate, renal impairment and respiratory tract infection).
Treatment is aimed at treating septic shock and Addison’s, with consideration of thyroid storm. Consult endocrine for additional advice/ intervention as required.
Polyglandular autoimmune syndrome type II ( PGA-II) consists of Addison disease plus either an autoimmune thyroid disease or type 1 diabetes mellitus associated with hypogonadism, pernicious anemia, celiac disease, and recent primary biliary cirrhosis.
olyglandular deficiency syndromes (PDS) are characterized by sequential or simultaneous deficiencies in the function of several endocrine glands that have a common cause. Etiology is most often autoimmune. Categorization depends on the combination of deficiencies, which fall within 1 of 3 types. Diagnosis requires measurement of hormone levels and autoantibodies against affected endocrine glands. Treatment includes replacement of missing or deficient hormones and sometimes immunosuppressants.
Aetiology
The etiology is most often autoimmune. Risk factors for development of autoimmunity include
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Genetic factors
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Environmental triggers
Genetic factors include the AIRE gene mutation, which is causative of type 1, and certain HLA subtypes, which are important in the development of types 2 and 3. Environmental triggers include viral infections, dietary factors, and other as yet unknown exposures.
Pathophysiology
The underlying autoimmune reaction involves autoantibodies against endocrine tissues, cell-mediated autoimmunity, or both and leads to inflammation, lymphocytic infiltration, and partial or complete gland destruction. More than one endocrine gland is involved, although clinical manifestations are not always simultaneous. The autoimmune reaction and associated immune system dysfunction can also damage nonendocrine tissues.
Classification
Three patterns of autoimmune failure have been described (see Table: Characteristics of Types 1, 2, and 3 Polyglandular Deficiency Syndromes), which likely reflect different autoimmune abnormalities. Some experts combine type 2 and type 3 into a single group.
Type 1
usually begins in childhood. It is defined by the presence of ≥ 2 of the following:
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Adrenal insufficiency (Addison disease)
Candidiasis is usually the initial clinical manifestation, most often occurring in patients < 5 yr. Hypoparathyroidism occurs next, usually in patients < 10 yr. Lastly, adrenal insufficiency occurs in patients < 15 yr. Accompanying endocrine and nonendocrine disorders (see Table: Characteristics of Types 1, 2, and 3 Polyglandular Deficiency Syndromes) continue to appear at least until patients are about age 40.
Type 2 (Schmidt syndrome)
usually occurs in adults; peak incidence is age 30. It occurs 3 times more often in women. It typically manifests with the following:
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Type 1 diabetes (autoimmune etiology)
More rare features may also be present
Type 3 is characterized by
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Glandular failure occurring in adults, particularly middle-aged women
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At least one of a variety of other disorders (see Table: Characteristics of Types 1, 2, and 3 Polyglandular Deficiency Syndromes)
Type 3 does not involve the adrenal cortex.