Autoimmune Polyglandular Syndrome (APS) type I and type II

For some, their Addison's diagnosis leads on from, or to, other autoimmune conditions. Those with Addison's together with underactive thyroid, dlabetes insipidus, hepatitis, pernicious anaemia, type 1 diabetes or vitiligo amongst others, might have a type of autoimmune polyglandular syndrome. Monitoring to track the onset of related conditions can help people with APS to reach earlier diagnosis and work towards a better quality of life while managing multiple autoimmune conditions.

According to NICE, Addison's disease may occur in isolation but is associated with other autoimmune conditions in 50–80% of cases. They reported that of all people with autoimmune Addison's disease, about two-thirds have an autoimmune polyendocrine syndrome with APS Type one accounting for 15% of people with Addison's disease and Type 2 being more common.

Source: https://cks.nice.org.uk/topics/addisons-disease/background-information/associated-conditions/

APS 1

Autoimmune polyendocrine syndrome type 1

(up to 15% of people with Addison's disease).

  • Usually autosomal recessive.
  • Typically presents in childhood.
  • Triad of Addison's disease, hypoparathyroidism, and chronic candidiasis.

May also be associated with type 1 diabetes mellitus, hypogonadism, premature ovarian insufficiency, pernicious anaemia, autoimmune thyroid disease, chronic active hepatitis, immunoglobulin A deficiency, chronic atopic dermatitis, keratoconjunctivitis, vitiligo, and alopecia.

APS 2

Autoimmune polyendocrine syndrome type 2
(more common).

Complex genetic trait with links to human leukocyte antigen (HLA) major histocompatibility complex.
Usually involves Addison's disease and autoimmune thyroid disease or type 1 diabetes mellitus.
May also include premature ovarian insufficiency, vitiligo, pernicious anaemia, coeliac disease, and hypoparathyroidism.

Table compliled by the ADSHG using information from the NICE website https://cks.nice.org.uk/topics/addisons-disease/background-information/associated-conditions/

APS Type 1 is also known as autoimmune polyendocrinopathy type 1 or APECED and you get fungal infections and other manifestations. It is caused by mutations in the autoimmune regulator gene and this condition is very uncommon. It is autosomal recessive condition (two copies of an abnormal gene must be present in order for the disease or trait to develop) usually with childhood onset and there is persistent or recurrent thrush (candidiasis) typically in the nails, mouth, gullet or elsewhere. There is hypoparathyroidism (where the body produces abnormally low levels of parathyroid hormone) leading to low calcium in 90% of people and 60% have adrenal insufficiency. Absent or early cessation of menstrual periods is common in women. There can be hypothyroidism (underactive thyroid) and rarely hypopituitarism (a rare disorder in which your pituitary gland fails to produce one or more hormones, or doesn't produce enough hormones) with diabetes insipidus (an uncommon disorder that causes an imbalance of fluids in the body).  There can be chronic active hepatitis (liver), malabsorption and hair loss and teeth problems as well as pernicious anaemia (where your immune system attacks healthy cells in your stomach, preventing your body absorbing vitamin B12 from the food you eat).

APS Type II is mostly adult in onset and 100% have adrenal insufficiency.  There are more than 20 gene variants which each contribute a small amount to the susceptibility to the condition. Autoimmune thyroid disease in 70% of people with APS Type 2. Mostly it is hypothyroidism (underactive thyroid) but hyperthyroidism(overactive thyroid) can occur. Type I diabetes occurs in 5-20% often before the diagnosis of Addison's disease. Premature ovarian failure can occur in women (5-20%) and very rarely there is diabetes insipidus (0.1%). There may be vitiligo (pale areas of skin), myasthenia (a chronic autoimmune disorder in which antibodies destroy the communication between nerves and muscle, resulting in weakness of the skeletal muscles), alopecia (hair loss), pernicious anaemia and immune thrombocytopenia purpura (low platelets).  Schmidt's syndrome is Addison's disease and autoimmune hypothyroidism and Carpenter syndrome is Addison's disease and autoimmune hypothyroidism and/or diabetes mellitus.

We are very grateful to ADSHG Clinical Panel members Professor John Wass and Professor Simon Pearce for providing the above detailed paragraphs about two types of APS.