PANCREATIC AUTOIMMUNE DISORDERS: EDT
Autoimmune forms of Diabetes:
- Type 1 diabetes (5-10%)
- Latent autoimmune diabetes in adults (5-10%)
- Type 2 diabetes
INSULIN-DEPENDENT DIABETES MELLITUS (IDDM)
ETIOLOGY
- AKA Type 1 diabetes mellitus
- Deficient in insulin production
- Immune destruction of the B cells of the
pancreatic islets
- Environmental factors:
o Coxsackievirus B
o Congenital rubella infection
- Genetic susceptibility factors: HLA-DR3, DR4,
DQ2, DQ8
o 90% of white patients have 1/both DR
antigens
o HLA DR3, DR4: higher risk of disease
development than from either antigen
o DR2: decreased in IDDM; gives protective
effect to the body
o HLA-DQw8: 2-6 fold increased risk for
diabetes
EPIDEMIOLOGY
- T1D happens often in childhood or
adolescence, but may occur at any age.
- It usually develops before age 30 years.
SIGNS AND SYMPTOMS
- Requires exogenous insulin to maintain normal
glucose level.
- Insulin deficiency
IMMUNOLOGIC MANIFESTATIONS
- CD4+ T lymphocyte: central in immune process
that leads to the development of diabetes
o Causes formation of islet cell autoantibodies
o B cell destruction
- T1D autoantibodies:
o Insulin autoantibodies (IAAs)
o Glutamic acid decarboxylase (GAD)
autoantibodies
o Islet cell antigen-2 (IA-2)
- These autoantibodies are also associated with
autoimmune endocrine disorders.
- Immunoglobulin of T1D patient competes with
the tissue receptor for insulin, causing
prevention of biologic effects of insulin.
- Some T1D autoantibodies also kill pancreatic
islet cells (common among young patients).
- Antireceptor antibody (InR): IgG directed to
insulin receptor; predominant to nonwhite
females
- IA-2: directed against phosphatase-type
membrane 37-kDa islet beta cell antigen
(ICA512)
LATENT AUTOIMMUNE DIABETES IN ADULTS
- Affect individuals aging >35 years old
- Frequently misdiagnosed as type 2 diabetes
- Progresses more rapidly to T1D than T2D
AUTOIMMUNE PANCREATITIS
- Heterogeneous disease
- Chronic pancreatitis with autoimmune
inflammatory process: prominent lymphocyte
infiltration with associated fibrosis
- Leads to organ dysfunction
ETIOLOGY
- Unknown cause
- Considered as systemic autoimmune disorder
- Associated with other AI disorders: rheumatoid
arthritis
EPIDEMIOLOGY
- Rare
- Occurs in both genders
- Common among individuals aging >50 years
old
SIGNS AND SYMPTOMS
- Generally variable
- Jaundice
- Abdominal pain
- Histology: collar-like periductal infiltrate
composed of lymphocytes and plasma cells
o Patients with this manifestation have
hypergammaglobulinemia (elevated serum
IgG or gamma globulin level)
- CT scan: diffuse pancreatic enlargement with a
halo around its peripheral rim
o Patients with this manifestation have
elevated serum IgG4
IMMUNOLOGIC MANIFESTATIONS
- Anti-carbonic anhydrase II antibody
- Antilactoferrin antibody
- Anti-smooth muscle antibody
- Increased number of CDR+ T lymphocytes
PANCREATIC AUTOIMMUNE DISORDERS: EDT
ADRENAL GLANDS o Pernicious anemia
ADDISON’S DISEASE o Myasthenia gravis, or any nonendocrine,
- Caused by idiopathic adrenal atrophy organ specific AI disorder
- Women are afflicted twice as men - No Addison’s disease present
- Presents in 3rd-4th decade of life - Genetically associated with HLA-DR3
- Genetically associated with HLA class II (DR3, - Common among females
DR4)
- Patients have low serum cortisol levels in the
presence of elevated levels of corticotrophin.
- Autoantibodies against
o Cortical elements
o Adrenal cell surfaces
- There is destruction of the ovarian stroma in
women with premature ovarian failure.

PITUITARY GLAND
SHEEHAN’S SYNDROME
- Lymphocytic adenohypophysitis
- Rapid decline in pituitary function
- Often in postpartum women
- Autoantibodies against pituitary cells
- Distinguished by a mononuclear infiltrate of the
pituitary and hypophysis

PARATHYROID GLAND
IDIOPATHIC HYPOPARATHYROIDISM
- Childhood disorder in type 1 polyglandular
syndrome
- Associated with complement-mediated
cytotoxicity of parathyroid cells
- Autoantibodies against endothelial cell proteins
and mitochondria

POLYGLANDULAR SYNDROMES
Type 1
- Mucocutaneous candidiasis
- Associated endocrinopathies during early
childhood
- 50% of patients develop Addison’s disease
- Manifests gonadal failure, alopecia, and
chronic hepatitis
- Has organ-specific autoantibodies
- Poorly defined defects in cell-mediated
immunity

Type 2
- AKA Schmidt’s syndrome
- Combined occurrence of IDDM/ autoimmune
thyroid disease with Addison’s disease
- Primarily in women in the 2nd/3rd decade of life
- Familial
- Genetically associated with: HLA-DR3

Type 3
- AI thyroid disease with 2 other AI disorders such
as:
o IDDM