Lecture 7

Clinical Immunology
6-11-2022
Immunological Diseases of
the Endocrine System
 Diabetes Mellitus Type I A:
• DM has two types I and II.

• Type I diabetes mellitus is an autoimmune

disease that leads to the destruction of
insulin-producing pancreatic beta cells and
absolute deficiency of insulin.
 Etiology of T1DM
• The etiology is unknown but there is genetic predisposition
and most patients have family history of DM type I.

• Some studies have found an increased development of

T1DM in children born to a mother that had Coxsackievirus
or another Enterovirus infection during pregnancy.
 Immunological features of T1DM
The immunological features of DM type I are noted
by the presence of circulating pancreatic
autoantibodies, these antibodies include:
1. Islet cell cytoplasmic antibodies (ICA),
2. Insulin autoantibodies (IAA),
3. Glutamic acid decarboxylase (GAD) antibodies.
•Type I DM is one of the most frequent chronic
diseases in children but can start at any age.
•The patient has hyperglycemia due to
immunological destruction of islet beta cell with
decrease in insulin secretion.
 Graves' disease:

•It is the most common cause of hyperthyroidism.

•It is an autoimmune disease result from production
of autoantibodies bind to TSH receptor on thyroid
cells, these antibodies named anti-TSHR antibodies.
•The anti-TSHR antibodies are the hallmark of the
disease.
 Effect of anti-TSHR Abs
•The anti-TSH Abs have action on receptors similar to
TSH action so Graves’ disease patient has
hyperthyroidism (low serum TSH, high serum T3, high
serum T4), goiter (enlarged thyroid gland),
exophthalmos, tremor, weight loss, heat intolerance,
sweating, insomnia, anxiety, and palpitation.
 Hashimoto's disease

•It is the second common cause of hypothyroidism

after the inadequate dietary intake of iodine.
•It is also known as Hashimoto's thyroiditis, an
autoimmune disease in which the thyroid gland is
gradually destroyed via cell-mediated immune
response and antibody-mediated immune response.
•There is elevated level of anti-thyroid peroxidase
antibodies (TPO Ab) in the serum, but seronegative
(without circulating autoantibodies) thyroiditis is also
possible.
The patient has fatigue, weight gain, feeling cold,
constipation, depression, possible goiter, and slowed
heart rate. The patient has features of hypothyroidism:
elevated TSH, decrease levels of T3 and T4.
 Addison’s disease
•It is an autoimmune disease with chronic disorder of adrenal
cortex.
•It is characterized by deficient production of adrenocortical
(steroid) hormones together with increased secretion of pituitary
adrenocorticotrophic hormone (ACTH).
•The presence of antibodies to the adrenal cortex enzyme
21-hydroxylase is characteristic of Addison's disease.
•Pathologic examination of the adrenal glands in autoimmune
Addison's disease reveals fibrosis with a mononuclear cell
infiltrate.
 •The patient has skin hyperpigmentation, hypoglycemia,
low blood pressure, GIT symptoms, weakness, weight
loss, and even death.
•It is diagnosed by the
1. Failure of serum cortisol to rise after an ACTH
stimulation test in the presence of elevated basal
ACTH levels, and
2. usually (>90%) 21-hydroxylase autoantibodies are
present.
 Autoimmune hypoparathyroidism:

•It is immune-mediated destruction of the parathyroid

glands.
•Anti-CaSR antibodies activated the calcium-sensing
receptor (CaSR) causing primary hypoparathyroidism.
•It is mostly disease of children.
•The parathyroid hormone regulates the calcium
metabolism in the body by increase the blood calcium
concentration.
•So, decrease in PTH cause hypocalcemia.
•The patient has clinical features of hypocalcemia:
spasm, periorbital paresthesia, anxiety, seizures, muscle
tone increased, orientation impaired, dermatitis,
impetigo, Chvostek sign and cardiomyopathy.
•The serum calcium level is low (5-7 mg/dL) while
normal level is 8.5 to 10.2 mg/dL, and
•the phosphorus level is elevated (7-12 mg/dL) while
normal level is 2.8 to 4.5 mg/dL.
•Levels of PTH (parathyroid hormone) are low when
measured by immunological assay.
 Premature ovarian failure:
Premature ovarian failure (POF) is defined as cessation (stop) of
ovarian function before the age of 40 years; the female has
amenorrhea, elevated gonadotropin levels, and hypoestrogenism
before age 40. The diagnostic criteria include:
1. amenorrhea or oligomenorrhoea for at least four months and
2. increased follicle-stimulating hormone (FSH) levels > 25
IU/L (normal1.5 to 12.4 IU/L) measured twice (with a
four-week interval).
 Immunological features of POF
1. Ovary: lymphocyte infiltration and other
inflammatory cells.

2. Serum: demonstration of circulating ovarian

antibodies in serum samples.