- Most common cause of hypothyroidism worldwide- Iodine deficiency.
- In areas of iodine sufficiency, most common cause- 1Autoimmune disease
(Hashimoto's thyroiditis) and 2Iatrogenic
causes (treatment of hyperthyroidism).
- Congenital Hypothyroidism
- Types-
1.
Transient- due to
1maternal TSH -R blocking antibodies or 2administration of
antithyroid drugs
2.
Permanent- due to
a.
Thyroid gland
dysgenesis in 80–85%
b.
Inborn errors of
thyroid hormone synthesis in 10–15%
c.
TSH -R antibody-mediated in 5%
o
The developmental
abnormalities are twice as common in girls.
o
Clinical features
§
prolonged
jaundice, feeding problems, hypotonia, enlarged tongue, delayed bone
maturation, and umbilical hernia
§
Symptoms &
signs- Harrison , Table 335-5 Signs and Symptoms of
Hypothyroidism (Descending Order of Frequency)
o
Diagnosis &
Treatment
§
neonatal
screening- measurement of TSH or T4
levels in heel-prick blood specimens.
§
Rx- T4
is instituted at a dose of 10–15 μg/kg per day & dose is adjusted by close
monitoring of TSH levels.
·
Autoimmune
Hypothyroidism
o
M:F = 1:4
o
Types
§
With Goitre – Hashimoto’s /goitrous thyroiditis
§
Without Goitre- Atrophic
thyroiditis
o
Phases
§
Subclinical Hypothyroidism- a phase of compensation when normal thyroid hormone
levels are maintained by a rise in TSH .
§
Clinical
hypothyroidism /Overt hypothyroidism- symptoms
more readily apparent at this stage (usually TSH
>10 mU/L).
o
Pathogenesis
§
In Hashimoto's
thyroiditis-
o
h lymphocytic infiltration (activated CD4+, CD8+ T
cells & B cells) of the thyroid with germinal center formation
o
Atrophy of the
thyroid follicles asso. with oxyphil metaplasia, absence of colloid
o
Mild to moderate
fibrosis.
§
In atrophic
thyroiditis,
o
Extensive
fibrosis
o
i lymphocyte infiltration
o
Nearly absent
thyroid follicles.
§
Predisposing Factors-
o
Genes-
§
HLA-DR3, -DR4 and -DR5
§
CTLA-4, a T cell–regulatory gene
o
High iodine
intake
§
CD8+ cytotoxic T
cells destroy their targets by either 1perforin-induced
cell necrosis or 2granzyme
B–induced apoptosis
§
Autoantibodies-
o
Anit-Tg and anti-TPO
- transplacental passage has no effect on the fetal thyroid.
o
Anti-TSH -R - transplacental passage may induce transient
neonatal hypothyroidism.
o
Clinical features
§
Signs & Symptoms- Harrison
§
Goitre
§
Myxedema-
non-pitting swelling of the skin due to increased dermal glycosaminoglycan content
which traps water.
§
i libido & fertility in both sexes.
§
Carpal tunnel and
other entrapment syndromes
§
Impairment of
muscle function with stiffness, cramps, and pain.
§
Hashimoto's
encephalopathy
o
steroid-responsive syndrome associated with TPO antibodies, myoclonus, and slow-wave activity
on EEG, but the relationship with thyroid autoimmunity or hypothyroidism is not
established
§
associated with
other autoimmune diseases
o
Vitiligo
o
Pernicious anemia
o
Addison's disease
o
Alopecia areata
o
Type 1 diabetes
mellitus
o
Celiac disease
o
Dermatitis
herpetiformis
o
Chronic active
hepatitis
o
Rheumatoid
arthritis
o
Systemic lupus
erythematosus (SLE )
o
Sjögren's
syndrome.
o
Lab. Evaluation
o
Differential
diagnosis
§
Iatrogenic
hypothyroidism
§
Secondary
hypothyroidism
o
Treatment
§
Clinical
Hypothyroidism-
§
Subclinical
Hypothyroidism-\
o
No Rx, when TSH levels < 10mU/L
o
Rx started if TSH h for >3
mths.
o
Rx- with a
low dose of levothyroxine (25–50 μg/d) with the goal of normalizing TSH
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