Thyroid Disorders

Dr Raghuveer Choudhary
Control Of Thyroid Hormone
Secretion
Control Of Thyroid Hormone
Secretion
Control Of Thyroid Hormone
Secretion

 TRH:
 Stimulus TSH secretion by anterior pituitary.
 In the absence of TRH, the secretion of TSH (and
T4) decreases to very low levels.
 THS acts on thyroid gland, where it increases
the secretion mainly of T4 by thyroid gland.
Control Of Thyroid Hormone
Secretion
Regulation of Secretion
 primary control is via pituitary TSH
 under the control of hypophyseotrophic TRH, and
 feedback from circulating T3 & T4
 211 AA glycoprotein made of 2 subunits, a & b
 each subunit is synthesised from a separate precursor
molecule and the TSH-a unit is identical to the a-
subunit of FSH & LH and differs only slightly from
hCG-a
 secretion is also,
  by stress and warmth
  by cold
Control Of Thyroid Hormone
Secretion
 Because the main
circulating form is T4
 T4 that is responsible
for most of the negative
feedback.
Effects of TSH on the Thyroid
When the pituitary is removed, thyroid function is depressed and the gland
atrophies; when TSH is administered, thyroid function is stimulated.

Within a few minutes after the injection of TSH, there are increases in iodide
binding; synthesis of T3, T4 , and iodotyrosines; secretion of thyroglobulin into the
colloid; and endocytosis of colloid. Iodide trapping is increased in a few hours;
blood flow increases;

and, with chronic TSH treatment, the cells hypertrophy and the weight of the gland
increases.

Whenever TSH stimulation is prolonged, the thyroid becomes detectably enlarged.

Enlargement of the thyroid is called a goiter.
Whenever TSH stimulation is prolonged,
the thyroid becomes detectably enlarged.
Enlargement of the thyroid is called a
goiter.
Control Of Thyroid Hormone
Secretion

 Decreased Free T4: Increased TSH

 Increased Free T4: Decreased TSH
 Changes in circulating T3 have minimal
effects on TSH secretion.
Overall Effects of Thyrotropin
(TSH) on the Thyroid
 TSH rapidly increase all steps in the
synthesis and degradation of thyroid
hormones:
 Iodide trapping, Thyroglobulin synthesis and
exocytosis into the follicular lumen, Pinocytotic
reuptake of iodinated thyroglobulin back into the
thyroid follicular cell , Secretion of T4 into the
blood.
 Overall Effects of Thyrotropin
(TSH) on the Thyroid
 Changes that occur more slowly
 Increased blood flow to the thyroid gland
 Increased hypertrophy of the thyroid cells, which
initially leads to increased size of the gland
Overall Effects of Thyrotropin
(TSH) on the Thyroid
 Goiter
 Excessive amounts of TSH eventually produce
a goiter.
 A goiter is simply an enlarged thyroid and does
not tell functional status.
 A goiter can be present in hypo-, hyper-, and
euthyroid states.
 There is no correlation between thyroid size
and function.
Patho-physiology:
Thyroid Gland
 Euthyroid: Normal thyroid function
 Hypothyroidism:
 Primary: Thyroid gland
 Secondary: Pituitary gland
 Tertiary: Hypothalmus
 Hyperthyroidism
 Primary
 Secondary
 Tertiary
Hypothyroidism
The syndrome of adult hypothyroidism is
generally called myxedema, although this term is
also used to refer specifically to the skin changes
in the syndrome.

Hypothyroidism may be the end result of a

number of diseases of the thyroid gland, or it may
be secondary to pituitary or hypothalamic failure.

In the latter two conditions, the thyroid remains

able to respond to TSH. Thyroid function may be
reduced by a number of conditions
For example, when the dietary iodine intake falls
below 50miro g/d, thyroid hormone synthesis is
inadequate and secretion declines.

As a result of increased TSH secretion, the thyroid

hypertrophies, producing an iodine deficiency
goiter that may become very large.

Such "endemic goiters" have been substantially

reduced by the practice of adding iodide to table
salt
Goiter
. Drugs may also inhibit thyroid function. Most do
so either by interfering with the iodide-trapping
mechanism or by blocking the organic binding of
iodine.

In either case, TSH secretion is stimulated by the

decline in circulating thyroid hormones, and a
goiter is produced.
.The thioureylenes, a group of compounds related
to thiourea, inhibit the iodination of
monoiodotyrosine and block the coupling reaction.
The two used clinically are propylthiouracil and
methimazole .

Iodination of tyrosine is inhibited because

propylthiouracil and methimazole compete with
tyrosine residues for iodine and become iodinated.

In addition, propylthiouracil but not methimazole

inhibits D2 deiodinase, reducing the conversion of
T4 to T3 in many extrathyroidal tissues.
In normal individuals, large doses of iodide act
directly on the thyroid to produce a mild and
transient inhibition of organic binding of
iodide and hence of hormone synthesis. This
inhibition is known as the Wolff–Chaikoff
effect.
In completely athyreotic adults, the BMR falls to
about 40%. The hair is coarse and sparse, the
skin is dry and yellowish (carotenemia), and cold
is poorly tolerated.
Mentation is slow, memory is poor, and in some
patients there are severe mental symptoms
("myxedema madness").
Plasma cholesterol is elevated
 Hypothyroidism in Infancy
 Cretinism:
 Cretinism is caused by extreme
hypothyroidism during fetal life,
infancy, or childhood.
 This condition is characterized
especially by failure of body
growth and by mental
retardation.
CRETINISM
Caused by extreme hypothyroidusm during fetal
life, infancy or childhood.

Characteristics:
a. Failure to grow
b. Mental retardation
c. Skeletal growth us characteristically more
inhibited than is soft tissue growth

- child is obese, stocky and short appearance

-tongue becomes large in relation to skeletal growth
CAUSES:

1. Congenital Cretinism – results from congenital

lack of a thyroid gland – failure of thyroid gland
to produce thyroid hormone

2. Endemic Cretinism – iodine lack in the diet

. Children who are hypothyroid from birth
or before are called cretins. They are
dwarfed and mentally retarded.
Worldwide, congenital hypothyroidism is
one of the most common causes of
preventable mental retardation.
Cretin
 Causes of Congenital Hypothyroidism

Maternal iodine deficiency

Fetal thyroid dysgenesis

Inborn errors of thyroid hormone synthesis

Maternal antithyroid antibodies that cross the placenta

Fetal hypopituitary hypothyroidism

If treatment is started at birth, the prognosis for
normal growth and development is good, and
mental retardation can generally be avoided; for
this reason, screening tests for congenital
hypothyroidism are becoming routine.

When the mother is hypothyroid as well, as in

the case of iodine deficiency, the mental
deficiency is more severe and less responsive to
treatment after birth
Hyperthyroidism
 Hyperthyroidism 

overactive thyroid gland

hyperthyroidism is characterized by
nervousness; weight loss; hyperphagia; heat
intolerance; increased pulse pressure; a fine
tremor of the outstretched fingers; warm,
soft skin; sweating; and a BMR from +10 to
as high as +100.
Causes of Hyperthyroidism.

Thyroid overactivity 
  Solitary toxic adenoma
  Toxic multinodular goiter
  Hashimoto thyroiditis
  TSH-secreting pituitary tumor
  Mutations causing constitutive activation of TSH receptor

  Other rare causes

Extrathyroidal 
  Administration of T3 or T4 (factitious or iatrogenic
hyperthyroidism)

 Ectopic thyroid tissue

,the most common cause is Graves disease (Graves
hyperthyroidism), which accounts for 60–80% of the
cases.
This is an autoimmune disease, more common in
women, in which antibodies to the TSH receptor
stimulate the receptor.
This produces marked T4 and T3 secretion and
enlargement of the thyroid gland (goiter). However,
due to the feedback effects of T4 and T3, plasma TSH
is low, not high.
Patient with exophthalmic
hyperthyroidism
 Another hallmark of Graves
disease is the occurrence of
swelling of tissues in the
orbits, producing protrusion
of the eyeballs
(exophthalmos). This occurs
in 50% of patients and often
precedes the development of
obvious hyperthyroidism.
Patho-physiology:
Thyroid Gland

Hyperthyridism Hypothyroidism
Thyroid function test ( TFT)
 Assess the function of Hypothalmmic-
Pituitary – Thyroid axis:
 T3, T4
 TSH
Pathologic changes
In Thyroid hormone secretion