Thyroid & Parathyroid Glands

By
Nutan Prakash
Asstt. Professor
Department of Biotechnology
Shree M. & N. Virani Science College
 Thyroid gland
• Largest endocrine gland, located anterior to
the thyroid cartilage of the larynx in the
neck. It is bi-lobed with a connecting
isthmus (a narrow non glandular median
part).

• The thyroid gland secretes three hormones:

• Thyroid follicular cells produces Thyroxin
(T4) & Tri-iodothyronine (T3)
• C Cells: Calcitonin (Involved in calcium & phosphate
homeostasis).

• Iodine is essential for the synthesis of thyroid hormones.

• Thyroglobulin is a glycoprotein and precursor for the

synthesis of T3 and T4. T4 and T3 contain four and three
atoms of iodine respectively, therefore, they are named so.
 T3 is secreted in smaller amounts but it is more active and
several times more potent than T4.
 Thyroid hormones stimulate the metabolic activities and
increases the oxygen consumption in most of the tissues of the
body (exception brain, lungs, testes and retina).
 Calcitonin is secreted when calcium level is high in the blood,
it then lowers the calcium level by suppressing release of
calcium ions from the bones.
Histology
 Thyroid tissue is composed of numerous closed spherical follicles,
each comprising of a rim of simple cuboidal epithelial cells
surrounding a mass of colloidal storage protein called thyroglobulin.
 Lying in between the thyroid follicles are groups of separate
larger epithelial cells, the parafollicular C cells, responsible for
the secretion of a peptide hormone calcitonin, involved in the
control of calcium metabolism.
Mechanism of Action of Thyroid Hormones

 Both T3 and T4 enter the target cell membrane by passive diffusion (and

also by active uptake), but T4 is immediately converted to the more active

T3 and inactive reverse T3 forms.

 Unlike the steroid hormones, T3 enters the cell nucleus directly via a

nuclear transport process (and an additional process involving a cytosolic

thyroid hormone binding protein [CTBP]), and reacts with specific thyroid

hormone receptors (TRs), already bound to target DNA regulatory elements;

 a nuclear protein TRAP (thyroid hormone receptor auxiliary protein) is

required for efficient binding of TRs to DNA.

The consequent increase (or decrease) in synthesis of specific proteins, mediates the

thyroid hormone ‘response’ of the target cell. T3 can also interact directly with

mitochondria to increase energy production.

 Hyperthyroidism

Grave's disease/ Basedow's disease/ Parry's disease Exophthalmic Goitre is caused

due to over secretion of thyroid hormones. It is a disease in which the person produces
antibodies that mimic the action of TSH but are not regulated by normal negative feed
back control. its symptoms include protrusion of eye balls, loss of weight, rise in body
temperature, rapid heart beat, nervousness, tremor and restlessness.

SIMPLE GOITRE EXOPTHALMIC GOITRE or GRAVE

•Due to deficiency of Iodine in the diet. disease
•Goitre only in neck, no effect on eyes •Due to over secretion of thyroid gland.
•Increased BMR, B.P and heart beat. •Goitre accompanied in eyes
•Restlessness and sluggishness. •Low BMR, B.P and heart rate.
Hyperthyroidism (thyrotoxicosis)
 Most commonly caused by an overactivity of the thyroid
gland itself resulting from an autoimmune condition known
as Graves’ disease. The serum of such patients contains
specific thyroid-stimulating immunoglobulins (TSIs) that
bind to the TSH receptors on the follicular cells, and like
natural TSH, stimulate the cells to produce thyroid
hormone.
 The disease is 5–8 times more prevalent in 40–50 year old
females than in males, and is commonly associated with
other autoimmune disorders such as myasthenia gravis,
Addison’s disease, and pernicious anaemia.
 The major symptoms of Graves’ disease are:
 High BMR- a general acceleration of body metabolism; increased
heat production leading to heat intolerance, excessive sweating and
warm skin.
 Weight loss (despite a good appetite), due to muscle wasting
(thyrotoxic myopathy); diarrhoea; menstrual disturbances.
 Rapid pulse, tremor, palpitations and other tachycardias (atrial
fibrillation in the elderly), hypertension, Restlessness, overanxiety,
nervousness, irritability, hyperexcitability and emotional instability.
 Eye changes- possible eyelid retraction and protrusion of the
eyeballs (exophthalmos) in about 50% of patients, due to thickening
of the extraocular muscles caused by lymphocyte infiltration and
deposition of mucopolysaccharide and oedema around the orbital
soft tissues.
 Diffuse toxic goitre (symmetrical swelling of the thyroid).
Thyroid Hyposecretion
 Adult Hypothyroidism
 Hypothyroidism can develop as a result of a functional
defect in the thyroid itself (primary hypothyroidism) or
as a consequence of reduced stimulatory input from
the pituitary (secondary hypothyroidism).
 Primary hypothyroidism is most commonly caused by
an autoimmune destruction of the thyroid gland,
leading to a deficiency in the amounts of circulating
thyroid hormones (Hashimoto’s thyroditis).
 The condition is typically slow to develop, has a
strong familial tendency and is most prevalent in
middle-aged women, although it may also occur in
men at any age.
 A painful diffuse swelling of the gland (goitre) may be
present in the early stages of the disease.
 The main symptoms of primary hypothyroidism include:
 Low BMR- a general slow-down of body processes, slow
movements and reflexes, muscle cramps.
 Weight gain and cold intolerance (impaired calorigenesis),

decreased sweating, constipation.

 Myxoedema- characteristic skin changes; the skin of both the

hands and face thickens and becomes coarse, dry and puffy,
due to subcutaneous deposition of semifluid
mucopolysaccharide material; hair loss.
 Tiredness/lethargy- weakness, slowness of thought, memory

impairment, depression, slow, hoarse speech, bradycardia.

 Serum T3/T4, levels are low, but TSH levels are high due to a

lack of negative feedback effects.

 Treatment. Thyroid hormone replacement therapy is necessary for life;

this is administered in the form of thyroxine sodium tablets (Eltroxin; 50

μg daily initially, rising to 100– 200 μg daily), or liothyronin. sodium

(T3) (Tertroxin; 20 μg tablets every 8 hours or by slow intravenous

injection), which has a more rapid onset of action, useful in cases of

severe hypothyroidism (myxoedema coma with hypothermia).

 Frequent measurements of serum TSH are made to check for adequacy of

the replacement therapy; patients also need to be advised on the

importance of taking the thyroid hormone replacements on a regular basis.

 CHILDHOOD (CONGENITAL)
HYPOTHYROIDISM
 Uncorrected hypothyroidism at birth (usually due to
ectopic location or failure of proper development of the
thyroid) leads to cretinism; infant subjects are dwarfed,
with a protruding tongue and abdomen, mentally retarded,
and have coarse scanty hair and dry, yellowish skin.
 Early diagnosis is essential (based on TSH assay),
followed by thyroxine replacement therapy (10 μg/kg up
to 50 μg daily).
 Development of primary hypothyroidism in early childhood,
(juvenile hypothyroidism), is usually characterized by stunted
growth, delayed sexual development and mental slowness,
usually reflected by poor performance at school.
 The replacement dose of thyroxine (25–200 μg daily) needs to be
carefully adjusted to ensure that catch-up growth progresses at a
normal rate.
 Some other important causes of hypothyroidism include:

1. Surgical removal (partial thyroidectomy) or radioactive iodine

treatment of thyroid tissue for the relief of hyperthyroidism.

2. Inadequate TSH production due to pituitary or hypothalamic

disease; this rare secondary condition is not normally accompanied

by a goitre or myxoedema, but is associated with deficiencies in the

other pituitary trophic hormones, and is therefore treated with a

combination of glucocorticoid/sex steroid and (later) thyroid

hormone replacement therapy.

3. Iodine deficiency: endemic goitre may result from a low dietary
intake of iodide (e.g. from seafood); this is pretty rare in Western
countries where iodized table salt is generally available, but may
still occur in certain parts of the world that are distant from the sea,
or in mountainous regions.
4. Amiodarone administration: the iodine-containing cardiac anti-
arrhythmic agent amiodarone (Cordarone X) can interfere with the
peripheral conversion of T4 to T3, leading to an increase in serum
T4 (and inactive rT3) levels; significant clinical symptoms of
hypothyroidism (or even hyperthyroidism) may develop in some
patients taking this drug, that usually reverse within a few weeks
following drug withdrawal. The drug is not therefore recommended
for use in patients with a history of thyroid disease.
Normal Regulation of Thyroid Hormones

 .
 Parathyroid glands
 The parathyroid glands consist of
four separate glands located on the
posterior surface of the lobes of the
thyroid gland.
 They consist of two types of cells
Chief cells (small) and Oxyphil
cells ( large).
 The chief cells secrete
parathormone or Collip's hormone
which is synthesized as a
preprohormone, which loses 25
amino acids to become the active
parathormone.
 This hormone regulates calcium and phosphate balance between
the blood and other tissues. The release of parathormone
increases blood calcium to normal by drawing calcium from the
bones into the plasma, by increasing calcium absorption in the
digestive tract, and by reducing loss of calcium in the urine.
 PTH has an effect that opposes the effect of calcitonin.
 The oxyphil cells are larger with a less granular cytoplasm, and
have no known hormonal function.
Control of Release
 Unlike other endocrine hormones, PTH secretion is not
controlled by the anterior pituitary gland: its secretion from
parathyroid chief cells is determined by the circulating blood
level of ionized Ca2+.
 A low plasma Ca2+ concentration directly stimulates PTH release
by the parathyroid glands, and a high level suppresses it
(negative feedback).
Hypersecretion (Hyperparathyroidism)

 Primary hyperparathyroidism is a fairly prevalent, and slowly developing

condition that is about 2–3 times more common in adult women than in men.
 The excess secretion of PTH causes hyperclacaemia and phosphaturia (excess
loss of phosphate in the urine) resulting in a low plasma phosphate level
(hypophosphataemia); a raised level of urinary cAMP may also be present.
 The disorder may be caused by a single chief cell tumour (adenoma) or
enlargement of one or all four of the parathyroids (hyperplasia) or by a
parathyroid carcinoma (rare).
 A secondary overactivity and hyperplasia of all four parathyroids
(not associated with hypercalcaemia) can also develop as a
compensatory response to longstanding hypocalcaemia due to
intestinal calcium/vitamin D malabsorption (or deficiency) or
chronic renal failure.
 PTH levels remain elevated until the cause of the hypocalcaemia
can be corrected. Mild hyperparathyroidism may produce few
clinical signs initially; however, chronic PTH excess may result
in symptoms directly attributable to the elevated blood calcium
 The main symptoms of hyperparathyroidism include:
1. Tiredness, depression, weakness, lethargy, dizziness,
excessive thirst, nausea, vomiting and dehydration (due to
excessive loss of urine), psychiatric disorders, cardiac
arrhythmias and possible heart block.
2. Renal stones (calculi) made from insoluble calcium
phosphate (or oxalate), due to increased urinary excretion
of Ca2+ and phosphate; this may cause renal colic and
haematuria (appearance of blood in the urine), eventually
leading to renal failure. Gallstones may also occur.
3. Gastrointestinal complaints: abdominal pain, constipation,
dyspepsia, peptic and duodenal ulceration.

4. Bone lesions due to generalized loss (resorption) of calcium

from bone. In severe cases, osteitis fibrosa (bone cysts)
accompanied by bone pain and increased incidence of fractures
can occur.

5. Hyperparathyroidism has been described as a disease of

‘bones, stones and abdominal groans.
Hyposecretion (Hypoparathyroidism)

 Lack of PTH causes hypocalcaemia and a high blood phosphate

level (hyperphosphataemia) due to increased reabsorption of
tubular phosphate. The most common cause is accidental damage
of the parathyroids during thyroid surgery (surgical
hypoparathyroidism).
 A persistent low plasma calcium level can induce;
1. Hyper-excitability of nerve and neuromuscular tissue,
characterized by a tingling sensation (paraesthesia: ‘pins and
needles’) in the face or fingers, muscle cramps and spasms
(particularly in the hands and feet) leading to hypocalcaemic
tetany and even epileptic seizures/convulsions.
2. Chvostek’s sign—a twitching of the facial muscles following
light tapping over the facial nerve, and
3. Trousseau’s sign—a characteristic tetanic spasm of the wrist
and fingers following over-inflation of a sphygmomanometer
cuff placed over the upper arm for more than three minutes.
4. Dental abnormalities, dry scaly skin and hair, brittle nails and
cataracts may also be present in more chronic persistent cases.