Thyroid functions &

its disorders

Dr. D. Sudha. M.D

Professor
Department of Physiology
ANATOMY OF THE THYROID GLAND
⚫ The thyroid gland lies in the anterior
aspect of neck

⚫ Thyroid gland has a "butterfly" shape, with

two lateral lobes that are connected by the
isthmus which crosses the trachea anteriorly
at the level of the 2nd tracheal cartilage

⚫ The arterial supply to the gland is superior

thyroid artery &the inferior thyroid artery
Thyroid
 The Thyroid Hormones
Thyroxine (known as T4 or L-3,5,3',5'-tetraiodothyronine)
Triiodotyronine (T3 or L-3,5,3'-triiodothyronine).
 Thyroid gland is made up of
numerous follicle
✓ Thyroid follicles - layer of simple
epithelium surrounding a gel-like pinkish
material called colloid.

✓ The principal cell is the most numerous

cell present in the simple epithelial layer
secreting the thyroid hormones as well as
thyroglobulin, a glycoprotein.

✓ Thyroid hormones are stored

extracellularly as part of the thyroglobulin
which is the main component of the colloid.
o The size of follicles and the height of principal
cells varies even within one section of the
gland.

o Inactive gland Epithelium is flat, vesicles are

large filled with colloid with no vacuoles

o Active gland- columnar cells, vesicles are small

& colloid with vacuoles near the edge
➢ Parafollicular cell found as single cells in
the epithelial lining of the follicle Appear as
large, clear cells since they do not stain well
with hematoxylin and eosin. They are called
parafollicular cells based on their location
and clear cells (C cells) based on the
appearance of their cytoplasm.

➢ Parafollicular cells secrete Calcitonin, a

hormone that lowers the level of calcium in
the blood
Thyroglobulin

⚫ Thyroglobulin is a glycoprotein formed by the

Follicular cells
⚫ Secreted into the colloid by exocytosis
⚫ Contains Tyrosine residues which are in
contact with the follicular cell surface
Synthesis of Thyroid Hormones

1. Iodide Trapping- active transport-iodide pump

2. Oxidation of iodide to iodine-peroxidase
3. Iodination of tyrosine forming DIT & MIT
4. Coupling / condensation- T3&T4
5. Pinocytosis of thyroglobulin by the cell
6. Proteolysis & release/secretion of hormones
into plasma
7. Deiodination of DIT&MIT- iodine released-forms
second iodide pool & recycled into hormone
synthesis
Synthesis of Thyroid Hormones
 Biosynthesis of thyroid hormones

⚫ Iodide trapping : The follicular cells take up

Iodides from plasma by active transport
(Iodide pump) T.S.H. stimulates this process
⚫ Oxidation of Iodide to Iodine: Iodide is
oxidised to Iodine by the peroxidase enzyme
system
⚫ Iodination of Tyrosine: Iodine is bound to
the tyrosine at the 3 position to form 3
monoiodotyrosine(MIT) & then 5position to
form
3 5 Diiodotyrosine(DIT)
⚫ Coupling of iodinated tyrosine to form
thyronines
Oxidative coupling of 2 DIT forms
Thyroxine(T4)
Coupling of one DIT with MIT
Deiodination of T4 T3

⚫ These coupling/condensation is catalysed by

Thyroid peroxidase
⚫ Small amounts of Reverse
triiodothyronine(RT3) which is 3
3’5’triiodothyronine is also formed
⚫ RT3 is biologically inactive
⚫ The MIT, DIT T3 T4 are in peptide linkage with
thyroglobulin.

⚫ Secretion: Thyroglobulin is not released as such

into the blood.
Release of Thyoid hormones

⚫ Thyroid epithelial cells ingest colloid by

endocytosis from their apical borders –
producing vacuoles in the colloid during
activity

⚫ Colloid-laden endosomes fuse with

lysosomes, which contain hydrolytic enzymes
that digest thyroglobluin, thereby liberating
free thyroid hormones.
 Release of Thyroid
hormones(contd)

⚫ Free thyroid hormones diffuse out of lysosomes

⚫ Through the basal plasma membrane of the cell
into blood
⚫ They quickly bind to carrier proteins for transport
to target cells.

The thyroid hormones are basically two tyrosines

linked together with the addition of iodine at 3 or 4
positions on the aromatic rings. The number and
position of the iodines is important
Calcitonin From Parafollicular cells
Release of Thyroid hormones
 The Thyroid Hormones
Thyroxine (known as T4 or L-3,5,3',5'-tetraiodothyronine)
Triiodotyronine (T3 or L-3,5,3'-triiodothyronine).
The thyroid hormones are basically two tyrosines linked together with
the addition of iodine at 3 or 4 positions on the aromatic rings. The
number and position of the iodines is important
Calcitonin From Parafollicular cells
⚫ In the peripheral tissues, T4 is converted
into the more active iodothyronine T3 - brought
about by a deiodination reaction
⚫ T4 more stable - Acts as precursor or
prohormone for T3
⚫ T3 is a more potent hormone than T4 but it has a
shorter half-life.
⚫ Another conversion in the periphery:
T4 is deiodinated to an inactive form (rT3).
⚫ The precise role of rT3 is not fully understood
⚫ It is thought to regulate the amount of active
iodothyronines in the periphery.
Transport
⚫ Thyroid hormones combine with plasma
proteins, mainly Thyroid Binding Globulin
(TBG). A small proportion also bind to
albumin and prealbumin (TBPA)
⚫ Less than 1% are free (unbound) in the
plasma.
⚫ Oestrogens increase the synthesis of
binding proteins
⚫ Androgens & Glucocorticoids decrease
TBG
Cold Warmth CONTROL OF THYROID FUNCTION
Regulation of thyroid synthesis and secretion –
+ - hypothalamic-pituitary-thyroid axis
Other Regulators
⚫ Estrogen increases TSH secretion
⚫  Iodide -  T3T4 – hence  TSH
⚫ Somatostatin, Glucocorticoids – inhibits TSH
secretion
⚫ Dopamine -  TSH
Actions of TSH
⚫ via cyclicAMP
⚫ Proteolysis of Thyroglobulin-within 30mts
⚫ Iodide trapping
⚫ Iodination Hrs or days
⚫ Coupling
 Functions
⚫ Thyroid is the only endocrine gland which has the
ability to store large amounts of hormone
extracellularly rather than in the secreting cell
(enough to meet the requirements for 2 to 3 months)
⚫ Secretes the thyroid hormones Tri-iodothyronine (T3 ) and
tetra-iodothyronine (T4 thyroxin) that help to regulate
the metabolic rate
⚫ also secretes calcitonin that helps control blood calcium
concentration
⚫ Secretes thyroglobulin.
Actions of thyroid hormone on
Growth & Development
⚫ Essential for normal growth, maturation &
differentiation of most tissues of body(along with
Growth hormone) evidenced by the growth-
retardation observed in thyroid deficiency

Thyroid hormone potentiates the effect of GH

(Permissive action)
⚫ Necessary for skeletal growth & maturation
⚫ Necessary for ossification of cartilage
 Calorigenic action (Basal Metabolic Rate)
⚫ T3 and T4  the BMR of almost all the cells in
the body except brain, gonads, spleen, lung &
accessory sex organs
⚫ Normal BMR(adult male)35-40kcal/m2
bodysur/hr
⚫ So O2 consumption & heat production is
Due to  in Na K ATPase activity &
 in size & number of Mitochondria
⚫  in thyroid hormones -  body temperature
↓ heat tolerance.
⚫  in thyroid hormones - body temperature
 tolerance to cold.
⚫ Protein Metabolism
Anabolic in physiological doses

Catabolic effect on Muscle-Myopathy-

weakness
On bone – osteoporosis
⚫ On carbohydrate
metabolism(Physiological)
Two effects that balance each other
1.  peripheral utilization of glucose (insulin like
action)- hypoglycemia
2.  Blood glucose (hyperglycemia)
Intestinal absorption of glucose
glycogenolysis Neoglucogenesis
 On Lipid metabolism
⚫ Lowers circulating cholesterol levels
⚫  the excretion of cholesterol in bile
Hypo thyroidism - plasma Cholesterol
Hyper thyroidism- plasma Cholesterol
 Effect on Nervous system
⚫ Necessary for normal development & activity
⚫ Must be present in adequate amount at the time of
birth and during 1st year
⚫ Normal levels of thyroid hormone are essential
to the development of the fetal and neonatal
brain.
⚫ Effects on CNS are thought to be due to the
potentiation of their catecholamine activity.
⚫ In the absence- defective myelination &
development of dendrites decreases - Mental
retardation
⚫ In adult deficiency - electrical activity of brain,
Memory loss mental lethargy-Myxoedema madness
ON C.V.S
⚫ Increases Heart rate, force of contraction,
cardiac output and systolic pressure
⚫ Due to  adrenergic receptors which
sensitivity of heart to catecholamines
⚫  the production of Myosin with high
ATPase activity
⚫  peripheral resistance & hence  diastolic
B.P
 On Skeletal Muscle
⚫ Optimal Thyroxine level is necessary for
efficient muscle function.
⚫ There is muscle weakness both in Hypo &
hyperthyroidism
⚫ Thyrotoxic Myopathy in hyerthyroidism is due
to Protein catabolism
⚫ Reproductive System
Optimal amount is necessary for normal
gonadal function
 Thyroid hormone

Women: Menorrhagia /Amenorrhea,

infertility & loss of libido
Men: Loss of Libido
 Thyroid hormone

Women: Oligomenorrhea / Amenorrhea

Men: Impotence
On vitamins
⚫ Necessary for the conversion of Carotene
to Vitamin A in liver
So in hypothyroidism there is
carotenemia giving rise to yellow colour of
the skin
 On Digestive System

⚫ Normal levels of T4 is necessary for

normal function of digestive system-
Hyperthyroidism - diarrhoea
appetite
Hypothyroidism- constipation,
Appetite
Other actions
⚫ For the formation of surfactant in lung alveoli.
⚫ For the maintenance of lactation in females
⚫ Necessary for RBC formation
Tests for Thyroid Function

⚫ Determination of SerumT3, T4 & TSH

⚫ Measurement of Protein bound Iodine(PBI)
⚫ Radio active Iodine Uptake
⚫ BMR
⚫ Serum cholesterol
⚫ CT - Scan
 Thyroid disorders - Cretinism
⚫ Infants who are hypothyroid
from birth

⚫ Child may be normal at birth,

effects appear within a week
⚫ ALL MILESTONES OF
DEVELOPMENT DELAYED
Cause: Maternal Iodine
deficiency
 Features
⚫ Dwarfism (stunted growth)
⚫ Gross retardation of mental
growth
⚫ Failure of sexual development
⚫ Pot belly, Protruding thick
tongue, Broad nose with
depressed bridge, skin coarse,
scanty hair,
⚫  BMR,  cholesterol,  T3,T4
Early detection and treatment
necessary
CRETINISM
Hypothyroidism in Adults-
Myxoedema
Most common in women
Cause:
Iodine Deficiency, Pituitary failure ,Autoimmune disease
Features:
⚫ Puffy face
⚫ Eyelids are baggy
⚫ Upper eyelid droop (Ptosis)
⚫ Periorbital edema
⚫ Edema of hands & feet
⚫ Deposition of fluid with mucoprotein,
⚫ obesity & weight gain
⚫ Skin dry, coarse, scaly
⚫ sensitivity to cold
⚫ Excessive loss of hair- outer third of eyebrow & scalp
Myxoedema
⚫ Decreasing mental activity,slowness of
thought &speech(slow cereberation)
⚫ Memory is impaired
⚫ Voice will be hoarse
⚫ Lethargy, muscular weakness &
fatiguability
⚫ Slow pulse, low B.P.,Heart may be dilated
E.C.G shows low potential waves
Anaemia is present
Sex functions depressed
Myxoedema
Investigations

⚫ Serum cholesterol  (>300mgm/dl)

⚫ BMR (-30 to -45)
⚫ Serum PBI 
⚫ T3 T4 
⚫ TSH
⚫ Antithyroglobulin antibodies may be present
Treatment :
Synthetic Thyroxine
HYPERTHYROIDISM
(Toxic goitre, Thyrotoxicosis, Grave’s disease)
Causes
⚫ Primary – Thyroid tumor

⚫ Secondary – TSH secreting Pit. Tumor

⚫ Iatrogenic – Administration of T3, T4

⚫ Autoimmune disorder
⚫ Thyroid stimulating immunoglobulin (TSI) / Long
acting Thyroid stimulator [LATS] / TSH Receptor
Stimulating Antibody TSHR(Stim) Ab.
Features
⚫ Mild to extreme wt. Loss
⚫ Fine tremor of hands.
⚫ Exophthalmos
⚫ CVS - HR - Sleeping pulse rate – High
output failure, PP, PR (Due to Vasodilation)
⚫ RS -  Pulmonary Ventilation, GIT – Diarrhea
⚫ CNS -  excitability, nervousness, loss of
sleep, anxiety.
⚫ Skin – Warm & Moist, Heat Intolerence,
Sweating +
⚫ Thyrotoxic myopathy – Muscle weakness,
fatigue, osteoporosis
⚫ Vitamin deficiency
Exophthalmos

⚫ Protrusion of the eye ball – Staring look, wide open

eyes
⚫ Sclera is seen above the cornea

⚫ In severe cases – stretching of optic nerve – Loss of

vision
⚫ Damage to the eye – because they cannot close the
eye
Cause: swelling of the retro – orbital tissue, &
degenerative changes of the extra occular muscles
(Due to TSI action)
 Goitre
⚫ Swelling in the neck – enlargement of the
thyroid gland
⚫ Symptomless – simple goitre – due to
iodine deficiency – occurs in mountain
dwellers – ENDEMIC GOITRE
⚫ Hypofunction - Inadequate Iodine - T3, T4
-  TSH
⚫ Goitrogens – Brascica family (Cabbage,
turnip) & Antithyroid drugs
ANTITHYROID DRUGS
⚫ Inhibit trapping if iodide: by competitive
inhibition – thiocyanate, percholorate

⚫ Inhibit oxidation, binding and coupling of iodine:

Methyl/propyl thiouracil, carbamizole

⚫ Iodides in large amounts have anithyroid effects

⚫ Iinhibit binding of iodine
⚫ Inhibit the effects of TSH on the gland
⚫ Diminish the release of the hormone

⚫ Beta adrenergic blockers –In hyperthyroidism

Thank You