Etiology and Pathogenesis of Thyrotoxicosis with a little light on clinical manifestations.

1. MOHIT SONI
MBBS 2nd Prof.

2. Thyro- thyroid
Toxic- morbid
Osis- condition of
 hyper-metabolic
state of thyroid
 elevated levels of free
T3 & T4 hormones,
 commonly seen in
women
 a/w infiltrative
opthalmopathy and
dermopathy.

3. THYROTOXICOSIS/HYPERTHYROIDISM
Thyrotoxicosis: syndrome of excess
FT3 and FT4
Hyperthyroidism: indicates thyroid
gland overactivity leading to
thyrotoxicosis
Thyrotoxicosis can result from
causes other than hyperthyroidism

4. pathogenesis
THYROTOXIC-
OSIS
PRIMARY
SECONDARY
TERTIARY

5. NEGATIVE FEEDBACK IS
INEFFECTIVE

6. THYROTOXICOSIS
A/W HYPERTHYROIDISM
PRIMARY (99%)
• Graves disease (diffuse
toxic hyperplasia)-85%
• Toxic multinodular goiter
• Toxic adenoma
SECONDARY
• TSH secreting pituitary
adenoma
TERTIARY
• Hypothalamic disease
NOT A/W
HYPERTHYROIDISM
• Subacute granulomatous
thyroiditis (de Quervains)
• Subacute lymphocytic
thyroiditis
• Struma ovarii,
choriocarcinoma,H.mole,
metastatic thyroid
carcinoma
• Exogenous thyroxin intake
(factitious thyrotoxicosis)

7. GRAVE’S DISEASE
TSH Antibody mimics action of TSH increased T3 & T4.

8. GROSS MORPHOLOGY
 Thyroid is
moderately, diffusely
& symmetrically
enlarged
 Weight 80-
90gm(normal 20-
30gm)
 Cut section-
homogenous, red-
brown & meaty

9. HISTO-PATHOLOGY
 Epithelial hyperplasia &
hypertrophy
 Formation of papillary
infoldings of epithelium
into lumina of follicles.
 Colloid-diminished thin ,
pale with scalloped
margins.
PAPILLARY
INFOLDINGS
SCALLOPED
MARGINS

10. TOXIC MULTINODULAR GOITER

11. GROSS MORPHOLOGY
 Multilobulated,
asymmetrically enlarged
gland.
 Cut section- irregular
nodules containing
variable amount of
brown gelatinous colloid.

12. HISTO-PATHOLOGY
 Colloid rich follicles lined
by flattened inactive
epithelium.
 Follicles are of varied
sizes.
 Areas of Haemorrhages
are seen.
 Fibrous scarring with foci
of calcification.
COLLOID RICH
FOLLICLE
VARIED SIZE OF
FOLLICLES

13. FOCI OF
CALCIFICATION
HAEMORRHAGE
SCARRING
SECONDARY
CHANGES

14. Sub acute lymphocytic thyroiditis
 It is a condition of thyroid resulting in its
destruction
 Due to formation of anti- thyroid peroxidase
antibodies thus causing TRANSIENT
HYPERTHYROIDISM

15. Sub acute granulomatous thyroiditis
Initiated by a viral infection,
This exposure leads to stimulation of T- lymphocytes.
damages thyroid follicular cells.
IT IS ALSO A CAUSE OF TRANSIENT HYPERTHYROIDISM

16. STRUMA OVARII
 Ovarian teratomas
{arising from totipotent
cells}, may contain a
thyroid tissue in it, thus
causing increased
thyroid hormones
levels.

19. Cardiac changes
 Elevated Cardiac Contractility
 Tachycardia
 Palpitations
 Cardiomegaly
 Arrythmias {most profoundly supra ventricular}
 Microscopic changes= focal lymphocytic &
eosinophilic infiltration, mild fibrosis, myofibril
fatty change & an increase in number & size of
mitochondria

20. GASTROINTESTINAL
 Hyper- motility
of gut
 Mal- absorption
 Diarrhoea
 Voracious
appetite !!

21.  OCULAr changes
OVER STIMULATION OF
SUPERIOR TARSAL !!!
WIDE, STARING & LID-LAG
PRESENT !!!

22. GRAVE’S EXOPTHALMOS
 Marked infiltration of retro-
orbital space by T cells.
 Accumulation of extra
cellular matrix components,
specifically GLYCOSAMINO-
GLYCANS- hyaluronic acid
and chondroitin sulfate.
 Fatty infiltration
 Swelling of extra ocular
muscles.

23. SKELETAL changes

24.  THYROID STORM
Severe form of thyrotoxicosis
characterized by
 Caused due to- untreated
over-active thyroid gland
 Rapid & Irregular heart beat
 High temp.
 Vomiting
 Diarrhoea
 Mental agitation

25. SUMMARY
Thyrotoxicosis can be caused by many
etiological agents, but the main causes are
Grave
disease
Toxic
multinodular
goiter
Toxic
adenoma