HYPERTHYROIDISM-lecture.pptfjffjjfjfjfjfj

Pharmacology

1. HYPERTHYROIDISMHYPERTHYROIDISM

2. background background
•Clinical syndrome resulting from exposure
of tissues to excess circulating levels of
free thyroid hormones
•It is five times more commoner in females

3. •Highly vascular gland located anteriorly in the
lower neck
• Synthesises and stores two important but
different types of hormones:
➢Iodothyronine hormone –Thyroxine (T4)
➢Triiodothyronine(T3) –released from T4 in the
peripheral tissues ; most active hormone
➢essential for normal growth and development
•Important role in energy metabolism

4. •The function of the thyroid gland is regulated
by a feedback mechanism involving
hypothalamic-pituitary axis in the brain.
• TSH from the anterior pituitary gland which is
regulated by the TRH from the
hypothalamus.
TSH stimulate T4 and T3 production from the
glands

5. THYROID HORMONESTHYROID HORMONES
•THYROXINE
• T4: (Thyroxine) is made exclusively in
thyroid gland
• Secretion of T4 to T3 : 10:1
• Potency of T4 to T3; 1:10
• T4 is the most important source of T3 by
peripheral tissue deiodination“ T4 to T3 “

6. Biosynthesis of Thyroid HormonesBiosynthesis of Thyroid Hormones
•Once taken up by the thyroid gland, iodide undergoes a series
of enzymatic reactions that convert it into active thyroid
hormone.
• The first step is the transport of iodide into the thyroid gland by
an intrinsic follicle cell basement membrane protein called
the sodium/iodide symporter (NIS). This can be inhibited by
such anions as thiocyanate (SCN-), pertechnetate (TcO4-),
and perchlorate (ClO4-).
•At the apical cell membrane a second I- transport enzyme
called pendrin controls the flow of iodide across the
membrane. Pendrin is also found in the cochlea of the
inner ear and if deficient or absent, a syndrome of
deafness and goiter, called Pendred's syndrome

7.  At the apical cell membrane, iodide is oxidized
by thyroidal peroxidase to iodine, in which form
it rapidly iodinates tyrosine residues within the
thyroglobulin molecule to form
monoiodotyrosine (MIT) and diiodotyrosine
(DIT).
This process is called iodide organification.
 Thyroidal peroxidase is transiently blocked by
high levels of intra-thyroidal iodide and blocked
more persistently by thioamide drugs.

8. Two molecules of DIT combine within the
thyroglobulin molecule to form L-thyroxine
(T4). One molecule of MIT and one molecule
of DIT combine to form T3.
In addition to thyroglobulin, other proteins
within the gland may be iodinated, but these
iodoproteins do not have hormonal activity.
Thyroxine, T3, MIT, and DIT are released from
thyroglobulin by exocytosis and proteolysis of
thyroglobulin at the apical colloid border.

10. Etiology Etiology
•Gravis disease-76%
•Multinodular goitre
•Autonomously functioning solitary thyroid
nodule
•Thyroiditis
Subacute
Pospartum
•Drugs - amiodarone

11. Grave’s disease Grave’s disease
•Autoimmune process in which serum IgG
antibodies bind to TSH receptors and
stimulate thyroid hormone production,
behaving like TSH
•These antibodies are called thyroid
stimulating antibodies
•Most pts are aged between 30-50

12. Clinical featuresClinical features
•Goitre- diffuse + bruit, nodular
•GIT
Wt loss despite normal or increased
appetite
Hyperdefaction (frequent bowel motions)
Diarrhea
Anorexia, vomiting

13. Clinical featuresClinical features
•Cardiorespiratory
Palpitations, sinus tachycardia
Increased pulse pressure
Ankle oedema in absence of cardiac
failure
Angina, cardiomyopathy, ccf
Dyspnoea, exacerbation of asthma

14. Clinical featuresClinical features
•Neuromuscular
Nervousness, irritability, psychosis
•Dermatology
Increased sweating, pruritus, palmar erythema,
Alopecia, vitiligo, myxoedema

15. Clinical featuresClinical features
•Reproductive
Amenorrhea/ oligomenorrhea
Infertility, spontaneous abortion
Loss of libido, impotence
•Ocular
 Excessive lacrimation, chemosis,
exophalmos, diplopia, papilloedema, loss
of visual acuity

16. Clinical featuresClinical features
•Other
Heat intolerance
Fatigue, apathy
Lyphadenopathy
Thirst
osteoporosis

17. Investigations Investigations
•Thyroid function tests- T3,T4, TSH
•TSH receptor antibody levels

18. Management Management
•Three methods
Antithyroid drugs
Subtotal thyroidectomy
Radioactive iodine

19. Treatment Treatment
•ANTITHYRIOD DRUGS :
•CARBIMAZOLE
•METHIMAZOLE
•PROPYLTHIOURACIL

20. CARBIMAZOLECARBIMAZOLE


These drugs inhibit thyroid hormone
production.
Full dose of carbimazole (40mg/day) are give
to suppress the thyroid gland completely while
replacing thyroid activity with100 mcg of
thyroxin daily once euthyroid state is achieved.
This continues for 18 months

21. METHIMAZOLEMETHIMAZOLE

•Same mechanism of action as
carbimazole
Dose; 30mg/day until someone is
euthyroid ( 4- 6 weeks)
Maintenance dose; 5-10mg

22. PROPYLTHIOURACILPROPYLTHIOURACIL
•Inhibits production of thyroxine hormone
and stops the conversion of T4 to T3 in the
peripherals.
•300 -450mg /day
•Maintenance dose of 50-100mg/day

23. Adverse effects Adverse effects
•Rash
•Fever
•Anorexia & nausea
•Agranulocytosis
•Aplastic Anaemia
•Thrombocytopenia
•Liver damage

24. Radioiodine Radioiodine
•Emits beta radiation that destroys the
gland.
•Cant be used in pregnant women.

25. Surgery Surgery
•Surgical remove of the gland in individuals
that cant use radioiodine.

26. Beta blockersBeta blockers
•Propranolol : used for symptomatic relief
•Blocks beta receptors that are activated by
increased amount of the horome.

27. Management of opthalmopathyManagement of opthalmopathy
•Steroid therapy- prednisolone 60 mg daily

28. Thyroid crisis- managementThyroid crisis- management
•Propranolol iv or orally
•Carbimazole 25mg 6 hrly
•Hydrocortisone 50mg 6 hrly
•Aspirin should be avoided since displaces
T4 from thyroid binding globulin

29. HYPOTHYROIDISM HYPOTHYROIDISM

30. introductionintroduction
•It may be primary from the disease of the
thyroid gland or secondary to
hypothalamic –pituitary disease

31. CLINICAL FEATURESCLINICAL FEATURES
•General;
Tiredness, wt gain, cold intolerance
Hoarseness
Goitre
Bradycardia
Constipation
Impotence
Skin problems

32. Thyroid PreparationsThyroid Preparations
These preparations may be synthetic (levothyroxine,
liothyronine, liotrix) or of animal origin (desiccated thyroid).
Synthetic levothyroxine is the preparation of choice for
thyroid replacement and suppression therapy because of its
1- stability
2- content uniformity
3- low cost
4- lack of allergenic foreign protein
5- easy laboratory measurement of serum levels
6- long half-life (7 days), which permits once-daily
administration.
• In addition, T4 is converted to T3 intracellularly; thus,
administration of T4 produces both hormones.

33. Although liothyronine (T3) is three to four times more potent
than levothyroxine, it is not recommended for routine
replacement therapy because of its
1- shorter half-life (24 hours), which requires multiple daily
doses
2- its higher cost
3- the greater difficulty of monitoring
4- adequacy of replacement by conventional laboratory tests.
5- its greater hormone activity and consequent greater risk of
cardiotoxicity,
T3 should be avoided in patients with cardiac disease. It is best
used for short-term suppression of TSH.

34. TreatmentTreatment
•Levothyroxine(T4)
•Dose: 50 -100microgram/day
•Liothyronine (T3)
•5-20microgram/day

35. Adverse effectsAdverse effects
•Increase in the metabolic rate
•Myocardial ischaemia
•Atrial fib