Drugs used in the treatment of hyperthyroidism, hypothyroidism, hyperparathyroidism and hypoparathyroidism

1. Drugs for thyroid &
parathyroid disorders
Dr. M. Ahsan (MBBS, MD)

2. Thyroid hormones
• Thyroid hormone is essential for normal
development, especially of the CNS.
• In the adult, thyroid hormone maintains
metabolic homeostasis and influences the
functions of virtually all organ systems
• Serum concentrations of thyroid hormones are
precisely regulated by the pituitary hormone
TSH in a negative-feedback system

3. Synthesis & release of thyroid hormones

4. Synthesis & Release
• Iodide uptake:
Iodine is actively taken up by the follicular cells under the influence of TSH
• Oxidation and iodination of tyrosine
Iodide is oxidised to iodinium ion (I+) by thyroid peroxidase.
I+ combines with tyrosine (on surface of thyroglobulin) to form MIT and DIT
• Coupling reaction
MIT + DIT = T3
DIT + DIT = T4
These reactions are catalysed by thyroid peroxidase

5. Synthesis & Release
• Storage & release
T3 and T4 formed on surface of thyroglobulin is transported to inner side of
follicle for storage as thyroid colloid
They are released by proteolysis and exocytosis under influence of TSH
• Peripheral conversion of T4 to T3
More T4 is released than T3 (4:1)
Circulating T4 is converted to T3 by iodothyronine 5’-deiodinase

6. Peripheral conversion
The conversion of T4 to T3
in the periphery is blocked
by propythiouracil, high
dose of propranolol and
glucocorticoids

7. Transport, Metabolism & Excretion
• T3 is 5 times more active than T4
• t ½ of T4 = 6-7 days t ½ of T3 = 1-2 days
• Thyroid hormones are bound to:
Thyroxine binding globulin (TBG)
Thyroxine binding prealbumin
Albumin
• Inactivation occurs by deiodination , decarboxylation and conjugation
mainly in the liver

8. Disorders of thyroid function

9. Drugs for hypothyroidism
• Levothyroxine (T4)
• Liothyronine (T3)
• Liotrix (T4/T3 combination)
Levothyroxine (T4) is preferred over T3
(liothyronine) or T3/T4 combination
products (liotrix) for the treatment of
hypothyroidism.
It is better tolerated than T3 preparations
and has a longer half-life

10. Levothyroxine (T4)
• Well absorbed from the stomach and
small intestine (80% absorption)
• Absorption increases on taking on an
empty stomach
• Available as tablets and liquid-filled
capsules for oral administration and as a
lyophilized powder for injection
• Levothyroxine is dosed once daily, and
steady state is achieved in 6 to 8 weeks.
• Toxicity is directly related to T4 levels and
manifests as nervousness, palpitations
and tachycardia, heat intolerance, and
unexplained weight loss.

11. Liothyronine (T3)
• Liothyronine is available as tablets
and an injectable form.
• Liothyronine absorption is nearly
100%, with peak serum levels 2–4
h following oral ingestion.
• Liothyronine may be used when a
more rapid onset of action is
desired, such as myxedema coma
• Liothyronine is less desirable for
chronic replacement therapy:
More-frequent dosing (t1/2 = 18–24
h)
Higher cost
Risk of arrhythmia

12. Uses of thyroxine
Mainly used as a supplement in hypothyroidism in:
• Children – Cretinism
• Adult hypothyroidism
• Myxoedema
• Simple or non-toxic goitre
• Myxoedema coma
• Subclinical hypothyroidism
• Nodular goitre
• Papillary carcinoma of thyroid

13. Drugs for hyperthyroidism: Thyroid Inhibitors
I. Hormone Synthesis Inhibitors
(Antithyroid drugs)
Propyltiouracil, Carbimazole,
Methimazole
II. Hormone Release Inhibitors
Iodides (Lugol’s iodine, Sodium
iodide, potassium iodide)
III. Destruction of thyroid tissue
Radioactive iodine
IV. Ionic inhibitors
Thiocynates, perchlorates, nitrates

14. Antithyroid drugs
• Inhibits the synthesis of thyroid hormones.
• They inhibit the enzyme thyroid peroxidase.
Thus inhibit:
Oxidation & Iodination of tyrosine residue
Coupling reaction
• Propylthiuracil also inhibits the peripheral conversion of T4 to T3

15. Pharmacokinetics of antithyroid drugs
• Rapidly absorbed orally
• Readily cross placenta and enter
milk
(so, they should be avoided in
pregnancy, except propylthiuracil
because it crosses less readily)
• The drugs are excreted in urine as
inactive conjugated form

16. Uses of antithyroid drugs
• To achieve spontaneous remission and control in:
Grave’s disease
Toxic nodular goitre
• Used prior to radioactive iodine
• Pre-operative control of hyperthyroidism
• Thyroid storm
(PTU is preferred because it can
inhibit peripheral conversion)
Methimazole is
preferred over PTU
because of
once daily dosing
(longer t ½ )
Lower incidence of
adverse effects
[Except in pregnancy: PTU
is preferred]

17. Adverse effects of antithyroid drugs
Adverse effects:
 Skin rashes (most
common)
 Nausea, headache
 Pain & stiffness in the
joints
 Loss or greying of
hair
 PTU is associated
with hepatotoxicity
and agranulocytosis
(rare)
Patients should be instructed to
immediately report the
development of sore throat or fever
and should discontinue their
antithyroid drug and
obtain a granulocyte count

18. Iodine and iodides
• It is the fastest acting agent
• Inhibits the release of thyroid hormones
• The gland shrinks in size and becomes firm and less vascular
The maximal effect occurs after 10–15 days of continuous therapy.
On continuous treatment there is loss of therapeutic effect!!
(thyroid constipation and thyroid escape)
Iodide is the oldest
remedy for disorders of
the thyroid gland. In
high
concentration, iodide
limits its own transport
and acutely and
transiently inhibits the
synthesis of thyroid
hormones.
(the Wolff-Chaikoff
effect)

19. Iodides
Uses:
• Pre-operative preparation before subtotal thyroidectomy
……given 7-10 days pre-operatively to shrink the gland, make it firm and
less vascular
• Thyroid storm (in conjunction with antithyroid drugs and propranolol)
(Lugol solution) consists of 5% iodine
and 10% potassium iodide
Typical doses include 16–36 mg (2–6 drops) of
Lugol solution
Adverse effect:
Hypersensitivity to iodine: angioedema and laryngeal oedema
Chronic intoxication causes ‘iodism’

20. Radioactive iodine
I-127: stable isotope
I-131, I-123, I-125: radioactive isotopes
I-131: t ½ = 8 days
• Commonly used iodine isotope for therapeutic and diagnostic purposes
• Emits γ and β particles.
• Taken as sodium salt by oral route

21. Radioactive iodine
• The radioactive iodine is actively taken up by the follicular cells
• It emits β particles which destroys thyroid parenchyma (up to 0.5-2 mm)
• There is negligible damage to adjacent tissue
Uses:
Grave’s disease
In patients who cannot undergo thyroidectomy (elderly patients)
Patients with existing heart disease
Toxic nodular goitre

22. Radioactive iodine
Advantages
• Risk of complications of surgery is
avoided
No Surgical scar
No injury to recurrent laryngeal nerve
No damage to parathyroid gland
• Cure is permanent
Disadvantages
• Permanent hypothyroidism
• Delayed onset
• Can not be used during pregnancy
• Avoided in young patients

23. Adjuvant therapy: Symptomatic treatment
• β- blockers (Propranolol):
Antagonize the sympathetic/adrenergic effects of thyrotoxicosis—
Reduce the tachycardia, tremor, and stare—and relieve palpitations,
anxiety, and tension.

24. Thyroid storm
Thyroid storm is an uncommon but life-threatening
complication of thyrotoxicosis
in which a severe form of the disease is usually
precipitated by an intercurrent medical problem
Treatment:
 Supportive measures
 Antithyroid drugs - PTU is preferred
(PTU impairs peripheral conversion of T4
→ T3)
 Oral iodides
 β -blockers
 Treatment of the underlying
precipitating illness

25. Drugs for parathyroid
disorders

26. Parathormone
• Parathyroid hormone (PTH) plays a key role in the regulation of calcium
and phosphate homeostasis and vitamin D metabolism
• When serum ionised calcium levels fall, PTH secretion rises
• Parathormone (PTH) acts on:
Skeleton  increases osteoclastic bone resorption and bone formation
Renal tubules  promotes reabsorption of calcium and reduce
reabsorption of phosphate
promotes the conversion of 25-hydroxyvitamin D to the active metabolite
 enhances calcium absorption from the gut

27. • Primary hyperparathyroidism is caused by autonomous secretion of PTH,
usually by a single parathyroid adenoma
• Presents with hypercalcemia with a raised PTH level
• Reduced bone mineral density (osteopenia or osteoporosis): most
common skeletal manifestation hyperparathyroidism
Treatment of life-threatening hypercalcemia in primary
hyperparathyroidism:
 IV fluids
 Bisphosphonates
 Calcitonin
 Cinacalcet
Primary Hyperparathyroidism

28. Hypoparathyroidism
• The most common cause of hypoparathyroidism is damage to
the parathyroid glands (or their blood supply) during thyroid
surgery.
• Treatment:
Oral calcium salts
Vitamin D analogues
PTH analogues

29. Calcitonin
• Calcitonin lowers plasma Ca2+ and phosphate concentrations in patients
with hypercalcemia.
• Calcitonin causes direct inhibition of osteoclastic bone resorption
• Calcitonin is administered through subcutaneous injection or nasal spray.
Uses:
• Hypercalcemia
• Disorders of increased skeletal remodeling, such as Paget disease

30. Calcimimetics: Cinacalcet
• Calcimimetics are drugs that mimic the stimulatory effect of Ca2+
• They act on the Calcium-sensing receptor (CaSR) to inhibit PTH secretion
by the parathyroid glands.
• Cinacalcet is the first and only approved drug in the class currently
• Uses:
• Secondary hyperparathyroidism
• Hypercalcemia due to primary hyperparathyroidism or parathyroid
carcinoma (as an alternative treatment to surgery)

31. Bisphosphonates
• Bisphosphonates are analogues of pyrophosphate
MOA:
• Bisphosphonates act by direct inhibition of bone resorption
• Bisphosphonates concentrate at sites of active remodeling  released in
the acid environment of the resorption lacunae  induce apoptosis in
osteoclasts

32. Bisphosphonates
• First-generation: medronate, clodronate, and etidronate
• Second-generation: alendronate and pamidronate
• Third-generation: risedronate and zoledronate
Uses:
• Post-menopausal osteoporosis
• Steroid-induced osteoporosis
• Paget disease
• Tumor-associated osteolysis
• Hypercalcemia
Increasingpotency

33. Bisphosphonates
Oral bisphosphonates can cause heartburn, esophageal
irritation, or esophagitis!!
Take with a full glass of water at least 30 min before
breakfast, and don’t lie down…..Remain upright!

34. PTH analogues
Teriparatide: synthetic PTH analogue
Recombinant human parathormone
Abaloparatide: synthetic PTHrP
• These agents are peptides: given by subcutaneous injection
• Teriparatide and abaloparatide are the only agents currently available that
increase new bone formation.
• Uses:
Severe osteoporosis in patients at a high risk for fracture
Hypocalcemia in patients with hypoparathyroidism (when not controlled by
calcium and Vit D)

35. Calcium
• Calcium is used in the treatment of calcium deficiency states and as a
dietary supplement
• Calcium chloride
• Calcium gluconate
• Calcium carbonate
• Calcium acetate
For control of milder hypocalcemic
symptoms, oral medication suffices,
frequently in combination with vitamin D or
one of its active metabolites
Given intravenously in the
treatment of severe hypocalcemic
tetany.

36. Vitamin D
• Cholecalciferol (vitamin D3)
• Calcitriol (1,25-dihydroxycholecalciferol)
• Ergocalciferol (calciferol) is vitamin D2: used typically in doses of 50,000–
200,000 units/d in conjunction with calcium supplements
• Doxercalciferol (1α-hydroxyvitamin D2), a prodrug: Used for secondary
hyperparathyroidism
Analogues of calcitriol used for secondary hyperparathyroidism:
• Calcipotriene
• Paricalcitol
• Maxacalcitol
Suppress PTH secretion by the parathyroid glands but
have less or negligible hypercalcemic activity.
They are a safer and more effective means of
controlling secondary hyperparathyroidism

37. Thank you

38. References
• Lippincott Illustrated Reviews: Pharmacology(6th ed.). Philadelphia,
PA: Wolters Kluwer.
• Goodman & Gillman’s: The Pharmacological Basis of Therapeutics,
13th edition. New York: McGraw-Hill, 2018

39. Recap

40. Recap