Treatment of Thyroid Disorders

Question 1

Where in the body is T4 converted to T3 ?

Answer 1

In kidney and liver

Question 2

Describe findings on a radionucleotide thyroid scan (123I- or 99mTcO4 -uptake) for Grave’s disease and subacute thyroiditis.

Answer 2

Refer to slides 3 on page 2 and 4 on page 3

In diffuse goitre (e.g. Grave’s), more of the iodine is taken up and accumulated.

In subacute thyroiditis, no intake of radioisotopes.

Question 3

Describe the main features of subacute thyroiditis.

Answer 3

Inflammation of the thyroid (e.g. post-infectious or AI) causes it to stop working (may be transient)

Acutely, release of stored thyroid hormones causes hyperT
Chronically, gland becomes exhausted, causing hypoT

Question 4

Identify the main modalities of treatment of thyroid disorders. What are the main cons of these ?

Answer 4

Radioactive iodine, anti-thyroid drugs and surgery

MAIN CON:
None interrupts AI process

Question 5

Identify main pharmacological treatment options for Hyperthyroidism.

Answer 5

• Thioureylenes (thioamides) including:

• Carbimazole (prodrug, better taken up by follicular cells; once inside cell, forms active form methimazole)
• Methimazole
• Propylthiouracil
• Radioactive Iodine (131I)
• β-blocker (e.g. Propranolol)
• Calcium supplements

Question 6

How do Thioamides (Carbimazole, methimazole, and propylthiouracil) treat hyperthyroidism ? How long does their effects last ?

Answer 6

• Decrease the synthesis of thyroid hormones.

- Inhibit thyroperoxidase so reducing the iodination of thyroglobulin (so suppresses T3/4). Acts over 3-4 weeks.

Question 7

How does iodine treat hyperthyroidism ?

Answer 7

• Converted to iodide and transiently reduces thyroid hormone secretion and vascularity of the gland
• Damages cells. Emits short-range β radiation and affects only the follicle cells.

Question 8

State dose and administration of radioiodine in hyperT treatment.

Answer 8

Radioiodine (131I) is given orally and is selectively taken up by the thyroid. Given as a single (high) dose and lasts about 2 months (Not during pregnancy/ lactation)

Question 9

Identify a side effect of radioiodine. How can this be treated ?

Answer 9

Hypothyroidism will eventually occur which can be treated with replacement therapy.

Question 10

How do Calcium supplements treat hyperthyroidism ?

Answer 10

Maintain normal bone density

Question 11

How do beta blockers treat hyperthyroidism ?

Answer 11

Outweight positive chronotropic, inotropic, and effects on CO of thyroid hormones.

Question 12

Describe the structure of thiomides which are essential for antithyroid activity.

Answer 12

The thiocarbamide group is essential for antithyroid activity

Question 13

Define Myxedema.

Answer 13

Term historically used to refer to HypoT (more specifically extreme form of hypothyroidism compounded by some stressful state, such as infection, MI or stroke), but also term used to describe dermatological changes associated with hypoT and hyperT conditions.

Question 14

Describe mechanism that cause myxedema.

Answer 14

Results from the accumulation of increased amounts of hyaluronic acid and chondroitin sulfate in the dermis in both lesioned and normal skin causing swelling/puffiness of the subcutaneous tissue.

Question 15

Distinguish between myxedema in hypoT and hyperT.

Answer 15

HyperT- symptoms limited to Pretibial myxedema (only 1-5% of patients)

HypoT- symptoms more prevalent and also include:
●Skin thickening
●Coarse skin
●Change in facial appearance

Question 16

State the changes in the following enzymes that occur in hypoT:

• T4
• T3
• TSH
• Any other biomarkers

Answer 16

HypoT:

• T4: low
• T3: possibly low too
• TSH: raised unless pituitary problem
• Possibly various anti-thyroid antibodies

Question 17

Describe the protirelin test.

Answer 17

Protirelin is TRH agonist: will bind to TRH receptors in the thyrotrophs, should stimulate TSH release and thyroid gland to release T3 and T4. If increase in T3/4, probably pituitary rather than thyroid defect.

Question 18

Identify the main causes of congenital hypothyroidism.

Answer 18

-Hypoplasia of the gland (agenesis/dysgenesis AKA incomplete maturation)

-Familial enzyme defects
(dyshormonogenesis, some enzymes involved are mutated, so don’t produce active form of thyroglobulin)

• Iodine deficiency (endemic cretinism) (born to women in areas where low iodine intake in diet)
• Intake of goitrogens during pregnancy
• Pituitary defects (cause lack of TSH)
• Idiopathic

Question 19

What are the main clinical features of congenital hypoT ?

Answer 19

• May have few or no clinical manifestations of thyroid deficiency
• The longer the condition goes undetected, the lower the IQ

Question 20

Identify the main causes of acquired hypothyroidism.

Answer 20

Iodine deficiency

Auto-immune thyroiditis (antibodies developing in blood to something you’ve been infected with, which end up attacking thyroid)

Thyroidectomy or RAI therapy (thyroid gland obliterated surgically or by radiation e.g. after tumor)

TSH or TRH deficiency (hypoT or pituitary defect e.g. adenoma in the thyroid)

Medications (iodide and cobalt)

Idiopathic

Question 21

What is the most common cause of hypoT ?

Answer 21

Hashimoto’s Disease

Question 22

Describe treatment for Hypothyroidism.

Answer 22

Levothyroxine (standard T4 replacement therapy for hypothyroidism)
Liothyronine (teatment of choice for myxedema coma)

Question 23

Explain mechanism of action of Levothyroxine.

Answer 23

Synthetic analogue of thyroxine - has all the actions of endogenous thyroxine

Question 24

Explain mechanism of action of Liothyronine.

Answer 24

Synthetic analogue of tri-iodothyronine - has all the actions of endogenous tri-iodothyronine