8. Treatment of thyroid disorders Flashcards
What are the major actions of the thyroid hormones?
Some of the T4 is converted to T3 by 5’ deiodinase (esp in kidney and liver)
T3 then bonds to a nuclear receptors results in gene transcription + protein synthesis.
Results:
1. GROWTH of soft tissue and bone maturation
2. CNS maturation
3. BMR increase
4. METABOLISM increase
5. CNS increase in CO
Note: Activation of nuclear receptors induce new protein synthesis which produce physiological effects
What are the BMR effects the proteins synthesised on T3 binding to nuclear receptor??
Increased….
- Na+/K+-ATPase
- O2 consumption
- Heat production
What are the metabolic effects the proteins synthesised on T3 binding to nuclear receptor??
Increased…
- Glucose absorption
- Glycogenolysis
- Gluconeogenesis
- Lipolysis
- Protein synthesis and degradation\
Hyperthyroidism, signs?
Anxiety/nervousness Eyelid retraction Diarrhoea Excessive sweats (due to high BMR) Insomnia Hand tremor Weight loss Goitre: Diffuse toxic goitre OR toxic nodular goitre High temp
Difference between Diffuse toxic goitre and toxic nodular goitre?
- Diffuse toxic goitre is an autoimmune disorder where antibodies to the TSH receptor stimulate thyroxine secretion.
- Toxic nodular goitre is caused by benign neoplasm/ adenoma
Causes of hyperthyroidism?
- Graves disease
- Overtreatment with thyroxine
- Thyroid adenoma (rare)
- Transient neonatal thyrotoxicosis (i.e. mother with Graves Disease)
- Excess iodine in diet (but VERY HIGH leads to hypothyroidism)
- Inflammation of thyroid i.e. thyroiditis. Eventually leads to thyroid destruction so then becomes hypothyroidism
What are the investigations in thyroid function?
Measure blood TSH, free T3 and T4 levels (i.e. not iodine bound)
Test for anti-thyroid antibodies (esp TSH receptors antibodies)
Radionucleotide thyroid scan viewed by a gamma camera (looking at 123I- or 99mTcO4 -uptake)
what chemicals are used in radionucleotide thyroid scan?
By uptake of…
123-Iodide
or
99m-TcO4
Treatment options of hyperthyroidism?
3 modalities
- Radioactive iodine
- Anti-thyroid drugs
- Surgery
None are optimal or interrupts the autoimmune process
Radioiodine treatment of hyperthyroidism: Administration? MoA? Contraindications? Eventually will lead to..
131-Iodine administration
Administration:
Orally given, in single dose which last 2 months
MoA: Cell damage by emitting short-range beta-radiation that affects only the follicle cells
Drug selective taken up by the thyroid
Contraindications:
Note to be given in pregnancy/lactation
Eventually will leads to hypothyroidism, which is then treated with replacement therapy.
Name 4 antithyroid drugs used in hyperthyroidism treatment?
- Thioureylenes (thioamides), carbimazole (methimazole) and propylthiouracil
- Iondine
- Beta-blockers
- Calcium supplements
Action of Thioureylenes (thioamides), carbimazole (methimazole) and propylthiouracil in hyperthyroidism?
Decrease the synthesis of thyroid hormones
Inhibit thyroperoxidase so reducing the iodination of thyroglobulin. Acts over 3-4 weeks.
Action of iodine drug treatment in hyperthyroidism?
Given orally in high doses
It is converted to iodide and transiently reduces thyroid hormone secretion and vascularity of the gland
Which beta-blocker is used in drug treatment of hyperthyroidism?
Propanolol
Action of calcium-supplements drug treatment in hyperthyroidism?
For the maintenance of normal bone density
The thioamide drugs which structural component is essential for it’s antithyroid activity?
The thiocarbamide group
Other past name for hypothyroidism?
Myxedema
Hypothyroidism:
- Origin?
- S/S?
Origin: Autoimmine
S/S:
- Low metabolic rate
- Slow sleep
- Deep hoarse voice
- Lethargy
- Bradycardia
- Cold sensitive
- Mental impairment
- Skin thickening
- Cretinism (in children)
What is cretinism?
Physical deformity and mental difficulties due to congenital thyroid dysfunction
What does myxedema also mean apart from hypothyroidism?
The dermatological changes assocaited with both hyperthyroid and hypothyroid conditions.
Results from the accumulation of hyaluronic acid and chondroitin sulfate in the dermis in both lesioned and normal skin causing swelling/puffiness of the subcut tissue
What are the investigation results seen in hypothyroidism?
Overal: decreased thyroid hormone levels. i.e.
- Low T4
- Low t3 (?)
- Raised TSH (not in pituitary problem, rest with protirelin)
- Various anti-thyroid antibodies (?)
What is the TSH level is hypothyroidism?
expection? Test?
-Raised TSH
Except in in Pituitary problem
Test with protirelin
Cause of hypothyroidism?
CONGENITAL or ACQUIRED…
Congenital:
- Hypoplasia of thyroid (agenesis/dysgenesis)
- Familial enzyme defects (dyshormonogenesis)
- Iodine deficiency (endemic cretinism)
- Intake of goitrogens during pregnancy
- Pituitary defects
- Idiopathic
Acquired:
- Iodine deficiency
- Auto-ummine thyroiditis
- Thyroidectomy or RAI therapy
- TSH or TRH deficiency
- Medications (iodide and cobalt)
- Idiopathic
Features of newborns with congenital hypothroidism?
- May have few or no clinical manifestations of thyroid deficiency
- The longer the condition goes undetected, the lower the IQ
What is Hashimoto’s disease?
Inflammation from Hashimoto’s disease, also known as autoimmune lymphocytic thyroiditis, often leads to an underactive thyroid gland (hypothyroidism) .
Most common cause of hypothyroidism
Antibodies found in hastimoto’s disease?
Thyroglobulin Ab
MIcrosomal Ab/thyroid peroxidase (TPO) Ab
TSH-R Ab (Blocking antibodies)
Epidemiology of hashitmotos?
Females
Runs in families
Hashimoto’s treatment (2)?
Levothyroxine (Synthetic analogue of thyroxine)
- Has all actions of endogenous thyroxine
- Standard T4 replacement therapy for hypothyroidism
Liothyronine- Synthetic analogue of tri-iodothyronine
- Has all the actions of the endogenous form
- Treatment of choice for myxedema coma (an extreme form of hypothyroidism compounded by come stressful state e.g. infection, myocardial infraction or stroke.
Congenita causes fo hypothyroidism?
Congenital:
- Hypoplasia of thyroid (agenesis/dysgenesis)
- Familial enzyme defects (dyshormonogenesis)
- Iodine deficiency (endemic cretinism)
- Intake of goitrogens during pregnancy
- Pituitary defects
- Idiopathic
Acquired causes for hypothroidism?
Acquired:
- Iodine deficiency
- Auto-ummine thyroiditis
- Thyroidectomy or RAI therapy
- TSH or TRH deficiency
- Medications (iodide and cobalt)
- Idiopathic
