L6 Thyroid Hormones 1 Flashcards
What hormones are produced by the thyroid follicle?
The iodothyronine hormones thyroxine (T4) and 3, 5, 3’-triiodothyronine (T3)
Role of T4 and T3 hormones
- essential for normal growth and development
- play an important role in energy metabolism
What happens when thyroid hormones are synthesised?
They are then stored as amino acid residues of thyroglobulin, a protein constituting the vast majority of the thyroid follicular colloid
What makes the thyroid a unique gland?
It has the ability to store great quantities of potential hormone as amino acid residues of thyroglobulin
How does the hypothalamus control T3 and T4 hormones?
- TRH is produced by the hypothalamus
- TRH stimulates the pituitary gland via the portal system
- This stimulates TSH production
- TSH acts directly on the thyroid, causing production of both T3 & T4
Role of thyroperoxidase (TPO)
TPO catalyses the iodination of thyroxine residues, and the coupling of iodothyronines to form either T3 or T4
How do anti-thyroid drugs work?
By blocking the iodination of thyroglobulin, which will prevent the production of T3 and T4. Anti-thyroids have direct effects on individual cells within the endocrine gland to prevent the production of their effector hormones.
What enzymes are used as substrates for conversion of thyroid hormones?
Deiodinase enzymes (D1, D2 & D3)
- associated with specific tissues
- each have very distinct actions
Which deiodinase enzymes are decreased in hypothyroidism?
D1 and D3
(D2 is increased)
Which deiodinase enzyme is responsible for T3 degradation?
D3
Quantity of thyroid hormone per litre in the thyroid pool
~8000µg
What is hypothyroidism?
A clinical syndrome resulting from a deficiency of thyroid hormones, which results in widespread organ-specific effects
Hypothyroidism in infants/children is characterised by?
marked slowing of growth and development, with serious permanent consequences, including mental retardation and short stature
Hypothyroidism with onset in adulthood leads to?
- diminished calorigenesis and oxygen consumption
- impaired cardiac, pulmonary, renal, GI & neurological functions
- deposition of glycosaminoglycans in intracellular spaces (particularly in skin & muscle)
What is myxedema?
Occurs in extreme cases of hypothyroidism - patients exhibit multiple organ abnormalities and progressive mental deterioration, skin appears very swollen and puffy
Classification of hypothyroidism
- Primary (most common)
- Secondary (pituitary TSH deficiency)
- Tertiary (hypothalamic TRH deficiency)
- Peripheral thyroid hormone resistance
Most characteristic pathological finding of hypothyroidism
the accumulation of glycosaminoglycans, mostly hyaluronic acid, in interstital fluids
What causes the accumulation of glycosaminoglycans, and what does it lead to?
The accumulation is due to decreased metabolism of glycosaminoglycans. The accumulation of this hydrophilic substance and the increased capillary permeability to albumin leads to interstitial non-pitting oedema in the skin, heart muscle and striated muscle.
What term is applied to newborn infants with hypothyroidism, and what is it characterised by?
‘Cretinism’
Severe iodine deficiency, mental retardation, short stature, characteristic puffy appearance of face & hands, frequently deaf mutism
Possible causes of neonatal hypothyroidism
- spontaneous
- exposure during pregnancy to iodides
- anti-thyroid drugs given to the mother
- inadvertent administration of radioactive iodine for thyrotoxicosis or thyroid cancer
Signs of neonatal hypothyroidism
respiratory difficulty, cyanosis, jaundice, poor feeding, hoarse cry, umbilical hernia, marked retardation of bone maturation
Hypothyroidism in children and adolescents is characterised by?
retarded growth and short stature
Common features of hypothyroidism in adults
easy fatiguability, cold sensitivity, weight gain, constipation, menstrual abnormalities (especially menorrhagia), muscle cramps
Physical findings of hypothyroidism in adults
- cool, rough, dry skin
- puffy face and hands
- hoarse, husky voice
- slow reflexes
Cardiovascular signs of hypothyroidism
- impaired ventricular contraction
- bradycardia
- increased peripheral resistance
- diminished cardiac output
- low voltage of QRS complexes and P and T waves
- cardiac enlargement (due in part to interstitial oedema)
What is often seen in patients with myxedema coma?
respiratory failure
What can occur as a result of slowed peristalsis in hypotension?
chronic constipation and occasionally severe faecal impaction in ileus
What can occur as a result of impaired renal function and decreased GFR in hypothyroidism?
impaired ability to excrete a water load, which predisposes the patient to hyponatremia, particularly from water intoxication if excessive free water is administered
4 mechanisms that may contribute to anaemia in patients with hypothyroidism
- Impaired haemoglobin synthesis as a result of T4 deficiency
- Increased iron loss with menorrhagia, as well as impaired intestinal absorption of iron
- Folate deficiency
- Pernicious anaemia, with vitamin B12-deficient megaloblastic anaemia
How does hypothyroidism affect the reproductive system?
- impairs the conversion of oestrogen precursors to oestrogens, resulting in altered FSH & LH secretion, which can lead to anovulatory cycles and infertility
- associated with menorrhagia
- men may have decreased libido and erectile dysfunction
Low serum FT4 and high serum TSH indicates?
primary hypothyroidism
Low serum FT4 and normal/low serum TSH indicates?
secondary hypothyroidism
How is hypothyroidism treated?
with T4
Levothyroxine is one of the most common synthetic T4 hormones
What is the advantage of administering T4 in hypothyroidism?
T4 is converted to T3 in peripheral tissues. Therefore, by giving T4 you have both hormones available even though only one is being administered.
What is the dose of levothyroxine based on?
The age of the patient. In a developing child, much higher levels of thyroxine are vital.
Effects of levothyroxine
- increases metabolic rate
- decreases TSH production from anterior pituitary
- converted to T3 in peripheral tissues
- replaces thyroid hormones in hypothyroidism
Is T3 or T4 more potent?
T3 is four times more potent than T4
Levothyroxine interactions
aluminium hydroxide, calcium supplements, cholestyramine, ferrous sulphate and sucralfate - all alter the rate of absorption of levothyroxine
What is the major toxic effect of T4 therapy?
Overdose - patients then can switch from having the symptoms & signs of hypothyroidism to hyperthyroidism e.g. palpitations & arrhythmias
How do you correct an overdose of synthetic T4?
by omitting the daily dose of T4 for about 3 days
What is thyrotoxicosis?
A clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones (toxicity of thyroid hormones). It results in a generalised acceleration of metabolic processes.
What causes most cases of thyrotoxicosis?
Hyperthyroidism
What is the most common presentation of thyrotoxicosis/hyperthyroidism?
Grave’s disease (diffuse toxic goitre)
What is known as Plummer disease?
Toxic adenoma
What is Grave’s disease characterised by?
an increase in T3 and T4 production
Why is Grave’s disease often considered an immune disorder?
TSH receptor antibodies will bind to TSH receptors, producing B cells with TSH receptor antibodies. These T cells multiply, and there is a genetic lack of suppressor T cells.
Why are significant ophthalmology presentations often associated with Grave’s disease?
TSH-R Abs can bind to receptors in the retro-orbital connective tissue, stimulating inflammatory cytokine production, which causes accumulation of glycosaminoglycans and swelling in the muscle & CT located behind the eyes
How is hyperthyroidism treated?
- anti-thyroid drugs (thioamides)
- radioiodine treatment (Iodine-131)
Examples of thioamides
Carbimazole
Methimazole
Propylthiouracil
How do thioamides work?
- inhibit iodination of tyrosine-Tg
- reduce deiodination of T4 to T3
- immunosuppressive effects in Grave’s disease
Most common adverse effect of thioamides
agranulocytosis (granulocyte count can be less than 250/µl)
(benign leukopenia is also observed)
Radioiodine treatment is contraindicated in?
children and pregnant women
What is a toxic adenoma?
A functioning adenoma which hypersecretes both T3 and T4 hormones, causing significant hyperthyroidism
Toxic adenoma gradually suppresses __ secretion.
endogenous TSH
Treatment for toxic adenoma
Mainly radioiodine therapy (in doses of 20-30 mCi) or surgery, as opposed to purely anti-thyroid drugs
When is surgery for toxic adenoma considered?
if the nodule is very large and causing symptoms such as dysphagia, neck pressure or difficulty breathing
High FT4 and low TSH suggests?
hyperthyroidism
