Hyperthyroidism Flashcards
Explain thyroid hormone synthesis
Thyrotrophin stimulating hormone is secreted by the APG by thyrotrophs. It enter the circulation, binding to TSH receptors on the basal surface of follicular cells.
Thyroid hormone synthesis:
1. Active transport of iodide into follicular cells via sodium-iodide symporter. The iodide pumps are located on the basal
membrane.
2. Pendrin pumps pump iodide from the follicle into the colloid, via the apical membrane.
3. Thyroglobulin consists of tyrosine residues, formed within the follicular ribosomes and inserted into secretory vesicles.
4. Thyroglobulin is exocytosed into the follicle lumen and iodinated. Iodide is activated by thyroid peroxidase.
5. Iodide binds to tyrosine residues on thyroglobulin forming 3-monoiodothyronine (MIT) and 3,5-diiodothyronine (DIT) upon further iodination.
6. The coupling of MIT & DIT occurs in the colloid forms triiodothyronine (T3), and tetraiodothyronine (T4) with the coupling of 2x DIT.
7. T3 and T4 are transported back into the follicular cells, being subjected to proteolytic cleavage of tyrosine residues. This liberates T3 & T4 from thyroglobulin and are subsequently released into circulation from the basal surface of follicular cells.
Explain the negative feedback system between the hypothalamus and APG, and the thyroid gland.
Thyroxine exerts a negative feedback effect on both thyrotrophs within the anterior pituitary gland and onto the TRH-secreting hypothalamic neurones.
What level of TSH will you find in a patient with primary hypothyroidism, where the thyroid gland has been destroyed by the immune system?
There is a high TSH (Reduced thyroxine synthesis from thyroid gland causes a loss of negative feedback).
What level of TSH will you find in a patient with secondary hypothyroidism, where the thyroid gland has been destroyed by the immune system?
There is a low TSH
Explain how thyroid replacement via medication works.
Oral levothyroxine is administered to patients with hypothyroidism, the dose is subsequently increased until TSH levels are normalised. Monitor TSH.
Explain the Wolff-Chaikoff effect.
The Wolff-Chaikoff effect is an autoregulatory function, whereby an excess of iodine inhibits thyroid peroxidase activity and, therefore, reduces iodothyronine production within thyroid follicular cells (Independent from serum-level of thyroid-stimulating hormone).
What is Graves’ disease?
Grave’s disease is an autoimmune condition characterised by increased thyroid- stimulating immunoglobulins (TSIs) that bind onto TSH receptors of the thyroid gland.
TSIs behave as an agonist, stimulating thyroid follicular cells to synthesise iodothyronines leading to Hyperthyroidism.
Induces thyroid gland enlargement (Smooth goitre).
List the symptoms of Graves’ disease.
Heat intolerance (Raised metabolism) Increase in body temperature Sweating Weight loss Higher BMR (Despite increased apetitite) Palpitations (Including atrial fibrillation or supraventricular tachycardias) Tremor Exophthalmos (Proptosis) Diarrhoea (occasional) Smooth goitre Oligomenorrhoea Warm velvety skin Muscle wasting Breathlessness Localised (Pretibial myxoedema)
What is a pretibial myxoedema and exophthalmos?
Exophthalmos - Ab bind to muscles behind the eye an
Pretibial myxoedema - the swelling (non-pitting) that occurs on the shins of patients with Graves’ disease: growth of soft tissue.
What is another name for hypothyroidism that is not to be confused with a symptom of hyperthyroidism?
Myxoedema
Why are palpitations associated with hyperthyroidism?
Iodothyronines increase the body’s sensitivity to adrenergic stimulation, therefore leading to increased stimulation of GS-linked beta-2 adrenergic receptors in the sinoatrial node. This results in an increase in heart rate and cardiac output. Thus, an abnormally elevated serum-level of thyroid hormones will induce a state of tachycardia and overstimulation. (An increase in sympathetic activation). Sympathetic activation > Palpitations, tremor in hands, lid lag (Adrenaline keeps eyelids open).
Describe how a smooth goitre would appear radioactive iodine image of the thyroid gland of a patient with Graves’ disease.
Diffuse enlargement and engorgement of thyroid gland (broken line indicates normal size of gland)
Diffuse goitre of moderate size and uniform radioiodine uptake.
Symmetrical
(Iodine uptake scan
(Radioactive iodine is administered)
Iodine 123 – radioactively labelled isotope)
What is Plummer’s disease?
Toxic multinodular goitre: Excess production of thyroid hormones from functionally autonomous thyroid nodules which do not require stimulation from TSH.
Not autoimmune related therefore there is no exophthalmos, or pretibial myxoedema (immunoglobulin driven)
Benign adenoma that is overactive
Low TSH due to negative feedback. Iodine uptake is predominantly conducted by the tumour, considering the thyroid gland is inactive, suppressed by the adenoma.
A thyroid scan reveals a benign overactive nodule (A hot nodule)
What is a solitary toxic nodule?
A toxic adenoma, whereby a single nodule undergoes hypertrophy and produces excess thyroid hormones.
What is Thyroid storm?
Uncontrolled hyperthyroidism > significant elevation in serum thyroid hormone, manifesting as an abnormally high heart rate, blood pressure and body temperature.
