Hyperthyroidism Flashcards
-> Function of endocrine glands: Summarise the function of the key endocrine glands, including the synthesis, regulation and physiological effects of their hormones. -> Endocrine disorders: Describe the clinical features and treatment options of endocrine disorders.
Which endocrine cells release TSH?
- Thyrotrophs within the anterior pituitary gland
Which cells respond to TSH?
- Follicular cells of the thyroid gland
How is iodine pumped into follicular cell of the thyroid gland?
- Sodium-iodine symporter (secondary active transport)
How is iodide pumped from the follicle into the colloid?
- Pendrin pumps within the apical membrane
How is iodine activated into iodide?
- Under the action of thyroid peroxidase in the presence of hydrogen peroxide
Where does iodination occur within the thyroid gland?
- Within the colloid
What are the two direct products of iodination of thyroglobulin within the colloid?
- Monoiodotyrosine (MIT) or Diiodotyrosine (DIT) molecules
Which thyroid pro-hormone is iodinated?
- Thyroglobulin
Which thyroglobulin residues are iodinated?
- Tyrosine residues
How is triiodothyronine (T3) formed?
- Coupling of MIT and DIT
How is tetraiodothyronine / thyroxine (T4) formed?
- Coupling of DIT molecules
Which thyroid hormone is active?
- T3
Tetraiodothyronine (Thyroxine, T4) is a prohormone converted by deiodinase enzyme into the more active metabolite triiodothyronine (T3)
Which structures are directly inhibited by thyroxine (fT4) via negative feedback mechanisms?
- Anterior pituitary gland (thyrotrophs)
- Hypothalamic neurones (secreting TRH)
What is the effect of thyroxine (fT4) on the heart rate?
- Sensitives beta adrenoreceptors to ambient levels of adrenaline and noradrenaline
- This increases the heart rate ( tachycardia and tremor in hands) → Lid lag
What are the common forms of hyperthyroidism (4)?
- Grave’s Disease (Autoimmune Disease)
- Plummer’s Disease (Non-Autoimmune Disease)
- Viral (de Quervain’s) thyroiditis
- Post partum thyroiditis
What is the pathophysiology of Grave’s disease (autoimmuune hyperthyroidism)?
- TSH Immunoglobulins binds to TSH receptors in the thyroid gland
- Stimulation of TSH receptors subsequently result in smooth goitre formation and hyperthyroidism
What are the clinical signs of Grave’s disease (3)?
- Elevated fT4
- Elevated fT3
- Insufficient TSH
What are the clinical features of Grave’s disease (10)?
- Respiration, facial flushing
- Muscle wasting
- Shortness of breath
- Heat intolerance
- Weight loss - despite increased appetite
- Localised myxoedema
- Tremor
- Sweating
- Palpitations
- Exophthalmos (proptosis)
Antibodies bind to muscles behind the eye and cause exophthalmos
What is pretibial myxoedema?
- The swelling that occurs on the shins (legs) of patients with Grave’s disease: growth of soft tissue
Not to be confused with myxoedema = hypothyroidism
What type of goitre is shown in a patient with Plummer’s disease (non-autoimmuune hyperthyroidism)?
-
Toxic nodular goitre
- Benign nodules of the thyroid gland (not autoimmune associated)
What are the clinical features of Plummer’s disease (8)?
- Weight loss - despite increased appetite
- Shortness of breath
- Palpitations
- Tachycardia
- Sweating
- Heat intolerance
- Diarrhoea
- Lid lag and other sympathetic features
What are the four main features of viral (de Quervain’s) thyroiditis?
- Painful dysphagia
- Hyperthyroidism (The thyroid gland is tender and palpable)
- Pyrexia (fever)
- Thyroid inflammation
How is hyperthyroidism induced in individuals with viral (de Quervain’s) thyroiditis?
- Round follicle is damaged, subsequently causing stored thyroxine within the colloid to be released
Describe the pattern of iodine uptake in an individual with viral (de Quervain’s) thyroiditis.
- There is no iodine uptake as the thyroid gland stops making thyroxine
How is hypothyroidism caused in individuals with viral (de Quervain’s) thyroiditis?
- Four weeks upon the onset of viral thyroiditis, stored thyroxine is depleted
What type thyroid scan is conducted to identify the type of goitre in hyperthyroidism (Grave’s or Plummer’s)?
- Iodine-123 scan
How is Grave’s disease diagnosed (distinguished from Plummer’s disease) (2)?
- Positive anti-TSH receptor antibody blood test
- Radioactive iodine uptake test
Diffuse goitre of moderate size and uniform radioiodine uptake
Which part of the thyroid gland uptakes iodine-123 in Plummer’s disease?
- The toxic nodular goitre
- The inactive thyroid gland is suppressed due to the adenoma.
What class of drug is the main anti-thyroid?
-
Thionamides
- Propylthiouracil (PTU)
- Carbimazole (CBZ)
What is the mechanism of action of thionamides?
- Inhibition of thyroid peroxidase and peroxidase transaminase, therefore reduce iodine activation and iodination of thyroglobulin into MIT & DIT
Which enzyme is inhibited by thionamides?
Thyroid peroxidase
What are the unwanted actions of thinamides (2)?
- Agranulocytosis (reduction in neutrophils) - neutropenia increases risk of sepsis
- Rashes (common)
Agranulocytosis is reversed witht he withdrawl of the drug
Which drug should be pre-operatively administered in hyperthyroid patients?
Potassium Iodide - induces Wolff-Chaikoff effect (10 days)
What effect does KI have in hyperthyroid patients (3)?
- Inhibits hydrogen peroxide generation and thyroid peroxidase
- Reduces vascularity and size of gland (atrophy of thyroid gland)
- Inhibits the iodination of thyroglobulin by inducing the Wolff-Chaikoff effect
Which effect demonstrates the auto-regulatory function of iodine control?
- Wolff-Chaikoff effect
What is the Wolff-Chaikoff effect?
- An autoregulatory function, whereby an excess ingestion of iodine inhibits thyroid peroxidase activity and thus reducing iodothyronine production within thyroid follicular cells, independent from the serum-level of thyroid-stimulating hormone (TSH)
