Hyper/hypothyroidism Flashcards
What are the 4 major histological components of the thyroid gland?
Follicle - secretory sac containing colloid
Colloid - mixture which contains prohormone thyroglobulin
Follicular cells - cells which make up the follicle
Parafollicular cells (C-cells) - calcitonin secreting cells
Describe the steps in the formation of thyroid hormone.
- Iodine taken up by follicular cells and passed into colloid.
- Iodine attaches to thryoglobulin forming either monoiodotyrosine (MIT) ot di-iodotyrosine (DIT)
- MIT+DIT = triiodothyronine (T3)
DID+DID = thyroxine (T4) - T3 and T4 stored in colloid
Describe the steps in the secretion of thyroid hormone.
- Thyroid releasing hormone (TRH) secreted from hypothalamus and acts on anterior pituitary gland to release thyroid stimulating hormone (TSH).
- TSH acts on G-protein coupled receptors on follicular cells which increases intracellular cAMP
- Stimulates transportation of T3/T4 into follicular cells by and then into the blood by pinocytosis
What is the active form of thyroid hormone?
T3 (triiodothyronine)
What transports thyroid hormone in the blood?
Thyroxine binding protein (70%)
Also transthyretin (20%) and albumin (5%)
Describe the steps in the action of thyroid hormone.
- T3/T4 enters cell through membrane transporter and T4 converted to T3 by de-iodinase 2 (D2) enzymes in cytoplasm
- T3 binds to and activates thyroid hormone receptor in the nucleus
- This converts inhibitoary co-repressor (CoR) to co-actuivator (CoA) protein which binds to thyroid response element (TRE) on DNA increasing metabolic rate
What enzyme converts T4 to T3 inside tissues?
Deiodinase 2 (D2)
What is hyperthyroidism?
What is thyrotoxicosis?
Why are they different?
Hyperthyroisism - overactive thyroid gland
Thyrotoxicosis - state arising when tissues exposed to excess thyroid hormone
Thyrotoxicosis can occur without hyperthyroidism e.g. excess exogenous thyroxine, ectopic thyroid tissue
What is primary hyperthyroidism?
Problem within the thyroid gland causing hypersecretion.
TFTs show:
- T3/4: high
- TSH: low
Diagnosis?
What test would you do next and why?
Primary hyperthyroidism
TSH receptor antibody (TRAb): helps differentiate Graves’ disease from mutinodular goitre/solitary toxic nodule
TRAb elevated - Graves
TRAb low - not Graves
What is Graves’ disease?
Autoimmune condition of the thyroid gland (thyroid receptor antibody - TRAb) causing hyperthyroidism
How does Graves’ disease present?
Tachycardia, anxiety, sweating, tremor Muscle weakness Weight loss and increased appetite Diarrhoea Light periods/amenorrhoea
Proptosis
Smooth goitre
What is pretibial myxoedema?
Swelling and lumpiness of shins from Graves’ disease
What is Thyroid Eye Disease (TED)?
Exopthalmus, lid retraction and painful eye movements caused by Graves’ disease
Are thyroid cancers normally
- hyperthyroid
- euthyroid
- hypothyroid?
Usually euthyroid
What is choriocarcinoma and why can it cause hyperthyroidism?
Tumour secreting human chorionic gonadotrophin (hCG)
Has a very similar structure to TSH (alpha chains identical, ß chain different) and can mimic its effects
What does amiodarone do to T3/4 levels and why?
What is the clinical significange of this?
Amiodarone inhibits deiodinase 1 (DIO1) which converts T4 to T3 resulting in high T4 and low T3
This tends to cause
- hyperthyroidism in iodine deficient areas
- hypothyroidism in iodine rich areas
TFTs show:
- T3/4: high
- TSH: high
Diagnosis?
Secondary hyperthyroidism
Dysfunctional hypothalamic-pituitary-thyroid axis producing excess TSH and consequent T3/4
TFTs show:
- T3/4: normal
- TSH: low
Diagnosis?
Subclinical hyperthyroidism
Biological state which has risk of progressing to overt hyperthyoidism
How is hyperthyroidism treated?
Anti-thyroid drugs (carbimazole, propylthiouriacil)
ß-blockers
Patient in first trimester of pregnancy is diagnosed with hyperthyroidism. What treatment do you prescribe?
Propylthiouracil
Name 2 anti-thyroid drugs and their different characteristics.
Carbimazole
- first line
- once daily
- less side effects
- more potent
Propylthiouracil
- second line (unless 1st trimester of pregnancy)
- twice daily
- more side effects
- less potent
What is the most important side effect to warn patients on anti-thyroid drugs (ATD) about?
Agranulocytosis
(warn patient verbally and in writing that if they get fever they must stop drugs and get urgent FBC)
Patient can never use ATD again.
How do you manage a patient with hyperthyroidism who developed agranulocytosis after using antithyroid medication?
Radioiodine
Thyroidectomy if radioiodine contraindicated (pregnancy, active thyroid eye disease)
What is the main risk in thyroidectomy?
Recurrent laryngeal nerve palsy
What is a thyroid storm?
Acute and serious attack of hyperthyroidism usually affecting hyperthyroid patient who suffers acute infection/surgery
How do you manage thyroid storms?
ABC
High dose antithyroid drugs
Hydrocortisole
Potassium iodide
TFTs show:
- T3/4: low
- TSH: high
Diagnosis?
What test would you do next and why?
Primary hypothyroidism
Anti-thyroid peroxidase (anti-TPO)
Would be raised in Hashimoto’s thyroiditis
How does Hashimoto’s thyroiditis present?
Weight gain, lethargy, puffy skin, bradycardia, consipation
Menorrhagia/amenorrhoea
Slow tendon jerks
Goitre
Why does hypothyroidism cause oligo/amenorrhoea?
Increased TRH increases prolactin secretion. Prolactin inhibits gonadotrophin action
What treatments can cause hypothyroidism?
Radiotherapy
Amiodarone
Lithium
Thyroidectomy
What is the commonest cause of hypothyroidism
- in the UK
- worldwide?
- Hashimoto’s thyroiditis
2. Iodine deficiency
TFTs show:
- T3/4: low
- TSH: low
Diagnosis?
Secondary hypothyroidism
Dysfunctional hypothalamic-pituitary-thyroid axis
TFTs show:
- T3/4: normal
- TSH: high
Diagnosis?
Subclinical hypothyroidism
What does hypothyroidism cause in babies? Why is this rare?
Cretinism: dwarfism and poor mental function (thyroid hormones important in brain development)
Guthrie screening test (5th day of life TFTs done) means this is rare
How do you treat primary hypothyroidism?
Slowly increase thyroid levels with daily levothyroxine (T4 tablets)
What doses of levothyroxine are used in
- normal patients?
- elderly?
- pregnant women?
- 50-100µg
- 25-50µg (half)
- Increase previous dose by 25µ
What is myxoedema coma?
Potentially fatal loss of brain function from severe hypothyroidism
How does myxoedema coma present?
Hypothyorid signs
Reduced mental status
Hypothermia
Respiratory failure
How do you manage myxoedema coma?
ABC Slowly rewarm Broad spectrum antibiotics Cautious thyroxine Hydrocortisone if adrenal failure
What is sick euthyroid syndrome?
Abnormal TFTs caused by non-thyroid illness
Avoid checking TFT in ill patient without clinical indication of thyroid pathology
What TFT pattern often shows in ill people?
Sick euthyroid syndrome
- T3/4: low
- TSH: low
How would resistance to thyroid receptor hormone alpha (TRa1/2 mutation) present?
Delayed development
Bradycardia
Chronic consiptation
How would resistance to thyroid receptor hormone beta (TRß1/2 mutation) present?
Increased T3/4 and TSH
Goitre
Affected colour vision
Is resistance to thyroid receptor alpha or beta more common?
resistance to thyroid receptor hormone beta is more common
What does thyroiditis show on scintigraphy?
Homogenously reduced iodine uptake
What is the classic effect of thyroidtitis on thyroid hormone levels?
Increased initially
Hypothyroid after
Euthyroid once inflammation settles
Name 3 causes of thyroiditis and when they would present.
De Quervian’s thyroiditis - after viral infection
Post-partum thyroiditis - after pregnancy
Drug induced thyroiditis - after treatment with amiodarone/lithium
What TFT pattern do multinodular goitres often show?
Subclinical hyperthyroidism
(normal T3/4, low TSH)
This can progress to primary hyperthyroidism (high T3/4, low TSH)
What investigations can be done if patient presents with breathlessness and a multinodular goitre?
CT scan
Flow volume loops
What does a multinodular goitre often show on scintigraphy?
Multiple nodules but one dominant nodule taking up most of the iodine
When is surgery indicated in toxic multinodular goitre?
Tracheal compression
Retrosternal extension
Cancer suspicion
