Thyroid physiology and pathology Flashcards
What hormones does thyroid tissue secrete?
Thyroxine (T4)
Tri-iodothyronine (T3)
Calcitonin
What hormone does the parathyroid glands secrete?
Parathyroid hormone
What are follicles in thyroid tissue?
Colloid spheres enclosed by follicular cells
Which cells secrete calcitonin?
Parafollicular C cells
What is colloid in thyroid tissue?
Tyrosine-containing, thyroglobulin filled spheres surrounded by follicular cells
Which chemical is taken up by follicular cells to initiate synthesis of T3 & T4?
Iodine
What does iodine do to form T3 & T4 once it has been taken into follicular cells?
Iodine attaches to tyronine residues on thyroglobulin to form MIT (monoiodotyrosine unit) and DIT (di-iodotyrosine unit)
These then couple to form T3 and T4
MIT + DIT = T3
DIT + DIT = T4
Where is newly formed T3 and T4 stored in the thyroid?
In the thyroglobulin
Which is the major biologically active thyroid hormone?
T3
Which is the most abundantly produced thyroid hormone?
T4
Which organs in the body convert T4 to T3?
Liver and kidney
What is the significance of T3 & T4 being lipophilic/hydrophobic?
Has to bind to plasma proteins to be transported in blood
What plasma proteins can T3 & T4 bind to for transport?
Thyroxine binding globulin (~70%)
Thyroxine binding prealbumin (~20%)
Albumin (~5)
In which form is T3 & T4 biologically active?
Unbound (from plasma proteins)
What effect do thyroid hormones have on basal metabolic rate?
Increase BMR:
Increase number & size of mitochondria
Increase oxygen use and rates of ATP hydrolysis
Increase synthesis of respiratory chain enzymes
What effect do thyroid hormones have on thermogenesis?
Increase thermogenesis
~ 30% temperature regulation due to thyroid hormone thermogenesis
What effect do thyroid hormones have on carbohydrate metabolism?
Increase blood glucose due to stimulation of glycogenolysis and gluconeogenesis
Increase insulin-dependent glucose uptake into cells
What effect do thyroid hormones have on lipid metabolism?
Mobilise fats from adipose tissue
Increase fatty acid oxidation in tissues
What effect do thyroid hormones have on protein metabolism?
Increased protein synthesis
What role do thyroid hormones play in the development of foetal and neonatal brains?
Myelinogenesis & axonal growth require thyroid hormones
What effect do thyroid hormones have on growth?
Required for growth hormone releasing hormone (GHRH) production and secretion
Required for glucocorticoid-induced GHRH release (permissive action)
GH/somatomedins require presence of thyroid hormone for activity (permissive action)
What is thyroid hormones permissive sympathomimetic action?
Thyroid hormones increase the number of beta-receptors, increasing cardiovascular responsiveness as tissues become more sensitive to noradrenaline and adrenaline
Rate and force of cardiac contraction increased
Which hormone is the major stimulant for release of T3 and T4 and from where is it secreted?
Thyroid stimulating hormone
Anterior pituitary
Which hormone is the major stimulant for release of thyroid stimulating hormone and from where is it secreted?
Thyrotrophin releasing hormone
Hypothalamus
When are thyroid hormone levels naturally highest?
Late at night
When are thyroid hormone levels naturally lowest?
Morning
What does a thyroid function test in Hashimotos show?
Low T3 & T4
High TSH
What does a thyroid function test in Graves disease show?
High T3 & T4
Low TSH
What is the onset of graves disease?
Gradual
Describe the swelling in Graves disease and does this cause dysphagia?
Diffuse enlargement
Painless swelling
Dysphagia only in bulky disease
What is the clinical thyroid status in thyroiditis?
Initially hyperthyroid, then hypothyroid
What are the symptoms of thyroiditis?
Acute onset
Flu-like symptoms
Tremor often present
No eye disease
What is the most common type of thyroid cancer?
Papillary
What is the second most common type of thyroid cancer?
Follicular
Between what ages does the risk of developing thyroid cancer in women increase?
15-40
What thyroid condition is development of papillary thyroid cancer associated with?
Hashimoto’s
How does papillary thyroid cancer tend to spread?
Through lymphatics
Where does papillary thyroid cancer spread haematogenously?
Bone
Brains
Lung
Liver
How does follicular carcinoma tend to spread?
Haematogenously
What investigations can be done if thyroid cancer suspected?
Ultrasound guided fine needle aspiration
May need excision biopsy of lymph node
What are some of the clinical predictors of thyroid malignancy?
New thyroid nodule aged 50 Vocal cord palsy History of radiation exposure to head and neck Male Nodule increasing in size
What is the preferred treatment option for thyroid cancer?
Surgery:
Sub-total thyroidectomy
Total thyroidectomy
Thyroid lobectomy with isthmusectomy
Which system is used in Ninewells to determine risk of post-op complications in patients who have just had thyroid cancer surgery?
AMES A - Age M - Metastatses E - Extent of primary tumour S - Size of primary tumour
What is involved in post-op care following thyroid surgery?
Calcium levels monitored and replaced if necessary
IV calcium if <1.8mm/L
Patients discharged on T3 and T4
When is whole body iodine scanning used?
In patients who have undergone total or sub-total thyroidectomy, between 3-6 months post-op
When are thyroid replacement medications stopped prior to whole body iodine scanning?
T3 - 2 weeks prior to scan
T4 - 4 weeks prior to scan
What is Grave’s disease?
An autoimmune disease causing hyperthyroidism - antibodies to TSH receptors, thyroglobulin and thyroid peroxisomes
Which antibody should be tested for if Grave’s disease suspected and why?
Anti-TSH antibody: more specific than peroxisome or thyroglobulin Abs
What is the triad of features in Grave’s disease?
Hyperthyroidism with diffuse enlargement of the thyroid
Eye changes (exophthalmos)
Pretibial myxoedema
What would TFTs show in primary thyroid disease?
Hypothyroidism - high TSH and low T3/T4
Hyperthyroidism - low TSH and high T3/T4
What would TFTs show in secondary thyroid disease?
Hypothyroidism - low TSH and low T3/T4
Hyperthyroidism - high TSH and high T3/T4
What is the first marker of hypothyroidism/pre-clinical hypothyroidism?
High TSH
T3 & T4 normal
What is pretibial myxoedema?
Accccumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis and other tissues, resulting in doughy appearance of skin seen classically in the shins: this is seen in Graves disease
What are some goitrous causes of hypothyroidism?
Hashimoto's thyroiditis Iodine deficiency Drug induced - amiodarone, lithium, IL-2, IFN-a, aminosalicylic acid Hereditary biosynthetic defects Maternally transmitted
What are some self-limiting causes of hypothyroidism?
Following withdrawal of suppressive thyroid therapy
Subacute thyroiditis and chronic thyroiditis with transient hypothyroidism
Postpartum thyroiditis
What are some of the non-goitrous causes of hypothyroidism?
Congenital developmental defect
Atrophic thyroiditis
Post-ablative (radioiodine, surgery)
Postradiation (e.g. for lymphoma)
What is the most common cause of hypothyroidism in the western world?
Hashimoto’s thyroiditis/autoimmune thyroiditis
What is Hashimoto’s thyroiditis?
Autoimmune destruction of the thyroid gland resulting in reduced thyroid hormone production
What antibodies are present in Hashimoto’s?
Thyroid peroxidase antibodies
What are some of the signs and symptoms of hypothyroidism?
Course, sparse hair Dull expressionless face Periorbital puffiness Pale cool 'doughy' skin Vitiligo Hypercarotenaemia Cold intolerance Pitting oedema Reduced heart rate Pericardial effusion Cardiac dilatation Hyperlipidaemia Decreased appetite Weight gain Constipation Deep hoarse voice Macroglossia Obstructive sleep apnoea Decreased intellectual and motor activities Depression Psychosis Muscle stiffness/cramps Carpal tunnel syndrome Menorrhagia Oligo- or amenorrhoea Hyperprolactinaemia
Why is it dangerous to rapidly restore metabolic rate in hypothyroidism?
May precipitate cardiac arrhythmias
How frequently should TSH be checked in treated hypothyroidism?
2 months after any dose change
Every 12-18 months once stable
What is the main treatment in hypothyroidism?
Thyroxine
When might dose requirement of thyroxine be increased?
During pregnancy
Who is typically affected by myxoedema coma?
Elderly women with long standing but frequently unrecognised or untreated hypothyroidism
What are some of the signs and symptoms of hyperthyroidism?
Palpitations Atrial fibrillation Cardiac failure (rare) Tremor Sweating Anxiety/nervousness Irritability Sleep disturbance Frequent, loose bowel movements Lid retraction Double vision "Bulging eyes" (Graves) Brittle, thinning hair Rapid fingernail growth Lighter/less frequent periods Muscle weakness - thighs & upper arms Weight loss Increased appetite Intolerance to heat
What does Graves disease show on scintigrapy?
Smooth symmetrical goitre
High uptake
What is the typical presentation of nodular thyroid disease?
Older patient
Insidious onset
Gland may feel nodular
What does nodular thyroid disease show on scintigraphy?
Assymetrical goitre
High uptake
What is sub-acute thyroiditis/de Quervains often associated with?
Viral infection - sore throat/fever
What do thyroid function tests show in de Quervains?
T4 - high in early stage, low in late, then normal
TSH - low in early stage, high in late, then normal
What does a scintigraphy scan show in sub-acute thyroiditis?
Low uptake
What is a thyroid storm?
A medical emergency - severe hyperthyroidism
What are the signs and symptoms of a thyroid storm?
Respiratory and cardiac collapse
Hyperthermia
Exaggerated reflexes
What oral medications can be given to treat hyperthyroidism?
Carbimazole
Propylthiouracil
Which treatment of hyperthyroidism is preferred in pregnancy?
Propylthiouracil
What treatment can be given to treat the sympathomimetic symptoms of hyperthyroidism?
Beta-blockers
What are the risks associated with thyroid surgery?
Scar
Hypothyroidism
Para-hypothyroidism
Reccurent laryngeal palsy
Where are TSH receptors found?
The surface of follicular cells
What effect does increased production of cAMP have on T3 and T4 levels?
Increases production and release of T3 and T4
Which patients are typically affected by Hashimoto’s?
Middle aged women
What are some of the risks associated with Hashimoto’s?
Increased risk of developing other auto-immune diseases
Increased risk of developing B cell lymphoma in the affected gland
What is a goitre?
Any enlargement of the thyroid gland
What are thyroid adenomas?
Discrete solitary mass composed of neoplastic thyroid follicles, encapsulated by a surrounding collagen cuff
Which thyroid carcinoma is derived from C-cells?
Medullary carcinoma
