PBL 3: Thyroid Gland Flashcards
where is the thyroid gland located
located in anterior neck, between C5-T1
Thyroid gland is an _______ gland. It has two lobes, connected with a middle part called the _______
endocrine
isthmus
The thyroid gland sits behind the strap muscles. what are they called
sternohyoid
sternothyroid
where are the parathyroid glands found and how many do we have
found on the posterior aspect of the two lobes of the thyroid gland
4
the compartment is bound by the __________ fascia
pretracheal
what does the Parathyroid gland produce
PTH
what are the cell types in the parathyroid gland
chief cells
oxyphil cells
water clear
what are the hormones of thyroid gland stored in
stored in cavities, surrounded by secretory cells (follicular cells)
what is a thyroid follicle
Small spherical grouping of follicular cells
The outer spherical layer - follicular cells
The inner cavity- colloid core (glycoprotein)
see pics
What does the colloid core consist of?
Thyroglobulin- Thyroid hormone precursor proteins
where are the parafollicular/C cells found
in between the follicular cells
what do parafollicular/C cells secrete?
Calcitonin- Ca lowering hormone
what epithelium are follicular cells normally?
Simple cuboidal epithelium
What happens to thyroid follicle structure when stimulated to release T4/T3
Follicular Cells become columnar and lumen is depleted of colloid
What happens to thyroid follicle structure when suppressed
Follicular Cells appear flattened and colloid accumulates in the lumen
what is the arterial supply of the thyroid gland
Superior thyroid arteries- supplies anterior and superior portion
Inferior Thyroid arteries- supplies posterior and inferior portion
what is the venous drainage of the thyroid gland
venous plexus formed by superior, middle and inferior thyroid vein
Superior + middle- drains into internal jugular vein
Inferior- drains into brachiocephalic vein
what regulates thyroid hormone action
hypothalamic- pituitary-thyroid axis
what does the hypothalamus secrete and what effect does that hormone have on the anterior pituitary gland
Secretes TRH (thyroid releasing hormone) TRH acts on thyrotrophs cells in anterior pituitary gland to release TSH (thyroid stimulating hormone)
what effect does TSH have on the thyroid gland
TSH acts on the thyroid gland to cause synthesis and secretion of T3/T4
what sub-units does TSH have
alpha- same as FSH, LH and HCG
beta- unique
how does negative feedback work in TSH secretion?
if T3 and T4 levels high:
T3 and T4 negative feedbacks to hypothalamus and pituitary gland to inhibit TSH production
what happens in primary hypothyroidism and give example
primary- problem with main organ
- Underproduction of T3/T4 due to abnormal thyroid gland
- High TSH but low T3/T4
- Hashimoto’s Thyroiditis
what happens in secondary hypothyroidism
- Underproduction of T3/T4 due to abnormal anterior pituitary gland
- Low TSH and T3/4
- Sheehan’s syndrome
what happens in tertiary hypothyroidism
- Underproduction of T3/T4 due to abnormal hypothalamus
- Low T3/T4, variable TSH, Low TRH
- RARE
what molecule is neccesary for thyroid hormone synthesis
Iodine
where is iodine found
how much iodine do our bodies need
seawater, fruit and vegetables
150-300 ug/day
where is iodine deficiency prominent and what does it lead to
high altitudes
leads to endemic goitre (enlarged thyroid)
Iodine is reduced to ______ and then absorbed in the _____
Iodide
GI tract
Describe the first step in thyroid hormone biosynthesis
Iodine transport
- Iodide transported into the follicular cells by Na/I active transporter against the chemical gradient from the basolateral membrane (energy required)
- iodide then diffuses to apex of cells and is transported by the protein- PRENDERIN into vesicles fused with the apical cell membrane
Describe the second step in thyroid hormone biosynthesis
organification
- Oxidation of iodide to iodine occurs in the vesicles and it binds to tyrosine residues on Thyroglobulin- in the colloid (this process is called organification and catalysed by the enzyme thyroid peroxidase)
- Iodine combines with tyrosine residues on thyroglobulin to form MIT or DIT
Describe the third step in thyroid hormone biosynthesis (T3 and T4 formation)
- Peroxidase then combines MIT+ DIT = T3 and DIT+DIT = T4. This takes place within the thyroglobulin proteins
- peroxidase is more efficient at combining 2 DIT therefore there is more T4*
- Endocytosis of thyroglobulin into follicular cells
- The endocytosed thyroglobulin undergoes proteolysis (lysosyme) to release the T4 and T3.
- T4 and T3 are transported out of the cell and into the circulation.
T_ is more metabolically active than T_
3
4
T_ released in greater amounts than T_
4
3
How does T4 become T3
T4 in the periphery undergoes 5’deiodination to form T3
how much of circulating thyroxine (T4) is free and bound
Free- 0.5%
Bound- 99.5%
what is the importance of free Thyroxine
- Free component is active and regulated, therefore, only free t4 is measured
- Bound to thyroid binding globulin, transthyretin and albumin
what is the active version of T and what does is bind to
T3 is the active version which binds to nuclear receptors
what are the thyroid hormone action on skeletal, cardiovascular and metabolic system
Skeletal: bone turnover
Cardiovascular: heart rate
Metabolic: lipids and glucose
what is the definition of Hyperthyroidism
Condition that occurs due to excessive production of thyroid hormone by thyroid gland
what are the causes of hyperthyroidism
– Auto immune- Graves’ disease
– Toxic adenoma- benign tumour of thyroid gland
– Multinodular goitre- excess production of thyroxine (T4) without requiring stimulation from TSH
– Thyroiditis- inflammation of thyroid gland leading to excess production of thyroxine
– Excessive administration of thyroxine- use of thyroxine to lose weight
what are the clinical features of Graves disease
1) Dysthyroid eye disease/ Graves’ Ophthalmopathy
- 50% of patients seen with this
- lid retraction and lid lag
- pre-orbital oedema (puffy eyes or swelling under eyes)
- proptosis (abnormal anterior protrusion of eyes)
- diplopia (double vision)
- optic nerve compression is rare
2) Dermopathy- Pretibial myxoedema
3) Thyroid acropachy- characterised by soft tissue swelling and finger clubbing
what are the clinical features of Hyperthyroidism
• Weight loss - Tachycardia • Tremor - Hypertension • Heat intolerance - Palpitations • Diarrhoea - Sweating
what are the treatment for Hyperthyroidism
Anti-thyroid drugs
Radioiodine therapy
Surgery
what are the anti-thyroid drugs.
describe mechanism of action and adverse effects
1) Carbimazole
Inhibits action of thyroid peroxidase enzyme- reduces thyroid hormone production
Adverse effects:
- Aplasia cutis
- Rash
- Bone marrow suppression so causes agranulocytosis
2) Propylthiouracil
Inhibits thyroid peroxidase
Inhibits T4 to T3 conversion
watch LFTs
How does radioiodine therapy work in treatment for Hyperthyroidism
- Use if beta emission to destroy thyroid tissues
what are the side effects of radioiodine therapy
may worsen eye disease - so need steroid cover
radiation risk
defer conception for 4 months
leads to hypothyroidism (main side effect)
What is the surgery for Graves disease and what are the complications
Removal of thyroid gland Complications: • Haemorrhage • Rec laryngeal palsy- hoarse voice • Permanent hypocalcaemia- damage to parathyroid glands • Hypothyroidism
what is the definition of hypothyroidism
Condition that occurs due to not enough production of thyroxine by thyroid gland
what are the causes of hypothyroidism
Primary- pathology of thyroid gland
Severe iodine deficiency
Autoimmune thyroiditis (Hashimotos)
- Destruction of the thyroid gland (anti TPO antibody)
- May be positive family history, more common in females
Thyroiditis
- Viral and often painful
Iatrogenic
- Thyroidectomy
- Following radio iodine therapy
- Drug-induced (Amiodarone, lithium, sunitinib)
Secondary- pathology of the pituitary gland
Pituitary disease
– Secondary hypothyroidism
what are the clinical features of hypothyroidism
– Depression – Lethargy – Weight gain – Bradycardia – Dry skin – Constipation – Cold intolerance – Poor concentration – Hoarseness – Menorrhagia – Coarse, thin hair – Anaemia – Slow relaxing reflexes – May have goitre
what is the treatment for hypothyroidism and what are the long-term goals
Levothyroxine
- Generally need 1.7-2.0 micrograms / kg /day
- Best taken on an empty stomach
- Avoid taking with proton pump inhibitors, ferrous sulphate or calcium
Long term goals:
– Resolve symptoms and normalise TSH
– Full suppression of TSH associated with Atrial
fibrillation and osteoporosis
what are the investigations for hypothyroidism
Measure
– Free T4
– TSH
• Primary hypothyroidism
– High TSH and low T4
• Secondary hypothyroidism
– Low TSH and low T4
Thyroid cancer has good prognosis if cancer is differentiated. give examples of the differentiated cell
- papillary
- follicular
- mixed
- medullary carcinoma of thyroid
thyroid cancer has poorer prognosis if cancer is undifferentiated. give examples of the undifferentiated cell
- anaplastic
- small cell
