Metabolism

Question 1

Functions of thyroid hormones

Answer 1

Normal growth development
Metabolic activity and oxygen requirements
Lipid and carb metabolism

Question 2

Embryology of thyroid

Answer 2

Week 4: thyroid appears from endodermal tissue
Week 5: thyroglossal duct breaks down and gland decends
Week 7: thyroid migrates anterior to trachea
Week 10: thryoglossal duct disappears
Week 12–20: thyroid functional
Week 20–26: thyroid independent

Question 3

Lingual thyroid

Answer 3

Failure of thyroid to migrate during development

Question 4

Thyroglossal cyst

Answer 4

Remnant of thyroglossal duct that didn’t break down

Can be seen moving up when patient protrudes tongue

Question 5

Anatomy of thyroid

Answer 5

Deep to sternohyoid
Anterior to recurrent laryngeal nerve and trachea cartilage rings 2 and 3
Right to oesophagus

Question 6

Blood supply of thyroid

Answer 6

Superior thyroid artery from external carotid artery

Inferior thyroid artery from subclavian artery (thyrocervical trunk)

Question 7

Medullary thyroid cancer

Answer 7

Aggressive cancer that secretes calcitonin

Question 8

Thyroglobulin

Answer 8

Storage form of T3/4 found in colloid of the thyroid

Question 9

Describe the process of T3/4 release

Answer 9

1) Iodine uptake into bloodstream is oxidised to iodide
2) Iodide rapidly incorporated into tyrosine molecules in follicular cells, then into thyroglobulin
3) At lumen interface, remaining iodide is catalysed to MIT and DIT by thyroid peroxidase (which required H2O2) and is stored in colloid as thyroglobulin
4) TSH from AP reaches follicular cell membrane which scallops in to allow endocytosis of “colloid drops” containing thyroglobulin and releases T4/3 into capillary

Question 10

Locations of NIS

Answer 10

Breast
Salivary glands
Ciliary body of eye
Gastric mucosa
Differentiated thyroid cancer cells

Question 11

Symptoms of thyrotoxicosis

Answer 11

Nervousness
Sweating
Weight loss
Heat sensitivity
Tachycardia
Weakness
Goitre
Skin changes
Tremor
Eye signs e.g., in Graves

Question 12

Causes of thyrotoxicosis

Answer 12

Thyroiditis
Graves
Amiodarone
Iodine
Thyroxine
Toxic nodule

Question 13

TSH and T4 levels in primary hypothyroidism

Answer 13

TSH will be high and T4 will be low

Question 14

TSH and T4 levels in secondary hypothyroidism

Answer 14

TSH will be normal or low and T4 will be low

Question 15

TSH and T4 levels in primary hyperthyroidism

Answer 15

TSH will be low and T4 will be high

Question 16

TSH and T4 levels in secondary hyperthyroidism

Answer 16

TSH will be high and T4 will be high

Question 17

NIS

Answer 17

Sodium iodine transporter
Iodide concentration in plasma is extremely low so it is “trapped” by NIS
Active transporter that exchanges 2 sodium ions for 1 iodide ion against its concentration gradient

Question 18

Parathyroid hormone functions

Answer 18

Stimulates osteoclastic bone resporption
Stimulates renal tubular reabsorption of calcium
Stimulates gut absorption of calcium by acting on the kidney to convert calcidiol to calcitriol

Question 19

3 things that can regulate PTH release

Answer 19

Serum ionized calcium
Serum phosphate
Serum 1,25 dihydroxyvitamin D

Question 20

ECF calcium

Answer 20

45% ionised, bioactive
10% complexed with anions
45% protein-bound

Question 21

Describe how PTH is released into the ECF

Answer 21

Calcium present in food enters the stomach. Magnesium acts as a cofactor to uptake calcium via the transmembrane calcium receptor. Calcium is uptaken into the parathyroid chief cell which activates PTH to be released into the ECF.

Question 22

Basic vitamin D metabolism

Answer 22

Sunlight absorbed by skin, which makes calciferol (also from diet)
Calcirefol is hydroxylated by the liver to make calcidiol
Calcidiol moves to the kidney where it is metabolised via PTH to calcitriol
Calcitriol uptaken by the kidney tubules, increasing calcium and phosphate absorption

Question 23

Parathyroid hormone-related peptide

Answer 23

Important paracrine regulator of breast, skin and bone

Produced in excess by some cancers, leading to hypercalcaemia (acts very similarly to PTH)

Question 24

Primary hyperparathyroidism

Answer 24

Overactive parathyroid gland causing bone breakdown and increased reabsorption of calcium
Causes PTH-dependent hypercalcemia

Question 25

Examples of vitamin-D dependent causes of hypercalcaemia

Answer 25

Sarcoidosis – granulomas express high levels of 1α-hydroxylase, the enzyme that catalyzes the hydroxylation of 25-OH vitamin D to its active form which increases calcium and phosphate reabsorption Vitamin D intoxication

Question 26

Hypoparathyroidism

Answer 26

Causes hypocalcaemia due to reduced release of PTH and therefore decreased absorption and resorption of calcium Can be caused by many things, including surgery, radiation, autoimmune disease, infiltrative diseases etc.

Question 27

Pseudohypoparathyroidism

Answer 27

Parathyroid hormone resistance | PTH levels will be high, calcium levels low and phosphate levels high

Question 28

Causes of hypoparathyroidism due to abnormalities of vitamin D metabolism

Answer 28

Vitamin D deficiency/resistance Renal failure Deficient 1α-hydroxylation

Question 29

PTH influence on phosphate

Answer 29

Promotes excretion of phosphate in urine and pulls it out of bone along with calcium

Question 30

Phosphatonins

Answer 30

Specifically regulate renal handling of phosphate, therefore causes phosphate wasting

Question 31

Causes of hyperphosphataemia

Answer 31

Increased input e.g. IV phosphate, cell death | Decreased excretion e.g. renal failure, PTH deficiency

Question 32

Causes of hypophosphataemia

Answer 32

Inadequate GI absorption e.g. due to vitamin D deficiency Respiratory alkalosis Renal loss

Question 33

How do phosphatonins contribute to hypophosphataemia?

Answer 33

FGF23 (derived from bone) inhibits the hydroxylation of inactive form of vitamin D and decreases sodium phosphate reabsoprtion in the kidney Together, there is an overall decrease in phosphate absorption leading to hypophosphataemia

Question 34

Osteomalacia

Answer 34

Failure of bone to mineralise Accumulation of unmineralised osteoid Can be calciopenic, phosphopenic or due to osteoblast dysfunction

Question 35

Autosomal Dominant Hypercalciuric Hypocalcaemia

Answer 35

Constitutive activation of calcium sensing receptor Parathyroids read plasma ionised calcium level as being higher than it really is, so PTH level is inappropriately low for a given calcium level No real treatment, can give small doses of vitamin D if recurrent symptoms are present