ENDOCRINOLOGY - PARATHYROID DISEASE

Question 1

What are the 3 forms of calcium in the blood that make up total calcium?

Answer 1

40% bound to albumin
45% is ionised calcium which is active
15% is bound to anions such as phosphate

Question 2

What can cause pseudohypocalcaemia?

Answer 2

Reduction in amount of albumin will reduce the amount of calcium

Question 3

What are the 3 controls of calcium homeostasis?

Answer 3

Vitamin D
parathyroid hormone
Calcitonin

Question 4

How does vitamin D regulate calcium levels?

Answer 4

Calcitriol can be released into the blood stream and stimulate intestinal epithelial cells to increase the synthesis of calbindin-D proteins which increase intestinal absorption of calcium by facilitating the transport of calcium.

Question 5

How does parathyroid hormone regulate calcium levels?

Answer 5

• Increases bone resorption
  • Increases renal reabsorption of calcium
  • Increasing synthesis of calcitriol

Question 6

How does parathyroid hormone increase bone resorption?

Answer 6

PTH upregulates osteoblasts expression of RANK-L which stimulates pre-osteoclasts to differentiate into osteoclasts.

Question 7

How does parathyroid hormone increase renal reabsorption of calcium?

Answer 7

PTH upregulates expression of specific channels in the DCT leading to increased reabsorption of calcium and increased excretion of phosphate.

Question 8

How does parathyroid hormone increase synthesis of calcitriol?

Answer 8

PTH upregulates expression of 1-alpha hydroxylase which catalyses the conversion of inactive 25-hydroxycholecalciferol into calcitriol

Question 9

How does calcitonin regulate calcium levels?

Answer 9

parafollicular cells secrete calcitonin which can inhibit osteoclasts and reduce bone resorption.

Question 10

How is calcitriol synthesised from a cholesterol precursor?

Answer 10

• 7-dehydrocholesterol is converted into vitamin D3 under the influence of UV radiation
• Vitamin D3 is converted to 25-hydroxyvitamin-D by 25 hydroxylase in the liver
• 1-alpha-hydroxylase converts 25-hydroxylase vitamin-D into 1,25-dihydroxyvitamin-D (calcitriol) - this is metabolically active

Question 11

Whats the mechanism for preventing calcitriol toxicity?

Answer 11

If levels of calcitriol become excessive, it is converted to 24,25-dihydroxycholecalciferol which is less active

Question 12

What causes hypoparathyroidism?

Answer 12

• Autoimmune
• Congenital e.g. Di George syndrome
• Radiation
• Surgery - thyroidectomy of parathyroidectomy
• Hypomagnesia - Mg is required for PTH secretion
• Pseudohypoparathyroidism - failure of target cells to respond to parathyroid hormone receptor
• Pseudopsuedohypoparathyroidism - morphological features of pseudohypoparathyroidism but with normal biochemistry

Question 13

What are the biochemical abnormalities in hypoparathyroidism?

Answer 13

Low PTH
Hypocalcaemia
Hyperphosphataemia

Question 14

What symptoms can hypoparathyroidism present with?

Answer 14

Paraesthesia of hands, feet and perioral
twitching facial muscles
Tetany
tiredness
mood changes, such as feeling irritable, anxious or depressed
dry, rough skin
coarse hair that breaks easily and can fall out
fingernails that break easily

Question 15

What are some signs of hypoparathyroidism?

Answer 15

Chvosteks sign
Trousseaus sign

Question 16

What is chvosteks sign?

Answer 16

facial muscles twitch after face is touched 1cm below zygomatic process)

Question 17

What is trousseaus sign?

Answer 17

Muscle spasm when blood pressure cuff is on

Question 18

What complications does severe hypocalcaemia have?

Answer 18

Seizures and cardiac arrhythmias

Question 19

How do you treat hypoparathyroidism?

Answer 19

Calcium and vitamin D supplements
Long term give recombinant human parathyroid hormone

Question 20

What is primary hyperparathyroidism?

Answer 20

When Parathyroid gland is responsible and makes parathyroid hormone independently from calcium levels. Stereotypically seen in elderly females with unquenchable third and n inappropriately normal or raised parathyroid hormone. About 80% are asymptomatic.

Question 21

What causes primary hyperparathyroidism?

Answer 21

Parathyroid adenoma - 80% most common (genetic mutation in a single cell or part of a MEN syndrome)
Hyperplasia - parathyroid cells divide excessively = growth of gland
Multiple adenoma
Parathyroid carcinoma

Question 22

What causes secondary hyperparathyroidism?

Answer 22

Chronic kidney disease (affects filtration of calcium, phosphate and affect synthesis of calcitriol)
Chronic lack of vitamin D

Question 23

What is tertiary hyperparathyroidism?

Answer 23

This happen when secondary hyperparathyroidism continues for a long period of time. It leads to hyperplasia of the glands. The baseline level of parathyroid hormone increases dramatically. Then when the cause of the secondary hyperparathyroidism is treated the parathyroid hormone level remains inappropriately high. This high level of parathyroid hormone in the absence of the previous pathology leads to high absorption of calcium in the intestines, kidneys and bones and causes hypercalcaemia.

Question 24

What is malignant hyperparathyroidism?

Answer 24

PTHrP is produced by some squamous cell lung cancers, breast cancers and renal cell cancers. This mimic PTH resulting in hypercalcaemia

Question 25

What are the symptoms of hyperparathyroidism?

Answer 25

stones, thrones, bones, groans, psychiatric overtones (kidney and gallstones, polyuria, bone pain, constipation, muscle weakness, confusion)

Secondary hyperparathyroidism may present with symptoms of CKD as this is commonly the cause. It may also cause renal osteodystrophy and calcification of blood vessels in soft tissues (due to high phosphate levels)

Tertiary hypoparathyroisims can cause elevated phosphate levels

Question 26

How is primary and tertiary hyperparathyroidism treated?

Answer 26

surgical removal of parathyroid glands
calcimimetics if this isnt possible

Question 27

How is secondary hyperparathyroidism treated?

Answer 27

This is treated by correcting the vitamin D deficiency or performing a renal transplant to treat renal failure.