Hypoparathyroidism

Question 1

primary hypoparathyroidism

• congenital cause
• biochemical analysis

Answer 1

PTH secretion is decreased due to gland failure

can be due to a congenital absence (DiGeorge syndrome) or autoimmune condition

decreased calcium and increased phosphate

Question 2

why is there increased phosphate in primary hypoparathyroidism

Answer 2

because PTH normally acts on the kidneys to eliminate phosphate

Question 3

causes of secondary hypoparathyroidism

Answer 3

• radiation
• para/thyroid surgery
• hypomagnesaemia (magnesium is required for PTH secretion)

Question 4

pseudohypoparathyroidism

Answer 4

failure of target cell to respond to PTH - this is due to a genetic defect due to the dysfunction of G protein (Gs alpha subunit) gene - GNAS1

there is low calcium, but PTH levels are raised appropriately

Question 5

what is pseudohypoparathyroidism associated with

Answer 5

bone abnormalities (McCune Albright), obesity, subcutaneous calcification, learning disability and brachydactyly

Question 6

McCune Albright syndrome

Answer 6

• Café-au-lait skin pigmentation (Coast of Maine appearance)
• Polyostotic fibrous dysplasia (affecting more than one bone)
• Precocious puberty, typically of females (earlier than normal)
• Thyroid nodules
• Pituitary – GH excess causes acromegaly features
• Cushing’s syndrome

due to post zygomatic mutation in GNAS affecting cAMP signalling

Question 7

brachydactyly

Answer 7

shortening of toes and fingers due to abnormally short bones

Question 8

pseudopseudo hypoarathyroidism

Answer 8

the morphological features of hypoparathyroidism but with normal biochemistry

patients can change between pseudo and pseudopseudo

Question 9

long term management of hypoparathyroidism

Answer 9

calcium supplement - 1-2mg per day

vitamin D

• 1 alpha calcidol 0.5-1mcg tablets
• cholecalciferol depot injection - 300,000 units every 6 months

Question 10

hypomagnesaemia

Answer 10

calcium release from cells is dependent on Mg, in Mg deficiency intracellular Ca is high (not extracellular)

Mg is needed for PTH release

in hypomagesaemia, skeletal and muscle receptors are less sensitive to PTH

Question 11

causes of hypomagesaemia

Answer 11

nephron fails to reabsorb Mg that is filtered out of the blood

diuretics - diminish Mg electrochemical gradient meaning more of the Mg ions are excreted in urine

PPI

genetic mutations in ion channels

GI illness

alcohol

pancreatitis

malabsorption

Question 12

treatment of hypomagesaemia

Answer 12

replace calcium and Mg