hyperparathyroidism

Question 1

definition of hyperparathyroidism

Answer 1

primary - increased secretion of PTH regardless of Ca

secondary - increased PTH secondary to hypocalcaemia

tertiary - autonomous PTH secretion following chronic secondary hyperparathyroidism

Question 2

aetiology of primary hyperparathyroidism

Answer 2

parathyroid gland ademoma, or hyperplasia (80% single adenoma, 18% hyperplasia/multiple adenoma)

parathyroid carcinoma (2%)

may be associated with multiple endocrine neoplasia (MEN 1)

Question 3

aetiology of secondary hyperparathyroidism

Answer 3

chronic renal failure

vit D deficiency

Question 4

what is MEN type 1

Answer 4

mutation in menin gene on chr 11

• parathyroid adenoma or hyperplasia
• pancreatic endocrine tumours
• pit adenomas

Question 5

what is MEN 2

Answer 5

mutation in RET gene on chr 10

• medullary thryoid carcinoma
• phaeochromocytoma
• parathyroid hyperplasia (MEN-2A)
• mucosal neuromas on lips and tongue (MEN-2B)

Question 6

epidemiology of hyperparathyroidism

Answer 6

primary

5 in 100000/yr

females more

40-60yrs

Question 7

presenting sx of primary hyperparathyroidism

Answer 7

asymptomatic when mild hypercalcaemia

polyuria bnut dehydrated

polydipsia

renal calculi

bone pain, fractures, osteopenia/porosis

abdo pain

pancreatitis

ulcers - duodenal more than gastric

nausea

constipation

psychological depression

lethargy

weak

HTN

Question 8

presenting sx of secondary hyperparathyroidism

Answer 8

symptoms of hypocalcaemia

underlying cause - chronic renal failure/vit D deficiency

Question 9

Ix for hyperparathyroidism

Answer 9

UE

serum Ca - high in primary/tertiary, low/normal secondary

phosphate - low in primary (unless in renal failure)/tertiary, high secondary

albumin - to calculate corrected ca

high ALKPHOS (from bone activity)

vit d - low in secondary

PTH levels - high/normal in primary, high in secondary

when parathyroid carcinoma - more likely to have marked hypercalcaemia with high serum PTH levels

primary - hyperchloraemic acidosis (normal anion gap) - from PTH inhibition of renal tubular reabsorption of bicarb

urine analysis

renal US - renal calculi

radiograph (not routine)

preop localisation - US od neck and technetium sestamibi scan

DEXA

Question 10

urine analysis in hyperparathyroidism

Answer 10

24hr high urine Ca

ddx includes familial hypocalciuric hypercalcaemia.

So if high/inappropriately normal PTH - Ca:creatinine clearance ratio measured to differentiate.

primary hyperparathyroidism (ratio>0.01) and FHH (ratio<0.01)

Calcium: creatinine clearance ratio:

• Urine calcium (mmol/L) [Plasma creatinine (mmol/L)/1000]
• Plasma calcium (mmol) Urine creatinine (mmol/L)

24hr urine collection should be sent for creatinine clearance and ca measurement

Question 11

XR for hyperparathyroidism

Answer 11

osteitis fibrosa cystica because of severe resorption - rare

• subperiosteal erosion of phalanges
• cysts
• brown tumours (osteolucent bone defects)
• diffuse porotic mottling of skull - from demineralisation (pepper pot skull)
• acro-osteolysis

sclerosis of superior and inferior vertebral margins with central demineralisation (rugger jersey sign)

renal calculi/nephrocalcinosis

Question 12

PTH in pts with hypercalcaemia secondary to malignancy, myeloma or granulomatous conditions (TB, sarcoidosis, lymphoma causing excess production of 1,25-dihydroxyvitamin D)

Answer 12

suppressed PTH

hypercalcaemia secondary to malignancy - treated with rehydration and IV pamidronate (a bisphosphonate).

Question 13

FHH

Answer 13

Autosomal dominant disorder caused by inactivating mutations in the gene encoding the calcium-sensing receptor on the parathyroid cells and in the kidneys.

Question 14

Mx for acute primary hyperparathyroidism

Answer 14

IV fluids (4-6 in 1st 24hr)

Question 15

conservative Mx for primary hyperparathyroidism

Answer 15

when dont meet surgical criteria

avoid exacerbating factors - thiazide diuretics

adequate hydration (6-8 glasses of water a day) - to prevent stones

moderate Ca and vit D intake

Question 16

surgical Mx of primary hyperparathyroidism

Answer 16

subtotal parathyroidectomy - prevents fractures and peptic ulcers

total parathyroidectomy in MEN1

indications: symptomatic or asymptomatic with ABCCrDE

• Age <50yrs
• BMD - T score <2.5
• calculi (renal stones)
• Creatinine clear reduced by 30%
• difficult to follow up
• elevated serum ca >0.25 mmol/L above upper limit of normal or 24hr urinary ca >10mmol

recurrence 8% over 10yrs

Question 17

Mx of secondary hyperparathyroidism

Answer 17

secondary - treat underlying renal failure.

Ca and Vit D supplements

phosphate binders

cinacalcet if PTH >85pmol/L and parathyroidectomy tricky

Question 18

complications of primary hyperparathyroidism

Answer 18

high PTH = high bone resorption, renal tubular Ca reabsorption, 1a-hydroxylation of vit D and intestinal Ca absorption = hypercalcaemia

Question 19

complications of secondary hyperparathyroidism

Answer 19

increased sitimulation of osteoclasts and bone turnover = osteitis fibrosa cystica

Question 20

complications of surgery for hyperparathyroidism

Answer 20

hypoparathyroidism

hypocalcaemia - hungry bones syndrome - check Ca daily for 14 days

recurrent laryngeal nerve palsy (<1%) = hoarse

Question 21

prognosis for hyperparathyroidism

Answer 21

primary - surgery curative for benign disease in most cases

secondary or tertiary - as for chronic renal failure

Question 22

sx and signs for hypercalcaemia

Answer 22

‘Bones, stones, groans, and psychic moans.’

Abdominal pain;

vomiting;

constipation;

polyuria;

polydipsia;

depression;

anorexia;

weight loss;

tiredness;

weakness;

hypertension,

confusion;

pyrexia;

renal stones;

renal failure;

ectopic calcification (eg cornea);

cardiac arrest.

ECG: reduced QT interval.

Question 23

role/action of PTH

Answer 23

increases osteoclast activity - releasing Ca and phos from bones

increases Ca and decreases phos reabsorption from the kidney

•active 1,25 dihydroxy-vitamin D3 production is increased.

Overall effect is high Ca2+ and reduced phos

Question 24

ddx for high ca and PTH

Answer 24

thiazides

lithium

familial hypocalciuric hypercalcaemia

tertiary hyperparathyroidism

primary hyperparathyroidism

Question 25

medical Mx of primary hyperparathyroidism

Answer 25

Cinacalcet (a ‘calcimimetic’) increases sensitivity of parathyroid cells to Ca2+ ( = reduces PTH secretion);

monitor Ca2+ within 1 week of dose changes;

SE: myalgia; low testosterone.

Question 26

aetiology of tertiary hyperparathyroidism

Answer 26

after prolongued secondary hyperparathyroidism

causes glands to act autonomously having undergone hyperplastic or adenomatous change

= increased Ca secretion form high PTH unlimited by feedback control

seen in chronic renal failure

Question 27

malignant hyperparathyroidism

Answer 27

parathyroid-related protein (PTHrP) is produced by sq cell lung cancer, breast and renal call ca

mimics PTH = high Ca, PTH low