hyperparathyroidism Flashcards
definition of hyperparathyroidism
primary - increased secretion of PTH regardless of Ca
secondary - increased PTH secondary to hypocalcaemia
tertiary - autonomous PTH secretion following chronic secondary hyperparathyroidism
aetiology of primary hyperparathyroidism
parathyroid gland ademoma, or hyperplasia (80% single adenoma, 18% hyperplasia/multiple adenoma)
parathyroid carcinoma (2%)
may be associated with multiple endocrine neoplasia (MEN 1)
aetiology of secondary hyperparathyroidism
chronic renal failure
vit D deficiency
what is MEN type 1
mutation in menin gene on chr 11
- parathyroid adenoma or hyperplasia
- pancreatic endocrine tumours
- pit adenomas
what is MEN 2
mutation in RET gene on chr 10
- medullary thryoid carcinoma
- phaeochromocytoma
- parathyroid hyperplasia (MEN-2A)
- mucosal neuromas on lips and tongue (MEN-2B)
epidemiology of hyperparathyroidism
primary
5 in 100000/yr
females more
40-60yrs
presenting sx of primary hyperparathyroidism
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
presenting sx of secondary hyperparathyroidism
symptoms of hypocalcaemia
underlying cause - chronic renal failure/vit D deficiency
Ix for hyperparathyroidism
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
urine analysis in hyperparathyroidism
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
XR for hyperparathyroidism
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
PTH in pts with hypercalcaemia secondary to malignancy, myeloma or granulomatous conditions (TB, sarcoidosis, lymphoma causing excess production of 1,25-dihydroxyvitamin D)
suppressed PTH
hypercalcaemia secondary to malignancy - treated with rehydration and IV pamidronate (a bisphosphonate).
FHH
Autosomal dominant disorder caused by inactivating mutations in the gene encoding the calcium-sensing receptor on the parathyroid cells and in the kidneys.
Mx for acute primary hyperparathyroidism
IV fluids (4-6 in 1st 24hr)
conservative Mx for primary hyperparathyroidism
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
surgical Mx of primary hyperparathyroidism
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
Mx of secondary hyperparathyroidism
secondary - treat underlying renal failure.
Ca and Vit D supplements
phosphate binders
cinacalcet if PTH >85pmol/L and parathyroidectomy tricky
complications of primary hyperparathyroidism
high PTH = high bone resorption, renal tubular Ca reabsorption, 1a-hydroxylation of vit D and intestinal Ca absorption = hypercalcaemia
complications of secondary hyperparathyroidism
increased sitimulation of osteoclasts and bone turnover = osteitis fibrosa cystica
complications of surgery for hyperparathyroidism
hypoparathyroidism
hypocalcaemia - hungry bones syndrome - check Ca daily for 14 days
recurrent laryngeal nerve palsy (<1%) = hoarse
prognosis for hyperparathyroidism
primary - surgery curative for benign disease in most cases
secondary or tertiary - as for chronic renal failure
sx and signs for hypercalcaemia
‘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.
role/action of PTH
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
ddx for high ca and PTH
thiazides
lithium
familial hypocalciuric hypercalcaemia
tertiary hyperparathyroidism
primary hyperparathyroidism
medical Mx of primary hyperparathyroidism
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.
aetiology of tertiary hyperparathyroidism
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
malignant hyperparathyroidism
parathyroid-related protein (PTHrP) is produced by sq cell lung cancer, breast and renal call ca
mimics PTH = high Ca, PTH low
