Parathyroid disorders and calcium homeostasis JB

Question 1

Why is calcium important?

Answer 1

ions essential for a multitude of cellular functions intracellular 2nd messenger, enzyme cofactor, neuromuscular excitability and skeletal integrity

Question 2

alterations in extracellular Calcium (ICa2+) result in short term and long term homeostatic changes

Answer 2

⇓ [ICa2+] results in the immediate release of pre-formed PTH and within hours an increase in gene transcription leads to increased in PTH mRNA and de novo PTH synthesis

Question 3

Explain the calcium receptor

Answer 3

•G-protein-coupled receptor

Question 4

what kind of receptor is the PTH receptor?

What are the actions of PTH?

Answer 4

G protein coupled receptor:

Bone: increases alcium and phosphate release (brone breakdown)

Renal: Ca reabsorption from distal tubule (can cuase hypokalaemia)
inhibits proximal phosphate reabsorption
synthesis of 1,25 vitamin D

1,25Vit D stimulates small intestinal receptors increasing absorption of ICa2

Question 5

What are the manifestations of hypercalcaemia?

Answer 5

Non specific: anorexia, abdominal pain, constipation, diarrhoea, lethargy, altered mental state, depression

GI: constipation, pancreatitis
Renal: calculus, chronic hypercalcaemic neuropathy
HTN

Question 6

how would you assess the cause of hypercalcemia & what would this mean?

Answer 6

If PTH levels elevated/normal in raised ca2+
- primary hyperparathyroidism is problem

If PTH suppressed and raised Ca2+
- non parathyroid mediated: malignancy(PTHrp, osteolytic masses), vitamin D excess, thyrotoxicosis, adrenal insufficiency, thiazide diuretics + adrenal insufficiency

Question 7

What is primary hyperparathyroidism

Answer 7

Characterised by raised calcium and non-suppressed PTH
• 1:500 general population COMMON
Increases with age, Female > male

Question 8

What ar ethe management ooptions for primary hyperparathyroidism?

Answer 8

Management:

• observe if mild biochemical disease (? HRT in menopausal women)
• parathyroidectomy if patient at risk of complicaitons
• medical therapy for severe hypercal (>3-3.5mmol/L)
• rehydration, bisphosphonates
• Calcimimetrics for PTH mediated hypercalcemia

Question 9

What special considerations would you consider in PHTH?

Answer 9

Familial hypocalcuric hypercalcaemia
•
Parathyroid hyperplasia (5%) PHPT)
- Sporadic

Question 10

What is familial isolated hyperparathyroidism?

Answer 10

Disorder of ICa2+ sensing due to CaR mutations
Characterised by lifelong mild-mod asymptomatic hypercalcemia

Autosomal dominant
– Generally considered benign (no nephrolithiasis), however older patients with FHH show high prevalence of chondrocalcinosis, possible increased risk of pancreatitis

– Elevated set point for Ca++- regulated PTH release (i.e. for any given level of serum Ca++, FHH patients have higher concentrations of PTH than normal

Question 11

What is MEN1?

what is it characterised by?

Answer 11

Multiple Endocrine Neoplasia Type 1, Wermer’s syndrome, MEA1
- characterised by a clinical phenotype of:
: parathyroid, enteropancreatic and pituitary neoplasia

Question 12

Describe the MEN1 genotype

Answer 12

610 aa product which behaves as a transcriptional co repressor of genes associated with cell growth.
- >80% of mutations predict a loss in function

There are numerous polymorphisms not associated with MEN1
10-20% of families have NO IDENTIFIABLE MUTATION!!