Hypercalcaemia/Parathyroid Disease

Question 1

How much of plasma calcium is bound to albumin?

Answer 1

40% (inactive)

Non-bound is ionized

Question 2

What effect do acidotic states have on ionized calcium level?

Answer 2

Increase ionized calcium level by decreasing protein binding

Question 3

What effect do alkalotic states have on ionized calcium level?

Answer 3

Decrease ionized calcium level by increasing protein binding

Question 4

What are the main factors controlling plasma calcium level?

Answer 4

PTH
Vit D
Calcitonin

Question 5

Where is PTH produced?

Answer 5

Chief cells in parathyroid glands

Question 6

When is PTH secreted?

Answer 6

Low plasma calcium
Low Vit D
High phosphate

Question 7

What are the effects of PTH?

Answer 7

Raises plasma calcium
-stimulates cal reabsorption from bone
-increases renal tubular cal reabsorption
-stimulates increased GI cal absorption (indirect)
Increases renal phosphate excretion

Question 8

Where is Vitamin D produced?

Answer 8

Synthesised in skin (D3 cholecalciferol)

Ingested (D2 ergocalciferol) –> hydroxylated in liver to 25-OH-D2/3 –> hydroxylated in kidney to active Vit D

Question 9

What are the effects of Vitamin D?

Answer 9

Increases absorption of calcium & phosphate from GI tract
Required for normal bone formation

Question 10

What are the causes of Vitamin D deficiency?

Answer 10

Inadequate sunlight exposure (rickets)
Malabsorptive conditions
Liver/kidney disease

Question 11

Where is Calcitonin produced?

Answer 11

Parafollicular C cells of thyroid gland

Question 12

When is Calcitonin secreted?

Answer 12

Increased plasma calcium

Question 13

What are the effects of Calcitonin?

Answer 13

Decreases plasma calcium by antagonising the effect of PTH on bone

Question 14

What determines intestinal uptake of calcium?

Answer 14

Ionized calcium levels in lumen

Presence of activated Vit D

Question 15

What determines renal excretion of calcium?

Answer 15

Na reabsorption in proximal tubule (90%)

PTH regulation in distal tubule (10%)

Question 16

What is hypercalcaemia?

Answer 16

Plasma calcium >2.5mmol/L

Question 17

What is the most common cause of hypercalcaemia?

Answer 17

1o hyperparathyroidism/malignancy (97%)

Question 18

What are the causes of excessive PTH secretion, leading to hypercalcaemia?

Answer 18

1o hyperparathyroidism
3o hyperparathyroidism
Ectopic PTH secretion (v. rare)

Question 19

What are the malignant causes of hypercalcaemia?

Answer 19

Myeloma
Metastatic deposits in bone
Paraneoplastic (SCC)

Question 20

What are the causes of excess Vit D, leading to hypercalcaemia?

Answer 20

Exogenous excess
Granulomatous disease (TB, sarcoid)
Lymphoma

Question 21

What are the causes of excess calcium, leading to hypercalcaemia?

Answer 21

Milk-alkali syndrome

-antacids increase absorption of calcium

Question 22

What are the other endocrine causes of hypercalcaemia?

Answer 22

Thyrotoxicosis

Addison’s

Question 23

What are the renal causes of hypercalcaemia?

Answer 23

Severe AKI

Question 24

What are the iatrogenic causes of hypercalcaemia?

Answer 24

Thiazide diuretics

Lithium

Question 25

What are the hereditary causes of hypercalcaemia?

Answer 25

Familial hypocalciuric hypercalcaemia

Question 26

What is the cause of 1o hyperparathyroidism?

Answer 26

Single parathyroid adenomas (80%) | Diffuse glandular hyperplasia (20%) - MEN IIa/IIb

Question 27

How can PTH levels distinguish b/w hyperparathyroidism & malignancy?

Answer 27

High in hyperparathyroidism | Low in malignancy

Question 28

What are the PTH/calcium levels like in 1o hyperparathyroidism?

Answer 28

PTH high | Calcium high

Question 29

How is 1o hyperparathyroidism managed?

Answer 29

Parathyroidectomy

Question 30

What is the major complication of parathyroidectomy?

Answer 30

Post-op hypocalcaemia | Give adcal for 14/7

Question 31

What is 2o hyperparathyroidism?

Answer 31

Physiological hypertrophy of all parathyroid glands, in response to hypocalcaemia

Question 32

In which pts is 2o hyperparathyroidism seen?

Answer 32

Renal disease | Vit D deficiency

Question 33

What are the PTH/calcium levels like in 2o hyperparathyroidism?

Answer 33

PTH high | Calcium low/normal

Question 34

What is the cause of 3o hyperparathyroidism?

Answer 34

Long-standing 2o hyperparathyroidism | Occurs mostly in renal failure

Question 35

What are the PTH/calcium levels like in 3o hyperparathyroidism?

Answer 35

PTH high Calcium high Phosphate grossly high

Question 36

What is the management of 2o hyperparathyroidism?

Answer 36

Address cause of hypocalcaemia

Question 37

What is the management of 3o hyperparathyroidism?

Answer 37

Parathyroidectomy

Question 38

How does 1o hyperparathyroidism present?

Answer 38

Often asymptomatic | Sx related to hypercalcaemia

Question 39

What are the sx of hypercalcaemia?

Answer 39

Bones - bone pain, fractures, muscle weakness Stones - renal stones, polyuria, AKI/CKD Groans - abdo pain, vom, const, pancreatitis, GI ulcers Moans - depression, confusion, tiredness, hypotonicity

Question 40

What investigations are appropriate in suspected 1o hyperparathyroidism?

Answer 40

``` PTH (raised) Ca (raised) PO4 (low) ALP (raised) 24hr urinary calcium (raised) DXA scan (assess osteoporosis) Technetium/USS (localise tumour) ```

Question 41

How can 1o hyperparathyroidism be distinguished from familial hypocalciuric hypercalcaemia?

Answer 41

In FHH low 24hr urinary calcium | Can use spot calcium:creatinine excretion

Question 42

How can 1o hyperparathyroidism be distinguished from 3o hyperparathyroidism?

Answer 42

``` Clinical presentation PO4 levels (low/normal in 1o) ```

Question 43

What syndromes is 1o hyperparathyroidism associated with?

Answer 43

Multiple Endocrine Neoplasia | -autosomal dominant

Question 44

What tumours does MEN I produce?

Answer 44

Parathyroid hyperplasia/adenoma Pancreatic endocrine tumours (gastrinoma/insulinoma) Pituitary adenoma

Question 45

What tumours does MEN IIa produce?

Answer 45

Thyroid medullary carcinoma Adrenal PCC Parathyroid hyperplasia

Question 46

What tumours does MEN IIb produce?

Answer 46

MEN IIa Mucosal neuromas Marfanoid appearance No hyper PTH

Question 47

What is the immediate management of a patient presenting w/ acute hypercalcaemia?

Answer 47

If Ca >3.5mmol/L AND sev sx - IV fluids (0.9% NaCl, 3-6L/24hrs, diuretics if overloaded) - Bisphosphonates (pamidronate, lowers Ca over 2-3/7) - Calcitonin (rapidly reduce Ca, short-lived) - Dialysis (if renal impairment)

Question 48

What is the non-immediate management of a patient presenting w/ acute hypercalcaemia?

Answer 48

Investigate/treat cause of hypercalcaemia

Question 49

When are steroids used in hypercalcaemia?

Answer 49

If hypercalcaemia due to myeloma, lymphoma or sarcoid

Question 50

What is the potentially life threatening complication of 1o hyperparathyroidism?

Answer 50

Reduced QT interval | Can lead to cardiac arrest