Disorders of parathyroid glands, calcium metabolism, and bone

Question 1

Describe the anatomy and function of the parathyroid glands and PTH

Answer 1

4 parathyroid glands located posterior to the thyroid gland. Contains chief cells (secrete PTH) and oxyphil cells (unknown function)

PTH increases plasma calcium by:

• increasing osteoclast resorption (fast)
• increasing calcium intestinal absorption (slow)
• increasing synthesis of 1,25-dihydroxyvitamin D
• increasing renal reabsorption of calcium
• increasing phosphate excretion

Question 2

Name 5 causes of hypercalcaemia

Answer 2

Primary hyperparathyroidism
-Single parathyroid adenoma (>80%)
-Diffuse hyperplasia of parathyroid glands (15-20%)
Malignancy
-Myeloma
-Bone metastases
-PTHrP (squamous lung, breast, renal cancers)

Excessive exogenous vitamin D
Granulomatous disease e.g. sarcoidosis, TB
Lymphoma

Drugs: Thiazide diuretics, Vit D analogues, Lithium

Long-term immobility

Question 3

Define mild and severe hypercalcaemia

Answer 3

Mild hypercalcaemia <3 mmol/L
Severe hypercalcaemia >3 mmol/L

Normal range 2.05-2.60 mmol/L

Question 4

Describe the presentation of hypercalcaemia

Answer 4

Asymptomatic
Stones: Renal colic and hypercalcaemic stones
Bones: Pain, osteoporosis, and pathological fractures
Psychic moans: Depression, confusion, hallucinations, coma
Abdominal groans: NaV, anorexia, constipation, pancreatitis, PUD

General: Tiredness, malaise, dehydration
Corneal calcification - asymptomatic marker for longstanding hypercalcaemia

Question 5

What investigations are used in hypercalcaemia?

Answer 5

Serum PTH*
Hyperchloraemic acidosis
Renal function - usually normal, CKD can be a cause
24hr urinary calcium
Elevated serum ALP - severe parathyroid bone disease

Radioisotope scanning
USS
CT/MRI

Question 6

Describe the presentation of acute severe hypercalcaemia

Answer 6

Dehydration
NaV
Nocturia/polyuria
Drowsiness
Altered consciousness

Serum calcium >3 mmol/L

Question 7

Outline the emergency treatment for severe hypercalcaemia

Answer 7

Treat immediately if serious ill or calcium >3.5 mmol/L

Fluid resus and maintenance* (3-4L in first 24h)

IV bisphosphonates - esp malignant or unknown cause
Prednisolone may be useful

Question 8

State the definitive management of primary hyperparathyroidism

Answer 8

Surgical removal of adenoma or hyperplastic glands

Question 9

What are the surgical indications for primary hyperparathyroidism?

Answer 9

Renal stones or impaired renal function
Bone involvement or marked reduction in bone density
Calcium >3.0 mmol/L
Young patient <50yrs
Previous episode of severe acute hypercalcaemia

Question 10

State 3 complications of parathyroid surgery

Answer 10

Postoperative hypocalcaemia*

Bleeding
Recurrent laryngeal nerve palsy

Question 11

List 4 causes of hypocalcaemia

Answer 11

Increased phosphate: CKD, phosphate therapy
Osteomalacia/rickets, vitamin D resistance
Vitamin D deficiency
Acute pancreatitis
Malabsorption e.g. Coeliac disease

Drugs: Calcitonin, bisphosphonates

Hypoparathyroidism: Surgical* (normally transient), DiGeorge syndrome, idiopathic hypoparathyroidism, severe hypomagnesium

Question 12

Describe the clinical features of hypoparathyroidism

Answer 12

Neuromuscular irritability
Neuropsychiatric manisfestations

Early: Paraesthesiae, circumoral numbness, cramps, anxiety, tetany
Late: Convulsions, laryngeal stridor, dystonia, psychosis

May prolong QTc on ECG

Question 13

What two signs indicate hypocalcaemia?

Answer 13

Chvostek’s sign: Tapping of facial nerve -> twitching of ipsilateral facial muscles

Trousseau’s sign: Inflation of BP cuff for 3 minutes induces tetany of fingers and wrist

Question 14

What investigations are done in hypocalcaemia?

Answer 14

Low serum calcium*

Additional:
Serum and urine creatinine
PTH levels
Parathyroid antibodies
Serum 25-hydroxyvitamin D
Magnesium

Question 15

Outline the management of hypocalcaemia

Answer 15

Cholcalciferol (Vitamin D3) for vitamin D deficiency
Hydroxyvitamin D for other causes - shorter half life and doesn’t require renal hydroxylation
PTH therapy for hypoparathyroidism

Oral calcium supplements in early stages
Emergency may require IV calcium gluconate

Question 16

Describe Chvostek’s sign

Answer 16

Tapping of facial nerve -> twitching of ipsilateral facial muscles

Indicates hypocalcaemia

Question 17

Describe Trousseau’s sign

Answer 17

Inflation of BP cuff for 3 minutes induces tetany of fingers and wrist

Indicated hypocalcaemia

Question 18

What investigations are suggestive of primary hyperparathyroidism?

Answer 18

Raised calcium
Low phosphate
Normal or raised PTH

Question 19

What investigations are suggestive of secondary hyperparathyroidism?

Answer 19

Normal or low calcium

High PTH

Question 20

Define Paget’s disease of the bone

Answer 20

A disease of excessive abnormal bone remodelling.
Localised areas of aggressive osteoclast-mediated bone resorption, followed by imperfect osteoblast-mediated bone repair.

Question 21

Which bones are frequently affected in Paget’s disease of the bone?

Answer 21

Pelvis (often asymmetric)
Proximal long bones
Spine
Skull

Question 22

How does Paget’s disease of the bone present?

Answer 22

75% are asymptomatic

Localised pain and tenderness
Increased bone size
Bowing deformities, bossing of skull
Kyphosis
Decreased range of motion

Question 23

What radiological features are seen with Paget’s disease of the bone?

Answer 23

Osteolytic (lucent) regions -> coarsened trabeculae and bony enlargement
Skull: thickened calvarium, osteoporosis circumscripta

Question 24

Describe the biomarkers of Paget’s disease of the bone

Answer 24

Elevated ALP

Normal calcium and phosphate

Question 25

Name 3 complications of Paget’s disease of the bone

Answer 25

Deafness (cranial nerve entrapment)
Pathological fractures
Paget's sarcoma (1%): more malignant than classic osteosarcoma
Skull thickening
High-output congestive cardiac failure

Question 26

Describe the treatment of Paget’s disease of the bone and its indications

Answer 26

Bisphosphonates (oral risedronate or IV zoledronate)

Indications: bone pain, skull or long bone deformity, fracture, periarticular Paget’s