Hyperparathyroidism

Question 1

Define primary hyperparathyroidism.

Answer 1

Autonomous overproduction of PTH causes derangement of calcium metabolism. In 80% this is due to a single parathyroid adenoma

Question 2

Define secondary hyperparathyroidism.

Answer 2

Any disorder that results in hypocalcaemia will elevate PTH and can cause this. The most frequent causes: CKD, malabsorption, and inadequate sunlight, acting via alterations in vitamin D, phosphorus, and calcium.

Question 3

What is the function of parathyroid hormone? (3)

Answer 3

Secreted in response to low ionized Ca2+ levels, by four parathyroid glands situated posterior to the thyroid. The glands are controlled by −ve feedback via Ca2+ levels.

PTH acts by:

• Bone:
  
  • ↑osteoclast activity releasing Ca2+ and PO43− from bones
• Kidney:
  
  • ↑Ca2+ and ↓PO43− reabsorption in the kidney
  • active 1,25dihydroxy-vitamin D3 production is ↑. Overall effect is ↑Ca2+ and ↓PO4.

Question 4

Describe how the parathyroid gland regulates calcium.

Answer 4

Question 5

What are the biochemical features of primary hyperparathyroidism?

Answer 5

• Raised (unsuppressed) PTH
• Raised or inappropriately normal Ca
• Low phosphate

Question 6

What is the difference between causes of primary and secondary hyperparathyroidism?

Answer 6

PRIMARY = no negative feedback, autonomous PTH release despite hypercalcaemia usually due to adenoma

SECONDARY = vitamin D deficiency so low calcium but high PTH from parathyroid hyperplasia which tries to normalise the serum calcium

Question 7

What is the aetiology of primary hyperparathyroidism?

Answer 7

Caused by:

1. parathyroid adenomas - 85%
2. inherited hyperfunctioning parathyroid gland - 10-20% (check for multi gland disease e.g. in MEN1/2/4)
3. parathyroid malignancy - 1%
4. external neck irradiation e.g. lithium therapy used for bipolar disorder may over-stimulate the parathyroid glands

Question 8

What are the three ways in which calcium is increased in primary hyperparathyroidism?

Answer 8

PTH secretion is not suppressed by high calcium levels –>

1. over-stimulation of bone resorption with cortical bone affected more than cancellous bone
2. reabsorption of calcium from the kidneys
3. conversion of 25-hydroxyvitamin D3 to its more active form of 1,25-hydroxyvitamin D3 (which is responsible for GI absorption of calcium)

Question 9

What are the signs and symptoms of primary hyperparathyroidism?

Answer 9

HYPERCALCAEMIA

“Stones, bones, abdominal moans, psychic groans” - REDUCED NEURONAL EXCITABILITY (atonal muscles)

• Stones – renal effects (you excrete Ca in kidneys)
  
  • Polyuria & thirst, nephrocalcinosis (calcium oxalate), renal colic, chronic renal failure
• Bones
  
  • Bone pain, osteoporosis/osteopenia, muscle weakness and high fatigability, paraesthesia, muscle cramps
• Abdominal moans - GI effects
  
  • Anorexia, nausea, dyspepsia, constipation, pancreatitis
• Psychic groans - CNS effects
  
  • Fatigue, depression, impaired concentration, memory loss, coma (usually >3mmol/L), poor sleep, anxiety

Hard, dense neck mass in parathyroid carcinoma.

Question 10

What investigations would you do for primary hyperparathyroidism?

Answer 10

• Serum calcium - high (normal is 2.2-2.6mmol/L)
• Serum PTH - high
• 25-hydroxyvitamin D
• Serum phosphorus - low
• 24hr urinary calcium - high or normal
• DXA scan with TBS- T scan of -1 to 1 is normal, >-2.5=osteopenia, <-2.5 = osteoporosis. TBS evaluates bone microstructure.

Question 11

What is the treatment of primary hyperparathyroidism?

Answer 11

1. Parathyroidectomy
2. Vitamin D supplementation - ergocalciferol
3. Monitor serum calcium, creatinine and bone density
4. Bisphosphonate - if osteoporosis is present
5. Cinacalcet - lowers serum calcium and PTH; modulates activity of calcium sensing receptor which regulates PTH secretion.

Question 12

What are the complications of parathyroidism and its treatment?

Answer 12

• Neck haematoma after surgery
• Recurrent/superior laryngeal nerve injury
• Hypocalcaemia after surgery - **
• Pneumothorax after surgery
• Osteoporosis
• Bone fractures
• Nephrolithiasis

Question 13

What is the aetiology of secondary hyperparathyroidism?

Answer 13

3 MAIN AETIOLOGIES:

1. CKD - loss of 1 alpha hydroxylase in the kidney (so no vit D conversion to active form) causing hyperphosphataemia and hypocalcaemia
2. malabsorption syndromes - fat malabsorption causes reduced absorption of Vit D and dietary calcium
3. chronic inadequate exposure to sunlight - sun helps synthesise 90-95% of required vitamin D

Other causes:

1. Diminished dietary Ca, Vit D intake
2. Malabsorption syndromes: lactose intolerance, pancreatic disease, Crohn’s disease, Coeliac disease, gastric bypass, Whipple’s disease
3. Increased requirement of calcium or increased loss - bone growth, after pregnancy/breastfeeding, bisphosphonate treatment, loop diuretics, rhabdomyolysis, sepsis
4. Diminished parathormone effect - CKD, pseudohypoparathyroidism (G-protein deficiency)

Question 14

List 5 causes of vitamin D deficiency that could lead to Ca deficiency and therefore secondary hyperparathyroidism.

Answer 14

1. Diet or GI malabsorption of dietary D2 eg coeliac disease, inflam bowel disease,
2. Lack of sunlight (so lack of UVB)
3. Renal failure (so no conversion to active form)
4. Liver failure (no D3 synthesis)
5. Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)

Question 15

What are the signs and symptoms of secondary hyperparathyroidism?

Answer 15

Signs and symptoms of hypocalcaemia:

• Pseudofractures
• These show neuromuscular irritability due to hypocalcaemia (enables greater Na+ influx, so MORE membrane excitability)
  
  • Chvostek’s Sign – tap facial nerve below zygomatic arch -> twitching of facial muscles = (positive sign)
  • Trousseau’s sign – inflate BT cuff for several minutes ->carpopedal spasm (positive sign). This is inducing tetany (clawing of the hand).
• Muscle cramps
• Bone pain on pressing - poorly mineralised osteoid becomes hydrated and cannot provide sufficient support for sensory fibres in the periosteum
• Paraesthesia/tingling
• Rickets - bowed legs/knock-knees
• Fractures

OR features of underlying malabsorption syndromes/ chronic renal failure

Question 16

What investigations would you do for secondary parathyroidism?

Answer 16

• Serum calcium - <2.10mmol/L
• Serum iPTH (intact) - >88nanograms/L
• Serum creatinine - high in CKD (>91.5micromol/L)
• Serum urea nitrogen - high in CKD
• Serum phosphorus - high in CKD
• Serum 25-hydroxyvitamin D - may be low
• Serum magnesium - may be low
• US neck - parathyroid gland hyperplasia

Question 17

How do you manage secondary hyperparathyroidism?

Answer 17

1. UV radiation exposure - 5 to 15 minutes/day between 10 a.m. and 3 p.m., on arms and legs or hands, face, and arms, during spring, summer, and autumn provides the body with its required 1000 international units of colecalciferol
2. Vitamin D supplementation - ergocalciferol
3. Calcium supplementation - Ca carbonate

In CKD stage 5 with PTH >800ng/K - parathyroidectomy

Question 18

What are the complications of secondary hyperparathyroidism?

Answer 18

1. Osteodystrophy - loss of Ca and Vit D causes demineralisation of the skeleton
2. Osteoporosis - loss of bone mass due to dysregulation between bone formation and resorption
3. Uraemia
4. Calciphylaxis - vascular and tissue manifestation of chronic hypercalcaemia; systemic calcification of the tunica media of small vessels

Prognosis - mirrors underlying disease.

Question 19

What is activated vitamin D called?

Answer 19

Calcitriol 1,25hydroxyvitamin D

Question 20

Where is 25 hydroxylase found?

Answer 20

Liver

Question 21

What is the diagnostic test for osteoporosis?

Answer 21

DEXA - very safe as much less radiation than XR

Question 22

What is the range for normal calcium levels in plasma?

Answer 22

2.2 - 2.6mmol/L

Question 23

What is a genetic cause of hypercalcaemia?

Answer 23

Familial hypocalcuric hypercalcaemia

Question 24

Who is more affected by primary hyperparathyroidism?

Answer 24

Females

Question 25

What is the Ca sensor and where is it found?

Answer 25

CaSR found in the parathyroid glands

Question 26

What can cause hypercalcaemia in malignancy?

Answer 26

PTHrP in small cell lung Ca Bone mets Haematological malignancy like myeloma

Question 27

What is the management of acute hypercalcaemia?

Answer 27

Fluids - 1L over 1hr +/- bisphosphonates if little response +/- treat cause

Question 28

What is tertiary hyperparathyroidism?

Answer 28

Long term 2o hyperparathyroidism causes parathyroid hyperplasia e.g. in CKD, which after transplant manifests like primary hyperparathyroidism.

Question 29

# (From Finals Revision Course) Patient presents with QT prolongation and signs of tetany. He had parathyroidectomy 2yrs ago and his GP has recently reviewed his medications. He is taking CalciChew, so what is the problem?

Answer 29

You have to use 1 alpha hydroxyvitamin D in hypoparathyroidism (e.g. 1alpha cacidiol or calcitriol These patients are not able to convert inactive vitamin D to active so will become calcium deficient. Calcichew alone is not enough because non hydroxylated forms of vitamin D cannot be converted to 1,25 hydroxylated vitamin D in the absence of PTH.