Endocrinology

Question 1

What is the effect of the parathyroid hormone (PTH) on calcium levels?

Answer 1

Increases plasma Ca2+

Question 2

What is the effect of calcitonin (CT) on calcium levels?

Answer 2

Decreases plasma Ca2+

Question 3

What is the effect of vitamin D on calcium levels?

Answer 3

Increases plasma Ca2+

Question 4

What other hormones have an effect on calcium levels?

Answer 4

Oestrogens
Growth hormone
Glucocorticoids

Question 5

What are the causes of primary hyperparathyroidism?

Answer 5

Primary hyperparathyoidism
- prevalent
- slowly developing condition
- common endocrine disorder
- 2 - 3 times more common in women than men
Excess parathyroid hormone causes hypercalcaemia and phosphaturia, low plasma phosphate and increased urinary cAMP
Caused by
- single chief cell tumour
- hyperplasia of one or more parathyroid glands
- parathyroid carcinoma
- rare
Can be associated with multiple endocrine neoplasia type 1 involving many endocrine glands

Question 6

What is the cause of secondary hyperparathyroidism?

Answer 6

Secondary overactivity and hyperplasia of all 4 glands (no hypercalcaemia)
- compensation of hypocalcaemia due to intestinal Ca2+ / vitamin D malabsorption, or deficiency or chronic renal failure

Question 7

What are the symptoms of hyperparathyroidism?

Answer 7

Bones Stones and Groans!

Tiredness
General malaise
Depression
Weakness
Lethargy
Dizziness
Excessive thirst
Anorexia
Nausea
Vomiting
Dehydration
Psychiatric disorders
Cardiac arrhythmias
Heart block
GI tract complaints
- abdominal pain
- constipation
- dyspepsia
- ulceration
Renal stones composed of insoluble calcium phosphate
Renal colic and haematuria
Renal failure
Gallstones
Bone lesions following excess resorption of Ca2+ from bone
More severe cases
- bone cysts
- bone pain
- fractures

Question 8

What is the first line treatment for hyperparathyroidism?

Answer 8

Surgical removal of overactive tissue
Condition can reoccur
- surgery will need to be repeated
Can get permanent hypoparathyroidism
Risk of damage to laryngeal nerves

Question 9

Which drugs can be used to treat hyperparathyroidism?

Answer 9

Cinacalet HCl used for refractory secondary hyperparathyroidism in
- end-stage renal disease
- primary hyperparathyroidism if surgery not possible
- parathyroid carcinoma
Monitor serum Ca2+ and PTH concentrations

Paricalcitol in chronic renal failure (vitamin D deficiency)

• synthetic vitamin D analogue
• secondary hyperparathyroidism

Question 10

What are the side effects of Cinacalet HCl (Mimpara)?

Answer 10

Nausea
Vomiting
Anorexia
Rash

Question 11

What is hypercalcaemic crisis treated with?

Answer 11

0. 9% NaCl infusion and rehydration fluids
   - combat dehydration
   - increase urinary Ca2+ excretion

Salmon calcitonin and pamidronate disodium used to inhibit bone resorption

Question 12

What are the causes of hypoparathyroidism?

Answer 12

Damage during thyroid surgery
Rare primary hypoparathyroidism
Autoimmune disease with antibodies against parathyroid tissue
Associated with other endocrine autoimmune conditions
- hypothyroidism
- type I diabetes
- adrenal insufficiency
Can also have psuedohypoparathyroidism
- hereditary
- bone and kidney insensitive to parathyroid hormone
Hypocalcaemia and high plasma phosphate

Question 13

What are the symptoms of hypoparathyroidism?

Answer 13

Hyperexcitability of nerve and neuromuscular tissues
- pins and needles
- muscle cramps
- muscle spasms
- epileptic seizures or convulsions
Chvostek's sign
- twitching of facial muscles after tapping 7th cranial nerve
Trousseau's sign
- tetanic spasm of wrist and fingers after over-inflation of a sphygmomanometer cuff for > 3 minutes
Dental abnormalities
Dry scaly skin and hair
Brittle nails
Cataracts

Question 14

What is the treatment for hypoparathyroidism?

Answer 14

Vitamin D supplements

• ergocalciferol
• vitamin D2
• vitamin D derivative
• dihydrotachysterol solution (AT10)
• enhance Ca2+ absorption and utilisation
• IV alfacalcidol

Need to check Ca2+ levels to prevent hypercalcaemia

Acute hypocalcaemic tetany treated with slow IV infusion of 10% calcium gluconate
- parathyroid hormone too expensive to use

Question 15

What are the therapeutic uses of calcitonin?

Answer 15

Clinical conditions associated with hyposecretion or hypersecretion of calcitonin are very rare
Can get oversecretion with medullary thyroid carcinomas or ectopic tumours
- no imbalance in plasma Ca2+ levels seen
- tumour marker
Removal of thyroid gland does not produce hypercalcaemia

Question 16

What is Paget’s disease?

Answer 16

Abnormal high rate of bone turnover

- excessive osteoclast bone resorption followed by increased osteoclast activity to repair damage

Question 17

How common is Paget’s disease?

Answer 17

Common chronic disease affecting ~0.5% of population
> 40 years old
Mainly men

Question 18

What are the symptoms of Paget’s disease?

Answer 18

Deformation of skull, spine, pelvis and long bones
Abnormal bone density
Plasma Ca2+ and phosphate normal
Can get increased alkaline phosphatase from osteoclasts
Joint and bone pain
Fractures
Bone deformaties
- bowed legs
Skull enlargement
- deafness
- squashes aural nerve
- blindness
- squashes optic nerve

Question 19

What is the treatment for Paget’s disease?

Answer 19

Bisphophonates
- adsorbed onto hydroxyapatite crystals
- slow rate of formation and dissolution of bone thus reducing resorption
- decrease production of cytokines by osteoblasts thus reduces osteoclast activity
Pamidronate disodium
- IV infusion
Risedronate sodium
- oral
Zoledronic acid
2 - 6 months
May need to monitor serum phosphate and alkaline phosphatase levels and urinary hydroxyproline

Question 20

What are the side effects of synthetic salmon calcitonin to treat Paget’s disease?

Answer 20

Nausea
Facial flushing
Allergic reactions
Malignancy with long term use

Question 21

What are hypercalcaemic states associated with?

Answer 21

Malignant disease

- bone metastases

Question 22

What is used to reduce plasma Ca2+ levels in hypercalcaemic states?

Answer 22

Salcatonin used subcutaneously or intramuscularly to reduce Ca2+ within 24 hours
- also used intravenously in severe cases

Question 23

What causes resistance to salcatonin?

Answer 23

Receptor downregulation or neutralising antibody function

Question 24

Give examples of bisphosphonates used to treat hypercalcaemic states

Answer 24

Ibandronic acid
Pamidronate disodium
Sodium clodronate
Zoledronic acid

Question 25

Give examples of clinical disorders of calcitriol

Answer 25

Vitamin D deficiency

Vitamin D excess

Question 26

How is vitamin D metabolised?

Answer 26

Egosterol ->
Ergocalciferol (vitamin D2) ->
Calciferol (active form vitamin D2)

Question 27

What does vitamin D deficiency cause in children?

Answer 27

Rickets

Question 28

What does vitamin D deficiency cause in adults?

Answer 28

Osteomalacia

Question 29

Where is vitamin D deficiency most common?

Answer 29

Middle and Far East

Question 30

What causes vitamin D deficiency?

Answer 30

Metabolic abnormality
- inherited absence or reduced activity of 1alpha-hydroxylase
- vitamin D-dependent rickets type 1, VDDR1
Vitamin D-dependent rickets type 2 (VDDR2, vitamin D- resistant rickets)
- common inherited condition
- defect in VDR gene
Intestinal fat malabsorption
Chronic liver disease
Lack of sunlight
- heavily veiled women
- elderly
- also have decreased synthesis in skin
Dietary lack
- poor diet
- vegans

Question 31

What are the symptoms of vitamin D deficiency in children?

Answer 31

Swollen growing ends of bone
Bone bent and deformed
- bowed legs

Question 32

What are the symptoms of vitamin D deficiency in adults?

Answer 32

Bone pain
Partial fractures
Muscle weakness
- can lead to falls and fractures

Question 33

What are the general symptoms of vitamin D deficiency?

Answer 33

Inadequate calcification of matrix and softening of skeleton due to hypocalcaemia
VDDR2
- high plasma levels of calcitriol
- severe alopecia

Question 34

What is the treatment for vitamin D deficiency?

Answer 34

Dietary prevention/insufficiency
- small oral doses
- 10-20 ug/400-800 IU daily)
- Ca2+ supplement
Deficiency in children
- need higher doses
- 400-10,000 units daily
Also used with anticonvulsants
- Calcichew D3 tablets
- CaCO3 + 400 units colecalciferol/vitamin D3
- calcium and ergocalciferol
- Ca2+ lactate
- Ca2+ phosphate
- 10 ug vitamin D2
- colecalciferol or ergocalciferol
- oral
Intestinal malabsorption/hepatic disease
- increase ergocalciferol dose up to 1 mg (40,000 IU)
Alfacalcidol
- used in severe renal impairment and for VDDR1
VDDR2
- treated with higher doses of vitamin D or active metabolites
Plasma and urinary Ca2+ carefully monitored for all patients to check for hypercalcaemia and vitamin D toxicity
Therapeutic doses should be OK in pregnancy
High doses of vitamin D supplements not used in breastfeeding women
- hypercalcaemia in babies

Question 35

What is the cause of hypervitaminosis D?

Answer 35

Overuse of vitamin D preparation
- > 10,000 units/day in adults for > 12 weeks dangerous
Sarcoidosis
- chronic
- benign
- unknown cause
- nodules of inflamed tissue in skin and other organs
- granulomas
Skin conditions associated with enhanced synthesis of vitamin D3 after exposure to sun or excessive ingestion of vitamin D

Question 36

What are the symptoms of hypervitaminosis D?

Answer 36

Hypercalcaemia
- tiredness
- anorexia
- nausea
- vomiting
Leads to more severe symptoms

Question 37

What is the treatment for hypervitaminosis D?

Answer 37

Reduce dose of vitamin D preparatin
Sarcoidosis
- systemic/local corticosteroids
- can resolve spontaneously