2.5 Disorders of Parathyroid Hormone Excess and Deficiency

Question 1

List 5 causes of hypocalcaemia, and explain them mechanistically

Answer 1

• Hyperphosphataemia (from renal failure/pohsphate therapy); negative ion binds to calcium, causing hypocalcaemia
• Hypoparathyroidism (surgical removal, congenital deficiency)
• Vit D deficiency/resistance (harder to encourage renal/gastro absorption)
• PTH resistance
• Drugs (bisphosphinates, calcitonin); decreases resorption -> hypocalc

Question 2

List some causes of hypercalcaemia, and explain them mechanistically

Answer 2

• Excessive PTH (parathyroid adenoma, rarely carcinoma, hyperparathyroidism)
• Excessive action of Vit D
• Malignancy, such as myeloma (systemic inflam -> increased osteoclastic acticity -> inc. Ca2+)
• Excessive calcium intake
• Drugs (thiazide diuretics, lithium)

Question 3

Explain 1°, 2°, and 3° hyperparathyroidism

Answer 3

Primary: hypersecretion at the level of the parathyroid (such as adenoma)

Secondary: at the level of calcium resorption (renal failure, vit D deficiency etc). Causes PTH hypersecretion.

Tertiary: prolonged 2° hyperparathyroidism causes parathyroid hyperplasia. When 2° is treated, hypercalcaemia

Question 4

Describe symptoms of hypercalcaemia by body system

Answer 4

• Gastro: anorexia, nausea/vomiting, constipation
• Renal: Polyuria/polydipsia (excessive thirst), nephrocalcinosis (can progress to kidney stones)
• Neuropsych: depression, decreased consciousness
• Cardio: arrhythmia (short QT), hypertension

Question 5

Other than systemic inflammation, how can malignancy cause hypercalcaemia?

Answer 5

Tumour produces PTH-related peptide (PTHrP); acts to increase calcium outside of normal feedback loops.

Question 6

Describe clinical features of hypocalcaemia (incl. ECG)

Answer 6

• Muscles cramp/spasm (decreased threshold of excitability)
• Parasthesiae
• Tetany (sustained contractions)
• Seziures
• Long QT interval (opposite of hyper-)

Question 7

Which protein carries calcium in the blood? How is it affected by inflammation, and how can this affect calcium levels?

Answer 7

• Most commonly bound to albumin
• Albumin decreases with systemic inflammation
• This can therefore lead to hypocalcaemia

Question 8

Describe the common causes of high/low calcium and PTH (all 4)

Answer 8

High Ca2+/High PTH: 1° hyperparathyroid

High Ca2+/Low PTH: Most often malignancy

Low Ca2+/High PTH: 2° hyperparathyroid

Low Ca2+/Low PTH: 1° hypoparathyroid

Question 9

Does MEN1 or MEN2 occur in 20% of patients with primary hyperparathyroidism from an adenoma?

Answer 9

MEN1

Question 10

True or false: there are very few possible anatomical variants of the parathyroid glands

Answer 10

• False
• The location of the parathyroids can vary greatly (above and below)

Question 11

What is familial hypocalciuric hypercalcaemia? Why is surgery contradindicated?

Answer 11

• Genetic increase in calcium setpoint
• Don’t remove parathyroid, since getting them within the normal range can cause symptomatic hypocalcaemia

Question 12

Do we perform surgery on everyone with primary hyperparathyroidism? What are the indicatoins?

Answer 12

• No; not everyone
• Only people with very high calcium, osteoporosis/fracture, or young (since they’ll have the problem for longer)

Question 13

Describe medical (non-surgical) treatment of hypercalcaemia

Answer 13

• First: rehydrate the patient (why?)
• Bisphosphinates/denosumab can be used to protect against fracture, but only reduce calcium in short term
• Cinacalcet can be used to decrease set point for calcium

Question 14

What does ALP stand for in blood tests? What are its implications in terms of bone?

Answer 14

• Stands for alkaline phosphatase
• Is one of the markers for bone turnover

Question 15

What is the link between PTH release and magnesium?

Answer 15

• Magnesium is required for production and release of PTH
• Therefore, extreme hypomagnesemia can cause hypocalcaemia