Parathyroids

• 80% solitary adenoma, 20% due to hyperplasia of all glands, 0.5% due to parathyroid carcinoma

Presentation

• Due to increased calcium – weakness, tiredness, depression, dehydration, polyuria and polydipsia, renal stones, abdominal pain, pancreatitis, ulcers
• Bone reabsorption can cause pain, fractures, osteopenia and osteoporosis
• There may be increased BP and long term increased cardiovascular risk

Tests

• Increased calcium and increased PTH. Differential with these results in;
  • Thiazide diuretics
  • Lithium
  • Familial hypocalciuric hypercalcaemia
  • Tertiary hyperparathyroidism
• Phosphate is generally reduced (unless there is renal failure), alk phos is increased from bone reabsorption  and 24hr urinary calcium is raised
• DEXA bone scan to assess for osteoporosis

Osteitis fibrosa cystica

• Bone marrow fibrosis and cyst formation due to severe reabsorption
• Appearance brown tumours, subperiosteal erosions of distal phalanges on hand x-ray, pepper pot skull on x-ray

Treatment

• Surgery
• Indications – high serum or urinary calcium, bone disease, osteoporosis, renal calculi, reduced renal function, age <50
• Complications – hypoparathyroidism, recurrent laryngeal nerve damage
• Mild symptoms don’t warrant surgery, advise increase fluids to prevent stone formation, avoid thiazides or high calcium or vitamin D intake

Secondary hyperparathyroidism

• Reduced calcium and raised PTH
• Causes – chronic renal failure, low vitamin D intake

Tertiary hyperparathyroidism

• Increased Ca and inappropriately raised PTH
• Occurs after prolonged secondary hyperparathyroidism causing the glands to act autonomously
• This causes raised calcium due to increased secretion of PTH unlimited by negative feedback
• Seen in chronic renal failure

Malignant hyperparathyroidism

• Parathyroid related protein is produced by squamous cell lung tumours, breast and renal cell carcinomas

Hypoparathyroidism

Primary hypoparathyroidism

• PTH secretion is reduced due to gland failure
• Calcium reduced, phosphate raised or normal
• Causes
  • Autoimmune
  • Di-George syndrome

Secondary hypoparathyroidism

• Radiation, surgery, hypomagnesaemia (Mg required for PTH secretion)

Pseudohypoparathyroidism

• Failure of target cell to respond to PTH

Multiple endocrine neoplasia (MEN)

• Inherited in an autosomal dominant fashion
• There are 3 types;
  • MEN1 – the mutation is in a TSG Menin. This results in;
    • Parathyroid hyperplasia/adenoma
    • Pancreatic endocrine tumours e.g. gastrinoma, insulinoma,
    • Pituitary adenoma usually prolactinoma or GH secreting tumour
    • Also associated with adrenal and carcinoid tumours
  • MEN2a associated with;
    • Thyroid – medullary thyroid carcinoma
    • Adrenal – phaeochomocytoma
    • Parathyroid hyperplasia
  • MEN2b has similar features to MEN2a plus mucosal neuromas and Marfanoid appearance but no hyperparathyroidism
  • Both MEN2a and MEN2b are associated with mutation in the ret proto-oncogene

Calcium physiology

• 40% is bound to albumin – it is the unbound ionised portion that is important
• Adjust total calcium for albumin by; adding 0.1mmol/L to the calcium concentration for every 4g/L that the albumin is below 40g/L and a similar subtraction for raised albumin

Control of calcium metabolism

• PTH
• Vit D
  • 1,25 dihydroxycholecalciferol is stimulated by reduced Ca and phosphate
  • It increases calcium and phosphate absorption from the gut and reabsorption of both from the kidneys
  • It enhances bone reabsorption and inhibits PTH release
  • Disordered regulation of 1,25(OH)2 Vit D underlies familial normocalcaemic hypercalciuria which is a major cause of calcium oxalate renal stone formation
• Calcitonin
  • Made in the C cells of the thyroid
  • Causes a reduction in the plasma calcium and phosphate but physiological role is unclear
• Magnesium
  • Low Mg prevents PTH release and may result in hypocalcaemia

Hypocalcaemia

Signs and symptoms

• Tetany, depression, perioral paraesthesia
• Trousseau’s sign – carpal-pedal spasm when the brachial artery is occluded
• Neuromuscular excitability – Chvostek’s sign – tapping of facial nerve causes facial muscles to twitch
• Can cause cataracts
• Prolongs the QT interval on the ECG

Causes

• If  phosphate is raised consider;
  • Chronic renal failure
  • Hypoparathyroidism
  • Pseudohypoparathyroidism
  • Acute rhabdomyolysis
• If phosphate is normal or low consider;
  • Osteomalacia
  • Over hydration
  • Pancreatitis
• In respiratory alkalosis the total calcium may be normal but ionised calcium is reduced

Treatment

• If symptoms are mild – give calcium
• If necessary add alfacalcidol (vitamin D)
• Treat CRF
• If symptoms are severe give 10ml of 10% calcium gluconate over 30mins

Hypercalcaemia

• Symptoms are described above also shortens the ECG QT interval

Causes

• Most commonly malignancy (myeloma, bone metastases, PTHrP) and primary hyperparathyroidism
• Other causes;
  • Sarcoidosis
  • Vit D intoxification
  • Familial benign hypocalciuric hypercalaemia

Treat

• Take bloods – U&Es, Mg2+, creatinine, calcium, phosphate, alk phos
• Give IV fluids
• Diuretics – furosemide
• Bisphophonates
• Steroids for sarcoidosis