Hyperparathyroidism

Involves overactivity of the parathyroid glands with high levels of parathyroid hormone (PTH)

Aetiology

Primary hyperparathyroidism

• Caused by uncontrolled parathyroid hormone produced directly by a tumour of the parathyroid glands

• This leads hypercalcaemia - fatigue, depression, bone pain, myalgia, nausea, thirst, polyuria, renal stones, osteoporosis

• Treated by surgically removing the tumour

Secondary hyperparathyroidism

• Insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones

• This causes hypocalcaemia

Tertiary hyperparathyroidism

• This happen when secondary hyperparathyroidism continues for a long period of time (e.g. renal failure), leading to hyperplasia of the glands

Summary of blood results

Pathophysiology

Functions of PTH

• Activates osteoclasts - increased bone reabsoption, releases calcium

• Increased reabsorption of calcium by renal tubules

• Increased urinary phospate excretion

• Increased synthesis of active forms of vitamin D

Regulation of PTH

• Normally the above functions would increase serum calcium, so inhibit PTH secretion

• PTH secretion is not terminated in hyperparathyroidism - continued osteoclasis

Fibrosa cystica

• The result of unchecked hyperparathyroidism, which results in an overproduction of PTH and continued osteoclasis

• Osteoporosis, brown tumours and osteitis

• Generalised, particularly phalanges, vertebrae and femur

• Prominent changes to cortical bone, medullary cancellous bone also affected

• Fibrovascular tissue in marrow spaces

• Osteoporotic bone prone to fracture

• Associated haemorrage elicits macrophage reaction and processes of organisation and repair

• Results in a mass of reactive tissue known as a brown tumour

• Can present as a lytic lesion on x-ray

• Late stage, rarely seen

Management

Primary Hyperparathyroidism

Definitive Treatment: Parathyroidectomy

• Indications for Surgery
• Symptomatic hyperparathyroidism
• Serum calcium > 1.0 mg/dL above upper normal limit
• Osteoporosis or fragility fractures
• Nephrolithiasis or nephrocalcinosis
• Reduced renal function (eGFR < 60 mL/min/1.73 m²)
• Age < 50 years

• Surgical Approaches
• Focused (minimally invasive) parathyroidectomy
• Bilateral neck exploration
• Intraoperative PTH monitoring to confirm cure

Medical Management (Non-Surgical Candidates)

• Annual serum calcium measurement

• Bone mineral density (DEXA) every 1–2 years

• Periodic renal function and imaging

• Calcimimetics (e.g., cinacalcet)
• Reduce PTH secretion by increasing calcium-sensing receptor sensitivity
• Effective in lowering serum calcium (does not improve bone density)

• Bisphosphonates
• Improve bone mineral density
• Do not lower serum calcium

• Vitamin D supplementation
• Used cautiously to correct deficiency while monitoring calcium levels

Secondary Hyperparathyroidism

Correction of Underlying Cause

• Optimization of renal disease management

• Control of hyperphosphatemia

Medical Therapy

• Dietary phosphate restriction

• Phosphate binders:
• Calcium-based binders
• Non-calcium binders (sevelamer, lanthanum)

• Active vitamin D analogues (calcitriol, alfacalcidol)

• Vitamin D receptor activators

• Cinacalcet or etelcalcetide

• Particularly useful in dialysis patients

• Parathyroidectomy indicated in refractory secondary hyperparathyroidism

• Indications include severe hyperparathyroidism with:
• Bone pain
• Fractures
• Calciphylaxis
• Failure of medical therapy

Tertiary Hyperparathyroidism

• Definitive Treatment
• Subtotal or total parathyroidectomy
• Indicated in persistent hypercalcemia and elevated PTH despite correction of renal failure

• Medical Therapy (Adjunctive)
• Calcimimetics for temporary control
• Monitoring and management of calcium-phosphate balance