Primary Hyperparathyroidism
Excess PTH secretion from one or more parathyroid glands causing hypercalcaemia. Commonest cause of hypercalcaemia in the community. ~85% due to solitary parathyroid adenoma. Most patients are asymptomatic (detected incidentally). Definitive treatment is parathyroidectomy.
Key Facts
Commonest cause of hypercalcaemia in community/outpatient setting: prevalence ~1-3 per 1,000; F:M 3:1; post-menopausal women most affected Causes: solitary parathyroid adenoma (~85%), 4-gland hyperplasia (~10-15%), parathyroid carcinoma (<1%), MEN1/MEN2A (multigland disease) Biochemistry: raised calcium + raised/inappropriately normal PTH (PTH should be suppressed in hypercalcaemia — if it's detectable/elevated, it's inappropriate) Classical symptoms (many patients now asymptomatic): 'bones, stones, abdominal moans, and psychic groans' — osteoporosis/osteitis fibrosa cystica, renal calculi, constipation/pancreatitis, depression/confusion Indications for surgery (NICE/International Consensus): symptomatic, Ca²⁺ >0.25 mmol/L above ULN, age <50, eGFR <60, T-score ≤−2.5, renal calculi, 24h urine Ca >10 mmol Surgery: parathyroidectomy — cure rate >95%; pre-operative localisation with sestamibi scan + USS neck; risk of hungry bone syndrome post-op (hypocalcaemia as bone remineralises)
Overview
Key Facts
Primary hyperparathyroidism is very common and usually detected incidentally on routine blood tests. Most patients are now asymptomatic. Parathyroidectomy is curative in >95% of cases. Patients not meeting surgical criteria are managed conservatively with monitoring.
Epidemiology
Prevalence ~1-3 per 1,000. F:M 3:1. Peak incidence: post-menopausal women (50-70 years). Incidence increasing due to routine calcium measurement.
Aetiology
Solitary adenoma (~85%), 4-gland hyperplasia (~10-15%), double adenoma (~5%), carcinoma (<1%). Hereditary: MEN1 (parathyroid hyperplasia + pituitary + pancreatic tumours), MEN2A (parathyroid + medullary thyroid cancer + phaeochromocytoma), familial hypocalciuric hypercalcaemia (FHH — benign, autosomal dominant CaSR mutation — MUST exclude before surgery).
Pathophysiology
Autonomous PTH secretion (not suppressed by hypercalcaemia) → increased bone resorption (osteoclast activation → calcium/phosphate release), increased renal calcium reabsorption, increased renal phosphate excretion, increased 1,25(OH)₂D₃ production → increased intestinal calcium absorption. Result: hypercalcaemia, hypophosphataemia, raised ALP (bone turnover).
Clinical Presentation
Asymptomatic (~80%)
- Incidental finding of raised calcium on routine bloods
Symptomatic ('Bones, Stones, Abdominal Moans, Psychic Groans')
Bones: osteoporosis, bone pain, pathological fractures, osteitis fibrosa cystica (brown tumours, subperiosteal resorption — advanced disease, now rare) Stones: renal calculi (~20%) — calcium oxalate/phosphate; nephrocalcinosis Abdominal moans: constipation, nausea, anorexia, peptic ulcer, pancreatitis (rare) Psychic groans: depression, anxiety, cognitive impairment, fatigue, insomnia
Other
- Polyuria, polydipsia (hypercalcaemia → nephrogenic DI)
- Proximal myopathy
- Short QT interval on ECG
Red Flags
- Very high calcium (>3.5 mmol/L) → hypercalcaemic crisis
- Renal impairment with hypercalcaemia → urgent assessment
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Malignancy-related hypercalcaemia | PTH LOW; PTHrP high (squamous, renal) or bone metastases | PTH, PTHrP, imaging |
| FHH | Benign; autosomal dominant; low urine Ca:Cr clearance ratio | Urine Ca:Cr ratio <0.01 |
| Vitamin D excess | Raised 25-OH-D, low PTH | Vitamin D level |
| Sarcoidosis | Raised 1,25(OH)₂D₃ (macrophage production), low PTH | 1,25 vitamin D, ACE |
| Thiazide diuretics | Reduced renal calcium excretion | Drug history |
Diagnosis / Investigation
Biochemical
- Serum calcium (adjusted): raised
- PTH: raised or inappropriately normal (KEY — in hypercalcaemia from other causes, PTH is suppressed)
- Phosphate: low or low-normal (PTH increases phosphate excretion)
- ALP: raised if significant bone disease
- Vitamin D (25-OH): check — deficiency common (replace before surgery)
- 24-hour urine calcium:creatinine clearance ratio: to exclude FHH (<0.01 = FHH; >0.02 = primary HPT)
- U&Es: renal function
Localisation (Pre-Operative)
- USS neck: identifies ~60-80% of adenomas
- Sestamibi (⁹⁹ᵐTc-MIBI) scan: functional scan; parathyroid adenomas retain tracer on delayed images; sensitivity ~80-90%
- 4D-CT: increasingly used when sestamibi/USS discordant
Complications Assessment
- DEXA scan: osteoporosis (lumbar spine, hip, distal radius)
- Renal USS: renal calculi
- X-ray: if bone pain (subperiosteal resorption — radial aspect of middle phalanges; pepper-pot skull)
Management
Indications for Parathyroidectomy (International Consensus)
- Symptomatic disease (any symptom)
- Serum calcium >0.25 mmol/L above ULN
- Age <50 years
- eGFR <60 mL/min
- T-score ≤−2.5 at any site
- Renal calculi or nephrocalcinosis
- 24-hour urine calcium >10 mmol/day
Surgery
- Focused (minimally invasive) parathyroidectomy: for localised adenoma; cure rate >95%
- Intraoperative PTH monitoring: confirms successful removal (PTH falls >50% within 10 minutes)
- Bilateral neck exploration: if localisation studies negative or multigland disease suspected
- Post-operative: monitor calcium (hungry bone syndrome — can cause severe hypocalcaemia); calcium + vitamin D supplementation pre-operatively if deficient
Conservative Management (If Not Meeting Surgical Criteria)
- Adequate hydration: >2L/day
- Avoid dehydration, immobilisation, thiazides
- Monitoring: 6-12 monthly calcium, annual eGFR, annual DEXA
- Cinacalcet 30-90mg BD: calcimimetic; reduces calcium and PTH; NICE TA117 (for patients who cannot have surgery)
Referral Criteria
- Endocrine surgery: all patients meeting surgical criteria
- Endocrinology: complex cases, genetic syndromes
- Clinical genetics: age <40, multigland disease, family history (MEN1/2A)
Prognosis
Parathyroidectomy: cure rate >95%; rapid normalisation of calcium; bone density improves over 1-2 years; renal stone risk decreases. Conservative management: calcium remains stable in majority; ~25% progress to meeting surgical criteria over 10 years. Untreated: increased cardiovascular mortality, fracture risk, renal impairment.
Other Relevant Information
Primary HPT vs Malignancy — Calcium Differentiation
| Feature | Primary HPT | Malignancy |
|---|---|---|
| PTH | HIGH/inappropriately normal | LOW |
| Calcium | Usually mildly raised | Often very high (>3.0) |
| Course | Chronic | Rapid/acute |
| Setting | Community/outpatient | Hospital/inpatient |
| Mechanism | Autonomous PTH | PTHrP, bone metastases, 1,25-D |
Indications for Surgery (Summary)
| Criterion | Threshold |
|---|---|
| Symptoms | Any |
| Ca²⁺ above ULN | >0.25 mmol/L |
| Age | <50 |
| eGFR | <60 |
| T-score | ≤−2.5 |
| Renal calculi | Present |