Hyperparathyroidism

Hyperparathyroidism presents in three forms: Primary (autonomous PTH secretion, usually from a single adenoma in 85% of cases), Secondary (compensatory PTH elevation from chronic renal failure or vitamin D deficiency), and Tertiary (autonomous hyperfunction after chronic secondary HPT). The classic clinical triad "Bones, Stones, Groans" describes skeletal manifestations (osteitis fibrosa cystica, brown tumors, subperiosteal resorption), renal calculi from hypercalciuria, and abdominal pain. Brown tumors are benign osteoclastic giant cell lesions (not malignant despite the name) that mimic metastases on imaging but resolve after parathyroidectomy. Biochemical diagnosis is key: elevated calcium WITH elevated PTH confirms primary HPT (malignancy causes elevated calcium with suppressed PTH). Surgical indications for primary HPT include: age under 50, calcium greater than 2.85 mmol/L, GFR less than 60, T-score less than -2.5, brown tumors, or renal stones—asymptomatic mild disease can be observed with monitoring.

Hyperparathyroidism is a disorder of excessive parathyroid hormone (PTH) secretion, leading to dysregulation of calcium and phosphate homeostasis. The condition is classified into three types based on mechanism.

Types:

• Primary HPT: Autonomous PTH secretion from parathyroid adenoma (85%), hyperplasia (10-15%), or rarely carcinoma (under 1%)
• Secondary HPT: Compensatory PTH elevation in response to chronic hypocalcemia (renal failure, vitamin D deficiency, malabsorption)
• Tertiary HPT: Autonomous PTH secretion developing after prolonged secondary HPT (typically post-renal transplant)

Parathyroid Hormone Physiology

PTH actions on calcium homeostasis:

Net result: Elevated serum calcium, reduced serum phosphate

Primary Hyperparathyroidism Pathogenesis

Secondary Hyperparathyroidism

Mechanism: Chronic hypocalcemia stimulates parathyroid glands to increase PTH secretion

Causes:

• Chronic kidney disease (most common): Reduced phosphate excretion and impaired 1-alpha hydroxylase (low active vitamin D)
• Vitamin D deficiency: Reduced intestinal calcium absorption
• Malabsorption (celiac, Crohn's): Inadequate calcium absorption
• Chronic loop diuretic use: Renal calcium wasting

Result: Normal or LOW calcium with elevated PTH (appropriate response)

Tertiary Hyperparathyroidism

Mechanism: After prolonged secondary HPT, parathyroid glands become autonomous (no longer responsive to calcium feedback)

Typical scenario: Renal transplant patient with previously high PTH now develops hypercalcemia post-transplant (glands continue secreting PTH autonomously)

Treatment: Requires parathyroidectomy (medical management ineffective)

Primary Hyperparathyroidism Presentation

Brown Tumors - Orthopaedic Manifestation

Definition: Osteoclastic giant cell lesions (osteitis fibrosa cystica) appearing as lytic bone lesions

Pathophysiology:

• Excessive PTH drives osteoclast activity
• Focal areas of bone resorption replaced by fibrous tissue and giant cells
• Hemorrhage within lesions produces hemosiderin (brown color grossly)

Clinical features:

• Lytic expansile lesions on X-ray (mimic metastases, myeloma, giant cell tumor)
• Most common sites: Jaw (mandible), ribs, pelvis, long bones
• Usually painless unless pathological fracture occurs
• May present as palpable bony swelling

Key point: Brown tumors are BENIGN and resolve after parathyroidectomy

Algorithm

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Primary Hyperparathyroidism - Surgical Indications

Surgical Options

Medical Management

For asymptomatic patients not meeting surgical criteria:

Monitoring:

• Serum calcium every 6-12 months
• eGFR annually
• DEXA scan every 1-2 years
• 24-hour urine calcium if nephrolithiasis develops

Conservative measures:

• Adequate hydration (2-3 L/day)
• Avoid thiazide diuretics (increase calcium)
• Maintain vitamin D sufficiency (25-OH vitamin D 50-75 nmol/L)
• Weight-bearing exercise

Pharmacological (if surgery declined):

• Calcimimetics (cinacalcet): Activates calcium-sensing receptor, lowers PTH and calcium
• Bisphosphonates: Prevent bone loss, do not treat hypercalcemia
• Not curative, only symptom control

Secondary Hyperparathyroidism Management

Treat underlying cause:

• CKD: Phosphate binders, activated vitamin D (calcitriol), calcimimetics
• Vitamin D deficiency: Vitamin D supplementation (cholecalciferol 50,000 IU weekly until replete)
• Malabsorption: Treat GI condition, oral or IV calcium/vitamin D

Renal osteodystrophy management:

• Control phosphate (under 1.5 mmol/L with binders)
• Maintain calcium (2.2-2.5 mmol/L)
• Suppress PTH (target 2-9x upper limit normal for CKD stage)
• Monitor for vascular calcification

• Normocalcaemic primary HPT — patients with consistently elevated PTH but persistently normal calcium (after excluding vitamin D deficiency, renal impairment and drugs). Whether and when to operate is unresolved; a proportion progress to classic hypercalcaemic disease.
• Surgery for mild/asymptomatic disease — the SIPH RCT shows a BMD benefit from surgery, but no randomised trial has yet shown a fracture-reduction benefit in mild disease, so the threshold for operating on patients who do not meet formal criteria remains debated.
• Non-classical (neurocognitive) symptoms — fatigue, low mood and cognitive complaints are common, but improvement after parathyroidectomy is inconsistent across studies, so these symptoms alone are a weak surgical indication.
• Localisation strategy — the optimal first-line imaging (ultrasound, sestamibi-SPECT, 4D-CT, or choline PET) varies by availability and expertise; negative imaging does NOT exclude an adenoma and should not deny a patient surgery by an experienced surgeon.
• Bilateral exploration vs focused surgery — focused MIP risks missing multigland disease; intraoperative PTH monitoring mitigates but does not eliminate this, and some centres still favour four-gland assessment.
• Cinacalcet's role — it lowers calcium but does not reliably improve BMD or cure disease, so it is reserved for patients unfit for or declining surgery rather than as an equivalent alternative.

Global Epidemiology

• Prevalence approximately 1-7 per 1000 adults; among the most common endocrine disorders after diabetes and thyroid disease.
• Female predominance roughly 3:1, peaking in postmenopausal women (age 50-70).
• In high-income settings with routine biochemistry screening, most cases are asymptomatic and detected incidentally; in regions where calcium is not measured routinely, patients still present late with florid skeletal disease (brown tumours, fractures) and renal stones, so the classic "bones, stones, groans" picture remains common.
• Secondary HPT prevalence tracks the burden of chronic kidney disease and vitamin D deficiency, which is high across much of South Asia, the Middle East and parts of Africa.

Side-by-Side Guideline Comparison

Registry and Outcome Notes

• There is no implant registry for parathyroid surgery; outcome benchmarks come from national audit and high-volume series (cure rates 95-99%, permanent hypoparathyroidism and recurrent laryngeal nerve injury each typically under 1-3%).
• Surgeon and centre volume are the strongest determinants of cure and complication rates — a recurring theme across health systems.

High- vs Limited-Resource Practice Variation

• Well-resourced settings: incidental biochemical diagnosis, dual-modality localisation (sestamibi plus ultrasound, with 4D-CT for reoperation), minimally invasive parathyroidectomy with rapid intraoperative PTH, and day-case surgery.
• Limited-resource settings: later presentation with overt bone disease; localisation may rely on ultrasound alone; bilateral neck exploration remains a robust default when rapid PTH assays or nuclear imaging are unavailable; vitamin D repletion before surgery is essential to limit hungry bone syndrome.