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Endocrinology
Endocrine Surgery
General Practice

Primary Hyperparathyroidism

High EvidenceUpdated: 2025-12-24

On This Page

Red Flags

  • Severe Hypercalcaemia (>3.5 mmol/L) -> Cardiac Arrhythmia
  • Acute Pancreatitis
  • Hypercalcaemic Crisis (Confusion/Coma)
  • Neck Hematoma (Post-op) -> Airway Obstruction
Overview

Primary Hyperparathyroidism

1. Clinical Overview

Summary

Primary Hyperparathyroidism (PHPT) is the autonomous overproduction of Parathyroid Hormone (PTH), leading to Hypercalcaemia. It is the most common cause of hypercalcaemia in the outpatient setting. (In hospitals, malignancy is more common). While classically associated with florid symptoms ("Bones, Stones, Groans"), 80% of modern patients are "asymptomatic", identified incidentally on routine biochemistry. [1,2]

The 3 Types of Hyperparathyroidism

  1. Primary: Problem in the gland (Adenoma). High Ca, High PTH.
  2. Secondary: Physiological compensation for low calcium (e.g., Vitamin D deficiency, CKD). Low/Normal Ca, High PTH.
  3. Tertiary: Autonomous overactivity following long-standing secondary HPT (e.g., post-renal transplant). High Ca, High PTH.

Clinical Pearls

The Diagnostic Trap: A "Normal" PTH does not exclude PHPT. If Calcium is high (e.g., 2.8 mmol/L), the PTH should be suppressed (less than 1.0 pmol/L). A PTH of 4.5 (normally 1.6-6.9) is inappropriately normal and confirms the diagnosis.

FHH Warning: Before sending a patient for neck surgery, you MUST exclude Familial Hypocalciuric Hypercalcaemia (FHH). This is a benign genetic condition requiring no treatment. Check Urine Calcium Clearance Ratio. If less than 0.01, it is FHH.

Vitamin D: Many PHPT patients are Vitamin D deficient. Replenishing Vitamin D is safe and essential pre-op to prevent Hungry Bone Syndrome (severe post-op hypocalcaemia).

2. Epidemiology

Demographics

  • Prevalence: 0.3% of general population. 3% of post-menopausal women.
  • Gender: Female:Male = 3:1.
  • Age: Peak 50-70 years.

Aetiology

  • Solitary Adenoma: 85% (Single gland).
  • Hyperplasia: 10-15% (All 4 glands).
  • Carcinoma: less than 1% (Very rare, Ca >3.5, palpable mass).
  • Genetic: MEN1, MEN2A.
3. Pathophysiology

Mechanisms

  1. Bone: PTH stimulates osteoclasts -> Resorption of Calcium and Phosphate.
  2. Kidney: PTH increases Calcium reabsorption (DCT) and dumps Phosphate (PCT). Also activates 1-alpha-hydroxylase to convert Vit D to active form.
  3. Gut: Active Vit D increases Calcium absorption.
  4. Net Effect: Hypercalcaemia + Hypophosphataemia.
4. Clinical Presentation

"Bones, Stones, Abdominal Groans, Psychic Moans"

Most patients have subtle symptoms only.

  1. Bones: Osteoporosis (DEXA T-score less than -2.5), Fragility fractures, Bone pain. rarely Osteitis Fibrosa Cystica (Brown tumours).
  2. Stones: Nephrolithiasis (Ca-Oxalate stones), Nephrocalcinosis, Polyuria (Nephrogenic Diabetes Insipidus).
  3. Abdominal Groans: Constipation, Nausea, Peptic Ulcer (Ca stimulates Gastrin), Pancreatitis.
  4. Psychic Moans: Fatigue, Depression, Brain fog, Confusion.

Cardiovascular

Hypertension (stiff vessels).
Common presentation.
Short QT interval.
Common presentation.
5. Clinical Examination
  • Neck: Usually normal (adenomas typically less than 1-2cm and soft/posterior). Palpable mass = Thyroid nodule or Parathyroid Cancer.
  • BP: Hypertension common.
  • Cornea: Band Keratopathy (calcium deposits) - rare.
6. Investigations

Biochemistry

  • Serum Calcium: Elevated (>2.60 mmol/L).
  • PTH: Elevated or Inappropriately Normal.
  • Phosphate: Low/Low-Normal.
  • Vitamin D: Check 25-OH-D.
  • U&E: Check renal function.

Exclusion Test (Mandatory)

  • 24hr Urinary Calcium / Calcium:Creatinine Clearance Ratio (CCCR):
    • < 0.01: FHH (Do not operate).
    • > 0.02: PHPT.

Localization Imaging (Pre-op)

  • Sestamibi Scan (99mTc-MIBI): Nuclear medicine scan. Adenomas stay "hot". (Sensitivity 80-90%).
  • Ultrasound Neck: Depends on operator.
  • 4D-CT: Used for failed localization or re-do surgery.
7. Management

Management Algorithm

        PRIMARY HYPERPARATHYROIDISM
        (High Ca + High/Normal PTH)
                    ↓
        EXCLUDE FHH (Urine Calcium)
                    ↓
        ASSESS SURGICAL INDICATIONS
       (Symptoms, Age less than 50, Ca &gt;2.85, 
        Osteoporosis, Renal Stones)
        ┌───────────┴───────────┐
       MET                     NOT MET
        ↓                       ↓
    LOCALIZATION              MONITOR
    (US + MIBI)             (Conservative)
    ┌───┴───┐                   ↓
 MATCH    NO MATCH         Ca rises? Or
   ↓         ↓            Bones worsen?
  MIP     EXPLORE               ↓
                           RECONSIDER

Surgical Management (Parathyroidectomy)

  • Indications (NICE / International Workshop):
    1. symptomatic (stones/fractures).
    2. Age < 50.
    3. Calcium > 2.85 mmol/L (>0.25 above limit).
    4. eGFR < 60.
    5. Osteoporosis (T-score < -2.5).
  • Technique:
    • Minimally Invasive Parathyroidectomy (MIP): Small incision if adenoma localised.
    • Bilateral Neck Exploration: If hyperplasia or negative scans.

Medical Management

  • Cinacalcet: Calcimimetic. Lowers serum calcium but does NOT improve bone density. Used if unfit for surgery.
  • Bisphosphonates: Improve bone density.
  • Hydration: Avoid dehydration.
8. Complications

Disease Complications

  • Hypercalcaemic Crisis: Severe dehydration, confusion, coma. Needs aggressive rehydration + Bisphosphonates.
  • Renal Failure: Stones/Calcinosis.

Surgical Complications

  • Hungry Bone Syndrome: Severe hypocalcaemia post-op as starved bones suck up calcium. Requires IV Calcium/Calcitriol.
  • Recurrent Laryngeal Nerve Palsy: Voice change.
  • Hematoma: Airway compromise.
9. Prognosis and Outcomes
  • Cure Rate: 95-98% with expert surgery.
  • Recurrence: Rare. Check for MEN syndrome if recurrence occurs.
  • Bone Density: Improves significantly (10-15%) in first year post-op.
10. Evidence and Guidelines

Key Guidelines

GuidelineOrganisationKey Recommendations
PHPT ManagementNICE NG132Refer all suitable patients for surgery.
Asymptomatic4th Intl WorkshopCriteria for surgery in asymptomatic patients.

Landmark Evidence

1. Surgery vs Observation

  • RCTs show surgery improves bone density and quality of life compared to observation, even in "asymptomatic" patients.
11. Patient and Layperson Explanation

What are parathyroids?

Four tiny glands (size of a grain of rice) behind your thyroid. They regulate calcium levels. They are nothing to do with the thyroid itself (despite the name).

What is the problem?

One of the glands has grown a small benign lump (adenoma) and is working overtime. It is pulling calcium out of your bones (making them weak) and putting it into the blood (causing kidney stones and fatigue).

Do I need an operation?

Ideally, yes. It is the only cure. The operation takes 30-60 minutes and usually leaves a very small scar.

What if I don't have surgery?

Your calcium might stay stable for years, but your bones will likely get thinner over time. We need to monitor your kidneys and bones closely.

12. References

Primary Sources

  1. NICE. Hyperparathyroidism (primary): diagnosis, assessment and initial management. NG132. 2019.
  2. Bilezikian JP, et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014.
13. Examination Focus

Common Exam Questions

  1. Diagnosis: "High Ca, Normal PTH?"
    • Answer: Primary Hyperparathyroidism (Inappropriately normal).
  2. Rule Out: "Urine Calcium Low?"
    • Answer: FHH (Familial Hypocalciuric Hypercalcaemia). Do not operate.
  3. Management: "Young patient less than 50?"
    • Answer: Surgery is indicated regardless of symptoms.
  4. Complication: "Tingling fingers post-op?"
    • Answer: Hypocalcaemia (Hungry Bone Syndrome).

Viva Points

  • Sestamibi: How does it work? Parathyroid adenomas are rich in mitochondria, which take up the Technetium tracer and wash out slower than the thyroid.
  • Brown Tumour: A misnomer. It is a giant cell reparative granuloma in the bone due to rapid turnover. It is not a neoplasm.

Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.

Last updated: 2025-12-24

At a Glance

EvidenceHigh
Last Updated2025-12-24

Red Flags

  • Severe Hypercalcaemia (&gt;3.5 mmol/L) -> Cardiac Arrhythmia
  • Acute Pancreatitis
  • Hypercalcaemic Crisis (Confusion/Coma)
  • Neck Hematoma (Post-op) -> Airway Obstruction

Clinical Pearls

  • **Vitamin D**: Many PHPT patients are Vitamin D deficient. Replenishing Vitamin D is safe and essential pre-op to prevent **Hungry Bone Syndrome** (severe post-op hypocalcaemia).
  • Resorption of Calcium and Phosphate.

Guidelines

  • NICE Guidelines
  • BTS Guidelines
  • RCUK Guidelines