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Tūhauora — Hyperparathyroidism Clinical Tool
Decision support for Primary & Secondary HPT · 5th International Workshop 2022 · KDIGO · AAES · ANZ Guidelines 2024
Clinical Decision Support
Hyperparathyroidism Clinical Decision Support
6
Guidelines
5
Calculators
2022
5th Workshop
ANZ
2024 Guidelines
Quick Tools
About This Tool
Clinical Decision Support OnlyThis tool assists qualified clinicians with lab interpretation, surgical decision-making, and guideline reference. It does not store patient data. All calculations are performed locally in your browser.
Guidelines referenced:
· 5th International Workshop on Primary HPT (2022)
· AAES Guidelines (2016)
· KDIGO CKD-MBD (2017)
· Endocrine Society of Australia / ANZBMS (2024)
· 5th International Workshop on Primary HPT (2022)
· AAES Guidelines (2016)
· KDIGO CKD-MBD (2017)
· Endocrine Society of Australia / ANZBMS (2024)
Diagnostic Algorithm — Primary HPT Overview
Core PrinciplePrimary HPT = elevated or inappropriately normal PTH in the setting of hypercalcaemia. Always correct calcium for albumin. Always check vitamin D before interpreting PTH — deficiency is the most common cause of secondary PTH elevation.
Step 1 — Confirm Hypercalcaemia
Albumin-corrected Ca ×2 samples. Ionised calcium if albumin unreliable. Check phosphate (typically low-normal in primary HPT due to PTH-driven phosphaturia).
Step 2 — Check Intact PTH
↑ or high-normal PTH + hypercalcaemia = Primary HPT. Suppressed PTH = non-PTH mediated cause (malignancy, vitamin D toxicity, granulomatous disease). Correct vitamin D deficiency first.
Step 3 — Exclude FHH
Calculate CCCR using 24h urine Ca/Cr and serum Ca/Cr. CCCR <1% = FHH likely (do NOT operate). CCCR >2% = Primary HPT. Use the FHH Calculator tab for the full workup.
Enter Laboratory Values
Calcium Studies
Required for corrected Ca
Normal: F <6.2 mmol/24h, M <7.5 mmol/24h
PTH & Bone Markers
15–65 pg/mL equivalent
Renal Function & Phosphate
Vitamin D Status
NZ: <50 deficient · 50–75 insufficient · >75 sufficient
Real-time Interpretation
Enter lab values on the left to see real-time interpretation and clinical guidance.
Patient Parameters
Use Payne formula: corrected Ca = measured Ca + 0.02 × (40 − albumin)
Threshold: >6.2 (F) or >7.5 (M) mmol/24h
Imaging & Clinical Findings
Surgical Criteria Assessment
Enter patient parameters to assess 5th International Workshop 2022 surgical criteria.
Criteria Reference — 5th International Workshop 2022 + AAES
Key PrincipleSurgery is recommended for ALL symptomatic patients. For asymptomatic patients, ANY single criterion below is sufficient to indicate surgery. Parathyroidectomy remains an option even if no criteria are met — it is the only cure.
| Criterion | Threshold | Guideline |
|---|---|---|
| Symptoms | Any symptomatic hypercalcaemia | Both |
| Age | <50 years | Both |
| Serum calcium | >0.25 mmol/L (1 mg/dL) above ULN | Both |
| BMD T-score | ≤−2.5 at any site (lumbar spine, hip, distal ⅓ radius) | Both |
| Vertebral fracture | Any fracture on imaging | Both |
| Renal function | eGFR <60 mL/min/1.73m² | Both |
| 24h urine calcium | >6.2 mmol/24h (women) or >7.5 mmol/24h (men) | 5th Workshop |
| Nephrolithiasis / nephrocalcinosis | Confirmed on imaging | Both |
| Neurocognitive / psychiatric symptoms | Present (weaker evidence) | AAES only |
| Cardiovascular disease | Present (weaker evidence) | AAES only |
FHH vs Primary HPT — Calcium:Creatinine Clearance Ratio (CCCR)
Why This Is CriticalFamilial Hypocalciuric Hypercalcaemia (FHH — CASR/AP2S1/GNA11 mutation) presents identically to primary HPT biochemically but parathyroidectomy is NOT curative and NOT indicated. CCCR <1% strongly suggests FHH. Always exclude before referring for surgery.
CCCR Inputs
Convert: µmol/L ÷ 1000 = mmol/L (e.g. 85 µmol/L = 0.085 mmol/L)
Formula
CCCR = (urine Ca × serum Cr) ÷ (serum Ca × urine Cr) × 100
All values in same units (mmol). Result = percentage.
All values in same units (mmol). Result = percentage.
Enter all four values to calculate CCCR.
Interpretation Thresholds
| CCCR | Interpretation |
|---|---|
| <1% | FHH likely — genetic testing, no surgery |
| 1–2% | Indeterminate — further investigation needed |
| >2% | Primary HPT likely — proceed with workup |
FHH vs Primary HPT — Clinical Differentiation
| Feature | Primary HPT | FHH |
|---|---|---|
| Serum calcium | Elevated (often >2.8) | Mildly elevated (often 2.6–2.8) |
| PTH | Elevated or high-normal | Normal or mildly elevated |
| 24h urine calcium | Often elevated | Low — hallmark feature |
| CCCR | >2% | <1% |
| Serum phosphate | Low-normal | Normal |
| Serum magnesium | Normal | Often mildly elevated |
| Family history | Usually negative | Often positive (autosomal dominant) |
| Symptoms | May be present | Usually asymptomatic throughout life |
| Mutations | Somatic (MEN1, CDC73) | CASR (80%), AP2S1, GNA11 |
| Sestamibi scan | Often positive | Negative |
| Treatment | Parathyroidectomy (curative) | No surgery — watchful waiting |
Important Caveats for CCCRFalsely low CCCR (mimicking FHH) seen with: vitamin D deficiency, CKD, thiazide diuretics, lithium use. Always correct vitamin D deficiency and repeat. Lithium causes a true FHH-like syndrome. If in doubt, refer to endocrinology and consider genetic testing.
Pre-operative Localisation Strategy
Critical PrincipleLocalisation imaging is for operative planning ONLY — not for diagnosis. Biochemical diagnosis must be established first. Aim for concordance between ≥2 modalities before minimally invasive parathyroidectomy (MIP). Negative or discordant imaging does not exclude primary HPT.
Recommended Approach
Tier 1 — First Line (All Patients)
🔊 Neck Ultrasound (USS)
Sensitivity ~75–80% for single adenoma. No radiation. Concurrent thyroid assessment (multinodular goitre relevant to operative planning). Operator dependent. Limited for retrosternal or ectopic glands. Should be performed by experienced operator.
Tier 1 — First Line (Concurrent)
☢️ Sestamibi Scintigraphy (Tc-99m MIBI ± SPECT/CT)
Sensitivity ~80–85% for single adenoma. Lower sensitivity for multiglandular disease (~20–40%) and small glands. SPECT/CT adds anatomical localisation. Concordance between USS + MIBI guides MIP — ~95% positive predictive value when concordant.
↓ If discordant, non-localising, re-operative neck, or multigland disease suspected
Tier 2 — Second Line
🔍 4D-CT (Four-dimensional CT)
Multi-phase CT (non-contrast + arterial + venous). Sensitivity 88–92% for single adenoma, better for multiglandular disease. Superior spatial resolution vs. USS/MIBI. Preferred for re-operative or complex cases. Radiation dose ~4–6 mSv. Best avoided in young patients or pregnancy.
Tier 2 — Second Line Alternative
🧲 MRI Neck
No ionising radiation — preferred in young patients, pregnant patients, or those with iodine contrast allergy. Sensitivity ~75–80%. Useful for ectopic mediastinal glands. Longer scan time, motion artefact. Not universally first-line due to availability.
↓ Persistent / recurrent HPT or failed prior surgery
Tier 3 — Specialist / Tertiary
🌟 18F-Fluorocholine PET/CT (FCH-PET)
Sensitivity >90%, superior spatial resolution. Especially useful in re-operative cases, multiglandular disease, or after negative conventional imaging. Increasingly available in NZ tertiary centres. Preferred emerging modality for complex cases. Also: 11C-choline PET/CT (requires on-site cyclotron).
Tier 3 — Specialist / Last Resort
🩸 Selective Venous Sampling (PTH gradient mapping)
Invasive catheterisation of jugular, thymic, and thyroid veins with PTH gradient analysis. Reserved for re-operative cases where non-invasive localisation has failed. Requires specialist interventional radiology. Sensitivity ~70–80% for lateralisation.
Modality Comparison
| Modality | Sensitivity (Single) | Multigland |
|---|---|---|
| Neck USS | 75–80% | Poor |
| Sestamibi ± SPECT/CT | 80–85% | 20–40% |
| 4D-CT | 88–92% | Better |
| MRI | 75–80% | Moderate |
| FCH-PET/CT | >90% | Good |
| Venous sampling | ~70–80% (lateralise) | Good |
Intraoperative PTH — Miami Criterion
Miami Criterion≥50% fall in PTH from peak pre-excision value at 10 min post-excision, WITH PTH falling into the normal range → predicted cure with ~95% accuracy.
Hereditary HPT Syndromes
Approximately 10-15% of primary HPT is hereditary. Suspect a syndrome in: age <40, multiglandular disease, recurrent HPT, parathyroid carcinoma, family history, or associated tumour features. Genetic testing and cascade family screening are recommended when a syndrome is identified.
MEN1 — Multiple Endocrine Neoplasia Type 1
Most common hereditary HPTGenetics
| Gene | MEN1 (menin tumour suppressor) |
| Locus | 11q13 |
| Inheritance | Autosomal dominant |
| Penetrance | >95% by age 50 |
| De novo rate | ~10% |
HPT Features
| Prevalence in MEN1 | ~95% (most common manifestation) |
| Onset | Typically 20-40s (earlier than sporadic) |
| Gland involvement | Multiglandular disease (~85%) |
| Carcinoma risk | Very low (<1%) |
| Surgery | Subtotal (3.5 gland) or total PTX + autograft; higher recurrence vs sporadic |
Associated Tumours (3 Ps)
| Organ | Tumour Type | Prevalence |
|---|---|---|
| Parathyroid | Multiglandular hyperplasia / adenoma | ~95% |
| Pituitary | Prolactinoma (most common), GH-oma, non-functioning | ~30-40% |
| Pancreas / duodenum | Gastrinoma (ZES), insulinoma, VIPoma, non-functioning NET | ~30-70% |
| Adrenal cortex | Non-functioning adenoma, cortical hyperplasia | ~20-40% |
| Thymic carcinoid | Neuroendocrine tumour (aggressive, male predominance) | ~2-8% |
| Bronchial carcinoid | Neuroendocrine tumour | ~2-5% |
| Skin | Facial angiofibromas, collagenomas, lipomas | Common |
Surveillance Annual: serum Ca, PTH, fasting gut hormones, prolactin, IGF-1. MRI pituitary every 3 years. CT/MRI pancreas annually if NET known or age >20.
MEN2A — Multiple Endocrine Neoplasia Type 2A
Genetics
| Gene | RET proto-oncogene (gain-of-function) |
| Locus | 10q11.2 |
| Inheritance | Autosomal dominant |
| Key codons | C634 (highest HPT risk), C611, C618, C620 |
HPT Features
| Prevalence in MEN2A | ~20-30% |
| Severity | Usually mild hypercalcaemia |
| Gland involvement | Multiglandular hyperplasia |
| Carcinoma risk | Very rare |
| Surgery timing | Often concurrent with prophylactic thyroidectomy |
Associated Tumours
| Organ | Tumour Type | Prevalence |
|---|---|---|
| Thyroid C-cells | Medullary thyroid carcinoma (MTC) — defining feature | ~95% |
| Adrenal medulla | Phaeochromocytoma (usually bilateral) | ~50% |
| Parathyroid | Multiglandular hyperplasia | ~20-30% |
| Skin | Cutaneous lichen amyloidosis (interscapular, codon 634) | Rare |
| Bowel | Hirschsprung disease (codons 618/620) | Rare |
Critical Always exclude phaeochromocytoma (plasma/urine metanephrines) BEFORE any surgery. Prophylactic thyroidectomy timing guided by RET codon risk category.
MEN4 — Multiple Endocrine Neoplasia Type 4
Rare — MEN1-like phenotypeGenetics
| Gene | CDKN1B (p27, cyclin-dependent kinase inhibitor) |
| Locus | 12p13 |
| Inheritance | Autosomal dominant |
| Frequency | Rare; <3% of MEN1-like cases |
Consider when MEN1-like phenotype but MEN1 sequencing is negative. Broader CDKN panel (CDKN1A, CDKN2B, CDKN2C) emerging in research.
Associated Features
| Feature | Notes |
|---|---|
| Primary HPT | Most common; often multiglandular |
| Pituitary adenoma | ACTH-secreting (Cushing), non-functioning |
| Pancreatic NET | Less frequent than MEN1 |
| Renal / uterine | Neuroendocrine tumours reported |
| Adrenal | Cortical tumours reported |
HPT-JT — Hyperparathyroidism-Jaw Tumour Syndrome
Elevated carcinoma riskGenetics
| Gene | CDC73 (formerly HRPT2; encodes parafibromin) |
| Locus | 1q25-q31 |
| Inheritance | Autosomal dominant |
| Penetrance | Variable; ~80% by age 70 |
HPT Features
| Prevalence | ~80% develop primary HPT |
| Gland involvement | Often single gland (cystic adenoma) |
| Carcinoma risk | ~10-15% — significantly elevated |
| Histology clue | Loss of parafibromin staining (IHC) |
| Recurrence | Common; multiple operations often needed |
Associated Features
| Feature | Notes |
|---|---|
| Jaw ossifying fibromas | Mandible > maxilla; locally aggressive; ~30% of cases |
| Renal lesions | Wilms tumour, hamartomas, cysts, renal cell carcinoma |
| Uterine tumours | Adenomyosis, leiomyomas, adenosarcoma (females) |
| Parathyroid carcinoma | Very high Ca (>3.0 mmol/L), very high PTH, palpable neck mass, jaw fibroma |
Key CDC73 germline testing recommended in ALL parathyroid carcinoma cases. Loss of parafibromin on IHC is a strong indicator.
FIHP — Familial Isolated Hyperparathyroidism
Genetics
| Genes | MEN1, CDC73, CASR, GCM2, AP2S1 |
| Inheritance | Autosomal dominant (usually) |
| Definition | 2+ first-degree relatives with HPT; no features of MEN1, MEN2A, or HPT-JT |
Clinical Notes
| Status | May be early / incomplete MEN1 or HPT-JT — diagnose with caution |
| Carcinoma risk | Elevated if CDC73 mutation identified |
| Action | Comprehensive gene panel; long-term surveillance; cascade family screening |
FHH — Familial Hypocalciuric Hypercalcaemia
Benign — surgery not indicatedSubtypes and Genetics
| Subtype | Gene | Mechanism |
|---|---|---|
| FHH1 (~65%) | CASR | Inactivating CaSR mutation — set-point shifted right |
| FHH2 (~10%) | GNA11 | G-protein alpha-11 subunit (downstream of CaSR) |
| FHH3 (~20%) | AP2S1 | Adaptor protein 2 sigma subunit; often more severe hypercalcaemia |
Clinical Features
| Inheritance | Autosomal dominant (heterozygous) |
| Ca | Mild-moderate hypercalcaemia (lifelong, usually asymptomatic) |
| PTH | Normal or mildly elevated (non-suppressed) |
| CCCR | <0.01 (key differentiator from primary HPT) |
| Urine Ca | Low despite hypercalcaemia |
| Family Hx | Hypercalcaemia in multiple generations, asymptomatic |
| NSHPT risk | Homozygous offspring of two FHH1 parents: life-threatening neonatal HPT |
Management No treatment needed. Parathyroidectomy does NOT correct hypercalcaemia — must exclude FHH before operating. Confirm with CCCR + family history + genetic testing.
NSHPT — Neonatal Severe Hyperparathyroidism
Life-threatening — urgent surgeryGenetics
| Gene | CASR (homozygous or compound heterozygous loss-of-function) |
| Mechanism | Complete loss of CaSR function — extreme hypercalcaemia from birth |
| Inheritance | Often born to two FHH1 parents (homozygous child) |
Clinical Features and Management
| Onset | First days to weeks of life |
| Ca | Severe (>3.5-4.0 mmol/L) |
| Features | Hypotonia, respiratory distress, failure to thrive, seizures, skeletal demineralisation, fractures |
| Treatment | Total parathyroidectomy (urgent); IV bisphosphonates / cinacalcet as bridge |
When to Suspect Hereditary HPT — Red Flags and Gene Panel
Clinical Triggers for Genetic Testing
| Age <40 at HPT diagnosis |
| Multiglandular parathyroid disease |
| Recurrent or persistent HPT after surgery |
| Parathyroid carcinoma (any age) |
| Family history of HPT, MEN, NET, or phaeochromocytoma |
| Associated pituitary, pancreatic, or adrenal tumour |
| Jaw ossifying fibroma |
| Renal hamartoma, Wilms tumour, or unexplained renal tumour |
| Medullary thyroid carcinoma or phaeochromocytoma |
| Loss of parafibromin on IHC |
| CCCR <0.01 (suspect FHH) |
Gene Panel Summary
| Syndrome | Gene(s) |
|---|---|
| MEN1 | MEN1 |
| MEN2A | RET |
| MEN4 | CDKN1B |
| HPT-JT / Parathyroid carcinoma | CDC73 |
| FHH / NSHPT | CASR, GNA11, AP2S1 |
| FIHP (other) | GCM2 |
Referral Refer to clinical genetics for counselling, germline panel testing, and cascade family screening when a hereditary syndrome is suspected or confirmed.
Primary HPT — Medical Management
Non-surgical Management Principles
| Intervention | Guidance |
|---|---|
| Vitamin D deficiency | Correct to ≥50 nmol/L — monitor Ca carefully as may transiently ↑ serum Ca but corrects secondary PTH elevation |
| Dietary calcium | Normal intake (1000–1200 mg/day) — do NOT restrict; calcium restriction increases PTH and bone resorption |
| Hydration | ≥2L/day to maintain urine output >2L — reduces nephrolithiasis risk |
| Thiazide diuretics | AVOID — increase renal tubular calcium reabsorption, worsen hypercalcaemia |
| Lithium | AVOID or use with caution — raises PTH set-point, causes FHH-like hypercalcaemia |
| Immobilisation | Avoid prolonged bed rest — increases bone resorption and hypercalcaemia |
Medical Therapies
| Agent | Effect | Indication |
|---|---|---|
| Alendronate / Risedronate (bisphosphonates) | ↑ BMD (cortical & trabecular), no effect on serum Ca or PTH | Osteoporosis, high fracture risk in non-surgical patients |
| Cinacalcet (calcimimetic) | ↓ PTH and ↓ serum Ca — does NOT improve BMD | Hypercalcaemia control when surgery contraindicated |
| HRT (postmenopausal women) | ↑ BMD, mild ↓ Ca | Osteoporosis + menopausal symptoms |
| Denosumab | ↑ BMD (limited data in primary HPT) | Consider if bisphosphonate intolerant |
Annual Surveillance Protocol (Non-surgical patients)Serum Ca + PTH + renal function: annually. BMD (DXA): every 1–2 years (include distal ⅓ radius). Renal imaging (USS): every 1–2 years. 25-OH Vit D: annually.
Secondary HPT (CKD) — KDIGO Management
Biochemical Targets
| Parameter | Target |
|---|---|
| Serum phosphate | <1.49 mmol/L (<4.6 mg/dL) |
| Serum calcium | <2.37 mmol/L — avoid hypercalcaemia |
| PTH (CKD G3a–G5 pre-dialysis) | Trend monitoring; target 2× ULN |
| PTH (Dialysis) | 2–9× ULN (i.e. ~14–62 pmol/L) |
| 25-OH Vitamin D | Correct deficiency in all CKD stages |
Treatment Ladder
| Step | Intervention | Notes |
|---|---|---|
| 1 | Dietary phosphate restriction | Limit processed foods, cola drinks |
| 2 | Phosphate binders | Ca-based if normocalcaemia; sevelamer carbonate if hypercalcaemia (reduces vascular calcification) |
| 3 | Active vitamin D (alfacalcidol / calcitriol) | ↓ PTH, prevents renal bone disease — monitor Ca |
| 4 | Calcimimetics | Cinacalcet (oral); Etelcalcetide (IV — preferred in-centre dialysis). ↓ PTH + ↓ Ca |
| 5 | Parathyroidectomy | Refractory secondary HPT; subtotal PTX most common (83%). Tertiary HPT post-transplant. |
Surgical Threshold — Secondary HPTParathyroidectomy for CKD: PTH persistently >9× ULN despite optimal medical therapy, with symptoms or complications (calciphylaxis, refractory pruritis, fractures, severe bone pain). Subtotal PTX preferred over total PTX + autotransplant in most centres.
Post-Parathyroidectomy Management
Hungry Bone SyndromeRisk highest in severe, prolonged primary or secondary HPT with high pre-op ALP. Rapid post-op fall in Ca, PO₄, Mg as skeleton re-mineralises. Can be severe and prolonged (weeks). Pre-load: start calcium and calcitriol before surgery if high risk. Monitor Ca 4-hourly ×48h post-op.
Immediate Post-op (0–72h)
Monitor: corrected Ca 4-hourly, phosphate BD, Mg OD
Target post-op Ca: 2.0–2.4 mmol/L
Tetany risk if Ca <1.9 mmol/L
IV calcium gluconate 10% if symptomatic or Ca <1.8
Check Chvostek / Trousseau signs
PTH at 24h post-op confirms cure (<ULN = cured)
Calcitriol 0.25–0.5 µg BD if hungry bone risk
Discharge & Follow-up
Calcium carbonate 500–1000mg TDS with meals
Calcitriol 0.25 µg BD (continue until normocalcaemic)
Vitamin D supplementation (cholecalciferol)
Recheck Ca at 1 week, 6 weeks, 6 months
Expect BMD ↑ 15–20% at 1–2 years post-op
24h urine Ca at 6 months (confirm cure)
PTH at 6 months — may take months to rise to normal
Confirming CureBiochemical cure = normocalcaemia at 6 months post-op. Persistent hypercalcaemia at 6 months = persistent disease (missed gland, ectopic). Recurrent hypercalcaemia after normalisation = recurrent disease (new adenoma or multiglandular).
Evidence Base & Key References
| Reference | Year | Focus |
|---|---|---|
| 5th International Workshop on Asymptomatic Primary HPT | 2022 | Gold standard guidelines for diagnosis, surgical criteria, and medical management of primary HPT |
| AAES Guidelines for Primary HPT (Wilhelm et al., JAMA Surgery) | 2016 | Surgical management; extends criteria to include neurocognitive and cardiovascular disease |
| KDIGO CKD-Mineral and Bone Disorder Guidelines | 2009, updated 2017 | Secondary HPT management in CKD — phosphate, calcium, PTH targets, treatment ladder |
| Endocrine Society of Australia / ANZBMS Position Statement (Milat et al., Clin Endocrinol) | 2024 | Australian & New Zealand specific guidance on primary HPT assessment and management |
| Cochrane Review — Parathyroidectomy in Adults (Pappachan et al.) | 2023 | Evidence for surgical vs. non-surgical management of primary HPT |
| NEJM — Primary Hyperparathyroidism (Insogna) | 2018 | Comprehensive clinical review |
| JAMA — Hypercalcaemia Review (Walker & Shane) | 2022 | Differential diagnosis and management of hypercalcaemia |
⚠️ Clinical Decision Support Tool
For use by qualified healthcare professionals only. This tool does not replace clinical judgement, specialist assessment, or locally validated guidelines. All calculations should be verified against current institutional and national protocols.
Guidelines referenced: 5th International Workshop on Primary HPT (2022) · AAES Guidelines (2016) · KDIGO CKD-MBD (2017) · Endocrine Society of Australia / ANZBMS Position Statement (2024) · Cochrane Review (2023)
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