Leeds Adult Primary Hyperparathyroidism Guideline

Publication: 06/07/2021  
Next review: 06/07/2024  
Clinical Guideline
CURRENT 
ID: 7056 
Approved By: LAPC 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Leeds Adult Primary Hyperparathyroidism Guideline

Summary of Guideline

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Background

This guideline should be used by medical professionals in Leeds to guide initial diagnosis and investigation of patients with possible primary hyperparathyroidism (PHPT). The guideline aims to standardise approach to management of PHPT.

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A) Primary Care

1. Diagnosis:

Calcium:
Patients presenting to primary care with typical symptoms of hypercalcaemia including constipation, thirst, frequent or excessive urination, evidence of osteoporosis/fragility fractures or renal calculi should have serum calcium checked. Please note serum calcium measurements referred to throughout this guideline should be serum albumin-adjusted calcium levels and not ionised calcium.
Serum calcium should be checked on a second occasion if the levels are as follows:

  1. Serum calcium greater than 2.6 mmol/l
  2. Serum calcium greater than 2.5 mmol/l with symptoms listed above

PTH:
In patients where the calcium levels meet the above criteria on 2 separate occasions a random PTH level should be taken along with a concurrent serum calcium. PHPT should be suspected if PTH levels are as follows:

  1. PTH above midpoint of reference range and aforementioned features of PHPT are present or
  2. PTH elevated or inappropriately normal with serum calcium greater than 2.6mmol/l

A suppressed PTH level i.e. below lower limit of normal range, is not suggestive of PHPT and an alternative diagnosis should be sought.
Patients with a serum calcium less than 2.6 and PTH in lower half of normal range do not require further assessment. In this context PTH levels do not need to be routinely repeated in primary care.

The specific scenario of normocalcaemic PHPT is a variant of PHPT in which there is a raised PTH level with a serum calcium in the upper-end of normal range. All causes of secondary hyperparathyroidism e.g., Vitamin D deficiency and renal impairment should be first excluded before coming to this diagnosis.

3. Referral:

All patients with suspected PHPT, where clinically appropriate, should be referred to the specialist Calcium Clinic via standard referral processes to Endocrinology at Leeds Teaching Hospitals NHS Trust. The referral will be triaged to the appropriate clinic by Consultant Endocrinologists.
In severe hypercalcaemia (greater than or equal to 3.0mmol/l) an urgent referral should be considered to on-call Endocrinology.

4. Primary care investigation:

When clinically appropriate further investigations can be initiated by primary care following referral to the Calcium Clinic:

  • Biochemical assessment: In addition to the bloods required for diagnosis, all patients should have vitamin D levels checked if no result within last three months. Guidance on vitamin D replacement in PHPT is included in these guidelines. Patients should also have an up-to-date U&Es checked and serum phosphate.
  • Bone assessment: If not conducted within the last 2 years, patients will require DXA scan to establish if there is any evidence of reduced bone mineral density. A wrist evaluation (note: if primary hyperthyroidism is ticked when the DXA is requested a wrist scan will be done or if in the clinical comments you note the request for a wrist scan is because of primary hyperparathyroidism then it will be done, along with spine and hip bone density can be useful here, (this gives an assessment of cortical bone loss which is accelerated in primary hyperparathyroidism). Spine x-rays may be indicated if there are symptoms consistent with potential vertebral fractures.
  • Renal assessment: Patients with suspected PHPT require imaging of renal tract, typically ultrasound scan, looking for nephrocalcinosis or renal calculi.

5. Primary care treatment:

In the interim, prior to the patient being reviewed in the Calcium Clinic, it is advised primary care replace vitamin D as follows:

  • Vitamin D less than 25nmol/l or serum calcium greater than 2.9mmol/l: seek specialist endocrine advice before considering vitamin D replacement via usual pathways.
  • Vitamin D 25-50nmol/l AND serum calcium less than 2.9mmol/l: commence Vitamin D replacement at 1000 units per day and recheck serum calcium in 10-14 days following commencing replacement. Stop vitamin D replacement if serum calcium increases to greater than 2.90mmol/L and seek advice from Endocrinology.

PHPT can be treated surgically, medically (with cinacalcet) or simply monitored. Appropriate triage to one of these three outcomes will occur after assessment in Calcium Clinic.
(see - Cinacalcet Hydrochloride - Amber Drug Guidance for the Treatment of Primary Hyperparathyroidism in Adults)
Osteoporosis and renal stones to be managed as per local guidance.

6. Long-term monitoring in primary care:

 

Following successful surgery

Unsuccessful surgery or non-surgically managed PHPT

Follow-up

Typically discharged to Primary care if biochemical cure, benign histology and no genetic cause following post-op review after 3-6 months

May be discharged to Primary Care or managed via nurse-led LTHT PHPT pathway- indicated in clinic letter

Biochemistry

Annual serum calcium check and maintain Vitamin D within normal range

At least annual serum calcium check and maintain Vitamin D within normal range. Some patients may require more frequent monitoring as determined by Calcium Clinic.

Bone

If confirmed osteoporosis on baseline DXA to have repeat DXA and FRAX assessment 2 years after surgery

At diagnosis and then 2-3 yearly thereafter if confirmed osteoporosis on baseline DXA and not being followed up for PHPT/osteoporosis management in secondary care

Renal

If confirmed renal stones- refer through local urology pathway. Repeat imaging not routinely required unless otherwise advised by specialists.

At diagnosis and then 2-3 yearly thereafter if not being followed up for PHPT/renal stones in secondary care

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B) Secondary Care

1. Diagnosis:

  • See section A2 above (Primary Care)

2. Inpatient Referral:

  • All patients with a biochemical diagnosis of PHPT, if clinically appropriate, should be referred at discharge to the specialist Calcium Clinic via standard referral processes to endocrinology for further management.
  • Inpatient advice for patients with PHPT can be obtained from the endocrinology team via usual inpatient advice pathways
  • This should be done urgently for patients with severe hypercalcaemia (greater than 3.0mmol/l) or who are very symptomatic.

3. Secondary care assessment/investigations:

  • Symptom assessment: symptoms associated with hypercalcaemia typically include constipation, thirst, memory/concentration issues, polyuria, nausea, vomiting, abdominal pain and confusion. Formal objective symptom scoring can be conducted using validated Pasieka Scoring Tool in Calcium Clinic.
  • Biochemical assessment: All patients will require up to date serum calcium, PTH, Vitamin D, U&Es and phosphate levels.
  • Bone assessment: Patients will require a baseline DXA scan (including wrist scan) to establish if there is any evidence of reduced bone mineral density. A T-score less than -2.5 at any anatomical site potentially meets surgical criteria. Additionally, if there are symptoms suggestive of vertebral fracture, there may be indication to arrange spine x-rays. All patients with confirmed PHPT should have a FRAX score calculated at baseline and treatment considered if high risk.
  • Renal assessment: establishing presence of renal end-organ damage through imaging (ultrasound/CT) of renal tract looking for nephrocalcinosis or renal calculi. Additionally, 24-hour urine collection to look for hypercalciuria and biochemical assessment of renal function (U&Es) should be conducted. Patients must be vitamin D replete and not on cinacalcet prior to conducting a 24-hour urine calcium measurement,
  • Genetics: To be considered in all patients aged under 40 years, known family history of associated genes, presence of multiglandular parathyroid disease or other tumours consistent with MEN or CDC73 disorders. Common genetic disorders screened for include; MEN1, MEN2A, CDC73 disorders and where appropriate CaSR mutations. Urine calcium:creatinine clearance ratio is conducted in all patients as a screening test for Familial Hypocalciuric Hypercalcaemia (only when vitamin D replete and not on cinacalcet).
  • Imaging: If the patient is a possible surgical candidate, imaging is helpful to ascertain whether there is an obvious parathyroid adenoma. It is essential in all patients planned for parathyroidectomy. Imaging usually takes the form of a parathyroid ultrasound +/- nuclear imaging i.e. CT-SPECT and will be arranged by the Calcium Clinic or endocrine surgery
  • Cardiovascular assessment: As per NICE guidance, all patients with confirmed PHPT should undergone formal assessment of cardiovascular risk e.g. QRISK3.

4. Secondary care treatment and management:

Acute management of hypercalcaemia in PHPT
All patients with severe hypercalcaemia (greater than 3.0mmol/l or severely symptomatic) and suspected PHPT should be referred urgently to the endocrine team.
Intravenous hydration is usually indicated, however the use of bisphosphonates or Denosumab needs to be determined by endocrinology on a case-by-case basis.

Surgical management
Curative treatment for PHPT is surgical removal of one or more parathyroid glands based on pre-operative imaging. Referral for parathyroidectomy is based on criteria recommended by the European guidelines for patients in whom surgery is clinically appropriate and are summarised below:

Category

Criteria

Symptomatic

Symptoms suggestive of PHPT

Asymptomatic

Biochemistry

  • Serum calcium more than 0.25mmol/l above the upper limit of normal i.e. greater than 2.85mmol/l

Bone

  • Evidence of T-score less than -2.5 at any site on DXA scan including lumbar spine, hip and wrist
  • Evidence of vertebral fractures on any imaging modality including x-ray, CT or MRI

Renal

  • Evidence of nephrocalcinosis or renal calculi on any renal tract imaging (ultrasound or CT)
  • CrCl less than 60ml/min
  • Evidence of hypercalciuria (greater than 10mmol/d)

Age

  • Aged under 50 years
  • All patients with PHPT who meet criteria for surgical management should be referred to the endocrine surgeons, after assessment in Calcium Clinic.
  • Post-surgery: serum calcium, PTH levels and histology should be checked prior to discharge. There may be a transiently suppressed PTH due to ‘parathyroid stunning’.
  • Serum calcium and PTH levels should be checked 3-6 months post-surgery and should be normal to be considered curative – this will usually be done in Calcium Clinic or endocrine surgery clinic.
  • Hypocalcaemia +/- hypomagnesaemia and raised alkaline phosphatase may indicate potential Hungry-Bone syndrome. This requires urgent advice from the endocrine team and immediate management. Patients with more severe parathyroid disease and higher pre-operative PTH are amongst those most at risk.
  • Prolonged hypocalcaemia with a suppressed or inappropriately normal PTH may indicate post-surgical hypoparathyroidism (usually when multiple parathyroid glands have been removed or following previous parathyroid removal) and this requires referral to the endocrine Calcium Clinic for specialist management.

Pharmacological management

Calcimimetics
Some patients may meet surgical criteria but surgery is against their wishes or the operation would be deemed high-risk. Calcimimetics e.g., cinacalcet may be considered but should only be started for PHPT by an endocrinologist or an endocrine surgeon. This may be appropriate in the following groups:

  • Serum calcium persistently greater than 2.85mmol/l with symptoms suggestive of PHPT
  • Serum calcium persistently greater than 3.00mmol/l with or without symptoms

Dose and response:

Bisphosphonates/Denosumab
May be considered in those with concurrent osteoporosis and/or high fracture risk. Management plan for osteoporosis in the context of PHPT will usually be formulated via the Calcium Clinic, and be made clear to primary care prior to discharge

Bisphosphonates or Denosumab would not be routinely considered for the management of chronic hypercalcaemia/PHPT in isolation.

Long-term Monitoring:

  • Some patients may not want/be suitable for surgery, have high risk of recurrence, be on cinacalcet or had unsuccessful surgery. These patients may require long-term follow-up.
  • Endocrinology at LTHT provide a nurse-delivered clinic for long term monitoring of PHPT. Patients may be referred here from the Calcium Clinic.
  • Alternatively, some patients, who are low risk, may be discharged to primary care with a monitoring plan and should follow section A6 above (long term monitoring in primary care).
  • In terms of osteoporosis- this is generally managed as per local guidelines. If fracture risk is high, it may be reasonable to commence treatment for osteoporosis before surgery, particularly when there is a significant wait list for surgery, or if surgery is not currently being considered.
  • If fracture risk is intermediate or low then reasonable to repeat FRAX and DXA 2 years post-surgery and re-evaluate at that time.

5. Information and support:

There are a number of resources that can be used to provide additional information and also support patients following a diagnosis of Primary Hyperparathyroidism. These can also be a good source of additional information for Health Care professionals. They are listed below.

Further information:
https://www.yourhormones.info/endocrine-conditions/primary-hyperparathyroidism/
https://www.endocrinology.org/media/3384/hyperparathyroidism-leaflet-dl-2-31_10.pdf

Patient Support:
https://parathyroiduk.org
https://www.endocrinology.org

6. Special Scenarios:

Leeds Teaching Hospitals NHS Trust is a specialist centre for parathyroid disease and operates a parathyroid MDT including endocrinologists, obstetricians, surgeons, endocrine nurses and specialist radiologists.
As per NICE guidance, local hospitals should consider referring the following groups to be managed by the specialist endocrine MDT:

  • Patients with recurrent PHPT or unsuccessful parathyroidectomy
  • Patients pregnant with PHPT
  • Patients with PHPT with abnormal histology reported post-operatively
  • Genetic PHPT including MEN1, MEN2A, CDC73 disorders
  • Patients with diagnostic uncertainty for PHPT

Declarations of Interest

There are no interests to declare from any of the named authors.

Provenance

Record: 7056
Objective:

To provide guidance on diagnosis, investigation & management of primary hyperparathyroidism specific to primary or secondary care, based on international & NICE guidance.

Clinical condition:

Primary Hyperparathyroidism

Target patient group: Patients with possible or confirmed primary hyperparathyroidism identified in primary and secondary care
Target professional group(s): Pharmacists
Primary Care Doctors
Secondary Care Doctors
Adapted from:

Evidence base

National Institute for Health and Care Excellence (2019) Hyperparathyroidism (primary): diagnosis, assessment and initial management (NICE guideline NG132). https://www.nice.org.uk/guidance/ng132
John P. Bilezikian et al, Guidelines for the Management of Asymptomatic Primary Hyperparathyroidism: Summary Statement from the Fourth International Workshop, The Journal of Clinical Endocrinology & Metabolism, Volume 99, Issue 10, 1 October 2014, Pages 3561–3569, https://doi.org/10.1210/jc.2014-1413
Pasieka JL et al Patient-based surgical outcome tool demonstrating alleviation of symptoms following parathyroidectomy in patients with primary hyperparathyroidism. World J Surg. 2002 Aug;26(8):942-9. doi: 10.1007/s00268-002-6623-y

Approved By

LAPC

Document history

LHP version 1.0

Related information

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