NICE releases guideline on initial management of Primary Hyperparathyroidism
NICE has released its 2019 guidelines on Hyperparathyroidism (primary): diagnosis, assessment and initial management.
Primary hyperparathyroidism (PHPT) is a disorder of one or more of the parathyroid glands. The parathyroid gland(s) becomes overactive and secretes excess amounts of parathyroid hormone (PTH). As a result, the blood calcium rises to a level that is higher than normal (called hypercalcemia). An elevated calcium level can cause many short-term and long-term complications.
Primary hyperparathyroidism is different from secondary hyperparathyroidism, which occurs when the parathyroid glands overproduce PTH in response to low blood levels of calcium; the low calcium level is caused by another condition, such as not being absorbed correctly from the intestines or kidney failure. In this setting, the parathyroid glands are responding appropriately and are not diseased/abnormal.
Following are the major recommendations:
1. Diagnostic testing in primary care
- Measure albumin-adjusted serum calcium for people with any of the following features, which might indicate primary hyperparathyroidism:
- symptoms of hypercalcaemia, such as thirst, frequent or excessive urination, or constipation
- osteoporosis or a previous fragility fracture (for recommendations on assessing the risk of fragility fracture in people with osteoporosis, see the NICE guideline on osteoporosis)
- a renal stone (for recommendations on assessing and managing renal stones, see the NICE guideline on renal and ureteric stones)
- an incidental finding of elevated albumin-adjusted serum calcium (2.6 mmol/litre or above).
- Consider measuring albumin-adjusted serum calcium for people with chronic non-differentiated symptoms.
- Do not measure ionised calcium when testing for primary hyperparathyroidism.
- Repeat the albumin-adjusted serum calcium measurement at least once if the first measurement is either:
- 2.6 mmol/litre or above or
- 2.5 mmol/litre or above and features of primary hyperparathyroidism are present. Base the decision to carry out further repeat measurements on the level of albumin-adjusted serum calcium and the person's symptoms.
Measuring parathyroid hormone
- Measure parathyroid hormone (PTH) for people whose albumin-adjusted serum calcium level is either:
- 2.6 mmol/litre or above on at least 2 separate occasions or
- 2.5 mmol/litre or above on at least 2 separate occasions and primary hyperparathyroidism is suspected.
- When measuring PTH, use a random sample and do a concurrent measurement of the albumin-adjusted serum calcium level.
- Do not routinely repeat PTH measurement in primary care.
- Seek advice from a specialist with expertise in primary hyperparathyroidism if the person's PTH measurement is either:
- above the midpoint of the reference range and primary hyperparathyroidism is suspected or
- below the midpoint of the reference range with a concurrent albumin-adjusted serum calcium level of 2.6 mmol/litre or above.
- Do not offer further investigations for primary hyperparathyroidism if:
- the person's PTH is within the reference range but below the midpoint of the reference range and
- their concurrent albumin-adjusted serum calcium level is below 2.6 mmol/litre.
- Look for alternative diagnoses, including malignancy, if the person's PTH is below the lower limit of the reference range.
2. Testing and assessment in secondary care
Measuring vitamin D
- For people with a probable diagnosis of primary hyperparathyroidism, measure vitamin D and offer vitamin D supplements if needed.
Excluding familial hypocalciuric hypercalcaemia
- To differentiate primary hyperparathyroidism from familial hypocalciuric hypercalcaemia, measure urine calcium excretion using any one of the following tests:
- 24-hour urinary calcium excretion
- random renal calcium:creatinine excretion ratio
- random calcium:creatinine clearance ratio.
Assessment after diagnosis
- For people with a confirmed diagnosis of primary hyperparathyroidism:
- assess symptoms and comorbidities
- measure eGFR (estimated glomerular filtration rate) or serum creatinine
- do a DXA (dual-energy X‑ray absorptiometry) scan of the lumbar spine, distal radius and hip
- do an ultrasound scan of the renal tract.
3. Referral for surgery
- Refer people with a confirmed diagnosis of primary hyperparathyroidism to a surgeon with expertise in parathyroid surgery if they have:
- symptoms of hypercalcaemia such as thirst, frequent or excessive urination, or constipation or
- end-organ disease (renal stones, fragility fractures or osteoporosis) or
- an albumin-adjusted serum calcium level of 2.85 mmol/litre or above.
- Consider referral to a surgeon with expertise in parathyroid surgery for people with a confirmed diagnosis of primary hyperparathyroidism even if they do not have the features listed in recommendation 1.3.1.
4. Surgical management
- Offer preoperative imaging (usually ultrasound) to people having surgery for primary hyperparathyroidism if it will inform the surgical approach.
- Consider a second preoperative imaging modality (usually a sestamibi scan) if it will further guide the surgical approach.
- Do not offer more preoperative imaging if the first-modality (usually ultrasound) and second-modality scans (usually a sestamibi scan) do not identify an adenoma or are discordant.
- Proceed with surgery, performed by a surgeon with expertise in 4‑gland exploration, even if preoperative imaging has not identified an adenoma.
- If preoperative imaging shows an ectopic adenoma, refer the person to a centre with the relevant expertise.
Type of surgery
- 1.4.6Offer a choice of either 4‑gland exploration or focused parathyroidectomy to people whose preoperative imaging shows a single adenoma in the neck. Discuss the choice of surgery with the person, and explain:
- what happens during each type of surgery
- how well each type of surgery works
- what types of anaesthesia are used
- how long each type of surgery is likely to take
- how large the resulting scars are likely to be
- the risks of each type of surgery.
- Offer 4‑gland exploration to people who have had preoperative imaging that does not identify a single adenoma.
- Consider 4‑gland exploration for people having surgery for primary hyperparathyroidism whose first-modality and second-modality scans are discordant.
Intraoperative PTH monitoring
- Do not use intraoperative PTH monitoring in first-time parathyroid surgery.
Follow-up after surgery
- Measure albumin-adjusted serum calcium and PTH before discharge after surgery for primary hyperparathyroidism to provide baseline information for later follow‑up.
- Measure albumin-adjusted serum calcium 3 to 6 months after surgery for primary hyperparathyroidism to confirm whether surgery has been successful.
- If albumin-adjusted serum calcium is within the reference range 3 to 6 months after surgery for primary hyperparathyroidism, regard the surgery as successful. Monitor albumin-adjusted serum calcium once a year.
- For people who have had unsuccessful surgery for primary hyperparathyroidism:
- conduct a multidisciplinary team (MDT) review at a specialist centre that includes:
- initial findings from surgery
- previous imaging and histology
- the clinical and biochemical indications for repeat surgery
- offer monitoring as set out in section 1.6.
- If repeat surgery is performed for primary hyperparathyroidism, it should be done at a centre with expertise in reoperative parathyroid surgery.
5. Non-surgical management
- Consider cinacalcet for people with primary hyperparathyroidism if surgery has been unsuccessful, is unsuitable or has been declined, and if their albumin-adjusted serum calcium level is either:
- 2.85 mmol/litre or above with symptoms of hypercalcaemia or
- 3.0 mmol/litre or above with or without symptoms of hypercalcaemia.
- For people whose initial albumin-adjusted serum calcium level is 2.85 mmol/litre or above with symptoms of hypercalcaemia, base decisions on whether to continue treatment with cinacalcet on how well it reduces symptoms.
- For people whose initial albumin-adjusted serum calcium level is 3.0 mmol/litre or above, base decisions on whether to continue treatment with cinacalcet on how well it reduces either symptoms or albumin-adjusted serum calcium level.
- Consider a bisphosphonate to reduce fracture risk for people with primary hyperparathyroidism and increased fracture risk.
- Do not offer bisphosphonates for chronic hypercalcaemia of primary hyperparathyroidism.
- Offer monitoring to all people diagnosed with primary hyperparathyroidism, as set out in table 1.
Table 1 Monitoring for people with primary hyperparathyroidism
|People who have had successful parathyroid surgery||People who have not had parathyroid surgery, or whose surgery has not been successful|
|Measure albumin-adjusted serum calcium once a year||Measure albumin-adjusted serum calcium and eGFR or serum creatinine once a year, unless the person is taking cinacalcet*.|
If the person is taking cinacalcet, offer monitoring as set out in the summary of product characteristics.
|If the person has osteoporosis, seek specialist opinion according to local pathways on monitoring.||Consider a DXA scan at diagnosis and every 2 to 3 years.|
|If the person has renal stones, seek specialist opinion according to local pathways on monitoring.||Offer ultrasound of the renal tract at diagnosis, when presenting and if a renal stone is suspected (for recommendations on assessing and managing renal stones.|
|For people who have had parathyroid surgery for multigland disease, or have disease that recurs after successful surgery, seek specialist endocrine opinion on monitoring.|
|For all people with primary hyperparathyroidism, assess cardiovascular risk and fracture risk in line with the NICE guidelines on cardiovascular disease and osteoporosis.|
|DXA, dual-energy X‑ray absorptiometry; EGFR, estimated glomerular filtration rate.|
* At the time of publication (May 2019), cinacalcet did not have a UK marketing authorisation for use after unsuccessful surgery for primary hyperparathyroidism. The prescriber should follow relevant professional guidance, taking full responsibility for the decision. Informed consent should be obtained and documented.
Care before pregnancy
- Offer parathyroid surgery to women who have primary hyperparathyroidism and are considering pregnancy.
Care during pregnancy
- Discuss the management of primary hyperparathyroidism for pregnant women with a MDT in a specialist centre, and refer the woman for specialist care if needed. The MDT should include:
- an obstetrician
- a physician with expertise in primary hyperparathyroidism
- a surgeon
- a midwife
- an anaesthetist.
- Do not offer cinacalcet to pregnant women with primary hyperparathyroidism.
- Do not offer a bisphosphonate to pregnant women with primary hyperparathyroidism.
- Be aware that women with primary hyperparathyroidism are at increased risk of hypertensive disease in pregnancy. For recommendations on diagnosing and managing hypertension in pregnant women, see the NICE guideline on hypertension in pregnancy.
- Consult a specialist centre MDT for advice on monitoring for pregnant women with primary hyperparathyroidism.