Because the symptoms of primary hyperparathyroidism (PHPT) are often similar to symptoms of a host of other medical conditions, PHPT may go undiagnosed. To help address this issue, the United Kingdom’s National Institute for Health and Care Excellence (NICE) developed a series of guidelines to aid in diagnosing PHPT.
The NICE 2019 Guidelines exist to aid medical providers in diagnosing & treating primary hyperparathyroidism. The NICE Guidelines can also help people struggling with symptoms of PHPT, along with families or caregivers of these individuals, determine what steps are needed to get a diagnosis.
In this guide, we break down the UK NICE Guidelines for PHPT and explain why they matter.
Initial Tests for Primary Hyperparathyroidism
There are several key signs of primary hyperparathyroidism that should compel a medical provider to start testing a patient for hyperparathyroidism. They include:
- Symptoms of hypercalcemia, including increased thirst, constipation, or frequent urination
- Osteoporosis or recent bone fractures that occurred after minimal trauma, if any (fragility fractures)
- Kidney stones
- Elevated albumin-adjusted serum calcium of 2.6 mmol/liter or above as detected during routine bloodwork
- Chronic, non-differentiated symptoms like mild confusion, fatigue, joint pain, irritability, depression, digestive issues, and insomnia
If a patient presents with any of these symptoms, the UK NICE 2019 Guidelines advise that a provider should consider measuring albumin-adjusted serum calcium (Ca), or the total amount of calcium in the blood.
A Ca finding that’s greater than or equal to 2.6 mmol/liter or greater than or equal to 2.5 mmol/liter with symptoms of primary hyperparathyroidism should prompt another Ca test. If the same Ca finding is present, the next step is to measure parathyroid hormone (PTH) at the same time as another Ca test.
If the PTH level is below the midpoint but still in the reference range and the patient’s Ca is less than 2.6 mmol/liter, the NICE Guidelines suggest no further PHPT testing is needed, as a different issue is the likely cause of any symptoms. If a patient’s PTH level is below the lower limit of the reference range, the patient may need to be tested for other conditions, such as hypoparathyroidism (under-producing parathyroid glands) and related issues.
Primary Hyperparathyroidism Diagnosis
There are two main instances in which the NICE Guidelines recommend that the treating provider seek out a specialist with experience treating hyperparathyroidism:
- Primary hyperparathyroidism is suspected and PTH is above the midpoint of the reference range
- PTH is below the midpoint of the reference range and Ca is 2.6 mmol/liter or above. A parathyroid specialist can conduct a series of tests to conclusively diagnose PHPT.
In either of these cases, a specialist will be able to order or conduct the next set of tests suggested by the NICE 2019 Guidelines. First, a specialist can measure vitamin D levels and recommend supplementation if needed. They can determine whether the symptoms are being caused by familial hypocalciuric hypercalcemia instead of PHPT by conducting the following tests:
- 24-hour urinary calcium & creatinine excretion
If familial hypocalciuric hypercalcemia (FHH) is the culprit, the specialist can recommend a patient’s next steps. FHH is an inherited, benign disorder that often doesn’t require treatment.
Primary hyperparathyroidism, on the other hand, does require treatment. Before deciding on a treatment plan, the UK NICE Guidelines recommend conducting a post-diagnosis assessment to:
- Assess the patient’s symptoms and pinpoint any co-occurring conditions (comorbidities)
- Order an ultrasound of the renal tract
- Conduct a dual-energy X-ray absorptiometry (DXA) scan of the distal radius, lumbar spine, and hip
- Measure eGFR (estimated glomerular filtration rate) or serum creatinine
By conducting this post-diagnostic assessment, a specialist can put together a treatment plan that best serves the patient’s needs.
Treating Primary Hyperparathyroidism
Once a patient has a confirmed diagnosis of primary hyperparathyroidism, the UK NICE Guidelines strongly encourage referral to a skilled parathyroid surgeon if a person also has increased thirst, excessive urination, constipation, osteoporosis, a recent fragility fracture, kidney stones, or albumin-adjusted serum calcium (Ca) greater than or equal to 2.85 mmol/liter. A patient may also be referred to a surgeon if they have no symptoms of PHPT but have been given a PHPT diagnosis after the appropriate tests.
If the patient agrees to surgery, the UK NICE 2019 Guidelines state that the parathyroid surgeon should consider conducting preoperative scans, including ultrasound and sestamibi scans, to help evaluate the parathyroid function and guide the plan for surgery.
The UK NICE Guidelines map out four different scenarios based on what the surgeon finds during the scans.
- No adenoma (benign tumor) present: The surgeon should consider four-gland exploration, a form of parathyroid surgery used to pinpoint and remove problem glands.
- One adenoma identified: The surgeon can offer a choice between four-gland exploration or focused parathyroid surgery to remove the adenoma.
- Inconsistent results: If different scans show different results, or if results are inconclusive based on the scans, a surgeon may want to consider four-gland exploration to closely examine the parathyroid glands.
- Ectopic adenoma identified: If a parathyroid adenoma appears during scans but is not in a typical location, a specialist may need to be contacted.
The UK NICE Guidelines stress that when a surgeon offers the choice of surgery to a patient, he or she should carefully explain the surgery, outline the risks involved, and share an estimated recovery time. If the patient refuses surgery, the NICE Guidelines name careful monitoring and treatment with cinacalcet tablets to help treat symptoms of PHPT. Another option, which applies only to patients at risk of bone fractures who are not also experiencing chronic hypercalcemia, is to prescribe bisphosphonates to help strengthen bones.
Monitoring Patients with Primary Hyperparathyroidism
Regardless of whether a patient undergoes surgery or not, the NICE Guidelines state that they should be assessed for any bone fracture or cardiovascular risks as a result of their condition. In addition to this basic monitoring, patients may need to undergo specific tests depending on their specific situation.
Successful Parathyroid Surgery
If a patient goes through with parathyroid surgery, the surgeon should measure postoperative albumin-adjusted serum calcium (Ca) and PTH levels before discharging the patient, and then again three to six months after surgery. The NICE Guidelines state that in a successful surgery, Ca and PTH levels will be within the reference range three to six months after surgery.
A surgeon can monitor a patient with yearly PTH and Ca tests to keep an eye on any changes. If the patient has kidney stones or osteoporosis as a result of primary hyperparathyroidism, they should consult with specialists in those areas to monitor the conditions.
No Surgery or Unsuccessful Parathyroid Surgery
If Ca and PTH levels are not within the reference range after three to six months, the surgery is considered unsuccessful. Albumin-adjusted serum calcium and eGFR (estimated glomerular filtration rate) or serum creatinine should be measured once a year unless the patient is taking cinacalcet.
A parathyroid specialist should evaluate whether patients taking cinacalcet should continue the treatment based on:
- Symptom reduction if the initial Ca was greater than or equal to 2.85 mmol/liter
- Symptom reduction or reduced Ca level if it was initially greater than or equal to 3.0 mmol/liter
The specialist should continue to monitor patients on cinacalcet and evaluate the need for adjustments every two to four weeks. A patient may need to undergo a dual-energy X-ray absorptiometry (DXA) bone density scan every two to three years.
Monitoring PHPT in Other Situations
If a patient experiences a reoccurrence of hyperparathyroidism after successful surgery, the UK NICE Guidelines recommend they be evaluated and monitored by an endocrine specialist. The same goes for anyone who’s been surgically treated for multi-gland parathyroid disease.
The UK NICE 2019 Guidelines recommend that pregnant women with hyperparathyroidism be evaluated and monitored by a multidisciplinary team consisting of an obstetrician, a physician with expertise in treating primary hyperparathyroidism, a midwife, a surgeon, and an anesthetist. Pregnant women should not take cinacalcet or bisphosphonate.
Staying Informed
The UK NICE Guidelines provide a standard framework for care that benefits providers and patients alike. Understanding the NICE Guidelines can help patients, family members, caregivers, and physicians stay informed about what the process of PHPT diagnosis, treatment, and monitoring should look like.
The NICE Guidelines also recommend that physicians give patients a thorough breakdown of:
- What the parathyroid glands do
- What primary hyperparathyroidism is
- What causes PHPT
- Symptoms of PHPT
- Diagnosis, treatment, and monitoring of PHPT
- Prognosis
- Potential effects on daily life
- Potential long-term effects
- Thorough explanation of all treatments and surgeries
- Advice on reducing symptoms through diet, exercise, hydration, and pain relief
Conclusion
All patients with calcium elevation and a diagnosis of primary hyperparathyroidism (after a comprehensive diagnostic work up) should have surgery.
Sharing this information and keeping an open line of communication between the physician, the patient, and the caregivers helps everyone stay on the same page throughout treatment. At the CENTER for Advanced Parathyroid Surgery, Dr. Babak Larian prioritizes communication with patients and works to make sure each person who comes through his doors feels seen, heard, and understood. If you have any symptoms of hyperparathyroidism and would like to discuss diagnosis and treatment according to the UK NICE Guidelines, schedule an appointment with Dr. Larian. No question is too big or small for him to tackle with you.
