Primary hyperparathyroidism
Often vague symptoms, simple diagnosis
“Otolaryngologist, head and neck surgeon Francis Hall discusses the diagnosis and treatment of primary hyperparathyroidism.”
Primary hyperparathyroidism is an uncommon disease that presents in many different ways. It is easy to screen for simply by requesting a serum calcium level. Routine blood tests usually include a full blood count, liver and thyroid function tests, urea and electrolytes, but not a serum calcium level. Therefore, the diagnosis is often overlooked.
How does it present?
Many patients with primary hyperparathyroidism have no symptoms and the diagnosis is only detected biochemically. The most common symptoms are vague, including chronic fatigue, body aches, difficulty sleeping, memory loss, poor concentration, depression and headaches. These symptoms are common in general practice, and most patients with these symptoms will not have primary hyperparathyroidism. However, some will, and unless a serum calcium level is included in screening blood tests, this diagnosis will be easily overlooked and a potential pathway to cure not offered. Only about 20 per cent of patients present with the classical symptoms we were taught at medical school:
- stones – kidney stones
- moans – abdominal pain due to constipation,
- bones – bone and muscle pain, fractures and
osteoporosis - groans – depression or psychosis.
How common is it?
The incidence of primary hyperparathyroidism varies from 0.5 to 21 per 100,000 person-years. This wide range is thought to be due to the wide variation in the percentage of a population having serum calcium measurement.
The disorder is significantly more common in women than in men, especially in postmenopausal women. Age-adjusted prevalence estimates are about 200 cases per 100,000 women and 100 per 100,000 men. Therefore, in a GP practice of 1500 patients, approximately two patients will have primary hyperparathyroidism.
How is it diagnosed?
Primary hyperparathyroidism is easy to diagnose; the following tests will be raised:
- serum albumin-adjusted calcium level
- parathyroid hormone (PTH) level
- 24-hour urinary calcium level.
It is important to exclude secondary hyperparathyroidism by checking the vitamin D level and kidney function (urea, creatinine, estimated glomerular filtration rate [eGFR]).
In familial hypocalciuric hypercalcaemia(FHH), you see a mildly elevated serum calcium level and either a normal or mildly elevated PTH level. FHH is due to a mutation in the calcium-sensing receptor and is easy to distinguish from primary hyperparathyroidism by the low 24-hour urinary calcium level. The diagnosis of FHH is confirmed by gene sequencing.
Thiazide diuretics may complicate the diagnosis of primary hyperparathyroidism, and lithium may induce hyperparathyroidism.
Once diagnosed, patients should be referred to a surgeon who performs parathyroidectomy or an endocrinologist for further assessment.
What is the role of imaging?
Imaging plays no role in diagnosis. Imaging of the bones (dual-energy x-ray absorptiometry) and urinary tract (renal ultrasound, CT scan of the kidneys) helps assess the effects on the bones and urinary tract. Imaging of the neck (ultrasound, sestamibi parathyroid scan, four-dimensional CT, SPECT-CT and MRI) helps the surgeon plan the operation by localising the site of the abnormal parathyroid gland. In rare cases, it may be seen in the chest.
What is the pathology?
Approximately 85 per cent of patients with primary hyperparathyroidism have an adenoma of one gland. Occasionally, adenomas may involve two glands. The remaining 15 per cent of patients have hyperplasia of all four glands.
Rarely, carcinoma of a parathyroid gland may be the cause of primary hyperparathyroidism. In parathyroid carcinoma, the calcium and PTH levels are usually very high.
What happens if not treated?
The long-term complications of leaving the disorder untreated include kidney stones, kidney failure, osteoporosis and fractures. Several studies show that severe classical primary hyperparathyroidism is associated with an increase in mortality. Some, but not all, reports have shown an association between even mild primary hyperparathyroidism and an increase in mortality from cardiovascular disease and cancer.
Who benefits from surgery?
Most symptomatic and asymptomatic patients benefit from surgery. In the 2022 guidelines for the evaluation and management of primary hyperparathyroidism, the indications for surgery in asymptomatic patients are:
- serum calcium level 0.25mmol/L above normal
- skeletal involvement – bone mineral density T-score less than -2.5
- renal involvement – eGFR or creatinine clearance <60ml/min; kidney stones; hypercalciuria >250mg per 24 hours in women or >300mg per 24 hours in men
- age over 50.
Surgery for primary hyperparathyroidism is usually highly successful, with many surgical series showing biochemical cure in more than 96 per cent of patients after one operation.
Are there any other treatments?
Yes, asymptomatic patients with primary hyperparathyroidism who do not meet the above criteria are usually best managed conservatively with hydration, observation and frequent reassessment of their biochemistry (calcium, phosphate, PTH, creatinine, eGFR).
Medical treatment includes avoiding dehydration, maintaining dietary calcium intake between 800mg and 1000mg daily, and maintaining a normal vitamin D level. Some patients will worsen, and once they become symptomatic or meet the criteria for surgery, will need to be referred for surgery.
Francis Hall is head of the department of otolaryngology, head and neck surgery at Te Whatu Ora Counties Manukau and has a private practice in Auckland. For further information, email francis@drfrancishall.co.nz
References
1. Bilezikian JP, Khan AA, Silverberg SJ, et al. Evaluation and management of primary hyperparathyroidism: Summary statement and guidelines from the fifth international workshop. J Bone Miner Res 2022;37(11):2293–2314.
2. Ye Z, Silverberg SJ, Sreekanta A, et al. The efficacy and safety of medical and surgical therapy in patients with primary hyperparathyroidism: A systematic review and meta-analysis of randomized controlled trials. J Bone Miner Res 2022;37(11):2351–72.