ED: Sometimes difficult to demonstrate, a parathyroid adenoma can be removed surgically. Removal often fixes the calcium metabolism problems pick up fortuitously when screening the presenting non-descript symptoms.
Affecting 0.2-0.5% of the ambulatory population, primary hyperparathyroidism (PHPT) is the commonest cause of hypercalcaemia, commonly found while investigating non-specific constitutional symptoms (e.g. lethargy, diminished cognitive performance and fibromyalgia symptoms) or in the patient presenting with newly diagnosed osteoporosis or symptomatic urolithiasis. A parathyroid adenoma(s) is usually the cause, and parathyroid surgery is highly successful in curing hypercalcaemia experienced hands, with most patients requiring one night in hospital, including those patients having a four gland exploration. Most recent surgical series from high volume centres report cure rates of over 90% with very low rates of surgical morbidity.
PHPT is always a biochemical diagnosis – parathyroid hormone (PTH) dependent hypercalcaemia, usually caused by a solitary benign adenoma, versus non PTH dependent (e.g. malignancy) – with PTH levels elevated or in the upper half of the reference range.
PHPT should be distinguished from secondary hyperparathyroidism where PTH is elevated with a low or normal serum total corrected and ionised calcium levels. This is not a surgical condition and commonly relates to vitamin D deficiency, renal impairment, malabsorption and anti-resorptive medications.
Familial hypocalciuric hypercalcaemia (FHH)
This is a rare, autosomal-dominant disorder of calcium sensing receptors. The patient with FHH can have biochemistry similar to PHPT (i.e. concurrent elevation of serum calcium and PTH) however this condition is also not surgically curable and parathyroidectomy should be avoided.
A family history of hypercalcaemia should raise suspicion of an FHH diagnosis. Patients characteristically have low urinary calcium excretion relative to the degree of hypercalcaemia. Urine calcium excretion assessment (measured as part of a fasting metabolic bone study) is important in working up the hypercalcaemic patient, and assists in distinguishing PHPT from FHH.
Surgery and PHPT
Parathyroidectomy is the only definitive treatment for PHPT. At diagnosis, a decision is made to either refer for parathyroidectomy or elect to pursue observational management, with any osteoporosis managed medically (i.e. anti-resorptives).
Some with PHPT have clear, non-controversial indications for surgery such as symptomatic renal calculi, hypercalcaemic crisis, or pathologic fracture or other forms of PHPT related bone disease.
In asymptomatic patients there is more controversy regarding surgery. This specific issue has been addressed by guidelines by the National Institute of Health (NIH) for surgical referral for asymptomatic PHPT (commenced 1990; revised 2002, 2008 and 2013).
Indications for parathyroidectomy in asymptomatic patients, according to the most current NIH guidelines, include a significant degree of hypercalcaemia (total adjusted calcium 0.25 mmol/L over upper normal limit), diagnosis of osteoporosis on DEXA, imaging demonstrated vertebral fracture, nephrolithiasis demonstrated on renal imaging, diminished renal function (creatinine clearance under 60cc/min) and patients under age 50.
Younger patients are recommended for surgery because PHPT related complications are more likely to develop over time.
Notably, the NIH criteria exclude constitutional and cognitive symptoms (fatigue, lassitude, memory disturbance etc.), which affect many PHPT patients and improve post-operatively but not in a predictable fashion.
Patients not meeting surgical referral criteria require long term surveillance in case they develop them. Recommended surveillance (NIH guidelines) includes annual biochemical evaluation of renal function and calcium assays and annual to biannual bone densitometry.
For those patients wishing to avoid long-term surveillance, parathyroidectomy can be offered even though the patient may not have surgical referral criteria. Some literature suggests surgery is a cost-effective alternative to long term monitoring.
Parathyroid imaging (whether CT, ultrasound, or sestamibi scintigraphy) is indicated for surgical planning rather than diagnosis. Parathyroid imaging can facilitate localisation of the enlarged parathyroid (adenoma), such that focused parathyroidectomy can be performed through smaller neck incision. Negative parathyroid imaging should not preclude surgical referral for parathyroidectomy, because despite the improving sensitivity of imaging, there remains a degree of truth in the adage, ‘The only localisation necessary is to find an experienced parathyroid surgeon’. Four gland parathyroid exploration in experienced hands remains a procedure with minimal morbidity and high cure rates.
References available on request.
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