Primary hyperparathyroidism

Primary hyperparathyroidism results from over-activity of one or more of the parathyroid glands, resulting in elevation of detectable PTH and hypercalcaemia, where there has been no pre-existing condition which has stimulated parathyroid activity. Over 90% of cases are related to a solitary parathyroid adenoma. In approximately 1% of cases, adenomata may exist in two or more glands. The remainder of cases are associated with four gland hyperplasia and where this occurs, especially if the glands are large and the patient is young, the clinician should be alerted to the possibility of MEN syndrome (see below).

Studies on the prevalence of the disease suggest that this is constant world-wide at 1/1000 population. The majority of cases are now detected from routine blood testing using multiphasic automated biochemistry machines and the detection rate is approximately 25 new cases/100 000 patients assayed.

Although it is now less common to see patients with overt symptoms or signs associated with primary hyperparathy-roidism, cases still present. The commonest clinical presentations are in patients who present with fractures, especially if through a bone cyst, or with renal calculi. Occasional patients are detected with hypercalcaemia associated with hypertension.

Despite the fact that 50% of patients are classified as 'asymptomatic', following treatment and cure of the hyper-calcaemia, many of these patients realise an improvement in their well-being with improved concentration, less depression, improved grip strength and an improvement in their Quality of Life scores. The elderly apparently mildly demented patient may suddenly recover mental function, and mild 'dementia' is therefore not a contraindication to parathyroidectomy, but rather an indication for treatment.

Three complications which tend to arise in the untreated case, may be irreversible and have a effect on the patient's long-term morbidity and mortality rates:

• Bone: It is estimated that patient presenting with primary hyperparathyroidism have bone mineral density only approximately 60-70% of the average population. Some patients have values much below this. Following parathyroidectomy, only a small proportion of this is re-couped. Since the majority of patients are middle-aged to elderly females, this aspect exacerbates any tendency to osteoporosis and predisposes to fractures.

• Cardiovascular system: Hypertension associated with hyperparathyroidism is irreversible once established.

• Kidney: Renal failure once established is irreversible.

Diagnosis

After confirmation of hypercalcaemia (either total calcium balanced against serum albumin or ionised calcium), other causes of hypercalcaemia must be excluded for example disseminated malignancy. The diagnosis of hyperparathy-roidism is confirmed by elevated intact PTH in the presence of hypercalcaemia.

In the past 5-10 years, major advances have been made in the pre-operative detection of the site of the abnormal parathyroid gland. Increasing expertise in ultrasound scanning, isotope studies using Sestamibi, and MRI scanning have all resulted in accurate localisation in over 90% of cases. Concordance between two of these modalities has a very high accuracy rate. Such accuracy has allowed mini- and laparoscopic exploration of the neck targeted to the affected gland alone with a high degree of success. Some experienced endocrine surgeons still advocate a full neck exploration with four glands visualisation but many surgeons are now changing to local targeted exploration as the primary procedure.

Management

Parathyroidectomy is the accepted treatment for primary hyperparathyroidism. Increasingly 'asymptomatic' patients being picked up incidentally by biochemical analysis are being offered surgery before the development of any long-term complications.

Four gland exploration and removal of the diseased gland is successful in curing the disease. Mini- or laparoscopic exploration with a single gland visualisation and removal, may afford the possibility that a second gland may rarely be missed. In this situation, many surgeons advocate a 'rapid PTH assay' to be performed within 20 min of surgery. A drop of 50% from a pre-operative value confirms that the disease has been cured.

The post-operative drop in serum calcium can take several hours to days to stabilise. Approximately 50% of patients become hypocalcaemic post-operatively and may require calcium and even vitamin D supplementation. Full bone re-mineralisation does not occur and the hypertension and abnormal renal function, if present, do not recover.

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