Three types of hyperparathyroidism exist, primary, second and tertiary. If the term hyperparathyroidism is employed without further qualification it typically implies primary hyperparathyroidism.

Primary Hyperparathyroidism

Primary hyperparathyroidism is an inappropriate elevation of the levels of parathyroid hormone. The excessive secretion of parathyroid hormone causes hypercalcaemia. The condition tends to present after the age of 50 years and is more common in women. Primary hyperparathyroidism can be asymptomatic or symptomatic. The symptomatic forms present with the features of hypercalcaemia.

Approximately 75-80% of cases are due to a parathyroid adenoma, around 10-20% are caused by diffuse hyperplasia and the remainder (less than 5%) are produced by a parathyroid carcinoma.

Parathyroid Adenoma

A parathyroid adenoma is a benign tumour of the chief cells of the thyroid gland. Only one parathyroid gland tends to be affected. The other parathyroid glands are atrophic because their secretion of parathyroid hormone is suppressed by the hypercalcaemia that the adenoma has caused.

Parathyroid adenomas normally weigh 500-5000mg and are therefore considerably heavier than a normal parathyroid gland. Adenomas tend not to contain fat. A compressed rim of normal parathyroid tissue may be seen around the edge of an adenoma. Occasionally, the adenoma can have a follicular rather than a more solid growth pattern and this can sometimes cause confusion with follicular lesions of the thyroid gland.

Many parathyroid adenomas are sporadic, but some are part of multiple endocrine neoplasia syndrome type 1.

Parathyroid Hyperplasia

Hyperplasia of the parathyroid glands can be an isolated phenomenon or can be part of multiple endocrine neoplasia syndrome type 1 or type 2. In each case all four parathyroid glands are usually enlarged, in contrast to an adenoma or carcinoma, although the hyperplasia is not always symmetrical between the glands. The hyperplasia affects the chief cells and as with an adenoma is accompanied by a considerable reduction in the quantity of fat within the gland. However, a rim of normal parathyroid tissue is not present. The combined weight of all four parathyroid glands in parathyroid hyperplasia is normally less than 1000mg.

Parathyroid Carcinoma

Carcinomas of the parathyroid gland are rare. As is the case with tumours of some other endocrine organs, the distinction between an adenoma and a carcinoma can be difficult. Parathyroid carcinomas are derived from the chief cells and can appear very similar to an adenoma in terms of the cytology of the cells and their microscopic arrangement. Carcinomas tend to involve only one parathyroid gland.

Invasion of adjacent organs and tissues and metastases are robust indicators of malignancy in a parathyroid tumour, but these variables are not very useful in a parathyroidectomy specimen because it is usually only the gland itself that is sent, without the surrounding tissue. From the perspective of managing the disease the aim is to make the diagnosis and institute treatment before metastases have developed; a metastasis will define the disease, but by that stage the information is almost always too late to be of use to improve the patient's prognosis.

In the absence of demonstrable invasion or metastasis, a few factors have been elucidated which favour a parathyroid tumour being a carcinoma rather than an adenoma. Carcinomas can be larger than adenomas and may exceed 10g. The degree of hypercalcaemia is often worse with a carcinoma. Carcinomas may show dense fibrous bands within the tumour.

Bone Pathology in Primary Hyperparathyroidism

The ability of parathyroid hormone to raise the concentration of calcium in the blood depends upon the action of PTH on bone. In hyperparathyroidism the prolonged, elevated levels of parathyroid hormone are harmful to the bone. The increased osteoclastic activity removes calcium from the bones. The osteoblasts attempt to compensate but are only able to make rather thin trabeculae and the bones effectively become osteoporotic.

In some cases the expanded bone marrow spaces are filled by fibrous tissue that contains numerous osteoclasts and regions of haemorrhage. Haemosiderin is produced from the clear up of the haemorrhage and this imparts a brown colour to the lesion and leads to the blunt designation of 'brown tumour'. Cystic change can occur and the term 'osteitis fibrosa cystica' has been applied.

Secondary Hyperparathyroidism

Secondary hyperparathyroidism occurs in chronic hypocalcaemia and is a persistent elevation of the levels of parathyroid hormone in response to this hypocalcaemia. It is usually caused by chronic renal failure.

Tertiary Hyperparathyroidism

Tertiary hyperparathyroidism only occurs after secondary hyperparathyroidism. In the face of the chronic overactivity of secondary hyperparathyroidism the parathyroid glands may sometimes behave in an autonomous fashion. If the chronic hypocalcaemia is corrected this autonomous function continues and the parathyroid glands persist in secreting elevated levels of parathyroid hormone. Hypercalcaemia results.


Disease specific investigations in primary hyperparathyroidism are limited. The hypercalcaemia can be confirmed by checking the blood calcium concentration. The level of parathyroid hormone in the blood can be measured and will be high in primary hyperparathyroidism; almost all other causes of hypercalcaemia should have a low PTH level.

Imaging of the neck is performed, although the glands may often not be visible. Nuclear medicine imaging that employs methoxyisobutylisonitrile (MIBI) labelled with metastable technitium-99 as the marker can help to locate the parathyroid glands.

Other investigations relate to evaluating the possible complications of the hypercalcaemia. Plain X-rays of the bones can show characteristic features (for example, the skull is said to resemble a pepper pot).

Asymptomatic hyperparathyroidism presents when a patient has their calcium level measured for another reason. The diagnosis of primary hyperparathyrodism is then made when the cause of the hypercalcaemia is investigated.

Parathyroid Cut Up

The treatment for primary hyperparathyroidism is parathyroidectomy. Many parathyroidectomy specimens are sent as frozen sections. Frozen section is used to confirm that the specimen is actually parathyroid tissue and also to try to determine if the cause of the hyperparathyroidism is a tumour of hyperplasia. This distinction can only be made if at least two glands are sent and one of the crucial variables is not the microscopic appearances but the weight. In the case of the tumour, the gland which contains the tumour will weigh considerably more than usual and the other gland will be small. In hyperplasia, both glands should be heavier than normal.

Smaller parathyroidectomy specimens may be all embedded for the frozen section itself. Larger specimens are serially sliced and all embedded after sampling for frozen section.