Other clinical examination can include grading of muscle weakness, which is done by asking the patient to stand from a seated position with their hands folded across their chest. Laboratory investigations include evaluating blood calcium and alkaline phosphatase, which are always increased in tertiary hyperparathyroidism. Other common results from laboratory investigations would include decreased vitamin D levels, elevated blood parathyroid hormone and hyperphosphatemia. Etiology
Hyperparathyroidism, in general, is caused by either tumorous growth in one or more parathyroid glands or a prolonged decrease in blood calcium levels or hypocalcaemia which in turn stimulates the production of parathyroid hormone release from the parathyroid gland. The parathyroid gland is located beside the thyroid gland in the neck, below and in front of the larynx and above the trachea. It is composed of four glands in total that monitor blood calcium levels via the calcium sensing receptors, a g-coupled protein receptor. The parathyroid glands main role is calcium homeostasis. Histologically, these glands are composed of chief cells and oxyphil cells with the chief cell primarily responsible for the storing and release of parathyroid hormone. These cells are arranged in a pseudo-follicular pattern similar to the thyroid follicles. Keratin staining is used to image the parathyroid hormone granules. Parathyroid hormone is responsible for the induction of increased calcium absorption in the gastrointestinal tract or gut and in the kidney. It also induces calcium and phosphate resorption from the bone by osteoclasts. Parathyroid hormone also plays a role in activating vitamin D from its pro form to its active form.
Oxyphil cells also appear hyperplasic however, these cells are much less prominent. Biochemically, there are changes in function between normal and nodular hyperplastic parathyroid glands. These changes involve proto-oncogene expression and activation of proliferative pathways while inactivating apoptotic pathways. In nodular parathyroid tissue increased expression of TGF-a, a growth factor, and EGFR, its receptor, results in aggressive proliferation and further downregulation of vitamin D receptors, which act to suppress hormone secretions. Furthermore, the proliferative marker, Ki67 is seen to be highly expressed in the secondary nodular hyperplastic state. Tumour suppressor genes have also been highlighted as being silenced or degraded in nodular hyperplastic parathyroid tissue. One such gene, p53, has been shown to regulate multiple tumour suppressor pathways and in tumorigenesis can be degraded by b-catenin. This pathway, in some aspect, is mediated by CACYBP, which is highly expressed in nodular parathyroid hyperplasia. Treatment
Early pharmaceutical treatment for tertiary hyperparathyroidism may include supplementing vitamin D and the use of cinacalcet. Cinacalcet acts to increase the sensitivity of the calcium sensing receptors to calcium leading to a reduction in parathyroid hormone release, however, its use has limited impact in those with tertiary hyperparathyroidism. These treatments are more likely only transient therapies before parathyroidectomy is performed. Indications for surgery in tertiary hyperparathyroidism commonly involve the development of chronic, severe conditions including osteopenia, persistent severe hypercalcemia, bone pain and pathologic fracture. Other indications include development of conditions such calciphylaxis.