Tertiary hyperparathyroidism shares many symptomatic features with that of primary hyperparathyroidism, as the two are defined by hypercalcemia. These symptoms can vary greatly from asymptomatic to conditions leading to decreased quality of life. Non-specific symptoms include feeling tired and thirsty, mood changes including, feeling blue, weak and irritable along with other symptoms like itching, headache, joint pain, forgetfulness and abdominal pain have also been noted. More specific symptoms related to elevated blood calcium and phosphate levels include bone pain or osteodynia and tenderness which are common and related to proximal muscle tenderness. Other signs can include pancreatitis, kidney stones, corneal calcifications, thinning of long bones, and hypodermic calcifications which may be palpable in some patients.Calciphylaxis, though uncommon, can develop in patients with tertiary hyperparathyroidism. The product of elevated calcium and phosphate, forming crystal structures, that are then deposited in blood vessels. These crystals cause an inflammatory response and can lead to the occlusion of smaller vessels. Further complications like secondary infections and necrosis can develop from this and can be fatal for some, making the monitoring of blood calcium and phosphate levels necessary.Conditions due to bone loss such as osteopenia and osteoporosis are common in tertiary hyperparathyroidism along with pathologic fractures. Pseudoclubbing of the digits can also be indicative of a severe tertiary hyperparathyroidism due to excess resorption at the distal phalanges.Diagnosis includes both clinical and laboratory investigations. Radiological investigations include looking for signs of bone loss in both the hands and pelvis which is characteristic of tertiary hyperparathyroidism.
Vitamin D is also responsible for increased blood calcium levels and works in conjunction with parathyroid hormone. Vitamin D is also partly responsible for the inhibition of parathyroid hormone release by binding Vitamin D receptors at the parathyroid gland. Tertiary hyperparathyroidism is defined by autonomous release of parathyroid hormone while in a hypercalcaemic state. Unlike primary hyperparathyroidism, hypercalcemia in the tertiary form is thought to be the result of resolution of secondary hyperparathyroidism rather than adenoma formation alone.Many of the mechanisms that drive the formation of tertiary hyperparathyroidism are due to outcomes of secondary hyperparathyroidism and so the tertiary from is said to be a continued progressive hyperparathyroidism. Secondary hyperparathyroidism occurs mainly in those who have chronic kidney disease or vitamin D deficiencies both of which lead to malabsorption of calcium and phosphate leading to decreased blood calcium levels inducing a hyperparathyroidism. Hyperphosphatemia in secondary hyperparathyroidism, due to increased parathyroid hormone, is thought to act directly on parathyroid glands and induce a hyperplasia or increased growth of the chief cells in particular. At the same time the hyperplasic parathyroid glands have reduced fibroblast-growth-factor-23 (FGF-23) and vitamin D receptor expression. FGF-23 is partly responsible for phosphate homeostasis and provides negative feedback to the parathyroid gland as does vitamin D.During prolonged secondary hyperparathyroidism increased blood phosphate levels drive hyperplasia of the parathyroid gland and this acts to reset calcium sensitivity at the calcium sensing receptors leading to tertiary hyperparathyroidism after resolution of the secondary form with the continued release of parathyroid hormone in the presence of hypercalcemia.