The primary disease of parathyroid glands is overactivity, with too much parathyroid hormone (PTH) being produced. In this condition, one or more of the parathyroid glands behaves inappropriately by making excess hormone regardless of the level of calcium. In other words, the parathyroid glands continue to make large amounts of parathyroid hormone even when the calcium level is normal and they should not be making hormone at all. The most common cause of excess hormone production is the development of a benign tumor in one of the parathyroid glands. This enlargement of one parathyroid gland is called a parathyroid adenoma which accounts for 87-93% of all patients with primary hyperparathyroidism. Typically, one of the parathyroid glands has developed a tumor which is secreting all the hormone. The other three glands are small and responding appropriately to the high calcium by becoming dormant. This out of control parathyroid gland is essentially never cancerous (less than 1 in 500), however, it slowly causes damage to the body because it induces an abnormally high level of calcium in the blood which can slowly destroy a number of tissues. Parathyroid adenomas typically are much bigger than the normal pea-sized parathyroid and will frequently be about the size of a walnut.

Approximately 7-11% of all patients with primary hyperparathyroidism will have an enlargement of all four parathyroid glands, a term called parathyroid hyperplasia. In this instance, all of the parathyroid glands become enlarged and produce too much parathyroid hormone. An even rarer situation occurs in approximately 3% of the people who have two parathyroid adenomas while having two normal glands.

Since hyperparathyroidism was first described in 1925, the symptoms have become known as "moans, groans, stones, and bones". Although most people with primary hyperparathyroidism claim to feel well when the diagnosis is made, the majority of these will actually say they feel better after the problem has been cured. This can only be known retrospectively when patients are allowed to comment on how they feel several months after the operation. Many patients who thought they were asymptomatic preoperatively will claim to sleep better at night, be less irritable, and find that they remember things much easier than they could when their calcium levels were high (nervous system problems).