Hyperparathyroidism

With hyperparathyroidism, “hyper” refers to over, and “parathyroid” refers to the parathyroid glands, so hyperparathyroidism refers to a condition where there is an overproduction of parathyroid hormone.

Parathyroid hormone comes from the parathyroid glands which are buried within the thyroid gland, and their main job is to keep blood calcium levels stable.

Now, the majority of the extracellular calcium, the calcium in the blood and interstitium, is split almost equally between two groups - calcium that is diffusible and calcium that is not diffusible.

Diffusible calcium is small enough to diffuse across cell membranes and is separated into two subcategories.

The first is free-ionized calcium, which is involved in all sorts of cellular processes like neuronal action potentials, contraction of skeletal, smooth, and cardiac muscle, hormone secretion, and blood coagulation, all of which are tightly regulated by enzymes and hormones.

The second category is complexed calcium, which is where the positively charged calcium is ionically linked to tiny negatively charged molecules like oxalate, which is a small anion that are normally found in our blood in small amounts.

The complexed calcium forms a molecule that’s electrically neutral but unlike free-ionized calcium it’s not useful for cellular processes.

Both of these are called diffusible because they’re small enough to diffuse across cell membranes.

Finally there’s the non-diffusible calcium which is bound to negatively charged proteins like albumin.

The resulting protein-calcium complex is too large and charged to cross membranes, leaving this calcium also uninvolved in cellular processes.

Changes in the body’s levels of extracellular calcium are detected by a surface receptor in parathyroid cells that’s called the calcium-sensing receptor.

These changes affect the amount of parathyroid hormone that’s released by the parathyroid gland.

The parathyroid hormone gets the bones to release calcium, it gets the kidneys to reabsorb more calcium so it's not lost in the urine, and it synthesizes calcitriol, which is also known as 1,25-dihydroxycholecalciferol, or active vitamin D.

Active vitamin D then goes on to cause the gastrointestinal tract to increase calcium absorption.

Altogether, these effects help to keep the extracellular levels of calcium within a narrow range that’s between 8.5 to 10 mg/dl.

So there are three types of hyperparathyroidism - primary, secondary, and tertiary.

In primary hyperparathyroidism, the parathyroid gland is responsible for the problem, because it makes parathyroid hormone independently of the calcium level.

Excess parathyroid hormone stimulates osteoclasts to break down bone and makes the kidneys hold on to calcium and get rid of phosphate - resulting in hypercalcemia and hypophosphatemia.

The excess calcium makes neurons less excitable, which leads to slower muscle contractions, and diminishes neuron firing in the central nervous system.

It also causes hypercalciuria - excess loss of calcium in urine - which can lead to dehydration. This is because there is just too much calcium to be reabsorbed by the kidneys.

Most often, primary hyperparathyroidism is caused by a single parathyroid adenoma, or benign tumor, which happens either because of a genetic mutation in a single cell or because of an inherited disorder like multiple endocrine neoplasia, which affects the parathyroid, pancreas, and pituitary glands.

Rarely, primary hyperparathyroidism is caused by hyperplasia, where parathyroid cells divide excessively causing growth of the glands, or by a parathyroid carcinoma, a cancerous tumor.

In secondary hyperparathyroidism, the parathyroid gland is normal, but it makes excess parathyroid hormone in response to chronic hypocalcemia - a low level of calcium - from another cause.