Hyperparathyroidism

Definitions & Key takeaways

Hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone (PTH), which regulates calcium levels in the blood. Hyperparathyroidism can be primary, secondary, or even tertiary.

Primary hyperparathyroidism usually results from PTH secretion by a parathyroid adenoma. It is characterized by excess PTH that leads to high blood calcium levels (hypercalcemia), bone mass loss, kidney stones, and other health problems, such as psychiatric issues.

Secondary hyperparathyroidism develops when there are conditions like chronic kidney disease, which can lead to low calcium, high phosphate, and low vitamin D levels. It is mainly characterized by osteodystrophy, in which there is bone weakening associated with bone pain and deformation.

Finally, there is tertiary hyperparathyroidism, which occurs because of chronic secondary hyperparathyroidism from kidney disease. This leads to hypercalcemia and phosphate imbalances.

Chapters:

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Introduction0:00–0:27

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.

Physiology0:27–2:39

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.

Pathophysiology2:39–3:33

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.

Primary hyperparathyroidism3:33–4:06

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.

Secondary hyperparathyroidism4:06–4:53

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.
Most often, the problem is with the kidneys, which aren’t filtering phosphate properly into urine or making enough calcitriol.
The hyperphosphatemia - or high level of phosphate - reduces the amount of free calcium ions in the blood by binding with them, and the lack of calcitriol means less calcium is absorbed by the intestine.
Secondary hyperparathyroidism can also be caused by a chronic lack of calcitriol either because of a lack of sunlight or because of poor intake or absorption of dietary vitamin D.

Tertiary hyperparathyroidism4:53–5:33

Tertiary hyperparathyroidism is basically a situation where individuals who have had secondary hyperparathyroidism for many years - develop primary hyperparathyroidism.
Specifically, parts of the parathyroid gland start making parathyroid hormone independently of blood calcium levels - resulting in hypercalcemia.
The level of phosphate in this tertiary hyperparathyroidism can vary. If the person still has chronic kidney disease, phosphate will be high.
But if the person has had a kidney transplant, then phosphate will be low because the new kidneys will be working properly in response to hypercalcemia.

Symptoms5:33–6:57

The symptoms of primary hyperparathyroidism can be remembered as ‘stones, thrones, bones, groans, and psychiatric overtones’.
Stones is for calcium-based kidney stones or gallstones that can form, thrones refers to the toilet to remind you of the polyuria or frequent urination that results from impaired sodium and water reabsorption.
Bones is for bone pain that results after chronic hormone-driven demineralization in order to release calcium. Groans is for constipation and muscle weakness, both of which are partly due to decreased muscle contractions.
Finally, psychiatric overtones refers to symptoms like a depressed mood and confusion. Secondary hyperparathyroidism can present with symptoms of chronic kidney disease as that is often the underlying cause.
Other secondary hyperparathyroidism symptoms include bone resorption, called renal osteodystrophy, and calcification in blood vessels and soft tissues, because the high levels of phosphate cause it to find and stick to any available calcium, which forms bone-like crystals in places that they shouldn’t be.
Tertiary hyperparathyroidism causes all of the same symptoms as primary hyperparathyroidism, but can also have elevated phosphate levels and as a result deposits of calcium-phosphate can settle in blood vessels and soft tissues.
Diagnosis of hyperparathyroidism is based on blood tests to confirm high levels of parathyroid hormone and then testing for blood levels of calcium, phosphate, and vitamin D to confirm the type of hyperparathyroidism.

Diagnosis6:57–7:37

Typically, primary hyperparathyroidism will have high calcium and low phosphate; secondary will have low calcium, high phosphate, and low vitamin D; and tertiary will have high calcium - but it’s distinguished from primary hyperthyroidism if the person has - or used to have - chronic kidney disease - and phosphate levels will depend on whether the person has had a kidney transplant.
Treatment of primary and tertiary hyperparathyroidism is done by removing the abnormal parathyroid glands with surgery. Calcimimetics, drugs that imitate the action of calcium by attaching to the calcium-sensing receptors on parathyroid cells, are used if surgery is not possible.

Treatment7:37–8:12

Sometimes with secondary hyperparathyroidism, surgery is used, but normally treatment is aimed at managing the hyperphosphatemia with phosphate binders and to increase the levels of vitamin D, using supplements and calcitriol analogs.
All right, as a quick recap, hyperparathyroidism is a condition where the body releases too much parathyroid hormone. Primary hyperparathyroidism is usually caused by a parathyroid adenoma, resulting in high calcium and low phosphate levels, with symptoms that can be summed up as ‘stones, bones, groans, thrones, and psychiatric overtones’.

Review8:12–8:57

Secondary hyperparathyroidism is usually caused by chronic kidney disease, resulting in low calcium, high phosphate, and low vitamin D levels, with symptoms including renal osteodystrophy.
Tertiary hyperparathyroidism is caused by chronic secondary hyperparathyroidism from kidney disease, resulting in hypercalcemia and either high or low phosphate, depending on whether the person still has kidney disease or not.