Hypoparathyroidism

Definitions & Key takeaways

Hypoparathyroidism is a condition characterized by the underproduction of parathyroid hormone (PTH). PTH is responsible for maintaining the correct levels of calcium and phosphorus in the blood. When PTH levels are low, calcium levels in the blood can drop, which can lead to symptoms like muscle weakness, cramps, and abnormal heart rhythms. Hypoparathyroidism is often caused by the surgical removal of the parathyroid glands, autoimmune destruction, or genetic conditions like DiGeorge syndrome.

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Introduction0:00–0:27

With hypoparathyroidism, “hypo” refers to under, and “parathyroid” refers to the parathyroid glands, so hypoparathyroidism refers to a condition where there is an underproduction 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.

Physiology0:27–2:38

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.

Pathology2:38–3:41

The most common cause of hypoparathyroidism is removal of the parathyroid glands during thyroid or parathyroid surgery. Another cause includes autoimmune polyendocrine syndrome type 1 which destroys parathyroid glands.
There’s are also genetic causes like DiGeorge syndrome, which is a deletion on the 22q11 part of the chromosome that causes a variety of immune and cardiac defects as well as parathyroid glands that can’t produce enough parathyroid hormone.
There’s also autosomal-dominant hypoparathyroidism caused by a mutation in the parathyroid cell’s calcium-sensing receptor.
Finally there’s pseudohypoparathyroidism type 1A, or Albright hereditary osteodystrophy, which is when the parathyroid hormone is not the problem at all, and instead the kidneys and bones simply don’t respond to parathyroid hormone because of a defect in their parathyroid hormone receptor.

Signs and symptoms3:41–4:43

Regardless of the cause, low levels of parathyroid hormone lead to hypocalcemia and hyperphosphatemia. This makes neurons more excitable, which can trigger tetany, or the involuntary contraction of muscles.
Other symptoms include paresthesia - numbness or tingling of hands, feets, and around the mouth, changes in cardiac output, and calcification in places like the basal ganglia or the lens of the eye.
The spontaneous firing of neurons leads to Chvostek's sign, which is when facial muscles twitch after the facial nerve is lightly finger tapped 1 cm below the zygomatic process.
It also can cause Trousseau's sign, which is where a blood pressure cuff occludes the brachial artery, and that pressure on the nerve is enough to make it fire, which results in a muscle spasm that makes the wrist and metacarpophalangeal joints flex.
If the hypocalcemia and hyperphosphatemia are severe, this can lead to life-threatening complications like severe seizures and cardiac arrhythmias.

Diagnosis4:43–5:03

Diagnosis is based on blood tests for parathyroid hormone, calcium, vitamin D, albumin, phosphorus, and magnesium. Also an electrocardiogram might have changes such as a prolonged QT, prolonged ST segment, and arrhythmias, like torsade de pointes and atrial fibrillation.

Treatment5:03–5:20

The immediate treatment for hypoparathyroidism is to give calcium and vitamin D supplements to bring calcium levels back to normal.
Long-term treatment can include taking recombinant human parathyroid hormone to make up for the body’s under-production.
All right, as a quick recap, hypoparathyroidism is a condition of under-production of parathyroid hormone. This causes low levels of extracellular calcium and high levels of phosphate.

Review5:20–5:46

This makes neurons more excitable, with symptoms including tetany and cardiac dysfunction. It is most often caused by surgical removal of the parathyroid glands, but can also be due to genetic conditions like DiGeorge syndrome.