17.5 The Parathyroid Glands

The parathyroid glands, tiny organs behind the thyroid, play a crucial role in calcium regulation. They produce parathyroid hormone (PTH), which works to increase blood calcium levels by targeting bones, kidneys, and intestines.

Disorders of the parathyroid glands can lead to serious health issues. Hyperparathyroidism causes high calcium levels and weakened bones, while hypoparathyroidism results in low calcium, muscle cramps, and potentially dangerous complications like seizures.

Parathyroid Glands

Location and Structure of Parathyroid Glands

There are typically four parathyroid glands (two superior, two inferior) embedded in the posterior surface of the thyroid gland. They're small and oval-shaped, each only about the size of a grain of rice.

The glands contain two main cell types:

• Chief (principal) cells are the functional workhorses. They secrete parathyroid hormone (PTH), the hormone responsible for regulating blood calcium levels.
• Oxyphil cells have no clearly established function. They appear during puberty and increase in number with age, but their role remains uncertain.

Parathyroid Hormone and Calcium Regulation

Parathyroid hormone (PTH), also called parathormone, has one primary job: raise blood calcium levels when they drop below normal. It does this by acting on three target sites.

Effects on bone:

1. Stimulates osteoclasts to break down bone matrix and release stored calcium into the bloodstream (this process is called bone resorption)
2. Increases calcium reabsorption from bone fluid surrounding osteocytes

Effects on kidneys:

1. Enhances calcium reabsorption in the distal convoluted tubules and collecting ducts, so less calcium is lost in urine
2. Reduces phosphate reabsorption, causing more phosphate to be excreted. This matters because phosphate binds to calcium in the blood. By dumping phosphate, free calcium levels rise.
3. Stimulates the enzyme that converts vitamin D into its active form, calcitriol ($1,25\text{-dihydroxyvitamin D}_3$), which then boosts calcium absorption in the gut

Effects on intestines:

PTH doesn't act on the intestines directly. Instead, it works indirectly through calcitriol production in the kidneys. Once calcitriol reaches the small intestine, it increases absorption of dietary calcium.

Effects of Parathyroid Disorders

Hyperparathyroidism means too much PTH is being secreted. There are two forms:

• Primary hyperparathyroidism results from a problem within the parathyroid glands themselves, such as an adenoma (benign tumor) or gland enlargement.
• Secondary hyperparathyroidism is a compensatory response. When blood calcium is chronically low (often from kidney disease or vitamin D deficiency), the glands ramp up PTH production to try to correct it.

Effects of hyperparathyroidism include:

• Hypercalcemia (elevated blood calcium)
• Weakened bones from excessive bone resorption
• Kidney stones, because the kidneys filter out the excess calcium
• Fatigue, muscle weakness, depression, and constipation
• Prolonged cases can progress to osteoporosis, with significantly decreased bone density and higher fracture risk

A classic memory aid for hyperparathyroidism symptoms: "bones, stones, groans, and moans" (bone pain, kidney stones, abdominal groans, and psychic moans like depression).

Hypoparathyroidism means too little PTH is being produced. The most common cause is accidental damage to or removal of the parathyroid glands during thyroid surgery. Autoimmune destruction and genetic conditions are less common causes.

Effects of hypoparathyroidism include:

• Hypocalcemia (low blood calcium)
• Muscle cramps, twitches, and spasms
• Tingling or numbness in the fingers, toes, and around the mouth (paresthesias)
• In severe cases, seizures and cardiac arrhythmias

If hypocalcemia becomes extreme, it can cause tetany, a condition of sustained, involuntary muscle contraction and spasms. Two clinical signs used to test for latent tetany are Chvostek's sign (tapping the facial nerve causes twitching of facial muscles) and Trousseau's sign (inflating a blood pressure cuff on the arm triggers carpal spasm).

Calcium Homeostasis and the Endocrine System

Calcium homeostasis depends on a balance between two opposing hormones:

• PTH (from the parathyroid glands) raises blood calcium levels.
• Calcitonin (from the parafollicular C cells of the thyroid gland) lowers blood calcium levels, primarily by inhibiting osteoclast activity and promoting calcium deposition into bone.

These two hormones form a negative feedback loop. When blood calcium rises above normal, calcitonin is released to bring it down. When blood calcium drops below normal, PTH is released to bring it back up. Together, they keep blood calcium within its narrow normal range (approximately $8.5\text{–}10.5 \text{ mg/dL}$).