68. Parathyroid abnormalities

Parathyroid hormone

Parathyroid hormone (PTH) is produced by chief cells in the parathyroid gland. It’s the most important hormone in regulating the serum calcium concentration.

PTH is secreted in response to:

• Decreased levels of serum (ionized) calcium (ionized calcium < 1.25 mM)
• Increased levels of serum phosphate (as phosphate creates a complex with calcium, causing the level of ionized calcium to decrease)
• Adrenaline
• Decreased levels of serum magnesium (not so important)

PTH has the following effects:

• Increases calcium reabsorption in the distal tubule
• Increases phosphate excretion in the tubules
• Activation of osteoclasts, causing release of calcium and phosphate from bones
• Increases vitamin D production
  • Vitamin D increases calcium and phosphate absorption from the intestines
  • Vitamin D increases calcium reabsorption in the kidney
  • Vitamin D stimulated bone mineralization

PTH’s effects come together to increase the serum calcium levels.

Hyperparathyroidism

Hyperparathyroidism can be classified as primary, secondary or tertiary:

• Primary hyperparathyroidism – due to increased autonomous production of PTH by the parathyroid glands in absence of stimulation
• Secondary hyperparathyroidism – increased production of PTH by the parathyroid glands due to increased stimulation
• Tertiary hyperparathyroidism – a complication of secondary hyperparathyroidism

Etiology

Primary hyperparathyroidism:

• Parathyroid adenoma
• Parathyroid hyperplasia
• Parathyroid carcinoma

By far the most frequent cause of primary hyperparathyroidism is parathyroid adenoma, which accounts for nearly 90% of cases.

Secondary hyperparathyroidism:

• Chronic renal failure (most common cause)
• Malnutrition
• Vitamin D deficiency

In secondary hyperparathyroidism there is a strong stimulus present, that stimulates the parathyroid glands to produce excessive amounts of PTH.

Tertiary hyperparathyroidism

• Long-term persistent secondary hyperparathyroidism

Pathomechanism

In chronic renal failure the kidney fails to excrete phosphate, which will build up in the blood and cause PTH to increase. In chronic renal failure the synthesis of vitamin D is also impaired.

In vitamin D deficiency the parathyroid glands lose their “partner hormone”, so the production of PTH must increase to maintain the normal calcium level.

In long-standing secondary hyperparathyroidism, the glands will become hypertrophic and hyperplastic. Even if the stimulus that originally caused the secondary hyperparathyroidism is removed the glands will still be overactive, causing tertiary hyperparathyroidism.

Clinical features

In primary hyperparathyroidism hypercalcaemia develops. In secondary hyperparathyroidism the calcium level is mostly normal. Hypercalcaemia does not develop. In tertiary hyperparathyroidism there may be hypercalcaemia.

most symptoms are related to hypercalcaemia, which will be discussed in the next topic. One important symptom is related to the elevated PTH itself, the formation of cyst-like brown tumors in the bones, called “generalized osteitis fibrosa cystica”.

Hypoparathyroidism

Hypoparathyroidism refers to decreased production of PTH. It can develop in hypercalcaemia (secondary) or it can be due to malfunction of the glands (primary).

Etiology

• Surgical removal of parathyroids
  • By accident during thyroidectomy
  • As treatment of hyperparathyroidism
• Autoimmune destruction of the parathyroids
• Parathyroid hypoplasia
• Infiltration of the glands
  • Haemochromatosis
  • Granulomatous disease
  • Wilson’s disease
  • Metastasis

The first two causes are the most common ones.

Pathomechanism

PTH increases bone resorption and activates osteoclasts, so hypoparathyroidism will increase bone deposition and inhibit osteoclasts. Calcification is common. Hypocalcaemia occurs.

Clinical features

Hypocalcaemia occurs; the symptoms of which are discussed in the next topic. Most symptoms of hypoparathyroidism are related to hypocalcaemia.

Certain manifestations are related to the low PTH level itself:

• Calcification of the basal ganglia
• Increased density of bone (osteosclerosis)

Pseudohyperparathyroidism

Pseudohyperparathyroidism is the condition where something other than PTH elicits PTH-like effects. It’s mostly caused by paraneoplastic syndromes where tumors produce parathyroid hormone-related protein (PTHrP). This protein has similar structure as PTH and will induce the same effects as PTH. Patients can develop hypercalcaemia.