Overview & Symptoms

Incidence increases with age, peaks between ages 40 – 70.

• 3:1 ratio of women to men.

Reason for this dysfunction is unknown.

Not triggered by a somatic (after birth) or hereditary (before birth) mutation in the DNA of the CASR protein.

• Primary Hyperparathyroidism (pHPT) is predominantly sporadic (not passed on genetically in families).

The affected parathyroid cells think the calcium level in the blood is always low even though it is actually normal (or even elevated).

• In response to this, the affected parathyroid cells increase production of Parathyroid Hormone (PTH) in order to raise calcium levels back to the normal range.
  • Review of Parathyroid Gland Function.

Consequently, higher calcium levels are less effective at inhibiting PTH production in these affected parathyroid cells.

• Loss of normal ‘teeter totter’ relationship of Calcium and PTH levels.
  • The end result is high calcium and high PTH levels at the same time.

As these cells enlarge and become more numerous, the parathyroid gland itself grows.

• This growth or enlarged parathyroid gland is called a Parathyroid Adenoma.
• The overwhelming majority of parathyroid adenomas are benign, < 0.1% are cancerous (malignant).

85% of the time, the cause for primary hyperparathyroidism is a single parathyroid adenoma.

10% of the time it is the results of two separate parathyroid adenomas forming.

• The cause for this is unknown, similar to single adenoma formation.

5% of the time, all 4 of the glands are involved, aka ‘4-gland hyperplasia.’

• The cause for this is unknown as well, thought to be slightly different from single and double adenomas though.
• Typically associated with milder elevations in calcium and PTH levels.
  • Still as symptomatic as single and double adenomas.

The size of these normal parathyroid cells and glands will stay the same size or sometimes shrink due to less PTH being produced.

Most of the time it is completely random, and not caused by drinking alcohol, smoking, diet, or other lifestyle choices.

There is increased risk with history of radiation exposure.

• Treatment of acne / tonsillitis / thymus in the 1950-60’s.
• Treatment of cancers in the head and neck.
  • Typically develops 10-40 years following exposure.
• Radioactive iodine treatment for hyperthyroidism or thyroid cancer.
  • 15-25 years later, mainly single adenoma disease.

Increased incidence with Lithium (drug used to treat psychiatric disorders) use over a chronic period (~ 10-15 years).

• ~15% of long-term users.
• Higher rate of double adenomas and 4-gland hyperplasia (e.g., multi-gland disease).

Rare hereditary causes:

• • Familial Isolated Hyperparathyroidism.
    • Very rare, < 1 % of pHPT.
    • Inherited Autosomal Dominant (only one parent needed to pass gene to children).
    • No increased risk with one first degree relative.
    • Must differentiate from FHH (read more in Primary Hyperparathyroidism Diagnosis).

• Multiple Endocrine Neoplasia (MEN).
  • MEN Type 1.
    • Pituitary adenomas, pancreaticoduodenal tumors, and primary hyperparathyroidism.
    • Earlier presentation, usually by age 20-25 (100% by age 40).
    • Typically presents as 4-gland hyperplasia treated with subtotal (3 & ½ gland) resection.
    • Increased incidence of supernumerary glands (therefore thymectomy considered as well).
  • MEN Type 2A.
    • Medullary thyroid carcinoma, pheochromocytomas, and parathyroid hyperplasia
    • Affecting only 20-40% patients, presents later (ages 35-40).
    • Typically multiple adenomas treated with focused excision of effected glands.
    • Critical to rule out pheochromocytoma prior to surgery (can result in life threatening uncontrollable heart rate and blood pressure).
      • Urine or serum catecholamine and metanephrines, or abdominal CT.
• Hyperparathyroidism – Jaw Tumor Syndrome.
  • Asynchronous (develops at different times) multiple adenomas.
  • Associated with bony masses in the mandible (jaw) and maxilla (cheeks / mouth).
  • Renal (kidney) cysts and Hamartomas.
  • Increased risk for parathyroid carcinoma.