23rd May 2025

Primary hyperparathyroidism

The causes of primary hyperparathyroidism are:

• Parathyroid adenoma (over 80% of cases)
• Hyperplasia (15-20%)
• Carcinomas (<1%)
• Familial cases can occur as part of multiple endocrine neoplasia syndrome (MEN 1 or MEN 2a) or familial isolated hyperparathyroidism (FIHPT)

Pathophysiology 

In normal physiology, low serum calcium levels stimulate PTH secretion whereas high calcium suppresses PTH secretion. In primary hyperparathyroidism PTH secretion is not suppressed by high calcium, resulting in hypercalcaemia, as well as raised PTH levels.

Most of the symptoms associated with hyperparathyroidism are due to hypercalcaemia. Hypercalcaemia can cause symptoms such as “bones, stones, abdominal groans and psychiatric moans”. These are expanded on below. Chronic excessive PTH leads to over-stimulation of bone resorption resulting in osteopenia. In severe cases this can result in osteitis fibrosa cystica which presents with subperiosteal resorption of distal phalanges, salt-and-pepper appearance of the skull and brown tumours of the long bones.
Chronic increased excretion of the calcium in urine can result in renal stones.

Presentation

• Asymptomatic
• Hypercalcaemia 
• Bone pain, muscle weakness, pseudogout, chondrocalcinosis, osteitis fibrosa cystica
• Renal stones 
• Polyuria and polydipsia 
• Abdominal groans: nausea and vomiting, peptic ulcer disease, constipation, anorexia, acute pancreatitis
• Neuropsychiatric manifestations: depression, anxiety, fatigue, memory problems.
• Cardiovascular manifestations: hypertension, bradycardia, Hypercalcaemic changes on ECG include: shortened QT interval, Osborn waves (J waves), Ventricular irritability and VF arrest.
• Physical examination of the neck is usually normal.

Investigations

Diagnosis of primary hyperparathyroidism is confirmed with repeated measures of serum calcium and intact serum PTH.
Certain conditions must be accounted for:

• Thiazide diuretics should be stopped 2 weeks before the calcium measurements. 
• Serum calcium should be adjusted for the serum albumin concentration. Ionised calcium levels can be a more accurate measure.
• 25-hydroxyvitamin D level should also be measured in the evaluation of primary hyperparathyroidism. 

Bloods may show the following: 

• elevated intact PTH level 
• elevated ionised serum calcium level 
• on more than one occasion

Other laboratory findings include 

• Mild hyperchloremic acidosis
• Hypophosphatemia 
• Mild to moderate increase in urinary calcium excretion rate.

Other investigations include radiographic studies. These are often used as a guide (not for diagnosis purposes) for surgeons should the patient wish to proceed with a parathyroidectomy. Tc-99m sestamibi scanning is often used with ultrasonography.

Management

Parathyroidectomy is the definitive treatment for primary hyperparathyroidism. 

Indications for surgery in an asymptomatic patient are the following:

• Age <50 years
• Inability to ensure appropriate follow-up
• Serum calcium >0.25 mmol/l (>1 mg/dl) above normal range
• Creatinine clearance <60mL/minute
• Bone mineral density T-score <-2.5 at lumbar spine, total hip, femoral neck, or distal third of radius and/or vertebral fracture by x-ray, CT, MRI or vertebral fracture assessment using dual-energy x-ray absorptiometry. 
• 24-hour urinary calcium >400 mg/day and increased stone risk by biochemical stone risk analysis
• Nephrolithiasis or nephrocalcinosis by x-ray, ultrasound, or CT.

If the patient is symptomatic, surgery should be considered regardless of the above criteria.

If the patient declines surgery or is an unsuitable surgical candidate, serum calcium and creatinine levels should be measured annually and bone density be measured every 1-2 years. Vitamin D should be given to those who are deficient. 

Bisphosphonates or cinacalcet are adjunctive therapies for those who do not undergo surgery.