23rd May 2025

Secondary hyperparathyroidism

Secondary hyperparathyroidism occurs when there is chronic hypocalcaemia, often caused by chronic kidney disease or vitamin D deficiency. This leads to an overproduction of parathyroid hormone. 

Any disorder that results in hypocalcaemia will elevate parathyroid hormone level and can cause secondary hyperparathyroidism.

Causes

• Vitamin D deficiency
• Chronic kidney disease
• Fat malabsorption (this can contribute to reduced absorption of vitamin D and dietary calcium) e.g., in Crohn’s disease, Coeliac disease, chronic pancreatitis, Whipple’s disease, post-gastric bypass surgery
• Diminished dietary intake of calcium
• Increased calcium loss or increased metabolic requirements e.g. after pregnancy and breastfeeding, bisphosphonate treatment, loop diuretics, rhabdomyolysis, sepsis.

Presentation

The clinical features of secondary hyperparathyroidism depend on the underlying cause. 

Severe vitamin D deficiency and hypocalcaemia present with neuromuscular irritability such as:

• Numbness or paraesthesia in fingers, toes, peri-orally
• Muscle cramps
• Laryngospasm
• Tetany 
• Seizures

Vitamin D deficiency can cause Rickets in children and Osteomalacia in adults which presents with muscle weakness and diffuse bone pain.

Signs of hypocalcemia:

• Chvostek’s sign: percussion over the facial nerve leads to abnormal contraction of the ipsilateral facial muscles
• Trousseau’s sign: often found when taking the patient’s blood pressure, inflation of the blood pressure cuff for a few minutes leads to involuntary contraction of the muscles of the hand and wrist

Investigations

Diagnosis is based on clinical picture, metabolic derangement (low/normal serum calcium and high parathyroid hormone).
First line investigations:

• Serum Calcium to be taken at the same time as iPTH.
• Either total or ionised calcium levels can be used. 
• Serum calcium levels may be normal or <2.10mmol/L
• Intact parathyroid levels are often >88 nanograms/L
• Renal function should be checked for CKD.
  

Other investigations:

• Phosphate: elevated phosphate levels in addition to elevated serum urea and creatinine can point towards a diagnosis of chronic kidney disease. 
• If phosphate levels are low the diagnosis points towards vitamin D deficiency.
• Serum 25-hydroxyvitamin D levels should be measured.
• Serum magnesium: High or low levels of magnesium can cause tissue resistance to PTH or reduced PTH production resulting in hypocalcaemia.

Management

Management of secondary hyperparathyroidism is by optimising medical management of the underlying condition. 

If the cause is lack of sunlight and vitamin D patients should be advised on safe sun exposure +/- vitamin D supplements.

If the cause is malabsorption-related, the underlying disorder should be treated (for example a gluten-free diet for coeliac disease or lactose-free diet in those who are lactose intolerant). Protease and lipase supplements for pancreatic insufficiency or corticosteroids and anti-inflammatory agents in inflammatory bowel disease. Vitamin D and calcium supplements can also be used.

If the secondary hyperparathyroidism is secondary to CKD, the first line management is dietary phosphate restriction (800-1000 mg/day). Serum phosphate levels should be monitored monthly in stage 5 CKD and every 3 months in stage 3-4 after initiation of the restriction.
A phosphate binder such as calcium acetate or Sevelamer can also be used with vitamin D supplementation if levels are low or vitamin D analogues if levels are normal.

In refractory secondary hyperparathyroidism in late-stage CKD, parathyroidectomy can be considered.