Secondary Hyperparathyroidism

How it develops

PTH is made by four small glands in the neck. It keeps blood calcium in range by releasing calcium from bone, reducing calcium loss in urine, and activating vitamin D in the kidneys.

In secondary hyperparathyroidism, something outside the parathyroid glands causes low calcium, low active vitamin D or high phosphate. The glands respond appropriately by making more PTH, and over time they enlarge. In long-standing kidney disease, the glands can become partly self-driven (tertiary hyperparathyroidism), producing PTH even when calcium is high.

Causes

Chronic kidney disease

Chronic kidney disease is the most common cause. As kidney function falls:

• the kidneys excrete less phosphate, so phosphate rises
• the kidneys activate less vitamin D, so calcium absorption falls
• a hormone called FGF23 rises, further reducing active vitamin D

All of these drive PTH up. This combination is called CKD-mineral and bone disorder (CKD-MBD). It is almost universal in people on dialysis. See dialysis-related disorders.

Vitamin D deficiency

Vitamin D deficiency reduces calcium absorption from food. PTH rises to maintain blood calcium by taking calcium from bone. This is common in people with little sun exposure, darker skin, obesity, older age and those who cover their skin.

Malabsorption

Celiac disease, inflammatory bowel disease, pancreatic insufficiency and weight-loss surgery reduce absorption of calcium and vitamin D.

Other causes

• Low calcium intake
• Medicines such as some anti-seizure drugs, loop diuretics, bisphosphonates and lithium (lithium can also cause primary hyperparathyroidism)
• Liver disease

Primary vs secondary hyperparathyroidism

See hyperparathyroidism.

Symptoms

Many people have no symptoms, and the condition is found on blood tests. When present:

• Bone pain and aches
• Weak bones and fractures
• Muscle weakness and cramps
• Itching, especially in kidney disease
• Joint pain
• In vitamin D deficiency: softening of bones (osteomalacia) in adults and rickets in children

In advanced kidney disease, complications include calcification of blood vessels and heart valves, and rarely calciphylaxis, a serious condition with painful skin ulcers.

Diagnosis

• PTH: raised
• Calcium: normal or low
• Phosphate: high in kidney disease, low or normal in vitamin D deficiency
• 25-hydroxyvitamin D: low in vitamin D deficiency
• Kidney function and alkaline phosphatase
• Bone density scan in some cases
• Neck ultrasound or other imaging if surgery is being considered

Treatment

Vitamin D deficiency and malabsorption

• Vitamin D supplements to restore normal levels
• Adequate calcium intake from diet or supplements
• Treating the underlying gut condition

PTH usually falls back to normal once vitamin D is replaced.

Chronic kidney disease

• Diet: limiting phosphate, especially phosphate additives in processed foods and colas, with help from a renal dietitian
• Phosphate binders taken with meals
• Vitamin D: nutritional vitamin D for deficiency, and active vitamin D (calcitriol or analogs) in more advanced disease
• Calcimimetics (cinacalcet or etelcalcetide), which make the parathyroid glands more sensitive to calcium and lower PTH
• Effective dialysis
• Parathyroidectomy: surgery to remove most parathyroid tissue for severe hyperparathyroidism not controlled by medicines
• Kidney transplant, after which PTH often improves, though some people develop tertiary hyperparathyroidism

Outlook

When caused by vitamin D deficiency, secondary hyperparathyroidism usually resolves with treatment. In kidney disease it is a long-term condition that needs ongoing monitoring and treatment to protect bones and blood vessels.

Frequently asked questions

What causes secondary hyperparathyroidism?

The most common causes are chronic kidney disease and vitamin D deficiency. Both lower calcium absorption or raise phosphate, prompting the parathyroid glands to make more hormone. Malabsorption conditions, weight-loss surgery, low calcium intake and some medicines can also cause it.

What is the difference between primary and secondary hyperparathyroidism?

In primary hyperparathyroidism, a problem within the parathyroid glands, usually a benign tumor, causes high PTH and high calcium. In secondary hyperparathyroidism, the glands are responding to low calcium or vitamin D from another cause, and blood calcium is normal or low.

What are the symptoms of secondary hyperparathyroidism?

Many people have no symptoms. When present, they include bone pain, weak bones and fractures, muscle weakness and cramps, joint pain and itching. In advanced kidney disease, calcium can build up in blood vessels and, rarely, cause painful skin ulcers.

How is secondary hyperparathyroidism treated?

Treatment targets the cause. Vitamin D deficiency is treated with vitamin D and calcium. In kidney disease, treatment includes phosphate restriction, phosphate binders, vitamin D, calcimimetic medicines and, for severe cases, surgery to remove parathyroid tissue.