What is Primary Hyperparathyroidism?
Primary hyperparathyroidism is a medical condition characterized by elevated parathyroid hormone levels due to excessive synthesis and release by the parathyroid gland. This typically occurs in the setting of a parathyroid adenoma (tumor). The condition usually affects elderly people and is more commonly seen in women. Parathyroid hormone is critical for proper metabolism and homeostasis of calcium. Patients with hyperparathyroidism frequently develop elevated serum calcium levels (hypercalcemia) –in fact, most cases of the disease are detected incidentally with on laboratory tests showing hypercalcemia.
Patients with significantly elevated parathyroid levels can develop features such as high blood pressure (hypertension), valvular calcifications, bone pain, abdominal pain, constipation, psychiatric symptoms, and kidney stones.
What Causes Primary Hyperparathyroidism?
Primary hyperparathyroidism is most often caused by a single parathyroid adenoma (tumor). Other possible causes include multiple-gland hyperplasia, multiple adenomas, or parathyroid carcinoma. There appears to be key proto-oncogenes and tumor suppressor genes implicated in the pathogenesis of parathyroid adenomas.
Patients with hyperparathyroidism cannot regulate parathyroid hormone levels according to calcium. Elevated parathyroid hormone levels lead to increased intestinal calcium absorption, calcium reabsorption in the kidney, and bone turnover. This results in high serum calcium levels in most cases. Excessively high serum calcium often causes hypertension, kidney stones, constipation, abdominal pain, and depression. High bone turnover can lead to decreased bone-mineral density (osteoporosis), which is a risk factor for hip fractures.
Secondary hyperparathyroidism is defined as hyperparathyroidism occurring as a result of another underlying disease. The most common cause of secondary hyperparathyroidism is chronic kidney disease (CKD). Impaired kidney function results in calcium, phosphate, and vitamin D regulation. All of these elements play an important role in calcium metabolism and ultimately lead to increase parathyroid hormone response.
Because of the interdependence of calcium, phosphate, vitamin D, and parathyroid hormone (PTH), it is difficult to elucidate the individual contributions of each of the various causes of parathyroid gland dysfunction in patients with CKD.
How Common is Hyperparathyroidism?
Primary hyperparathyroidism is the 3rd most common hormone (endocrine) disorder. It is the most common cause of hypercalcemia. The condition often requires referral to an endocrinology and ear, nose, and throat specialist.
Most people develop the disease around age 50-65.
Signs and Symptoms
Primary hyperparathyroidism is most often detected incidentally on labs due to an elevated calcium level. Symptoms and signs may occur in the setting of significant hypercalcemia and classically include:
- Cardiovascular - hypertension, arrhythmia, hypertrophy, vascular & valvular calcification
- Osteitis fibrosa cystica – bone pain
- Renal findings – nephrolithiasis, nephrocalcinosis, chronic renal insufficiency
- Neuropsychological complaints – depression, memory impairment
- Decreased bone mineral density – osteopenia, osteoporosis
- Gastrointestinal findings - abdominal pain, constipation, gastritis/GERD
- Muscle weakness
Individuals may also experience urinary frequency (polyuria) and excessive thirst (polydipsia). Severely elevated calcium levels can result in cardiac arrhythmias and even lead to death.
Hyperparathyroidism is most commonly diagnosed in asymptomatic individuals who are incidentally found to have elevated calcium on routine laboratory tests. The work up of hypercalcemia includes checking a parathyroid hormone (PTH) level. Patients with hyperparathyroidism will either have an elevated PTH level or a normal level in the setting of elevated calcium levels. Occasionally, hyperparathyroidism is diagnosis in individuals presenting with kidney stones (nephrolithiasis)
Your doctor will usually order additional tests such as urinary calcium excretion, 25-hydroxyvitamin D. If the diagnosis has been confirmed and surgery is being planned, your doctor will typically order a localization imaging study such as ultrasound, nuclear studies (technetium-99m sestamibi), computed tomography (CT), or magnetic resonance imaging (MRI).
Hyperparathyroidism Medication and Treatment
The treatment of acute symptomatic hypercalcemia related to hyperparathyroidism may include:
- Intravenous fluids
- Loop diuretics – Lasix (furosemide)
- Bisphosphonates – Reclast, Zometa (zoledronic acid)
- Corticosteroids – Deltasone (prednisone), Solumedrol (methylprednisolone)
- Calcitonin – especially useful in hyperparathyroidism
Long-term treatment of symptomatic hyperparathyroidism typically includes parathyroid surgery as this leads to a cure. Parathyroid surgery is also associated with a decreased risk of kidney stones, improved bone density, and reduced fracture risk.
Asymptomatic individuals with increased risk for disease progression or end-organ damage may also benefit from surgery. Some patients, have a preference for surgery over medications as it is the only treatment that leads to cure. Occasionally, patients that are not surgical candidates are prescribed Sensipar (cinacalcet) or bisphosphonate therapy such as Fosamax (alendronate).
- Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med 2004; 350:1746. - https://www.ncbi.nlm.nih.gov/pubmed/15103001
- Rubin MR, Bilezikian JP, McMahon DJ, et al. The natural history of primary hyperparathyroidism with or without parathyroid surgery after 15 years. J Clin Endocrinol Metab 2008; 93:3462. - https://jamanetwork.com/journals/jamasurgery/fullarticle/2542667
- Utiger RD. Treatment of primary hyperparathyroidism. N Engl J Med 1999; 341:1301. - https://www.nejm.org/doi/full/10.1056/NEJM199910213411709
The above information is an educational aid only. It is not intended as medical advice for individual conditions or treatments. Talk to your doctor, nurse or pharmacist before following any medical regimen to see if it is safe and effective for you.