Hyperparathyroidism – Diagnosis, Symptoms, and Treatment

What is Primary Hyperparathyroidism?

Primary hyperparathyroidism is a medical condition characterized by elevated parathyroid hormone levels due to excessive synthesis and released by the parathyroid gland. This typically occurs in the setting of a parathyroid adenoma (tumor). The condition usually affects older 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). Most cases of the disease are detected incidentally, with 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?

Single parathyroid adenoma (tumor) is the most common cause of primary hyperparathyroidism. Other possible causes include multiple-gland hyperplasia, multiple adenomas, or parathyroid carcinoma. There appear to be critical 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), a risk factor for hip fractures.

Secondary hyperparathyroidism is 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. These elements play an essential role in calcium metabolism and ultimately lead to increased parathyroid hormone response.

Because of the interdependence of calcium, phosphate, vitamin D, and parathyroid hormone (PTH), it is challenging 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 endocrinologist and an ear, nose, and throat specialist.

Most people develop the disease around age 50-65.

Signs and Symptoms

Primary hyperparathyroidism is most often detected incidentally in 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.

Diagnosis

Hyperparathyroidism is most commonly diagnosed in asymptomatic individuals who are incidentally found to have elevated calcium on routine laboratory tests. The workup of hypercalcemia includes checking a parathyroid hormone (PTH) level. Patients with hyperparathyroidism will either have an elevated PTH level or an average level in the setting of high calcium levels. Occasionally, hyperparathyroidism is a 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 prefer surgery over medications as it is the only treatment that leads to a cure. Occasionally, patients that are not surgical candidates are prescribed Sensipar (cinacalcet) or bisphosphonate therapy such as Fosamax (alendronate).

References:

1. Bilezikian JP, Silverberg SJ. Clinical practice. Asymptomatic primary hyperparathyroidism. N Engl J Med 2004; 350:1746. - https://www.ncbi.nlm.nih.gov/pubmed/15103001
2. 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
3. Utiger RD. Treatment of primary hyperparathyroidism. N Engl J Med 1999; 341:1301. - https://www.nejm.org/doi/full/10.1056/NEJM199910213411709