Hyperparathyroidism: Clinical sciences

Hyperparathyroidism is when excess parathyroid hormone, or PTH for short, is produced. PTH is produced by the parathyroid glands, which lie behind the thyroid, and it controls calcium balance in the body.

Now, primary hyperparathyroidism occurs when the parathyroid glands autonomously make too much PTH.

In contrast, secondary hyperparathyroidism is caused by an appropriate rise in PTH levels, as the parathyroid glands attempt to correct hypocalcemia caused by other conditions, such as vitamin D deficiency, or chronic kidney disease.

Finally, there’s tertiary hyperparathyroidism, which is usually caused by long-standing secondary hyperparathyroidism that eventually results in parathyroid hyperplasia and unregulated, autonomous PTH overproduction.

Now, if your patient presents with a chief concern suggesting hyperparathyroidism, you should first perform an ABCDE assessment to determine if your patient is unstable or stable.

If unstable, stabilize the airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry, as well as cardiac telemetry. Finally, if needed, provide supplemental oxygen.

Here’s a high-yield fact to keep in mind! Patients with hyperparathyroidism can develop severe or rapidly progressing hypercalcemia, which can cause lethargy, stupor, or even coma. Additionally, an ECG may reveal bradycardia, atrioventricular block, or a shortened QT interval. To normalize serum calcium, you should start intravenous hydration; and diuretics, like furosemide; or bisphosphonates, like zoledronic acid can also be used.

Now, let’s go back to the ABCDE assessment and discuss the stable patients. First, obtain a focused history and physical examination. Many patients with hyperparathyroidism are asymptomatic, but some may report personality and mood changes, trouble concentrating, and even altered mental status. They might also experience gastrointestinal issues, such as abdominal pain, nausea, anorexia, and constipation. Additionally, history might reveal musculoskeletal pain as well as polyuria and polydipsia. Finally, there could be a history of chronic kidney disease, vitamin D deficiency, nephrolithiasis, or low-impact bone fractures.

On the flip side, physical exam findings are typically nonspecific and might include muscle weakness, diminished deep tendon reflexes and signs of dehydration, like dry mucous membranes and poor skin turgor.

Now, here’s another high-yield fact! There’s a mnemonic for the signs and symptoms of hypercalcemia: “groans, bones, stones, thrones, and psychiatric overtones.” Groans represent constipation and muscle weakness, which occur due to decreased muscle contractions. Bones is for bone pain resulting from chronic bone demineralization, while stones refers to nephrolithiasis, since hypercalcemia can lead to hypercalciuria in an attempt to excrete the excess calcium. Finally, thrones refers to the toilet, to remind you of polyuria; and psychiatric overtones remind you of mood changes or altered mental status.

If your patient presents with these signs and symptoms, suspect hyperparathyroidism, and order labs, including a CMP and serum PTH level.

Once you’ve got the results, assess the serum PTH and calcium levels, and don’t forget to correct the serum calcium if albumin levels are abnormal!

Consider alternative diagnosis Now, if the patient’s PTH is low or normal, your patient does not have hyperparathyroidism, so consider alternative diagnoses.

On the flip side, if the serum PTH and calcium are both elevated, diagnose primary hyperparathyroidism.

Next, assess for features of multiple endocrine neoplasia, or MEN, types 1 and 2A.

If the personal or family history reveals a pituitary or pancreatic tumor, order genetic testing to look for mutations in the MEN1 gene. If the mutation is present, diagnose MEN1.

On the other hand, if history reveals pheochromocytoma, or medullary thyroid cancer, order genetic testing to look for mutations in the RET gene. If the mutation is present, diagnose MEN2A.

If an MEN syndrome is diagnosed, be sure to treat any coexisting conditions.

And if the history reveals no coexisting endocrine disorders, we’re looking at sporadic primary hyperparathyroidism.

For both sporadic and MEN-related cases, after primary hyperparathyroidism is confirmed, you should order imaging studies like a neck ultrasound and a Tc-99m sestamibi scintigraphy to localize the affected parathyroid gland; and a DEXA scan to assess bone mineral density.

Now, the preferred treatment for primary hyperparathyroidism is parathyroidectomy, so consult the surgical team.

Alternatively, if your patient is asymptomatic, or not a surgical candidate, you can consider medical management. This includes vitamin D supplementation, bisphosphonates to improve bone mineral density, and calcimimetics to reduce serum calcium levels. Monitor serum calcium and 24-hour urine calcium levels annually, and order regular abdominal ultrasounds to screen for nephrolithiasis; and DEXA scans to monitor bone mineral density.

Now, here’s a clinical pearl! Some rare conditions that cause elevated PTH and serum calcium can mimic primary hyperparathyroidism, including familial hypocalciuric hypercalcemia and lithium-induced hypercalcemia.