Is a Parathyroid Nodule Serious?
A parathyroid nodule is clinically significant and requires immediate biochemical evaluation to determine if it represents functional disease (primary hyperparathyroidism), which can cause serious complications including osteoporosis, nephrolithiasis, and in rare cases, parathyroid carcinoma.
Understanding Parathyroid Nodules vs. Thyroid Nodules
The term "parathyroid nodule" typically refers to an incidentally discovered mass on imaging that appears to arise from parathyroid tissue rather than thyroid tissue. This distinction is critical:
- Parathyroid incidentalomas (PTI) are nodules discovered during thyroid ultrasound whose location and appearance suggest abnormal parathyroid tissue, with a prevalence of approximately 1.2% among patients undergoing thyroid sonography 1
- 37.5% of parathyroid incidentalomas represent functioning parathyroid adenomas causing primary hyperparathyroidism, making biochemical evaluation mandatory 1
- Parathyroid carcinoma, though rare, must be considered in the differential diagnosis of any parathyroid mass and carries significant morbidity and mortality if not treated with en bloc resection 2
Immediate Diagnostic Workup Required
When a parathyroid nodule is identified on imaging, the following biochemical evaluation is mandatory:
- Measure intact parathyroid hormone (PTH) to assess for hyperparathyroidism 3, 1
- Measure total serum calcium AND ionized calcium, as occult primary hyperparathyroidism may present with normal total calcium but elevated ionized calcium 3
- Measure serum phosphorus and albumin to complete the biochemical profile 3
- Obtain bone densitometry if hyperparathyroidism is confirmed, as osteoporosis is a common complication 3
Critical Pitfall to Avoid
Do not rely solely on total serum calcium to exclude hyperparathyroidism. Clinically significant primary hyperparathyroidism may present with persistently normal total calcium but elevated ionized calcium and PTH, particularly in cases of large parathyroid adenomas 3. One case report documented a 2.2-cm hypervascular parathyroid adenoma with PTH of 90 pg/mL (elevated), normal total calcium of 9.9 mg/dL, but elevated ionized calcium of 5.9 mg/dL, associated with osteoporosis 3.
Clinical Significance Based on Functional Status
If Biochemistry Confirms Primary Hyperparathyroidism
Surgical parathyroidectomy is indicated when:
- Severe hyperparathyroidism with hypercalcemia that precludes medical therapy 4
- Hyperphosphatemia that precludes vitamin D sterol therapy 4
- Symptomatic disease including nephroureterolithiasis, bone pain, or osteoporosis 5
- Calciphylaxis with PTH >500 pg/mL (55.0 pmol/L), as parathyroidectomy may provide clinical improvement 4
The efficacy of surgical parathyroidectomy for symptomatic hyperparathyroidism is well-documented, with normalization of PTH and calcium levels postoperatively 4, 3.
If Biochemistry Shows Normal Parathyroid Function
Surveillance is appropriate for non-functioning parathyroid lesions, though the concomitant presence of multinodular goiter or macronodular autoimmune thyroiditis decreases the probability that the lesion represents primary hyperparathyroidism 1.
Imaging Characteristics and Diagnostic Approach
Parathyroid lesions on ultrasound may appear as:
- Hypoechoic oval nodules located posterior or lateral to the thyroid 3
- Hypervascular masses with increased blood flow on Doppler 3
- Cystic lesions with clear fluid containing markedly elevated PTH on aspiration 6
When Imaging is Equivocal
Ultrasound alone cannot reliably differentiate parathyroid from thyroid nodules. If a mass is identified and biochemistry suggests hyperparathyroidism:
- 99mTc-Sestamibi scan should be performed to confirm parathyroid origin, showing increased uptake in the region of the suspected parathyroid lesion 3
- CT with contrast may reveal an enhancing oval lesion with attenuation characteristics slightly different from thyroid tissue 3
- Ultrasound-guided fine-needle aspiration (UG-FNA) with immunohistochemistry can distinguish parathyroid from thyroid tissue when performed by experienced cytopathologists 6
Parathyroid imaging with 99mTc-Sestamibi, ultrasound, CT, or MRI is particularly important prior to re-exploration surgery in cases of recurrent or persistent hyperparathyroidism 4.
Special Considerations
Coexistence with Thyroid Disease
- Thyroid nodules are frequently detected in patients with primary hyperparathyroidism, and conversely, parathyroid lesions may be discovered during thyroid evaluation 5
- In areas of iodine deficiency, thyroid nodules detected by ultrasound in hyperparathyroid patients should be evaluated by scintigraphy even if TSH is normal, as compensated hot thyroid nodules may coexist 5
- If both parathyroid adenoma and hot thyroid nodules are present, combined parathyroid and partial thyroid resection should be performed 5
Parathyroid Carcinoma
Though rare, parathyroid carcinoma must be considered when:
- A tender nodule is present at the thyroid pole that has been present for years 2
- PTH is markedly elevated (three times the upper limit of normal or higher) 2
- En bloc resection is the treatment of choice, as disease prognosis is influenced by the extent of initial resection and the presence of metastases 2
Summary Algorithm
- Identify parathyroid nodule on imaging (ultrasound showing hypoechoic, hypervascular, or cystic mass posterior/lateral to thyroid)
- Measure PTH, total calcium, ionized calcium, phosphorus, and albumin immediately
- If PTH elevated or ionized calcium elevated (even with normal total calcium):
- Obtain 99mTc-Sestamibi scan for localization
- Obtain bone densitometry
- Refer to endocrine surgeon for parathyroidectomy
- If biochemistry normal:
- Consider surveillance with repeat ultrasound
- Reassess if symptoms develop
The key message: A parathyroid nodule is serious if it represents functioning disease, which occurs in more than one-third of cases. Biochemical evaluation is mandatory and cannot be deferred.