Can you describe the presentation, diagnosis, and treatment of parathyroid adenoma?

Parathyroid Adenomas: Presentation, Diagnosis, and Treatment

Clinical Presentation

Parathyroid adenomas cause primary hyperparathyroidism (PHPT) in 80-85% of cases, presenting most commonly with asymptomatic hypercalcemia discovered on routine laboratory testing, though symptomatic patients may experience bone pain, nephrolithiasis, weakness, and neuropsychiatric symptoms. 1, 2, 3

Key Clinical Features:

• Hypercalcemia with inappropriately normal or elevated parathyroid hormone (PTH) is the biochemical hallmark that distinguishes PHPT from other causes of hypercalcemia 2
• Classic symptomatic presentation includes recurrent kidney stones, bone demineralization with pain, muscle weakness, and gastrointestinal complaints 1, 4
• Hypertension is a recognized secondary manifestation, as PHPT is listed as a secondary cause of hypertension in major cardiovascular guidelines 4
• Pediatric cases are rare but typically present with symptomatic hypercalcemia, though asymptomatic presentations can occur 2
• Palpable neck mass is uncommon but may occur with giant adenomas (>2-3 cm) 1

Important Diagnostic Pitfall:

Urinary calcium excretion is usually normal or high in PHPT, which helps distinguish it from familial hypocalciuric hypercalcemia (FHH), where urine calcium-to-creatinine ratio is characteristically low 2

Diagnostic Approach

Biochemical Confirmation (Required First):

Diagnosis requires biochemical confirmation with elevated serum calcium and elevated or inappropriately normal PTH levels before any imaging is performed. 5, 4

• Measure serum calcium and intact PTH simultaneously 5
• Include 25-OH Vitamin D levels to exclude hypovitaminosis D as a secondary cause of elevated PTH 5
• Imaging has no role in diagnosing hyperparathyroidism—it is only indicated for preoperative localization when surgery is planned 5, 4

Preoperative Imaging for Localization:

The combination of ultrasound and 99mTc-sestamibi SPECT/CT is the preferred initial imaging approach, with sensitivities of 76-80% for ultrasound and 93% for sestamibi SPECT/CT. 5

First-Line Imaging:

• Ultrasound is recommended as the initial study by the American Association of Endocrine Surgeons, offering the advantage of concomitant thyroid evaluation with a pooled sensitivity of 76-80% and positive predictive value of 93% 5
• 99mTc-sestamibi scintigraphy with SPECT/CT achieves sensitivity of 93% and PPV of 96%, superior to planar imaging alone 5
• The combination of both modalities is highly sensitive for adenoma localization and facilitates minimally invasive parathyroidectomy 5, 2

When Initial Imaging Fails:

• Four-dimensional CT (4-D CT) is utilized when ultrasound and sestamibi are nonlocalizing, equivocal, or discordant 5, 6
• [18F] F-choline PET/CT can detect ectopic adenomas missed by conventional imaging 7
• Selective venous sampling is reserved for reoperative cases with persistent or recurrent PHPT after noninvasive examinations yield nonlocalizing results, with reported sensitivity of 94% 5

Common Causes of Nonlocalization:

Adenomas may be nonlocalizable by ultrasound due to ectopic location (submandibular, mediastinal, intrathymic), far posterior position, small size (<5mm), multigland disease, or concomitant thyroid pathology 5, 3, 7

Treatment

Surgical excision of the abnormal parathyroid tissue is the only definitive cure for PHPT and is indicated even in asymptomatic patients due to long-term morbidity from chronic hypercalcemia including bone demineralization, nephrolithiasis, and cardiovascular effects. 5, 4, 6

Surgical Approach Selection:

Minimally invasive parathyroidectomy (MIP) with intraoperative PTH monitoring is the preferred approach when preoperative imaging confidently localizes a single adenoma, offering shorter operating times and faster recovery compared to bilateral neck exploration. 6, 1

MIP Requirements:

• Confident preoperative localization through concordant imaging (sestamibi and/or 4D-CT showing same location) 6
• Intraoperative PTH monitoring to confirm adequate resection, with expected >50% decline from baseline within 10-20 minutes after adenoma removal 6, 1
• Median operative time of 80 minutes with minimal blood loss (median 15ml) 8

When Bilateral Neck Exploration is Necessary:

• Multigland disease (multiple adenomas or four-gland hyperplasia) affects 15-20% of PHPT cases and requires exploration of all glands 6
• Discordant, nonlocalizing, or equivocal imaging mandates bilateral exploration 5, 6
• Transcervical thymectomy should be performed concurrently due to risk of supernumerary or intrathymic glands, particularly in hereditary syndromes 5

Special Surgical Considerations:

In patients with concomitant thyroid nodules, thyroid lobectomy or total thyroidectomy may be performed simultaneously. 1, 8

For intrathyroidal parathyroid adenomas (1-6% of cases), careful distinction from thyroid malignancy is essential, as cytological similarities can lead to more extensive surgery than necessary. 3

Postoperative Management:

Monitor ionized calcium every 4-6 hours for the first 48-72 hours postoperatively, and if calcium falls below 0.9 mmol/L, initiate calcium gluconate infusion at 1-2 mg elemental calcium/kg/hour. 4

• Transition to oral supplementation with calcium carbonate 1-2 g three times daily plus calcitriol up to 2 μg/day when oral intake is possible 4
• Expect PTH and calcium levels to decrease in all patients postoperatively; failure to normalize suggests persistent disease 1, 8
• Hungry bone syndrome can occur, particularly after removal of large or long-standing adenomas, requiring aggressive calcium and vitamin D replacement 4

Defining Surgical Outcomes:

• Persistent hyperparathyroidism is defined as hypercalcemia beyond 6 months postoperatively, indicating surgical failure 6
• Recurrent disease is hypercalcemia developing after 6+ months of normocalcemia 6
• No recurrence was observed in properly selected and executed cases on follow-up 8

Genetic Evaluation

In pediatric patients and young adults with PHPT, genetic testing for multiple endocrine neoplasia type 1 (MEN1), MEN2, and hyperparathyroid-jaw tumor syndrome should be performed, as hereditary syndromes account for a significant proportion of cases in this age group. 5, 2

• MEN1 presents with parathyroid hyperplasia or multiple adenomas, requiring subtotal or total parathyroidectomy with autotransplantation 5
• MEN2A carriers with "moderate" risk RET alleles have variable risk for PHPT and should avoid central neck dissection during prophylactic thyroidectomy to preserve parathyroid glands 5
• Surveillance recommendations for at-risk individuals include annual serum calcium and intact PTH measurements beginning at age 8-16 years depending on syndrome and mutation 5