Water-Clear Cell Parathyroid Adenoma Causing Delayed Diagnosis and Negative Imaging in Primary Hyperparathyroidism.

Parathyroid water-clear cell adenomas are rare causes of primary hyperparathyroidism, with fewer than 30 cases reported in the medical literature worldwide. Over the years, these tumors have been associated with delayed diagnosis and treatment, as well as challenges in the management of hyperparathyroidism. We report the case of a 36-year-old female with a medical history of stage IV chronic kidney disease who presented with a large parathyroid adenoma composed predominantly of clear cells. Her diagnosis was delayed due to negative preoperative imaging findings despite markedly elevated parathyroid hormone levels of 1,100 pg/mL (reference range: 10-65 pg/mL) and serum calcium of 10.9 mg/dL (reference range: 8.0-10.5 mg/dL) while on cinacalcet therapy. A sestamibi parathyroid scan with SPECT/CT failed to localize the adenoma. However, given that the patient met multiple criteria for surgery-including young age, distal forearm osteoporosis, and a creatinine clearance below 60 mL/min-she was referred for parathyroidectomy. Intraoperatively, a large parathyroid adenoma was identified, which had not been detected on preoperative imaging. Histopathologic examination revealed a predominance of clear cells with fewer than 10% oxyphil cells and fewer than 5% chief cells, consistent with the water-clear cell subtype of parathyroid adenoma. Sestamibi imaging depends on delayed radiotracer washout from mitochondria-rich oxyphil cells; therefore, the high false-negative rate for this subtype may be attributed to its glycogen-rich, mitochondria-poor cytoplasm, which allows rapid tracer washout. Recognizing these tumors is crucial for the early diagnosis and appropriate management of primary hyperparathyroidism.