A 26-year-old woman of Korean and Irish descent was evaluated for chronic hypercalcemia and complaints of fatigue, body and joint aches, and dental pain for ~4 years. She had no history of kidney stones or other medical problems except for multiple dental caries. Her mother had been treated for tuberculosis in Korea, and her maternal aunt had neck surgery in Korea at ~age 70 reportedly for a parathyroid problem. Physical examination revealed a BMI of 23.3, BP 114/68, P 68, weight 63.6 kg, and absence of dental or jaw lesions and was otherwise unremarkable.
Laboratory studies 4 years prior to presentation revealed calcium levels of 10.3 mg/dL (8.4-10.2 mg/dL) and 10.8 mg/dL, phosphorus 2.4 mg/dL (2.5-4.5 mg/dL), 25 vit D 22 ng/dL (10 to 100 nM), albumin 4.4 g/L (3.4-5.4 g/dL), chloride 106 mM (96-106 mM), and creatinine 0.63 mg/dL (0.52-1.04 mg/dL). She underwent extensive evaluation over 2 years with results of blood and urine studies shown in Table 1 (daughter). Studies revealed mildly elevated calcium and calcitriol and low normal PTH. PPD and chest X-ray were negative, and urine testing favored FHH; however, she refused genetic testing citing the literature on the Internet, suggesting that PHPT is often misdiagnosed as FHH. CT imaging was performed to assess kidney stones, which were absent but, instead, showed a ~3 cm indeterminate lesion of the left iliac wing. It appeared benign on MRI (Figure 1(a)), and subsequent biopsy revealed results consistent with osteitis fibrosis cystica (Figures 1(b)-1(d)). This prompted concern for an atypical case of PHPT with low PTH levels. Further testing revealed low normal values for PTH by dilution, mid-molecule PTH, and PTHrp (Table 1). Dual-energy X-Rray absorptiometry (DXA-Hologic) revealed bone densities and Z scores of 0.717 (Z - 1.2), 0.81 (Z - 2.1), 0.797 (Z - 1.2), and 0.346 (Z - 1.4), in g/cm2, at the femoral neck, spine, hip, and ultra distal forearm, respectively. Parathyroid Tc-99 sestamibi revealed equivocal tracer retention in the right thyroid lobe, yet neck ultrasonography revealed several lymph nodes but no parathyroid adenoma. A 4D CT scan of the neck showed mild prominence of the parathyroid glands and unexpected bilateral mediastinal and hilar lymphadenopathy.
Pulmonary lymph node biopsy revealed noncaseating granulomas consistent with sarcoidosis. A two-month trial of prednisone, 60 mg/d tapered to 20 mg/d, resulted in a normalization of calcitriol, 61 pg/mL and 37 pg/mL (18-72 pg/mL), at weeks 4 and 6, respectively, but no change in calcium, 10.9 mg/dL and 10.8 mg/dL, or PTH, 13 pg/mL and 16 pg/mL (10-65 pg/mL), respectively. Subsequent CT scanning of the chest revealed resolution of lymphadenopathy, and given the combination of elevated calcium, normal PTH, and low urine calcium, suspicion for FHH remained. The bone pathology was reviewed extensively and remained curious, yet its interpretation was not strictly limited to osteitis fibrosis cystica. At this time, she refused further medical evaluation and sought consultation from an endocrine surgeon.
The case was presented and discussed at a multidisciplinary treatment conference, and the patient was counselled by the endocrine surgeon that parathyroid surgery was unproven in this scenario but could be considered based on her symptoms and she requested to proceed with parathyroidectomy. She underwent a subtotal parathyroidectomy with intraoperative PTH measurements, with a drop from 32 pg/mL to 9 pg/mL, 10 minutes after subtotal resection, leaving a remnant of approximately 20 mg of the left lower parathyroid gland. Intraoperatively, the parathyroid glands appeared minimally hyperplastic, and upon histologic review, they were each composed of 50-80% parathyroid epithelial cells with the rest composed of adipose tissue. Final pathology demonstrated that the left and right upper and left lower parathyroid glands weighed 20, 16, and 15 mg, respectively; two appeared histologically normal and one was hypercellular (Figures 1(g) and 1(h)). She developed postoperative hypoparathyroidism, with calcium 7.2 to 9.1 mg/dL and PTH < 3 to 5 pg/mL, but was maintained on calcitriol and reported an overall improvement in wellbeing and resolution of fatigue and body aches.