MON-750 - Persistent Hypercalcemia after Subtotal Parathyroidectomy Revealing Atypical Familial Hypocalciuric Hypercalcemia

Familial hypocalciuric hypercalcemia (FHH) is a well-recognized, autosomal dominant disorder characterized by mild hypercalcemia, relative hypocalciuria, and normal to elevated parathyroid hormone (PTH) levels. FHH is most commonly caused by inactivating mutations in the calcium-sensing receptor (CASR) gene. Distinguishing FHH from primary hyperparathyroidism (PHPT) may be challenging in atypical presentations; potentially leading to delayed diagnosis or unnecessary surgical intervention.
We present a case of atypical FHH in a 45-year-old patient with recurrent hypercalcemia and a significant maternal family history of hyperparathyroidism. Initial biochemical evaluation revealed a serum calcium of 11.3 mg/dL with a PTH level of 109 pg/mL which is consistent with PHPT. 25-hydroxy Vitamin D levels routinely were above 40 ng/mL. A 24-hour urinary calcium excretion was in the normal range of 189 mg/24 hours and therefore lowered initial suspicion for FHH. Unfortunately Ca/Cr was unable to be calculated, as urine calcium and urine creatine were performed at different times. At this point, the patient opted to not repeat and instead wanted to be worked up for surgical intervention. This was a limitation of our workup, as the CCCR is the most specific urinary test for FHH. The patient later obtained parathyroid sestamibi imaging but this failed to identify a definitive adenoma; thus further complicating the diagnostic workup.
Given the persistent hypercalcemia, combined with normal to high PTH, and in conjunction with a strong family history of PHPT, the patient underwent a subtotal (3.5-gland) parathyroidectomy. This included resection of the left superior, inferior, right superior, and partial resection of the right inferior gland. Intraoperative PTH monitoring showed an appropriate decline. However, postoperative assessment revealed persistent hypercalcemia. This prompted reconsideration of the diagnosis.
Genetic testing using a hereditary hyperparathyroidism panel identified a heterozygous pathogenic CASR variant, c.2383C>T (p.Arg795Trp); confirming FHH type 1. This case highlights the particular diagnostic complexity of atypical FHH; specifically when urinary calcium excretion is within normal range and family history overlaps with PHPT. Patients with persistent hypercalcemia and conflicting lab results should consider early genetic testing to avoid unnecessary surgical intervention. Increased awareness of atypical FHH presentations may improve diagnostic accuracy and patient outcomes.

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