Collision Diagnoses: Primary Hyperparathyroidism Layered on Familial Hypocalciuric Hypercalcemia

Abstract

Objective: Describe the presentation, work-up, and management of a rare co-occurrence of familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism (PHPT) in a single patient. Additionally, to explore the challenges in diagnosing in such patients, summarize the previous literature on this uncommon occurrence, and explore the possible etiologies for it. Methods: Case presentation from a tertiary care academic medical system. Results: Successful diagnosis and surgical management, returning the patient to his previously asymptomatic FHH baseline. Conclusion: FHH and PHPT are both causes of hypercalcemia. Very rarely, these two conditions can occur simultaneously in the same patient. The relationship between these two entities when they present concurrently is complex, likely the result of particular CASR mutations causing greater parathyroid cellular proliferation and an increased predisposition to developing PHPT. These rare patients can be difficult to diagnose, but when recognized appropriately and managed with surgery for the PHPT component, they can achieve an asymptomatic FHH state. (AACE Clinical Case Rep. 2018;4:e362-e366) Abbreviations: CASR = calcium-sensing receptor gene; CaSR = calcium-sensing receptor protein; DXA = dual-energy X-ray absorptiometry; FEca = fractional excretion of calcium; FHH = familial hypocalciuric hypercalcemia; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone

Concomitant familial hypocalciuric hypercalcemia and single parathyroid adenoma: a case report

“…Reevaluation is necessary if the patient presents residual hypercalcemia after parathyroidectomy. In this case, as in a few others, PHPT develops in a patient with known FHH, which may lead to diagnostic delay, as the clinicians may be more likely to attribute the hypercalcemia to the known disease [10,13]. Later presentation of hypercalcemic symptoms or organ manifestations, as in our patient developing general malaise and chronic pancreatitis with no obvious cause, should lead to diagnostic reevaluation.…”

“…A small number of cases have reported parathyroid adenoma in patients with FHH [6][7][8][9][10][11][12][13]. In this case report we present a 47-year-old man with severe hypercalcemia, genetic FHH, and a significant parathyroid adenoma at the lower left gland, without clinically actionable variants in MEN1.…”

A novel CASR variant in a family with familial hypocalciuric hypercalcaemia and primary hyperparathyroidism

“…Another patient of German origin was found to have a novel c.1651A>G p.(Arg551Gly) variant ( 11 ). More recently, one patient was found to have a c.2208G>C, p.(Gly670Arg) variant in the CASR gene ( 12 ). A common feature to all these cases is the fact they all presented with hypercalcaemia along with overlapping features common to both FHH and PHPT.…”