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Abstract
Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients; (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT; (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p < 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.
Highlights
Homozygous sickle cell disease (SCD), known as sickle cell anemia, is one of the most prevalent monogenic disorders in the world and is most found in sub-Saharan Africans or people with African ascendance [1]
Primary hyperparathyroidism is an endocrine disorder caused by the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands, with the diagnosis generally being established on the association of hypercalcemia, elevated PTH levels and high urinary calcium excretion [18]
This retrospective monocentric study in Tenon Hospital between January 2011 and December 2020 (Assistance Publique des Hôpitaux de Paris, France) included three different cohorts of patients: (1) Renal stone patients referred to our Department of Physiology for hypercalcemia with a final diagnosis of Primary hyperparathyroidism (pHPT); (2) Homozygous SCD patients referred to our department for a routine metabolic evaluation; (3) Patients referred for hypercalcemia with a final diagnosis of inactive calcium-sensing receptor (CaSR) mutation, called familial hypocalciuric hypercalcemia (FHH), after gene sequencing
Summary
Homozygous sickle cell disease (SCD), known as sickle cell anemia, is one of the most prevalent monogenic disorders in the world and is most found in sub-Saharan Africans or people with African ascendance [1]. Primary hyperparathyroidism (pHPT) is an endocrine disorder caused by the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands, with the diagnosis generally being established on the association of hypercalcemia, elevated PTH levels and high urinary calcium excretion [18]. This disease was not a focus in SCD patients, despite several case reports [19,20], until a recent paper by Denoix et al reported a 5% prevalence of pHPT [21,22]. This raised the issue of the biochemical features of these patients compared to pHPT renal stone patients and, more broadly, of the determinants of the handling of renal tubular calcium in an SCD population
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