Primary Hyperparathyroidism in Sickle Cell Disease: An Unknown Complication of the Disease in Adulthood

Abstract

Primary hyperparathyroidism (pHPT) is the third most common endocrine disorder and usually affects patients between 60 and 70 years of age. To our knowledge, this condition has never been studied in young patients with sickle cell disease (SCD). Our objective was to describe the clinical and biological characteristics of pHPT in adult patients with SCD and its management. We conducted a retrospective study that included SCD patients who were diagnosed with pHPT in four SCD referral centers. pHPT was defined by the presence of elevated serum calcium levels with inappropriate normal or increased parathyroid hormone (PTH) serum levels or histopathological evidence of parathyroid adenoma or hyperplasia. Patients with severe renal impairment (GFR <30 mL/min) were excluded. Twenty-eight patients (18 women, 64%; 22 homozygous genotype, 79%) were included. The median age at pHPT diagnosis was 41 years (interquartile range –IQR- 31.5–49.5). The median serum calcium and PTH concentration were, respectively, 2.62 mmol/L (IQR 2.60–2.78) and 105 pg/mL (IQR 69–137). Bone mineral density (BMD) revealed very low BMD (≤−2.5 SD) in 44% of patients explored (vs. 12.5% among 32 SCD patients matched for SCD genotype, sex, age, and BMI, p = 0.03). Fourteen patients (50%) received surgical treatment, which was successful in all cases, but four of these patients (29%) presented with pHPT recurrence after a median time of 6.5 years. Three of these patients underwent a second cervical surgery that confirmed the presence of a new parathyroid adenoma. These results suggest that SCD is a condition associated with pHPT in young subjects. SCD patients with pHPT have a high risk of very low BMD. A diagnosis of pHPT should be suspected in the presence of mild hypercalcemia or low BMD in SCD patients.

Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

“…Our data show a high prevalence of pHPT, reaching 6.8% of our SCD patients, consistent with previous reports [ 21 , 22 ]. To our knowledge, our study is the first to point out that pHPT SCD patients have a similar biological phenotype to that of FHH patients, which is characterized by hypercalcemia with inappropriate PTH levels and low urinary calcium excretion [ 24 , 25 ].…”

“…However, the biological pattern shown in Figure 1 looks very similar, despite genuine pHPT in SCD patients being responsible for the stress associated with the handling of renal calcium tubular in SCD population. Daily calcium intake and bone status was unfortunately lacking in this study and should be part of the metabolic workup in this population, as the prevalence of very low bone mass density in pHPT SCD patients was reported in one study [ 21 ].…”

“…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 ]. SCD patients with pHPT were further analyzed and reported to mainly experience adenoma (90% of patients who underwent surgical treatment) and to be mostly clinically asymptomatic with mild hypercalcemia.…”

The Utility of the Cl:PO4 Ratio in Patients With Variant Versions of Primary Hyperparathyroidism

“…Classic primary hyperparathyroidism (pHPT), a state of excess PTH release coupled with hypercalcemia, is due to a parathyroid adenoma (80%), followed by sporadic parathyroid hyperplasia, and very rarely parathyroid carcinoma, or one of the multiple endocrine neoplasia syndromes. 1 The increase in PTH and calcium negatively affects the patient and presents as fatigue, constipation, mental slowing, kidney stones, bone pain, and fractures due to osteopenia/porosis. Hypercalcemia accelerates small- and medium-size vessel occlusive disease, leading to heart and cerebrovascular ischemic conditions.…”

“…When parathyroid hormone (PTH) is released from the parathyroids, it acts on the intestines and kidneys to increase calcium absorption, stimulate osteoclasts in the bone to induce bone remodeling, and therefore increases levels of calcium in circulation. Classic primary hyperparathyroidism (pHPT), a state of excess PTH release coupled with hypercalcemia, is due to a parathyroid adenoma (80%), followed by sporadic parathyroid hyperplasia, and very rarely parathyroid carcinoma, or one of the multiple endocrine neoplasia syndromes 1 . The increase in PTH and calcium negatively affects the patient and presents as fatigue, constipation, mental slowing, kidney stones, bone pain, and fractures due to osteopenia/porosis.…”