Endocrine Manifestations of Primary Hyperoxaluria

Shatha Murad, MD; Yuval Eisenberg, MD

Disclosures

Endocr Pract. 2017;23(12):1414-1424. 

In This Article

Abstract and Introduction

Abstract

Objective: Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder of oxalate overproduction. It is associated with urolithiasis and nephrocalcinosis, which progress to end-stage renal disease and systemic oxalosis. As oxalate deposits in tissues, non–parathyroid hormone (nonPTH)-mediated hypercalcemia, oxalate osteopathy, primary hypothyroidism, and primary hypogonadism develop. In this review, we will present a case of PH1 and provide an overview of this clinical entity and its endocrine manifestations.

Methods: We conducted a PubMed search for articles related to PH1. The terms "primary hyperoxaluria," "nonPTH mediated hypercalcemia," "hypothyroidism," and "hypogonadism" were used to identify pertinent literature.

Results: Given the rarity of PH1, there is scant literature regarding the incidence and clinical significance of endocrine manifestations of this disorder. There are rare reports of hypercalcemia secondary to osteoclast-stimulating activity of macrophages in bone granulomas, which occur in response to oxalate deposits. We report that hypercalcemia may also be mediated by 1,25-dihydroxyvitamin D and PTH-related protein (PTHrP). Primary hypothyroidism and primary hypogonadism are thought to be due partly to calcium oxalate deposition in thyroid and testicular tissue. The presented case is the first to report PTHrP-mediated hypercalcemia and primary hypogonadism in a patient with PH1.

Conclusion: PH1 is a metabolic disease with significant morbidity and mortality. Owing to its rarity, it is not widely recognized in the field of endocrinology, despite presenting with several endocrinopathies. Recognition of endocrine disturbances can result in early and successful treatment, limiting morbidity and improving quality of life in these challenging patients.

Introduction

Primary hyperoxaluria (PH) is a rare autosomal recessive disorder characterized by errors in metabolism leading to excessive production of oxalate.[1] Oxalate is a metabolic end product that forms a poorly soluble salt, calcium oxalate, which is mainly excreted by the kidneys.[2] Increased excretion and deposition of calcium oxalate in renal tubules and renal parenchyma leads to tubular toxicity, urolithiasis, and nephrocalcinosis and eventual progression to end-stage renal disease (ESRD).[3] When glomerular filtration rates drop below 30 to 45 mL/min/1.73 m2 of body surface area, the kidneys are unable to excrete serum oxalate efficiently, leading to systemic oxalosis.[4] Deposition of calcium oxalate has been described in kidneys, skeleton, blood vessels, heart, joints, skin, bone marrow, retina, central nervous system, and rarely, liver, spleen, thymus, thyroid, and testes.[3,5] This can result in musculoskeletal pain, increased risk of fracture,[6] arthropathy,[7] growth retardation,[6] arrhythmias,[8] atherosclerosis,[8] stroke,[5] retinopathy,[9] resistant anemia and pancytopenia,[10] hypercalcemia,[11–17] hypothyroidism,[17–19] and hypogonadism.

There are three known PH subtypes, each with inherited defects in liver-specific enzymes, leading to overproduction of oxalate.[3] PH1 is the most common and severe form, with a prevalence of 1 to 3 cases per million population and making up 70 to 80% of PH cases worldwide.[20]

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