Biochemical Predictors and Clinical Characteristics for the Development of Cytopenia and Bone Marrow Involvement...

The clinical features associated with primary hyperparathyroidism (PHPT) giving rise to bone marrow fibrosis are poorly documented. We hypothesised that the severity of PHPT may contribute to the development of this complication.

We identified two clinical cases managed within our clinical service and reviewed case reports and cohort studies using search terms, inter alia, 'primary hyperparathyroidism,' 'pancytopenia,' 'myelofibrosis' and 'bone marrow fibrosis,' utilising PubMed, Google Scholar, Microsoft Academic Search and Web of Science. We excluded patients with chronic renal failure and/or secondary hyperparathyroidism. Studies lacking a histological assessment of bone marrow were also excluded.

We identified a total of 41 reports that satisfied our search criteria, comprising individual cases and three previously reported cohorts. Of these, 27 cases were excluded as they had secondary hyperparathyroidism from renal failure, or because an alternative aetiology for bone marrow fibrosis, such as toxin exposure, was identified. In addition, one large cohort of patients with PHPT and cytopenia was excluded due to the absence of a bone marrow biopsy and missing key biochemical and skeletal data. The included reports consisted of 11 individual cases of bone marrow fibrosis associated with PHPT, along with 2 small cohorts of 17 and 8 patients, respectively. Common clinical features across the 11 case reports included markedly elevated parathyroid hormone (PTH) levels (mean ± SD: 130 ± 95.8 pmol/L; normal range: 1.1-6.9 pmol/L), low serum 25-hydroxyvitamin D (median [IQR]: 20.0 [17.0-30.0] nmol/L; normal range: 75-150 nmol/L) and significantly elevated alkaline phosphatase (ALP) (median [IQR]: 361 [293-1372]) U/L; normal range: 30-120 U/L). Bone marrow fibrosis in this instance is reversible following excision of the culprit parathyroid lesion.

Bone marrow fibrosis associated with PHPT occurs predominantly in the setting of severe biochemical disease, characterised by markedly elevated PTH and ALP levels and may present with variable patterns of cytopenia. While symptom duration varies widely, disease severity rather than chronicity appears to be the principal determinant for bone marrow involvement. Haematological abnormalities are reversible following parathyroidectomy, highlighting the importance of timely diagnosis and intervention.