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Open access

Radu Mihai and Rajesh V Thakker

Background.

Permanent post-surgical hypoparathyroidism (POSH) is a major complication of anterior neck surgery in general and of thyroid surgery in particular. Depending of diagnostic criteria, up to 10% of patients undergoing bilateral thyroid surgery develop POSH. This leads to a multitude of symptoms that decrease the quality of life and burden the healthcare provision through complex needs for medication and treatment of specific complications, such as seizures and laryngospasm.

Methods.

Narrative review of current medical treatments for POSH and of the experience accumulated with parathyroid allotransplantation.

Results.

In most patients, POSH is controlled with regular use of calcium supplements and active vitamin D analogues but a significant proportion of patients continue to experience severe symptoms requiring repeated emergency admissions. Replacement therapy with synthetic PTH compounds (PTH1-34, Natpara® and PTH1-84, teriparatide, Forsteo®) has been assessed in multicentre trials, but the use of this medication is restricted by costs and concerns related to the risk of development of osteosarcoma.

Based on recent case reports of successful allotransplantation of parathyroid tissue between siblings, there is renewed interest in this technique. Data on selection of donors, parathyroid cell preparation before allotransplantation, site and timing of transplantation, need for immunosuppression and long-term outcomes are reviewed.

Conclusion.

A prospective trial to assess the efficacy of parathyroid allotransplantation in patients with severely symptomatic protracted post-surgical hypoparathyroidism is warranted.

Free access

Fadil M Hannan, Nicholas A Athanasou, James Teh, Christopher L M H Gibbons, Brian Shine, and Rajesh V Thakker

Oncogenic osteomalacia (OOM) is characterised by tumour production of fibroblast growth factor 23 (FGF23) that results in hypophosphataemia and renal phosphate wasting, reduced 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and osteomalacia. Here, we demonstrate the roles of serum FGF23 and 1,25(OH)2D3, together with the lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), as biomarkers for OOM. A previously well 52-year-old man presented with a 2-year history of generalised musculoskeletal pain and proximal myopathy. He had hypophosphataemia, elevated serum alkaline phosphatase activity, low serum 1,25(OH)2D3 and a reduced tubular maximum of phosphate/glomerular filtration rate. These findings indicated a diagnosis of OOM, but magnetic resonance imaging (MRI) and octreotide scintigraphy did not identify any tumours. Treatment with oral phosphate and calcitriol resolved the symptoms and biochemical abnormalities within 6 months. Four years later, he relapsed whilst on treatment with oral phosphate and calcitriol. Serum FGF23 concentration was elevated and MRI identified a 2 cm tumour within Hoffa's fat pad of the left knee. Removal of the tumour resulted in a complete resolution of symptoms and normalisation of the serum biochemical abnormalities including serum FGF23. Histology demonstrated a phosphaturic mesenchymal tumour, mixed connective tissue variant (PMTMCT), which revealed immunostaining with anti-LYVE-1 antibody and hence the presence of lymphatic vessels. Serum FGF23 and 1,25(OH)2D3 were found to be reliable biomarkers for OOM. In addition, the demonstration of lymphatics in the PMTMCT helps to distinguish this tumour from most typical benign haemangiomas.

Open access

Ruth T Casey, Gerlof D Valk, Camilla Schalin-Jäntti, Ashley B Grossman, and Rajesh V Thakker

In viral pandemics, most specifically Covid-19, many patients with neuroendocrine neoplasms (NENs), including phaeochromocytomas, paragangliomas and medullary thyroid carcinoma, may develop Covid-19 in a mild or severe form, or be concerned about the influence of viral infection relative to their anti-tumoral therapy. In general, newly presenting patients should be assessed, and patients recently receiving chemotherapy, targeted therapy or radionuclide therapy, or showing tumour growth, should be closely followed. For previously diagnosed patients, who have indolent disease, some delay in routine follow-up or treatment may not be problematic. However, patients developing acute secretory syndromes due to functional neuroendocrine neoplasms (such as of the pancreas, intestine or lung), phaeochromocytomas and paragangliomas, will require prompt treatment. Patients with life-threatening Covid-19-related symptoms should be urgently treated and long-term anti-tumoral treatments may be temporarily delayed. In patients with especially aggressive NENs, a careful judgement should be made regarding the severity of any Covid-19 illness, tumour grade, and the immunosuppressant effects of any planned chemotherapy, immunotherapy (e.g. interferon-alpha), targeted therapy or related treatment. In other cases, especially patients with completely resected NENs, or who are under surveillance for a genetic disorder, a telephone or delayed consultation may be in order, balancing the risk of a delay against that of the possible development of Covid-19.