Background:
Diagnosing primary hyperparathyroidism during pregnancy is difficult due to changes in parathyroid hormone (PTH), calcium and 1,25 Vitamin D absorption and the presence of parathyroid hormone-related peptide (PTHrP)1. Our case demonstrates that rapid PTH degradation with in individuals, and delayed laboratory processing of samples can influence the interpretation of PTH.
Case:
TL, 27yo F G5P1M4, was transferred to our tertiary centre at 25-weeks’ gestation with pancreatitis. She had recurrent pancreatitis from an unclear aetiology with associated exocrine insufficiency. Previously 2014, she had a caesarian-section at 32-weeks’ gestation due to pancreatitis and severe pre-eclampsia. Retrospectively, she was hypercalcaemic at that time, however, was not previously investigated.
On presentation to our centre in 2022, she was hypercalcaemic (CorrCa 3.12mmol/L, ionised calcium 1.54mmol/L). Her creatinine was 43umol/L and vitamin D 117nmol/L. The urinary calcium:creatinine ratio was 0.0124.
Initial PTH was low but not completely supressed at 1.7pmol/L (1.0pmol/L-7.0pmol/L). Serial testing of PTH levels unexpectedly varied. A lower PTH level was noted in samples that had delayed processing times (Figure 1). Samples processed immediately found PTH to be inappropriately normal in keeping with PTH-dependent hypercalcaemia.
We hypothesised that PTH variability was impacted by the time to sample analysis. PTH stability was assessed on the Atellica Assay by collecting paired blood samples (SST and EDTA tubes) from 10 individuals (n=5 pregnant, n=5 non-pregnant) and comparing them to TL’s samples. Each pair was serially measured for PTH second-hourly for 10 hours. No significant difference was observed between SST and EDTA samples at baseline. However, as time progressed, large variations in PTH hormone were detected in both SST and EDTA tubes for control subjects (11% reduction and 5.3% increase at 10 hours, respectively) (Figure 2). Comparatively, TL’s PTH fell even more rapidly during this time by 38.1% and 12.5% in the SST and EDTA tube respectively.
Ultrasonography and 4D-CT of the neck confirmed a 5x9x6mm right inferior parathyroid adenoma. TL was refractory to medical therapy and proceeded to a parathyroidectomy on day 26 of admission. Her calcium subsequently normalised and she proceeded to an uneventful term delivery.
In summary, PTH becomes more unstable over time and may degrade rapidly in some individuals, making the diagnosis of PTH-dependent hypercalcaemia challenging. This case demonstrates the immense value in having a responsive chemical pathology team. With their assistance, we were able diagnose and offer curative treatment for a young pregnant woman with significant morbidity relating to hypercalcaemia.