Case summary:
A 35-year-old primiparous woman, who had previously undergone a kidney transplant 4 years ago for stage 5 chronic kidney disease (CKD) caused by IgA nephropathy, was referred by her nephrologist to the endocrine clinic for evaluation of her parathyroid hormone (PTH)-dependent hypercalcaemia during her 11th week of pregnancy. Prior to her transplant, she had undergone haemodialysis for 13 months. Her regular medications include prednisone, tacrolimus, azathioprine, aspirin and nifedipine.
Upon reviewing her test results, it was found that a plasma corrected calcium level was 2.82 mmol/L (reference range 2.15-2.55), with an elevated serum PTH level of 7.2 pmol/L (reference range 1.6-6.9). A serum 25-hydroxyvitamin D level was sufficient at 60 mmol/L. Phosphate was 0.87 mmol/L (reference range 0.8-1.5), creatinine level 70 umol/L, and estimated glomerular filtration rate (eGFR) >90 ml/min/1.73m2. 24-hour urine calcium:creatinine ratio was 0.0159 ruling out familial hypocalciuric hypercalcaemia. Pre-transplant test results showed significantly elevated serum PTH levels of 103-136.4 pmol/L and post-transplant there were intermittent episodes of mild hypercalcaemia (range 2.60-2.69 mmol/L) and PTH elevation (7.9-9.2 pmol/L).
The patient was advised to drink at least 3 litres of fluids per day. A parathyroid sestamibi scan and neck ultrasound were planned for the second trimester, but the patient expressed hesitation despite reassurance of the low radiation risk. Unfortunately, due to the development of pre-eclampsia, the patient delivered her baby prematurely at 28 weeks gestation. Postpartum plasma calcium levels remained persistently elevated at 2.81 mmol/L, with serum PTH levels also elevated at 10.6 pmol/L.
Seven months later, the patient returned to the clinic with a strong desire to undergo curative parathyroidectomy surgery in order to plan her second pregnancy and reduce the risk of pre-eclampsia. Parathyroid sestamibi scan revealed delayed uptake in both the left and right inferior poles of the thyroid, while the neck ultrasound showed a multinodular goitre with five colloid nodules and a solid nodule measuring 1.0cmx0.7cm in the left inferior aspect, suggesting the presence of a single adenoma.
The patient was referred to an experienced head and neck surgeon who performed a parathyroid neck exploration. All four parathyroid glands were visibly enlarged, and the surgeon proceeded to subtotal parathyroidectomy (removing 3.5 of the 4 hyperplastic glands). The postoperative PTH level remained mildly elevated at 8.5 pmol/L. However, considering the normalised serum calcium level and risk of postoperative hypoparathyroidism, it was decided not to remove any additional parathyroid tissue.
During a post-operative clinic visit, the patient was advised that a high-calcium diet might help to suppress the serum PTH level during a period of enhanced calcium uptake into the skeleton. Bone Mineral Density (BMD) by DXA (Lunar Prodigy) revealed osteopenia in the lumbar spine (L2-L4; BMD 1.012g/cm2, T-score -1.6 SD) and normal bone densities in the hip and forearm. These bone densities were stable when compared to a previous DXA in 2018. Fasting bone turnover markers were not elevated. Despite the persistently elevated serum PTH level, the plasma calcium level remained within the normal range. Due to excessive weight gain, the patient was advised to switch from dairy products to calcium supplements in order to reduce caloric intake.
Literature review:
Post transplant hyperparathyroidism (PT-HPT) is a common occurrence in kidney transplant patients, and while it usually resolves within a year, recent studies have shown that it can persist in a significant percentage of recipients at the one-year mark (17-50%) [1].
Several risk factors contribute to PT-HPT including prolonged dialysis, the use of calcimimetic drugs, pre-transplant levels of PTH exceeding 31.8 pmol/L, and hypercalcaemia at the time of transplantation [2]. The clinical manifestations of PT-HPT mimic primary hyperparathyroidism and differ from the secondary hypoparathyroidism observed in non-transplant chronic kidney disease (CKD) patients. Complications of PT-HPT include increased mortality, higher risk of graft failure, decreased bone density and increased fracture rate [3].
Managing hypercalcaemia resulting from PT-HPT is challenging due to the lack of large-scale randomised controlled trials to guide treatment decisions. While imaging studies may occasionally identify a single parathyroid adenoma, the more common scenario is that of diffuse hyperplasia. Cinacalcet can be considered as a treatment option since it reduces serum PTH and calcium levels without negatively impacting graft function. In cases of moderate to severe hypercalcaemia or when patients experience symptoms, parathyroidectomy is the preferred treatment option [4].
Limited data is available on managing hypercalcaemia in pregnancy related to PT-HPT. Hypercalcaemia poses significant risks for both the mother and the foetus, including pre-eclampsia, miscarriage, nephrolithiasis, pancreatititis and neonatal hypocalcaemia [6]. The treatment approach for PT-HPT in pregnancy would be similar to that of primary hyperparathyroidism and involves maintaining an adequate fluid intake (at least 3 litres per day). Depending upon the severity of the condition, parathyroidectomy surgery may be considered during the second trimester [5].
Key messages:
References