Pregnancy outcome in a renal transplant recipient with residual mild tertiary hyperparathyroidism
Article first published online: 22 OCT 2004
BJOG: An International Journal of Obstetrics & Gynaecology
Volume 112, Issue 1, pages 124–125, January 2005
How to Cite
Morton, A., Dalzell, F., Isbel, N. and Prado, T. (2005), Pregnancy outcome in a renal transplant recipient with residual mild tertiary hyperparathyroidism. BJOG: An International Journal of Obstetrics & Gynaecology, 112: 124–125. doi: 10.1111/j.1471-0528.2004.00314.x
- Issue published online: 22 OCT 2004
- Article first published online: 22 OCT 2004
A 26 year old woman presented for preconception counselling. Eight years previously, she had received a live related kidney transplant for end-stage renal failure due to reflux nephropathy. Five years later, bilateral native nephrectomies were performed because of severe hypertension, with angiography excluding significant stenosis of the renal transplant artery. Inactive problems were previous disseminated tuberculosis and herpes zoster. Her medications included azathioprine, prednisolone, felodipine, atenolol, hydralazine, ranitidine, sodium bicarbonate and iron. Serum creatinine had ranged between 0.14 and 0.18 mmol/L during the preceding two years, 24-hour urine protein was 0.72 g/day, haemoglobin was 97 g/dL and serum urate was 0.34 mmol/L.
There was evidence of mild residual tertiary hyperparathyroidism with ionised calcium 1.4 mmol/L (normal 1.2–1.3 mmol/L), corrected calcium 2.74 mmol/L (2.15–2.6 mmol/L) and serum parathyroid hormone 14 pmol/L (1–7 pmol/L). Bone mineral density a year earlier was normal. She was commenced on iron and folate supplements, and methyldopa and labetalol were substituted for atenolol, hydralazine and felodipine with good control of blood pressure on home and office monitoring.
No information on outcomes of pregnancy complicated by tertiary hyperparathyroidism could be obtained from a literature search, nor on personal communications with leading authorities in the areas of transplantation, renal disease and pregnancy. Six months later she conceived. At 13 weeks, serum testing estimated a risk of trisomy 21 of 1:16. This was assumed to be a false result related to her renal dysfunction. A nuchal translucency scan estimated the risk at 1:7000. By 17 weeks of gestation, haemoglobin had fallen to 82 g/dL with serum ferritin 222 μg/L. Darbopoetin 30 μg a week was commenced with the haemoglobin rising to 118 g/dL over the next eight weeks. At 30 weeks of gestation, her blood pressure rose without other evidence of superimposed pre-eclampsia. Darbopoetin was ceased and nifedipine was added because of intolerance of higher doses of methyldopa. At 32 weeks of gestation, she was admitted to the hospital because of progressive hypertension. Serum creatinine had risen from 0.14 to 0.16 mmol/L in the preceding week (normal for pregnancy 0.04–0.07 mmol/L), serum urate was 0.4 mmol/L, the degree of proteinuria was stable,and there was loss of variability on cardiotocogram. After betamethasone administration, caesarean section was performed with delivery of a male infant with birthweight 1568 g. The mothers' blood pressure and renal function improved after delivery with excellent blood pressure control on irbesartan alone and serum creatinine of 0.12 mmol/L at the time of discharge six days postpartum. She elected not to breastfeed because of uncertainty regarding the safety of azathioprine. During the course of pregnancy and the postpartum period, her degree of hypercalcemia was stable (Fig. 1). The paediatric team was notified of the risk of neonatal hypocalcemia and tetany prior to delivery. Her son's calcium was checked on cord blood then on a daily basis. He was noted to have mild hypocalcemia 24 hours after delivery with ionised calcium 0.95 mmol/L (normal 1.00–1.18 mmol/L) and was treated with intravenous calcium gluconate. Hyaline membrane disease was of moderate severity requiring nasal continuous positive airway pressure for five days, prematurity associated jaundice was treated with phototherapy, patent ductus arteriosus was treated with indomethacin and non-descent of the right testicle was noted at birth. An ultrasound of the kidneys and urinary tract was normal.
Tertiary hyperparathyroidism occurs when there is hypercalcemia due to autonomously hyperfunctioning parathyroid tissue following prolonged parathyroid stimulation by prior hypocalcemia in the setting of renal failure. It is usually due to four-gland parathyroid hyperplasia, as distinct from a single gland adenoma which makes up more than 80% of cases of primary hyperparathyroidism. Residual hyperparathyroidism after renal transplantation is common, with as few as 22.6% of patients having normal parathyroid hormone concentrations after transplantation.1–3 Predictive factors include pre-transplantation parathyroid hormone levels and post-transplantation graft function. Indications for surgical intervention for persistent hyperparathyroidism after renal transplantation include corrected calcium greater than 3.0 mmol/L more than one year post-graft and symptomatic hypercalcemia. This is the first case of pregnancy outcome in a woman with tertiary hyperparathyroidism of which we are aware. A recent review noted 145 cases of primary hyperparathyroidism in pregnancy reported in the literature to date.4 The management of primary hyperparathyroidism in pregnancy is controversial. Maternal complications of primary hyperparathyroidism in pregnancy including hyperemesis gravidarum, pancreatitis, hypercalcemic crisis and nephrolithiasis have been reported to occur in up to 67% of mothers. Up to 80% of fetuses or neonates in pregnancies to affected mothers have been reported to have complications including miscarriage, stillbirth or neonatal death in 31% of pregnancies, and neonatal tetany in 19%. Based upon this, some authors recommend neck exploration in the second trimester in all pregnant women with primary hyperparathyroidism. These complication rates, however, are from older literature where the maternal disease was severe, and some authors suggest observation is reasonable in those women who are asymptomatic with mild hypercalcemia. Early neonatal hypocalcemia in infants of diabetic mothers or those who are premature usually occurs in the first 24–48 hours of life. Hypocalcemia in infants born to mothers with primary hyperparathyroidism tends to occur towards the end of the first week of life, although this may present as late as 10 weeks of age. Signs reported in affected infants include irritability, rapid eye blinking and jerking, facial grimacing and convulsions. It would seem reasonable therefore to measure serum calcium on a daily basis in infants of mothers with hyperparathyroidism, although it is important to warn mothers of the possibility of late onset hypocalcemia and the need for assessment should their infant manifest signs suggestive of this.
Other than mild neonatal hypocalcemia, the complications observed in this pregnancy are in keeping with the degree of maternal renal dysfunction and hypertension preconception, and seem unlikely to be related to the mothers' tertiary hyperparathyroidism. The neonatal course was consistent with prematurity at 32 weeks. We conclude that based upon this case, mild maternal tertiary hyperparathyroidism is not a contraindication to pregnancy, and can be safely observed without intervention. Serum testing for trisomy 21 may be unreliable in the setting of renal dysfunction and other means of quantifying risk such as nuchal translucency should be used.5,6
Accepted 9 May 2004