CASE REPORT

Pregnancy outcome in a renal transplant recipient withresidual mild tertiary hyperparathyroidism

Adam Morton,a Fiona Dalzell,b Nicole Isbel,c Tony Pradob

Case report

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 ne-

phrectomies were performed because of severe hyperten-

sion, with angiography excluding significant stenosis of the

renal transplant artery. Inactive problems were previous dis-

seminated 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 dur-

ing 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 hyper-

parathyroidism 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 supple-

ments, 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 Ag/L. Darbopoetin

30 Ag 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 pre-

ceding 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 im-

proved 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 cal-

cium gluconate. Hyaline membrane disease was of mod-

erate 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.

Discussion

Tertiary hyperparathyroidism occurs when there is hy-

percalcemia due to autonomously hyperfunctioning para-

thyroid 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

BJOG: an International Journal of Obstetrics and GynaecologyJanuary 2005, Vol. 112, pp. 124–125

D RCOG 2004 BJOG: an International Journal of Obstetrics and Gynaecology www.blackwellpublishing.com/bjog

aMater Hospital, South Brisbane, AustraliabMater Private Clinic, South Brisbane, AustraliacPrincess Alexandra Hospital, Woolloongabba, Australia

Correspondence: Dr A. Morton, Mater Hospital, South Brisbane 4101,

Australia.

DOI: 10.1111/j .1471-0528.2004.00314.x

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 symp-

tomatic 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 hyperpara-

thyroidism in pregnancy is controversial. Maternal compli-

cations of primary hyperparathyroidism in pregnancy

including hyperemesis gravidarum, pancreatitis, hypercal-

cemic 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. Hypocalce-

mia in infants born to mothers with primary hyperparathy-

roidism 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 convul-

sions. 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 complica-

tions 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 hyperpara-

thyroidism 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

References

1. Vlcek J, Binswanger U, Keusch G, Zaruba J. Hyperparathyroidism

after kidney transplantation: a retrospective case controlled study. Klin

Wochenschr 1991;69:669–673.

2. Torres A, Rodriguez AP, Concepcion MT, et al. Parathyroid function in

long-term renal transplant patients: importance of pre-transplant PTH

concentrations. Nephrol Dial Transplant 1998;13(Suppl 3):94–97.

3. Botha JF, Botha JR. Parathyroid function after successful renal

transplantation. S Afr J Surg 1997;35:113–116.

4. Schnatz PF, Curry SL. Primary hyperparathyroidism in pregnancy:

evidence-based management. Obstet Gynecol Surv 2002;57:365–376.

5. Cararach V, Casals E, Martinez S, et al. Abnormal renal function as a

cause of false-positive biochemical screening for Down’s syndrome.

Lancet 1997;350:1295.

6. Karidas CN, Michailidis GD, Spencer K, Economides DL. Biochemi-

cal screening for Down syndrome in pregnancies following renal

transplantation. Prenat Diagn 2002;22:226–230.

Accepted 9 May 2004

Fig. 1. Ionised calcium and parathyroid hormone levels during pregnancy and postpartum.

CASE REPORT 125

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