Journal of Taibah University Medical Sciences (2013) 8(1), 50–53

Taibah University

Journal of Taibah University Medical Sciences

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Case Report

Calcium homeostasis in a patient with hypoparathyroidism during

pregnancy, lactation and menstruation
a,* b
Omar M. Al Nozha, SSCIM and Pardis Malakzadeh-Shirvani, MD

a
Department of Medicine, Faculty of Medicine, Taibah University, Almadinah Almunawwarah, Kingdom of Saudi Arabia
b
Jewish General Hospital, McGill University, Montreal, Quebec, Canada

Received 26 September 2012; revised 11 November 2012; accepted 4 January 2013

KEYWORDS Abstract Objective: To report a case of hypoparathyroidism post-thyroidectomy in a woman with

Calcium; variable calcium requirements during pregnancy
Hypoparathyroidism; Methods: Clinical and biochemical data were reviewed, and management of hypocalcaemia is
Lactation; described.
Pregnancy; Results: We report on a 37-year-old pregnant woman with hypoparathyroidism post-thyroidec-
PTHrP tomy who had been on stable doses of calcitriol and calcium for many years. During her first preg-
nancy, her calcium requirement increased; however, she was found to be hypercalcaemic
peripartum. She resumed menstruation while breastfeeding and experienced hypocalcaemic symp-
toms around menstruation. Her second pregnancy was complicated by profound symptomatic hyp-
ocalcaemia at 9 weeks of pregnancy, coinciding with the cessation of breastfeeding and mimicking
‘hungry bone syndrome’. This has not been described previously.
Conclusion: Our case confirms that the calcium requirement is increased during early pregnancy
and after weaning but is decreased during late pregnancy, puerperium and lactation. This case high-
lights the importance of close follow-up of calcium levels in women with hypoparathyroidism dur-
ing gestation and lactation, especially for consecutive pregnancies.
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Introduction decrease in late pregnancy, puerperium and during lactation.1,2

Kovacs et al.,3 in their review of calcium disorders during preg-
Although there is controversy about the calcium requirements nancy and lactation, listed some of the reasons for the conflict-
during early pregnancy, there is general agreement that they ing data, such as interpreting the physiological drop in total
* Corresponding address: Assistant Professor of Medicine, Department of Medicine, Faculty of Medicine, Taibah University, P.O. Box 30088,
Almadinah Almunawwarah 41477, Kingdom of Saudi Arabia. Tel.: +966 48618100; fax: +966 48484800.
E-mail: alnozhah@hotmail.com (O.M. Al Nozha)
Peer review under responsibility of Taibah University.

Production and hosting by Elsevier

1658-3612 ª 2013 Taibah University. Production and hosting by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.jtumed.2013.01.003
 O.M. Al Nozha and P. Malakzadeh-Shirvani
calcium in early pregnancy as an increased requirement. A case
report of a woman in whom primary hypoparathyroidism was
diagnosed during pregnancy suggests exacerbation of such
symptoms in early pregnancy.4 Case reports indicate that the
calcium requirement is increased after cessation of
breastfeeding.5
There is a paucity in literature on perimenstrual hypocal-
caemic symptoms. Maternal calcium homeostasis has an
important role during pregnancy because of the calcium
requirements of the growing foetus.6 Calcium regulation is
especially important in patients with hypoparathyroidism.
Kovacs et al.1 reviewed case reports of lower calcium and cal-
citriol (1,25-dihydroxy vitamin D) in women with hypopara-
thyroidism during pregnancy than before conception, which
are due to alterations in parathyroid hormone (PTH)-related
peptide (PTH-rp) and other hormones such as oestrogen and
perhaps placental lactogen and prolactin, which regulate in-
creased production of calcitrol by the maternal kidney and de-
cidua. Hypoparathyroid patients absorb less calcium through
the intestine because of loss of vitamin D activation; however,
the increased endogenous calcitriol during pregnancy, which is
not mediated by PTH, eventually increases intestinal calcium
absorption.1,7,8 Hence, the main mediator of changes in mater-
nal calcium metabolism appears to be PTH-rp secretion from
the placenta and mammary glands (post partum and during
lactation), with some contribution from the foetal parathyroid
gland during pregnancy.8 Prostaglandin E2 is also thought to
release calcium from the body stores and may thus increase
the level of blood calcium during delivery. An abrupt drop
in prostaglandin post partum can produce hypocalcaemia.9
Many case reports have been published showing the in-
creased calcium needs of women with hypoparathyroidism
during pregnancy.1,8,10–14 Salle et al.15 described a woman with
an increased calcitriol requirement until the end of pregnancy
but persistently low calcifidiol (25-hydroxy vitamin D), which
remained in the range observed in most pregnant women in
France. Her low calcifidiol cannot, however, be explain the in-
creased calcitriol requirement, as the levels of calcifidiol vary
widely, depending on diet and season, and are decreased to-
wards the end of pregnancy and at term.8
‘Hungry bone syndrome’ is seen as hypocalcaemia after sur-
gery for hyperparathyroidism in patients with severe, pro-
longed disease. We describe calcium homeostasis during
pregnancy coinciding with the cessation of breastfeeding and
mimicking ‘hungry bone syndrome’, which has not been de-
scribed previously.
Case report
A 37-year-old woman was followed-up at the prenatal clinic of
the Jewish General Hospital in Montreal, Quebec, Canada, for
calcium and thyroid hormone regulation during pregnancy.
She had undergone remote thyroidectomy for a benign thyroid
nodule with subsequent hypoparathyroidism that persisted
postoperatively for more than 10 years. During her first preg-
nancy, she had an increased calcium requirement during the
first two trimesters and was found to be hypercalcaemic peri-
partum, starting a few days before delivery until 2 weeks post
partum, with a calcium level (corrected for albumin) of 2.67–
2.74 mmol/l (normal range, 2.12–2.62 mmol/l). Her calcium
and calcitriol intake were adjusted accordingly. The infant
51
Table 1: Results of laboratory investigations at presentation to
the emergency department.
Test Result Normal range
Calcium corrected for albumin (mmol/l) 1.85 2.12–2.62
Ionized calcium (mmol/l) 1.04 1.20–1.35
Albumin (g/l) 40 35–51
Magnesium (mmol/l) 0.88 0.70–1.23
Phosphate (mmol/l) 1.38 0.70–1.45
Creatinine (lmol/l) 57 40–85
Blood urea nitrogen (mmol/l) 5.6 2.5–7.0
Bicarbonate (mmol/l) 23 22–31
Thyroid-stimulating hormone (mU/l) 0.22 0.4–4.5
Alkaline phosphatase (U/l) 101 35–145
was born at term in April 2008 with no complications. While
she was continuously breastfeeding, she menstruated in Octo-
ber and November 2008, at which time she experienced hypo-
calcaemic symptoms. In January 2009, she presented to our
prenatal clinic for her second pregnancy at 9 weeks of gesta-
tion. She had stopped breastfeeding 1 week previously, at
8 weeks of gestation, once she realized that she was pregnant.
Her medication at that time included calcium 2.4 g, calcitriol
0.25 lg and L-thyroxine 100 lg daily.
At presentation, she complained of peri-oral and cheek
numbness with tingling in her hands despite compliance with
her medication. Her vital signs were normal, Chvostek and
Trousseau signs were positive and the rest of the physical
examination was unremarkable. The results of the laboratory
investigations are shown in Table 1; calcifidiol, calcitriol,
PTH and PTH-rp were not measured. The patient was admit-
ted and received 11 g of 10% calcium gluconate intravenously.
Her calcium level was eventually stabilized on oral calcium 8 g
and calcitriol 1 lg daily; the change in calcium level with med-
ication is shown in Table 2. Her calcium requirement de-
creased gradually by the fourth month of gestation, and she
was receiving 4 g calcium and 0.5 lg calcitriol daily near the
end of pregnancy. Her calcium requirement did not decrease
during lactation as had been expected, but she remained stable
on the reduced doses of calcium and calcitriol.
Discussion
This case report confirms the increased requirements for
calcium and calcitriol during early pregnancy. Most observa-
tional studies indicate increased levels of calcitriol and PTH-
rp towards the end of pregnancy.1 One showed that calcitriol
levels peak at term and then drop post partum. Similarly,
the level of PTH-rp is higher at term than during pregnancy
and is maximal 6 weeks post partum. There have been reports
of mothers with untreated hypoparathyroidism who experi-
enced tetany during pregnancy and whose infants had skeletal
findings at birth indicative of intrauterine hyperparathyroid-
ism,12–14 confirming that calcium requirements can be de-
creased by the activity of the fetal parathyroid gland but
also indicating that the increased calcium requirements during
pregnancy should be treated with adequate calcitriol and cal-
cium to prevent hyperparathyroidism in infants.
Kohlmeier and Marcus7 reported that some investigators
found increased free calcitriol as early as the first trimester
while others found no increase until the last month of gesta-
52 Calcium homeostasis in a patient with hypoparathyroidism during pregnancy, lactation and menstruation
Table 2: Changes in calcium concentrations with treatment.
Day 1 Day 2
Treatment
Calcium gluconate, 10% (g/day) 3 2
Calcium carbonate (g/day) 4 5
Calcitriol (Rocaltrol) (lg/day) 0.5 0.75
Calcium measure
Ionized calcium (mmol/l) 0.87 0.96
Total calcium (mmol/l) 1.67 1.86
*
Patient discharged and subsequently followed as an outpatient.
tion, despite persistently elevated levels of the bound form in
normal pregnant women. Currently, there is no clear explana-
tion of the discrepancies in the literature with regard to cal-
cium requirements in early pregnancy. They may be due to
vitamin D stores before conception, and further investigation
is warranted to explore this possibility.
Oral calcium and calcitriol requirements are decreased dur-
ing lactation in hypoparathyroid women.1,5,8,13,16,17 Mather
et al.5 suggested that PTH-rp and prolactin activity account
for the decreased calcium and calcitriol, as the PTH-rP levels
in these women are comparable to or even higher than those
reported in women with intact parathyroids during lactation.
Even in non-lactating women with prolactinomas, PTH-rP
was present in a higher concentration than in controls, and lac-
tating women had still higher levels. Other studies show that
calcitriol levels fall to below normal and eventually increase
during lactation,5,8 indicating that hormones other than
PTH-rp must be responsible for elevated calcitriol during preg-
nancy and the involvement of mechanisms other than calci-
triol. Increased intestinal absorption of calcium mediated by
PTH-rp is another possible explanation for the decreased
requirements for calcium and calcitriol during lactation. Kalk-
warf et al.16 found that increased intestinal absorption of cal-
cium during lactation occurs only after menstruation has
recommenced. They speculated that the low oestrogen concen-
tration and increased bone resorption mediated by PTH-rp
during lactation elevate the serum calcium concentration,
which inhibits signals that stimulate intestinal calcium absorp-
tion. When menstruation recommences, oestrogen levels are
increased and calcium levels are decreased, leading to increased
intestinal calcium absorption by increased calcitriol.16,17
We consider that our patient’s hypocalcaemic symptoms in
the perimenstrual period were probably due to the increase in
oestrogen, which was not completely compensated by in-
creased calcitriol and increased intestinal calcium absorption.
Hypocalcaemia in a hypoparathyroid woman during menstru-
ation was described previously.18 Mallette reported that the
calcitriol level increased when hypoparathyroid patients were
taken off oral contraceptives. Graham et al.19 found no weekly
fluctuation in serum and urine calcium and phosphate with the
menstrual cycle in six women with well-controlled postopera-
tive hypoparathyroidism. Further research is needed to clarify
the etiology of hypocalcaemia associated with menses and why
this occurs only in certain hypoparathyroid women.
The significantly increased calcium and calcitriol require-
ments of our patient early in her second pregnancy may have
been due to the coincident cessation of breastfeeding of her
first child. Weaning is associated with a drop in PTH-rp and
Day 3 Day 4 Day 5 Day 6* Day 7 Day 8
2 2 2 0 0 0
6 7 7 7 8 8
0.75 0.75 0.75 0.75 1 1
0.93 1.04 1.10 1.01 0.98 1.10
2.04 2.23 2.11 2.0 2.14 2.2
an elevation in PTH in women with an intact parathyroid,
whereas the calcium and calcitriol requirements are increased
after weaning in hypoparathyroid women. We hypothesize
that, as PTH-rp and PTH act through the same receptor,
our patient was probably in the high bone turnover state asso-
ciated with elevated PTH-rp (‘hungry bone syndrome’). Her
post-weaning hypocalcaemia probably resulted from acute
reversal of the PTH-rp-induced contribution of bone to mainte-
nance of the serum calcium concentration, exacerbated by the
high levels of oestrogen in early pregnancy. The final effect of
PTH-rp reduction and oestrogen elevation would be an imbal-
ance between osteoblast-mediated bone formation and osteo-
clast-mediated bone resorption, and perhaps other changes
affecting calcium fluxes (such as excretion through the kidneys),
leading to a marked net increase in bone uptake of calcium.
These inconsistencies with regard to calcium and calcitriol
requirements during pregnancy in hypoparathyroid women
obviate guidelines on management. Some studies in the litera-
ture and our own observations indicate, however, that calcium
requirements increase during early pregnancy and decrease to-
wards term. We would agree with Callies et al.,10 who sug-
gested that the serum calcium concentration should be kept
within the lower normal range (2.00–2.20 mmol/l) by daily
supplementary calcium and calcitriol. Further adjustments
should be made to maintain the physiological requirements
during pregnancy. Overall, hypoparathyroid women must be
followed-up closely to prevent undue consequences, especially
during pregnancy, lactation and weaning.
Conclusions
This case confirms that the exogenous calcium requirement of
hypoparathyroid women is increased during early pregnancy
and after weaning but is decreased during late pregnancy,
puerperium and lactation. As conflicting results have been re-
ported with regard to calcium requirements, especially during
early pregnancy, management of hypoparathyroidism during
pregnancy and lactation is challenging; however, there is gen-
eral agreement that exogenous calcium requirements decrease
in late pregnancy, puerperium and during lactation.1–4 In spite
of the lack of consensus or clear guidelines for the manage-
ment of hypoparathyroidism in pregnancy, the general rule is
to continue calcium supplementation with calcitriol through-
out pregnancy. Calcitriol and calcium doses should be adapted
as the pregnancy progresses on the basis of close follow-up for
symptoms of hypocalcaemia and serum ionized calcium levels
(not total serum calcium).3
 O.M. Al Nozha and P. Malakzadeh-Shirvani
Author contributions
Both authors contributed equally in literature review and the
manuscript writing of this case report.
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