Case Report

Excessive calcium ingestion leading to milk-alkali syndrome

C S Bailey1, J J Weiner2, O M Gibby3 and M D Penney1

1
Department of Clinical Biochemistry; 2Department of Obstetrics and Gynaecology; 3Department of Endocrinology,
Royal Gwent Hospital, Cardiff Road, Newport, South Wales NP20 2UB, UK
Corresponding author: Catherine S Bailey. Email: Catherine.Bailey@gwent.wales.nhs.uk

Abstract
This report describes the presentation and clinical course of a 40-year-old woman who had an emergency admission for
eclampsia. During routine investigations, she was found to have profound hypercalcaemia, the cause of which was identified
as milk-alkali syndrome, caused by self-medication with antacid tablets for dyspepsia. Treatment with aggressive rehydration,
bisphosphonates and discontinuation of antacid tablets restored normocalcaemia. The patient made a full recovery with
no long-term side-effects. Her male infant was safely delivered with no deleterious effects of exposure to high calcium
concentrations in utero.

Ann Clin Biochem 2008; 45: 527– 529. DOI: 10.1258/acb.2008.008006

Case The patient remained on ICU for 24 hours prior to trans-

A 40-year-old woman presented to the Accident and
Emergency Department with a loss of consciousness, fits
and hypertension (Glasgow Coma Scale [GCS] 15, blood
pressure 169/90 mmHg, pulse 90 beats/minute). She was a
known manic-depressive who was prescribed lithium car-
bonate and the antidepressant venlafaxine, and had a
history of domestic abuse, illicit drug use and pre-
eclampsia. Prior to admission, she had complained of
malaise and fatigue. On examination, she was found to be
38 weeks pregnant (Gravida 8, Para 5). The pregnancy had
been concealed and she had therefore not received any ante-
natal care.
Differential diagnoses on admission were overdose,
eclampsia and encephalitis. Blood taken for routine investi-
gations showed her to be markedly hypercalcaemic (cor-
rected calcium 4.71 mmol/L) with mild renal impairment
(Table 1). Despite this, in light of previous history and clini-
cal presentation, a diagnosis of eclampsia was made. The
patient was given a bolus of 4 g MgSO4 over 15 minutes fol-
lowed by an infusion of 1 g/hour and transferred to theatre
for an emergency caesarean section.
A live male infant was delivered (2.335 kg, apgar 3 and 8
at 1 and 10 minutes, respectively) and transferred to the
neonatal intensive care unit (NICU).
Following surgery, the patient was transferred to the ICU
where she was sedated and ventilated. A rehydration
regimen with normal saline was commenced and di-sodium
pamidronate (15 mg twice daily) to treat the hypercalcae-
mia, together with ramipril to stabilize her blood pressure.
A computed tomography scan of her head to rule out a
pathological cause for the fits was normal.
fer to the high-dependency unit and subsequently the obste-
tric ward. During this time, her calcium concentrations fell,
her blood pressure normalized, bisphosphonate and fluid
treatment were stopped on days 4 and 5, respectively.
Owing to the onset of depression, lithium therapy was
recommenced on day 5.
Biochemical investigations to elucidate the cause of her
hypercalcaemia were unhelpful, demonstrating normal
thyroid, adrenal and parathyroid function, normal tumour
markers and normal serum and urine electrophoresis
(Table 2).
A review by the endocrine team revealed that during
pregnancy she had stopped lithium therapy but had contin-
ued to take venlafaxine. During pregnancy, she had suffered
with thirst and had developed nocturia 3 –4 times per night.
She was a smoker (20 –60 per day) and had frequent bouts
of bronchitis. She denied alcohol and illicit drug use.
There was no family history of calcium, parathyroid or
other endocrine problems. Upon further questioning, the
patient revealed that she regularly took an unknown multi-
vitamin preparation and because of dyspepsia during preg-
nancy had self-medicated with antacids (approximately 24
tablets per day) and four pints of milk per day. This resulted
in a calcium intake of approximately 11 g/day (normal
calcium intake 700– 900 mg/day).
In the absence of any other identifiable cause for the
hypercalcaemia and its resolution upon withdrawal of
excess calcium intake, a retrospective diagnosis of milk-
alkali syndrome (MAS) was made.
The patient made a full recovery from the eclamptic
episode and two weeks after presentation remained

Annals of Clinical Biochemistry 2008; 45: 527– 529

528 Annals of Clinical Biochemistry Volume 45 September 2008
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Table 1 Routine investigations performed during the course of admission

Day 1 Day 2 Day 3 Day 5 Day 7 Day 10
Sodium (mmol/L) 133 139 140 141 – 142
Potassium (mmol/L) 3.3 4.0 3.6 3.5 – 4.5
Chloride (mmol/L) 93 107 109 110 108
Urea (mmol/L) 10.7 11.7 10.2 5.0 – 3.0
Creatinine (mmol/L) 164 150 104 79 – 62
Calcium (mmol/L) 4.53 3.45 3.03 2.33 2.17 2.21
Albumin (g/L) 33 19 22 27 32 34
Corrected calcium (mmol/L) 4.71 3.91 3.43 2.63 2.37 2.37
Phosphate (mmol/L) 1.08 0.92 0.72 – – 0.77
Random glucose (mmol/L) 5.3 4.0 – – – –
Urate (mmol/L) 0.78 0.62 0.53 0.35 – –
CRP (mg/L) ,10 25.4 86.1 15.6 – –
Lithium (mmol/L) ,0.20 – – – 0.32 0.36
Hb (g/dL) 12.9 8.3 10.1 10.1 – 9.8
WCC (109/L) 19.1 11.8 12.4 10.7 – 13.1
Platelets (109/L) 185 128 202 358 – 565
pH 7.576 7.468 7.449 – – –
pCO2 (kPa) 6.2 4.5 5.2 – – –
pO2 (kPa) 12.9 10.3 10.0 – – –
Bicarbonate (mmol/L) 32 23.9 26.6 – – –

CRP, C-reactive protein; WCC, white cell count


Day of admission

normocalcaemic (corrected calcium 2.37 mmol/L; reference MAS is characterized by the metabolic triad of hypercal-
range 2.2– 2.6 mmol/L). The infant made good progress caemia, renal impairment and metabolic alkalosis together
on NICU and was discharged home with no apparent ill with a history of excess calcium and absorbable alkali
effects caused by the exposure to high concentrations of intake. The symptoms associated with the condition are
calcium in utero. consistent with those observed in hypercalcaemic states
(e.g. nausea, vomiting, urinary frequency and electrocardio-
graphy changes). If left unrecognized, it can lead to meta-
Discussion static calcification, renal failure and death.
MAS is a rare, serious and potentially life-threatening cause The mechanisms through which the metabolic sequelae
of hypercalcaemia. Typically, it is thought of as a historical develop have been characterized5 and create a vicious
disease occurring as a complication of the treatment of circle leading to perpetuation of symptoms. Ingested
peptic ulcer disease using the Sippy regimen: an antacid calcium is primarily absorbed in the duodenum, under the
regimen aimed at neutralizing gastric acid and to promote regulation of 1,25 OH2 vitamin D, where it reacts with the
healing of peptic ulcers.1,2 The advent of histamine-2 (H2) intestinal acid to produce ionized calcium.6 This may be
receptor blockers for the treatment of peptic ulcers in the neutralized by sodium bicarbonate to produce a CaCO3
early 1980’s has significantly reduced the incidence of the precipitate, which further reacts with inorganic phosphate
condition; however, a small number of cases continue to to form a precipitate or be absorbed in the duodenum
be reported, with the majority linked to over-the-counter leading to the development of hypercalcaemia. The hyper-
antacid preparations.3,4 calcaemia causes a renal concentrating defect because of
resistance to the action of arginine vasopression on the col-
lecting duct: a form of nephrogenic diabetes insipidus. The
Table 2 Investigations performed in the assessment of resultant dehydration and volume depletion may worsen
hypercalcaemia the hypercalcaemia and the concomitant vomiting associ-
Test Result Reference range ated with hypercalcaemia worsens the volume depletion.
Volume depletion leads to a reduction in the glomerular fil-
PTH (Day 2) 13 12– 65 ng/L
PTH (Day 7) 32 12– 65 ng/L
tration rate (GFR), while hypercalcaemia causes arteriolar
Free T4 12.9 10.3 – 25 pmol/L vasoconstriction in the kidney leading to a reduction in
TSH 0.39 0.20 – 4.50 mU/L tubular sodium re-absorption, acute tubular necrosis,
s-ACE 17 8– 52 IU/L nephrocalcinosis and tubulointerstitial fibrosis. This can
AFP 60 0– 10 ku/L cause renal dysfunction through decreased GFR or direct
PTH-rp ,7.0 0– 2.6 pmol/L
1,25 (OH2) vitamin D ,7.0 8– 50 ng/mL
tubular damage.
CA125 31 IU/l 0– 30 U/mL The development of metabolic alkalosis is not due solely
CA19-9 6 0– 60 U/mL to the ingestion of alkaline substances, such as the calcium
Random cortisol 407 100– 680 nmol/L carbonate found in antacid tablets, as even in large
CEA 1 0– 5 mg/L
amounts the quantity of absorbable alkali contained
PTH, parathyroid hormone; TSH, thyroid-stimulating hormone; within them is not sufficient to cause a metabolic alkalosis.7
AFP, alphafetoprotein; s-ACE, serum angiotensin converting enzyme Instead, the alkalosis develops because of the

................................................................................................................................................
hypercalcaemia and the associated suppressed parathyroid
hormone (PTH) that stimulate the Naþ/Hþ exchanger to
secrete hydrogen ions and therefore increase the renal
re-absorption of bicarbonate. Alkalosis causes increased
calcium resorption in the distal collecting system of the
kidney, compounding the degree of hypercalcaemia.
Treatment of MAS is reliant on discontinuation of the
source of excess calcium and absorbable alkali, coupled
with volume repletion and if necessary, calciuric therapy.
Volume repletion is aggressive and aimed at breaking the
perpetuating cycle of metabolic abnormalities triggered by
the hypercalcaemia. During volume repletion, it is essential
that electrolyte concentrations are monitored and depleted
analytes replaced. Fluid balance must also be assessed and
volume overload treated with diuretics. If necessary, calcito-
nin therapy can be used to promote calciuria. In patients
whose calcium concentrations fail to fall following rehydra-
tion and pharmacological interventions, haemodialysis
using a calcium-free dialysate may be useful.
The risk of developing MAS during pregnancy is
increased due to a state of increased calcium absorption,
mediated by human placental lactogen, 1,25 di-hydroxy
vitamin D and prolactin.8 This, together with the potential
for volume depletion caused by hyperemesis, may predis-
pose pregnant women to develop MAS.9 In addition to
the deleterious effects on maternal health caused by MAS,
the exposure of the fetus to hypercalcaemia in utero can
cause significant morbidity and mortality.10 Despite this,
only a small number of cases are reported in the
literature.4,11,12
The patient described in this report was a multiparous
woman who presented with seizures associated with
eclampsia. Routine biochemical investigations demon-
strated significant hypercalcaemia and a metabolic alkalosis,
which was subsequently attributed to MAS caused by the
ingestion of a large number of antacid tablets coupled
with a high milk intake, resulting in a total calcium intake
in excess of 11 g per day. Unexpectedly, serum PTH
measured on day 2 was low-normal. The reason for the
lack of suppression of PTH in the presence of hypercalcae-
mia is unclear although it may be in part related to the
24 hours of aggressive rehydration and pamidronate
therapy that had been administered prior to sample
Bailey et al. Milk-alkali syndrome 529
collection. During this 24-hour period, the serum calcium
fell from 4.71 to 3.91 mmol/L and the rate and the magni-
tude of this change may have had an effect on serum PTH
concentrations. However, there is no evidence in the litera-
ture to support this theory. Following treatment, the hyper-
calcaemia resolved and three months after discharge the
patient remained normocalcaemic.
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(Accepted 16 April 2008)