A 38-year-old man was admitted
because of postprandial vomiting for 2 weeks. He had been
diagnosed as having type 2 diabetes mellitus and hypertension
since 6 years earlier before this admission for which he had
been taking nateglinide and losartan daily, respectively. The
latest serum creatinine was 0.9 mg/dl and glycosylated
hemoglobin (HbA1c) was 7.8% one month prior this admission. He
had been in a habit of alcohol consumption, betel nut chewing
and smoking for more than 5 years. He had been otherwise well
until one month earlier when he noted poor appetite, nausea
and a weight loss of 2 kg in one month. The symptom was
accompanied by abdominal distention and slight abdominal pain.
Two weeks prior to this admission, he developed vomiting after
meals, and the vomitus was formed, undigested food and did not
contain blood or bile. One week later, he developed general
malaise and daily urine amount decreased, followed by
constipation 3 days before this admission.
On arrival at this hospital, he
was ill-looking and appeared in respiratory distress. The
conjunctivae was relatively pale. The blood pressure measured
at the Emergent Department was 116/67 mmHg which was lower
than what he usually recorded. The pulse rate 88 beats per
minute, respirations 26 breaths per minute. The conjunctiva
was pale and sclera not icteric. Pupils were isocoric with
prompt light reflex. No lymph nodes were palpable. His breath
sounds were clear. There were no audible cardiac murmurs. The
abdomen was soft and flat without tenderness. The liver and
spleen were not palpable, and no shifting dullness was noted.
Her bowel sounds were normoactive. No flank percussion
tenderness was noted. The extremities were warm without
cyanosis. There were no skin rashes or discoloration.
Serum creatinine was 6.9 mg/dL and
pyuria and urine turbidity were noted. Serum calcium was 4.05
mmol/dL and a test of arterial blood gas while he was
breathing ambient air revealed pH 7.47, PCO2 43.7 mmHg, PO2
64.6 mmHg, and HCO3-
31.7
mEq/L with a base excess of 7.4 mEq/L.
Chest radiography was negative and abdominal radiography while
he was in supine position revealed intestines containing
much fecal material. Aminotransferse, amylase, and lipase levels were
normal. Under the impression of hypercalcemia with acute renal
failure, he was admitted to this hospital.
After admission, hydration and
diuretics were continued and betal nut-related milk-alkali
syndrome was highly suspected because of acute renal failure,
hypercalcemia and metabolic alkalosis. Serum intact
parathyroid hormone (iPTH) level was <3.00 pg/mL (reference
range, 12-72 pg/mL). immunofixation electrophoresis [IFE]
showed no monoclonal gammopathy. After hydration was
administered, his serial laboratory data showed improving
renal function and resolution of hypercalcemia one day later.
Insulin was replaced by nateglinide daily after renal function
improved. After the hypercalcemia and acute renal failure
resolved, he was discharged and follow-up at OPD. After
discharge, he quitted betel nut chewing and cigarette smoking.
< Laboratory data
> 1. Hemogram on
arrival at this hospital
WBC /μl |
RBC M/μl |
Hb g/dl |
Hct % |
MCV fL |
MCHC g/dl |
PLT K/μl |
12.27 |
4.01 |
10.1 |
38.1 |
95.0 |
34.4 |
255 |
Meta % |
Band % |
Seg % |
Eos % |
Baso % |
Mono % |
Lym % |
0 |
0 |
75.5 |
2.3 |
0.2 |
8.1 |
13.9 |
2. Biochemistries and serum electrolytes on arrival at this
hospital
Test |
BUN mg/dl |
Cre mg/dl |
Na mmole/L |
K mmole/L |
Ca mmole/L |
P mg/dl |
Mg mmole/l |
Reference value |
4.5-24 |
0.6-1.3 |
135-148 |
3.5-5.3 |
2.02-2.60 |
2.7-4.5 |
0.7-1.03 |
Result |
48.3 |
6.9 |
131 |
4.1 |
4.05 |
4.3 |
0.33 |
Test |
Glucose Mg/dL |
GOT U/L |
GPT U/L |
T-Bilirubin mg/dl |
|
|
|
Reference value |
70-110 |
♂<37,<31♀ |
♂<41,<31♀ |
0.2-1.2 |
|
|
|
Result |
123 |
28 |
18 |
1.03
|
|
|
|
3. Urinalysis on arrival at this hospital
Variables |
Sp Gr. |
PH |
Protein mg/dl |
Glucose g/dl |
Ketone |
OB |
Urobil EU/dl |
Result |
1.01 |
7.5 |
20 |
- |
- |
- |
0.1 |
Variables |
Bil |
RBC /HPF |
WBC /HPF |
Epi /HPF |
Cast /LPF |
Crystal |
Bacteria |
Result |
- |
- |
20 |
- |
- |
- |
- |
< Discussion
> Hypercalcemia in an
adult who is asymptomatic is usually due to primary
hyperparathyroidism. In malignancy-associated hypercalcemia
the disease is usually not occult; in such patients the
interval between detection of hypercalcemia and death is often
<6 months. Accordingly, if an asymptomatic individual has
had hypercalcemia or some manifestations of hypercalcemia,
such as kidney stones, for >1 or 2 years, it is unlikely
that malignancy is the cause. Nevertheless, differentiating
primary hyperparathyroidism from occult malignancy can
occasionally be difficult, and careful evaluation is required,
particularly when the duration of the hypercalcemia is
unknown. Hypercalcemia that is not related to
hyperparathyroidism or malignancy can result from excessive
vitamin D action, high bone turnover from any of several
causes, or from renal failure. Dietary history and a history
of ingestion of vitamins or drugs are often helpful in the
diagnosis of some of the less frequent causes. PTH
immunoassays based on double-antibody methods serve as the
principal laboratory test in differential diagnosis.
A detailed
history may provide important clues regarding the etiology of
the hypercalcemia. Chronic hypercalcemia is most commonly
caused by primary hyperparathyroidism, as opposed to the
second most common etiology of hypercalcemia, an underlying
malignancy. The history should include medications, previous
neck surgery, and systemic symptoms suggestive of sarcoidosis
or lymphoma.
Once
true hypercalcemia is established, the second most important
laboratory test in the diagnostic evaluation is a PTH level
using a two-site assay for the intact hormone. Increases of
PTH levels are often accompanied by hypophosphatemia. In
addition, serum creatinine should be measured to assess renal
function; hypercalcemia may impair renal function, and renal
clearance of PTH may be altered depending on the fragments
detected by the assay. If the PTH level is increased (or
"inappropriately normal") in the setting of an elevated
calcium and low phosphorus, the diagnosis is almost always
primary hyperparathyroidism. Since individuals with familial
hypocalciuric hypercalcemia (FHH) may also present with mildly
elevated PTH levels and hypercalcemia, this diagnosis should
be considered and excluded because parathyroid surgery is
ineffective in this condition. A calcium/creatinine clearance
ratio (calculated as urine calcium/serum calcium divided by
urine creatinine/serum creatinine) of <0.01 is suggestive
of FHH, particularly when there is a family history of mild,
asymptomatic hypercalcemia. Ectopic PTH secretion is extremely
rare.
A suppressed
PTH level in the face of hypercalcemia is consistent with
non-parathyroid-mediated hypercalcemia, most often due to a
underlying malignancy. Although a tumor that causes
hypercalcemia is generally overt, a PTHrP level may be needed
to establish the diagnosis of hypercalcemia related to
malignancy. Serum 1,25(OH)2
D levels are
increased in granulomatous disorders, and clinical evaluation in combination
with laboratory testing will generally provide a confirmatory diagnosis.
Milk-alkali syndrome
Intensive treatment with
calcium-containing antacids and milk was first used in the
early 20th century for the treatment of peptic ulcer disease
and sometimes was associated with toxicity, eventually known
as the milk alkali syndrome. Despite the introduction of H2
blockers and proton pump inhibitors for the treatment of
peptic ulcer disease, the milk alkali syndrome continues to
occur but is seen more frequently in older women who are
receiving treatment for osteoporosis. The milk alkali syndrome
provides a unique opportunity to discuss calcium homeostasis
in a setting in which the primary calcium regulatory hormones,
parathyroid hormone (PTH) and calcitriol, are not overtly
abnormal.
Betel nut
Betel nut is a common
masticatory drug used in Far East Asia, India, and the South
Pacific. It is used daily by 600 million people worldwide, yet
is unknown to most Western physicians. As the world becomes
more culturally and ethnically interconnected, physicians of
emergency service will encounter the complications related to
use of betel nut. Significant illness can be associated with
its use, including exacerbation of asthma, cholinergic crisis,
cardiac arrhythmias, acute psychosis, milk-alkali syndrome,
and oropharyngeal tumors. Betel nut use refers to a
combination of three ingredients: the nut of the betel palm
(Areca catechu), part of the Piper betel vine, and lime.
Anecdotal reports have indicated that small doses generally
lead to euphoria and increased flow of energy while large
doses often result in sedation. Although all three ingredients
may contribute to these effects, most experts attribute the
psychoactive effects to the alkaloids found in betel nuts
< References
>
- Nelson BS, Heischober B. Betel nut:
a common drug used by naturalized citizens from India, Far
East Asia, and the South Pacific Islands. Ann Emerg Med
1999;34:238-43. 2.
- Wu KD, Chuang RB, Wu FL, Hsu WA, Jan
IS, Tsai KS. The milk-alkali syndrome caused by betelnuts in
oyster shell paste. J Toxicol Clin Toxico. 1996;34:741-5. 3.
- Lin SH,
Lin YF, Cheema-Dhadli S, Davids MR, Halperin
ML. Hypercalcaemia and metabolic alkalosis with betel nut
chewing: emphasis on its integrative
pathophysiology. Nephrol Dial Transplant 2002;17:708-14.
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