Unexpected outcome ( positive or negative) including adverse drug reactions

CASE REPORT

Syndrome of inappropriate antidiuretic hormone

secretion: a story of duloxetine-induced
hyponatraemia
Adae Opoku Amoako,1 Carina Brown,2 Timothy Riley1
1
Department of Family and SUMMARY and constipation. On presentation, the patient had
Community Medicine, Penn Hyponatraemia is the most commonly encountered symptoms of nausea but had not vomited. She
State Milton S Hershey Medical
Center, Hershey, Pennsylvania, electrolyte abnormality in clinical practice. Syndrome of denied loss of sensation, weakness, difficulty with
USA inappropriate antidiuretic hormone secretion (SIADH) memory and other neurological symptoms. She
2
Penn State College of accounts for nearly 60% of all hyponatraemias. Selective also denied any shortness of breath, chest pain and
Medicine, Hershey, serotonin reuptake inhibitors (SSRIs) are well known to other pulmonary symptoms. The patient’s medica-
Pennsylvania, USA
have side effects of SIADH. There have been few tions on admission included aspirin, pantoprazole,
Correspondence to reported cases of serotonin norepinephrine reuptake polyethylene glycol and quinapril, as well as 30 mg
Dr Adae Opoku Amoako, inhibitors (SNRIs) causing SIADH-induced hyponatraemia. duloxetine, daily. She was not on any diuretic. On
adae_amoako@[Link] Duloxetine is one type of SNRI used to treat several physical examination, she appeared euvolemic,
conditions, including depression and diabetic without signs of dehydration or volume overload.
Accepted 25 March 2015
neuropathy. We present a case of a 76-year-old woman An abdominal X-ray revealed adynamic ileus.
with a history of fibromyalgia who had recently been During initial evaluation, she was found to have
prescribed duloxetine for her condition. On admission to serum sodium of 124 mmol/L.
the hospital, her sodium decreased to a low of
118 mmol/L. Evaluation for other causes of INVESTIGATIONS
hyponatraemia yielded negative results. Duloxetine was The patient’s serum osmolality was 254 mmol/L
discontinued and after 3 days the patient’s sodium and her urine osmolality was 415 mmol/L. Urine
increased to 130 mmol/L. The purpose of this case sodium was found to be 150 mmol/L. Her sodium
report is to highlight the importance of having suspicion continued to decline to as low as 118 mmol/L.
for rare but real side effects of medications such as Thyroid-stimulating hormone (TSH) was found to
duloxetine. be normal at 2.25 mIU/mL and early morning free
cortisol was 1.50 mg/dL. Free T3 was low at
2.7 pmol/L but free T4 was normal at 1.46 ng/dL.
BACKGROUND Haemoglobin was 13.9 g/dL and potassium was
Hyponatraemia, defined as a serum sodium level less 4.3 mmol/L
than 135 mmol/L, is the most commonly encoun-
tered electrolyte abnormality in clinical practice. DIFFERENTIAL DIAGNOSIS
Hospitalised patients and the elderly are at increased Differential diagnosis in the setting of the history
risk of developing hyponatraemia.1 Although often and laboratory findings included adrenal insuffi-
found incidentally on laboratory results, patients ciency and hypothyroidism-induced hyponatraemia.
with hyponatraemia can manifest with headache, However, with a cortisol level of 1.50 mg/dL,
change in mental status, seizures or loss of conscious- adrenal insufficiency was less likely. Regarding
ness. Syndrome of inappropriate antidiuretic hypothyroidism, it appeared that the patient’s
hormone secretion (SIADH) accounts for nearly hypothyroidism was under control, with a normal
60% of hyponatraemia by some studies.2 SIADH is TSH level. She had also carried this diagnosis for a
characterised by clinical euvolemia, low serum osmo- long time with stable sodium. The combination of
lality, inappropriately elevated urine osmolality and
urine sodium greater than 40 mmol/L. Other types of
euvolemic hyponatraemia causes, such as thyroid dys-
function and adrenal insufficiency, must be excluded.
Some of the most common causes of SIADH include
medications such as antiepileptics and antidepres-
sants. A case–control study found that serotonergic
antidepressants increase the risk of hyponatraemia
fourfold.3

To cite: Amoako AO,

Brown C, Riley T. BMJ Case
CASE PRESENTATION
Rep Published online: We present a case of a 76-year-old woman with a
[please include Day Month history of debilitating fibromyalgia, diet-controlled
Year] doi:10.1136/bcr-2014- type II diabetes and hypertension. She presented to Figure 1 The progression of the patient’s serum
208037 the emergency department with abdominal pain sodium in relation to duloxetine administration.
Amoako AO, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208037 1
 Unexpected outcome ( positive or negative) including adverse drug reactions

Figure 2 Algorithm for the differential diagnosis and approach to a patient with euvolemic hyponatraemia.

normal TSH, decreased T3 and a higher than expected cortisol DISCUSSION

level in the setting of hypothyroidism corresponds with euthyr- This case emphasises the diagnostic criteria for SIADH, including
oid sick syndrome and not a true hypothyroid state. A true euvolemia, in the setting of elevated urine osmolality and low
hypothyroid state usually has a low cortisol level. Other differ- serum osmolality (figure 2). Physicians must be aware that medica-
entials to consider in euvolemic hyponatraemia are diuretics use tions that interact with serotonergic pathways commonly cause
and other causes of SIADH such as traumatic brain injury, some SIADH.4 There have been several case reports of
cancers and other medications. Our patient was not on diuretics duloxetine-induced SIADH, some of which suggest that the
and had not had an injury to the brain. She was also not on elderly population is at particularly high risk of drug-induced
other medications that result in SIADH except for the duloxe- hyponatraemia.5 It is suggested that SSRIs and SNRIs such as
tine. It is worth mentioning that hypothyroidism has been duloxetine cause SIADH by increasing ADH secretion via stimula-
reported to be a cause of paralytic ileus. Our patient’s hypothy- tion of α adrenergic and serotonergic receptors in the hypothal-
roid state was due to euthyroid sick syndrome and could have amus.6 Until 2012, previous case reports showed that most
certainly contributed to her ileus. duloxetine-induced SIADH were in women.7–9 This was the case
in our patient. However, in 2012, Choi et al10 reported a case of
duloxetine-induced SADH in a middle-aged male. In most of the
TREATMENT cases reported, hyponatraemia resulted after 2–3 days of starting
The patient was restricted to 1 L of water per day for 6 days. medication. Our patient had started the medication 2 days prior to
She was also administered 0.5 mg sodium chloride tablets twice admission. Treatment of SIADH includes removing the inciting
a day for 5 days. This was increased to three times a day after agent and restricting fluids. In more extreme cases, salt tablets and
no improvement was seen with the former. When a further hypertonic saline may be used.11
three days passed without improvement, the dose was increased
to 1 mg three times daily. On further evaluation, it was discov-
ered that duloxetine had been started 2 days prior to admission.
Learning points
Prior to start of the medication the patient’s serum sodium was
132 mmol/L. The duloxetine was discontinued three days after
the patient’s serum sodium had slowly risen from 118 mmol/L ▸ Consider rare side effects of medications when work ups for
to 129 mmol/L (figure 1). suspected conditions are normal.
Regarding her ileus, the patient had minimal relief from poly- ▸ Medications that interact with serotonergic pathways
ethylene glycol alone so Senna was added to the regimen. In commonly cause syndrome of inappropriate antidiuretic
addition to medications, the patient was turned frequently and hormone secretion (SIADH).
encouraged to ambulate. A repeat abdominal X-ray showed ▸ Treatment for SIADH includes removing the inciting agent
resolved ileus. and restricting fluids.

OUTCOME AND FOLLOW-UP

The patient was discharged at a later date with serum sodium of Competing interests None declared.
130 mmol/L. Patient consent Obtained.

2 Amoako AO, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208037

 Unexpected outcome ( positive or negative) including adverse drug reactions
Provenance and peer review Not commissioned; externally peer reviewed. 6 Roxanas MG. Mirtazapine-induced hyponatraemia. Med J Aust 2003;179:453–4.
7 Stovall R, Brahm NC, Crosby KM. Recurrent episodes of serotonin-reuptake
inhibitor-mediated hyponatremia in an elderly patient. Consult Pharm
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Amoako AO, et al. BMJ Case Rep 2015. doi:10.1136/bcr-2014-208037 3