Severe hyponatremia secondary to rectal adenocarcinoma: Mckittrick–Wheelock syndrome

McKittrick–Wheelock syndrome is a rare condition described in the context of distal colorectal tumours (in particular villous adenomas, although there have been cases in tubulovillous adenomas and adenocarcinomas), consisting of extreme acute depletion of electrolytes related to secretory diarrhoea. It is difficult to estimate the prevalence of this syndrome, as it is believed to be underdiagnosed, with only the most severe cases being identified.¹

We present the case of an 80-year-old female patient with locally advanced adenocarcinoma of the rectum, for which she underwent a first intervention with a colostomy performed. She subsequently started adjuvant radiotherapy prior to definitive surgery. The patient was referred to Accident and Emergency after suffering a syncope. Blood tests (Table 1) showed no blood gas abnormalities. The family reported abundant rectal discharge of transparent watery secretions in the previous days. Suspecting McKittrick–Wheelock syndrome, fluid and electrolytic replacement was started with 0.9% saline, but there was no response regarding blood analysis values. She was switched to a 3% hypertonic saline infusion, and sodium levels went up in subsequent tests. After stabilising the patient’s blood sodium, we transitioned to oral replacement (500 mg of NaCl every eight hours) with good tolerance, and she had sodium levels at the discharge of 134 mEq/l. She made a good recovery as an outpatient, maintaining adequate electrolyte levels and undergoing surgery one month later without complications in the immediate postoperative period.

Table 1.

Laboratory test results in Accident and Emergency.

Plasma
Na (corrected)	119 mEq/l
K	5.5 mEq/l
Osmolality, calculated	275 mOsm/kg
Creatinine	3.81 mg/dl
Urine
Na	13 mmol/l (54–190)
K	94 mmol/l (20–80)

McKittrick–Wheelock syndrome was first described in 1954 in the context of extensive villous adenomas (>3–4 cm in diameter) in the rectosigmoid region. This type of adenoma has the particular characteristic of producing enormous amounts of mucin, which has a high concentration of electrolytes (mainly sodium, potassium and chlorine). This leads to significant secretory diarrhoea, as the secretions volume exceeds the rectal mucosa’s reabsorption capacity. The symptoms consist of profuse diarrhoea, initially without repercussions at the analytical and haemodynamic level, thanks to renal adaptation. However, although the time frame can vary, they will develop dehydration, acute kidney injury of prerenal aetiology and electrolyte imbalances such as hyponatraemia, which can become severe.² Most patients are asymptomatic, in what is called the “latent phase” and may remain so for several years until they reach the “decompensation phase”.¹ This can make diagnosis complex, especially in cases where there are no haemodynamic repercussions. In the case reported here, the patient already had deterioration in her general condition and analytical repercussions, with acute impairment of kidney function and severe hyponatraemia.

When making a differential diagnosis of hyponatraemia, first of all, it is essential to confirm that it is true hyponatraemia, with decreased plasma osmolality. Extracellular volume then needs to be assessed, which, in our case, was decreased due to dehydration. Lastly, when making the differential diagnosis of the origin of the losses, it is important to quantify ions in urine.³ Our patient had a low urinary sodium concentration, suggesting that the losses were secondary to diarrhoea and supporting the suspicion of McKittrick–Wheelock syndrome.

The pathophysiology of this syndrome is not fully understood, but immunohistochemical studies have shown an overexpression of COX-2 and an increase in prostaglandin E2 in the secretions.⁴ The treatment of choice is intensive fluid therapy prior to surgical excision of the tumour, which brings about a complete cure. However, alternatives have been proposed, such as the use of indomethacin or octreotide for patients who are either not eligible for or are awaiting surgery.¹

In conclusion, McKittrick–Wheelock syndrome should be suspected in a patient with a previous medical history of colorectal carcinoma and secretory diarrhoea with repercussions on fluid/electrolytic balance. Clinical suspicion in these cases is particularly important, as early diagnosis and early surgical treatment determine the patient’s future survival.

Funding

The authors declare that this article did not receive any funding.