Hrev_master [page 82] [Emergency Care Journal 2018; 14:7703] Emergency Care Journal 2018; volume 14:7703 Abstract McKittrick-Wheelock syndrome is a rare condition character- ized by secretory diarrhea due to villous adenoma of the colon, acute renal failure, dehydration, electrolyte and acid-base disor- ders. Diagnosis requires high suspicion especially when the pres- entation is unusual. Although potentially fatal for its complica- tions, if promptly diagnosed and treated it is completely reversible. We present a case of a 67-year-old man who presented with syn- cope and diarrhea. On admission arterial blood gas test showed a complex acid-base disorder that led clinicians to further investiga- tions and to point out a correct diagnosis. Introduction Since its first description in 19541 only a few cases of McKittrick-Wheelock syndrome (MWS) have been described in literature. This rare syndrome is characterized by secretory diar- rhea, often without pain, caused by a secretory colorectal tumor, most notably villous adenomas.2,3 Adenomas of the colon are usu- ally asymptomatic or cause mild gastrointestinal symptoms, but a range from 0.76-2.4% of them could become secretory4 leading, potentially, to a severe loss of fluid and electrolyte due to a muci- nous diarrhea. The consequences are severe dehydration with acute renal failure, significant electrolyte abnormalities and acid-base imbalance, making MWS a potentially lethal condition.2,3 Over 100 cases of MWS have been reported in literature,4 despite that some authors believe it is not rare as often thought.5 Considering that MWS is a potential life-threatening condition it’s essential to include it in the work up of a patient with diarrhea, depletion syn- drome, electrolyte and acid-base abnormalities. Sometimes acid- base imbalance can provide precious information for the diagnosis as in our case of MWS with a triple acid-base disorder. Case Report A 67-year-old man presented to our Emergency Department with head trauma, secondary to orthostatic syncope. His recent medical history showed watery diarrhea for the previous 3 days (5- 6 times per day) without fever nor abdominal pain. His past med- ical history was not relevant apart from a cholecystectomy, a pre- vious perianal abscess and lower back pain. He was not taking medications. Vital signs were normal (BP 120/80 mmHg, HR 96/min, SpO2 on room air 97%, apyretic). On physical examina- tion the patient showed evidence of fluid depletion with dry mucous membranes and obtundation. Abdomen examination was normal. Electrocardiogram revealed U waves. Chest-radiograph and head CT scan were unremarkable. Arterial blood gas test high- lighted mild alkalemia (pH 7.491; pCO2 19.6 mmHg; pO2 116 mmHg; HCO3 - 14.8 mEq/L; Anion Gap 35.2 mEq/L; lactic acid 6.4 mmol/L; Na+ 116 mEq/L; Cl- 66 mEq/L). Blood tests demonstrated hemoconcentration, neutrophilic leukocytosis, renal failure, hyponatremia, hypokalemia and hypochloremia. Serum biochem- istry is shown in Table 1. A contrast-enhanced CT scan of the abdomen put on view a pseudo-nodular thickening of the rectosig- moid colon with narrowing of the lumen and upstream dilatation. After admission renal failure and electrolyte disorders improved with intravenous fluids and electrolyte replacement. A colonoscopy showed a voluminous polypoid mass with villous appearance in the rectum at 10 cm from the anal orifice, extending to the rectosigmoid junction and involving the 50% of the bowel lumen. The histopathological examination diagnosed a tubulovil- lous adenoma with areas of high-grade dysplasia. The final diag- nosis was hypovolemia, acute renal failure, electrolyte and acid- base imbalance in patient with mucous diarrhea and tubulovillous adenoma. On hold of surgical treatment, the persistence of diarrhea with severe fluid loss and hyponatremia required hospital re- admission for hydroelectrolytic replacement. Therefore, anterior resection of the rectum was performed. Postsurgical recovery was Correspondence: Pietro Formagnana, Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, V.le Golgi 19, 27100 Pavia, Italy. Tel.: +39.0382.502571. E-mail: pietro.formagnana01@universitadipavia.it Key words: McKittrick-Wheelock syndrome; Metabolic alkalosis; Mucinous diarrhea; Electrolyte disorders. Contributions: the authors contributed equally. Conflict of interest: the authors declare no potential conflict of interest. Funding: none. Received for publication: 18 July 2018. Accepted for publication: 27 August 2018. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright P. Formagnana et al., 2018 Licensee PAGEPress, Italy Emergency Care Journal 2018; 14:7703 doi:10.4081/ecj.2018.7703 The McKittrick-Wheelock syndrome: A rare case with a complex acid-base disorder Pietro Formagnana,1 Marianna Piombo,1 Costanza Caccia Dominioni,1 Giulia Gori,1 Michele Santoro,2 Ivo Casagranda3 1Department of Internal Medicine, IRCCS Policlinico San Matteo Foundation, Pavia; 2Emergency Department, General Hospital Cardinale Panico, Tricase; 3Specialization School of Internal Medicine, University of Pavia, Pavia, Italy Non -co mmerc ial us e o nly [Emergency Care Journal 2018; 14:7703] [page 83] positive, with progressive clinical improvement and complete reversal of the biochemical abnormalities. Discussion MWS is classically characterized by a triad: i) chronic secreto- ry diarrhea due to a colorectal tumor; ii) severe dehydration with acute renal failure; iii) electrolyte abnormalities and acid-base imbalance.6,7 According to literature most of reported cases are due to vil- lous adenoma, with some cases secondary to adenocarcinoma or neuroendocrine tumor.8 Only a little percentage (0.76-2.4%) of vil- lous adenomas become secretory4 and the etiopathogenesis of this process is not completely clear. Secretory and nonsecretory villous adenomas show differences on microscopic and ultrastructural examinations. Secretory adenomas are characterized by abundant and atypical mucin-filled goblet cells that produce exaggerated mucus amount with abnormal composition.2 Furthermore, evi- dences support the hypothesis of a secretagogue mediated diarrhea, due to the activation by tumor of PGE2 and adenylate cyclase path- ways, that are responsible of water and electrolyte depletion from adenoma cells.2,9,10 Despite many authors suggest a strict dichoto- my between secretory and non-secretory villous adenomas2 some evidences support the hypothesis of a secretory continuum, making cases of MWS the extreme end.11 The result of losses can reach to 1.5-3.5 L of fluid/day with large amount of electrolyte,12 leading some author to use the expression neoplastic cholera.13 Characteristically in early stages these losses can be compensated by renal adaptation and oral intake, but as tumor size increases compensatory mechanisms become exhausted.3 Moreover, this is the reason why almost only distal tumors are implicated in MWS genesis, preventing adequate water and electrolyte reabsorption.8 Clinical picture may change from patient to patient and symp- toms are usually related to electrolyte depletion and acute renal failure.14 First of all, diagnosis requires a high index of suspicion. Choi et al.15 suggest that in case of prerenal failure, electrolyte abnormalities and diarrhea, the existence of an intestinal adenoma should always be considered. Despite aggressive hydroelectrolyte disorders correction can be consider the cornerstone of successful management, definitive treatment requires endoscopic16 or surgical excision of the tumor.6,8 Some studies have shown the usefulness of indomethacin and somatostatin especially for poor surgical candidate.4,9,10 The case we described meets the diagnostic criteria of MKS, such secretory diarrhea due to villous adenoma, acute renal failure and electrolyte and acid-base disorders. Clinical features were sim- ilar to those already reported in literature.8,15 Despite above, our patient shown a complex and rare acid-base disorder. In fact, most of the villous adenomas secrete potassium and bicarbonate leading to hyperchloremic metabolic acidosis that could be complicated by an anion gap metabolic acidosis secondary to renal failure.6 Sometimes, as in our patient, adenomas could excrete mainly chlo- ride rather than bicarbonate with potassium, causing metabolic alkalosis.17 If we analyze our patient’s acid-base balance we can find a triple acid-base disorders: i) anion gap metabolic acidosis (AG 34.6 mEq/L) secondary to renal failure and to a lesser extent to hyperlactatemia (6.4 mmol/L); ii) metabolic alkalosis due to enteric chloride secretion and water loss with renal HCO3 - reten- tion (identified on the basis of Na/Cl ratio > 1.5 [1.76] and ΔAG>ΔHCO3 - [22>10]) and iii) respiratory alkalosis probably related to anxiety. In this way alkalemia is the result of the balance between alkalosis (metabolic and respiratory) and metabolic acido- sis. Therefore, as Pucci et al.18 suggest, even if the most common acid-base balance feature in MWS is metabolic acidosis, the pres- ence of metabolic alkalosis in a patient with mucous diarrhea and renal failure should raise the suspicion of a chloride-excreting vil- lous adenoma. Conclusions To our knowledge only a few cases with MWS and metabolic alkalosis have been reported.18,19 Moreover most of authors have focused on electrolyte disorders3,8,12,15 giving less importance to the acid-base imbalance. MWS syndrome is a rare condition that may develop life-threatening complications, but if promptly diagnosed and treated is completely reversible. Complex acid-base disorders are the outcome of the interplay between different pathophysiolog- ical mechanisms and the accurate interpretation of acid-base bal- ance can provide precious information to the clinicians. The coex- istence of metabolic alkalosis and mucous diarrhea (with or whithout renal failure) should raise the suspicion of a chloride- excreting villous adenoma leading to an early diagnosis. References 1. McKittrick LS, Wheelock FC Jr. Carcinoma of the colon. Springfield, IL: Charles C. Thomas Publisher; 1954;61. 2. Older J, Older P, Colker J, Brown R. Secretory villous adeno- mas that cause depletion syndrome. Arch Intern Med 1999;159:879-80. 3. Lee YS, Lin HJ, Chen KT. McKittrick-Wheelock syndrome: a rare cause of life-threatening electrolyte disturbances and vol- ume depletion. J Emerg Med 2012;43:e171-3. 4. Kagan MD, Schmidt K, Sangha G. Indomethacin therapy effective in a patient with depletion syndrome from secretory villous adenoma. BMJ Case Rep 2017;2017:bcr2016217211. 5. Caliskan C, Makay O, Firat O, et al. McKittrick-Wheelock syndrome: is it really rare? Am J Emerg Med 2010;28:105-6. 6. Podestà MA, Cucchiari D, Merizzoli E, et al. 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