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Surreptitious laxative abuse
GASTROENTEROLOGY
CLINICAL
77:7RO-786,1979
CONFERENCE
Surreptitious A. I. MORRIS
Laxative
Abuse
and L. A. TURNBERG
Department of Medicine, United Kingdom
Hope
Hospital,
University
Vast amounts of laxatives are consumed in the Western world. This unsurprising statement is illustrated by the following figures. In 1975, in the USA, $130 million were spent on laxatives, and in the UK, the National Health Service spent E7 million’ and probably several times this amount was sold over the counter. Between 15 and 30% of the population over the age of 60 take laxatives regularly,” and they can choose from among the 700 or so different preparations available in the USA’ or the 200 available in the UK.4 The larger variety produced in the USA probably reflects the greater spirit of competitiveness in American industry rather than a severer degree of national constipation for, if anything, bowel “awareness” is more prominent in the UK. The carefully refined, fiber-depleted diet, so rightly under attack of late, is clearly a prime factor in leaving ‘civilized’ man with his hard, infrequent, and puny stool, but the need for laxatives often arises from less mechanical motives. The belief that a daily evacuation is essential for good health is common, and the guilt feelings or sense of failure associated with low production rates may have more to do with the development of laxative addiction than with dietary deficiencies. That long continued use of laxatives may provoke significant bowel damage is now clear, and in most cases, improvement follows careful explanation to sensible patients followed by a slow weaning process. There remains a small group of laxative abusers who surreptitiously ingest purgatives and who go to extraordinary lengths to conceal this fact from their medical attendants while complaining of the consequences of their actions. These patients are among the most difficult that a gastroenterologist may meet. Not infrequently, they have undergone repeated intensive, ofRcceivcd January 10,1979.Acccptcd May 17,1979. Address rcqucsts for reprints to: Professor L.A. Turnberg, Dopartment of Medicine, Hope Hospital, University of Manchester School of Medicine, Salford, M6 8HD, U.K. WC arc grateful to Dr. D.R. Cullen for allowing us to study his patient and for his helpful comments. 0 1979 by the American Gastroenterological Association 0016-5085/79/100780-07$02.00
of Manchester
School
of Medicine,
Salford,
ten uncomfortable, investigation in several hospitals, and some have been subjected to mutilating surgery without ever admitting their penchant for purging.’ Excellent recent reviews of this difficult disturbance are available.“,” It is helpful to have a clearly defined plan of investigation in patients with chronic severe watery diarrhea, so that these patients can be detected early. This at least is likely to reduce the number of unnecessary tests and promotes logical management. The following case illustrates some of these problems and indicates one possible rational approach to investigation.
Case History A 54.yr-old domestic assistant presented in February 1974 with a 6-mo history of diarrhea. She was passing up to ten motions per day, with fresh blood on most occasions and with some tenesmus. She had no other symptoms but claimed a 21.lb weight loss. Physical examination was normal. Initial investigation revealed normal hematologic and biochemical profiles. Barium enema examination was normal with no evidence of “paradoxical constipation,” but sigmoidoscopy revealed a friable, granular mucosa which on biopsy showed the changes of nonspecific colitis. Despite treatment with sulphasalazine and steroid retention enemata, further relapses occurred and the diarrhea became more persistent. Repeated investigations were all normal except for a second rectal biopsy, which showed an active colitis with crypt abscesses. There was no response to local or systemic steroids, codeine, or a variety of other antidiarrheal agents. Despite the severity of her diarrhea, the patient suffered no systemic effects. By June 1976, the diarrhea was “completely refractory” and, as its severity was apparently disproportionate to the extent of the distal proctitis, reinvestigation for an additional cause was undertaken. Fecal volumes of 2.5 liter/ day were measured; the stools were of a liquid consistency and contained little blood or mucus. A s-day fecal fat collection, a barium examination of the stomach and small bowel, and a jejunal biopsy were all normal, as were a breath hydrogen test for bacterial overgrowth, urinary 5HIAA excretion, and thyroid function tests. Repeated locker searches for purgatives as well as urine and fecal tests for senna and phenolphthalein were negative.
LAXATIVE
October 1979
Therapeutic trials of large doses of local and systemic steroids, sulphasalazine, mebeverine, and codeine failed to control the diarrhea, and dietary manipulations, first with a low- and then with a high-residue diet, as well as a lactose-free diet, were all ineffective. In 1977, hypokalemia was noted (serum potassium 2.6 mmol/liter) for the first time. The patient was passing ten motions per day with three to four motions at night, and her fecal output had risen to 5.5 liter/day of watery stool with little or no blood. A 5-day fecal fat (volume 26 liters) was “59% above the upper limit of normal,” but there was no other evidence of malabsorption or bacterial overgrowth. Detailed investigation for a hormone-secreting tumor was undertaken. A pentagastrin test showed hypochlorhydria, and this, together with the recent development of hypokalaemia, prompted consideration of the Verner Morrison syndrome. Isotopic and ultrasonic scans of the pancreas were normal, as was pancreatic angiography. Plasma gastrin, VIP, GIP, glucagon, pancreatic polypeptide, calcitonin, and prostaglandin E concentrations were all normal (Dr. S. Bloom, Royal Postgraduate Medical School). Stool and urine tests for purgatives were repeatedly negative. In October 1977, the patient was referred to the gastrointestinal unit at Hope Hospital for further investigation.
A. Volume
The line of investigation proposed here presupposes that routine tests have been or are being performed. These are likely to include sigmoidoscopy, barium studies of the intestinal tract, and stool cultures, and many patients will have had a jejunal biopsy and tests of absorptive function. The patients under discussion are those in whom diarrhea persists, but the diagnosis remains elusive, despite these investigations. It is helpful to determine early in the course of investigation whether persistent watery diarrhea is due to an osmotic cause (e.g., disaccharidase deficiency) or intestinal secretion. It is often possible to differentiate these types of watery diarrhea on the basis of fairly simple observations of stool output (Figure 1).First, the volume, osmolality, and electrolyte concentrations of 24hr stool collections should be measured on two or three occasions. In many patients who complain bitterly of diarrhea, admission to hospital and measurement of stool volume reveal outputs of 200 ml/day or less, an amount within the normal range. This information is clearly
-+
Questionable diarrhea ? Irritable bowel sydrome
MO:::::
B. Na and K concentrations
and osmolality effect
1 ((Na) + (K)) X 2 = osmolality. . “Secretory” Consider:
781
A Logical Plan of Investigation
&
:
ABUSE
Diarrhea unchanged /
of i-day f\
((Na) + (K)) x 2 < osmolality. k
diarrhea
“Osmotic”
Hormone-secreting tumors Consider: Pancreatic cholera syndrome (VIP) Zollinger-Ellison syndrome (gastrin) Medullary Carcinoma thyroid (? prostaglandins ? calcitonin) Ganglioneuroma Carcinoid (5HT) Purgative abuse (Cascara, senna) Diuretic abuse / Postileectomv, bile salt-induced colonic secretion Alcoholism Usually suspected Inflammatory bowel disease on other grounds Lymphoma Villous adenoma
Diarrhea ceases /
diarrhea
Lactase or rarer dissaccharidase deficiencies Glucose/galactose malabsorption Surreptitious osmotic purgative ingestion Malabsorption syndromes, e.g., celiac disease
Figure 1. Stool measurement flow chart
782
MORRIS
AND TURNBERG
of value, and several possibilities should then be considered. First, the diarrhea may be intermittent and/or exaggerated in the patient’s mind, and it is most likely to be due to the so-called irritable bowel syndrome. Secondly, the patient may be taking laxatives intermittently. Thirdly, consideration should be given to the possibility that the patient has anal sphincter incompetence, and specific questioning may reveal this when it has been missed in a “routine” history. Careful examination for neurologic abnormalities and studies of rectal pressure and sphincter competence are then indicated. A “secretory” cause for the diarrhea is highly unlikely with persistently normal volume losses. In patients with larger volume diarrhea, the sum of the cation concentrations, sodium and potassium, multiplied by 2, provides an approximate indication of total ionic constitution of the stools. This figure should approximately equal the measured stool osmolality in secretory diarrhea. On the other hand, in the case of osmotic diarrhea, the measured stool osmolality will exceed the calculated total ionic concentration because of the presence of other unabsorbed solutes. In osmotic diarrhea, the osmolar gap will usually exceed 100 mmol - liter-‘, whereas in secretory diarrhea, the gap will be generally not more than 30 or 40 mmol . liter’. A second useful test that helps differentiate osmotic from secretory diarrhea is the effect on stool volume and osmolality of a 48- to 7%hr fast, this period being covered by an intravenous infusion of saline and nutrients. In the case of an osmotically induced diarrhea, fasting should stop the diarrhea, whereas an intestinal secretory diarrhea will continue virtually unabated. These simple tests of stool volume, sodium and potassium concentrations, and osmolality, during feeding and fasting, will often indicate the direction of further investigation. These tests are not always helpful, however. When the diarrhea is of relatively small volume, that is, 500 ml/ day, the differentiation may not be clear cut. In some diseases, osmotic and secretory elements may each be present. Such may be the case in malabsorption syndromes where unabsorbed fatty acids may stimulate colonic secretion and unabsorbed water-soluble nutrient adds an osmotic load. Some secretory diarrheas may improve on fasting, too. For example, bile salt-induced colonic secretion in ileectomized patients will cease during fasting when bile salts are not liberated into the intestine. If purgative addicts stop their laxative intake when they fast, their diarrhea will also improve. The position is thus not absolutely clear cut, but the information gained is more often helpful than not. In patients with an “osmotic diarrhea” pattern, a search can then be made for the nonabsorbed solute,
GASTROENTEROLOGY
Vol. 77, No. 4, Part 1
the most likely cause being disaccharidase deficiency. Other rarer causes include glucose/galactose malabsorption and osmotic purgative ingestion. In those patients with a “secretory” pattern, a search for potential secretory hormones may have to be undertaken (Figure 1). In centers in which the facilities exist, it may be helpful to examine the intestinal defect more directly using intestinal perfusion techniques, but this is not essential to reach a diagnosis. Other simple initial screening tests that may help elucidate the cause include a locker search for purgatives and screening tests in urine and stool for purgatives. The former is, however, of questionable legality, although it is carried out in many such cases. Tests for phenolphthalein are simple, because this indicator changes color in alkali. Addition of alkali to stool or urine will reveal the pink color indicative of this particular purgative. Aloes and aloin turn alkaline urine red, too. A simple qualitative test for senna in urine has been described recently.6.7 This color reaction is based on more complex quantitative assays of senna alkaloids. Sisocodyl can be detected by a chromatographic method.’ Osmotic purgative ingestion is less simple to detect because the relevant ions are present normally in the stool. However, excess fecal sulfate, derived from sodium or magnesium sulfate ingestion, can be demonstrated by the white precipitate produced in acid extracts of feces by barium chloride, and this can be quantified.’ Fecal sulfate concentrations are normally less than 4.5 mmol * liter-‘.‘” Magnesium can be measured in fecal water by atomic absorption spectrophotometry. A wide range of magnesium concentrations has been reported in normal stool dialysate,Y the variability presumably being related to dietary intake. Although concentrations in stool water may be as high as 98 mmol * liter-‘,” the amount usually excreted will not be more than 20 mmol/day in subjects taking an average diet. Measurement of volume and electrolyte output in urine may be helpful too, since a diuresis associated with diarrhea suggests the possibility of surreptitious ingestion of diuretics.3
Investigation
of Present Case
It was clear that despite previous intensive investigation, an obvious cause for profound watery diarrhea had not been discovered. Initially, the possibility that the proctocolitis might be responsible for the diarrhea was excluded by colonoscopy, which showed only mild but definite changes of proctitis in the distal 39 cm of the bowel with normal mucosa above that. It seems unlikely that this mild disease was responsible for the severe diarrhea.
October
LAXATIVE
1979
Stool collections were instituted and the result of the first three days’ collections are shown in Table 1. The stool volume fell by 50% over these 3 days, and there was a large solute gap between the calculated total ionic concentrations and stool osmolality. This solute gap also decreased as the stool volume decreased. These results suggested the presence of an osmotically induced diarrhea due to a solute, which diminished in amount over these 3 days. However, this was unlikely to account for the very low stool osmolality of 176 mOsmo1 * liter-’ on day 3; an alternative explanation was required. In order to confirm the osmotic element of the diarrhea, the patient was placed on a 72-hr total fast with parenteral feeding. We expected this procedure to lead to a rapid decrease in stool volume, but surprisingly, her diarrhea remained unchanged, suggesting an additional secretory cause. In order to clarify this further, small bowel perfusion studies were performed using a triple lumen perfusion tube technique.‘” Measurements of net transmucosal transport of water and electrolytes were made in both the jejunum and ileum using isotonic plasma-like solutions with and without glucose. In the glucose-free perfusion studies, the subject was absorbing 84 ml of water per 30 cm of jejunum per hour, and 40 ml of water per 30 cm per hour in the ileum. These values rose with the addition of glucose (20 mM/liter) to 129 and 62 ml of water per 30 cm per hour in the jejunum and ileum, respectively. These values are similar to those found in normal subjects, as was the absorption of sodium and chloride. Despite the observation of absorption of salt and water at both sites in the small bowel, the patient had had diarrhea immediately before the perfusion studies and during and after the procedure. It was tentatively concluded that the diarrhea at this time was probably arising from the colon. The paradoxic observations of an apparently coionic secretory diarrhea and an osmotic diarrhea, suggested by initial stool measurements, were in part explained by nursing staff’s discovery of a large container of “Sennokot” (senna) tablets in the patient’s bedside table. This paradoxic possession of laxatives by a patient with diarrhea prompted us to conclude that she had a colonic secretory diarrhea due to senna, at
Table 1.
Stool Measurements
ABUSE
783
least while undergoing investigations in our department. Further thought about the initial 3day period following admission, when the patient’s stool volume and osmolar gap appeared to decrease, suggested the possibility that she might have been taking an osmotic purgative before her transfer to our unit. The most likely osmotic purgative was magnesium sulfate, and tests confirmed that her stools did indeed contain excess magnesium. Fecal magnesium concentrations, measured by atomic absorption spectrodephotometry, were 166, 58, and 21 mmol/liter, tected serially in the first 3 days’ stool collections. These indicate a daily output of 456, 116, and 29 mmol for those 3 days, respectively. We thus presumed that the patient had been taking a magnesium-containing osmotic purgative immediately before her transfer to our unit, but that the change from a familiar to an unfamiliar hospital precipitated a change to a more convenient purgative in the form of senna tablets. Subsequently, her physicians in the referring hospital found a jar of magnesium sulfate (“bath salts”) in her bathroom. The very low stool osmolality on the 3rd day after admission, however, required another explanation. Stool osmolalities below 250 mOsmo1 * ll’ are unlikely to occur naturally in diarrhea1 disease in adults. The suspicion in this case, therefore, must be that she deliberately added tap water or, less likely, urine to the stool to increase its bulk. The very low ionic concentrations support this view. It seemed, then, that the patient had a versatile imagination, taking an osmotic purgative initially, then adding water to her stool when this purgative became unavailable, and finally taking “Sennokot” as a more convenient means of fooling her physicians. The source of this latter aperient is not known, but it is conceivable that a visitor brought it to her. On confrontation, the patient denied all knowledge of any purgative ingestion. Psychiatric assessment was refused, and although she had been a widow for 2 yr and had lived alone during this time, she denied feeling depressed or unduly anxious. A formal assessment of her personality was not undertaken The subsequent management of this patient be-
During First 3 Days After Admission ((Na+) + (K’)) x 2
Stool volume (ml) Day 1 Day 2 Day 3
2750 2050 1400
Osmolality (mOsm 291 226 176
liter-‘)
(mMo1 124 84 86
liter-‘)
Osmolar
gap (mMol 167 142 90
liter-‘)
784
MORRIS
AND TURNBERG
GASTROENTEROLOGY
came easier with the fair degree of certainty that her medical attendants then had about the cause of her diarrhea. Further investigation was considered unnecessary, and although the patient continued to deny taking purgatives, her diarrhea slowly improved, and some 6 mo later, she remained clinically well with only occasional complaints of moderate diarrhea.
Pathogenesis Abuse
of Surreptitious
Laxative
The underlying psychologic factors that lead patients into surreptitious laxative abuse are complex and in any one individual may be impossible to elucidate. Undoubtedly, patients seek and gain considerable attention from medical personnel as well as from relatives or friends. It is likely that this behavior represents one of the modes of presentation of hysteria that may occur in patients with a variety of personality types.” All the features of hysterical behavior, including the capacity for self-deception, lack of insight, and manipulation of relatives, friends, and physicians, often in the absence of an obvious motive for gain,“, may be detected in surreptitious laxative abusers. The sort of stressful circumstances that might precipitate this problem are often not clearly greater than those encountered in a random sample of the population. Furthermore, the denial that most patients make when given the evidence that they are taking laxatives is not simply deliberate lying. They do not admit this possibility even to themselves. Our patient’s shock at being faced with this idea was indistinguishable from that of a normal person faced with the suggestion that she is deliberately provoking the symptoms of which she complains. This internal “block” often allows patients to continue taking purgatives when they have been told of their physicians’ conclusions. It also helps explain why patients can suffer such severe symptoms and undergo prolonged, often uncomfortable investigations without revealing the cause. Some have even undergone intestinal resections and ileostomies.‘,” In our patient, it seems likely that the justifiable attention gained as a result of her undoubted proctitis was found to be a comfort and that this experience provided her with a symptom that she could maintain relatively easily and for which she could accept continued attention. The psychologic reasons for her embarking on this course are obscure, because although she was widowed and lived alone, she had not been obviously unhappy. It is possible that she had a “hysterical” personality, but this was not obvious.
Consequences Ingestion
of Chronic
Vol. 77, No. 4, Part 1
Laxative
The clinical picture of a chronic laxative abuser, either overt or surreptitious, includes watery diarrhea, abdominal discomfort, sometimes pain, muscle weakness, and lassitude together with hypokalemia, melanosis coli, and the barium enema appearance of a “cathartic colon.” In surreptitious abusers, the symptoms have commonly persisted for very many years and patients have required repeated hospital admissions for investigation and for correction of dehydration and of hypokalemia, often profound. The literature is replete with descriptions of patients who have had a variety of operations including repeated laparotomies, adrenalectomy, partial pancreatectomy, and bowel resections, all, of course to no avai1.2.4 The ‘“cathartic colon,” which occurs in some 10% of surreptitious laxative abusers, may be abnormal sigmoidoscopically, radiologically, and histologically. Melanosis coli may be recognized sigmoidostopically as black pigmentation in the mucosa, maximal in the rectum and distal colon.13 It was present in 4.7% of 553 patients sigmoidoscoped as part of a routine bowel investigation.‘” Melanosis coli rarely involves the small bowel and avoids the colonic lymphoid follicles that stand out as small, pinheadsized, pale patches.” Polyps remain unpigmented, too.15 It can be detected histologically in many mild cases where it may not be visible macroscopically and can occur as early as 4 mo after starting purgatives. The pigment is confined to macrophages superficially within the lamina propria of the mucosa. In severe cases, melanosis coli may extend into the submucosa.” Anthracene derivatives have been particularly incriminated (senna, cascara, aloes), and other types of laxatives are mostly innocent of this effect.‘” Despite the name, the pigment is probably not melanin and may be derived from a combination of lipofuscin with anthraquinone” or from degenerated mitochrondria’” or other intracellular organelles. Melanosis coli has been provoked experimentally in monkeys fed cascara.‘” Its importance lies in the clue that it provides about laxative ingestion. Furthermore, the presence of Melanosis coli indicates recent laxative ingestion, because the pigmentation disappears within 1 yr of stopping laxatives.” Radiologically, the cathartic colon has been well described as being dilated, abnormally distensile, hypomotile, and with poor or absent haustral markof ings.” There may be “pseudo-strictures”-areas spasm that persist for several hr. The right side of the colon and terminal ileum are particularly affected. The colon may be long and redundant, but it is uncertain whether this is the cause of the constipation or the result of persistent purgation.
October
LAXATIVE
1979
There is evidence of histologic damage, too. Apart from melanosis coli, the bowel wall is thinned, but the most characteristic change is in the damage to the intrinsic nerves of the mysenteric plexus, which show axonal degeneration and loss. Smith” demonstrated well the axonal fragmentation produced by a number of cathartics, but particularly by senna. Presumably, the purgatives are directly toxic to the nerve plexuses, but the mechanisms are unknown. Similar myenteric damage has been provoked in mice by administration of senna.*’ Undoubtedly, this change results in the bowel distension, hypomotility, and abnormalities visible radiologically, including the absent haustrae and pseudo-strictures. Our patient had none of these structural changes in the colon. The lack of melanosis provides a hint that senna was not her first choice of laxative; magnesium salts are unlikely to induce this change. Electrolyte disturbances, particularly sodium and potassium depletion, may lead to a variety of symptoms. Episodes of lassitude and weakness are common, and confusion and dementia, although well recognized, can give rise to diagnostic difficulties.’ The loss of about 2 liters of stool per day is a potent cause of dehydration. Sodium concentrations in diarrheal stools of this magnitude are similar to those in plasma, unless the diarrhea is largely due to an osmotic purge. Thus, the loss of 100-140 meq of sodium per liter of stool will readily lead to sodium depletion. The mechanism for hypokalemia, which may be dramatic and occasionally fatal, is more complex, however. Losses in stool water, where concentrations approach plasma values, are of the order of 5-15 meq . liter’ of stool. Sodium depletion, however, leads to a secondary hyperaldosteronism, which induces the kidney to retain sodium but to lose potassium, which in turn must encourage the development of potassium depletion. Hypokalemia itself damages the renal tubules, and consequent renal failure plus the dehydration are troublesome complications. Steatorrhea has been reported”,‘” and malabsorption of xylose was detected, suggesting that the defect results from disturbed small intestinal mucosal function. The mechanism for this is unclear, however, and requires further investigation. The report of osteomalacia, owing to malabsorption of calcium, is probably based on this small intestinal defect, and in this case, withdrawal of phenolphthalein ingestion allowed the osteomalacia to improve.24 Hypokalemia can impair the ability of pancreatic ,+cells to release insulin2” and, indeed, carbohydrate intolerance, with glycosuria and hyperglycaemia, has been recorded.R.‘3 In one patient, hypoproteinemia due to a protein-losing enteropathy was described,” but the mechanism for this result of laxative ingestion has not been elucidated.
ABUSE
785
Diagnosis and Management Whatever the underlying cause, the prolonged intensive investigation of our patient speaks for the difficulties encountered in making a diagnosis even when it is considered early. The detection of magnesium salts is relatively more difficult than simple testing for senna and phenolpthalein. However, the plan of investigation indicated here, including the straightforward measurements of stool osmolality, undoubtedly pointed the way to a correct diagnosis. Even when the diagnosis has been made, there are considerable difficulties still to be overcome in management. A simple statement of the facts to the patient may give the physician some satisfaction but is unlikely to help the patient very much. The underlying personality defect will not change, but careful, repeated, and long-continued discussions with the patient and near relatives may improve the particular problem of laxative abuse. Thus, management of these patients shifts rightly from the potentially hazardous area of gastrointestinal investigation to the less traumatic one of psychotherapy.
References M: A new look at laxative action. Gastro1. Binder H, Donowitz enterology 69:1001-1005,1975 2. Cook WT: Laxative abuse. In Clinics Im Gastroenterology. Vol. 6. No. 3. 659-673, 1977 3. Connell AM, Hilton C, Irvine G, Leonard-Jones JE, Misiewicz JJ: Variation of bowel habit in Iwo populations. Br Med 1 ii:3093-1099,1965 JH: Laxative abuse. Gut 15:758-766, 1974 4. Cummings SG, Fordtran JS: Intractable 5. Krejs GH, Walsh JH, Morawski diarrhoea. Intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics. Am J Dig Dis 22:280-292,1977 P: Qualitative determination of 6. Kaspi T, Royds RB, Turner senna in urine. Lancet i:l162, 1978 7. British Pharmacopia. London, HMSC), 1973, p 418 8. Heizer WD, Warshaw AL, Waldman TA, Laster L: Protein losing gastroenteropathy and malabsorption associated with factitious diarrhoca. Ann Intern Mcd 68:839-852, 1968 A, Morrison RBI, Ng ST, Howard 9. Wrong 0, Metcalf-Gibson AV: In viva dialysis of facccs as a method of stool analysis. 1. Technique and results in normal subjects. Clin Sci 28:357-375, 1965 10. Cooper H, Levitan R, Fordtran JS. Ingelfinger FJ: A method for studying absorption of water and solute from the human small intcstinc. Gastrocnterology 501-7, 1966 the hysterical personality and 11. Chodoff P, Lyons H: Hysteria, ‘hysterical’ conversion. Am J Psychiatry l14:734-740, 1958 Third edition. London, 12. Slater E, Roth M: Clinical Psychiatry. Balliere, Tindall & Cassell, 1969, p 104-116 13. Sleisengcr MH. Fordtran JS: Gastrointestinal Disease. Second edition. Philadelphia. W.B. Saunders Co., 1978, p 1860 14. Bockus HL, Willard JH, Bank J: Mclanosis coli: the etiologic significance of the anthracenc laxatives: a report of 41 cases. JAMA loll-6,1933 BC, Dawson IMP: Gastrointestinal Pathology. Ox15. Morson ford, Blackwell, 1972, p 585-587 coli. Experimental observations on its 16. Spcare GS: Melanosis
786
17. 18. 19. 20.
21.
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AND TURNBERG
production and elimination in 23 cases. Am J Surg 82631, 1951 Smith B: Pathologic changes in the colon produced by anthraquinone purgatives. Dis Colon Rectum X%455-458,1973 Schrodt GR: Melanosis coli: a study with the electron microscope. Dis Colon Rectum 6277.1963 Roden D: Melanosis coli: a pathological study: its experimental production in monkeys. Ir J Med Sci 654-674,194O Wittaesch JH, Jackman RJ, MacDonald JR: Melanosis coli: general review and study of 887 cases. Dis Colon Rectum 1:172-1861958 Heillman N, Bernstein C: Roentgen abnormalities of the large
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24.
25.
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and small intestine associated with prolonged cathartic ingestion. Radiology 65:549-556,1955 Smith B: Effect of irritant purgatives on the myenteric plexus in man and the mouse. Gut 9:139,1968 Cummings JH, Sladen GE, James OFW, Sarner M, Misiewicz JJ: Laxative-induced diarrhoea: a continuing clinical problem. Br Med J 1:537-541,1974 Frame B, Guiana HL, Frost HM, Reynold WA: Osteomalacia induced by laxative (phenolphthalein) ingestion. Arch Intern Med 128:794-796.1971 Conn JW: Hypertension, the potassium ion and impaired carbohydrate tolerance. N Engl J Med 273:1135-1143,1965
CLINICAL
77:7RO-786,1979
CONFERENCE
Surreptitious A. I. MORRIS
Laxative
Abuse
and L. A. TURNBERG
Department of Medicine, United Kingdom
Hope
Hospital,
University
Vast amounts of laxatives are consumed in the Western world. This unsurprising statement is illustrated by the following figures. In 1975, in the USA, $130 million were spent on laxatives, and in the UK, the National Health Service spent E7 million’ and probably several times this amount was sold over the counter. Between 15 and 30% of the population over the age of 60 take laxatives regularly,” and they can choose from among the 700 or so different preparations available in the USA’ or the 200 available in the UK.4 The larger variety produced in the USA probably reflects the greater spirit of competitiveness in American industry rather than a severer degree of national constipation for, if anything, bowel “awareness” is more prominent in the UK. The carefully refined, fiber-depleted diet, so rightly under attack of late, is clearly a prime factor in leaving ‘civilized’ man with his hard, infrequent, and puny stool, but the need for laxatives often arises from less mechanical motives. The belief that a daily evacuation is essential for good health is common, and the guilt feelings or sense of failure associated with low production rates may have more to do with the development of laxative addiction than with dietary deficiencies. That long continued use of laxatives may provoke significant bowel damage is now clear, and in most cases, improvement follows careful explanation to sensible patients followed by a slow weaning process. There remains a small group of laxative abusers who surreptitiously ingest purgatives and who go to extraordinary lengths to conceal this fact from their medical attendants while complaining of the consequences of their actions. These patients are among the most difficult that a gastroenterologist may meet. Not infrequently, they have undergone repeated intensive, ofRcceivcd January 10,1979.Acccptcd May 17,1979. Address rcqucsts for reprints to: Professor L.A. Turnberg, Dopartment of Medicine, Hope Hospital, University of Manchester School of Medicine, Salford, M6 8HD, U.K. WC arc grateful to Dr. D.R. Cullen for allowing us to study his patient and for his helpful comments. 0 1979 by the American Gastroenterological Association 0016-5085/79/100780-07$02.00
of Manchester
School
of Medicine,
Salford,
ten uncomfortable, investigation in several hospitals, and some have been subjected to mutilating surgery without ever admitting their penchant for purging.’ Excellent recent reviews of this difficult disturbance are available.“,” It is helpful to have a clearly defined plan of investigation in patients with chronic severe watery diarrhea, so that these patients can be detected early. This at least is likely to reduce the number of unnecessary tests and promotes logical management. The following case illustrates some of these problems and indicates one possible rational approach to investigation.
Case History A 54.yr-old domestic assistant presented in February 1974 with a 6-mo history of diarrhea. She was passing up to ten motions per day, with fresh blood on most occasions and with some tenesmus. She had no other symptoms but claimed a 21.lb weight loss. Physical examination was normal. Initial investigation revealed normal hematologic and biochemical profiles. Barium enema examination was normal with no evidence of “paradoxical constipation,” but sigmoidoscopy revealed a friable, granular mucosa which on biopsy showed the changes of nonspecific colitis. Despite treatment with sulphasalazine and steroid retention enemata, further relapses occurred and the diarrhea became more persistent. Repeated investigations were all normal except for a second rectal biopsy, which showed an active colitis with crypt abscesses. There was no response to local or systemic steroids, codeine, or a variety of other antidiarrheal agents. Despite the severity of her diarrhea, the patient suffered no systemic effects. By June 1976, the diarrhea was “completely refractory” and, as its severity was apparently disproportionate to the extent of the distal proctitis, reinvestigation for an additional cause was undertaken. Fecal volumes of 2.5 liter/ day were measured; the stools were of a liquid consistency and contained little blood or mucus. A s-day fecal fat collection, a barium examination of the stomach and small bowel, and a jejunal biopsy were all normal, as were a breath hydrogen test for bacterial overgrowth, urinary 5HIAA excretion, and thyroid function tests. Repeated locker searches for purgatives as well as urine and fecal tests for senna and phenolphthalein were negative.
LAXATIVE
October 1979
Therapeutic trials of large doses of local and systemic steroids, sulphasalazine, mebeverine, and codeine failed to control the diarrhea, and dietary manipulations, first with a low- and then with a high-residue diet, as well as a lactose-free diet, were all ineffective. In 1977, hypokalemia was noted (serum potassium 2.6 mmol/liter) for the first time. The patient was passing ten motions per day with three to four motions at night, and her fecal output had risen to 5.5 liter/day of watery stool with little or no blood. A 5-day fecal fat (volume 26 liters) was “59% above the upper limit of normal,” but there was no other evidence of malabsorption or bacterial overgrowth. Detailed investigation for a hormone-secreting tumor was undertaken. A pentagastrin test showed hypochlorhydria, and this, together with the recent development of hypokalaemia, prompted consideration of the Verner Morrison syndrome. Isotopic and ultrasonic scans of the pancreas were normal, as was pancreatic angiography. Plasma gastrin, VIP, GIP, glucagon, pancreatic polypeptide, calcitonin, and prostaglandin E concentrations were all normal (Dr. S. Bloom, Royal Postgraduate Medical School). Stool and urine tests for purgatives were repeatedly negative. In October 1977, the patient was referred to the gastrointestinal unit at Hope Hospital for further investigation.
A. Volume
The line of investigation proposed here presupposes that routine tests have been or are being performed. These are likely to include sigmoidoscopy, barium studies of the intestinal tract, and stool cultures, and many patients will have had a jejunal biopsy and tests of absorptive function. The patients under discussion are those in whom diarrhea persists, but the diagnosis remains elusive, despite these investigations. It is helpful to determine early in the course of investigation whether persistent watery diarrhea is due to an osmotic cause (e.g., disaccharidase deficiency) or intestinal secretion. It is often possible to differentiate these types of watery diarrhea on the basis of fairly simple observations of stool output (Figure 1).First, the volume, osmolality, and electrolyte concentrations of 24hr stool collections should be measured on two or three occasions. In many patients who complain bitterly of diarrhea, admission to hospital and measurement of stool volume reveal outputs of 200 ml/day or less, an amount within the normal range. This information is clearly
-+
Questionable diarrhea ? Irritable bowel sydrome
MO:::::
B. Na and K concentrations
and osmolality effect
1 ((Na) + (K)) X 2 = osmolality. . “Secretory” Consider:
781
A Logical Plan of Investigation
&
:
ABUSE
Diarrhea unchanged /
of i-day f\
((Na) + (K)) x 2 < osmolality. k
diarrhea
“Osmotic”
Hormone-secreting tumors Consider: Pancreatic cholera syndrome (VIP) Zollinger-Ellison syndrome (gastrin) Medullary Carcinoma thyroid (? prostaglandins ? calcitonin) Ganglioneuroma Carcinoid (5HT) Purgative abuse (Cascara, senna) Diuretic abuse / Postileectomv, bile salt-induced colonic secretion Alcoholism Usually suspected Inflammatory bowel disease on other grounds Lymphoma Villous adenoma
Diarrhea ceases /
diarrhea
Lactase or rarer dissaccharidase deficiencies Glucose/galactose malabsorption Surreptitious osmotic purgative ingestion Malabsorption syndromes, e.g., celiac disease
Figure 1. Stool measurement flow chart
782
MORRIS
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of value, and several possibilities should then be considered. First, the diarrhea may be intermittent and/or exaggerated in the patient’s mind, and it is most likely to be due to the so-called irritable bowel syndrome. Secondly, the patient may be taking laxatives intermittently. Thirdly, consideration should be given to the possibility that the patient has anal sphincter incompetence, and specific questioning may reveal this when it has been missed in a “routine” history. Careful examination for neurologic abnormalities and studies of rectal pressure and sphincter competence are then indicated. A “secretory” cause for the diarrhea is highly unlikely with persistently normal volume losses. In patients with larger volume diarrhea, the sum of the cation concentrations, sodium and potassium, multiplied by 2, provides an approximate indication of total ionic constitution of the stools. This figure should approximately equal the measured stool osmolality in secretory diarrhea. On the other hand, in the case of osmotic diarrhea, the measured stool osmolality will exceed the calculated total ionic concentration because of the presence of other unabsorbed solutes. In osmotic diarrhea, the osmolar gap will usually exceed 100 mmol - liter-‘, whereas in secretory diarrhea, the gap will be generally not more than 30 or 40 mmol . liter’. A second useful test that helps differentiate osmotic from secretory diarrhea is the effect on stool volume and osmolality of a 48- to 7%hr fast, this period being covered by an intravenous infusion of saline and nutrients. In the case of an osmotically induced diarrhea, fasting should stop the diarrhea, whereas an intestinal secretory diarrhea will continue virtually unabated. These simple tests of stool volume, sodium and potassium concentrations, and osmolality, during feeding and fasting, will often indicate the direction of further investigation. These tests are not always helpful, however. When the diarrhea is of relatively small volume, that is, 500 ml/ day, the differentiation may not be clear cut. In some diseases, osmotic and secretory elements may each be present. Such may be the case in malabsorption syndromes where unabsorbed fatty acids may stimulate colonic secretion and unabsorbed water-soluble nutrient adds an osmotic load. Some secretory diarrheas may improve on fasting, too. For example, bile salt-induced colonic secretion in ileectomized patients will cease during fasting when bile salts are not liberated into the intestine. If purgative addicts stop their laxative intake when they fast, their diarrhea will also improve. The position is thus not absolutely clear cut, but the information gained is more often helpful than not. In patients with an “osmotic diarrhea” pattern, a search can then be made for the nonabsorbed solute,
GASTROENTEROLOGY
Vol. 77, No. 4, Part 1
the most likely cause being disaccharidase deficiency. Other rarer causes include glucose/galactose malabsorption and osmotic purgative ingestion. In those patients with a “secretory” pattern, a search for potential secretory hormones may have to be undertaken (Figure 1). In centers in which the facilities exist, it may be helpful to examine the intestinal defect more directly using intestinal perfusion techniques, but this is not essential to reach a diagnosis. Other simple initial screening tests that may help elucidate the cause include a locker search for purgatives and screening tests in urine and stool for purgatives. The former is, however, of questionable legality, although it is carried out in many such cases. Tests for phenolphthalein are simple, because this indicator changes color in alkali. Addition of alkali to stool or urine will reveal the pink color indicative of this particular purgative. Aloes and aloin turn alkaline urine red, too. A simple qualitative test for senna in urine has been described recently.6.7 This color reaction is based on more complex quantitative assays of senna alkaloids. Sisocodyl can be detected by a chromatographic method.’ Osmotic purgative ingestion is less simple to detect because the relevant ions are present normally in the stool. However, excess fecal sulfate, derived from sodium or magnesium sulfate ingestion, can be demonstrated by the white precipitate produced in acid extracts of feces by barium chloride, and this can be quantified.’ Fecal sulfate concentrations are normally less than 4.5 mmol * liter-‘.‘” Magnesium can be measured in fecal water by atomic absorption spectrophotometry. A wide range of magnesium concentrations has been reported in normal stool dialysate,Y the variability presumably being related to dietary intake. Although concentrations in stool water may be as high as 98 mmol * liter-‘,” the amount usually excreted will not be more than 20 mmol/day in subjects taking an average diet. Measurement of volume and electrolyte output in urine may be helpful too, since a diuresis associated with diarrhea suggests the possibility of surreptitious ingestion of diuretics.3
Investigation
of Present Case
It was clear that despite previous intensive investigation, an obvious cause for profound watery diarrhea had not been discovered. Initially, the possibility that the proctocolitis might be responsible for the diarrhea was excluded by colonoscopy, which showed only mild but definite changes of proctitis in the distal 39 cm of the bowel with normal mucosa above that. It seems unlikely that this mild disease was responsible for the severe diarrhea.
October
LAXATIVE
1979
Stool collections were instituted and the result of the first three days’ collections are shown in Table 1. The stool volume fell by 50% over these 3 days, and there was a large solute gap between the calculated total ionic concentrations and stool osmolality. This solute gap also decreased as the stool volume decreased. These results suggested the presence of an osmotically induced diarrhea due to a solute, which diminished in amount over these 3 days. However, this was unlikely to account for the very low stool osmolality of 176 mOsmo1 * liter-’ on day 3; an alternative explanation was required. In order to confirm the osmotic element of the diarrhea, the patient was placed on a 72-hr total fast with parenteral feeding. We expected this procedure to lead to a rapid decrease in stool volume, but surprisingly, her diarrhea remained unchanged, suggesting an additional secretory cause. In order to clarify this further, small bowel perfusion studies were performed using a triple lumen perfusion tube technique.‘” Measurements of net transmucosal transport of water and electrolytes were made in both the jejunum and ileum using isotonic plasma-like solutions with and without glucose. In the glucose-free perfusion studies, the subject was absorbing 84 ml of water per 30 cm of jejunum per hour, and 40 ml of water per 30 cm per hour in the ileum. These values rose with the addition of glucose (20 mM/liter) to 129 and 62 ml of water per 30 cm per hour in the jejunum and ileum, respectively. These values are similar to those found in normal subjects, as was the absorption of sodium and chloride. Despite the observation of absorption of salt and water at both sites in the small bowel, the patient had had diarrhea immediately before the perfusion studies and during and after the procedure. It was tentatively concluded that the diarrhea at this time was probably arising from the colon. The paradoxic observations of an apparently coionic secretory diarrhea and an osmotic diarrhea, suggested by initial stool measurements, were in part explained by nursing staff’s discovery of a large container of “Sennokot” (senna) tablets in the patient’s bedside table. This paradoxic possession of laxatives by a patient with diarrhea prompted us to conclude that she had a colonic secretory diarrhea due to senna, at
Table 1.
Stool Measurements
ABUSE
783
least while undergoing investigations in our department. Further thought about the initial 3day period following admission, when the patient’s stool volume and osmolar gap appeared to decrease, suggested the possibility that she might have been taking an osmotic purgative before her transfer to our unit. The most likely osmotic purgative was magnesium sulfate, and tests confirmed that her stools did indeed contain excess magnesium. Fecal magnesium concentrations, measured by atomic absorption spectrodephotometry, were 166, 58, and 21 mmol/liter, tected serially in the first 3 days’ stool collections. These indicate a daily output of 456, 116, and 29 mmol for those 3 days, respectively. We thus presumed that the patient had been taking a magnesium-containing osmotic purgative immediately before her transfer to our unit, but that the change from a familiar to an unfamiliar hospital precipitated a change to a more convenient purgative in the form of senna tablets. Subsequently, her physicians in the referring hospital found a jar of magnesium sulfate (“bath salts”) in her bathroom. The very low stool osmolality on the 3rd day after admission, however, required another explanation. Stool osmolalities below 250 mOsmo1 * ll’ are unlikely to occur naturally in diarrhea1 disease in adults. The suspicion in this case, therefore, must be that she deliberately added tap water or, less likely, urine to the stool to increase its bulk. The very low ionic concentrations support this view. It seemed, then, that the patient had a versatile imagination, taking an osmotic purgative initially, then adding water to her stool when this purgative became unavailable, and finally taking “Sennokot” as a more convenient means of fooling her physicians. The source of this latter aperient is not known, but it is conceivable that a visitor brought it to her. On confrontation, the patient denied all knowledge of any purgative ingestion. Psychiatric assessment was refused, and although she had been a widow for 2 yr and had lived alone during this time, she denied feeling depressed or unduly anxious. A formal assessment of her personality was not undertaken The subsequent management of this patient be-
During First 3 Days After Admission ((Na+) + (K’)) x 2
Stool volume (ml) Day 1 Day 2 Day 3
2750 2050 1400
Osmolality (mOsm 291 226 176
liter-‘)
(mMo1 124 84 86
liter-‘)
Osmolar
gap (mMol 167 142 90
liter-‘)
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GASTROENTEROLOGY
came easier with the fair degree of certainty that her medical attendants then had about the cause of her diarrhea. Further investigation was considered unnecessary, and although the patient continued to deny taking purgatives, her diarrhea slowly improved, and some 6 mo later, she remained clinically well with only occasional complaints of moderate diarrhea.
Pathogenesis Abuse
of Surreptitious
Laxative
The underlying psychologic factors that lead patients into surreptitious laxative abuse are complex and in any one individual may be impossible to elucidate. Undoubtedly, patients seek and gain considerable attention from medical personnel as well as from relatives or friends. It is likely that this behavior represents one of the modes of presentation of hysteria that may occur in patients with a variety of personality types.” All the features of hysterical behavior, including the capacity for self-deception, lack of insight, and manipulation of relatives, friends, and physicians, often in the absence of an obvious motive for gain,“, may be detected in surreptitious laxative abusers. The sort of stressful circumstances that might precipitate this problem are often not clearly greater than those encountered in a random sample of the population. Furthermore, the denial that most patients make when given the evidence that they are taking laxatives is not simply deliberate lying. They do not admit this possibility even to themselves. Our patient’s shock at being faced with this idea was indistinguishable from that of a normal person faced with the suggestion that she is deliberately provoking the symptoms of which she complains. This internal “block” often allows patients to continue taking purgatives when they have been told of their physicians’ conclusions. It also helps explain why patients can suffer such severe symptoms and undergo prolonged, often uncomfortable investigations without revealing the cause. Some have even undergone intestinal resections and ileostomies.‘,” In our patient, it seems likely that the justifiable attention gained as a result of her undoubted proctitis was found to be a comfort and that this experience provided her with a symptom that she could maintain relatively easily and for which she could accept continued attention. The psychologic reasons for her embarking on this course are obscure, because although she was widowed and lived alone, she had not been obviously unhappy. It is possible that she had a “hysterical” personality, but this was not obvious.
Consequences Ingestion
of Chronic
Vol. 77, No. 4, Part 1
Laxative
The clinical picture of a chronic laxative abuser, either overt or surreptitious, includes watery diarrhea, abdominal discomfort, sometimes pain, muscle weakness, and lassitude together with hypokalemia, melanosis coli, and the barium enema appearance of a “cathartic colon.” In surreptitious abusers, the symptoms have commonly persisted for very many years and patients have required repeated hospital admissions for investigation and for correction of dehydration and of hypokalemia, often profound. The literature is replete with descriptions of patients who have had a variety of operations including repeated laparotomies, adrenalectomy, partial pancreatectomy, and bowel resections, all, of course to no avai1.2.4 The ‘“cathartic colon,” which occurs in some 10% of surreptitious laxative abusers, may be abnormal sigmoidoscopically, radiologically, and histologically. Melanosis coli may be recognized sigmoidostopically as black pigmentation in the mucosa, maximal in the rectum and distal colon.13 It was present in 4.7% of 553 patients sigmoidoscoped as part of a routine bowel investigation.‘” Melanosis coli rarely involves the small bowel and avoids the colonic lymphoid follicles that stand out as small, pinheadsized, pale patches.” Polyps remain unpigmented, too.15 It can be detected histologically in many mild cases where it may not be visible macroscopically and can occur as early as 4 mo after starting purgatives. The pigment is confined to macrophages superficially within the lamina propria of the mucosa. In severe cases, melanosis coli may extend into the submucosa.” Anthracene derivatives have been particularly incriminated (senna, cascara, aloes), and other types of laxatives are mostly innocent of this effect.‘” Despite the name, the pigment is probably not melanin and may be derived from a combination of lipofuscin with anthraquinone” or from degenerated mitochrondria’” or other intracellular organelles. Melanosis coli has been provoked experimentally in monkeys fed cascara.‘” Its importance lies in the clue that it provides about laxative ingestion. Furthermore, the presence of Melanosis coli indicates recent laxative ingestion, because the pigmentation disappears within 1 yr of stopping laxatives.” Radiologically, the cathartic colon has been well described as being dilated, abnormally distensile, hypomotile, and with poor or absent haustral markof ings.” There may be “pseudo-strictures”-areas spasm that persist for several hr. The right side of the colon and terminal ileum are particularly affected. The colon may be long and redundant, but it is uncertain whether this is the cause of the constipation or the result of persistent purgation.
October
LAXATIVE
1979
There is evidence of histologic damage, too. Apart from melanosis coli, the bowel wall is thinned, but the most characteristic change is in the damage to the intrinsic nerves of the mysenteric plexus, which show axonal degeneration and loss. Smith” demonstrated well the axonal fragmentation produced by a number of cathartics, but particularly by senna. Presumably, the purgatives are directly toxic to the nerve plexuses, but the mechanisms are unknown. Similar myenteric damage has been provoked in mice by administration of senna.*’ Undoubtedly, this change results in the bowel distension, hypomotility, and abnormalities visible radiologically, including the absent haustrae and pseudo-strictures. Our patient had none of these structural changes in the colon. The lack of melanosis provides a hint that senna was not her first choice of laxative; magnesium salts are unlikely to induce this change. Electrolyte disturbances, particularly sodium and potassium depletion, may lead to a variety of symptoms. Episodes of lassitude and weakness are common, and confusion and dementia, although well recognized, can give rise to diagnostic difficulties.’ The loss of about 2 liters of stool per day is a potent cause of dehydration. Sodium concentrations in diarrheal stools of this magnitude are similar to those in plasma, unless the diarrhea is largely due to an osmotic purge. Thus, the loss of 100-140 meq of sodium per liter of stool will readily lead to sodium depletion. The mechanism for hypokalemia, which may be dramatic and occasionally fatal, is more complex, however. Losses in stool water, where concentrations approach plasma values, are of the order of 5-15 meq . liter’ of stool. Sodium depletion, however, leads to a secondary hyperaldosteronism, which induces the kidney to retain sodium but to lose potassium, which in turn must encourage the development of potassium depletion. Hypokalemia itself damages the renal tubules, and consequent renal failure plus the dehydration are troublesome complications. Steatorrhea has been reported”,‘” and malabsorption of xylose was detected, suggesting that the defect results from disturbed small intestinal mucosal function. The mechanism for this is unclear, however, and requires further investigation. The report of osteomalacia, owing to malabsorption of calcium, is probably based on this small intestinal defect, and in this case, withdrawal of phenolphthalein ingestion allowed the osteomalacia to improve.24 Hypokalemia can impair the ability of pancreatic ,+cells to release insulin2” and, indeed, carbohydrate intolerance, with glycosuria and hyperglycaemia, has been recorded.R.‘3 In one patient, hypoproteinemia due to a protein-losing enteropathy was described,” but the mechanism for this result of laxative ingestion has not been elucidated.
ABUSE
785
Diagnosis and Management Whatever the underlying cause, the prolonged intensive investigation of our patient speaks for the difficulties encountered in making a diagnosis even when it is considered early. The detection of magnesium salts is relatively more difficult than simple testing for senna and phenolpthalein. However, the plan of investigation indicated here, including the straightforward measurements of stool osmolality, undoubtedly pointed the way to a correct diagnosis. Even when the diagnosis has been made, there are considerable difficulties still to be overcome in management. A simple statement of the facts to the patient may give the physician some satisfaction but is unlikely to help the patient very much. The underlying personality defect will not change, but careful, repeated, and long-continued discussions with the patient and near relatives may improve the particular problem of laxative abuse. Thus, management of these patients shifts rightly from the potentially hazardous area of gastrointestinal investigation to the less traumatic one of psychotherapy.
References M: A new look at laxative action. Gastro1. Binder H, Donowitz enterology 69:1001-1005,1975 2. Cook WT: Laxative abuse. In Clinics Im Gastroenterology. Vol. 6. No. 3. 659-673, 1977 3. Connell AM, Hilton C, Irvine G, Leonard-Jones JE, Misiewicz JJ: Variation of bowel habit in Iwo populations. Br Med 1 ii:3093-1099,1965 JH: Laxative abuse. Gut 15:758-766, 1974 4. Cummings SG, Fordtran JS: Intractable 5. Krejs GH, Walsh JH, Morawski diarrhoea. Intestinal perfusion studies and plasma VIP concentrations in patients with pancreatic cholera syndrome and surreptitious ingestion of laxatives and diuretics. Am J Dig Dis 22:280-292,1977 P: Qualitative determination of 6. Kaspi T, Royds RB, Turner senna in urine. Lancet i:l162, 1978 7. British Pharmacopia. London, HMSC), 1973, p 418 8. Heizer WD, Warshaw AL, Waldman TA, Laster L: Protein losing gastroenteropathy and malabsorption associated with factitious diarrhoca. Ann Intern Mcd 68:839-852, 1968 A, Morrison RBI, Ng ST, Howard 9. Wrong 0, Metcalf-Gibson AV: In viva dialysis of facccs as a method of stool analysis. 1. Technique and results in normal subjects. Clin Sci 28:357-375, 1965 10. Cooper H, Levitan R, Fordtran JS. Ingelfinger FJ: A method for studying absorption of water and solute from the human small intcstinc. Gastrocnterology 501-7, 1966 the hysterical personality and 11. Chodoff P, Lyons H: Hysteria, ‘hysterical’ conversion. Am J Psychiatry l14:734-740, 1958 Third edition. London, 12. Slater E, Roth M: Clinical Psychiatry. Balliere, Tindall & Cassell, 1969, p 104-116 13. Sleisengcr MH. Fordtran JS: Gastrointestinal Disease. Second edition. Philadelphia. W.B. Saunders Co., 1978, p 1860 14. Bockus HL, Willard JH, Bank J: Mclanosis coli: the etiologic significance of the anthracenc laxatives: a report of 41 cases. JAMA loll-6,1933 BC, Dawson IMP: Gastrointestinal Pathology. Ox15. Morson ford, Blackwell, 1972, p 585-587 coli. Experimental observations on its 16. Spcare GS: Melanosis
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17. 18. 19. 20.
21.
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production and elimination in 23 cases. Am J Surg 82631, 1951 Smith B: Pathologic changes in the colon produced by anthraquinone purgatives. Dis Colon Rectum X%455-458,1973 Schrodt GR: Melanosis coli: a study with the electron microscope. Dis Colon Rectum 6277.1963 Roden D: Melanosis coli: a pathological study: its experimental production in monkeys. Ir J Med Sci 654-674,194O Wittaesch JH, Jackman RJ, MacDonald JR: Melanosis coli: general review and study of 887 cases. Dis Colon Rectum 1:172-1861958 Heillman N, Bernstein C: Roentgen abnormalities of the large
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24.
25.
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and small intestine associated with prolonged cathartic ingestion. Radiology 65:549-556,1955 Smith B: Effect of irritant purgatives on the myenteric plexus in man and the mouse. Gut 9:139,1968 Cummings JH, Sladen GE, James OFW, Sarner M, Misiewicz JJ: Laxative-induced diarrhoea: a continuing clinical problem. Br Med J 1:537-541,1974 Frame B, Guiana HL, Frost HM, Reynold WA: Osteomalacia induced by laxative (phenolphthalein) ingestion. Arch Intern Med 128:794-796.1971 Conn JW: Hypertension, the potassium ion and impaired carbohydrate tolerance. N Engl J Med 273:1135-1143,1965