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A glucagonoma is a rare tumor of the alpha cells of the pancreas that results in up to a 1000-fold overproduction of the hormone glucagon. Alpha cell tumors are commonly associated with glucagonoma syndrome, though similar symptoms are present in cases of pseudoglucagonoma syndrome in the absence of a glucagon-secreting tumor. more...

Gardner's syndrome
Gastric Dumping Syndrome
Gastroesophageal reflux
Gaucher Disease
Gaucher's disease
Gelineau disease
Genu varum
Geographic tongue
Gerstmann syndrome
Gestational trophoblastic...
Giant axonal neuropathy
Giant cell arteritis
Gilbert's syndrome
Gilles de la Tourette's...
Gitelman syndrome
Glanzmann thrombasthenia
Glioblastoma multiforme
Glucose 6 phosphate...
Glycogen storage disease
Glycogen storage disease...
Glycogen storage disease...
Glycogenosis type IV
Goldenhar syndrome
Goodpasture's syndrome
Graft versus host disease
Graves' disease
Great vessels transposition
Growth hormone deficiency
Guillain-Barré syndrome


Fewer than 250 cases of glucagonoma have been described in the literature since their first description by Becker in 1942. Because of its rarity (fewer than one in 20 million worldwide), long-term survival rates are as yet unknown.


The primary physiological effect of glucagonoma is an overproduction of the peptide hormone glucagon, which enhances blood glucose levels through the activation of catabolic processes including gluconeogenesis and lipolysis. Gluconeogenesis produces glucose from protein and amino acid materials; lipolysis is the breakdown of fat. The net result is hyperglucagonemia, decreased blood levels of amino acids (hypoaminoacidemia), anemia, diarrhea, and weight loss of 5-15 kg.

Necrolytic migratory erythema (NME) is a classical symptom observed in patients with glucagonoma and is present in 80% of cases. Associated NME is characterized by the spread of erythematous blisters and swelling across areas subject to greater friction and pressure, including the lower abdomen, buttocks, perineum, and groin.

Diabetes mellitus also frequently results from the insulin and glucagon imbalance that occurs in glucagonoma. Diabetes mellitus is present in 80-90% of cases of glucagonoma, and is exacerbated by preexisting insulin resistance.


A blood serum glucagon concentration of 1000 pg/mL or greater is indicative of glucagonoma (the normal range is 50-200 pg/mL).

Blood tests may also reveal abnormally low concentrations of amino acids, zinc, and essential fatty acids, which are thought to play a role in the development of NME. Skin biopsies may also be taken to confirm the presence of NME.

A CBC can uncover anemia, which is an abnormally low level of hemoglobin.

The tumor itself may be localized by any number of radiographic modalities, including angiography, CT, MRI, PET, and endoscopic ultrasound. Laparotomy is useful for obtaining histologic samples for analysis and confirmation of the glucagonoma.


Heightened glucagon secretion can be treated with the administration of octreotide, a somatostatin analog, which inhibits the release of glucagon. Doxorubicin and streptozotocin have also been used successfully to selectively damage alpha cells of the pancreatic islets. These do not destroy the tumor, but help to minimize progression of symptoms.

The only curative therapy for glucagonoma is surgical resection, where the tumor is removed. Resection has been known to reverse symptoms in some patients.


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Constipation in women - Women's Health Update
From Townsend Letter for Doctors and Patients, 6/1/03 by Tori Hudson

Constipation affects almost everyone at some point in their life. Usually, it is temporary and resolves on its own, but for others it is chronic, frustrating, and can cause significant discomfort and problems.

For women and those who are elderly, constipation may be significant enough to cause them to seek medical attention. It is one of the most common gastrointestinal complaints and it has been estimated that at least 4.5 million people, two thirds of them women, suffer constipation that is frequent and problematic enough to require medical attention. Even with that many individuals who suffer, it lends itself to considerable self-treatment efforts, and lack of discussion with the physician due to embarrassment, and is therefore underreported.

Because of the higher incidence in women, health care practitioners who specialize in women's health play a key role in evaluation and management of constipation. Although a seemingly simple problem, individuals with chronic constipation, new onset of constipation or severe constipation have a wide array of possible causes that require evaluation, diagnosis, management, and at times, referral. To add to the potential complexity, a specific etiology is not found at least half the time.

Due to the prevalence of constipation in women and in the aging individual, clinicians need to understand the physiology, evaluation and array of treatment options to be able to properly address this condition in the increasingly female and elderly demographics in our clinical practice.


Patients seem to have varying definitions of constipation. For some it means straining and for others it means infrequent. For yet others, they would consider a bowel movement once per week as normal since they've had it their whole life. To most individuals though, normal bowel habits are having a movement every day. Most complementary and alternative medicine (CAM) providers would also agree that a daily bowel movement is normal. That may not be a reasonable expectation for women, although I would argue that it is optimal. The bowel frequency of women is generally less than that of men. (1) Studies have been done that suggest that the majority of women have bowel movements no more often than every other day. (2) It may be that there is a range of normal, from three times per week to three times per day. It is important to clarify the details of what they mean by constipation when taking a history.

The first line of information is the patient's subjective perceptions, but there are some objective criteria that are helpful and needed in order to define constipation as a clinical entity. Currently, there is a standard of two or more of the following symptoms that an individual experiences for 3 or more months without the use of laxatives:

* straining with defecation more than 25% of the time

* lumpy or hard stools more than 25% of the time

* incomplete evacuation fore than 25% of the time

* two or less bowel movements per week

From a CAM perspective, these guidelines may be less than adequate from the point of view of preventive medicine. There is a long tradition in natural medicine that "toxemia," or the build-up of endogenous toxins is at least in part related to slow colonic transit time. Basically, the longer the stool sits in the large intestine, the longer the exposure of toxins to the mucosa and blood stream that can then lead to increased absorption.


All studies are in agreement that significantly more women than men report constipation and that the prevalence increases with age. In 1989, an analysis on national data reported that the prevalence of frequent or chronic constipation was about 2%. (3) Constipation was three times more common in women and after age 65, it rose to 8% in women and 4% in men. In 1990, the first National Health and Nutrition Examination Survey reported a higher incidence in the general population of 12.8% with the ratio of women to men being more than 2 to 1 (18.2% vs 7%). (4) For those over 60, it affected 25.3%.

Pregnant women may have greater problems, as many as 38%, although there is not good research in this area. The majority of the problems are in the third trimester and often persist for several months. Pregnancy and vaginal delivery may also have long lasting adverse effects on bowel function by weakening the pelvic floor muscles.


The process of eliminating solid wastes involves fluid absorption, solid compaction, and transport by the colon, all via impulses from the enteric nervous system. A delay in transit time leads to excessive water absorption by the colon. This results in smaller, harder stools that are more difficult to pass. Peristaltic waves generated by the smooth muscle in the colonic walls propel stool through the system. If there is a reduction in the frequency and duration of these waves, the transit time slows. Normal transit time is about 6 hours in the small intestine and 36 to 72 hours in the large intestine. The role of the rectum is to store and then evacuate stool by strong muscular actions. The urge to defecate is initiated by the contact of stool with receptors in the anal canal. If the anal sphincters and pelvic floor muscles contract rather than relax when receiving the urge stimulus, defecation cannot occur which is called anismus or anorectal dyssynergia. Abnormal dilatation of the rectum or colon, rectal pr olapse or rectocele, or Herschsprung's disease can also lead to obstruction of defecation.

It is worth speculating why women have a higher incidence of constipation. Certainly pelvic floor dysfunction after pregnancy could be an explanation for some of the cases. Longer transit times have been noted in the third trimester and during the luteal phase when progesterone levels are high. Other hormonal influences may influence physiological changes in water absorption, peristalsis, and transit time. Psychological differences may also be a source of the higher incidence in women. Slower transit time has been associated with depression caused by sexual abuse.5 Depression, more common in women, is also more common in women with other bowel problems such as irritable bowel syndrome.


Most cases of constipation result from no identifiable specific cause (idiopathic). This is determined to be primary constipation and is divided into two types - delayed transit time and outlet obstruction associated with some kind of anorectal dysfunction. Typical symptoms reported by the patient are pain or straining during defecation.

Secondary constipation is due to either dietary problems, lack of exercise, lack of enough water intake, laxative abuse, medications, surgeries, irritable bowel syndrome, other metabolic or endocrine disorders, disorders of the nervous system, mechanical compression, psychological disorder, and pregnancy. (see list)

Secondary Causes of Constipation Abdominal or pelvic surgery

Dietary habits

Low fiber intake

Low intake of fluids

High consumption of animal fats

High consumption of refined sugar

High caffeine intake

High alcohol intake

Eating disorders

Endocrine disorders






Irritable Bowel Syndrome

Lifestyle/Personal habits

Changes in routine

Ignoring the urge to defecate

Laxative abuse

Lack of exercise


Mechanical compression or obstruction

Anal fissures

Colorectal strictures






Postoperative adhesions

Rectal prolapse


Ulcerative proctitis



Arthritis drugs


Opiates and narcotics




Parkinson's drugs



Calcium channel blockers




Monoamine oxidase inhibitors

Vincristine chemotherapy agents





Metabolic conditions






Connective tissue disorders


Muscular dystrophy


Neurogenic disorders


Brain tumor

Chagas' disease

Hirschsprung's disease

Lumbar disc disease

Multiple sclerosis


Parkinson's disease


Spinal cord injuries







Fortunately, most of the cases of constipation are idiopathic and do not involve serious disorders. However, a thorough history and physical examination are needed to exclude the more serious as well as specific concerns and to determine who requires a more thorough evaluation. Constipation may be the first symptom that arises in cancer or other secondary causes so it is important to be thorough in the initial history and physical exam and not to discount their problem and to not hesitate in more extensive testing. In a history it is important for the clinician to gain clear information about bowel frequency, stool consistency and size, presence of blood or mucus, straining or pain, bloating or pain, diet, exercise, medication, supplements, laxatives or enemas, recent life stressors, and a good review of systems in order to recognize indications of other more systemic problems. Physical examination will involve recognizing clues to metabolic and endocrine disorders, digital rectal examination, abdominal and p elvic exam, and neurological exam.

Laboratory tests may include a complete blood count to rule out anemia, serum electrolytes and glucose, serum calcium and thyroid stimulating hormone. More specialized tests need to be done in cases where there is a suspicion of a more serious disease or obstruction, and when symptoms persist despite good treatment. These tests may include occult stool, sigmoidoscopy or colonoscopy, abdominal X-ray, barium studies, transit time studies, anorectal function studies, and more specialized tests to rule out the numerous disorders that may be an underlying cause.

Therapeutic Approach

Most would agree that the high incidence of constipation in the US correlates with a low fiber diet, low fluid intake, and being sedentary. Whether or not this will solve their constipation, it is fundamental to start here when there is no evidence of obstruction, impaction or anismus.

A daily fiber intake is recommended to be 20 to 35 g daily. This can be accomplished with a diet stressing whole grain breads, bran cereal, legumes, fresh fruits and vegetables, and therapeutic foods such as prunes. Limiting caffeinated beverages and alcohol is also important because they are diuretics. Intake of eight glasses of water or unconcentrated fruit juice daily is also important. Remember that some individuals will have a difficult time with increased dietary fiber. They may need to go slow in order to avoid gas, bloating and discomfort. When making dietary changes, it not only takes time to accomplish these changes, it may take 2 to 3 months for the results to manifest. Increasing physical activity is also fundamental to toning abdominal muscles, and proper enervation to the colon.

The use of laxatives requires some medical knowledge because they work in different ways. We should consider these temporary solutions to relieve symptoms and to help retrain the bowel. There are six basic laxative types:

1. Bulk-forming laxatives.

These can be derived from psyllium, extracted from the husk of Plantag ovata, ground flax seeds, or methylcellulose, a synthetic material. Their basic function is to absorb water in the intestine to soften the stool. They can also result in increased flatulence and bloating. They do act faster than food fiber but slower than other laxatives and typically take about a week to work. Bulk-forming laxatives improve transit time and are very compatible with dietary modifications.

2. Emollients and stool softeners

These agents aid the mixing of watery and fatty substances in the bowel both to soften the stool and to lubricate the stool so it can be passed easier. They also prevent dehydration by stimulating fluid secretion. They can be taken orally or rectally and typically work very fast, usually within 24 hours. If a patient is in pain because of hard stool, this is an appropriate choice. Glycerin suppositories or mineral oil are common examples. Mineral oil should be used sparingly because it can decrease absorption of fat-soluble vitamins. Herbs such as buckthorn bark can also soften the stool.

3. Saline laxatives

Magnesium salts have been used for decades. They are poorly absorbed in the intestines and exhibit a sponge-like action to draw water into the colon to soften the stool and promote transit. They act fairly quickly, as do the stool softeners. Magnesium sulfate is more potent than magnesium citrate or magnesium hydroxide and should be used with caution. Individuals with renal impairment or hypertension should avoid saline laxatives.

4. Hyperosmoties

These are the new laxatives on the block. Oral prescription medications, they create a high concentration gradient to draw fluid out of the bloodstream into the colon. Examples include lactulose, lactitol and sorbitol. These products can produce some bloating and flatulence and produce effects in 2 to 3 days.

5. Osmotics

Polyethylene glycol electrolyte solution is the product that is normally given to empty the colon before a colonoscopy. It can also be used to treat severe fecal impaction. Aprescription, MiraLax is a newer prescription for use in constipation using polyethylene glycol.

6. Bowel stimulants

These laxatives act on elimination mechanisms by stimulating sensory nerve endings in the colonic mucosa to trigger peristalsis. They also promote fluid secretion into the colon and improve the consistency of the stool. Aloe, senna, cascara sagrada, and castor oil are all potent laxatives that can produce a rapid response. They should be used for more severe cases and should not be used long term.

Herbalists, Naturopathic physicians, and other CAM providers knowledgeable in herbal medicine also consider the use of restoring normal colonic microflora with lactobacillus species, enhancing the digestive process with digestive enzymes, and the use of herbal digestive aids (gentian root, cinammon, dandelion root, lemon balm, licorice root, turmeric root, ginger root, yarrow, and more), as fundamental tools in treating individuals with constipation.

Behavioral therapy with biofeedback may yield some success with anismus as well as reducing the effects of stress in general. Enemas are used to induce contractions by distending the colon. High colonics may be used sparingly for the same purpose. Abdominal massage from right to left can promote peristalsis. Hydrotherapy treatments that stimulate colon function (external applications of alternating hot and cold; or a traditional naturopathic treatment called, "constitutional hydrotherapy"). Warm water enemas or colonics may be useful for fecal impaction as well. Surgical interventions are the last resort and are rarely necessary.

Initial sample treatment plan for mild uncomplicated constipation: (try for 2 to 3 months before adding other therapies)


Because constipation affects women more than men, it especially concerns those primarily delivering health care to women. Most women will only need reassurance, education and basic advice. Others will need further evaluation and/or more sophisticated treatment interventions, whether exclusively natural methods, conventional methods, or an integration of both. The goal is to assure that they do not have a significant underlying cause, provide relief, improve general health, provide prevention strategies for the future, and to accomplish these things with minimal side effects.


(1.) Heaton K, Radvan J, Cripps H, et al. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. 1992; 33:818-824.

(2.) Toglia M. Pathophysiology of anorectal dysfunction. Obstet Gynecal Clin North Am. 1998; 25:771-780.

(3.) Sonnenberg A, Koch T. Epidemiology of constipation in the United States. Dis Colon Rectum. 1989;32:1-8.

(4.) Sandier R, Jordan M, Shelton B. Demographic and dietary determinants of constipation in the US population. Am J Public Health. 1990;80:185-289.

(5.) Devroede G, Girard B, Boucheoucha M, et al. Idiopathic constipation by colonic dysfunction: relationship with personality and anxiety. Dig Dis Sci. 1989;34:1425-1433.

COPYRIGHT 2003 The Townsend Letter Group
COPYRIGHT 2003 Gale Group

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