The causes of dandruff are similar to the causes of baldness (see page 72), but a brief review will be made here because certain skin conditions should be added. Pityriasis simplex capitis is probably the most common cause, although no definite etiology has been established. Autoimmune disorders such as lupus erythematosus should be considered. Inflammatory disorders include ringworm (tinea capitis), impetigo, and seborrheic dermatitis. Idiopathic skin disorders such as psoriasis and lichen planus cause dandruff. These disorders can all be recalled by the same mnemonic that was applied in baldness, that is, HAIR.

  • H—Hereditary lesions include eczema and psoriasis.

  • A—Autoimmune disorders include lupus.

  • I—Inflammatory diseases include ringworm, impetigo, and seborrheic dermatitis. I also stands for idiopathic and thus includes pityriasis simplex capitis.

  • R—Radiation dermatitis.

The workup of dandruff is similar to that of baldness (see page 72).

Decreased Respirations, Apnea, and Cheyne–Stokes Breathing

Nurses frequently become distressed and summon the intern during the night about these signs. Cheyne–Stokes respirations are a frequent source of bewilderment because they may occur at times with no direct evidence of damage to the nervous system. It would be interesting to discuss the physiology of respiration at length in this section, but it will be of little help in the differential diagnosis of apnea and in slow or Cheyne–Stokes respirations except in a few instances. In all cases, these are a result of an insult to the respiratory centers in the brain by some etiologic agent. The causes of these signs can best be remembered by the mnemonic VINDICATE.

  • V—Vascular includes cerebral thrombosis, embolism, and especially hemorrhage of the brainstem, which may cause depressed respirations or periodic apnea. Diffuse cerebral arteriosclerosis is another cause in this category.

  • I—Inflammatory disorders signify encephalitis, poliomyelitis, meningitis, and brain abscesses, particularly with increased intracranial pressure.

  • N—Neoplasms of the brainstem (primary or metastatic) and neoplasms of the cerebrum are associated with increased intracranial pressure and may cause depression of respirations and Cheyne–Stokes breathing.

  • D—Degenerative diseases of the brain, including senile and presenile dementia and Schilder disease, may cause these signs in the terminal stages.

  • I—Intoxication is an important category of etiologies of depressed or irregular respirations because the toxic substance may not be obvious at first. Failure of any organ system to function may lead to respiratory depression. When there is respiratory failure from emphysema or other causes, carbon dioxide (CO2) builds up in the blood and CO2 narcosis develops. In this state the important stimulus of high blood CO2 on the respiratory centers is gradually lost and anoxia is the only stimulus left. Periodic or Cheyne–Stokes breathing frequently develops in the following manner: During respiration the blood oxygen builds up to a level at which the respiratory stimulus to anoxia is lost. Respirations cease. During apnea the blood oxygen falls to a point where there is sufficient anoxia to kick the respiratory center over again. The electrolyte disturbances and buildup of toxins in uremia, the high blood ammonia and other toxins that result from hepatic failure, and the anoxia of congestive heart failure (CHF) may all lead to apnea or depressed respirations.

Exogenous toxins are more commonly the cause in young people. Alcoholism, morphine, barbiturates, and a host of tranquilizers will cause respiratory depression in sufficient quantities.

  • C—Congenital disorders that cause these respiratory disturbances include Tay–Sachs disease, cerebral palsy, glycogen storage disease, reticuloendothelioses, epilepsy, and cerebral aneurysms with subarachnoid hemorrhage.

  • A—Autoimmune disorders such as lupus erythematosus and multiple sclerosis (MS) must be considered in this category.

  • T—Trauma is another frequent cause of apnea or Cheyne–Stokes respiration. Cerebral concussion, subdural, epidural, and intracerebral hematomas all may cause depressed respirations, especially when associated with increased intracranial pressure.

  • E—Endocrine disease reminds the reader that whereas diabetic coma may begin with Kussmaul breathing, in the advanced stages bradypnea and Cheyne–Stokes respirations develop from the severe acidosis. Pituitary and suprasellar tumors may grow sufficiently to compress the brainstem and cause apnea.

Approach to the Diagnosis

Obviously, the association of other signs and symptoms will determine the workup in most cases. The most important things to do are to order a blood urea nitrogen (BUN) level, electrolytes, fasting blood sugar (FBS), arterial blood
gases, and a drug screen and to check for increased intracranial pressure by examining the eye grounds. If the history or physical findings suggest increased intracranial pressure, and other metabolic studies (e.g., BUN) are normal, a mannitol or urea drip is begun while awaiting the results of other investigations such as computed tomography (CT) scan, electroencephalogram (EEG), and echoencephalogram. A neurosurgeon should be consulted immediately.

Decreased respirations, apnea, and Cheyne–Stokes breathing.

Delayed Puberty

Because most of the causes of delayed puberty are hormonal in origin, the key to recalling them will be visualizing the anatomy, particularly the endocrine glands.

  • Hypothalamus and pituitary: Lack of gonadotropin-releasing hormone from hypothalamic disorders such
    as Laurence–Moon–Biedl syndrome, space-occupying lesions, trauma, or infection may cause delayed puberty in girls and boys. Chromophobe adenomas, prolactinomas, craniopharyngiomas, trauma, granulomas, and vascular lesions may decrease the production of growth hormone and other pituitary hormones causing delayed puberty.

  • Thyroid: Both hypothyroidism and hyperthyroidism in children may cause delayed puberty.

  • Adrenal gland: Visualizing this organ will prompt the recall of congenital adrenocortical hyperplasia and Cushing syndrome.

  • Ovaries: Ovarian dysgenesis (Turner syndrome etc.), autoimmune oophoritis, and Noonan syndrome are associated
    with delayed puberty in girls. A masculinizing tumor of the ovary will present with delayed puberty on occasion.

  • Testicles: Irradiation, Klinefelter syndrome, Noonan syndrome, castration, and anorchism may cause delayed puberty in boys. Mumps rarely is the cause.

Delayed puberty.

The above method of recall will omit the chronic illnesses such as anorexia nervosa, malnutrition, renal failure, tuberculosis, celiac disease, collagen disease, and cyanotic heart disease that may cause delayed puberty. It also will not prompt the recall of drugs that cause delayed puberty such as thyroid hormone, anabolic steroids, and androgens in girls and thyroid hormones in boys. It is important to remember that over half the cases of delayed puberty in boys and 16% of cases in girls are due to constitutional delayed puberty.

Approach to the Diagnosis

The physician is frequently consulted early about this problem by an overprotective parent, so it is important to remember that there is little cause for alarm until age 15 in boys and age 14 in girls. Nevertheless, a workup may be started early if other telltale signs of pathology such as short stature, web neck, or small or absent testicles are found. The workup will probably include a thyroid profile, serum testosterone (boys), estradiol (girls), and follicle-stimulating hormone (FSH) and luteinizing hormone (LH) assay. Urine gonadotropins are less expensive screening tests. Pelvic ultrasound and CT scans of the abdomen and pelvis will help to identify ovarian and adrenal causes. A CT scan or magnetic resonance imaging (MRI) of the brain will identify most pituitary causes.

Other Useful Tests

  • Testicular biopsy (Klinefelter syndrome)

  • Buccal smear for Barr bodies (Klinefelter syndrome)

  • Complete blood count (CBC) and chemistry panel (renal failure)

  • Gynecology consult

  • Psychiatric consult

  • Visual field examination (pituitary tumor)

  • Serum growth hormone assay (pituitary tumor)

  • Urine drug screen (drug abuse)

  • Serum free cortisol (Cushing syndrome)

  • Full karyotyping (Klinefelter syndrome, Turner syndrome)

  • Laparoscopy (ovarian dysgenesis)

  • Serum prolactin (pituitary tumor)

  • Endocrine consult


The differential diagnosis of delirium is very similar to that for coma, and one finds the mnemonic VINDICATE useful in this regard.

  • V—Vascular disorders of the brain including hemorrhage, embolism, thrombosis, and arteriosclerosis may cause delirium.

  • I—Inflammatory disorders of the nervous system that may cause delirium include viral encephalitis, meningitis, syphilis, malaria and other parasites, rabies, and cerebral abscess. Generalized infections, usually when associated with fever, may be responsible.

  • N—Neoplasms of the brain are not usually associated with delirium until the end stages at which time the cause will be obvious.

  • D—Deficiency disorders that may be associated with delirium include Wernicke encephalopathy, pellagra, and pernicious anemia. Delirium may be associated with degenerative disorders such as Alzheimer disease.

  • I—Intoxication by an enormous number of exogenous and endogenous substances may cause delirium. Alcohol, cocaine, heroin, phencyclidine (PCP), marijuana, lead, arsenic, and manganese are just a few of the exogenous substances. Endogenous substances include uremia, ammonia from hepatic failure, hyperinsulinemia, diabetic ketosis, and porphyria. Delirium may be associated with the withdrawal of a patient from alcohol and/or any drug including morphine, cocaine, or tobacco.

  • C—Convulsive disorders may be associated with delirium either during or after the seizure.

  • A—Autoimmune disorders such as lupus erythematosus are associated with inflammation of vasculitis in the brain causing delirium.

  • T—Trauma may cause a concussion, cerebral hemorrhage, or subdural or epidural hematoma leading to delirium.

  • E—Endocrine disorders associated with delirium include insulinoma and diabetes.

Approach to the Diagnosis

It is essential to get a history of drug or alcohol use from the patient or family, and a drug screen may be done in most cases. Infection is another common cause. The workup should also include a CBC, sedimentation rate, urinalysis, antinuclear antibody (ANA) analysis, chemistry panel, serum and urine osmolality to rule out SIADH, and electrolytes. A CT scan or MRI of the brain will be necessary in most cases. It may be wise to administer intravenous thiamine and glucose while awaiting the results of blood work. If there is a fever, blood cultures and possibly a spinal tap (after a CT scan or MRI has ruled out a space-occupying lesion) may be indicated. Arterial blood gas analysis and carboxyhemoglobin should be determined. A neurologist or neurosurgeon needs to be consulted early in the workup.

Other Useful Tests

  • EEG (seizure disorder)

  • Venereal disease research laboratory (VDRL) test (neurosyphilis)

  • Carotid sonogram (carotid thrombosis)

  • Four-vessel angiography (transient ischemic attack [TIA])

  • Glucose tolerance test (diabetes, insulinoma)

  • Blood smear for malarial parasites (malaria)

  • Psychiatric consult

  • Urine porphobilinogen (porphyria)


A delusion is a persistent false belief. The feeling that one is being followed or watched, that one has a bad odor even after frequent and careful bathing, that one is superior to others—all are examples of delusions. Although most patients presenting with a delusion have a functional disorder, the astute clinician knows the organic disorders of the brain that may be associated with a delusion. The mnemonic VINDICATE forms a simple method for ready recall of these disorders.

  • V—Vascular disorders suggest cerebral arteriosclerosis with lacunar infarcts or cerebral emboli.

  • I—Inflammatory disorders suggest cerebral abscess, tuberculomas, viral encephalitis (e.g., herpes simplex), and general paresis.

  • N—Neoplasms, both primary and metastatic, should always be considered, as these are potentially treatable.

  • D—Degenerative diseases include senile and presenile dementia, Huntington chorea, diffuse sclerosis, and many other conditions.

  • I—Intoxication brings to mind alcoholism, bromism, chronic use of both “uppers” and “downers,” lysergic acid diethylamide (LSD), and cannabis. Uremia, CO2 narcosis, chronic anoxia, electrolyte disorders, and early hepatic coma should also be considered.

  • C—Congenital diseases suggest Schilder disease, mongolism, Wilson disease, and many other conditions associated with mental retardation.

  • A—Autoimmune diseases focus on lupus erythematosus, allergic angiitis, and MS.

  • T—Trauma facilitates the recall of concussion and chronic subdural hematomas.

  • E—Endocrine disorders include suprasellar tumors that invade the hypothalamus, acromegaly, hypopituitarism, hyperthyroidism, Cushing syndrome, and adrenal insufficiency. Parathyroid dysfunction can also cause delusions.

Approach to the Diagnosis

The important thing to do before referring these patients to a psychiatrist is to perform an evaluation of the mental status and a neurologic examination. Memory of recent events, orientation in time and place, ability to perform serial sevens, and interpretation of proverbial phrases should all be tested for. Psychologic testing may be warranted in borderline cases as well as an EEG, CT scan, skull roentgenogram, and spinal tap. A drug screen may also be indicated. Additional tests are listed below.

Depression, Anxiety, and Other Abnormal Psychic States

It is simple enough to administer a sedative and refer the emotionally distressed patient to a psychiatrist, but the astute diagnostician will want to rule out an organic disease first. Almost every endocrine disease is associated with emotional disturbances, all of which are potentially curable. In addition, electrolyte and other metabolic disturbances, chronic anoxia, or failure of any organ system may lead to anxiety, depression, or a psychotic state. The mnemonic VINDICATE will help to recall this important group of disorders.

  • V—Vascular diseases include myocardial infarction, CHF, cerebral arteriosclerosis, and thrombosis.

  • I—Inflammatory diseases recall syphilis, encephalitis, tuberculosis, brain abscess, influenza, pneumonia, and any prolonged infectious state, particularly that of the hospitalized patient with tubes in every orifice.

  • N—Neoplasms include cerebral tumors, tumors of the endocrine glands, and any neoplasm which is metastatic or which affects the metabolism of the body by a hormone or enzyme which it secretes. Pancreatic carcinoma is frequently associated with depression.

  • D—Degenerative diseases and deficiency diseases suggest presenile and senile dementia, pellagra, Wilson disease, and atrophy of the various endocrine glands.

  • I—Intoxication suggests lead poisoning, alcoholism, bromism, hypercalcemia, hypocalcemia, manganese toxicity, hypokalemia, hypovolemia, uremia, anoxia from pulmonary disease, anemia, heart disease, and corticosteroid therapy, as well as many other drugs. Porphyria may cause depression or a psychotic state.

  • C—Congenital suggests the depression associated with many congenital neurologic diseases: epilepsy, muscular dystrophy, Friedreich ataxia, myotonic dystrophy, and the depression associated with congenital heart disease and congenital defects of many organ systems.

  • A—Autoimmune diseases include MS and lupus erythematosus.

  • T—Traumatic disorders include the now well-recognized posttraumatic neurosis or depression, neurocirculatory asthenia, and postconcussion syndrome. Compensation neurosis should be mentioned here. Sexual abuse is a common cause in children.

  • E—Endocrine diseases include hypopituitarism, acromegaly, hypothyroidism, apathetic hyperthyroidism,

    hypoparathyroidism, hyperparathyroidism, diabetes mellitus, insulinoma, hypogonadism, menopause, Cushing syndrome, and adrenal insufficiency.


Depression, anxiety, and other abnormal psychic states.

Approach to the Diagnosis

If the patient is experiencing suicidal ideation, a referral to a psychiatrist is made immediately. The association of other symptoms and signs is all important. For example, anxiety, tremor, tachycardia, and diaphoresis may suggest alcohol withdrawal or hyperthyroidism. A triiodothyronine (T3) level, total thyroxine (T4) level, and free thyroxine index (FT4), urine for porphobilinogen, serum electrolytes, toxicology screen, lead level, 24-hour urine, 17-ketosteroid level, and 17-hydroxycorticosteroid level should be done on anyone suspected of having endogenous depression.
(Possibly all depressed patients should get this screen.) Skull x-ray film, EEG, CT scan, and even a spinal tap (to rule out MS and lues) may be worthwhile when other neurologic signs are present.

Diarrhea, Acute

Acute diarrhea is most likely infectious. Beginning with the smallest organism and working up to the largest will help recall the most common types of infectious diarrhea. The smallest organism prompts the recall of viral gastroenteritis. A midsized organism would suggest Staphylococcus, Salmonella, cholera, botulism, Campylobacter, Escherichia coli, Clostridium difficile, and bacillary dysentery. Moving up to the next largest organism, one would recall amebic dysentery and giardiasis. Both of these conditions move on to become chronic diarrhea if left untreated. Patients with acquired immunodeficiency syndrome (AIDS) may have acute diarrhea from cryptosporidiosis. This organism is responsible for worldwide epidemics of diarrhea. Finally, larger organism such as Trichinella spiralis may also be associated with acute diarrhea.

Acute diarrhea is also caused by many drugs such as antibiotics, colchicine, ethacrynic acid, digitalis, and quinidine. Pseudomembranous enterocolitis is a severe diarrhea that follows antibiotic administration. Another form of noninfectious acute diarrhea is associated with ulcerative colitis and Crohn disease. This is often characterized by grossly bloody stools.

Approach to the Diagnosis

The history may help differentiate many causes of acute diarrhea. Fever would help to distinguish Salmonella, Shigella, and Campylobacter jejuni. Blood in the stool also suggests Salmonella, Shigella, and Campylobacter, but may also be due to ulcerative colitis, amebic dysentery, or pseudomembranous colitis. If there is no blood in the stool, the patient most likely has viral gastroenteritis, staphylococcal toxin diarrhea, or traveler’s diarrhea. If other members of the family are experiencing the same symptoms, the clinician should look for staphylococcal toxin diarrhea or botulism. Vomiting is associated with toxic staphylococcal gastroenteritis and viral gastroenteritis, but is unlikely with giardiasis and pseudomembranous colitis.

All patients need to provide a stool sample for occult blood, culture, and smear for ovum parasites, and Giardia antigens. If there is a history of antibiotic use, the stool should be tested for C. difficile toxin B.

Other Useful Tests

  • Stool smear for leukocytes

  • Culture for Campylobacter or Yersinia

  • Sigmoidoscopy

  • Colonoscopy

  • Stool for Giardia antigen

  • Swallowed string test (Giardiasis)

Diarrhea, Chronic

The differential diagnosis of diarrhea may be approached from either an anatomic or a physiologic basis. The anatomic approach is used in Table 22. In the stomach and duodenum, pernicious anemia and Zollinger–Ellison syndrome are prominent causes. A carcinoma may form a fistula with the transverse colon and cause diarrhea. Viral gastroenteritis and Giardia infection may also be prominent causes.

Liver and biliary tract diseases of all types may cause diarrhea (steatorrhea) by decreasing the secretion of bile. Ampullary carcinoma and cirrhosis are illustrated here, but one should not forget the diarrhea of chronic cholecystitis. The pancreas is the source of important digestive enzymes; as a result, chronic pancreatitis and pancreatic carcinomas may be associated with diarrhea (steatorrhea) in adults, whereas cystic fibrosis should be considered in children. The pancreatic islet cell tumors may secrete gastrin or vasoactive intestinal peptide, causing diarrhea.

Most of the lesions causing diarrhea are in the small intestine. Thus, cholera, Salmonella, Staphylococci, typhoid, and tuberculosis attack here. The carcinoid syndrome, various polyps (especially Peutz–Jeghers), and regional ileitis are also important causes. Toxins and drugs (see Table 23) are common causes acting here, as are pellagra and other vitamin deficiencies and food allergies. Systemic autoimmune diseases such as scleroderma and Whipple disease are also important. Mesenteric artery insufficiency or obstruction should be considered both here and in the colon.

A wide variety of etiologic agents cause diarrhea by their action on the colon.

  • V—Vascular diseases include ischemic colitis.

  • I—Infectious agents such as bacillary dysentery (Shigella), Escherichia coli, Campylobacter, Yersinia, and amebiasis may ulcerate or inflame the colon.

  • N—Neoplasms such as carcinomas and polyps cause chronic irritation and exudates from the colon with hypermotility and diarrhea.

  • D—Degenerative lesions of the muscularis that cause diverticulosis and allow overgrowth of bacteria and chronic
    inflammation may lead to diarrhea, but this may be classified under the idiopathic category as well.


  • I—Intoxicating substances, osmotic cathartics, and antibiotics (by allowing overgrowth of bacteria and fungi) may involve the colon (e.g., pseudomembranous colitis). Mucous colitis or irritable bowel syndrome may best be classified as idiopathic. Laxative abuse is a frequent cause of chronic diarrhea.

  • C—Congenital lesions of the colon include the solitary diverticulum of the cecum, malrotation (more frequently associated with intestinal obstruction), and familial polyposis.

  • A—Autoimmune disease of the colon is common and includes both ulcerative colitis and granulomatous colitis.

    Table 22 Diarrhea—Anatomic Classification

    Degenerative and Deficiency
    Intoxication or Idiopathic
    Autoimmune or Allergic
    Stomach and Duodenum   Viral gastroenteritis
    Carcinoma with fistula into intestines Pernicious anemia
    Iron deficiency
        Surgery (e.g., blind loop) Zollinger–Ellison syndrome
    Liver and Biliary Tract   Chronic cholecystitis and lithiasis Neoplasm obstructing bile ducts Cirrhosis Cirrhosis        
    Pancreas   Chronic pancreatitis Pancreatic carcinoma
    Islet cell adenoma
      Radiation Cystic fibrosis     Pancreatic cholera
    Small Intestine Mesenteric artery insufficiency Cholera
    Escherichia coli
    Pyridoxine deficiency
    Other drugs
    Peutz–Jeghers diverticulum (Meckel) Regional ileitis
    Whipple disease
    Fistula Hypoparathyroidism
    Addison disease
    Large Intestine Mesenteric artery insufficiency Shigella
    Other parasites
    Carcinoma and other neoplasms
      Mucus colitis
    Familial polyposis Ulcerative colitis
    Granulomatous colitis
    Food allergy

  • T—Trauma is not a common cause of diarrhea anywhere in the intestinal tract, but certainly surgically induced fistulas may occur in the colon or anywhere else.

  • E—Endocrine disorders do not usually affect the colon directly.

Having considered the local causes of diarrhea, do not forget reflex diarrhea from diseases of other organs, such as pyelonephritis, salpingo-oophoritis, and central nervous system diseases.

Using Table 23, the reader can develop the differential diagnosis of diarrhea with physiology. Diarrhea may result from increased intake of fluids or bulk foods; hyposecretion of enzymes necessary for digestion of food; hypersecretion of gastrointestinal (GI) fluids and enzymes; malabsorption of various substances, particularly protein and fat; exudations of pus induced by granulomatous or ulcerative colitis and Salmonella or Shigella infections; hypermobility from stimulation by cathartics, various hormones (e.g., vasoactive intestinal peptides and gastrin); and hypomobility from autonomic dysfunction as occurs in diabetic neuropathy.

Approach to the Diagnosis

If possible stop all drugs that may be the cause immediately. Whichever method is applied (anatomic or physiologic), most causes of diarrhea can be recalled before interviewing the patient. Then one can proceed to ask the right questions to eliminate each suspected cause. Are other members of the family affected? Is there a history of recent travel abroad? Combinations of symptoms and signs will assist greatly in narrowing the differential diagnosis. For example, chronic diarrhea and copious mucus without blood suggests irritable bowel syndrome. Chronic diarrhea with mucus and blood suggests ulcerative colitis.

Physical examination is often unrewarding but it may disclose a hepatic, rectal, or pelvic source for the diarrhea; it may also indicate that the diarrhea is a sign of a systemic disease (e.g., scleroderma or hyperthyroidism). Rectal examination may reveal a fecal impaction. A warm stool examination for pus, pH (acid stool suggests lactase deficiency), fat and meat fibers, blood, ova, and parasites is most essential. Stool for immunoassay for lactoferrin may indicate bacterial infection. A stool culture is done. Proctoscopy (immediately if there is blood) followed by colonoscopy, barium enema, and upper GI series is usually necessary in all cases. A CT scan of the abdomen is occasionally necessary.

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