A 16-year-old girl is brought to a pediatrician because her mother is concerned about her weight loss over the last

year. When the pediatrician attempts to interview the girI, she is clearly hostile, denies that she has any medical problem, and states that she is just trying to "Iook good." The girI's height is 175 cm (5'9") and her weight is 41.4 kg (91 pounds). AIthough the girl is unwilling to discuss her weight with the physician, her mother reports that her daughter is convinced that she is too fat. The mother states that the girl is always finding excuses to not eat, or at the most, to eat only a few bites of fruit, even though she is still interested in cooking elaborate meals for her family. On one occasion, she discovered her daughter vomiting after a meaI, and believes that the vomiting was self-induced.
Question 1 of 6

Which of the following is the normal range for body mass index (BMI)? / A. Below 16 / B. 16-19 / C. 19-25 / D. 25-35 / E. Over 35 Explanation - Q: 1.1
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The correct answer is C. Body mass index is coming into increasing use when evaluating weight problems, because it provides a simple calculation that allows individuals of a variety of heights and weights to be classified as underweight, overweight, or in the normal range. The normal range for BMI is 19 to 25. Individuals with BMI below 16 (choice A) are considered anorexic and those with BMI 16-19 (choice B) are considered underweight. Individuals with BMI 25-35 (choice D) are considered mildly to moderately obese and those with BMI greater than 35 (choice E) are considered severely obese.

Question 2 of 6

This girI's body mass index is which of the following? / A. 10.5 / B. 13.5 / C. 16.5 / D. 21.5 / E. 27.5 Explanation - Q: 1.2
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The correct answer is B. Body mass index was originally a European concept, and is calculated as the body weight in kilograms divided by the square of the height in meters. In this country, we need to convert from pounds to kilograms and from feet and inches to meters in order to perform the calculation (a calculator helps). This girl's body weight is 91 pounds, which is divided by the conversion factor 2.2, yielding 41.4 kilograms. Her height is 5 x 12 + 9 = 69 inches, which is divided by the conversion factor 39.4 to get the height in meters, in this case 1.75 meters. Now calculate the BMI as 41.4 kilograms/ (1.75 meters x 1.75 meters) = 13.5. This girl has a BMI in the anorexic range.
Question 3 of 6

Which of the following is the most likely diagnosis? / A. Anorexia nervosa / B. Binge eating disorder / C. Body dysmorphic disorder / D. Bulimia nervosa / E. Normal adolescent developmental issues / F. Orthorexia nervosa Explanation - Q: 1.3
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The correct answer is A. It is not uncommon for individuals with severe eating disorders to be very unwilling to seek help, as in this case. This markedly underweight girl, who is still convinced that she is fat and is dieting compulsively, most likely has anorexia nervosa. Anorexia nervosa is best understood as an eating disorder with a large psychological component in which an individual engages in the relentless pursuit of thinness. As many as 50% of anorexics also have binge and purge behavior. On a practical basis, the condition is usually diagnosed when the weight is 85% or less than what is expected for age and height. The psychological component usually includes a perception of being overweight despite evidence to the contrary, a terror of gaining weight, and a denial of the dangers of very low weight. Many theorists cite our society's preoccupation with slenderness as the premier standard for female beauty as a major contributing factor to this disease. While over 90% of patients with anorexia are young women who develop it in their teens to early 20's (peak age 16), the condition can also be seen in children, middle-aged adults, boys, and men. Binge eating disorder (choice B) refers to binge eating not followed by vomiting, and is often accompanied by obesity. Body dysmorphic disorder (choice C) is separated from anorexia nervosa by psychiatrists because it is based on a preoccupation with "ugliness" rather

than "fat"; patients with this condition are likely to make numerous statements like "my nose is terrible." In body dysmorphic disorder, the focus is generally on a part of the body (face, buttocks) rather than the body image as a whole. Bulimia nervosa (choice D) is characterized by episodes of binge eating followed by vomiting or purging with laxatives. There is some overlap with anorexia nervosa, but many patients have normal weight to mild obesity. Normal adolescent developmental issues (choice E) often involve concern for weight, self-image and sexual attractiveness. However, the case steps outside the normal range. The girl's overall weight, the hostility regarding discussing these issues, and the self-induced vomiting are all indications of something outside the range of normal. Orthorexia nervosa (choice F), while not a formally accepted medical classification, is a term in common use in the discussion of eating disorders, and refers to a pathologic fixation on eating "pure" or "superior" food.
Question 4 of 6

This girl would most likely also have which of the following menstrual disorders as a complication of her condition? / A. Amenorrhea / B. Dysfunctional uterine bleeding / C. Premenstrual syndrome / D. Primary dysmenorrhea / E. Secondary dysmenorrhea Explanation - Q: 1.4
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The correct answer is A. Women with anorexia nervosa do not usually have menstrual periods. Many medical specialists require the presence of amenorrhea before making a diagnosis of anorexia nervosa in women. Depending upon the age at which the anorexia begins, they may either never have periods (primary amenorrhea) or may have periods that cease when they lose weight (secondary amenorrhea). The other conditions listed are not specifically related to anorexia nervosa. Dysfunctional uterine bleeding (choice B) is abnormal uterine bleeding (prolonged flow, irregular flow, or profuse flow) not associated with tumor, inflammation, or pregnancy. Premenstrual syndrome (choice C) refers to the presence of nervousness, irritability, emotional instability, anxiety, headaches, edema, or mastalgia during the 7 to 10 days before the onset of menstruation.

Dysmenorrhea is menstrual pain, and may be either primary (choice D) and unrelated to demonstrable reproductive pathology or secondary (choice E) to other reproductive disease.
Question 5 of 6

The most common cause of death in this condition is arrhythmia, which is usually related to which of the following electrolyte abnormalities? / A. High serum calcium / B. High serum iron / C. Low serum magnesium / D. Low serum potassium / E. Low serum sodium Explanation - Q: 1.5
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The correct answer is D. While many fluid and electrolyte abnormalities can be seen in patients with anorexia nervosa, low serum potassium is particularly common, and may cause a fatal arrhythmia. The low serum potassium is usually initially due to very low intake, but may be exacerbated by processes that increase body potassium losses, such as with vomiting, diuretic use, or heavy laxative use. Large numbers of mild cases of anorexia nervosa are never diagnosed and may not develop severe medical problems. Mortality rates among diagnosed cases are surprisingly high, and may be up to 10-20% among the most severe cases without effective intervention. In addition to arrhythmias, anorexics may develop potentially fatal liver or renal disease, teeth problems, esophageal rupture (in bulimics compulsively vomiting), a weakened immune system, anemia, malnutrition, impaired mentation, and salivary duct stones. Severe anorexics are initially treated with hospitalization to prevent death, suicide, and medical crises. It is of particular concern to the medical community serving these patients that our present system of health maintenance organizations often limits the hospitalization of these individuals to less than one month, when four or more months may be required to bring them away from the edge of death. Psychiatric help is usually only effective after a near normal weight has been medically achieved. The other answers listed in the choices are distracters.

Question 6 of 6

Over the next several years, in addition to the treatment of her current condition, this girl should also be monitored for the possible onset of which of the following? / A. Acute stress disorder / B. Agoraphobia / C. Conversion disorder / D. Depression / E. Panic disorder / F. Substance abuse Explanation - Q: 1.6
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The correct answer is D. Between 50% to 80% of patients diagnosed with anorexia nervosa also suffer from depression at some point in their lives. Acute stress disorder (choice A) is defined by mental reexperiencing of a traumatic event, avoidance of stimuli that remind the person of the event and a host of secondary symptoms including sleep disruption or excess, withdrawal from the world, impulsive behavior, headaches and somatic complaints. Symptoms must resolve in less than one month. If they do not, we use the diagnosis of posttraumatic stress disorder. There is no association between anorexia and acute stress disorder. Agoraphobia (choice B) suggests a fear of being open, vulnerable and exposed when out and about in the community. There is no link between this anxiety disorder and anorexia. Conversion disorder (choice C) is defined by the loss of physical functioning due to psychological etiology. Generally, the symptom is focused on the loss of the use of a limb or one of the primary senses. There is no correlation of this disorder with anorexia. Panic disorder (choice E) is characterized by the occurrence of three panic attacks in a three-week period. A panic attack is an overwhelming, sudden physiological arousal featuring tachycardia, profuse sweating, hyperventilation, and feelings of doom and dread. There is no association between anorexia and panic disorders. Substance abuse (choice F) is relatively uncommon with anorexic patients. They seem obsessively concerned with which types of substances they are willing to put into their bodies. A 30-year-old woman has noticed a gradual increase in weight over the past eighteen months. The fat deposition has occurred mostly in the

face, neck, trunk, and abdomen. She has also noticed an increase in black facial hairs that has been accompanied by acne. Physical examination reveals the presence of purple abdominal striae, but generalized hyperpigmentation is absent. A poorly-healed laceration is observed on the right shin. BIood pressure is 155/100 mm Hg. The physician suspects Cushing disease.
Question 1 of 5

Which of the following sets of hormone levels would be most consistent with this diagnosis?

Explanation - Q: 2.1

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The correct answer is D. Pituitary ACTH-dependent Cushing syndrome (Cushing disease) is the most frequent cause of Cushing syndrome. It is responsible for 70% of reported cases. It is characterized by increased plasma ACTH and increased serum cortisol. Another hallmark of Cushing disease is the absence of the normal diurnal rhythm in plasma cortisol. This rules out choice C, which shows a prominent decrease in PM cortisol levels. Plasma ACTH is typically only modestly increased. Hyperpigmentation is rare. Choice A is incorrect because serum cortisol levels are low. The increased plasma ACTH is consistent with primary adrenal insufficiency (Addison disease). Choice B is incorrect because serum cortisol levels are low. The lower-thannormal plasma ACTH is consistent with secondary (pituitary) adrenal insufficiency. Choice E shows increased serum cortisol and absence of diurnal rhythm, but plasma ACTH is below normal. These laboratory values would be consistent with Cushing syndrome caused by a cortisol-secreting adrenal adenoma

(primary hypercortisolism).
Question 2 of 5

ACTH measured in blood drawn from which of the following vessels would give the best indication of direct anterior pituitary secretion? / A. Inferior petrosal sinus / B. Internal jugular vein / C. Sigmoid sinus / D. Sphenoid sinus / E. Transverse sinus Explanation - Q: 2.2
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The correct answer is A. This question may seem difficult, but the key is the fact that the pituitary is located near the cavernous sinuses. Venous drainage from the anterior pituitary, although variable, can be expected to flow, via the nearby cavernous sinuses, posteriorly into the superior and inferior petrosal sinuses before draining, via the sigmoid sinuses, into the internal jugular veins. A skilled invasive radiologist can sample blood bilaterally from the inferior petrosal sinuses. If the ACTH concentration in the sinus blood is greater than twice the concentration in a peripheral vein, Cushing disease is likely. Bilateral sampling of blood from the inferior petrosal sinuses can also locate the tumor to one side or the other. The internal jugular vein (choice B) receives blood from a number of other veins in addition to the petrosal sinuses. Hence, the pituitary ACTH is diluted considerably by the time it reaches the jugular vein. The sigmoid sinus (choice C) receives drainage via the petrosal sinuses before flowing into the internal jugular vein, but also receives flow from the larger transverse sinuses (choice E), which dilutes the ACTH concentration. The transverse sinus receives drainage from a number of cerebral and cerebellar locations, which does not include flow from the anterior pituitary. The sphenoid sinus (choice D) is part of the nasal system. It is an air-filled cavity and does not carry blood.
Question 3 of 5

Which of the following is considered the regulated step in steroid hormone synthesis in the zona fasciculata? / A. Cholesterol to pregnenolone / B. Corticosterone to aldosterone / C. 11-Deoxycortisol to cortisol

/ /

D. Pregnenolone to progesterone E. Progesterone to 17- -hydroxyprogesterone Explanation - Q: 2.3

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The correct answer is A. The conversion of cholesterol to pregnenolone is considered the rate-limiting and regulated step in steroid biosynthesis in the zona fasciculata, which secretes the glucocorticoid, cortisol. ACTH binds to a membrane-associated receptor and increases cAMP formation. The subsequent activation of protein kinases and phosphorylation results in increased expression of LDL receptors and activation of cholesterol esterase. The increase in LDL receptors increases the delivery of cholesterol to the zona fasciculata. The activation of cholesterol esterase increases the liberation of intracellular cholesterol from cholesterol esters. ACTH also induces a mitochondrial protein called steroidogenic acute regulatory (StAR) protein. StAR functions to shuttle cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane, where the cholesterol side chain cleavage enzyme converts it to pregnenolone. Corticosterone is converted to aldosterone (choice B) in the zona glomerulosa, but not in the zona fasciculata. This is also a regulated step. Angiotensin II acts via a membrane-associated receptor to increase the activity of aldosterone synthase (a combination of two enzymes with 18hydroxylase activity) and, hence, increase aldosterone synthesis and secretion. 11-deoxycortisol is converted to cortisol (choice C), primarily in the zona fasciculata, but also in the zona reticularis. The enzyme responsible is 11hydroxylase, a mitochondrial enzyme. 11-hydroxylase is not regulated by ACTH. Pregnenolone is converted to progesterone (choice D) in all steroid secreting tissues. The enzymes responsible are 3-ol dehydrogenase and D4,5isomerase. These enzymes are cytoplasmic, and are not regulated by ACTH. The conversion of progesterone to 17-progesterone (choice E) is catalyzed by 17-hydroxylase, which is cytoplasmic. This enzyme is not found in the zona glomerulosa, which explains why this layer of the adrenal cortex does not secrete cortisol or sex steroids. 17-hydroxylase is not regulated by ACTH.

Question 4 of 5

MRI of the pituitary with gadolinium enhancement shows an 8 mm mass which is subsequently removed using microsurgery. Pathologic examination of the mass would most likely show which of the following? / A. Benign adenoma / B. Craniopharyngioma / C. Diffuse hyperplasia of corticotroph cells / D. Malignant adenocarcinoma / E. Metastatic breast carcinoma

Explanation - Q: 2.4

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The correct answer is A. A benign pituitary adenoma is present 90% of the time in patients with Cushing disease. The tumor is usually less than 10 mm in diameter. These microadenomas are not encapsulated, but are surrounded by a rim of compressed normal anterior pituitary cells. The microadenomas also typically exhibit bundles of perinuclear microfilaments surrounding the nucleus (Crooke's changes). Electron microscopy shows the presence of secretory granules (200-700 nm in diameter) within the cytoplasm of the adenoma cells. It should be noted that 10% of adults between 20 and 50 years of age have incidental pituitary tumors and no apparent symptoms. Craniopharyngioma (choice B) is the most common tumor that impairs hypothalamic-pituitary function in children and young adults. It may also occur in adults. These intracranial tumors are usually benign, but may become large before being detected. Endocrine abnormalities are common, but may be discovered only after other symptoms related to increased intracranial pressure become manifest. Growth hormone deficiency is the most common endocrine abnormality, but any of the anterior pituitary hormones may be diminished. Diffuse hyperplasia of corticotroph cells (choice C) of the anterior pituitary is rare. When it does occur, it is presumably due to excessive stimulation of the pituitary by corticotropin-releasing hormone (CRH) secreted by a benign hypothalamic gangliocytoma. Malignant adenocarcinoma (choice D) is rare in the anterior pituitary. These tumors are not functional and do not secrete ACTH. Breast tumor cells (choice E) have been known to metastasize to the anterior pituitary. These are space-filling growths that compromise pituitary function. They do not secrete ACTH.
Question 5 of 5

Following the pituitary microsurgery, the patient complains of being confused, fatigued and nauseated. She also has hypoglycemia. Cold

intolerance is not present. Treatment with which of the following is most likely indicated? / A. Estrogen / B. FIudrocortisone (mineralocorticoid) / C. Human growth hormone / D. Hydrocortisone (glucocorticoid) / E. Thyroxine Explanation - Q: 2.5
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The correct answer is D. The prolonged increase in cortisol due to the ACTH-secreting adenoma will have suppressed ACTH secretion from the uninvolved corticotrophs of the anterior pituitary. Following removal of the adenoma, the pituitary will not secrete enough ACTH at first, leading to adrenal insufficiency. The symptoms of the patient are all consistent with low blood levels of cortisol. Glucocorticoid replacement is indicated, and may be needed for up to a year before normal function of the pituitary returns. Depending on the extent of the pituitary microsurgery, a significant number of gonadotrophs might also be removed and lead to hypogonadotropic hypogonadism. In this case, estrogen (choice A) replacement may be necessary. However, the symptoms of this patient are not consistent with estrogen deficiency. Since aldosterone secretion from the zona glomerulosa of the adrenal cortex is primarily regulated by angiotensin II, removal of an ACTH-secreting pituitary adenoma has little effect on its blood level. Hence, mineralocorticoid (choice B) replacement is rarely required. Pituitary microsurgery also has the potential to remove somatotrophs. However, growth hormone deficiency is not likely, given the fact that about 50% of the cells in the anterior pituitary are somatotrophs. Furthermore, somatotrophs are located primarily in the lateral wings of the pituitary, while ACTH-secreting corticotrophs tend to be more medial. Hence, growth hormone (choice C) replacement is less likely to be required than cortisol replacement. Removal of thyrotrophs is also possible with pituitary microsurgery. However, the patients symptoms are not consistent with hypothyroidism, and thyroxine (choice E) replacement is not required.

A 35-year-old man presents to his physician with a 40-pound weight loss over the preceding 4 months. The man has not been dieting, but has

been having abdominal pain, nausea, and diarrhea. He has also had a chronic cough. Sputum studies demonstrate Pneumocystis carinii, and esophagogastroduodenoscopy with biopsy demonstrates Candida and Herpes in the esophagus.
Question 1 of 9

The pathogen which causes this patient's underlying disease is a member of which of the following groups of viruses? / A. Caliciviridae / B. Coronaviridae / C. FIaviviridae / D. Picornaviridae / E. Retroviridae Explanation - Q: 3.1
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The correct answer is E. This man with multiple infections probably has AIDS, in which "wasting" due to infection and weight loss is common. All three of this patient's secondary infections (Pneumocystis pneumonia, Candida esophagitis, and Herpes esophagitis) are considered to be "AIDSdefining illnesses," that indicate that the patient's HIV infection has progressed to the point of producing profound immunosuppression. HIV is a member of the Lentivirus subgroup of retroviruses. This viral family is characterized by prolonged infections, often with a latent period. These viruses are usually inadequately opposed by the host immune response, and often can infect the nervous system. The Retroviridae also include the oncovirus group that includes the human T-cell Leukemia/Lymphotropic virus. The Caliciviridae (choice A) includes the Norwalk virus and the virus that causes Hepatitis E. Coronaviruses (choice B) cause upper respiratory illnesses. Flaviviruses (choice C) include the Hepatitis C virus, yellow fever virus, dengue virus, and several encephalitis viruses. Picornaviruses (choice D) include poliovirus, coxsackieviruses, echoviruses, hepatitis A virus, and rhinoviruses.

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Approximately how many people worldwide are infected with the virus that causes this patient's underlying disease? / A. 430,000 / B. 750,000 / C. 1 million / D. 16 million / E. 33 million Explanation - Q: 3.2
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The correct answer is E. Currently, about 33 million people worldwide have HIV infection, and there have been 16 million (choice D) deaths. The vast majority of these cases are in developing countries in Africa and Southeast Asia. In the United States, we presently have approximately 1-2 million (choice C) individuals with asymptomatic HIV infection and nearly 750,000 individuals (choice B) with AIDS. Over 430,000 (choice A) of US patients have died of AIDS.

Question 3 of 9

Which of the following is the most frequent means of transmission worldwide for the virus that causes this patient's underlying disease? / A. Accidental needle exposures by health care workers / B. Infected blood products / C. Perinatal transmission / D. Sexual contact / E. Shared needles by drug abusers

Explanation - Q: 3.3

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The correct answer is D. Over 70% of HIV infection is acquired via sexual transmission. You may not be aware that worldwide HIV infection is more common in heterosexual men and women than in homosexual men. Most HIV cases in the US were initially in male homosexuals. However, more recently there has been a shift in the demographics and the majority of new cases of HIV infection are in the heterosexual population. Infection of health care workers through accidental needle exposures (choice A) is now rare in the United States because of the widespread use of universal blood precautions. In this country, contaminated blood products (choice B) only rarely transmit

the HIV virus. In contrast, in developing countries, contaminated blood products are an important problem, as many of these countries have high HIV rates and do not have the financial resources to adequately screen the blood. Most children who develop AIDS acquire the infection perinatally (choice C). Most of the individuals in the United States who acquire AIDS via a parenteral route are intravenous drug abusers who share needles (choice E).
Question 4 of 9

This virus has a particularly high affinity for which of the following? / A. CD4 T Iymphocytes and B cells / B. CD4 T Iymphocytes and monocytes. / C. CD8 T Iymphocytes and B cells / D. CD8 T Iymphocytes and CD4 T Iymphocytes / E. CD8 T Iymphocytes and monocytes Explanation - Q: 3.4
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The correct answer is B. HIV has a particular tendency to bind to CD4 T lymphocytes (helper T lymphocytes) and monocytes and then become internalized. Most other cells, include CD8 T lymphocytes (suppressor T cells) and B cells, are not particularly susceptible to the HIV virus.

Question 5 of 9

This virus uses which of the following enzymes to produce a DNA copy of itself? / A. Integrase / B. gp120 / C. p24 / D. Protease / E. Reverse transcriptase Explanation - Q: 3.5
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The correct answer is E. The viral enzyme reverse transcriptase is used to generate a DNA copy from RNA. This viral DNA is then inserted into the host DNA, which allows the virus to "hide" in the host DNA, and also permits more copies to be made. Reverse transcriptase is a product of the gene Pol, which also codes for integrase (choice A, which integrates proviral dsDNA into host DNA) and

protease (choice D, which cleaves polyprotein). The Env gene codes for gp120 (choice B, a surface protein that binds CD4 on the host cell and is responsible for tropism) and gp41 (a transmembrane protein for cell fusion). The Gag gene codes for group-specific antigens including p24 (choice C, a capsid protein), p7p9 (core nucleocapsid proteins), and p17 (matrix proteins that stabilize the envelope). The HIV genome also has several regulatory genes including LTR (integration and virus gene expression), Tat (transactivator of transcription that functions in upregulation), Rev (upregulates transport of transcripts to cytoplasm), and Nef (decreases major histocompatibility complex type I expression on infected T cells, thereby protecting the infected cells from the immune system).
*** Stop manually reprinting mechanically printed! Automate! *** Question 6 of 9

Which of the following is the typical period of latency between initial infection with this virus and development of clinically evident disease? / A. 1 year / B. 6 years / C. 11 years / D. 16 years / E. 21 years Explanation - Q: 3.6
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The correct answer is C. HIV infection remains a mostly fatal illness, since it still eventually causes a profound immunosuppression, which leaves individuals vulnerable to a variety of other infections. While there is some variation from case to case (dependent upon both the size of the initial inoculation and host resistance factors), it typically takes 11 years in untreated cases for HIV infection to progress to clinical AIDS. The introduction of regimens of multiple antiretroviral drugs and prophylaxis against opportunistic pathogens may be changing this pattern, but it is still too early to know to what degree.

Question 7 of 9

The patient is prescribed a non-nucleoside reverse transcriptase inhibitor. Which of the following agents was most likely prescribed? / A. Indinavir

/ / / /

B. Lamivudine C. Lopinavir D. Nevirapine E. Zidovudine Explanation - Q: 3.7

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The correct answer is D. As we have developed a wider variety of methods of treating AIDS, the task of remembering the different drugs that can be used has become more complex. Most of the useful drugs with direct activity against the HIV virus block either reverse transcriptase or protease. Of the drugs listed in the choices, only nevirapine is classified as a non-nucleoside reverse transcriptase inhibitor. Indinavir (choice A) and lopinavir (choice C) and are classified as protease inhibitors. Lamivudine (choice B) and zidovudine (choice E) are thymidine analogues that block reverse transcriptase.

/ / / / /

A. Amphotericin B B. CIotrimazole C. Ganciclovir D. Pyrimethamine E. Trimethoprim/sulfamethoxazole Explanation - Q: 3.8

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The correct answer is E. The choices of drugs for the therapy of the wide variety of secondary infections AIDS patients develop is also of considerable concern to medical personnel. Pneumocystis pneumonia is most often treated with trimethoprim/sulfamethoxazole (Bactrim), with an alternative drug for patients allergic to trimethoprim/sulfamethoxazole being pentamidine. Early steroid therapy may also be helpful in hospitalized patients with Pneumocystis pneumonia who have a PaO2 less than 70 mm Hg. Amphotericin B (choice A) is a systemic antifungal agent typically used in AIDS patients to treat cryptococcal meningitis. Clotrimazole (choice B) is used in AIDS patients to treat oral candidiasis.

Ganciclovir (choice C) is used in AIDS patients to treat CMV infections. Pyrimethamine (choice D) is used in AIDS patients to treat toxoplasmosis.
Question 9 of 9

Individuals with this patient's underlying disease also have an increased chance of developing which of the following cancers? / A. BIadder cancer / B. Breast cancer / C. Cervical cancer / D. Prostate cancer / E. Testicular cancer Explanation - Q: 3.9
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The correct answer is C. Individuals with AIDS also have an increased cancer rate of tumors known to have viral associations, including Kaposi's sarcoma (related to infection with Human Herpes Virus 8); Burkitt's, immunoblastic, and primary CNS lymphomas (related to Ebstein-Barr virus infection); and invasive cervical cancer (related to HPV infection). Cancers of the bladder, breast, prostate, and testes (choices A, B, D, and E) are not related to any known viral infection. A 3-year-old boy is evaluated by a pediatric endocrinologist because of excessive weight gain. The boy has had problems since birth. He was noted to have neonatal central hypotonia, which has improved somewhat since 1 year of age. He was also noted as a baby to have an unusually long head (dolichocephaly) with almond-shaped eyes and a small mouth. His testes were undescended and he had a small penis. Initially, he had feeding problems with poor weight gain in infancy, but since 1 year of age he has shown excessive weight gain. As a baby, he was lethargic and had a weak cry. His motor milestones and speech development have been delayed.

Question 1 of 5

Which of the following is the most likely diagnosis? / A. Angelman syndrome / B. Down syndrome

/ / /

C. Prader-Willi syndrome D. Triple X syndrome E. Turner syndrome Explanation - Q: 4.1

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The correct answer is C. In general, when you encounter a child who has had problems since infancy and who has a distinctive facial appearance, you should consider the possibility that the child has a genetic abnormality (often that involves all or a significant portion of a chromosome). Excessive weight gain is a specific cue to think of Prader-Willi syndrome, although you should be aware that, as illustrated in this case, this may not develop until 1 to 6 years of age. The other conditions listed in the answer options do not have a marked tendency to develop obesity. Angelman syndrome (choice A) is often considered together with Prader-Willi syndrome for genetic reasons (see question 3 below), but has a very different clinical presentation with severe mental retardation, gait irregularities, and a tendency to uncontrolled laughter ("happy puppet" syndrome). Down syndrome (choice B) is characterized by mental retardation, abnormal facies (with a flat hypoplastic face with short nose and small low set ears), a tendency to develop lenticular opacities, heart disease, leukemia, and Alzheimer disease. Triple X syndrome (choice D) produces phenotypic females that are usually apparently normal. Turner syndrome (choice E) produces phenotypic females with short stature, hypogonadism, amenorrhea, webbed neck, and a predisposition for coarctation of the aorta.

Question 2 of 5

This patient's probable genetic disorder most likely involves which of the following chromosomes? / A. 15 / B. 18 / C. 21 / D. X / E. Y Explanation - Q: 4.2
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The correct answer is A. Prader-Willi syndrome is due to a defect in the long arm of chromosome 15 in the 15q11-q13 region. Associate chromosome 18 (choice B) with Edwards syndrome (trisomy 18). Associate chromosome 21 (choice C) with Down syndrome (trisomy 21). Associate the X chromosome (choice D) with Turner syndrome (XO), triple X syndrome (XXX), and Klinefelter syndrome (XXY). Associate the Y chromosome (choice E) with Klinefelter syndrome (XXY).
*** Visit http://www.structurise.com/kleptomania for new versions *** Question 3 of 5

This patient's probable genetic disorder is often cited as an example of which of the following genetic mechanisms? / A. Genetic imprinting / B. Monosomy / C. Robertsonian translocation / D. Trinucleotide repeats / E. Trisomy Explanation - Q: 4.3
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The correct answer is A. Genetic imprinting refers to the finding that certain genes must come from a specific parent in order to function. The molecular basis of the phenomenon appears to be that male and female germ cells apparently add methyl groups to different areas of DNA as a posttranslational modification. These areas of methylation then affect when and how the affected genes are transcribed. (This is part of a broader phenomenon that determines how cells differentiate, based on which genes are "turned on" or turned off.") There has been a great deal of research interest in both Prader-Willi syndrome and Angelman syndrome (see brief description in the discussion of question 1) since it was discovered that these two very different conditions both seemed to be due to a deletion in the same area of chromosome 15. The initial understanding was that if the deletion was in the father's chromosome, then Prader-Willi syndrome occurred, while if it was in the mother's, Angelman syndrome occurred. In practice, for the USMLE, this is probably the level of detail you will need to remember. (What actually turns out to be the case is that in this region of the genome there are at least two genes that require paternal imprinting and whose absence causes Prader-Willi syndrome, and there is at least one gene requiring maternal imprinting, whose absence causes Angelman syndrome.) With respect to the other choices listed in the question, associate monosomy

X (choice B) with Turner syndrome (monosomies involving autosomal chromosomes are fatal in utero). Robertsonian translocations (choice C) are a specialized form of translocation in which the centromeres of two acrocentric chromosomes appear to have fused to make a new chromosome containing both long arms of the original chromosomes; this can which behave like a trisomy, and accounts for some cases of Down syndrome. Trinucleotide repeats (choice D) are highly repeated short segments of DNA that tend to be seen in autosomal dominant diseases that show progression in severity with succeeding generations, such as Fragile X syndrome and Huntington disease. Common trisomies (choice E) include Down syndrome, Edwards syndrome, and Patau syndrome.
Question 4 of 5

If this child goes on to develop morbid obesity, which of the following complications would be most likely to occur? / A. Aortic dissection / B. Crohn disease / C. Diabetes mellitus / D. Pheochromocytoma / E. Zollinger-EIIison syndrome Explanation - Q: 4.4
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The correct answer is C. The Prader-Willi patients have markedly increased appetite secondary to hypothalamic dysfunction and a much less than normal caloric need (secondary primarily to low muscle mass, which may be somewhat ameliorated by growth hormone supplementation during childhood and adolescence). To maintain a normal weight, they require a daily caloric intake about half of those of normal individuals, only around 1000 calories per day. If they do not have this severe of a dietary restriction, they will eventually develop morbid obesity, which is often complicated by diabetes mellitus type II. Other complications to which they are particularly vulnerable include osteoporosis often with scoliosis, hypertension, right-sided heart failure, a tendency to pick at skin lesions, dental problems, and a tendency to have an exaggerated response to sedatives and anesthetics. The other choices listed in the question are distracters and are not associated with Prader-Willi syndrome.

Question 5 of 5

Over the next decade, this child has progression of his disease. When he is seen as a teenager, he is noted to be mildly mentally retarded, and shows multiple behaviors distressing to those around him. He spends a great deal of time ravenous and being pre-occupied with food to the point of breaking windows to get into the locked kitchen and storeroom. He almost always sleeps poorly, and has temper tantrums, violent outbursts, obsessive-compulsive behavior, a tendency to be argumentative, and he steals (most often food or things to get money for food) and lies (most often about food). He is late going through puberty. The physiologic basis of the feeding and sleep problems that dominate this clinical picture is thought to primarily involve dysfunction of which of the following parts of the brain? / A. Cerebellum / B. Cerebral cortex / C. Hypothalamus / D. Medulla / E. Pons Explanation - Q: 4.5
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The correct answer is C. The genetics of Prader-Willi syndrome are fascinating, and the disease is often taught to medical students by geneticists. While this can leave a medical student with a great appreciation of how far we have progressed in our ability to sort through the genetic basis of disease, it has the disadvantage that the clinical side of the picture is often comparatively neglected. It tends to be forgotten that Prader-Willi syndrome is a disease with a fairly high incidence of 1:12,000-15,000 (affecting both sexes and all races), which may have a devastating impact on the patient and family. This question illustrates some of the problems that are seen. Severe hypothalamic dysfunction leading to chronic insatiable hunger and chronic sleep deprivation (which may be aggravated by obesity-related sleep apnea) are thought to be a major part of the underlying cause of most of these patients' sometimes striking behavior problems, and are believed to be related to severe dysfunction of the hypothalamus. Added to their unhappiness are the problems that come with the irritability this produces, particularly when it affects interpersonal relationships with those around them. The families of these patients are also usually very unhappy as well, secondary to concern about the patient, constant emotional turmoil, the financial pressures of chronic illness, and often nearly irreconcilable differences among family members about how to fairly allocate financial and time resources between the affected child and other family members. (Often what evolves is that one parent becomes the affected child's principal advocate and caregiver, while the other parent becomes the advocate and caregiver for the remainder of the family.) The other choices listed in the question are distracters.