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USMLE Step 2 CK Lecture Notes 2018 Surgery 2018th Edition Carlos Pestana
USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME), neither of which sponsors or endorses this product.
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USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Editors
Joseph J. Lieber, MD
Associate Director of Medicine
Elmhurst Hospital Center
Associate Professor of Medicine
Associate Program Director in Medicine for Elmhurst Site
Icahn School of Medicine at Mt. Sinai New York, NY
Frank P. Noto, MD
Assistant Professor of Internal Medicine
Site Director, Internal Medicine Clerkship and Sub-Internship
Icahn School of Medicine at Mt. Sinai New York, NY
Hospitalist
Elmhurst Hospital Center New York, NY
The editors would like to acknowledge Manuel A. Castro, MD, AAHIVS, Amirtharaj Dhanaraja, MD, and Aditya Patel, MD, and Irfan Sheikh, MD for their contributions.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
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Chapter 1:
Chapter
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Learning Objectives
Preventive Medicine 1
Chapter Title #
❏ Describe appropriate screening methods as they apply to neoplasms of the colon, breast, cervix, and lung
❏ Describe epidemiological data related to incidence and prevention of common infectious disease, chronic illness, trauma, smoking, and travel risks
CANCER SCREENING
A 39-year-old woman comes to the clinic very concerned about her risk of developing cancer. Her father was diagnosed with colon cancer at age 43, and her mother was diagnosed with breast cancer at age 52. She is sexually active with multiple partners and has not seen a physician since a car accident 15 years ago. She denies any symptoms at this time, and her physical examination is normal. She asks what is recommended for a woman her age.
Screening tests are done on seemingly healthy people to identify those at increased risk of disease. Even if a diagnostic test is available, however, that does not necessarily mean it should be used to screen for a particular disease.
• Several harmful effects may potentially result from screening tests.
• A ny adverse outcome that occurs (large bowel perforation secondary to a colonoscopy) is iatrogenic.
• Screening may be expensive, unpleasant, and/or inconvenient.
• Screening may also lead to harmful treatment.
Finally, there may be a stigma associated with incorrectly labeling a patient as “sick.”
For all diseases for which screening is recommended, effective intervention must exist, and the course of events after a positive test result must be acceptable to the patient. Most important, the screening test must be valid, i.e., it must have been shown in trials to decrease overall mortality in the screened population. For a screening test to be recommended for regular use, it has to be extensively studied to ensure that all of the requirements are met.
Note
Tamoxifen prevents cancer by 50% in those with >1 family member with breast cancer.
The 4 malignancies for which regular screening is recommended are cancers of the colon, breast, cervix, and lung.
Colon Cancer
In the patient with no significant family history of colon cancer, screening should begin at age 50. The preferred screening modality for colon cancer is colonoscopy every 10 years. Other choices include annual fecal occult blood testing and sigmoidoscopy with barium enema every 5 years.
In the patient with a single first-degree relative diagnosed with colorectal cancer before age 60 or multiple first-degree relatives with colon cancer at any age, colonoscopy should begin at age 40 or 10 years before the age at which the youngest affected relative was diagnosed, whichever age occurs earlier. In these high-risk patients, colonoscopy should be repeated every 5 years. The U.S. Preventive Services Task Force (USPSTF) does not recommend routine screening in patients age >75.
Breast Cancer
The tests used to screen for breast cancer are mammography and manual breast exam. Mammography with or without clinical breast exam is recommended every 1–2 years from age 50–74. The American Cancer Society no longer recommends monthly self-breast examination alone as a screening tool. Patients with very strong family histories of breast cancer (defined as multiple first-degree relatives) should consider prophylactic tamoxifen, discussing risks and benefits with a physician. Tamoxifen prevents breast cancer in high-risk individuals.
Cervical Cancer
Note
Prostate Screening
USPSTF concludes that the current evidence is insufficient to assess the balance of benefits/risks of prostate cancer screening in men age <75. It recommends against screening in men age >75. For USMLE, do not screen for prostate cancer.
The screening test of choice for the early detection of cervical cancer is the Papanicolaou smear (the “Pap” test). In average risk women, Pap smear screening should be started at age 21, regardless of onset of sexual activity. It should be performed every 3 years until age 65.
As an alternative, women age 30–65 who wish to lengthen the screening interval to every 5 years can do co-testing with Pap and HPV testing. In higher risk women, e.g., HIV, more frequent screening or screening after age 65 may be required.
Lung Cancer
Current recommendations for lung cancer screening are as follows:
• A nnual screening with low-dose CT in adults age 55–80 who have a 30-pack-year smoking history and currently smoke or have quit within past 15 years
• Once a person has not smoked for 15 years or develops a health problem substantially limiting life expectancy or ability/willingness to have curative lung surgery, screening should be discontinued
Clinical Recall
Which of the following patients is undergoing an inappropriate method of screening as recommended by the USPSTF?
A. A 5 0-year-old man gets his first screening for colon cancer via colonoscopy
B. A 5 0-year-old woman gets her first screening for breast cancer via mammography
C. A 17-year-old woman is screened for HPV via a Pap smear after her first sexual encounter
D. A 65-year-old man with a 30-pack-year smoking histor y gets a lowdose CT
E. A 21-year-old woman with a high risk of developing breast cancer is given tamoxifen
Answer: C
TRAVEL MEDICINE
A 44-year-old executive comes to the clinic before traveling to Thailand for business. He has no significant past medical history and is here only because his company will not let him travel until he is seen by a physician. The patient appears agitated and demands the physician’s recommendation immediately.
It is important to set up a pretravel counseling session 4–6 weeks before the patient’s departure.
Hepatitis A infection is travelers’ most common vaccine-preventable disease. Hepatitis A infection is possible wherever fecal contamination of food or drinking water may occur. Infection rates are particularly high in nonindustrial countries. If a patient is leaving within 2 weeks of being seen, both the vaccine and immune serum globulin are recommended. A booster shot given 6 months after the initial vaccination confers immunity for approximately 10 years.
All travelers to less-developed countries should get hep A vaccine.
Hepatitis B vaccination is recommended for patients who work closely with indigenous populations. Additionally, patients who plan to engage in sexual intercourse with the local populace, to receive medical or dental care, or to remain abroad for >6 months should be vaccinated.
Malaria: Mefloquine is the agent of choice for malaria prophylaxis. It is given once per week; it may cause adverse neuropsychiatric effects such as hallucinations, depression, suicidal ideations, and unusual behavior. Doxycycline is an acceptable alternative to mefloquine, although photosensitivity can be problematic. For pregnant patients requiring chemoprophylaxis for malaria, chloroquine is the preferred regimen.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Note
Patients must get Pneumovax, meningococcal, and Haemophilus vaccines 2 weeks before a splenectomy.
Rabies vaccination is recommended for patients traveling to areas where rabies is common among domesticated animals (India, Asia, Mexico). Chloroquine can blunt the response to the intradermal form of rabies vaccine. Therefore, in patients who require malaria prophylaxis, in addition to rabies prophylaxis the intramuscular form of the vaccine should be administered. Rabies vaccination is not considered a routine vaccination for most travelers.
Typhoid vaccination is recommended for patients who are traveling to developing countries and will have prolonged exposure to contaminated food and water. Typhoid vaccination comes in 2 forms, an oral live attenuated form and a capsular polysaccharide vaccine given parenterally. The live attenuated form (1) needs to be refrigerated, and (2) is contraindicated in patients who are HIV-positive. The polysaccharide vaccine is given intramuscularly as a single injection. Side effects include irritation at the injection site. Fever and headache are rare adverse reactions to the vaccine. The polysaccharide vaccine is the preferred form for almost all subjects as it is well-tolerated and convenient (no need for refrigeration). It is safe for HIV patients.
Polio: Adults who are traveling to developing countries and have never received a polio vaccine should receive 3 doses of the inactivated polio vaccine. Patients who have been previously immunized should receive a 1-time booster. The live attenuated polio vaccine is no longer recommended because of the risk of vaccine-associated disease.
Patients traveling to areas where meningococcal meningitis is endemic or epidemic (Nepal, sub-Saharan Africa, northern India) should be immunized with the polysaccharide vaccine. Additionally, Saudi Arabia requires immunization for pilgrims to Mecca. Patients with functional or actual asplenia and patients with terminal complement deficiencies should also receive the vaccine. Meningococcal vaccine is now routinely administered at age 11.
To prevent traveler’s diarrhea, patients should be advised to avoid raw and street vendor salads, unwashed fruit, and tap/ice water. Patients who experience mild loose stools without fever or blood can safely take loperamide. Treatment with a fluoroquinolone or azithromycin is reserved for patients with moderate to severe symptoms.
IMMUNIZATIONS
A 52-year-old man comes to the clinic for a health maintenance evaluation. His recent colonoscopy showed no evidence of carcinoma. Recent serum fasting glucose, serum cholesterol, and blood pressure are all within normal limits. The patient has a history of smoking and continues to smoke 2 packs per day. He was diagnosed with COPD 3 years ago.
Immunization is the best method available for preventing serious infectious disease. Between 50,000–70,000 adults die every year from preventable infectious disease (influenza, invasive pneumococcal disease, and hepatitis B). Surveys have shown that among patients who have an indication for any vaccination, very few actually receive it (pneumococcal vaccination 20%, influenza 40%, hepatitis B 10%). For this reason, the American College of Physicians recommends that every patient’s immunization status be reviewed at age 50; evaluate risk factors for specific vaccinations at that time.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
• Most patients received a primary immunization against tetanus and diphtheria as children.
• For those adults who were never vaccinated, give 3 doses. The principle is that adults require a total of 3 vaccinations against tetanus and diphtheria.
– Give the first 2 doses 1−2 months apart – Give the third dose 6–12 months later
– Give a booster vaccination every 10 years for life; one of the boosters should use Tdap instead of Td booster. If the wound is dirty, revaccinate after 5 years.
Influenza Vaccine
Influenza vaccines is recommended annually for all adults regardless of age. Patients who have a history of cardiopulmonary disease, diabetes mellitus, or hemoglobinopathy, or are age 50+ residents of chronic care facilities derive the greatest benefit from an annual influenza vaccination. Pregnant women who will be in their second or third trimester during the influenza season should also receive the vaccine.
Pneumococcal Vaccine
Pneumococcal vaccine is indicated for all adults age ≥65. Additionally, the following individuals should receive the vaccine regardless of age:
• T hose with history of sickle-cell disease or splenectomy
• T hose with history of cardiopulmonary disease, alcoholism, or cirrhosis
• A laskan natives and certain Native American populations
• Immunocompromised patients (patients with hematologic malignancies, chronic renal failure, or nephrotic syndrome; HIV-positive patients; or patients receiving immunosuppressive medications)
Revaccination should be performed in healthy patients who received their initial vaccination age <65 and were age <60 at the time of primary vaccination. Patients with a high risk of fatal infection (CKD, asplenic patients, immunocompromised patients) should be revaccinated 1x after 5 years. No one gets >1 booster shot per lifetime.
Hepatitis B Vaccine
Hepatitis B vaccine is recommended when there is a history of IV drug abuse, male homosexuality, household or sexual contact with hepatitis B carriers, or frequent exposure to blood/ blood products. Additionally, patients with a history of chronic liver disease should receive the vaccine. Immunity is confirmed serologically.
It is also recommended for all children through age 18, those with STIs, those who are sexually active but not monogamous, workers with occupational exposure to blood, and prison inmates.
Hepatitis A Vaccine
The hepatitis A vaccine protects against the virus in >95% of cases. There are 2 types of vaccine, both of which stimulate active immunity against a future infection.
• One contains inactivated hepatitis A virus
• One contains a live but attenuated virus
For the best protection, give the vaccine in 2 doses: initial dose and then a booster 6–12 months later. Protection against hepatitis A begins approximately 2–4 weeks after the initial vaccination.
In the United States, the vaccine is strongly recommended for all children age 12–23 months in an attempt to eradicate the virus nationwide. There are also recommendations that the following populations be vaccinated:
• A ll children age >1 year
• People whose sexual activity puts them at risk
• People with chronic liver disease
• People who are being treated with clotting factor concentrates
• People who are living in communities where an outbreak is present
Hepatitis A is the most common vaccine-preventable virus acquired during travel, so people travelling to places where the virus is common (Indian subcontinent, Africa, Central America, South America, the far East, and Eastern Europe) should be vaccinated.
Varicella Vaccine
The varicella vaccine is a live attenuated vaccine recommended for use in all adults who lack a history of childhood infection with varicella virus. Being a live attenuated vaccine, varicella vaccine should not be given to immunocompromised patients, HIV-positive patients when symptomatic or <200 CD4 cells, or pregnant women.
Patients age ≥60 are recommended to receive the varicella zoster (shingles) vaccine, which has been shown to reduce the risk of zoster and its associated pain (post-herpetic neuralgia). It is indicated regardless of whether there is a history of shingles, as it is possible to have a second herpes zoster infection.
Measles, Mumps, Rubella Vaccine
The measles, mumps, rubella (MMR) vaccine is a live attenuated vaccine usually given in childhood. Healthy adults born after 1956 should receive 1 dose of the vaccine. Pregnant women and immunocompromised patients should not be vaccinated. HIV-positive patients who are asymptomatic may receive the vaccine.
Meningococcal Vaccine
The meningococcal vaccine is recommended for everyone at age 11 visit. It is also recommended for young adults living in dormitories or barracks, people exposed to outbreaks, those with asplenia or terminal complement deficiencies, those who travel to endemic regions (traveling to Mecca), and those exposed to Neisseria meningitidis.
Human Papillomavirus (HPV) Vaccine
The human papillomavirus (HPV) vaccine is recommended for women age 9–26, regardless of sexual activity. It should not be administered in pregnancy. The regimen is in 3 doses: 0, 2, and 6 months.
Herpes Zoster Vaccine
The zoster vaccine is a live vaccine that has been shown to reduce the incidence of shingles by 50%. It has also been shown to reduce the number of cases of post-herpetic neuralgia, as well as the severity and duration of pain/discomfort associated with shingles. The vaccine is, basically, a larger-than-normal dose of the chicken pox vaccine, as both shingles and chickenpox are caused by the same virus, varicella zoster virus (VZV).
The shingles vaccine (Zostavax), a live vaccine given as a single injection, is recommended for adults age ≥60, whether they have already had shingles or not. Some people report a chickenpoxlike rash after receiving it. The vaccine should not be given to the following individuals:
• T hose with a weakened immune system due to HIV/AIDS or another disease that affects the immune system
• T hose who are receiving immune system-suppressing drugs or treatments, such as steroids, adalimumab (Humira), infliximab (Remicade), etanercept (Enbrel), radiation or chemotherapy
• T hose who have neoplasia, which affects the bone marrow or lymphatic system, such as leukemia or lymphoma
Clinical Recall
In which of the following patients will the vaccination have the greatest benefit?
A. Routine hepatitis A vaccination in a 2-month-old infant
B. Influenza vaccine in a 16-year-old asymptomatic high school student
C. VZ V vaccination given to an AIDS patient with CD4 count 100
D. Pneumococcal vaccination given to a 48-year-old male COPD patient
E. H BV vaccination given to a heart failure patient
SMOKING
Answer: D
A 25-year-old man comes to the clinic for evaluation of a stuffy nose and fever. Over the course of the interview, the patient states that he smokes 3 packs of cigarettes per day and has been doing so for the last 7 years.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Note
Do not use varenicline in patients with a history of psychiatric disease.
Smoking is responsible for 1 in every 5 deaths in the United States. Smoking cessation is the most preventable cause of disease. Physicians can take the following steps to assist:
• ASK about smoking at every visit.
• A DVISE all smokers to quit at every visit.
• ATTEMPT to identify those smokers willing to quit.
• ASSIST the patient by setting a quit date (usually within 2 weeks) and using nicotine patches/gum, the oral antidepressant bupropion or varenicline as supportive therapy. Varenicline and bupropion are more effective than patches.
• A RRANGE follow-up. If the quit attempt was successful, then provide positive reinforcement. If it was not successful, then determine why the patient smoked and elicit a recommitment to smoking cessation. Most patients require several attempts before being successful.
Monotherapy treatment for smoking cessation includes nicotine replacement therapy (transdermal nicotine patches, gum, lozenges, inhalers), bupropion, and varenicline.
• Bupropion lowers the seizure threshold so do not use in cases of alcohol abuse.
• Varenicline causes an increased rate of suicidal thoughts, so first screen for depression.
Place a follow-up call 1–2 weeks after quit date. The use of pharmacotherapy doubles the effect of any tobacco cessation intervention.
OSTEOPOROSIS
All women age >65 should be given DEXA bone density scan. Screening should begin at age 60 if there is low body weight or increased risk of fractures. A bone density test uses x-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are tested are in the spine, hip and forearm. Bone density test results are reported in 2 numbers: T-score and Z-score.
The T-score is the bone density compared with what is normally expected in a healthy young adult of the same sex. The T-score is the number of units—standard deviations—that bone density is above or below the average.
• T-score >2.5 SD indicates the likelihood of osteoporosis and increased risk of fracture.
• T he diagnosis of osteoporosis by DEXA scan also means that treatment should be initiated with bisphosphonates, oral daily calcium supplementation, and vitamin D.
The Z-score is the number of standard deviations above or below what is normally expected for someone of the same age, sex, weight, and ethnic or racial origin.
• Z -score ≤-2 may suggest that something other than aging is causing abnormal bone loss (consider drugs causing osteoporosis such as corticosteroids).
• T he goal in this case is to identify the underlying problem.
ABDOMINAL AORTIC ANEURYSM
U/S should be done once in men age >65 who have ever smoked. There are no screening recommendations for male nonsmokers and women, regardless of smoking history.
HYPERTENSION, DIABETES MELLITUS, AND HYPERCHOLESTEROLEMIA
A 45-year-old man comes to the physician anxious about his health. Five years ago his mother was diagnosed with diabetes and high cholesterol. He is worried about his health and risk for heart disease. Physical examination is within normal limits.
Cholesterol screening should commence at age 35 in men who have no risk factors for coronary artery disease. In both men and women with risk factors, screening should be done routinely after age 20. Management should not be determined by an isolated reading because cholesterol levels may fluctuate between measurements. Repeat in 5 years in low-risk individuals.
Screening for diabetes mellitus should be considered only for patients with hypertension (>135/80 mm Hg). Diabetes mellitus is diagnosed in either of these situations:
• Two fasting glucose measurements are >125 mg/dL, HbA1c >6.5%
• R andom glucose >200 mg/dL accompanied by symptoms
There is insufficient evidence for or against routine screening. The strongest indication is for those with hypertension and hyperlipidemia.
Screening is recommended for elevated blood pressure in those age >18, at every visit. Screening is not recommended for carotid artery stenosis with duplex.
ALCOHOL ABUSE
A 55-year-old man comes to the office for evaluation of a sore throat. The patient admits that he was recently fired from his job and is having marital problems at home. The patient has no significant past medical history, and physical examination is within normal limits. He attests to drinking 3 shots of whiskey every day after work.
Physicians should screen for alcohol abuse by using the CAGE questionnaire:
Have you ever felt the need to: Cut down on your drinking?
Have you ever felt: Annoyed by criticism of your drinking?
Have you ever felt: Guilty about your drinking?
Have you ever taken a morning: Eye opener?
A positive screen is 2 “yes” answers. One “yes” should raise the possibility of alcohol abuse.
VIOLENCE AND INJURY
A 27-year-old woman presents to the emergency department complaining of right-arm pain. When asked how she sustained the injury, she states that she fell down the steps in front of her house. The patient appears anxious and nervous. On physical examination there are various 2 cm wide lacerations on her buttocks.
Injuries are the most common cause of death in those age <65. The role of the physician is to advise patients about safety practices that can prevent injury, e.g., using seat belts, wearing bicycle helmets, and not driving after drinking alcohol.
Identifying women who are at increased risk of physical or sexual abuse is an essential role for a physician. Simply asking them if they have been hit, kicked, or physically hurt can increase identification by >10%.
Clinical Recall
Which of the following is indicated in a 65-year-old male smoker?
A. Digital rectal e xamination with PSA level
B. Meningococcal vaccination
C. Varicella-zoster vaccination
D. Varicella-zoster vaccination and hepatitis A vaccination
E. Varicella-zoster vaccination and abdominal ultrasound
Answer: E
Learning Objectives
Endocrinology 2
Chapter Title #
❏ List presenting signs and therapeutic approaches to disease of the anterior pituitary, posterior pituitary, thyroid, parathyroid, and adrenal glands
❏ Describe disorders that cause hypogonadism or affect the testes
❏ Describe disorders of carbohydrate metabolism
DISEASES OF THE PITUITARY GLAND
The pituitary is surrounded by the sphenoid bone and covered by the sellar diaphragm, an extension from the dura mater. It lies in the sella turcica near the hypothalamus underneath the optic chiasm.
The pituitary is divided into 2 lobes:
• Adenohypophysis (or anterior lobe) (80% of pituitary)
• Neurohypophysis (or posterior lobe), the storage site for hormones produced by neurosecretory neurons (supraoptic and paraventricular nuclei) within the hypothalamus: ADH (antidiuretic hormone or vasopressin) and oxytocin
There is a close relationship between the hypothalamus and the pituitary. The hypothalamus regulates the release of hormones from the anterior pituitary by different hypothalamic releasing and inhibiting hormones (hypothalamic–pituitary axis).
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Optic chiasm
Third ventricle Hypothalamus
Releases inhibiting hormones
Anterior lobe
Anterior pituitary cells
Supraoptic paraventricular Nucleus
Stalk
GH, prolactin, TSH, ACTH, LH, FSH
Portal blood system
Posterior lobe (ADH oxytocin storage)
As a sample summary, the hypothalamus secretes releasing factors for each respective pituitary stimulatory hormone. Each pituitary hormone stimulates release of the active hormone from the final target gland. The active hormones then inhibit release of releasing factors and stimulatory hormones from the hypothalamus and pituitary gland, respectively. This is feedback inhibition, and it leads to a steady state of both respective hormones involved in the axis.
Clinically, note the following to screen and diagnose diseases:
• Disease states involving overproduction of target hormones lead to suppressed levels of pituitary hormones.
• Disease states involving underproduction of target hormones lead to increased levels of pituitary hormones.
Figure 2-1. Pituitary Gland
Figure 2-1. Pituitary Gland
Hypothalamus
Releasing factors
Pituitary
Stimulating hormones
Target Glands
Thyroid Adrenal Cortisol Gonads (ovarian, testes)
Estrogen, testosterone T4, T3
Figure 2-2. Summary of Action
Figure 2-2. Summary of Action
DISEASES OF THE ANTERIOR PITUITARY
Syndromes causing excess production of hormones usually arise from benign tumors of a single cell type.
• Microadenomas (more common) are tumors <1 cm in diameter.
• Macroadenomas (less common) are tumors >1 cm in diameter. Larger tumors can occasionally compress the optic chiasm and cause visual deficits.
Table 2-1. Pituitary Adenomas by Function
Hyperprolactinemia
A 32-year-old woman sees her physician because she has noticed milk-like discharge from her breasts the past 4 weeks. She also states that she has not menstruated in 2 months. The examination reveals galactorrhea but is otherwise normal.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Note
Cabergoline is used more often than bromocriptine because of a better side-effect profile. It is the preferred treatment for galactorrhea.
Excess prolactin secretion is a common clinical problem in women and causes the syndrome of galactorrhea-amenorrhea. The amenorrhea appears to be caused by inhibition of hypothalamic release of gonadotropin-releasing hormone (GnRH) with a decrease in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion. Prolactin inhibits the LH surge that causes ovulation. The LH/FSH-producing cells are not destroyed, just suppressed.
Although hyperprolactinemia is also seen in men, gynecomastia and especially galactorrhea are very rare. The most common presenting symptom in men is erectile dysfunction and decreased libido.
Hyperprolactinemia can be seen in natural physiologic states such as pregnancy, early nursing, hypoglycemia, seizure, exercise, stress, sleep, cirrhosis, nipple stimulation, and chronic renal failure (due to PRL clearance).
Autonomous production of prolactin occurs with pituitary adenomas; these so-called prolactinomas are the most common functioning pituitary adenomas, accounting for 60% of all pituitary tumors. They are usually microadenomas when they occur in women and macroadenomas in men, usually presenting with visual field deficits, etc. Macroadenomas can obstruct the pituitary stalk, increasing prolactin release by blocking dopamine transport from hypothalamus (stalk effect). Other examples are tumors such as craniopharyngioma, meningioma, and dysgerminoma; empty sella; and trauma.
Hyperprolactinemia can also occur with decreased inhibitory action of dopamine. This occurs with the use of drugs that block dopamine synthesis (phenothiazines, metoclopramide) and dopamine-depleting agents (α-methyldopa, reserpine). Tricyclic antidepressants, narcotics, cocaine, SSRIs, and risperidone can also cause increased prolactin.
Stimuli that overcome the normal dopamine inhibition can also lead to hyperprolactinemia. An example of this is primary hypothyroidism (resulting in an increase in thyrotropinreleasing hormone [TRH]) and subsequently an increase in prolactin release.
Always check TSH in patients with elevated prolactin.
Clinical Presentation. Hyperprolactinemia presents with galactorrhea, menstrual abnormalities amenorrhea/oligomenorrhea, osteopenia and osteoporosis in long-standing cases, infertility, and gynecomastia in women; men present with hypogonadism, erectile dysfunction, decreased libido, gynecomastia, and infertility. Men typically do not develop galactorrhea. Women are detected earlier because of menstrual symptoms. Hence, microadenomas are more common in women.
Diagnosis. Always exclude states such as pregnancy, lactation, hypothyroidism and medications before starting the workup of hyperprolactinemia. Prolactinomas may co-secrete growth hormone (GH).
• Prolactin level should be commensurate with tumor size
– Prolactin 100 ng/mL correlates with tumor approximately 1 cm
– Prolactin 200 ng/mL correlates with tumor approximately 2 cm
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Management. Treat initially with cabergoline or bromocriptine (a dopamine-agonist), which will reduce prolactin level in hyperprolactinemia. Dopamine normally inhibits prolactin release.
• About 90% of patients treated with cabergoline have a drop in prolactin to <10% of pretreatment levels.
• Reserve surgery only for those adenomas not responsive to cabergoline/ bromocriptine or associated with significant compressive neurologic effects.
• Surgery is more effective for microadenomas than macroadenomas (only 30% of macroadenomas can be successfully resected, with long-term recurrence >50%).
• Use radiation therapy if drug therapy and surgery are ineffective at reducing tumor size and prolactin level.
Clinical Recall
Which of the following therapeutic options is most appropriate in the management of prolactinoma?
A. Somatostatin
B. Surgical resection
C. Transsphenoidal resection
D. R adiation therapy
E. C abergoline
Acromegaly
Answer: E
Acromegaly (called gigantism in children) is a syndrome of excessive secretion of growth hormone (GH). It is an insidious, chronic debilitating disease associated with bony and soft tissue overgrowth, and increased mortality.
Note
A basal, fasting, morning PRL >100−200 mg/L (normal <20 mg/L) in a nonpregnant woman indicates a need for a pituitary MRI.
Wikimedia, Philippe Chanson and Sylvie Salenave
Figure 2-3. Acromegaly Facial Features
Note
The most common cause of death in acromegaly is cardiovascular mortality.
Acromegaly is caused by a pituitary adenoma (usually macroadenoma in 75% of the cases that produce GH). Rarely ectopic tumors can produce growth hormone-releasing hormone (GHRH) and cause this syndrome. Less than 1% are malignant. GH is produced by 20% of pituitary tumors.
Clinical Findings. GH excess occurs most frequently around decades 3–5. The following findings may be seen.
• Various skeletal and soft tissue changes
• Enlargement of the hands and feet, coarsening of facial features, and thickened skin folds; increase in shoe, hat, glove, and ring size
• Enlarged nose and mandible (prognathism and separation of teeth), sometimes causing underbite
• Deeper voice
• Increased sweating
• Obstructive sleep apnea
• Enlarged internal organs, including heart, lung, spleen, liver, and kidneys
• Interstitial edema, osteoarthritis, and entrapment neuropathy (carpal tunnel syndrome)
• Menstrual problems (common) due to co-secretion of prolactin by GH-producing tumor
• Cardiac anomalies (10–20%) such as hypertension, arrhythmia, hypertrophic cardiomyopathy, and accelerated atherosclerosis
• Proliferated articular cartilage, causing severe joint disease
Diagnosis. Patients with acromegaly have symptoms for ~9 years before the diagnosis is made. The best initial test is IGF-1 level, which is significantly elevated. The confirmatory test is GH measurement after 100 g of glucose is given orally; if GH remains high (>5 ng/mL), it is positive and suggests acromegaly. Normally, glucose load should completely suppress levels of GH.
Measurement of insulin-like growth factor (IGF) or somatomedin correlates with disease activity.
Radiologic studies such as MTI and CT are used to localize the tumor but should be done only after GH excess is documented biochemically. MRI is superior to CT in that it will show a tumor in 90% of people with acromegaly.
Management. The objectives are to decrease GH levels to normal, stabilize or decrease tumor size, and preserve normal pituitary function. Transsphenoidal surgery provides a rapid response. Hypopituitarism can result in 10–20%. Primary treatment is surgery.
Somatostatin analogues are the drugs of choice. Octreotide and lanreotide reduce GH values (70% of patients) and cause partial tumor regression (20–50% of patients). Octreotide is the best medical therapy for acromegaly. The main side effect of concern with somatostatin analogues is cholestasis, leading to cholecystitis.
Dopamine-agonists such as bromocriptine and cabergoline are used if surgery is not curative, with 10% of patients responding to these drugs.
Pegvisomant is a growth hormone analogue which antagonizes endogenic GH by blocking peripheral GH binding to its receptor in the liver. Important to note, pegvisomant is a second-line agent.
Radiotherapy, used only if surgery and drug therapy do not work, results in slow resolution of disease and hypopituitarism in 20% of patients.
Complications of acromegaly can arise from pressure of the tumor on the surrounding structures or invasion of the tumor into the brain or sinuses. Other complications include cardiac failure (most common cause of death in acromegaly), diabetes mellitus, cord compression, and visual field defects.
Hypopituitarism
Hypopituitarism is partial or complete loss of anterior function that results from any lesion which destroys the pituitary or hypothalamus or which interferes with the delivery of releasing and inhibiting factors to the anterior hypothalamus. GH and gonadotropins (FSH, LH) are typically lost early.
Large pituitary tumors, or cysts, as well as hypothalamic tumors (craniopharyngiomas, meningiomas, gliomas) can lead to hypopituitarism. Pituitary adenomas are the most common cause of panhypopituitarism; the mass compresses the gland, causing pressure, trauma, and necrosis.
Pituitary apoplexy is a syndrome associated with acute hemorrhagic infarction of a preexisting pituitary adenoma and manifests as severe headache, nausea or vomiting, and depression of consciousness. It is a medical and neurosurgical emergency.
Inflammatory diseases can lead to hypopituitarism: granulomatous diseases (sarcoidosis, tuberculosis [TB], syphilis), eosinophilic granuloma, and autoimmune lymphocytic hypophysitis (usually associated with other autoimmune diseases such as Hashimoto thyroiditis and gastric atrophy). Trauma, radiation, surgery, infections, and hypoxia may also damage both the pituitary and hypothalamus.
Vascular diseases such as Sheehan postpartum necrosis (initial sign being the inability to lactate) and infiltrative diseases including hemochromatosis and amyloidosis may induce this state as well.
Stroke can also damage these cells. Stroke can cause central diabetes insipidus due to damage of hypothalamus and/or posterior pituitary.
Clinical Findings. The following hormones appear in the order in which they are lost in hypopituitarism.
• Gonadotropin deficiency (LH and FSH) can occur in women and lead to amenorrhea, genital atrophy, infertility, decreased libido, and loss of axillary and pubic hair.
• In men, decreased LH and FSH results in impotence, testicular atrophy, infertility, decreased libido, and loss of axillary and pubic hair.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
• GH deficiency occurs next and is not clinically detectable in adults, though it may manifest as fine wrinkles and increased sensitivity to insulin (hypoglycemia). GH deficiency gives an asymptomatic increase in lipid levels and a decrease in muscle, bone, and heart mass. It also may accelerate atherosclerosis, and it increases visceral obesity.
• GH deficiency in children results in growth failure and short stature.
• T hyrotropin (TSH) deficiency results in hypothyroidism with fatigue, weakness, hyperlipidemia, cold intolerance, and puffy skin without goiter.
• Adrenocorticotropin (ACTH) deficiency occurs last and results in secondary adrenal insufficiency caused by pituitary disease.
• T here is decreased cortisol, which results in fatigue, decreased appetite, weight loss, decreased skin and nipple pigment, and decreased response to stress (as well as fever, hypotension, and hyponatremia).
Electrolyte changes like hyperkalemia and salt loss are minimal in secondary adrenal insufficiency because aldosterone production is mainly dependent on the renin-angiotensin system. ACTH deficiency does not result in the salt wasting, hyperkalemia, and death that are associated with aldosterone deficiency.
Diagnosis. The first step in diagnosing pituitary insufficiency is to measure GH, TSH, LH, and IGF-1. The most reliable stimulus for GH secretion is insulin-induced hypoglycemia. After injecting 0.1 μ/kg of regular insulin, blood glucose declines to <40 mg/dL; in normal conditions that will stimulate GH levels to >10 mg/L and exclude GH deficiency. Random GH and IGF levels are not sensitive enough to diagnose GH deficiency. This is why a provocative test is used.
Arginine infusion can also stimulate growth hormone release. Measure GH levels after infusing arginine. This is less dangerous because it does not lead to hypoglycemia.
To diagnose ACTH deficiency, basal cortisol levels may be preserved (the problem could be only in response to stress). Insulin tolerance test is diagnostic and involves giving 0.05–0.1 U/kg of regular insulin and measuring serum cortisol; plasma cortisol should increase to >19 mg/dL. Metyrapone tests for decreased ACTH production. Metyrapone blocks cortisol production, which should increase ACTH levels. A failure of ACTH levels to rise after giving metyrapone would indicate pituitary insufficiency. Cosyntropin (ACTH) stimulation may give abnormally low cortisol output if pituitary insufficiency has led to adrenal atrophy.
To diagnose gonadotropin deficiency in women, measure LH, FSH, and estrogen. In males, measure LH, FSH, and testosterone. To diagnose TSH deficiency, measure serum thyroxine (T4) and free triiodothyronine (T3), which are low, with a normal to low TSH.
Management. Management of hypopituitarism involves treating the underlying causes. Multiple hormones must be replaced, but the most important is cortisol.
Empty Sella Syndrome (ESS)
ESS is in the differential diagnosis of enlarged sella caused by pituitary tumors. In ESS, the sella has no bony erosion. It is caused by herniation of the suprasellar subarachnoid space through an incomplete diaphragm sella. No pituitary gland is visible on CT or MRI. The syndrome can be primary (idiopathic) and is also associated with head trauma and radiation therapy. Most patients with these syndromes are obese, multiparous women with headaches; 30% will have hypertension. Endocrine symptoms are absent. Therapy is reassurance.
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
What is the best initial test to diagnose acromegaly?
A. 100 g oral glucose tolerance test
B. Insulin-like growth factor-1 levels
C. M RI of the brain
D. Pituitar y biopsy
E. Adrenal venous sampling
DISEASES OF THE POSTERIOR PITUITARY
Answer: B
Vasopressin (or antidiuretic hormone [ADH]) and oxytocin are synthesized in neurons of the supraoptic and paraventricular nuclei in the hypothalamus, then transported to the posterior pituitary lobe to be released into the circulatory system. A deficiency of ADH will cause diabetes insipidus (DI), while an excess of ADH will cause syndrome of inappropriate secretion of ADH (SIADH).
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Basilar cisterns CSF
Diabetes Insipidus
Diabetes insipidus (DI) often starts in childhood or early adult life. Men > women.
• Central diabetes insipidus (CDI) is a disorder of the neurohypophyseal system, caused by partial or total deficiency of ADH.
– Results in excessive, dilute urine and increased thirst associated with hypernatremia
– Causes include neoplastic or infiltrative lesions of the hypothalamus or pituitary (60% also have partial or complete loss of anterior pituitary function); in the hypothalamus these lesions can be secondary to adenoma, craniopharyngioma, etc.; in the pituitary gland, adenoma, leukemia, or sarcoid histocytosis can lead to DI
– Other causes include pituitary or hypothalamic surgery, radiotherapy, severe head injuries, anoxia, hypertension, meningitis
– Idiopathic DI starts in childhood.
– Encephalitis, TB, and syphilis may affect the pituitary as well.
• Nephrogenic diabetes insipidus (NDI) is caused by renal resistance to the action of vasopressin. It can be idiopathic or it can be secondary to hypercalcemia, hypokalemia, sickle cell disease, amyloidosis, myeloma, pyelonephritis, sarcoidosis, or Sjögren syndrome.
– Causes include drugs (lithium, demeclocycline, colchicine)
Clinical Findings. Clinical findings of DI include polyuria, excessive thirst, polydipsia (16–20 L/d), hypernatremia with high serum osmolarity and coexisting low urine osmolarity and urine specific gravity <1.010. Nocturia is expected.
Hypertonicity is not usually present if the patient has an intact thirst mechanism and can increase water intake to keep up with urinary loss.
Figure 2-5. Posm versus Uosm during Dehydration in Normal Subjects
Figure 2-5. Posm versus Uosm during Dehydration in Normal Subjects
Diagnosis. The water deprivation test compares Uosm after dehydration versus Uosm after vasopressin.
• In a normal person, the response to fluid restriction is decreased urine volume and increased urine osmolality.
• In DI, urine volume remains increased despite volume depletion.
• A DH will be decreased in central DI and increased in nephrogenic DI. If a patient falls to the right of the shaded area, the diagnosis is DI.
Serum
The differential diagnosis of DI includes primary disorders of water intake (psychogenic polydipsia, drug-induced polydipsia from chlorpromazine, anticholinergic drugs, or thioridazine) and hypothalamic diseases.
Management. Management for CDI includes the following:
• Hormone replacement with vasopressin subcutaneously or desmopressin subcutaneously, orally, or intranasally
• Drugs to stimulate the secretion of ADH or increase release (chlorpropamide, clofibrate, or carbamazepine)
• HCTZ or amiloride (for NDI) to enhance the reabsorption of fluid from proximal tubule
• Chlorthalidone
• Correction of any calcium and/or potassium abnormalities
USMLE® is a joint program of The Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.
Figure 2-6. Water Restriction Test NDI
Central DI Normal
Figure 2-6. Water Restriction Test
Syndromes Associated with Vasopressin (ADH) Excess
Syndromes associated with ADH excess involve a mechanism of defense against hypovolemia or hypotension. This includes adrenal insufficiency, excessive fluid loss, fluid deprivation, and probably positive-pressure respiration.
Excessive release of ADH from the neurohypophysis is associated with drugs or diseases (SIADH).
Syndrome of Inappropriate Antidiuretic Hormone
Syndrome of inappropriate antidiuretic hormone (SIADH) has many causes:
• Malignancy such as small cell carcinoma, carcinoma of the pancreas, and ectopic ADH secretion
• Nonmalignant pulmonary disease such as tuberculosis, pneumonia, and lung abscess
• CNS disorder such as head injury, cerebral vascular accident, and encephalitis
• Drugs such as chlorpropamide, clofibrate, vincristine, vinblastine, cyclophosphamide, and carbamazepine
In general, increased ADH causes water retention and extracellular fluid volume expansion without edema or hypertension, owing to natriuresis. The water retention and sodium loss both cause hyponatremia, which is a key feature in SIADH. Hyponatremia and concentrated urine (Uosm > 300 mOsm) are seen, as well as no signs of edema or dehydration. When hyponatremia is severe (sodium <120 mOsm), or acute in onset, symptoms of cerebral edema become prominent (irritability, confusion, seizures, and coma).
• No equal concentration of atrial natriuretic peptide
• L ow blood urea nitrate (BUN), low creatinine, low serum uric acid, and low albumin
Management. Treat underlying causes. Restrict fluid to 800–1,000 mL/d to increase serum sodium (in chronic situations when fluid restriction is difficult to maintain, use demeclocycline which inhibits ADH action at the collecting duct [V2]). Conivaptan and tolvaptan are V2 receptor blockers indicated for moderate to severe SIADH. For very symptomatic patients (severe confusion, convulsions, or coma), use IV hypertonic saline (3%) 200–300 mL in 3–4 h. The rate of correction should be 0.5–1 mmol/L/h serum Na.
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were, let it go! She owned no kinship with that unhappy ghost. Serene, middle-aged, respected and respectable, she walked on again out of that vanishing past into the warm tangible present. And at any moment now she might meet Anne. She had turned down a wide walk leading to one of the Fifth Avenue entrances of the Park. One could see a long way ahead; there were people coming and going. Two women passed, with some noisy children racing before them, a milliner’s boy, whistling, his boxes slung over his shoulder, a paralytic pushing himself along in a wheeled chair; then, coming toward her from the direction of Fifth Avenue, a man who half-stopped, recognized her, and raised his hat.
BOOK II.
VIII.
“CHRIS!” she said.
She felt herself trembling all over; then, abruptly, mysteriously, and in the very act of uttering his name, she ceased to tremble, and it came flooding in on her with a shock of wonder that the worst was already over—that at last she was going to be free.
“Well, well,” she heard him saying, in that round full voice which always became fuller and more melodious when it had any inner uncertainty to mask; and “If only,” she thought, “it doesn’t all come back when he laughs!”
He laughed. “I’m so glad glad,” he reiterated, as if explaining; and with the laugh in her ears she still felt herself as lucidly, as incredibly remote from him.
“Glad?” she echoed, a little less sure of her speech than of her thoughts, and remembering how sometimes the smile in his eyes used to break up her words into little meaningless splinters that she could never put together again till he was gone.
“Of your good luck, I mean.... I’ve heard, of course.” And now she had him, for the first time, actually reddening and stammering as she herself used to do, and catching at the splinters of his own words! Ah, the trick was done—she could even see, as they continued to face each other in the searching spring light, that he had reddened, thickened, hardened—as if the old Chris had been walled into this new one, and were not even looking at her out of the windows of his prison.
“My good luck?” she echoed again, while the truth still danced in her ears: the truth that she was free, free, free—away from him at last, far enough off to see him and judge him!
It must have been his bad taste—the bad taste that could lead him into such an opening as that—which, from the very first, she had felt
in him, and tried not to feel, even when she was worshipping him most blindly.
But, after all, if she felt so free, why be so cruel? Ah, because the terror was still there—it had only shifted its ground. What frightened her now was not the thought of their past but of their future. And she must not let him see that it frightened her. What had his last words been? Ah, yes—. She answered: “Of course I’m very happy to be at home again.”
He lowered his voice to murmur: “And I’m happy for you.”
Yes; she remembered now; it was always in emotional moments that his tact failed him, his subtlety vanished, and he seemed to be reciting speeches learned by heart out of some sentimental novel— the very kind he was so clever at ridiculing. They continued to stand facing each other, their inspiration spent, as if waiting for the accident that had swept them together to whirl them apart again.
Suddenly she risked (since it was better to know): “So you’re living now in New York?”
He shook his head with an air of melancholy. “No such luck. I’m back in Baltimore again. Come full circle. For a time, after the war, I was on a newspaper there; interviewing film-stars and base-ball fans and female prohibitionists. Then I tried to run a Country Club—awful job! All book-keeping, and rows between members. Now Horace Maclew has taken pity on me; I’m what I suppose you’d call his private secretary. No eight-hour day: he keeps me pretty close. It’s only once in a blue moon I can get away.”
She felt her tightened heart dilating. Baltimore wasn’t very far away; but it was far enough as long as he had anything to keep him there. She knew about Horace Maclew, an elderly wealthy bibliophile and philanthropist, with countless municipal and social interests in his own town, and a big country-place just outside it. No; Mr. Maclew’s private secretary was not likely to have many holidays. But how long would Chris resign himself to such drudgery? She wanted to be kind and say: “And your painting? Your writing?” but she didn’t dare.
Besides, he had probably left both phases far behind him, and there was no need, really, for her to concern herself with his new hobbies, whatever they might be. Of course she knew that he and she would have to stand there staring at one another till she made a gesture of dismissal; but on what note was she to make it? The natural thing (since she felt so safe and easy with him) would have been to say: “The next time you’re in town you must be sure to look me up—”. But, with him, how could one be certain of not having such a suggestion taken literally? Now that he had seen she was not afraid of him he would probably not be afraid of her; if he wanted a good dinner, or an evening at the Opera, he’d be as likely as not to call her up and ask for it.
And suddenly, as they hung there, she caught, over his shoulder, a glimpse of another figure just turning into the Park from the same direction; Anne, with her quick step, her intent inward air, as she always moved and looked when she had just left her easel. In another moment Anne would be upon them.
Mrs. Clephane held out her hand: for a fraction of a second it lay in his. “Well, goodbye; I’m glad to know you’ve got a job that must be so interesting.”
“Oh—interesting!” He dismissed it with a gesture. “But I’m glad to see you,” he added; “just to see you,” with a clever shifting of the emphasis. He paused a moment, and then risked a smile. “You don’t look a day older, you know.”
She threw her head back with an answering smile. “Why should I, when I feel years younger?”
Thank heaven, an approaching group of people must have obstructed her daughter’s view! Mrs. Clephane hurried on, wanting to put as much distance as she could between herself and Chris’s retreating figure before she came up with her daughter. When she did, she plunged straight into the girl’s eyes, and saw that they were still turned on her inward vision. “Dearest,” she cried gaily, “I can see by your look that you’ve been doing a good day’s work.”
Anne’s soul rose slowly to the surface, shining out between deep lashes. “How do you know, I wonder? I suppose you must have been a great deal with somebody who painted. For a long time afterward one carries the thing about with one wherever one goes.” She slipped her arm in Kate’s, and turned unresistingly as the latter guided her back toward Fifth Avenue.
“It’s dusty in the Park, and I feel as if I wanted a quick walk home. I like Fifth Avenue when the lights are just coming out,” Mrs. Clephane explained.
All night long she lay awake in the great bed of the Clephane spareroom, and stared at Chris. While they still faced each other—and after her first confused impression of his having thickened and reddened—she had seen him only through the blur of her fears and tremors. Even after they had parted, and she was walking home with Anne, the shock of the encounter still tingling in her, he remained far off, almost imponderable, less close and importunate than her memories of him. It was as if his actual presence had exorcised his ghost. But now—
He had not vanished; he had only been waiting. Waiting till she was alone in her room in the sleeping house, in the unheeding city. How alone, she had never more acutely felt. Who on earth was there to intervene between them, when there was not a soul to whom she could even breathe that she had met him? She lay in the darkness with terrified staring eyes, and there he stood, his smile deriding her —a strange composite figure, made equally of the old Chris and the new
It was of no use to shut her eyes; he was between lid and ball. It was of no use to murmur disjointed phrases to herself, conjure him away with the language of her new life, with allusions and incantations unknown to him; he just stood there and waited. Well, then—she would face it out now, would deal with him! But how? What was he to her, and what did he want of her?
Yes: it all came to the question of what he wanted; it always had. When had there ever been a question of what she wanted? He took what he chose from life, gathered and let drop and went on: it was the artist’s way, he told her. But what could he possibly want of her now, and why did she imagine that he wanted anything, when by his own showing he was so busy and so provided for?
She pulled herself together, suddenly ashamed of her own thoughts. In pity for herself she would have liked to draw the old tattered glamour over him; but there must always have been rents and cracks in it, and now it couldn’t by any tugging be made to cover him. No; she didn’t love him any longer; she was sure of that. Like a traveller who has just skirted an abyss, she could lean over without dizziness and measure the depth into which she had not fallen. But if that were so, why was she so afraid of him? If it were a mere question of her own social safety, a mean dread of having her past suspected, why, she was more ashamed of that than of having loved him. She would almost rather have endured the misery of still loving him than of seeing what he and she looked like, now that the tide had ebbed from them. She had been a coward; she had been stiff and frightened and conventional, when, from the vantage-ground of her new security, she could so easily have been friendly and generous; she felt like rushing out into the streets to find him, to speak to him as she ought to have spoken, to tell him that she was not in the least afraid of him.
And yet she was! She supposed it was the old incalculable element in him, that profound fundamental difference in their natures which used to make their closest nearness seem more like a spell than a reality. She understood now that if she had always been afraid of him it was just because she could never tell what she was afraid of....
If only there had been some one to whom she could confess herself, some one who would laugh away her terrors! Fred Landers? But she would frighten him more than he reassured her. And the others—the kindly approving family? What would they do but avert their eyes and beg her to be reasonable and remember her daughter? Well—and her daughter, then? And Anne? Was there any one on earth but Anne who would understand her?
The oppression of the night and the silence, and the rumour of her own fears, were becoming intolerable. She could not endure them any longer. She jumped up, flung on her dressing-gown, and stole out of her room. The corridor was empty and obscure; only a faint light from the lower hall cast its reflection upward on the ceiling of the stairs. From below came the pompous tick of the hall clock, as loud as a knocking in the silence.
She stole to her daughter’s door, and kneeling down laid her ear against the crack. Presently, through the hush, she caught the soft rhythmic breath of youthful sleep, and pictured Anne, slim and motionless, her dark hair in orderly braids along the pillow. The vision startled the mother back to sanity. She got up stiffly and stood looking about her with dazed eyes.
Suddenly the light on the stairs, the nocturnal ticking, swept another vision through her throbbing brain. In just such a silence, before the first cold sounds of the winter daylight, she had crept down those very stairs, unchained the front door, slipped back one after another of John Clephane’s patent bolts, and let herself out of his house for the last time. Ah, what business had she in it now, her hand on her daughter’s door? She dragged herself back to her own room, switched on the light, and sat hunched up in the great bed, mechanically turning over the pages of a fashion-paper she had picked up on her sitting-room table. Skirts were certainly going to be narrower that spring....
IX.
“LILLA—but of course he comes for Lilla!” she exclaimed. She raised herself on her elbow, saw the bed-lamp still burning, and the fashion-paper on the floor beside the bed. The night was not over; there was no grayness yet between the curtains. She must have dropped into a short uneasy sleep, from which Lilla’s loitering expectant figure, floating away from her down an alley of the Park, had detached itself with such emphasis that the shock awoke her.
Lilla and Chris but of course they had gone to the Park to meet each other! Why should he have happened to turn in at that particular gate, at that particular hour, unless to find some one who, a few yards off, careless and unconcerned, was so obviously lingering there to be found?
The discovery gave Kate Clephane a sensation of actual physical nausea. She sat up in bed, pushed her hair back from her damp forehead, and repeated the two names slowly, as if trying from those conjoined syllables to disentangle the clue to the mystery. For mystery there was; she was sure of it now! People like Lilla Gates and Chris did not wander aimlessly through Central Park at the secret hour when the winter dusk begins to blur its paths. Every moment of such purposeless lives was portioned out, packed with futilities. Kate had seen enough of that in her enforced association with the idlers of a dozen watering-places, her dreary participation in their idling.
And how the clue, now she held it, explained everything! Explained, first of all, why Chris, the ready, the resourceful, had been so tonguetied and halting when they met. Why had she not been struck by that before? She saw now that, if she was afraid of him, he was a thousand times more afraid of her! And how could she have imagined that, to a man like Chris, the mere fact of running across a discarded mistress would be disconcerting, or even wholly unpleasant? Who better than he should know how to deal with such emergencies? His past must be strewn with precedents. As her
memory travelled back over their life together she recalled their having met, one day at Hadrian’s Villa, a little woman, a Mrs. Guy So-and-so—she had even forgotten the name! She and Chris had been wandering, close-linked—for the tourist season was over, and besides, they cared so little who saw them—through the rich garlanded ruins, all perfume and enchantment; and there, in their path, had stood a solitary figure, the figure of a young woman, pretty, well-dressed, with a hungry melancholy face. A little way behind her, a heavy elderly gentleman in blue goggles and an overcoat was having archæological explanations shouted into his deaf ear and curved hand by a guide with a rasping German accent—and Chris, exclaiming: “By Jove, there are the So-and-sos!” had advanced with outstretched hand, introduced the two women, and poured out upon the melancholy newcomer a flood of laughing allusive talk, half chaff, half sentiment, and all as easily, as unconcernedly as if her great eyes had not, all the while, been pleading, pleading with him to remember.
And then, afterward, when Kate had said to him: “But wasn’t that the woman you told me about once, who was so desperately unhappy, and wanted to run away with you?” he had merely answered: “Oh, not particularly with me, as far as I remember—” and she had hugged his arm closer, and thought how funny he was, and luxuriously pitied the other woman.
Yes; that was the real Chris; always on the spot, easy-going and gay. The stammering evasive apparition in the Park had no resemblance to that Chris; Kate knew instinctively that it was not the fact of meeting her that had so disturbed him, but the fact that, for some reason, the meeting might interfere with his plans. But what plans? Why, his plans with Lilla—which would necessarily bring him in contact with the clan, since they so resolutely backed Lilla up, and thus expose him to—to what? To Kate’s betraying him? For a moment she half-laughed at the idea.
For what could she do to injure him, after all? And, whatever his plans were, how could he ever imagine her interfering with them, when to do so would be to betray her own secret? She lay there in the dreary dawn and tried to work her way through the labyrinth. And
then, all at once, it came to her: what if he wanted to marry Lilla? And what more probable than that he did? It was evident that living with his people and administering Mr. Maclew’s philanthropies was not a life that he would have called “fit for a dog”. He liked money, she knew, for all his careless way; he wanted to have it, but he hated to earn it. And if he married Lilla there would be plenty of money. The Drovers would see to that—Kate could imagine nothing more likely to unloose their purse-strings than the possibility of “settling” Lilla, and getting rid of the perpetual menace that her roving fancies hung over her mother’s neatly-waved head. Chris, of course, was far too clever not to have seen that, and worked out the consequences in his own mind. If Lilla had been plain and dowdy he wouldn’t even have considered it—Kate did him that justice. If he liked money he liked it in a large lordly way, and only as one among several things which it was convenient but not essential to have. He would never do a base thing for money; but, after all, there was nothing base in marrying Lilla if he liked her looks and was amused by her talk, as he probably was. There was one side of Chris, the side Kate Clephane had least explored, and was least capable of understanding, which might very well find its complement in Lilla....
Kate’s aching eyes continued to strain into the future. If that were really his plan, of course he would be afraid of her! For he knew her too, knew her ever so much better than she did him, and would be sure to guess that, much as she would want to cover up their past, she would not hesitate a moment between revealing it and doing what she called her duty Her duty—how he used to laugh at the phrase! He told her she had run away from her real duties only for the pleasure of inventing new ones, and that to her they were none the less duties because she imagined them to be defiances. It was one of the paradoxes that most amused him: the picture of her flying from her conscience and always meeting it again in her path, barely disguised by the audacities she had dressed it up in.
Yes; evidently he had asked himself, on the instant, what she would do about Lilla; and the mere fact made her feel, with a fierce desperation, that she must do something. Not that she cared a straw about Lilla, or felt the least “call” to save her—but to have Chris in
the family, in the group, to have to smile at him across the Clephane dinner-table, the Drover dinner-table, all the family dinner-tables, to have to keep up, for all the rest of her life, the double pretence of never having liked him too much, and of now liking him enough to gratify the pride and allay the suspicions of the family—no, she could not imagine herself doing it! She was right to be afraid of him; he was right to be afraid of her.
The return to daylight made her nocturnal logic seem absurd; but several days passed before her agitation subsided. It was only when she found life continuing undisturbed about her, Anne painting for long rapturous hours, Lilla following her same bored round of pleasure, the others placidly engaged in their usual pursuits, and no one mentioning Chris’s name, or apparently aware of his existence, that the shadow of her midnight imaginings was lifted.
Once or twice, as the sense of security returned, she thought of letting Chris’s name fall, ever so casually, in Fred Landers’s hearing. She never got as far as that; but one day she contrived, in speaking of some famous collection of books just coming into the market, to mention Horace Maclew.
Landers’s eye kindled. “Ah, what books! His Italian antiphonals are probably the best in the world.”
“You know him, then? How—is it long since you last saw his library?” she stammered.
He considered. “Oh, years; not since before the war.”
Her heart rose on the mounting hope. “Oh, not since then?... I suppose he must have a very good librarian?”
“Used to have; the poor chap was killed in the war, I believe. That reminds me that I heard the other day he was looking for some one.”
“Looking for a librarian?” She heard her voice shake. “Not for a private secretary?”
She thought he looked surprised. “I don’t think so; but I really don’t remember. I know he always has a lot of scribes about him; naturally, with so many irons in the fire. Did you happen to hear of any one who was looking for that sort of job? It might be a kindness to let Maclew know.”
She drew her brows together, affecting to consider. “Where did I hear of some one? I can’t remember either. One is always hearing nowadays of people looking for something to do.”
“Yes; but of few who can do anything. And Maclew’s the last man to put up with incompetence. You must come and see him with me. He’s not an easy customer, but he and I are old members of the Grolier Club and he lets me bring a friend to see his library occasionally. I’ve always promised to take Anne, some day when she’s going on to Washington.”
Kate’s heart gave a sharp downward plunge. That “Take Anne” reverberated in her like a knell. What a fool she had been to bring the subject up! If she had not mentioned Horace Maclew’s name Landers might never have thought of his library again; at least not of the promise to take Anne there. Well, it was a lesson to hold her tongue, to let things follow their course without fearing or interfering. Happily Anne, more and more absorbed in her painting, seemed to have no idea of a visit to Washington; she had never mentioned such a plan, beyond once casually saying: “Oh, the Washington magnolias ... some spring I must go there and paint them.”
Some spring ... well, that was pleasantly indefinite. For Chris was not likely to remain long with Horace Maclew. Where had Chris ever remained long? Kate Clephane did not know, now, whether to tremble at that impermanence or be glad of it. She did not know what to think about anything, now that the thought of Chris had suddenly re-introduced itself into the smooth-running wheels of her existence.
Then, as the days passed, her reassurance returned again, and it was with a stupefied start that one afternoon, crossing the Park on her way to the studio, she once more caught sight of Lilla Gates. This time the person for whom she had presumably been waiting was with her, and the two stood in close communion. The man’s
back was turned, but his figure, his attitude, were so familiar to Kate that she stopped short, trembling lest she should see his face.
She did not see it. He and Mrs. Gates were in the act of leave-taking. Their hands met, they lingered for a last word, and then separated, each hastening away in a direction other than Kate’s. She continued to stand motionless after they had vanished, uncertain yet certain. It was Chris—but of course it was Chris! He came often to New York, then, in spite of what he had said about the difficulty of getting away. If he had said that, it was probably just because he wanted to keep his comings and goings from Mrs. Clephane’s knowledge. And that again would tally with what she suspected as to his motives. She turned sick, and stood with compressed lips and lowered head, as if to close her senses against what was coming. At length she roused herself and walked on.
Lilla.... Lilla.... Chris and Lilla!
She kept on her way northward, following the less frequented byways of the Park. It was early yet, and she wanted to walk off her agitation before joining Anne at the studio.
Lilla.... Lilla.... Chris and Lilla!
Something must be done about it, something must be said—it was impossible that this affair, whatever it was, should go on unchecked. But had she, Kate Clephane, any power to prevent it? Probably not —her intervention might serve only to precipitate events. Well, at least she must know what was coming—must find out what the others knew Her excitement increased instead of subsiding: as she walked on she felt the tears running down her face. Life had seemed, at last, so simple, so merciful, so soothing; and here were all the old mysteries and duplicities pressing on her again. She stopped, out of breath, and finding herself at the extreme northern end of the Park, with the first street-lights beginning to gem the bare trees. The need to be with Anne suddenly seized her. Perhaps, by dropping a careless word or two, she might learn something from her daughter—learn at least if the baleful Lilla were using the girl as a confidant, as that brief scene in the studio had once suggested. On that point, at any rate, it was the mother’s right, her duty even, to be
informed. She had made no appointment to meet Anne that afternoon; and she hastened her pace, fearing to find that her daughter had already left the studio....
A light through the transom reassured her. She put her key in the lock, threw off her cloak in the little entrance-hall, and pushed open the door beyond. The studio was unlit except by the city’s constellated lamps, hung like a golden vintage from an invisible trellising of towers and poles, and by the rosy gleam of the hearth. Anne’s easel had been pushed aside, and Anne and another person were sitting near each other in low chairs, duskily outlined against the fire. As Mrs. Clephane crossed the threshold a man’s voice was saying gaily: “What I want is a rhyme for astrolabe. I must have it! And apparently there is none; at least none except babe. And so there won’t be any poem. That’s always my luck. I find something ... or somebody ... who’s just what I want, and then....”
Kate Clephane stood still, enveloped by the voice. It was the first time she had heard those laughing confiding inflexions addressed to any ear but hers. Southern sunshine scorched her; the air seemed full of flowers. She hung there for a moment, netted in tightening memories; then she loosed her hold on the door-handle and advanced a few steps into the room. Her heels clicked on the bare floor, and the two by the fire rose and turned to her. She fancied her daughter’s glance conveyed a faint surprise—was it even a faint annoyance at her intrusion?
“Mother, this is Major Fenno. I think you know him,” the girl said. Chris came forward, simple, natural, unembarrassed. There was no trace of constraint in his glance or tone; he looked at Mrs. Clephane almost fraternally.
“Dear Mrs. Clephane—a rhyme for astrolabe!” he entreated, with that half-humorous way he had of flinging the lasso of his own thought over anybody who happened to stray within range; and then, with one of his usual quick transitions: “I got a chance to run over to New York unexpectedly, and I heard you were in town, and went to see you. At your house they told me you might be here, so I came, and Miss Clephane was kind enough to let me wait.”
“I was afraid you weren’t coming,” the girl added, looking gravely at her mother.
In spite of the blood drumming in her head, and the way his airy fib about having heard she was in town had drawn her again into the old net of their complicities, Kate was steadied by his composure. She looked from him to Anne; and Anne’s face was also composed.
“I had the luck,” Chris added, “to meet Miss Clephane after I was invalided home. She took pity on me when I was in hospital on Long Island, and I’ve wanted to thank her ever since. But my boss keeps me on a pretty short chain, and I can’t often get away.”
“It’s wonderful,” said the girl, with her quiet smile, “how you’ve got over your lameness.”
“Oh, well—” he had one of his easy gestures—“lameness isn’t the hardest thing in the world to get over Especially not with the care I had.”
Silence fell. Kate struggled to break it, feeling that she was expected to speak, to say something, anything; but there was an obstruction in her throat, as if her voice were a ghost vainly struggling to raise its own grave-stone.
Their visitor made the automatic motion of consulting his wrist-watch. “Jove! I hadn’t an idea it was so late. I’ve got barely time to dash for my train!” He stood looking in his easy way from mother to daughter; then he turned once more to Kate.
“Aren’t you coming over to see the great Maclew library one of these days? I was just telling Miss Clephane—”
“Uncle Fred has always promised to take me,” the girl threw in.
“Well, that settles it; doesn’t it, Mrs. Clephane?” This time he wavered a second before the “Mrs.”, and then carried it off triumphantly “As soon as you can make a date, will you wire me? Good!” He was holding out his hand. Kate put hers in it; she did not mind. It was as if she had laid a stone in his palm.
“It’s a go, then?” he repeated gaily, as he shook hands with Anne; and the door closed on him.
“Major Fenno”— Kate repeated the name slowly as she turned back toward the fire. She had never heard of his military rank. “Was he wounded?” she asked her daughter suddenly.
“At Belleau Wood—didn’t you know? I thought you might have—he was mentioned in despatches. He has the Legion of Honour and the D.S.M.” Anne’s voice had an unwonted vibration. “But he never talks of all that; all he cares about is his writing,” she added.
She was gathering up her brushes, rubbing her pallet with a rag, going through all the habitual last gestures with her usual somewhat pedantic precision. She found something wrong with one of the brushes, and bent over the lamp with it, her black brows jutting. At that moment she reminded her mother of old Mrs. Clephane; somehow, there was an odd solace in the likeness.
“If he comes for anybody it’s for Lilla,” the mother thought, as her eyes rested on her daughter’s stern young profile; and again she felt the necessity of clearing up the mystery. On the whole, it might be easier to question Anne, now that the name had been pronounced between them.
Major Fenno—and he had been wounded.... And all he cared about was his writing.
X.
AFTER all, she was not going to be able to question Anne about Lilla. As she faced the situation the next day—as she faced the new Chris in her path—Kate Clephane saw the impossibility of using him as a key to her daughter’s confidence. There was one thing much closer to her now than any conceivable act of Chris’s could ever be; and that was her own relation to Anne. She simply could not talk to Anne about Chris—not yet. It was not that she regarded that episode in her life as a thing to be in itself ashamed of. She was not going, even now, to deny or disown it; she wanted only to deny and disown Chris. Quite conceivably, she might have said to her daughter: “Yes, I loved once—and the man I loved was not your father.” But to say it about Chris! To see the slow look of wonder in those inscrutable depths of Anne’s eyes: a look that said, not “I blame you”, or even “I disapprove you”, but, so much more scathingly, just: “You, mother— and Chris?”
Yes; that was it. It was necessary for her pride and dignity, for her moral safety almost, that what people like Enid Drover would have called her “past” should remain unidentified, unembodied—or at least not embodied in Chris Fenno. Yet to know—to know!
There were, of course, other sources of enlightenment; if there were anything in her theory of a love-affair between Lilla and Chris, the family were probably not unaware of it. Kate had the sense that they never had their eyes off Lilla for long. But it was all very well to plan to talk to them—the question remained, how to begin? Before trying to find out about Lilla she would first have to find out about them. What did she know of any one of them? Nothing more, she now understood, than their glazed and impenetrable surfaces.
She was still a guest among them; she was a guest even in her daughter’s house. It was the character she had herself chosen; in her dread of seeming to assert rights she had forfeited, to thrust herself into a place she had deserted, she had perhaps erred in the
other sense, held back too much, been too readily content with the easy part of the week-end visitor.
Well—it had all grown out of the other choice she had made when, years ago, she had said: “Thy gods shall not be my gods.” And now she but dimly guessed who their gods were. At the moment when her very life depended on her knowing their passwords, holding the clue to their labyrinth, she stood outside the mysterious circle and vainly groped for a way in.
Nollie Tresselton, of course, could have put the clue in her hand; but to speak to Nollie was too nearly like speaking to Anne. Not that Nollie would betray a confidence; but to be divined and judged by her would be almost as searing an experience as being divined and judged by Anne. And so Kate Clephane continued to sit there between them, hugging her new self in her anxious arms, turning its smooth face toward them, and furtively regulating its non-committal gestures and the sounds that issued from its lips.
Only the long nights of dreamless sleep were gone; and her heart stood still each time she slipped the key into the studio door.
“Mother, Uncle Fred wants to take us to Baltimore next week to see the Maclew library; you and Lilla and me.”
Anne threw it over her shoulder as she stood before her easel, frowning and narrowing her lips at the difficulty of a branch of red pyrus japonica in a brass pot, haloed with the light of the sunlit window.
Kate, behind her, was leaning back indolently in a deep wicker armchair. She started, and echoed in a blank voice: “Next week?”
“Well, you see, I’ve promised to spend a few days in Washington with Madge Glenver, who has taken a house at Rock Creek for the spring. This is just the moment for the magnolias; and I thought we might stop at Baltimore on the way, and Uncle Fred could bring you and Lilla back from there.”
It sounded perfectly simple and sensible; Anne spoke of it in her usual matter-of-course tone. Her mother tried for the same intonation in answering, with a faint touch of surprise: “Lilla too?”
Anne turned around completely and smiled. “Oh, Lilla particularly! You mustn’t speak of it yet, please—not even to Aunt Enid—but there’s a chance ... a chance of Lilla’s marrying.”
Kate’s heart gave a great bound of relief or resentment—which? Why, relief, she instantly assured herself. She had been right then— that was the key to the mystery! And why not? After all, what did it matter to her? Had she, Kate, ever imagined that Chris’s love-affairs would cease when she passed from his life? Wasn’t it most probably in pursuit of a new one that he had left her? To think so had been, at any rate, in spite of the torturing images evoked, more bearable than believing he had gone because he was tired of her. For years, as she now saw, she had been sustained by her belief in that “other woman”; only, that she should take shape in Lilla was unbelievably humiliating.
Anne continued to smile softly down on her mother. In her smile there was something veiled and tender, as faint as sunlight refracted from water—a radiance striking up from those mysterious depths that Kate had never yet reached. “We should all be so glad if it happened,” the girl continued; and Kate said to herself: “What she’s really thinking of when she smiles in that way is her own marriage....” She remembered the cryptic allusion of the football-faced youth at the Opera, and the way those vigilant lids of Anne’s had shut down on her vision.
“Of course—poor Lilla!” Mrs. Clephane absently assented. Inwardly she was saying to herself that it would be impossible for her to go to Baltimore on that particular errand. Chris and Lilla—Chris and Lilla! The coupled names began again to jangle maddeningly through her brain. She stood up and moved away to the window. No, she couldn’t!
“Next week, dear? It doesn’t matter—but I think you’ll have to go without me.” She spoke from the window, without turning her head toward her daughter, who had gone back to the easel.
