Question 1

A 65-year-old woman comes to the office to discuss the results of a screening DXA test. She has been healthy all her life, has no chronic medical conditions, and takes no medications. The patient experienced menopause at age 52; she was treated with combined estrogen/progestin menopausal hormone therapy due to hot flashes but discontinued the treatment after a few months due to concerns regarding adverse effects. She has experienced a 1 cm (0.4 in) loss of height since that time. The patient quit smoking 30 years ago and drinks wine only on social occasions. She lives alone and has no children. Her mother died of breast cancer at age 56 and her father died at age 82 from a stroke. BMI is 22 kg/m². Physical examination is unremarkable. DXA reveals a T score of −2.1 and −2.6 at femoral neck and lumbar spine, respectively. Complete blood count, comprehensive metabolic panel, and serum phosphorus are normal. Which of the following additional investigations should be performed for this patient at this time?

Accepted Answer

11ec193a_97d0_2225_853d_b7040720391c_MD0002_00 Osteoporosis is a common disorder in postmenopausal women. It has a long asymptomatic phase, and treatment can reduce the risk of fracture in patients with osteoporosis. It is therefore an ideal subject for a routine screening program. Screening for osteoporosis by DXA is recommended for women age ≥65, and for younger women with significant risk factors (eg, prior low-trauma fracture, long-term glucocorticoid use, low body weight). Screening DXA is typically performed at the lumbar spine and hips; a T score ≤−2.5 at any location is consistent with osteoporosis. Osteoporosis is most commonly due to age-related bone loss, which accelerates following menopause in most women. However, patients with a new diagnosis of osteoporosis warrant a basic laboratory evaluation for reversible secondary causes. Typical studies include serum chemistries (eg, calcium, phosphorus, albumin, total protein, and renal and hepatic function markers) and complete blood count. In addition, vitamin D stores should be assessed with a 25-hydroxyvitamin D level. Intake of adequate amounts of vitamin D and calcium helps reduce bone loss. (Choice A) Many experts advise measurement of 24-hour urine calcium excretion, especially in women who are likely to have inadequate intestinal absorption of calcium (eg, malabsorptive syndromes) or signs of excess calcium excretion (eg, kidney stones). However, this should be performed only after correction of vitamin D deficiency, and patients should have adequate intake of calcium (1,000-1,200 mg/day) for 2 weeks prior to the test. (Choice C) Spinal imaging (eg, lateral spine x-ray) is indicated for patients with low bone density who are most likely to have vertebral fracture, including women age ≥70 (men age ≥80), loss of height >4 cm, self-reported vertebral fracture, and systemic glucocorticoid therapy >3 months. This patient's minimal loss of height does not require imaging. (Choice D) Patients with a new diagnosis of osteoporosis warrant a basic laboratory evaluation for reversible secondary causes. (Choice E) Serum protein electrophoresis is indicated in patients with evidence of a possible plasma cell dyscrasia (eg, multiple myeloma), such as anemia, renal insufficiency, hypercalcemia, or proteinuria. Educational objective: Patients with osteoporosis warrant laboratory testing for reversible secondary causes. The evaluation should include serum chemistries (eg, calcium, phosphorus, albumin, total protein, and renal and hepatic function markers) and complete blood count. In addition, vitamin D stores should be assessed with a 25-hydroxyvitamin D level. __________ References: Clinician's guide to prevention and treatment of osteoporosis (http://www.ncbi.nlm.nih.gov/pubmed/25182228) American Association of Clinical Endocrinologists and American College of Endocrinology clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis. 2016 executive summary. (http://www.ncbi.nlm.nih.gov/pubmed/27643923)

Question 2

A 65-year-old man comes to the office a month after sustaining a nondisplaced left femoral neck fracture in a ground-level fall.  He underwent internal fixation of the left hip and was discharged to a skilled nursing facility.  The patient is now able to ambulate with a cane.  He has no bone pain, previous fractures, diarrhea, or loss of height.  Medical history is significant for hypertension treated with hydrochlorothiazide.  The patient does not use tobacco or alcohol.  There is no family history of osteoporosis or thyroid disorders.  Since hospital discharge, the patient has taken adequate amounts of calcium and vitamin D via diet and oral supplementation.
Vital signs are normal.  The surgical scar has healed well and physical examination is unremarkable.
Laboratory tests show normal complete blood count, basic metabolic panel, hepatic function tests, TSH, 24-hour urinary calcium, and 25-hydroxyvitamin D.  DXA reveals T-scores of −2.0 in the femoral neck and −2.5 in the lumbar spine.  Plain radiograph of the spine is normal.
Which of the following is the most appropriate next step in evaluation of this patient?

Accepted Answer

11ec193a_97d3_a49e_853d_65068be105ff_MD0002_00 In contrast to women, in whom osteoporosis is usually due to physiologic bone loss following menopause, osteoporosis in men is more likely due to secondary causes (eg, glucocorticoid use, excessive alcohol intake). As many as two-thirds of elderly men with hip fractures have hypogonadism, which is often not associated with other specific symptoms of testosterone deficiency (eg, changes in body hair, loss of libido). This patient with osteoporosis (low bone mineral density [BMD] on DXA) and a fragility fracture has no clear etiology for his low BMD; therefore, an early-morning serum testosterone assay is indicated. Some men with hypogonadism who have osteoporosis may benefit from testosterone replacement therapy, which increases BMD. Additional tests for men with osteoporosis should include blood cell counts, serum chemistries (eg, electrolytes, calcium, phosphorus), liver function tests, albumin and total serum protein, alkaline phosphatase, TSH, and 25-hydroxyvitamin D. A 24-hour urine calcium assay can also be considered during initial testing, but vitamin D deficiency must be corrected before this test is ordered. Some experts also recommend a parathyroid hormone level (especially in patients with hypercalcemia) and a tissue transglutaminase antibody assay (especially in patients with evidence of malabsorption). (Choice A) A common cause of osteoporosis is excess glucocorticoids. However, screening for hypercortisolism with a 24-hour urine cortisol assay is necessary only for those with clinical features of Cushing syndrome. Cushing syndrome (Choice B) Hyperprolactinemia in men typically presents with central hypogonadism due to suppression of GnRH (and subsequently LH) secretion. Common symptoms include erectile dysfunction and loss of libido. Osteoporosis is a possible manifestation, due to low testosterone production. However, serum testosterone levels should be obtained first because, if serum testosterone is normal, hyperprolactinemia is unlikely and there is no need to measure prolactin. (Choice C) In addition to localized osteolytic lesions, multiple myeloma can cause generalized bone loss. However, this is a less common cause of osteoporosis, and testing with serum and urine protein electrophoresis is needed only for those with additional features suggestive of myeloma (eg, anemia, parathyroid hormone-independent hypercalcemia, vertebral fracture). (Choice E) Bone turnover markers (eg, urine N-telopeptide) can assess ongoing bone loss and may be useful if the need for antiresorptive therapy is uncertain. However, antiresorptive therapy is indicated for this patient due to established osteoporosis with a fragility fracture; measurement of bone turnover markers would not further improve his care. Educational objective: Osteoporosis in men is often due to secondary causes. Elderly men with hip fractures frequently have hypogonadism and should be screened with an early-morning serum testosterone assay. __________ References: Osteoporosis in men. (http://www.ncbi.nlm.nih.gov/pubmed/24019112)

Question 3

A 26-year-old woman comes to the office due to persistent fatigue and inability to lose weight. She has also experienced hair loss and dry skin. The patient was diagnosed with primary hypothyroidism 2 years ago and was started on levothyroxine therapy, which she takes on an empty stomach every morning. She exercises 5 times per week, follows very strict caloric restrictions, and has eliminated gluten-containing foods from her diet. Medical history is unremarkable, and the patient has never been pregnant. In addition to levothyroxine, she also takes a cyclic estrogen-progestin oral contraceptive. The patient is sexually active with one partner and does not use tobacco, alcohol, or illicit drugs. Blood pressure is 124/80 mm Hg and pulse is 70/min. BMI is 26 kg/m². The thyroid gland is diffusely enlarged, firm, and nontender, and the remainder of the physical examination is normal. Laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient's condition?

Accepted Answer

This patient has primary hypothyroidism, most likely due to chronic lymphocytic (Hashimoto) thyroiditis (eg, diffuse, nontender goiter). She is on appropriate levothyroxine replacement therapy, and although she has persistent symptoms, her normal TSH indicates that she is in a biochemically euthyroid state (some experts suggest checking free T4 for confirmation in such patients, but this is not routinely needed). However, the symptoms of hypothyroidism are nonspecific and overlap extensively with other common conditions (eg, affective disorders, sleep disorders, anemia). Some patients report a greater sense of well-being when their levothyroxine dose is titrated to maintain TSH in the lower half of the normal range, but the dose should not be increased further in an attempt to improve symptoms (Choice D) as doing so may increase the risk of thyrotoxic complications (eg, hypertension, osteoporosis). This patient is on an appropriate dose of levothyroxine; other causes for her symptoms should be sought. (Choice A) Clinicians sometimes add liothyronine (T3) to levothyroxine (T4) in an attempt to alleviate residual symptoms. However randomized studies have shown no benefit of this approach over levothyroxine monotherapy, and the short half-life of liothyronine can lead to nonphysiologic fluctuations in thyroid hormone levels. (Choice C) Estrogen-containing oral contraceptives stimulate synthesis of thyroxine-binding globulin, necessitating a higher dose of levothyroxine to maintain free hormone levels. However, this patient's normal TSH indicates that this effect has been accounted for. In addition, although weight gain is commonly attributed to oral contraceptives, this has not been confirmed in controlled trials. (Choice E) Selenium supplements can lower thyroid peroxidase antibody levels in Hashimoto thyroiditis and may decrease levothyroxine dose requirements in some patients. However, this patient is biochemically euthyroid, and evidence does not show clinically significant enhancements in thyroid function in such patients. Educational objective: Primary hypothyroidism is treated with levothyroxine, with the dose adjusted to maintain serum TSH in the normal (or low-normal) range. Further dose increases or the addition of liothyronine (T3) are not recommended. Hypothyroid symptoms are nonspecific, and patients with residual symptoms should be evaluated for alternate etiologies. __________ References: Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association task force on thyroid hormone replacement. (http://www.ncbi.nlm.nih.gov/pubmed/25266247) Risks and safety of combination therapy for hypothyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/27137849)

Question 4

A 36-year-old woman comes to the office for follow-up of hypothyroidism.  She has no current symptoms.  The patient was diagnosed with hypothyroidism secondary to Hashimoto's thyroiditis 4 years ago.  She takes 150 µg levothyroxine daily before breakfast and her dose has been stable for the last year.  Physical examination, including thyroid examination, is normal.
Thyroid function tests are as follows:

Which of the following is the best next step in management of this patient?

Accepted Answer

11ec193a_97cd_14dd_853d_3d7c830e844e_MD0002_00 Synthetic levothyroxine (LT₄) is the preferred replacement therapy for hypothyroidism. Most actions of the thyroid hormone in the body are mediated through triiodothyronine (T₃), which is secreted in active form by the thyroid gland (15%-20%) and also converted from thyroxine (T₄) in extrathyroidal tissues (80%-85%). Because a large percentage of T₃ is formed from T₄ conversion in the peripheral tissues, patients with hypothyroidism are usually able to achieve adequate T₃ levels with LT₄ treatment alone. ₄ ₃ ₄ ₃ ₄ ₃ ₄ The recommended therapeutic goal in patients with primary hypothyroidism is to maintain TSH within the normal reference range. Serum TSH is the most reliable marker of levothyroxine replacement therapy in hypothyroid patients as it reflects the biologic activity of thyroid hormones in the tissues (ie, hypothalamus). For this reason, TSH alone is usually sufficient to monitor LT₄ treatment in patients with primary hypothyroidism. However, despite this recommendation, thyroid hormone levels are frequently ordered by practitioners along with TSH to monitor LT₄ therapy. ₄ ₄ (Choices A and D) In most patients on LT₄ therapy who have a TSH within the reference range, circulating T₃ levels will also be within the reference range. In some cases, treatment with LT₄ alone may fail to restore plasma T₃ to a level within the reference range despite a normal TSH. However, the significance of this low T₃ is unknown, and the American Thyroid Association recommends against increasing the LT₄ dose, treating with combination LT₄ and liothyronine (T₃), or switching to liothyronine alone in these patients. ₄ ₃ ₄ ₃ ₃ ₄ ₄ ₃ (Choice C) Levels of free T₄ above the reference range are often observed during replacement therapy with LT₄, especially if the blood sample is drawn 1-3 hours after LT₄ administration. This condition is not associated with adverse events, and the dose of LT₄ should not be changed. ₄ ₄ ₄ ₄ (Choice E) Thyroid peroxidase (TPO) antibodies are useful for diagnosis in cases of subclinical hypothyroidism, recurrent miscarriages, and euthyroid diffuse goiters. However, there is no benefit to measuring TPO antibodies once the diagnosis of Hashimoto's thyroiditis has been established (as in this patient). Educational objective: The therapeutic goal in primary hypothyroidism is to maintain TSH levels within the normal reference range by replacement with levothyroxine. Levothyroxine dose adjustment should be based on TSH levels alone rather than direct measurement of thyroid hormone levels. __________ References: Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. (http://www.ncbi.nlm.nih.gov/pubmed/23246686)

Question 5

A 29-year-old woman comes to the office due to amenorrhea.  She has not had a menstrual period since an uncomplicated vaginal delivery 13 months ago.  The patient stopped breastfeeding 7 months ago but still has some milky discharge from both breasts.  She has no other symptoms.  The patient has a 10-year history of hypothyroidism, for which she takes levothyroxine, the dose of which was increased during her pregnancy.
On breast examination, bilateral milky discharge is expressed.  There are no palpable masses, skin changes, or axillary lymphadenopathy.  The remainder of the physical examination is normal.
Laboratory results are as follows:
 Urine pregnancy test is negative.
Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

11ec193a_97d7_2715_853d_db32c2de8be9_MD0002_00 Prolactin levels naturally increase during pregnancy due to stimulation from high estrogen levels, peak at delivery, and then normalize within 1-2 months after delivery, even with continued breastfeeding. Although prolactin levels increase transiently above basal levels with response to suckling, this response significantly diminishes a few weeks after delivery. This patient is no longer breastfeeding and is not currently taking any medications (eg, antipsychotics) that would explain increased prolactin levels. The most likely cause of this patient's elevated prolactin is a prolactinoma (ie, lactotroph adenoma). Prolactinomas can present with secondary amenorrhea, bilateral milky nipple discharge (ie, galactorrhea), and hypogonadism. A significantly elevated prolactin (>200 ng/mL) level usually indicates a prolactinoma. In any patient who has hyperprolactinemia and is not taking any medication known to increase prolactin levels, an MRI of the head should be performed to screen for a pituitary mass (Choice D). Additional evaluation of prolactinomas includes formal visual field testing due to the potential for the pituitary mass to compress the optic chiasm. Prolactinomas that cause hypogonadism (eg, amenorrhea) or neurologic symptoms (eg, headaches, visual disturbances) secondary to mass effect are treated first-line with dopamine agonists (eg, cabergoline, bromocriptine) and followed with serial MRIs. Surgery (eg, transsphenoidal resection) is reserved for patients who fail medical therapy. (Choice A) Patients with nipple discharge may require breast imaging (eg, ultrasound, mammogram) to evaluate for malignancy. However, breast cancer is associated with unilateral serous or serosanguinous discharge. This patient's markedly elevated prolactin level and bilateral nipple discharge make prolactinoma a more likely diagnosis. (Choice C) A progestin withdrawal test (ie, medroxyprogesterone for 5-10 days) induces menstrual bleeding in patients with amenorrhea if there is sufficient estrogen priming of the endometrium. This patient may or may not bleed following medroxyprogesterone depending on her estrogen status, but this would not address the hyperprolactinemia. (Choice E) Hypothyroidism leads to high thyrotropin-releasing hormone (TRH), which stimulates prolactin release and causes mild hyperprolactinemia. Although this patient's TSH is slightly elevated, mild hypothyroidism does not cause a markedly elevated prolactin level of >200 ng/mL. In addition, serum TSH is the most sensitive test to diagnose hypothyroidism and monitor response to levothyroxine therapy and therefore can be used alone to adjust dosage without checking total T4, free T4, or free T3 levels. Educational objective: Pituitary prolactinomas (ie, lactotroph adenomas) present with galactorrhea, amenorrhea, and hyperprolactinemia. A prolactin level >200 ng/mL usually indicates a prolactinoma. Diagnosis is confirmed via MRI of the head. First-line treatment is with dopamine agonists (eg, cabergoline, bromocriptine). __________ References: Diagnosis and treatment of pituitary adenomas: a review. (http://www.ncbi.nlm.nih.gov/pubmed/28170483) Menstrual cycle abnormalities in patients with prolactinoma and drug-induced hyperprolactinemia. (http://www.ncbi.nlm.nih.gov/pubmed/28670538)

Question 6

A 52-year-old man comes to the clinic with concerns about his sexual desire. The patient's libido was previously normal but has progressively diminished over the last 6 months. The patient has also experienced fatigue and malaise without weakness or weight changes. He says, "I just do not feel like myself anymore." The patient is married and has 2 children. He reports a satisfying relationship with his wife, although his recent symptoms have been a source of tension between them. The patient's medical issues include gastroesophageal reflux, irritable bowel syndrome, and chronic low back pain from a workplace injury 2 years ago. He underwent spinal surgery after the incident but has had continuing pain, requiring opioid treatment for the last 2 years. Current medications include omeprazole, long-acting oxycodone, and as-needed acetaminophen and polyethylene glycol. He does not use alcohol, tobacco, or illicit drugs. Vital signs are within normal limits. BMI is 26 kg/m². Physical examination shows normal muscle bulk and body hair distribution. Auscultation of the heart and lungs is normal. Extremities are warm with palpable pulses. The testicles are small in volume with no tenderness or palpable masses. Neurological examination is normal, and visual fields are full to confrontation. Strength is normal in the extremities. Morning serum total testosterone level is 180 ng/dL (normal 300-1200 ng/dL), which is consistent on repeat evaluation. Subsequent laboratory testing shows the following: Which of the following is the most likely cause of the patient's diminished sexual desire?

Accepted Answer

This patient has decreased libido and fatigue associated with testicular atrophy. He also has a persistently low serum testosterone with inappropriately low FSH and LH levels, which is consistent with secondary (central) hypogonadism rather than primary gonadal dysfunction (Choice E). In the setting of a chronic pain disorder and long-term opioid use, this is most likely opioid-related hypogonadism. Chronic opioid use leads to decreased gonadotropin-releasing hormone secretion and is a common cause of hypogonadism. The hypothalamic-pituitary-adrenal axis can be affected as well. Opioid-related hypogonadism is common in patients on chronic opioid therapy. Additional manifestations can include depression, hot flashes, night sweats, osteoporosis, and menstrual irregularities (in women). The ideal management of opioid-related hypogonadism is cessation of opioid therapy, although dose reduction and rotating opioid types may sometimes be adequate. If symptoms continue and the patient cannot be withdrawn from opioids, androgen replacement therapy may be needed. (Choice B) A primary mood disorder could explain some of this patient's clinical features, including decreased libido. However, his testicular atrophy and metabolic markers of central hypogonadism are more consistent with opioid-related hypogonadism. (Choice C) Serum testosterone levels and sexual function commonly diminish with age. However, libido is typically intact, and this patient is too young to attribute his symptoms to age. (Choice D) Although this patient's gonadotropin levels are low, his TSH (and free T4) levels are normal and he has no specific manifestations of pituitary dysfunction. The primary effect in opioid-related hypogonadism is in the hypothalamus. Educational objective: Chronic opioid use leads to decreased gonadotropin-releasing hormone secretion, and is a common cause of hypogonadism. Patients can develop decreased libido and other manifestations of hypogonadism. Management options include discontinuation, dose reduction, or rotation of opioid types, or androgen replacement therapy. __________ References: Opioid related endocrinopathy. (http://www.ncbi.nlm.nih.gov/pubmed/26461076)

Question 7

A 50-year-old woman comes to the office due to involuntary leakage of urine. The leakage started a year ago and currently occurs several times a day when the patient coughs, sneezes, laughs, or stands up. She also sometimes has loss of urine during sexual intercourse. The patient awakens to urinate once each night; she has had no dysuria, hematuria, urinary urgency, or fecal incontinence. She has had 2 vaginal deliveries. Her incontinence makes her self-conscious during social interactions and she has stopped participating in exercise classes. Her general health is otherwise good. Physical examination is within normal limits, except for a BMI of 32 kg/m². Pelvic examination reveals mild uterine prolapse. A cough with a full bladder elicits an immediate release of a small amount of urine. Urinalysis is normal. Post-voiding urinary residual volume is 20 mL. The patient is currently collecting information in a voiding diary regarding fluid intake, voiding frequency, and amount of urine. Which of the following is the best next step in management of this patient?

Accepted Answer

11ec193a_97d8_3886_853d_eb2edcc93157_MD0002_00 This patient has stress urinary incontinence based on involuntary leakage of urine with coughing, sneezing, or exertion. Patients with stress incontinence are initially managed conservatively with lifestyle changes (eg, restricting fluid intake, weight loss, smoking cessation). Pelvic floor muscle training (eg, Kegel exercise) is recommended to strengthen the pelvic floor musculature; this may help with decreasing the frequency and volume of urine loss. Bladder training with frequent, timed voiding can keep urine volumes low and is helpful when combined with pelvic muscle exercises. (Choice B) Medications usually are not effective for stress incontinence treatment. Duloxetine (a serotonin-norepinephrine reuptake inhibitor) is approved in Europe for treatment of stress incontinence with benefit in some patients. However, it is not approved for treatment of stress incontinence in the United States. (Choice C) An incontinence pessary is inexpensive and safe and can be considered for patients who fail conservative therapy. These devices have a compliance rate of only about 50%, but they are useful in patients who wish to avoid surgery. (Choice D) Surgery for stress incontinence has the highest cure rate and includes mid-urethral sling or Burch retropubic colposuspension. However, surgery is invasive and usually reserved for patients who fail conservative management. (Choice E) Urodynamic testing evaluates urine storage and evacuation, and may help diagnose the incontinence type in patients with mixed symptoms (eg, stress, urgency). However, it is not well standardized and has inconsistent reproducibility in the same patient. Educational objective: Patients with stress urinary incontinence should be evaluated for modifiable risk factors. Initial treatment is with behavioral therapy and pelvic floor muscle exercises. Surgical therapy should be reserved for those who fail noninvasive therapy. __________ References: Diagnosis of urinary incontinence. (http://www.ncbi.nlm.nih.gov/pubmed/23668444) Pelvic floor muscle training: underutilization in the USA. (http://www.ncbi.nlm.nih.gov/pubmed/26757904) Duloxetine versus placebo for the treatment of North American women with stress urinary incontinence. (http://www.ncbi.nlm.nih.gov/pubmed/14501737)

Question 8

A 30-year-old woman without significant past medical history comes to the physician with a palpable lump in her neck.  She has no associated symptoms and no family history of thyroid or other endocrine disorders.  Her TSH level is 1.3 µU/mL (normal 0.5-5.0 µU/mL).  Thyroid ultrasound shows a 16-mm round, hypoechoic nodule in the right lobe of the thyroid.  There is no lymph node enlargement.
Which of the following is the most appropriate course of action?

Accepted Answer

11ec193a_97d4_40df_853d_abc12e05d539_MD0002_00 Thyroid nodules can be malignant in 4%-6% of cases. The likelihood of malignancy can be estimated based on nodule size, historical factors, TSH level, and ultrasound characteristics: Historical risk factors include a personal or first-degree family history of thyroid cancer, head/neck or total body radiation exposure in childhood, rapid nodule growth, and cervical lymphadenopathyLow (suppressed) TSH levels suggest a hyperfunctioning nodule, which is usually benign; a normal or elevated TSH raises risk of thyroid malignancySuspicious ultrasound findings include larger nodules, microcalcifications, increased nodular vascularity, hypoechoic appearance, and indistinct nodule margins Historical risk factors include a personal or first-degree family history of thyroid cancer, head/neck or total body radiation exposure in childhood, rapid nodule growth, and cervical lymphadenopathy Low (suppressed) TSH levels suggest a hyperfunctioning nodule, which is usually benign; a normal or elevated TSH raises risk of thyroid malignancy Suspicious ultrasound findings include larger nodules, microcalcifications, increased nodular vascularity, hypoechoic appearance, and indistinct nodule margins Fine-needle aspiration (FNA) is recommended in patients with high risk for malignancy based on initial assessment. In most cases, patients with a normal/elevated TSH and a solid nodule >1 cm in diameter should be evaluated further with FNA. initial assessment (Choice A) Anti-thyroid peroxidase (TPO) antibodies suggest Hashimoto's thyroiditis (chronic autoimmune thyroiditis). They are most often assayed in patients with goiter or with thyroid nodules and elevated TSH. However, TPO antibodies do not exclude malignancy or alter indications for FNA. (Choice C) Repeat thyroid ultrasound in 6-12 months is recommended for patients with FNA showing benign thyroid nodules. This patient would first need FNA to evaluate whether the nodule is benign or malignant. (Choice D) Surgery is indicated for patients with FNA showing cytological features (definitive or suspicious) of malignancy, non-diagnostic cytology on multiple FNAs, or compressive symptoms. (Choice E) Thyroid scintigraphy is used to assess hyperfunctioning nodules or a multinodular goiter in patients with low TSH, which is not present in this patient. Educational objective: TSH and thyroid ultrasound should be performed in all patients with thyroid nodules. The risk of malignancy can be assessed based on historical risk factors, TSH, nodule size, and ultrasound characteristics. High-risk nodules should be further evaluated with fine-needle aspiration. __________ References: Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. (http://www.ncbi.nlm.nih.gov/pubmed/19860577) Ultrasonographic evaluation of thyroid nodules: comparison of ultrasonographic, cytological, and histopathological findings. (http://www.ncbi.nlm.nih.gov/pubmed/19859839)

Question 9

A 66-year-old woman is seen in the outpatient clinic for follow-up.  The patient has no current symptoms.  She has a history of hypothyroidism and takes levothyroxine replacement therapy.  The patient's other medical problems include hypertension and acid reflux disease.  She underwent dual-energy x-ray absorptiometry 2 months ago, which was normal.  Her TSH level is <0.01 mU/L.  Despite a long discussion, the patient refuses to decrease the dose of levothyroxine as lower doses make her feel "exhausted and sleepy all the time."
Which of the following is a possible complication of levothyroxine overreplacement in this patient?

Accepted Answer

A number of serious adverse effects are associated with overtreatment of hypothyroidism with levothyroxine, including excessive bone loss and cardiac arrhythmias (eg, atrial fibrillation). The risk of bone loss and arrhythmias from overtreatment is higher in older patients, particularly those with markedly suppressed TSH (<0.1 mU/L). Nonspecific symptoms (eg, fatigue, weight gain) in patients with hypothyroidism are frequently attributed to undertreatment, and patients often request supratherapeutic dosing of thyroid supplements to increase energy and facilitate weight loss. As a result, overtreatment of hypothyroidism is not uncommon in clinical practice but should be discouraged. Also, the addition of liothyronine in a patient who is biochemically euthyroid on levothyroxine is not associated with improved outcomes and is not indicated. However, dosing of levothyroxine to maintain TSH in the low-normal range is not associated with adverse effects and may be adequate to satisfy patient concerns. (Choice B) There is no proven association of dementia with thyrotoxicosis. Patients with severe thyrotoxicosis may have acute reversible changes in mental status ranging from mild inattention to loss of consciousness. (Choice C) Hypothyroidism increases LDL, whereas LDL levels decrease in thyrotoxicosis. (Choice D) Ophthalmopathy, characterized by an increase in volume of retro-orbital tissues with proptosis, is an extrathyroidal manifestation of Graves' disease but is not seen in other causes of thyrotoxicosis. Lid lag and lid retraction without proptosis can be seen with thyrotoxicosis due to any cause. (Choice E) A high TSH level is a risk factor for thyroid cancer, but a low TSH level may be protective. Educational objective: Overtreatment of hypothyroidism with levothyroxine is associated with an increased risk of excessive bone loss and atrial fibrillation. __________ References: Serum thyroid-stimulating hormone concentration and morbidity from cardiovascular disease and fractures in patients on long-term thyroxine therapy. (http://www.ncbi.nlm.nih.gov/pubmed/19906785)

Question 10

A 56-year-old woman is evaluated for persistent fatigue. A year ago, she developed panhypopituitarism following resection of a large nonfunctional pituitary tumor. Current treatment includes hydrocortisone and levothyroxine, with her most recent dose adjustment a few months ago. The patient has had no associated headaches, excessive urination, visual disturbances, or weight change. Vital signs are normal. BMI is 26 kg/m² with no change in weight over the last 6 months. Physical examination is unremarkable. Laboratory results are as follows: An MRI of the pituitary 6 months ago showed no residual pituitary tumor. Which of the following is the most appropriate next step in management of this patient's disorder?

Accepted Answer

11ec193a_97d1_5aa8_853d_df6aa3538384_MD0002_00 Pituitary tumors are the most common cause of central (secondary) hypothyroidism, which can arise due to compressive effects of the tumor or as a complication of surgery or radiation therapy. The diagnosis is established by a low serum free T4 associated with a low (or inappropriately normal) TSH. This patient has central hypothyroidism and is on levothyroxine therapy but her persistent fatigue suggests possible under-replacement. Unlike primary hypothyroidism, TSH in central hypothyroidism demonstrates minimal response to levothyroxine supplementation. Nearly all patients with central hypothyroidism on thyroid replacement therapy have undetectable TSH; and patients whose levothyroxine dose is inadequate (eg, due to decreased absorption or increased metabolic demands) most often do not exhibit a rise in TSH. Therefore, levothyroxine dosing in central hypothyroidism should be based on serum free T4 levels, with the dose adjusted to maintain T4 in the high-normal range. (Choices A and D) T3 is produced primarily by deiodination of T4 in peripheral tissues. Serum T3 levels (total and free) correlate poorly with overall thyroid physiologic status and are less reliable than T4, although they are occasionally used in the evaluation of hyperthyroidism in patients with normal T4 levels, in those with alterations in thyroid-binding proteins, or in those with euthyroid sick syndrome. T3 has a shorter half-life than T4, and liothyronine (T3) therapy can lead to fluctuations in physiologic status and increased risk of thyrotoxicosis. Studies have not shown superiority of combined replacement over levothyroxine (T4) alone. (Choice C) Disruption of other pituitary hormones is common in central hypothyroidism. However, insulin-like growth factor 1 levels (eg, as used in the assessment of growth hormone deficiency) can be low in a hypothyroid state, and adequate levothyroxine dosing should be confirmed before measuring insulin-like growth factor 1. (Choice E) A low (ie, suppressed) TSH in primary hypothyroidism indicates over-replacement and warrants a dose reduction. However, this relationship does not hold in central hypothyroidism. Educational objective: Levothyroxine therapy in central hypothyroidism should be based on serum free T4 levels, with the dose adjusted to maintain T4 in the high-normal range. TSH in central hypothyroidism demonstrates minimal responsiveness to levothyroxine and may not rise in patients with inadequate replacement. __________ References: Clinical review: central hypothyroidism: pathogenic, diagnostic, and therapeutic challenges. (http://www.ncbi.nlm.nih.gov/pubmed/22851492)

Question 11

A 24-year-old woman comes to the office for emergency contraception. The patient had unprotected intercourse with her boyfriend 2 nights ago after a condom broke. She is not using any form of contraception other than condoms with spermicide. Her last menstrual period was 2 weeks ago. The patient has no medical problems and has had no surgeries. She takes no daily medications and does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. BMI is 26 kg/m². On speculum examination, there is a mucopurulent discharge at the cervical os; no vaginal bleeding is noted. The uterus is small and mobile. There are no adnexal masses or tenderness. Urine pregnancy test is negative. Which of the following is the best next step in management of this patient?

Accepted Answer

11ec193a_97d6_8ad3_853d_6bd613664974_MD0002_00 Emergency contraception (postcoital contraception) is indicated in patients with recent unprotected intercourse who do not want to become pregnant. In patients close to ovulation, the probability of pregnancy is as high as 30%. Emergency contraception works by either delaying ovulation (eg, oral contraceptives, levonorgestrel) or inhibiting fertilization (eg, copper-containing intrauterine device [IUD]). The contraception should be provided as soon as possible as efficacy decreases with time after intercourse. The most effective emergency contraceptive is a copper-containing IUD, which is 99% effective in preventing pregnancy and can be placed up to 120 hours after intercourse. However, the copper-containing IUD is contraindicated in patients with acute cervicitis or active pelvic infection due to the risk of ascending infection (ie, pelvic inflammatory disease) (Choice B). Therefore, in this patient with mucopurulent cervical discharge suggestive of acute cervicitis, the best option is a single dose of oral levonorgestrel (ie, Plan B) due to its high efficacy (85% preventive), availability, ease of use, and low side-effect profile. Levonorgestrel should be given within 72 hours of unprotected intercourse. mucopurulent cervical discharge (Choice A) A high-dose regimen of oral contraceptives is a second-line option for emergency contraception due to a higher risk of failure and often intolerable side effects (eg, persistent nausea). (Choice C) The etonogestrel subcutaneous implant is a long-acting, reversible contraceptive. This implant has a slow onset of action (up to 7 days after insertion) and is therefore not a form of emergency contraception. (Choice E) Methotrexate is indicated in the management of hemodynamically stable patients with ectopic pregnancies. Although methotrexate can cause fetal demise and spontaneous abortion, it is not currently indicated for pregnancy prevention or termination. Educational objective: Emergency contraception should be provided as soon as possible in patients who had unprotected intercourse. First-line options include the copper-containing intrauterine device and oral levonorgestrel pill. __________ References: Practice bulletin no. 152: emergency contraception. (http://www.ncbi.nlm.nih.gov/pubmed/26287787) Emergency contraception. (http://www.ncbi.nlm.nih.gov/pubmed/27261868)

Question 12

A 23-year-old woman comes to the office due to palpitations, increased frequency of bowel movements, and a 4.5-kg (10-lb) weight loss despite adequate food intake.  The patient's symptoms also include redness of the eyes associated with tearing, grittiness, and photophobia, as well as intermittent diplopia when reading or watching television.  Medical history is unremarkable; she has never been pregnant.  The patient is not sexually active.  She has smoked half a pack of cigarettes a day for the last 2 years.
Blood pressure is 138/66 mm Hg and pulse is 110/min and regular.  The patient appears anxious.  The thyroid gland shows diffuse symmetrical enlargement without tenderness.  A thyroid bruit is audible.  Ocular examination shows bilateral proptosis with conjunctival injection and periorbital edema.
Laboratory evaluation shows a serum TSH level of 0.005 μU/mL and a free thyroxine level of 4.1 ng/dL (normal: 0.9-2.4).  Thyroid scintigraphy shows 24-hour radioactive iodine uptake of 56% (normal: 10%-30%) with a diffuse pattern.
The patient is started on a beta blocker and oral prednisone.  Which of the following additional interventions should be initiated at this time?

Accepted Answer

11ec193a_97d3_085d_853d_dfd4cc62e90f_MD0002_00 This patient has hyperthyroidism associated with a diffuse goiter and increased radioiodine uptake consistent with Graves disease. She also has moderate Graves ophthalmopathy, with ocular irritation, photophobia, and diplopia. Initial management of patients with hyperthyroidism should include a beta blocker (eg, propranolol) to control adrenergic symptoms. Systemic glucocorticoids are indicated for those with moderate (oral) or severe/progressive (intravenous) ophthalmopathy. Smoking cessation is also advised as smoking is associated with increased progression of ophthalmopathy. In addition, this patient should be started on an antithyroid drug (ATD) to inhibit synthesis of thyroid hormone. ATDs can be used to achieve remission in patients with mild Graves disease, or to attain a euthyroid state in preparation for more definitive treatment in those with more significant disease (such as this patient). Methimazole is usually preferred due to the risk of hepatotoxicity with propylthiouracil, although propylthiouracil is recommended in the first trimester of pregnancy due to the teratogenic effects of methimazole (Choice B). (Choice C) Radioactive iodine (RAI) ablation can be considered for definitive therapy in patients with moderate to severe Graves disease, in whom an ATD alone is unlikely to achieve remission. However, RAI can worsen ophthalmopathy and should be avoided in patients with significant ocular symptoms. (Choice D) Selenium deficiency is associated with an increased risk of Graves ophthalmopathy. Supplementation appears to reduce symptoms in patients with mild ophthalmopathy, but the benefits are uncertain in regions where selenium deficiency is uncommon, including the United States. (Choice E) Thyroidectomy is the preferred definitive therapy for patients with large goiters, obstructive symptoms, or suspected thyroid cancer. It is also recommended for those with significant ophthalmopathy, in whom RAI may cause an exacerbation of symptoms. However, thyroidectomy is usually performed with the patient in a euthyroid state on an ATD. Educational objective: Antithyroid drugs (eg, methimazole) can induce remission in patients with mild Graves disease. They are also used to attain a euthyroid state in preparation for definitive treatment with radioactive iodine or thyroidectomy in patients with moderate to severe disease. Radioactive iodine can worsen Graves ophthalmopathy and should be avoided in patients with significant ocular symptoms. __________ References: Graves' ophthalmopathy: epidemiology and natural history. (http://www.ncbi.nlm.nih.gov/pubmed/24583420) An update on the medical treatment of Graves' hyperthyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/25185644) Radioiodine therapy versus antithyroid medications for Graves' disease. (http://www.ncbi.nlm.nih.gov/pubmed/26891370)

Question 13

A 66-year-old woman comes to the office to review the results of her recent DXA scan of the hips and spine.  She has a history of essential hypertension, osteoarthritis, and acid reflux disease.  Current medications include lisinopril, omeprazole, and acetaminophen as needed.  She has never smoked and has no history of fractures or falls.
Height is 165 cm (5 ft 5 in) and weight is 70 kg (154.3 lb).
Laboratory testing, including renal function, electrolytes, TSH, and parathyroid hormone level, is normal.
Results of the DXA scan are as follows:
 Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

11ec193a_97cd_d82f_853d_e1b80230a5bc_MD0002_00 This patient is at risk for osteoporosis based on age and female sex. In addition, she takes omeprazole, which can increase bone loss. Osteoporosis screening is recommended for women age >65 and younger women who have additional risk factors for osteoporosis. The World Health Organization and the International Society for Clinical Densitometry define osteopenia as a T score of −1.1 to −2.4 and osteoporosis as a T score <−2.5. In the lumbar spine, the average bone density at L1-L4 should be used rather than bone density at individual vertebrae. The final diagnostic interpretation is based on the lowest T score at the lumbar spine and either hip (total proximal femur or femoral neck). This patient has a lowest T score of −2.9 (at the left hip) and therefore meets diagnostic criteria for osteoporosis rather than osteopenia (Choice B). (Choice A) Fracture risk estimated with the FRAX risk assessment tool can be used to guide management in patients age >50 who have osteopenia and have not previously taken specific therapy for osteoporosis. This patient has osteoporosis, and treatment (eg, bisphosphonate therapy) is indicated even without calculation of a FRAX score. FRAX risk assessment tool (Choice D) Peripheral bone density (eg, calcaneus, forearm) is not recommended for routine use due to lack of standardization but can be considered in certain circumstances, such as morbid obesity (exceeding the weight limit of the DXA machine) or metal implants in the spine or hips (eg, joint replacements). In addition, forearm measurement is recommended in primary hyperparathyroidism, in which bone loss is more pronounced in cortical rather than cancellous bone. (Choice E) Z scores are used to compare an individual's bone density with others the same age and can identify abnormal bone loss that is disproportionate to that expected from aging. Z scores are useful for fracture risk estimation in young premenopausal women or in children but are less helpful in postmenopausal women. Educational objective: Osteopenia is defined as a T score of −1.1 to −2.4 and osteoporosis as a T score <−2.5. Diagnostic interpretation is based on the lowest T score at the lumbar spine (average bone density at L1-L4) and either hip. < __________ References: Screening, diagnosis and treatment of osteoporosis: a brief review. (http://www.ncbi.nlm.nih.gov/pubmed/25568654) What is the utility of distal forearm DXA in primary hyperparathyroidism? (http://www.ncbi.nlm.nih.gov/pubmed/22258698)

Question 14

A 55-year-old man comes to the office due to fatigue and inability to maintain satisfactory erections during intercourse. He has also noticed decreased early-morning erections and sexual desire. The patient has had no headaches, visual symptoms, polyuria, head injuries, or motor weakness. He has been trying to lose weight with diet and exercise. Medical history is notable for prediabetes, hypertension, and hypertriglyceridemia, and current medications include lisinopril, atorvastatin, and aspirin. The patient's father had type 2 diabetes mellitus and died of sudden cardiac arrest at age 74; his sister has hypothyroidism. He lives with his wife and 20-year-old son. Blood pressure is 142/74 mm Hg and pulse is 78/min. BMI is 38 kg/m². Body and facial hair distribution is normal. Visual fields are normal on confrontation. Testes are normal in size but have a soft consistency. The remainder of the physical examination is normal. Laboratory results are as follows: Which of the following is the best next step in evaluation of this patient's symptoms?

Accepted Answer

11ec193a_97cf_85e4_853d_f1325edb544c_MD0002_00 This patient has symptoms (ie, decreased libido, possible early testicular atrophy) that warrant testing for hypogonadism. His loss of early-morning (nonsexual) erections suggests an organic (rather than psychogenic) cause of erectile dysfunction. Hypogonadism is common in men with obesity and/or diabetes/prediabetes, likely due to dysfunction of the hypothalamic pituitary axis. Other specific features that should prompt evaluation for androgen deficiency include loss of body hair, gynecomastia, hot flashes, and an unexplained decrease in bone density. In contrast, nonspecific symptoms (eg, fatigue, weakness, weight changes) alone do not warrant testing in most cases. The initial step in evaluation of male hypogonadism is a morning serum total testosterone level. However, testosterone shows significant variability, and low levels should be confirmed on repeat testing. (Choice A) Although obesity and diabetes are associated with true hypogonadism, these conditions are also associated with decreased levels of sex hormone-binding globulin, leading to spuriously low total testosterone levels. If the initial total testosterone level is low, measurement of free testosterone levels should be considered to confirm true hypogonadism in patients with these conditions; however, testing is not recommended in the initial workup of hypogonadism because it requires specialized assays that can be expensive and inaccurate and are not always readily available. (Choices B and C) If testosterone is low, serum FSH and LH levels can distinguish primary (elevated LH and FSH) from secondary (low/normal FSH and LH) hypogonadism. MRI of the pituitary should be considered in patients with secondary hypogonadism and for those with severe hypogonadism (eg, testosterone <150 ng/mL), deficiencies of additional pituitary hormones (eg, TSH, growth hormone), hyperprolactinemia, or mass effect symptoms (eg, visual field defects). (Choice D) Nocturnal penile tumescence can be useful in differentiating psychogenic (normal) and organic (reduced tumescence) causes of erectile dysfunction. However, it is not commonly used in clinical practice, and the decreased morning erections in this patient suggest an organic cause. Educational objective: Clinical features that warrant evaluation for androgen deficiency include decreased libido, erectile dysfunction, testicular atrophy, loss of body hair, gynecomastia, hot flashes, and an unexplained decrease in bone density. Nonspecific symptoms (eg, fatigue, weakness, weight changes) alone do not warrant testing in most cases. The initial step is a morning serum testosterone level, and low levels should be confirmed on repeat testing. __________ References: Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/20525905)

Question 15

A 55-year-old-man comes to the office due to erectile dysfunction. He has normal libido but has been unable to maintain a satisfactory erection to have intercourse. The patient often wakes up in the morning with an erection. He has no history of testicular injury or peripheral vision loss. Medical history includes end-stage renal disease resulting from idiopathic focal segmental glomerulosclerosis. Peritoneal dialysis was started 6 months ago due to intractable fluid retention despite high-dose diuretic therapy, and he is being evaluated for possible renal transplant. The patient does not use tobacco, alcohol, or illicit drugs. Temperature is 37.1 C (98.7 F), blood pressure is 138/82 mm Hg, pulse is 76/min, and respirations are 12/min. BMI is 25 kg/m². Visual fields are normal on confrontation. Testes are normal in size and consistency, and cremasteric reflex is present. There is trace edema at the ankles and feet. Laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient's erectile dysfunction?

Accepted Answer

11ec193a_97ce_4d61_853d_45e8a0640c64_MD0002_00 Most men with end-stage renal disease (ESRD) experience sexual dysfunction. Manifestations can include low libido, erectile dysfunction, decreased frequency of intercourse, and infertility. Sexual dysfunction in ESRD is usually multifactorial. Common contributing factors include vascular/vasoactive impairment, peripheral and autonomic neuropathy, gonadal dysfunction, psychological stress, concurrent medications, and medical comorbidities. The initial evaluation of sexual dysfunction in patients with ESRD should include a clinical review for possible contributing factors (eg, medications, vascular disease) and limited laboratory testing (eg, serum testosterone, prolactin levels). Most patients with erectile dysfunction respond to phosphodiesterase inhibitors (eg, sildenafil). This patient's normal nonsexual morning erections suggest a possible psychogenic component, but this is unlikely to be the only factor in a patient with ESRD, and the effectiveness of psychotherapy for sexual dysfunction in men with ESRD is unknown. (Choice A) Impaired gonadal function in ESRD can lead to low serum testosterone levels, decreased libido, and erectile dysfunction. However, this patient has normal libido and a normal serum testosterone level; testosterone supplementation is unlikely to be beneficial. (Choice B) This patient has no clinical features (eg, visual field defects) to suggest a pituitary mass lesion. Men with ESRD often have elevated prolactin levels due to increased production and decreased clearance. The levels can be corrected with dopamine agonists (eg, bromocriptine), but this has not been shown to improve sexual function. (Choice C) Alprostadil (prostaglandin E1) can be administered intraurethrally or injected into the penile shaft and causes vasodilation of the cavernosal arteries. It may be used as second-line therapy in men who fail phosphodiesterase inhibitors but is associated with a risk of local bleeding in uremic men who often have platelet dysfunction. (Choice E) Sexual dysfunction in men with ESRD often improves following renal transplant and may also improve with correction of concurrent anemia and zinc deficiency. However, dialysis does not usually improve sexual function, regardless of modality. Educational objective: Most men with end-stage renal disease experience sexual dysfunction (eg, low libido, erectile dysfunction, decreased frequency of intercourse, infertility). Contributing factors include vascular impairment, peripheral and autonomic neuropathy, gonadal dysfunction, psychological stress, concurrent medications, and medical comorbidities. Most patients respond to phosphodiesterase inhibitors (eg, sildenafil). __________ References: Phosphodiesterase type 5 inhibitor treatment for erectile dysfunction in patients with end-stage renal disease receiving dialysis or after renal transplantation. (http://www.ncbi.nlm.nih.gov/pubmed/23346948)

Question 16

A 42-year-old man comes to the office after his blood pressure was found to be 146/92 mm Hg at a health fair. The patient has had no unusual headaches, blurry vision, polyuria, chest pain, or shortness of breath. He has no significant prior medical conditions and takes no medications. HIV testing 3 years ago was negative. The patient's father was diagnosed with colon cancer at age 65, and his brother underwent a thyroidectomy for differentiated papillary thyroid cancer at age 34. The patient has a current 15-pack-year smoking history and does not drink alcohol or use illicit drugs. Blood pressure is 140/90 mm Hg, and pulse is 68/min and regular. BMI is 27 kg/m². Repeat blood pressure measurement after 5 minutes is 140/92 mm Hg. Physical examination is unremarkable. Nonfasting laboratory results are as follows: Urine microalbumin/creatinine ratio, TSH, and ECG are normal. A fasting lipid profile has been ordered. Which of the following additional tests is recommended at this time?

Accepted Answer

11ec193a_97d2_6c1c_853d_b180982ed649_MD0002_00 The prevalence of type 2 diabetes mellitus is increased in patients with hypertension, at least in part due to shared risk factors (eg, obesity, sedentary lifestyle). Furthermore, hypertensive patients who also have diabetes are at elevated risk for cardiovascular complications (eg, myocardial infarction, stroke). For these reasons, screening for diabetes is recommended for patients with a new diagnosis of hypertension. Identifying comorbid diabetes is also important because it may influence the choice of antihypertensive therapy (eg, ACE inhibitor). Screening tests for diabetes include fasting blood glucose, hemoglobin A1c, and a 2-hour oral glucose tolerance test (used primarily in pregnant women). Nonfasting glucose levels can be helpful, especially when very high (≥200 mg/dL), but are less specific, and mild elevations (as in this patient) should be confirmed with a fasting glucose or hemoglobin A1c. Screening is also appropriate for patients who are overweight or obese and those who have a sedentary lifestyle, first-degree family history of diabetes, or history of gestational diabetes. (Choice B) Screening for lung cancer with an annual low-dose CT scan of the chest is indicated for patients age 50-80 who have a ≥20-pack-year smoking history and who currently smoke or quit within the last 15 years. In light of this patient's younger age and <20-pack-year history, screening is not recommended. (Choices C and D) Testing for primary hyperaldosteronism with a plasma aldosterone/renin activity ratio is appropriate for patients with resistant hypertension (ie, uncontrolled despite an appropriate multidrug regimen) or hypertension with significant hypokalemia. Screening for pheochromocytoma with plasma fractionated metanephrines is appropriate for patients with severe, labile, or resistant hypertension. These tests are not needed for routine evaluation of uncomplicated hypertension. (Choice E) Screening for thyroid malignancy with ultrasound is indicated for patients at high risk for thyroid cancer (eg, multiple endocrine neoplasia type 2, childhood neck irradiation). This patient's brother had papillary thyroid cancer, which is usually sporadic and does not warrant screening of family members. Educational objective: The prevalence of type 2 diabetes mellitus is increased in patients with hypertension, and patients with both hypertension and diabetes are at increased risk for cardiovascular complications. Patients with hypertension should be screened for diabetes with a fasting glucose level, hemoglobin A1c, or oral glucose tolerance test. __________ References: Diabetes mellitus: screening and diagnosis. (http://www.ncbi.nlm.nih.gov/pubmed/26926406)

Question 17

A 52-year-old woman comes to the office to follow up elevated blood pressure, which was 140/100 mm Hg during a routine preventive visit 4 weeks ago. The patient feels well and has experienced no recent weight changes, headaches, chest pain, palpitations, or polyuria. Medical history is notable only for gastroesophageal reflux disease managed with dietary modification, and she takes no medications. Screening colonoscopy at age 50 was normal. She drinks 1 or 2 glasses of wine most days and does not use tobacco or illicit drugs. The patient is an only child, and her parents have no unusual health history. Blood pressure is 138/100 mm Hg and pulse is 72/min. BMI is 27 kg/m². The patient appears mildly overweight but comfortable. Physical examination is otherwise unremarkable. Laboratory results are as follows: Urinalysis is normal. ECG shows normal sinus rhythm with no significant abnormalities. Which of the following additional studies is most appropriate for this patient?

Accepted Answer

11ec193a_97d4_dd21_853d_0b2e5a66cc43_MD0002_00 This patient has a new diagnosis of hypertension. The initial evaluation of hypertension is oriented toward the following objectives: Detecting end-organ damage that may require more aggressive managementAssessing other cardiovascular risk factorsScreening for common secondary causes of hypertension if indicated (eg, abrupt onset, onset at age <30, unexplained hypokalemia)Identifying concurrent conditions and metabolic abnormalities that could influence the choice of antihypertensive therapy Detecting end-organ damage that may require more aggressive management Detecting end-organ damage that may require more aggressive management Assessing other cardiovascular risk factors Assessing other cardiovascular risk factors Screening for common secondary causes of hypertension if indicated (eg, abrupt onset, onset at age <30, unexplained hypokalemia) Screening for common secondary causes of hypertension if indicated (eg, abrupt onset, onset at age <30, unexplained hypokalemia) Identifying concurrent conditions and metabolic abnormalities that could influence the choice of antihypertensive therapy Identifying concurrent conditions and metabolic abnormalities that could influence the choice of antihypertensive therapy Both hypothyroidism and hyperthyroidism can raise blood pressure: Hyperthyroidism causes increased systolic and pulse pressure, whereas hypothyroidism typically causes increased diastolic pressure with decreased pulse pressure; thyroid disease can also lead to lipid abnormalities. Untreated thyroid disease can impair the response to antihypertensive management, but treatment of the underlying thyroid condition can often normalize blood pressure without additional antihypertensive therapy. Therefore, according to American College of Cardiology/American Heart Association guidelines, patients with hypertension warrant screening for thyroid disease with a serum TSH as part of the initial laboratory evaluation (regardless of symptoms) and if they have clinical features of thyroid disease (eg, heat/cold intolerance, weight loss/gain, warm/cold skin). (Choice A) Renal ultrasonography is useful to evaluate hypertension in patients with diffuse atherosclerosis or evidence of renovascular hypertension (eg, atrophic kidney, recurrent flash pulmonary edema, abdominal bruit, onset of severe hypertension at age >55) but is not needed in patients with uncomplicated hypertension. (Choice B) This patient has a normal serum calcium level, making hyperparathyroidism less likely. Although hypertension has been associated with hyperparathyroidism (including normocalcemic hyperparathyroidism) in some studies, this is an inconsistent observation. (Choices C and D) Testing for primary hyperaldosteronism with a plasma aldosterone to plasma renin activity ratio is appropriate for patients with resistant hypertension (ie, uncontrolled despite an appropriate multidrug regimen) or hypertension with significant hypokalemia. Screening for pheochromocytoma with plasma fractionated metanephrines is appropriate for patients with severe, labile, or resistant hypertension. These tests are not needed for routine evaluation of uncomplicated hypertension. Educational objective: Both hyperthyroidism and hypothyroidism can raise blood pressure. Untreated thyroid disease can impair the response to antihypertensive management, but many patients experience normalization of blood pressure when the underlying thyroid disorder is treated. Patients with hypertension warrant screening for thyroid disease in the initial laboratory evaluation. __________ References: Thyroid and the heart. (http://www.ncbi.nlm.nih.gov/pubmed/24662620)

Question 18

A 42-year-old man comes to the office for further evaluation after a high blood pressure reading on an automated machine at a supermarket. He has no chronic medical problems and takes no medications. The patient has felt fatigued lately, which he attributes to stress at work. He also reports constipation and a 4.5-kg (10-lb) weight gain since he stopped exercising 9 months ago. The patient smoked cigarettes for a few years in college but has not smoked for the last 20 years. He does not use alcohol or illicit drugs. The patient lives with his girlfriend and has no children. Blood pressure is 145/95 mm Hg and pulse is 66/min. Repeat blood pressure after 10 minutes is 135/85 mm Hg. BMI is 31 kg/m². The patient appears mildly obese, but the remainder of the examination is normal. Fasting laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient's metabolic abnormalities?

Accepted Answer

11ec193a_97d1_f6ea_853d_95e937c3eed3_MD0002_00 This patient has mild hypertriglyceridemia and suboptimal levels of total cholesterol, LDL, and HDL. In addition, he has other features (ie, fatigue, weight gain, constipation) that suggest undiagnosed hypothyroidism. Hypothyroidism is a common cause of dyslipidemia and is associated with an increased risk for coronary events. Patients can also have hypertension, elevated hepatic transminases, and nonalcoholic fatty liver disease (due to defective hepatic lipoprotein clearance). Current guidelines recommend screening for thyroid disorders with serum TSH in all patients with newly diagnosed dyslipidemia, particularly if they have findings suggestive of hypothyroidism. In addition, if not previously checked, TSH should be measured prior to initiation of statin therapy, as untreated hypothyroidism increases the risk of statin-induced myopathy (Choice C). The dyslipidemia in hypothyroidism improves with levothyroxine therapy. (Choice A) Once this patient's hypothyroidism is corrected, any residual lipid abnormalities may be amenable to lifestyle changes (eg, exercise, weight loss). However, his lipids are likely to normalize once he achieves a euthyroid state. (Choice B) In addition to dyslipidemia, hypothyroidism can raise blood pressure due to increased systemic vascular resistance. However, the elevated blood pressure often improves with the treatment of hypothyroidism and may not require antihypertensive therapy. (Choice D) Apolipoprotein B100 is a structural component of LDL and functions as a ligand for the LDL receptor. Apolipoprotein B100 levels correlate with cardiovascular risk and can be used to assess residual risk in patients with dyslipidemia who have achieved optimal lipid levels. However, this test is rarely needed for clinical decision-making and is not necessary for this patient at this time. Educational objective: Hypothyroidism is a common cause of dyslipidemia. Patients with dyslipidemia should be screened for hypothyroidism with serum TSH. Dyslipidemia due to hypothyroidism improves with levothyroxine therapy. __________ References: Thyroid function testing in patients with newly diagnosed hyperlipidemia. (http://www.ncbi.nlm.nih.gov/pubmed/24217672) Secondary causes of dyslipidemia. (http://www.ncbi.nlm.nih.gov/pubmed/22658245)

Question 19

A 50-year-old woman comes to the office to follow up type 2 diabetes mellitus. She was diagnosed 5 years ago and is treated with metformin at the maximal tolerated dose. She has been unable to lose weight despite following a healthy diet and exercising at least 5 times a week. The patient has no chronic complications of diabetes but has had recurrent episodes of vaginal candidiasis in the last 2 years. She works as a commercial bus driver for a tourist company and does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. BMI is 27 kg/m². Physical examination is otherwise unremarkable. Serum creatinine is 1 mg/dL, fasting glucose is 156 mg/dL, and hemoglobin A1c is 7.9%. Six months ago her A1c was 7.2%. When added to metformin, which of the following medications is most appropriate for this patient?

Accepted Answer

11ec193a_97cc_2a7b_853d_d5d9902495d2_MD0002_00 This patient with elevated BMI has uncontrolled type 2 diabetes mellitus despite appropriate diet, exercise, and metformin therapy. The addition of a second drug is indicated, and the choice should take into account efficacy, risk of hypoglycemia, weight gain, and other adverse effects. A glucagon-like peptide-1 (GLP-1) receptor agonist (eg, exenatide, liraglutide, dulaglutide) is most appropriate for this patient as it is likely to bring her hemoglobin A1c down to the target range while inducing significant weight loss without increasing the risk of hypoglycemia. The major side effects of GLP-1 receptor agonists are nausea, vomiting, abdominal pain, and diarrhea; these gastrointestinal effects typically abate in the first few weeks of therapy. Contraindications to nearly all GLP-1 receptor agonists include personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 and history of pancreatitis. Exenatide is also contraindicated in severe renal insufficiency. (Choice A) Basal insulin is likely to optimize glycemic control. However, insulin therapy would be suboptimal in this patient as it is associated with weight gain and risk of hypoglycemia and could complicate her licensure requirements as a commercial motor vehicle driver (eg, may require exemption via the Federal Diabetes Exemption Program). (Choice B) Dipeptidyl peptidase-4 inhibitors (eg, sitagliptin) affect the same pathway as GLP-1 agonists and are weight neutral and very safe. However, they are only modestly efficacious, with an average decline in hemoglobin A1c of 0.5%. (Choice D) Sodium-glucose cotransporter-2 (SGLT-2) inhibitors (eg, canagliflozin) decrease blood glucose levels by increasing urinary excretion of glucose. SGLT-2 inhibitors increase the risk of vaginal candidiasis, particularly in women with a history of previous infections, making the group unattractive for this patient. (Choice E) Although sulfonylureas (eg, glimepiride) are inexpensive and very effective, like insulin they can cause weight gain and hypoglycemia. Educational objective: Glucagon-like peptide-1 receptor agonists are very effective antidiabetic agents with additional benefits of weight loss and low risk of hypoglycemia. __________ References: GLP-1 receptor agonists: a review of head-to-head clinical studies. (http://www.ncbi.nlm.nih.gov/pubmed/25678953)

Question 20

An 82-year-old woman comes to the office due to fatigue. For the last 6 months since her husband died, she has had low energy associated with decreased appetite. The patient has had no weight change, fevers, chills, or night sweats. She sleeps 5-6 hours a night. Medical history is notable for hypertension, depression, and osteoporosis, for which she takes hydrochlorothiazide, sertraline, and alendronate, respectively. She does not smoke, and she drinks alcohol only once or twice a year on social occasions. Temperature is 36.8 C (98.2 F), blood pressure is 128/82 mm Hg, and pulse is 68/min. BMI is 24 kg/m². On examination, the patient is awake, alert, and cooperative. Neck examination is normal with no goiter. Cardiopulmonary examination is normal. Neurologic examination shows normal cranial nerves and motor strength. Ankle reflexes are absent. Laboratory studies show normal glucose, electrolytes, and blood counts. TSH is 7.2 µU/mL, and free T4 is 1.1 ng/dL (normal: 0.9-1.7 ng/dL). Which of the following is the most appropriate next step in management of this patient's symptoms?

Accepted Answer

11ec193a_97d5_c782_853d_09b642abb9d2_MD0002_00 This patient has subclinical hypothyroidism, defined as a serum TSH above the upper limit of normal with serum free T4 in the normal range. Subclinical hypothyroidism is often associated with symptoms that suggest a hypothyroid state, but in most cases symptoms are vague and highly nonspecific (eg, fatigue, constipation). Treatment of subclinical hypothyroidism is recommended for all patients with TSH ≥10 or those age <70 with convincing hypothyroid symptoms or features associated with progression to overt hypothyroidism (eg, enlarging goiter, elevated anti-thyroid peroxidase antibody titer). In contrast, older (age ≥70) patients with subclinical hypothyroidism warrant more conservative management. Levothyroxine replacement in this population confers less benefit than in younger patients and carries an increased risk for adverse events (eg, atrial fibrillation). In addition, some experts believe that the true normal TSH range in older patients may be higher than in younger patients, and levels as high as 8 µU/mL may represent physiologic euthyroidism in patients age >80. In lieu of treatment, older patients should be monitored with periodic retesting (eg, in 1-3 months and every 6-12 months thereafter), and treatment should be considered for those who progress to overt hypothyroidism (Choice A). (Choice C) T3 is produced primarily in peripheral tissues; serum levels correlate poorly with thyroid status. Free T3 levels have some utility in evaluating hyperthyroidism but are not recommended in hypothyroidism. (Choice D) Thyroid ultrasound is primarily used for evaluation of patients with a palpable goiter or thyroid nodules. It is not indicated in routine evaluation of hypothyroid conditions. (Choice E) Thyrotropin (TSH) receptor antibodies are involved in the pathogenesis of Graves disease, the most common cause of hyperthyroidism. Serum titers have little utility in evaluation of hypothyroidism. Educational objective: Subclinical hypothyroidism is defined as a serum TSH above the upper limit of normal with a serum free T4 level in the normal range. Patients age ≥70 with subclinical hypothyroidism should generally not be treated but should have periodic monitoring for progression to overt hypothyroidism. __________ References: Thyroid hormone therapy for older adults with subclinical hypothyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/28402245)

Exam 3: Office/Health Center