Question 1

A 56-year-old woman was found to have a TSH level of 0.2 μU/mL on routine laboratory testing.  She has had no symptoms suggestive of thyrotoxicosis.  She reports good energy level and no change in body weight.  The patient has mild hypertension, for which she is on hydrochlorothiazide.  Family history is negative for any thyroid disorder.  She does not use tobacco or alcohol.  She does not have allergies to any medications.  The patient had her menopause about 3 years ago.  She has never received hormone replacement therapy.  She takes adequate amounts of calcium and vitamin D supplementation.  Bone mineral density using dual photon absorptiometry was within normal range about 6 months ago.  Examination is unremarkable, including examination of the thyroid gland.  Free T4 levels and free T3 are well within normal limits.  What is the next best step in this patient's care?

Accepted Answer

Explanation: The patient has subclinical thyrotoxicosis, which is defined as suppressed TSH levels along with normal thyroid hormone levels. The most common causes of subclinical thyrotoxicosis are treatment with levothyroxine, nodular thyroid disease, Graves' disease, and thyroiditis. Subclinical thyrotoxicosis induced by levothyroxine is simply treated by reducing the dose. In some cases, the etiology cannot be determined, and TSH becomes normal if repeated in a few weeks. Patients who have mildly suppressed TSH, no symptoms, normal heart rhythm, and normal bone density are not intensively investigated because no treatment is necessary, and there is a high chance of normalization of TSH levels. Repeating TSH after 6-8 weeks is generally performed. (Choices A, B, C, and E)This patient did not have any indication for aggressive intervention. In symptomatic patients (eg, persistent fatigue), an antithyroid drug in a small dose (eg, methimazole 5-10 mg/day) is generally started after performing a radioactive iodine uptake and scan. If the symptoms improve with antithyroid drugs, radioactive iodine ablation is usually performed. Patients with multinodular goiter have a 5%-10%/year chance of becoming overtly thyrotoxic; therefore, treatment in such patients is warranted. Patients with atrial fibrillation and low bone densities also require treatment. Educational objective: Patients who have mildly suppressed TSH but normal T4 and T3, no symptoms, normal heart rhythm, and normal bone density are not intensively investigated because no treatment is necessary and there is a high chance of normalization of TSH levels.

Question 2

A 66-year-old man is found to have bilateral breast enlargement during a routine office visit. The patient reports no breast pain/discomfort, headaches, or vision abnormalities but has had decreased libido and "low energy" for the past several months. Medical problems include hypertension, hyperlipidemia, and osteoarthritis. The patient takes chlorthalidone, simvastatin, and acetaminophen as needed. He does not use over-the-counter or herbal supplements. The patient drinks 1 or 2 alcoholic beverages during social events and does not use tobacco or illicit drugs. He is married and has several adult children. Family history is notable for breast cancer in a maternal aunt. Vital signs are within normal limits. BMI is 32 kg/m². Examination shows normal body hair distribution and no skin rash. Breast examination reveals 2-cm, round, and firm tissue behind the areolas bilaterally with no overlying skin changes or nipple discharge. There are no enlarged lymph nodes. External genitalia are normal in size and appearance, and no testicular masses are present. The remainder of the physical examination is normal. Laboratory results are as follows: Serum chemistry panel and liver aminotransferases are within normal limits, and serum testosterone level is unchanged on repeat testing. Which of the following is the most likely explanation for this patient's breast abnormality?

Accepted Answer

Explanation: This patient has new-onset, bilateral gynecomastia with otherwise normal examination findings. Gynecomastia is benign glandular proliferation of the male breast tissue and is common in neonates, adolescent boys, and older (especially obese) men. Physiologic gynecomastia in older men is related to an imbalance of estrogen to testosterone due to decreased testicular testosterone production and increased conversion of testosterone to estrogen by aromatase in peripheral (mainly adipose) tissue. Breast examination in physiologic gynecomastia typically shows symmetric, firm enlargement of the breast tissue concentrically under the nipple areolar complex. Initial evaluation should include serum chemistries to exclude hepatic and renal disease. Hormonal studies typically include TSH, serum testosterone, and measurement of estrogen, prolactin, LH, and hCG. Patients with benign examination and biochemical findings can be followed, and many have spontaneous resolution. (Choice A) Breast cancer is an uncommon cause of gynecomastia. Findings to suggest breast carcinoma include unilateral, eccentric enlargement of breast tissue, hard or fixed masses, and associated lymphadenopathy or skin changes. (Choice B) Cirrhosis is a common cause of gynecomastia but is typically associated with other signs of hyperestrogenism, such as spider angiomata, loss of sexual hair, testicular atrophy, and palmar erythema. This patient's light alcohol intake and normal hepatic markers make significant cirrhosis unlikely. (Choice C) Medications are a common, potentially reversible cause of gynecomastia. However, this patient takes no medications associated with gynecomastia (eg, spironolactone, cimetidine, 5-alpha-reductase inhibitors, ketoconazole). (Choice E) Pseudogynecomastia refers to excess fat deposition in the breast rather than glandular enlargement. Pseudogynecomastia typically causes diffuse breast enlargement rather than the firm, circumscribed abnormality seen in this patient. Educational objective: Physiologic gynecomastia is benign glandular proliferation of male breast tissue due to an imbalance between levels of estrogen and androgens. It is common in older (especially obese) men due to decreased testicular testosterone production and increased conversion of testosterone to estrogen in peripheral tissue. References: Gynecomastia: pathophysiology, evaluation, and management. (http://www.ncbi.nlm.nih.gov/pubmed/19880691)

Question 3

An 83-year-old woman with mild cognitive impairment comes to the office due to a feeling of "not being myself."  The patient has lived in an assisted living facility since her husband died 2 years ago.  She is accompanied by a caregiver, who notes that the patient has developed progressive changes in behavior and personality over the last several months.  The patient has often refused meals and snacks and has had decreased participation in group activities that she previously enjoyed.  She also gets agitated very easily and often "wants to be left alone."  Medical history is notable for hypertension, heart failure with preserved ejection fraction, and osteoporosis.  The patient was also diagnosed with atrial fibrillation 6 months ago, and apixaban and escalating doses of metoprolol succinate were prescribed.  She has never used tobacco, alcohol, or illicit drugs.  Temperature is 37.4 C (99.3 F), blood pressure is 150/60 mm Hg, pulse is 92/min, and respirations are 22/min.  Oxygen saturation is 97% on room air.  Weight is 68.7 kg (151.5 lb); a month ago, it was 72.3 kg (159.4 lb).  Ocular examination is normal.  There is no nuchal rigidity or thyroid enlargement.  The heart has an irregularly irregular rhythm, and the chest is clear to auscultation.  No focal neurologic deficits are present and the patient's gait appears stable.  Laboratory tests show normal complete blood count, serum chemistry panel, and urinalysis.  ECG shows atrial fibrillation with nonspecific T-wave abnormalities.  Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bec4_0373_8f63_897fe3171436_MD0005_00 Hyperthyroidism in older patients often presents with atypical manifestations. In contrast to younger patients, older individuals may not have classic hyperadrenergic findings (eg, palpitations, tachycardia). Older patients are also more likely to have lethargy, apathy, decreased appetite, and weight loss (often termed "apathetic hyperthyroidism") or have muscle weakness (myopathy). In these patients, atrial fibrillation and heart failure can be readily triggered by thyrotoxicosis, but tachycardia may be absent due to concurrent medications (eg, beta blockers) or underlying cardiac conduction system disease. Approximately half of older patients with hyperthyroidism do not have a palpable goiter. Common causes of thyrotoxicosis in older patients include excess dosing of levothyroxine, nodular thyroid disease, and Graves disease (the proportion due to nodular thyroid disease increases with age). This patient has had a subacute change in neurocognitive function associated with weight loss, a mild temperature elevation, widened pulse pressure (likely due to hyperthyroidism-induced increase in cardiac output with concomitant decrease in systemic vascular resistance), and new-onset atrial fibrillation requiring escalating beta-blocker doses. Her thyroid function should be assessed, starting with a serum TSH level. (Choice A) This patient's resting heart rate remains in the high-normal range, despite escalating doses of metoprolol, and may be a manifestation of hyperthyroidism. Decreasing the dose of metoprolol may unmask the thyrotoxicosis and lead to an unstable tachycardia. (Choice B) Indications for neuroimaging (eg, CT scan or MRI of the brain) include acute or rapidly progressive confusion, impaired arousal, possible history of trauma, and focal neurologic findings. Imaging would also be considered if no correctable cause is identified on initial assessment. However, more basic evaluations (eg, thyroid function tests) should be done first. (Choice D) Cholinesterase inhibitors (eg, donepezil, rivastigmine) are indicated for mild to moderate dementia. This patient's baseline mild cognitive impairment does not warrant cholinesterase inhibitor therapy, and pharmacologic treatment is not indicated until correctable causes of her decline have been ruled out. (Choice E) Depression in the elderly commonly presents with apathetic symptoms. However, thyroid dysfunction should be ruled out before treatment for depression is started. In addition, depression would not explain atrial fibrillation requiring escalating doses of a beta blocker. Educational objective: Thyrotoxicosis in older patients often presents with atypical symptoms, including lethargy, apathy, weight loss, and decreased appetite without characteristic hyperadrenergic features. References: Older subjects with hyperthyroidism present with a paucity of symptoms and signs: a large cross-sectional study. (http://www.ncbi.nlm.nih.gov/pubmed/20392869)

Question 4

A 67-year-old man comes for follow-up of coronary artery disease. He is currently feeling well. Three months ago, he was hospitalized for chest pain; coronary angiography revealed 85% narrowing in the mid right coronary artery, and a drug-eluting stent was placed. In addition, TSH was noted to be low. The patient now walks 2-3 miles a day without angina, dyspnea, or lower extremity claudication. He states, "I am very happy that I lost 5 lb since my hospitalization. I also gave up smoking and drinking. I feel like I got my life back." Current medications include aspirin, clopidogrel, metoprolol, lisinopril, and atorvastatin. The patient's father died from a heart attack at age 56, and his mother has osteoporosis and hypertension. Blood pressure is 134/76 mm Hg and pulse is 65/min. BMI is 28 kg/m². Physical examination, including examination of the thyroid gland, is normal. Repeat thyroid function results are as follows: Radioactive iodine uptake is increased, with a homogeneous distribution on thyroid scan. Which of the following is the most appropriate management for this patient?

Accepted Answer

Explanation: 11ec2b69_bec9_0c8e_8f63_21a0540033eb_MD0005_00 Subclinical hyperthyroidism is defined as low TSH with normal thyroid hormone concentrations. Transient fluctuations in thyroid markers can be seen (particularly with acute illness), but patients who have persistently suppressed TSH levels warrant further evaluation. This patient has a diffusely increased radioiodine uptake consistent with Graves disease, with worsening of thyroid function test results possibly due to iodinated dye administration during his recent cardiac catheterization. Other common causes of subclinical hyperthyroidism include exogenous thyroid hormone, nodular thyroid disease (thyroid adenoma or toxic multinodular goiter), and inflammatory thyroiditis (eg, silent thyroiditis, subacute [de Quervain] thyroiditis). Severe TSH suppression (<0.1 µU/mL) is associated with a higher risk for progression to overt hyperthyroidism and warrants treatment. Patients with mildly suppressed TSH levels (0.1-0.5 µU/mL) often experience spontaneous remission and can usually be monitored with periodic thyroid function tests. However, those with increased risk for complications due to age (>65) or comorbid conditions (eg, heart disease, osteoporosis) warrant consideration for treatment with antithyroid medication or radioactive iodine. In light of this patient's TSH <0.1 μU/mL, age >65, and comorbid coronary artery disease, treatment should be offered at this time (Choice D). (Choice A) Beta blockers (eg, metoprolol) are used in thyrotoxicosis to control hyperadrenergic symptoms (eg, palpitations, tachycardia). This patient's heart rate is at goal (<70/min) and he is asymptomatic; no increase in dosage is necessary. (Choice C) The diagnosis of Graves disease has been established in this patient by a diffusely increased thyroidal uptake of radioactive iodine. The presence of thyrotropin receptor antibodies is also associated with Graves disease but would not provide any additional information. (Choice E) Ultrasonography is useful for evaluating thyroid nodules but is not required in this patient, who has no palpable nodules and diffuse radioiodine uptake. Educational objective: Subclinical thyrotoxicosis is defined as low TSH with normal thyroid hormone concentrations. Treatment with antithyroid medication or radioactive iodine is warranted for patients who have TSH levels persistently <0.1 µU/mL or who are at increased risk due to age (>65) or comorbid conditions (eg, heart disease, osteoporosis). References: 2016 American Thyroid Association guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis. (http://www.ncbi.nlm.nih.gov/pubmed/27521067) Subclinical hyperthyroidism and cardiovascular risk: recommendations for treatment. (http://www.ncbi.nlm.nih.gov/pubmed/23563523)

Question 5

A 25-year-old man comes to the office with a 2-month history of fatigue, palpitations, sweating, and heat intolerance.  The symptoms are becoming more distressing and are keeping the patient awake at night.  The patient has no diplopia, eye pain or redness, decreased vision, neck pain, or proximal muscle weakness.  Medical history is unremarkable, and he currently takes no medications.  He smoked for approximately a year during college but quit after graduation.  The patient drinks alcohol socially but does not use recreational drugs.  Family history is positive for hypothyroidism in his mother.  Temperature is 36.7 C (98 F), blood pressure is 130/70 mm Hg, pulse is 115/min (regular), and respirations are 18/min.  Examination shows an anxious, thin man in no acute distress.  There is mild lid lag but no conjunctival erythema or proptosis.  Extraocular movements and pupillary reflexes are intact.  Mild diffuse nontender enlargement of the thyroid gland is noted.  The skin is warm and moist.  Cardiac examination is unremarkable except for tachycardia.  Neurologic examination shows a fine hand tremor and brisk symmetrical reflexes but is otherwise unremarkable.  Laboratory tests show normal complete blood count, basic metabolic profile, and urinalysis.  Thyroid function test results are as follows:  Radioactive iodine uptake at 24 hours is 36% (normal: 8%-25%), and scan shows a diffuse uptake pattern.  Serum thyroid-stimulating immunoglobulin level is mildly elevated. Treatment options are explained to the patient.  Six weeks later, he returns to the office and says that his symptoms have resolved.  Blood pressure is 120/80 mm Hg and pulse is 82/min.  Eye examination reveals no lid lag.  The thyroid examination is unchanged, and the rest of the examination is unremarkable.  Which of the following tests is most likely to be helpful in this patient?

Accepted Answer

Explanation: Laboratory evaluation to assess thyroid function is typically performed 4-6 weeks after initiation of antithyroid drug (ATD) treatment and then every 2-3 months. TSH may remain suppressed for several months after initiation of therapy and does not accurately reflect thyroid functional status (Choice E). For this reason, total T3 and free T4 levels should be used to assess efficacy of ATD therapy, especially early in the treatment course. This patient has symptomatically improved; if his total T3 and free T4 levels are normalized he can proceed to definitive therapy. (Choices A and B) The major life-threatening side effects of ATDs are agranulocytosis and hepatotoxicity. Agranulocytosis usually occurs within 90 days of initiation and presents with fever, chills, or sore throat. If patients on ATDs develop these symptoms, a white blood cell count with differential should be obtained; if agranulocytosis is confirmed, the ATD should be stopped immediately. Blood counts are often ordered at baseline but do not need to be repeated in the absence of symptoms. Hepatotoxicity is a potential adverse effect of propylthiouracil but is rare with methimazole. As with blood counts, hepatic markers are typically ordered at baseline but do not need to be repeated in the absence of symptoms (eg, pruritus, jaundice, loss of appetite). (Choice C) Autoantibodies to the TSH receptor may assist in the initial diagnosis of Graves disease. They are also used to predict relapse in patients who have been treated with an ATD; persistent titers correlate with an increased risk of relapse. However, TSH receptor antibodies do not reflect thyroid functional status or response to treatment. Educational objective: Serum total T3 and free T4 levels are used to assess thyroid function during treatment with antithyroid drugs. TSH may remain suppressed for several months following initiation of therapy and does not reliably reflect thyroid functional status. References: Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. (http://www.ncbi.nlm.nih.gov/pubmed/21700562)

Question 6

A 68-year-old man is brought to the emergency department by his daughter due to confusion and lethargy.  The patient's daughter reports that he lives alone and has type 2 diabetes mellitus and hypertension.  He takes aspirin, enalapril, and glipizide.  He is afebrile.  Blood pressure is 99/59 mm Hg, pulse is 132/min, and respirations are 22/min.  The patient appears drowsy and is barely communicative.  Examination shows dry mucous membranes, absent jugular venous distention, clear lung fields, and normal heart sounds.  The abdomen is soft, nontender, and nondistended.  Neurologic examination shows disorientation to time and place.  The patient moves all extremities and examination shows no meningeal signs.  Laboratory results are as follows:  An ECG shows atrial fibrillation with a rapid ventricular response.  Nonspecific T wave changes are present.  Which of the following is the best initial approach to managing this patient?

Accepted Answer

Explanation: This patient's clinical presentation and markedly elevated glucose are consistent with a hyperosmolar hyperglycemic state (HHS). Both HHS and diabetic ketoacidosis (DKA) occur in patients with poorly controlled diabetes. Patients with type 2 diabetes mellitus tend to develop HHS as opposed to DKA, which is ruled out in this patient by negative serum ketones. In patients with HHS, the serum bicarbonate is generally near the lower limits of normal (as seen in this patient); in contrast, those with DKA frequently have an anion gap acidosis (due to ketoacid production). In HHS, dehydration (evidenced by this patient's dry mucous membranes and tachycardia) occurs from an osmotic diuresis caused by hyperglycemia. In addition, this patient likely has a mild acute renal failure, although comparison with a baseline creatinine is necessary. In HHS, neurologic symptoms ensue because of markedly increased serum osmolality. Sodium levels can be decreased or increased in patients with HHS; this patient's hypernatremia is likely exacerbating his altered mental status. Patients with HHS are frequently hyperkalemic due to a relative insulin insufficiency and hyperosmolality; this is in spite of an overall body potassium deficit caused by increased urinary excretion. The first step in the management of HHS is aggressive fluid resuscitation (typically with isotonic saline), as these patients frequently have had a fluid loss of 8-10 liters. (Choice A) Aggressive reduction of serum potassium level should be avoided in patients with HHS who are hyperkalemic. These patients have an overall potassium deficiency that would become unmasked with fluids and insulin. Potassium supplementation is frequently necessary when the serum level falls below 5.3 mEq/L. (Choice B) Rapid lowering of blood glucose with insulin can be harmful since it creates an osmotic gradient between the central nervous system and intravascular space. Instead the focus should be on vigorous fluid resuscitation. Intravenous insulin should be started after the patient has been partially resuscitated (2-3 liters). (Choice C) This patient's atrial fibrillation is likely secondary to stress from a HHS. Treatment with rate control agents such as beta blockers or calcium channel blockers would be needed eventually, but aggressive fluid resuscitation should be the first priority. This patient's somewhat low blood pressure makes it a challenge to use these medications. Volume resuscitation will improve both the hypotension and the tachycardia. (Choice D) In atrial fibrillation rate control is as effective as rhythm control. This patient's rhythm will likely revert back to sinus rhythm once the stress of his HHS has been resolved; therefore rhythm control medications are unnecessary at this time. Educational objective: Aggressive volume resuscitation is necessary in patients with a hyperosmolar hyperglycemic state (HHS), since they are generally severely volume depleted. Intravenous insulin should be started after the patient has been partially resuscitated. Aggressive management of hyperkalemia should be avoided in these patients since these patients generally have a total body potassium deficit. References: Physiopathology and management of hyperosmolar hyperglycemic nonketotic dehydration. (http://www.ncbi.nlm.nih.gov/pubmed/6801794) Hyperosmolar hyperglycemic state. (http://www.ncbi.nlm.nih.gov/pubmed/15887451)

Question 7

A 34-year-old woman comes to the physician after several months of amenorrhea. Several home pregnancy tests have been negative. Her past medical history is insignificant. She is married with 2 children and has no plans to have more. Her body mass index is 23 kg/m². Physical examination is unremarkable. Serum prolactin level is 500 ng/mL (normal 5-20 ng/mL). Magnetic resonance imaging of the head shows a 5-mm pituitary mass. This patient is at high risk of developing which of the following if left untreated?

Accepted Answer

Explanation: 11ec2b69_bec2_2eb1_8f63_099eed493b97_MD0005_00 This patient has a symptomatic prolactinoma with secondary amenorrhea and a very high prolactin level. Prolactinomas are a relatively common cause of amenorrhea, infertility, and galactorrhea in women. Elevated prolactin levels suppress gonadotropin-releasing hormone, luteinizing hormone, and estradiol, leading to symptoms of hypogonadism including hot flashes, vaginal dryness, and potentially osteoporosis if left untreated. Male patients can develop symptoms of hypogonadism and gynecomastia. Large adenomas may also cause headaches and compression of the optic chiasm, leading to visual field defects (bitemporal hemianopsia). The diagnosis of prolactinoma is strongly suggested by a prolactin level >200 ng/mL (normal 5-20 ng/mL). Mild elevations (20-200 ng/mL) may also be due to a prolactinoma, but other causes such as medications (eg, certain antipsychotics), nipple stimulation, pregnancy, hypothyroidism, and stress should also be considered. If prolactinoma is suspected, magnetic resonance imaging of the pituitary can confirm the diagnosis. In most cases, hyperprolactinemia will respond to treatment with dopamine agonists (eg, cabergoline, bromocriptine), which decrease both the size and prolactin secretion of the adenoma. Surgical intervention can be considered in patients who fail to improve with dopamine agonist therapy, especially if they have significant neurologic symptoms. (Choice A) Prolactin receptors have been identified in coronary artery plaques, suggesting that prolactin may have some effect on the behavior of coronary atherosclerosis. However, studies have not found an association between prolactinoma and incidence of coronary disease. (Choice C) Dopamine agonists, which were initially developed for treatment of Parkinson's disease, suppress production of prolactin and are first-line treatment for prolactinomas. Otherwise, there is no association between prolactinomas and Parkinson's disease. (Choice D) Large pituitary adenomas may induce a mass effect on surrounding structures in the brain, leading to neurologic symptoms. Primary adenocarcinoma of the pituitary, however, is extremely rare. (Choice E) Polycystic ovarian syndrome (PCOS) is a common cause of infertility in women. There are a few case reports of prolactinoma associated with PCOS, and anecdotal evidence suggests it may be causative. However, PCOS is not a common manifestation of prolactinoma. Educational objective: Prolactinoma is a common cause of amenorrhea and infertility in women. Other endocrine effects include galactorrhea in women, gynecomastia in men, and symptoms of hypogonadism in both sexes. Long-term suppression of sex hormone production by prolactinoma in women can lead to osteoporosis. The primary treatment of prolactinoma is dopamine agonists such as cabergoline, which inhibit prolactin secretion and cause regression of tumor size. References: Diagnosis and treatment of hyperprolactinemia: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/21296991) 2012 update in the treatment of prolactinomas. (http://www.ncbi.nlm.nih.gov/pubmed/22503806)

Question 8

A 47-year-old man comes to the office with his wife due to a gradually decreasing sex drive and difficulty sustaining an erection during sexual intercourse over the past 1-2 years.  They have had satisfying sexual interactions in the past and have 2 teenage children.  On questioning, the patient is unable to recall any spontaneous nocturnal erections of late.  Medical history is otherwise unremarkable and he takes no medications.  He does not use tobacco or alcohol.  Family history is significant for diabetes mellitus in his father and uncle.  Temperature is 37 C (98.6 F), blood pressure is 126/84 mm Hg, pulse is 74/min, and respirations are 14/min.  The patient has a dark complexion with sparse body hair.  The thyroid is normal to palpation.  Lung auscultation and heart sounds are normal.  The abdomen is nondistended, soft, and nontender, with the liver edge palpable 1 cm below the right costal margin.  External genitalia appear normal, with a mild decrease in testicular volume.  Visual fields are full to confrontation.  Laboratory results are as follows:  Which of the following is the best management strategy for this patient?

Accepted Answer

Explanation: 11ec2b69_bebe_370a_8f63_51eb653af5ae_MD0005_00 This patient has erectile dysfunction, testicular atrophy, and a low serum testosterone level. His gonadotropin levels are low, suggesting a pituitary cause (secondary hypogonadism). Common causes of acquired secondary hypogonadism include use of anabolic steroids, chronic glucocorticoid or opioid use, hyperprolactinemia, chronic kidney or liver disease, diabetes, and pituitary tumors. In addition, he has elevated hepatic transaminases with hepatomegaly, hyperpigmentation, and a family history of diabetes. These features are concerning for hereditary hemochromatosis (HH), an autosomal recessive disorder characterized by iron deposition in a variety of tissues, leading to multisystem organ damage. Clinical manifestations of HH usually appear in the fourth to sixth decade, with women presenting later due to menstrual iron loss. The initial evaluation includes serum iron studies, which show increased levels of iron, ferritin, and transferrin saturation. The diagnosis is confirmed with genetic testing for hemochromatosis-associated mutations (eg, HFE). The preferred means of treating HH is therapeutic phlebotomy, with removal of approximately 1 unit of blood each week until iron stores normalize. (Choice A) Dietary modification in HH has little impact, as patients have an excess absorption of iron of only 0.5-1 mg/day compared with a total body iron content of 20,000 mg or more. Therapeutic phlebotomy removes approximately 250 mg each week and is a much more effective means of depleting iron stores. (Choice B) Liver transplantation is indicated for patients with HH who develop advanced liver disease with cirrhosis. However, it is not a first-line treatment and is unlikely to be needed in this patient. (Choice C) Penicillamine is used to increase the excretion of copper (not iron) and is used in the treatment of Wilson disease. Wilson disease also causes chronic liver disease but is much rarer than HH, presents at an earlier age, and is associated with significant neurologic symptoms (eg, movement disorders). (Choice D) Glucocorticoids are not indicated for the treatment of HH and could worsen this patient's hyperglycemia and hypogonadism. Educational objective: Hereditary hemochromatosis can cause secondary hypogonadism. It is associated with increased serum levels of iron, ferritin, and transferrin saturation. The diagnosis is confirmed with genetic testing for HFE mutations. The preferred treatment is therapeutic phlebotomy. References: Hereditary hemochromatosis. (http://www.ncbi.nlm.nih.gov/pubmed/23418762)

Question 9

A 29-year-old woman, gravida 1 para 0, at 26 weeks gestation comes to the office for a routine prenatal visit. She reports no contractions, vaginal bleeding, or leakage of fluid. There is good fetal movement. The patient has a history of polycystic ovarian syndrome. This pregnancy was conceived through ovulation induction but has otherwise been uncomplicated. She has no other chronic medical conditions or previous surgeries. The patient walks for 30-45 minutes 5 days a week. She takes prenatal vitamins and folate supplementation daily. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/80 mm Hg and pulse is 89/min. BMI is 27 kg/m². Fetal heart tones are 150/min. Fundal height is 28 cm. Third-trimester laboratory results are as follows: The appropriate evaluation is completed and the patient is diagnosed with gestational diabetes mellitus. She is started on a diabetic diet and continues to exercise regularly, with an hour of brisk walking on most days. The patient returns 3 weeks later for a routine prenatal visit and for evaluation of her glycemic control. She reports compliance with her diet and checks her fasting and post-prandial blood glucose values daily. Blood pressure is 136/70 mm Hg and pulse is 80/min. Fetal heart tones are 140/min. During the third week of the patient's regimen, fasting blood glucose values are 100-110 mg/dL, and 2-hour post-prandial glucose values are 122-158 mg/dL. Which of the following is the most accurate?

Accepted Answer

Explanation: 11ec2b69_bebc_1426_8f63_6fcc4cd3f1d0_MD0005_00 Although gestational diabetes mellitus (GDM) is associated with an increased risk for obstetrical complications (eg, preeclampsia) and neonatal complications (eg, macrosomia, shoulder dystocia, hypoglycemia), adequate glucose control minimizes these risks. Poor maternal glycemic control leads to fetal hyperglycemia and hyperinsulinemia, resulting in macrosomia. In addition, severe maternal hyperglycemia can cause chronic uteroplacental insufficiency and fetal growth restriction. GDM is also a risk factor for long-term complications, including type 2 DM, obesity, and cardiovascular disease in offspring. Patients with GDM monitor fasting and either 1- or 2-hour postprandial blood glucose levels. Target glucose levels are: Fasting <95 mg/dL 1-hour postprandial <140 mg/dL or 2-hour postprandial <120 mg/dL This patient's blood glucose levels are higher than these targets despite compliance with dietary modifications (Choice A). Therefore, anti-hyperglycemic medication is indicated. Insulin, metformin, and glyburide are all acceptable agents for control of gestational diabetes when dietary modifications do not achieve adequate glycemic control (Choice E). Although there is some transplacental passage of insulin, it is not teratogenic. Metformin can cross the placenta, and the transplacental passage of glyburide is not well established; however, both medications appear to be safe in pregnancy. (Choice B) Glipizide is not typically used in the management of GDM. Glyburide, another sulfonylurea, is more commonly used for management of GDM but is associated with a higher risk of neonatal hypoglycemia than insulin. (Choice C) Diet, maintaining an appropriate weight, regular exercise, and breastfeeding can minimize the risk of developing type 2 diabetes mellitus. Type 1 DM is an autoimmune disease and insulin use does not reduce the risk of its development. Educational objective: Inadequate control of gestational diabetes mellitus increases the risk for fetal macrosomia and shoulder dystocia. If adequate glucose control cannot be achieved by diet and exercise, anti-hyperglycemic agents are initiated. References: Standards of medical care in diabetes--2014. (http://www.ncbi.nlm.nih.gov/pubmed/24357209) Benefits and risks of oral diabetes agents compared with insulin in women with gestational diabetes: a systematic review. (http://www.ncbi.nlm.nih.gov/pubmed/19104375) Practice bulletin no. 137: gestational diabetes mellitus. (http://www.ncbi.nlm.nih.gov/pubmed/23969827) Insulin and glyburide therapy: dosage, severity level of gestational diabetes, and pregnancy outcome. (http://www.ncbi.nlm.nih.gov/pubmed/15672015) Trends in glyburide compared with insulin use for gestational diabetes treatment in the United States, 2000-2011. (http://www.ncbi.nlm.nih.gov/pubmed/24807336) Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. (http://www.ncbi.nlm.nih.gov/pubmed/23712381)

Question 10

A 33-year-old woman comes to the office for evaluation of hypercalcemia. She was recently seen in the emergency department for uncomplicated appendicitis and was found to have a serum calcium level of 10.7 mg/dL. The patient underwent a laparoscopic appendectomy and was released the following day. Prior to this, she had not seen a physician in over 7 years. She now feels well and has no other medical problems. The patient has had 2 uneventful pregnancies and her menstrual periods are normal. She is divorced and currently not sexually active. She does not use tobacco, alcohol, or illicit drugs. Her mother has had "a high calcium level for a long time," but the patient does not know if she received any specific treatment. Blood pressure is 123/68 mm Hg and pulse is 87/min with regular rhythm. BMI is 22 kg/m². Physical examination is normal with well-healing abdominal wounds. Laboratory results are as follows: Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bebf_487c_8f63_911658f586ca_MD0005_00 This patient has mild, asymptomatic hypercalcemia. In light of a high-normal parathyroid hormone (PTH) level and low urinary calcium excretion, this is consistent with familial hypocalciuric hypercalcemia (FHH). FHH is an autosomal dominant disorder caused by mutations of the calcium-sensing receptor (CaSR) that lead to decreased sensitivity to calcium. Normally, high-normal calcium levels suppress PTH secretion, but in FHH, higher calcium concentrations are required to suppress PTH release. Concurrently, the defective CaSR causes increased reabsorption of calcium in renal tubules. higher calcium concentrations The most common cause of hypercalcemia with an elevated PTH is primary hyperparathyroidism (PHPT). PHPT must be differentiated from FHH as FHH follows a benign course, whereas untreated PHPT can lead to osteoporosis, nephrolithiasis, and chronic kidney disease. FHH can be distinguished from PHPT by assessment of urinary calcium excretion. FHH is associated with low urinary calcium levels (typically <100 mg/24 hours). Although PHPT causes increased reabsorption of calcium, net excretion is increased (often >300 mg/24 hours) due to accelerated bone turnover. Urine calcium excretion can be more precisely assessed using the urine calcium/creatinine clearance ratio (UCCR): UCCR is usually <0.01 in FHH compared to >0.02 in PHPT. If UCCR is low, the diagnosis of FHH is confirmed by testing for CaSR mutations. (Choice A) Mutations in the RET proto-oncogene are the most common cause of the multiple endocrine neoplasia (MEN) types 2A and 2B, which are also typically autosomal dominant. MEN 2A is associated with PHPT due to parathyroid hyperplasia, but urinary calcium excretion would be increased. (Choice B) Excess secretion of PTH-related peptide causes humoral hypercalcemia of malignancy, characterized by severe (eg, >14 mg/dL) hypercalcemia and suppressed PTH. (Choices C and E) Parathyroidectomy is indicated for patients with PHPT who have symptomatic hypercalcemia or additional complications (eg, osteoporosis, chronic kidney disease). Ultrasound of the neck is often used to localize a parathyroid adenoma in preparation for surgery. Parathyroidectomy is not indicated for FHH. Educational objective: Familial hypocalciuric hypercalcemia (FHH) is a benign autosomal dominant disorder characterized by mild hypercalcemia with a normal or mildly elevated parathyroid hormone level. FHH can be distinguished from primary hyperparathyroidism (PHPT) by urinary calcium excretion, which will be low in FHH and elevated in PHPT. References: Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/23425644) Familial hypocalciuric hypercalcemia: a review. (http://www.ncbi.nlm.nih.gov/pubmed/21986511)

Question 11

A 26-year-old woman, gravida 1 para 0, at 16 weeks gestation comes to the clinic for follow-up prenatal care.  She was diagnosed with Graves disease during her first trimester and was treated with propylthiouracil, which was changed to methimazole 3 weeks ago.  The patient has gained 7 kg (15.4 lb) over the last 4 months.  She also has experienced increasing fatigue and states, "My breasts feel very full."  The patient has had no palpitations or shortness of breath, but her sleep has been interrupted by frequent urination.  Her mother has hypothyroidism, which is treated with levothyroxine.  The patient has never used tobacco, alcohol, or illicit drugs.  Temperature is 37.2 C (99 F), blood pressure is 112/72 mm Hg, pulse is 90/min and regular, and respirations are 18/min.  No murmurs are heard on cardiac auscultation.  Thyroid examination shows mild, diffuse enlargement with no tenderness or bruit.  Deep tendon reflexes are brisk but symmetrical.  The remainder of the physical examination is normal.  Thyroid function test results are as follows:  Which of the following is the most appropriate management for this patient?

Accepted Answer

Explanation: Management of hyperthyroidism during pregnancy can be challenging as physiologic changes in the thyroid axis can resemble mild thyrotoxicosis, with: Increased total T4 High-normal or mildly elevated free T4 Suppressed TSH The interpretation of thyroid hormone and TSH levels should be based on pregnancy-specific reference ranges (normal total T3 and T4 can be approximated by 1.5 x nonpregnant reference ranges). Mild thyrotoxicosis during pregnancy does not require treatment. However, moderate-to-severe thyrotoxicosis due to Graves disease or nodular thyroid disease should be treated with thionamide antithyroid drugs (eg, methimazole, propylthiouracil). Propylthiouracil is preferred in the first trimester due to the potential teratogenicity of methimazole (aplasia cutis), whereas methimazole is preferred in the second and third trimesters (and in nonpregnant patients) due to the risk of hepatotoxicity with propylthiouracil (Choice B). Overtreatment of hyperthyroidism during pregnancy can lead to fetal hypothyroidism and goiter, so treatment should be titrated to maintain a mild hyperthyroid state. This patient's test results are appropriate for hyperthyroidism in pregnancy, and her current therapy should be continued without any dose adjustments (Choices D and E). (Choice A) Beta blockers are used to control the hyperadrenergic symptoms of hyperthyroidism (eg, tachycardia, palpitations). Short-term (<6 weeks) use of metoprolol or propranolol (but not atenolol) is considered safe in pregnancy. However, this patient's symptoms (weight change, fatigue, breast fullness, frequent urination) can be attributed to normal pregnancy and she is not overtly tachycardic; therefore, beta blockers are not necessary. Educational objective: Hyperthyroidism in pregnancy is treated with antithyroid drugs. Overtreatment of maternal hyperthyroidism can cause fetal hypothyroidism and goiter, so treatment should be titrated to maintain a mild hyperthyroid state. Propylthiouracil is preferred in the first trimester (due to the teratogenic effects of methimazole), but methimazole is preferred in the second and third trimesters (due to the hepatotoxicity of propylthiouracil). References: 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. (http://www.ncbi.nlm.nih.gov/pubmed/28056690)

Question 12

A 32-year-old woman, gravida 3 para 2, comes to the office at 10 weeks gestation to establish prenatal care.  She has mild nausea and anxiety and has not gained any weight during the pregnancy because of decreased food intake due to the nausea.  The patient's first pregnancy was complicated by hyperemesis gravidarum but her second pregnancy was uneventful.  She has no medical problems and her only medication is a daily prenatal vitamin.  Her mother has a thyroid nodule and her father has type 2 diabetes mellitus, hyperlipidemia, and hypertension.  The patient eats a vegan diet and does not use tobacco, alcohol, or illicit drugs.  Blood pressure is 126/82 mm Hg and pulse is 94/min and regular.  The thyroid gland is normal.  There is no lid lag or proptosis.  Chest auscultation is unremarkable.  Laboratory results are as follows:  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bec8_975c_8f63_e32880fdb3db_MD0005_00 Thyroid hormone production increases during pregnancy to cope with metabolic demands. This is accomplished by 2 mechanisms: Estrogen stimulates synthesis of thyroxine-binding globulin, leading to an increased pool of bound thyroid hormone. Thyroid hormone production subsequently increases to maintain free hormone levels. hCG (which shares a common alpha subunit with TSH and a very similar beta subunit) directly stimulates TSH receptors. This results in increased thyroid hormone production with feedback suppression of pituitary TSH release. In patients with normal thyroid function, the net effect can resemble subclinical hyperthyroidism with increased total T4, normal (or mildly elevated) free T4, and suppressed TSH. This patient is clinically euthyroid, with a physiologic increase in total T4 and decrease in TSH. Although she has nonspecific symptoms (eg, nausea, anxiety), her vital signs and thyroid examination are normal, with no evidence of lid lag (seen in most cases of hyperthyroidism) or proptosis (seen with Graves disease). No additional workup is necessary at this time. (Choice A) Free T4 assays in pregnancy are unreliably low due to assay artifact. Measurement of total T4 is preferred during pregnancy. (Choice B) Total T3 is primarily used as a secondary test for hyperthyroidism in patients with suppressed TSH and normal T4. This patient is clinically euthyroid and a T3 assay is not needed. (Choice D) Antithyroid drugs are used in pregnancy for the treatment of overt hyperthyroidism; propylthiouracil is preferred during the first trimester and methimazole in the second and third. This patient is clinically euthyroid; therefore, antithyroid treatment is not indicated. (Choice E) Thyroid ultrasound is indicated for the evaluation of thyroid nodules and multinodular goiter. This patient has a normal thyroid examination. Educational objective: Thyroid hormone production increases during pregnancy to cope with metabolic demands. Estrogen causes an increase in thyroxine-binding globulin, leading to increased total (but not free) thyroid hormone levels. hCG directly stimulates TSH receptors, causing increased production of thyroid hormones. References: Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/22869843)

Question 13

A 54-year-old woman comes to the emergency department with palpitations.  She has experienced paroxysmal atrial fibrillation for the past 6 months.  She has had extensive investigations for an underlying cause, including echocardiography and thyroid function testing, which were normal.  The patient was started on amiodarone 6 weeks ago by her cardiologist and did well in the interim.  She has had no change in her weight or intolerance to hot or cold temperatures.  Her other medications include atenolol and low-dose aspirin.  On physical examination, the patient appears comfortable.  Her blood pressure is 132/82 mm Hg and heart rate is 112/min and irregular.  Laboratory studies show a normal complete blood count and basic metabolic panel.  ECG shows atrial fibrillation with rapid ventricular response.  Thyroid function markers are as follows:  
What is the most likely explanation for this patient's thyroid function tests?

Accepted Answer

Explanation: 11ec2b69_bec9_a8d0_8f63_83ebd4c52d54_MD0005_00 Amiodarone may cause significant thyroid dysfunction due to its high iodine content, direct effects on thyroid follicular cells, and changes in thyroid hormone metabolism. There are 3 thyroid-related syndromes associated with amiodarone use: Amiodarone decreases the peripheral conversion of T4 to T3. As in this patient, this may result in higher T4, lower T3, and normal or mildly elevated TSH (<20 mU/L). The thyroid test abnormalities are most prominent in the first 1-3 months after starting amiodarone and may become less apparent afterward. These patients are clinically euthyroid. The high iodine content in amiodarone inhibits thyroid hormone synthesis, leading to primary hypothyroidism (Wolff-Chaikoff effect). Amiodarone can also induce thyrotoxicosis (amiodarone-induced thyrotoxicosis [AIT]) due to either increased thyroid hormone synthesis (AIT type 1) or destructive thyroiditis (AIT type 2). In both AIT subtypes, TSH will be low. (Choice B) Aspirin in high doses (>2 g/day) displaces thyroid hormone from thyroid hormone-binding proteins, leading to an increased thyroid hormone effect with subsequently decreased TSH, total T3, and total T4. Low-dose aspirin does not have a significant effect. (Choice C) Propranolol, a non-cardioselective beta blocker, decreases conversion of T4 to T3 and is therefore useful in thyrotoxic emergencies. However, atenolol, a cardioselective beta blocker, has no effect on thyroid function. (Choice D) Thyroid function abnormalities, referred to as euthyroid sick syndrome (ESS), can occur in acutely ill patients. Most patients with ESS will have a low T3; however, in severe cases, T4 and TSH can be low as well. Mildly elevated TSH may occur during the recovery phase of the illness. (Choice E) Hyperthyroid patients with Graves' disease have elevated circulating thyroid hormone and low TSH levels. Educational objective: Amiodarone decreases the peripheral conversion of T4 to T3, causing increased serum T4 and decreased serum T3 levels with normal to borderline elevated TSH. References: Amiodarone and the thyroid. (http://www.ncbi.nlm.nih.gov/pubmed/15989900)

Question 14

A 54-year-old woman is brought to the emergency department due to disorientation.  She was recently on vacation and received treatment with high-dose oral prednisone for severe poison ivy dermatitis.  In the emergency department, her temperature is 37 C (98.6 F), blood pressure is 138/80 mm Hg, pulse is 102/min, and respirations are 22/min.  The mucous membranes are dry.  Laboratory results show random blood glucose of 1020 mg/dL with a normal anion gap.  Her hemoglobin A1c is 7.6%.  The patient is started on intravenous fluids and an intravenous insulin infusion.  After a day on intravenous insulin, her mental status is normal and she is transitioned to subcutaneous regular human insulin based on a sliding scale.  Her finger stick blood glucose readings are 200-250 mg/dL.  Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bec0_f62e_8f63_836eea4d1546_MD0005_00 This patient has type 2 diabetes with a hyperglycemic hyperosmolar nonketotic state (HHS), characterized by very high glucose (frequently >1000 mg/dL), mental status changes, and no associated ketoacidosis. The most common causes of HHS include infections, major illnesses, dehydration, and drugs such as corticosteroids, antipsychotics, diuretics, sympathomimetic agents, and beta blockers. Initial management of HHS includes high-flow intravenous (IV) fluids, continuous IV insulin infusion, and careful potassium replacement. Patients with HHS initially require very high doses of IV insulin due to insulin resistance induced by stress, infection, corticosteroids, and hyperglycemia. Subcutaneous insulin is generally started once the glucose has been corrected to <200 mg/dL and the patient is able to eat consistently. Short-acting human insulin or insulin analogue (lispro, aspart, or glulisine) should be given for meals as well as intermittent correctional boluses based on the level of blood glucose (sliding scale). However, short-acting insulin alone is not sufficient for glycemic control in most hospitalized patients, and basal insulin (eg, detemir, glargine) should be added as well (Choices D and E). (Choices B and C) Oral anti-diabetic agents are not typically used in hospitalized patients, particularly in those with poorly controlled diabetes. Oral medications could be considered at the time of discharge or post-hospital follow-up. Educational objective: Hyperglycemic hyperosmolar nonketotic state is characterized by severe hyperglycemia, acute mental status changes, and absence of ketoacidosis. Initial management includes intravenous fluids and continuous insulin infusion. Stabilized patients can transition to subcutaneous insulin with a basal-bolus regimen. References: Evidence-based management of hyperglycemic emergencies in diabetes mellitus. (http://www.ncbi.nlm.nih.gov/pubmed/21978840) Hyperosmolar hyperglycemic state. (http://www.ncbi.nlm.nih.gov/pubmed/15887451)

Question 15

A 28-year-old male presents with polyuria and polydipsia.  Lately, he has been getting up at least six times  during the night to urinate.  He denies any past medical problems.  He is currently on no medications.  His family history is unremarkable.  He migrated from India four years ago.  He chews tobacco, but does not smoke.  He denies alcohol use.  Physical examination reveals a blood pressure of 160/94 mmHg.  He weighs 165 pounds and is 5' 7" tall.  The thyroid gland is normal to palpation.  There is no abdominal bruit.  The rest of the physical examination is unremarkable.  His potassium level is 3.2 mEq/L.  Hypokalemia is confirmed on repeat testing.  What is the next best step in the evaluation of this patient?

Accepted Answer

Explanation: The patient presents with hypertension and hypokalemia, which are characteristic of primary hyperaldosteronism (Conn's syndrome). His polyuria can be explained by the hypokalemic state, which causes an impaired urinary concentrating ability. The commonly used screening test involves the measurement of plasma aldosterone to plasma renin activity ratio, and a ratio of 30 or more is suggestive of excessive aldosterone secretion from the adrenal gland. Patients with excessive aldosterone secretion of the adrenal gland have suppressed renin activity and elevated levels of plasma aldosterone. Because many patients with essential hypertension have suppressed renin activity, aldosterone level over 15 ng/dl is required to interpret the test correctly. (Choice A) This patient does not have any clinical features of Cushing's syndrome. Therefore, 24-hour urinary cortisol levels would not be useful. Cushing's syndrome can sometimes cause hypokalemia due to the action of excessive glucocorticoid on the mineralocorticoid receptor. (Choice C) Deoxycorticosterone also has mineralocorticoid activity. Deoxycorticosterone levels can be useful in patients with hypokalemia and hypertension who have suppressed levels of both renin and aldosterone. Suppression of both renin and aldosterone suggests that some other mineralocorticoid like deoxycorticosterone is responsible for causing this mineralocorticoid excess syndrome. (Choice D) Secondary hyperaldosteronism is seen in patients with renal artery stenosis. One of the common causes of renal artery stenosis is fibromuscular dysplasia, which is predominantly seen in young females. Male sex and absence of abdominal bruit makes renal artery stenosis unlikely in the patient described in this vignette. (Choice E) Although a measurement of 24-hour urinary potassium level will demonstrate kaliuresis, this will not determine the cause of the patient's hypokalemia and hypertension. EducationalObjective: Patients with spontaneous hypokalemia and hypertension should be investigated for hyperaldosteronism. One of the best screening test for this disorder is measurement of plasma aldosterone to plasma renin activity (not renin levels) ratio.

Question 16

A 68-year-old woman comes to the emergency department due to a month-long history of increasing palpitations.  She has had no associated chest pain or shortness of breath but has experienced unusual fatigability.  The patient has also noted a 4-kg (8.8-lb) weight loss on her home scale and has been waking with increasing frequency at night to urinate.  She was diagnosed with osteopenia on bone densitometry at age 65; she increased her intake of "milk, yogurt, cheese, and other foods with lots of calcium" and started a vitamin D supplement, but repeat DXA 2 months ago revealed a significant interval decline in bone density.  The patient's medical history is otherwise unremarkable, and she does not use tobacco, alcohol, or illicit drugs.  Her mother died of breast cancer at age 62 and her father died in a motor vehicle collision at age 40.  Temperature is 36.7 C (98 F), blood pressure is 151/68 mm Hg, pulse is 122/min, and respirations are 16/min.  The thyroid gland is diffusely enlarged and nontender.  Lid lag is noted on eye examination.  The lungs are clear to auscultation.  The heart has an irregularly irregular tachycardia with a variable intensity of S1.  Laboratory results are as follows:  Which of the following should be addressed next in treatment of this patient's condition?

Accepted Answer

Explanation: 11ec2b69_bec4_c6c5_8f63_7743567b6d72_MD0005_00 This patient has symptomatic hyperthyroidism, likely due to Graves disease (diffuse goiter, elevated free T4, suppressed TSH). She also has hyperthyroid complications including rapid atrial fibrillation (irregularly irregular tachycardia with variable S1 intensity) and progressive bone loss with mild hypercalcemia. Cardiovascular manifestations are common and can include other supraventricular arrhythmias (eg, atrial flutter, paroxysmal atrial tachycardia), hypertension, coronary vasospasm, myocardial ischemia, and congestive heart failure. Thyroid hormones cause an increase in sympathetic activity due to increased responsiveness to catecholamines, which is responsible for many of the symptoms of hyperthyroidism (eg, palpitations, tachycardia, anxiety, tremors). Atrial fibrillation occurs in 10%-20% of patients with hyperthyroidism. Beta blockers (eg, propranolol, atenolol) are recommended to ameliorate hyperadrenergic symptoms and control heart rate and should be initiated as soon as hyperthyroidism is noted. The patient can then be considered for specific treatment including antithyroid medications (eg, methimazole), radioiodine ablation, or thyroidectomy. However, these interventions can take several weeks, and so patients should be treated initially with beta blockers to manage symptoms caused by excessive sympathetic activity (Choice C). (Choice B) Hyperglycemia is common in thyrotoxicosis due to insulin resistance. However, this patient has only mild hyperglycemia, which is likely to improve with treatment of the underlying condition. Increased urination is common in hyperthyroidism due to increased thirst and hypercalcemia and does not indicate more severe hyperglycemia. (Choice D) Electrical cardioversion can restore sinus rhythm in atrial fibrillation, but patients with hyperthyroidism and an uncorrected hyperadrenergic state will likely fail to convert or maintain sinus rhythm. Patients should be treated first with beta blockers, followed by antithyroid therapy to achieve euthyroidism prior to cardioversion. Cardioversion also increases the risk for thromboembolism in patients without adequate anticoagulation. (Choice E) Systemic glucocorticoids inhibit conversion of T4 to T3 and are occasionally used for life-threatening hyperthyroidism/thyroid storm, which is characterized by pronounced tachycardia (eg, >140/min), hyperpyrexia, and altered mental status. They are also used in some patients with subacute (de Quervain) thyroiditis (which would cause neck pain) who do not respond to nonsteroidal anti-inflammatory drugs and for certain patients with amiodarone-induced thyrotoxicosis. Educational objective: Cardiovascular manifestations (eg, supraventricular arrhythmias) are common in hyperthyroidism due to excessive sympathetic activity. Patients with symptomatic tachycardia or those in atrial fibrillation must be treated initially with beta blockers to control symptoms and heart rate. References: Hyperthyroidism and cardiovascular complications: a narrative review on the basis of pathophysiology. (http://www.ncbi.nlm.nih.gov/pubmed/24273583) Short-term effects of ß-adrenergic antagonists and methimazole in new-onset thyrotoxicosis caused by Graves' disease. (http://www.ncbi.nlm.nih.gov/pubmed/22975536)

Question 17

A 52-year-old woman comes to the office for follow-up after a forearm fracture. She experienced a nondisplaced radial fracture in a ground-level fall a week ago, and was treated with casting in the emergency department. The patient has a history of chronic constipation but has had no polyuria, bone pain, hematuria, or headaches. Medical history is notable for borderline hypertension that has been stable for several years with dietary modification. Her only medications include calcium and vitamin D supplements that she started after experiencing menopause a year ago. The patient has a 15-pack-year smoking history but quit 20 years ago; she does not use alcohol or illicit drugs. Her mother has osteoporosis and her father had type 2 diabetes mellitus and hypertension. Blood pressure is 157/98 mm Hg and pulse is 72/min. BMI is 28 kg/m². Physical examination shows a cast on the right forearm but is otherwise unremarkable. Laboratory results are as follows: Serum calcium a year ago was 10.9 mg/dL. DXA reveals a T-score of −2.6 at the lumbar spine and −1.8 at the femoral neck. Which of the following is the best management for this patient?

Accepted Answer

Explanation: 11ec2b69_bec1_6b60_8f63_bd393af4b0ba_MD0005_00 This patient with a recent fracture and evidence of osteoporosis on DXA (T-score <−2.5) has mild hypercalcemia with an elevated parathyroid hormone level (ie, parathyroid hormone-dependent hypercalcemia), most likely due to primary hyperparathyroidism (PHPT). (Familial hypocalciuric hypercalcemia can also cause parathyroid hormone-dependent hypercalcemia but is much less common and would be associated with urinary calcium excretion <200 mg/day and a positive family history.) PHPT is most commonly due to a parathyroid adenoma but may also be caused by multiglandular parathyroid hyperplasia or, rarely, parathyroid carcinoma. PHPT usually is asymptomatic or causes only mild, nonspecific symptoms (eg, constipation); it typically is detected on testing performed for other reasons.Parathyroidectomy is recommended for patients who have symptomatic hypercalcemia (eg, bone pain, abdominal pain, psychiatric symptoms), complications (eg, osteoporosis, nephrolithiasis, chronic kidney disease), or elevated risk for complications (eg, moderate to severe hypercalcemia). In addition, patients age <50 are likely to develop complications later in life and should undergo parathyroidectomy even if they are asymptomatic. This patient has osteoporosis with a fragility fracture and warrants parathyroidectomy. (Choice A) Bisphosphonate use is common in postmenopausal women with osteoporosis. However, in patients with PHPT, although short-term use of bisphosphonates can increase bone density, long-term data showing a reduced fracture risk are not available and there is concern about the risks of prolonged use (eg, osteonecrosis of the jaw). Bisphosphonates may be considered in patients with PHPT who are high-risk surgical candidates or refuse surgery. (Choice B) Combined estrogen-progestin hormone replacement therapy can improve bone density in postmenopausal women with PHPT. However, there is no evidence showing a reduced fracture risk. In light of the additional risks (eg, breast cancer, stroke), hormone replacement is not advised as primary therapy in PHPT. (Choice D) Asymptomatic patients with PHPT who do not have indications for parathyroidectomy can be followed with periodic serum calcium, creatinine, and DXA. This patient has osteoporosis, which may worsen without surgical intervention. (Choice E) Thiazide diuretics have a mild calcium-sparing effect and are often recommended for the management of hypertension in patients at risk for osteoporosis. However, they can worsen hypercalcemia in PHPT and should be avoided. Educational objective: Parathyroidectomy is recommended for patients with primary hyperparathyroidism who have symptomatic hypercalcemia, complications (eg, osteoporosis, nephrolithiasis, chronic kidney disease), or increased risk for complications (eg, moderate to severe hypercalcemia). In addition, patients age <50 are likely to develop complications later in life and should undergo parathyroidectomy. References: Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. (http://www.ncbi.nlm.nih.gov/pubmed/25162665)

Question 18

A 25-year-old man comes to the office with a 2-month history of fatigue, palpitations, sweating, and heat intolerance.  The symptoms are becoming more distressing and are keeping the patient awake at night.  The patient has no diplopia, eye pain or redness, decreased vision, neck pain, or proximal muscle weakness.  Medical history is unremarkable, and he currently takes no medications.  He smoked for approximately a year during college but quit after graduation.  The patient drinks alcohol socially but does not use recreational drugs.  Family history is positive for hypothyroidism in his mother.  Temperature is 36.7 C (98 F), blood pressure is 130/70 mm Hg, pulse is 115/min (regular), and respirations are 18/min.  Examination shows an anxious, thin man in no acute distress.  There is mild lid lag but no conjunctival erythema or proptosis.  Extraocular movements and pupillary reflexes are intact.  Mild diffuse nontender enlargement of the thyroid gland is noted.  The skin is warm and moist.  Cardiac examination is unremarkable except for tachycardia.  Neurologic examination shows a fine hand tremor and brisk symmetrical reflexes but is otherwise unremarkable.  Laboratory tests show normal complete blood count, basic metabolic profile, and urinalysis.  Thyroid function test results are as follows:  Radioactive iodine uptake at 24 hours is 36% (normal: 8%-25%), and scan shows a diffuse uptake pattern.  Serum thyroid-stimulating immunoglobulin level is mildly elevated. 
Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bec5_d838_8f63_fd70748403ca_MD0005_00 This patient has Graves disease with a positive thyroid-stimulating immunoglobulin assay and diffusely increased uptake on radioiodine scintigraphy. Patients with symptomatic hyperthyroidism should be started on a beta blocker (eg, propranolol) to reduce symptoms, with additional measures to decrease thyroid hormone production and achieve a euthyroid state. Modalities include antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy; there is no gold standard treatment, and choice of therapy depends on the specifics of the case, clinician experience, and patient preference. ATDs inhibit synthesis of thyroid hormone. They can be used in short courses to achieve remission in mild cases and for chronic management in poor operative candidates or those who wish to avoid surgery or RAI therapy. In patients with more significant symptoms (as in this patient), ATDs are useful to induce a euthyroid state in preparation for surgery or RAI therapy. 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 A). RAI is appropriate for patients who cannot tolerate ATDs, those who wish to avoid surgery, or those in whom an ATD alone is unlikely to achieve remission. Due to diffuse injury to the gland, most patients treated with RAI for Graves disease develop residual hypothyroidism and require long-term thyroid replacement therapy. RAI is contraindicated in pregnancy and lactation. RAI could be considered for definitive therapy in this patient; however, due to his significant symptoms, a beta blocker should be administered first (Choice B). Surgery is preferred for those with large goiters, obstructive symptoms, or suspected thyroid cancer and is also recommended for those with significant ophthalmopathy in whom RAI may cause an exacerbation of symptoms (Choice D). (Choice C) Prednisone is recommended for patients with moderate to severe Graves ophthalmopathy (eg, exophthalmos, periorbital edema, vision changes) prior to definitive treatment with surgery or RAI. This patient's mild lid lag does not require prednisone. He should receive ATDs and a beta blocker given his symptoms. Educational objective: Patients with Graves disease should be started on a beta blocker to reduce hyperthyroid symptoms, followed by specific treatment to achieve a euthyroid state. Modalities include antithyroid drugs, radioactive iodine, and surgical thyroidectomy. References: Hyperthyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/27038492)

Question 19

A 24-year-old female maintained on methimazole for the treatment of Graves disease comes to your office after having a positive urine pregnancy test. She complains of mild nausea, but does not have any other symptoms. Her last menstrual period was five weeks ago. She was diagnosed with Graves disease approximately eight months ago. Her clinical symptoms of hyperthyroidism have markedly improved since starting methimazole. She is married and has no children. She does not smoke or drink alcohol. Her mother has hypothyroidism. She takes no other medications. She has no medication allergies. Her menstrual cycles were previously regular. Physical examination reveals a mildly enlarged, smooth, non-tender thyroid gland. Thyroid function tests performed last week showed a TSH of 0.7 mU/L and total T₄ of 15.2 μg/dL (normal 4 to 12 μg/dL). What is the best next step in this patient's management?

Accepted Answer

Explanation: This patient's hyperthyroidism has been relatively well maintained on her dose of methimazole. Her current TSH is just below the normal range. While her total T₄ is elevated, it is expected to be higher than normal during pregnancy because of increased thyroid binding globulin synthesis. Thionamide medications are the treatment of choice for hyperthyroidism in pregnancy since both radioiodine and surgery should be avoided. However, methimazole is a potential teratogen and should not be used during the first trimester. These teratogenic effects consist of scalp defects, tracheoesophageal fistula, and choanal atresia. During the first trimester, pregnant patients should be switched to propylthiouracil, which carries less risk of birth defects. For the second and third trimesters, patients are often switched back to methimazole because propylthiouracil carries a risk of liver failure. (Choice A) Beta-blockers can be given if a pregnant patient has symptoms of hyperthyroidism despite the use of thionamide medications, although an attempt should be made to avoid beta-blockers since they can potentially result in harmful effects on the fetus. The most important step at this time is to switch methimazole to propylthiouracil in order to avoid its teratogenic effects. (Choice C) Methimazole can be used in the second and third trimesters of pregnancy, but should be avoided during the first trimester because of its teratogenic effects. (Choice D) Surgery can be considered for pregnant patients with severe symptoms despite thionamide use, but in general an attempt should be made to avoid surgery during pregnancy. (Choice E) Radioiodine therapy is absolutely contraindicated during pregnancy because it can ablate the fetal thyroid gland. Educational objective: Thionamides are the treatment of choice for hyperthyroidism during pregnancy. Propylthiouracil should be used in the first trimester because of concerns of teratogenic effects with methimazole. Patients should be switched to methimazole for the second and third trimesters because of potential liver failure in patients taking propylthiouracil.

Question 20

A 14-year-old boy comes to the office with his mother for a well-child visit.  He is in 9th grade and recently joined the football team.  His diet is well-varied and includes fruits, vegetables, meat, and dairy.  He had rhinorrhea and cough last week that resolved on its own.  Otherwise, the patient has no medical problems and takes no medications.  Height has increased by 7.5 cm (3 in) since his last physical, and he has gained 3.2 kg (7 lb); BMI is at the 65th percentile.  The mother leaves the room while the patient undergoes physical examination and continued discussion with his health care provider.  The boy is not sexually active.  He drinks 1 or 2 beers on weekends and has never tried cigarettes or drugs.  When asked if he would like to discuss any additional issues in private, the boy says, "This is so embarrassing, but I think something is wrong.  My chest is getting bigger.  I didn't want to tell my mom because my grandma died from breast cancer last year."  Physical examination shows a nervous and alert boy.  Palpation of the chest reveals a 3-cm (1.2-in), firm, mobile mass beneath the areola bilaterally.  There is no skin dimpling or nipple discharge.  The testes are descended bilaterally, and genital examination reveals Tanner stage III pubic hair.  A 0.5-cm soft, mobile node is palpated on his right anterior cervical chain.  The remainder of the physical examination is unremarkable.  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bebc_d777_8f63_cbbae7a77900_MD0005_00 Physiologic gynecomastia is very common in pubertal boys due to relative excess estrogen production and resulting imbalance of estrogen and androgens. Patients present during mid-puberty (ie, Tanner stage III-IV) with a unilateral or bilateral mass or lump beneath the areola. This breast tissue is typically small (<4 cm), firm, tender, and disc-like in shape. Physiologic gynecomastia must be differentiated from pseudogynecomastia (deposition of fat in overweight or obese boys), which will not present as a palpable mass. Breast tissue may slowly increase in size, but pubertal gynecomastia resolves within a year in the majority of boys. Although gynecomastia can cause embarrassment and anxiety, medical intervention is not necessary and reassurance and observation are indicated at this time. (Choices A, B, and E) An evaluation is indicated for signs of pathologic gynecomastia. Breast cancer is exceedingly rare in this population, but skin dimpling, rapidly increasing mass size, or axillary lymphadenopathy warrant imaging (eg, ultrasound) and/or tissue biopsy. A serum prolactin level should be obtained in the presence of galactorrhea to evaluate for a prolactinoma. In addition, gynecomastia in a prepubertal boy warrants evaluation by an endocrinologist to assess for pathologic hormonal imbalance (eg, hyperthyroidism, hCG-secreting tumor). (Choice C) Many exogenous substances, including marijuana and anabolic steroids, can exaggerate the physiologic imbalance of estrogens and androgens and cause gynecomastia. Although this patient should be counseled on substances that can worsen his physiologic gynecomastia, a urine toxicology screen is not necessary in a patient with no history of substance abuse. Educational objective: Gynecomastia is a common physiologic finding in pubertal boys. Presentation includes a small, often tender, subareolar mass that may grow but typically resolves within a year. No treatment is required. References: Gynecomastia in adolescent males. Page(s): PMC3706045 (http://www.ncbi.nlm.nih.gov/pubmed/3706045) Gynecomastia: clinical evaluation and management. Page(s): PMC3987263 (http://www.ncbi.nlm.nih.gov/pubmed/3987263)

Exam 1: Advanced Clinical Medicine