Question 1

A 76-year-old woman with a history of hypertension, type 2 diabetes mellitus, coronary artery disease, heart failure with preserved ejection fraction, and atrial fibrillation comes to the office for a follow-up visit.  The patient says, "I feel exhausted all the time, and my feet are often swollen at the end of the day.  I have also gained several pounds over the past 3 months."  She has had no chest pain, dyspnea, orthopnea, or dizziness.  Her medications include low-dose aspirin, metoprolol, lisinopril, furosemide, metformin, insulin glargine, and a daily multivitamin supplement.  The patient underwent electrical cardioversion for persistent atrial fibrillation 6 months ago and has since been taking amiodarone.  Two months ago, anticoagulation was discontinued due to recurrent falls related to gait disturbance from diabetic neuropathy.  Blood pressure is 134/70 mm Hg with no postural changes, pulse is 58/min and regular, and oxygen saturation is 96% on room air.  Weight is 77 kg (170 lb), which is 4.5 kg (10 lb) more than her recorded weight a few months ago.  With the head of the bed elevated to 30 degrees, the jugular venous pressure is 2 cm above the sternal angle.  Hepatojugular reflux is absent.  Lung fields are clear to auscultation.  Trace edema is noted at the ankles.  Decreased vibratory and light touch sensation is present in the distal lower extremities.  The remainder of the physical examination is normal.  Serum creatinine is 0.8 mg/dL, sodium is 132 mEq/L, and potassium is 3.7 mEq/L.  Which of the following is the most appropriate next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_bece_15a7_8f63_d34cae31c0b4_MD0005_00 Amiodarone can cause thyroid dysfunction due to its high iodine content and intrinsic effects on thyroid metabolism. Both hypothyroidism and hyperthyroidism can occur, although the former is more common. The large iodine load suppresses synthesis of thyroid hormone (Wolff-Chaikoff effect), and amiodarone itself directly inhibits the conversion of T4 to T3. In patients with normal thyroid function, this can lead to a transient subclinical hypothyroidism in the first few months of amiodarone therapy. However, in patients with pre-existing chronic lymphocytic (Hashimoto) thyroiditis, it can cause overt and prolonged hypothyroidism. Conversely, amiodarone can cause hyperthyroidism due to increased thyroid hormone synthesis in patients with nodular thyroid disease or latent Graves disease (amiodarone-induced thyrotoxicosis type 1), or due to destructive thyroiditis with release of preformed thyroid hormone (amiodarone-induced thyrotoxicosis type 2). This patient's clinical (fatigue, weight gain, bradycardia) and laboratory (hyponatremia) features are likely due to hypothyroidism, and her serum TSH level should be checked. Patients on chronic amiodarone therapy should have periodic monitoring of TSH (every 3-4 months). (Choices A, B, and E) Mineralocorticoid receptor antagonists (eg, spironolactone, eplerenone) or escalating doses of loop diuretics (eg, furosemide) are indicated for certain patients with heart failure that is symptomatic despite therapy with an ACE inhibitor and a beta blocker. B-type natriuretic peptide is released from ventricular myocytes in response to high filling pressures and is useful for differentiating decompensated heart failure from other causes of dyspnea. However, this patient has no dyspnea or orthopnea, and her lung fields and jugular venous pressure are normal. Her other clinical features, including edema, are likely due to hypothyroidism. (Choice D) Hypothyroidism due to amiodarone can be easily treated with levothyroxine, although higher-than-normal doses may be required due to the decreased conversion of T4 to T3. Amiodarone need not be discontinued. Educational objective: Amiodarone can cause thyroid dysfunction due to its high iodine content and intrinsic effects on thyroid metabolism. Both hypothyroidism and hyperthyroidism can occur, with the former being more common. TSH levels should be monitored every 3-4 months in patients on chronic amiodarone therapy. References: Amiodarone-induced thyroid dysfunction. (http://www.ncbi.nlm.nih.gov/pubmed/24067547)

Question 2

A 25-year-old man comes to the emergency department because of headache, palpitations, sweating, and irritability.  He came directly from the health club, which he joined a few weeks ago.  He states that after every exercise session during evening, before dinner, he develops similar symptoms and he gets symptomatic relief by consuming granola bars.  He was diagnosed with type 1 diabetes mellitus eight years ago.  He takes a combination of NPH and regular insulin before breakfast and supper.  He states that he is very compliant with his insulin and meals.  He does not have any other symptoms or chronic complications of diabetes.  His blood pressure is 110/80 mmHg, pulse is 100/min, temperature is 36.7C (98F) and respirations are 14/min.  He is slightly diaphoretic but completely alert and awake.  His neurological examination is nonfocal.  The rest of the examination is unremarkable. Which of the following is the most appropriate step to prevent further hypoglycemic episodes in this patient?

Accepted Answer

Explanation: Exercise increases non-insulin-mediated glucose uptake by the exercising muscles. A lower dose of insulin is generally required during exercise. NPH is intermediate-acting insulin with peak actions after four to six hours of injection, and its effects can last up to 16 to 18 hours. Reducing the morning NPH insulin dose is likely to reduce this patient's hypoglycemic symptoms during the evening hours. Alternatively, the patient can eat granola bars (or any other source of glucose) before he exercises. Checking his blood sugar level before and after exercise to assess the impact of exercise may be of benefit. Avoiding insulin injection to the exercising limb may be helpful. All patients with type 1 diabetes with a blood sugar level of more than 250 and/or ketonuria should refrain from exercising. Acute effects of exercise on the blood glucose level are more commonly seen in patients with type 1 than type 2 diabetes. (Choice A) It is important to understand that normal individuals have basal insulin production even without food intake, while most type 1 diabetics are dependent on exogenous insulin administration for survival because they do not have endogenous insulin. Daily basal insulin should be provided to type 1 diabetics by two injections of intermediate acting insulin (NPH, lente) or one dose of long acting insulin (glargine). Discontinuation of the morning dose of NPH is likely to result in unwanted elevations of the blood glucose level in evening hours. (Choices B and D)The injection of regular insulin in the morning is responsible for controlling the blood sugar level of diabetics during breakfast. Lowering the regular insulin dose in the morning is likely to cause post-breakfast elevations of the blood sugar level. Similarly, lowering the dose of regular insulin before dinner is likely to result in unwanted elevations of the post-dinner blood glucose level. (Choice E)Oral hypoglycemic agents are not used in patients with type 1 diabetes mellitus. Educational objective: Hypoglycemic episodes during exercise in type 1 diabetics can be managed by decreasing the insulin dose, eating before exercising, and avoiding injections of insulin in the exercising limbs. Type 1 diabetics do not have endogenous insulin production and require basal insulin by injection of twice-daily NPH or one injection of glargine insulin at bedtime.

Question 3

A 35-year-old woman comes to the office due to hot flashes. Her last menstrual period was a year ago, and she began having hot flashes 4 months ago. The patient's symptoms have become progressively worse and are starting to interfere with sleep and normal daily activities. Medical history is notable for Hodgkin lymphoma, for which she underwent treatment with chemotherapy and radiation 18 months ago. Family history is unremarkable. The patient lives with her husband and 2 children, and underwent a tubal ligation after the delivery of her second child 5 years ago. She does not use tobacco or alcohol. Current medications include calcium and vitamin D supplements. Blood pressure is 110/70 mm Hg and pulse is 80/min. BMI is 19 kg/m². Physical examination, including breast and pelvic examination, is unremarkable. Laboratory results show a normal complete blood count and basic metabolic panel. LH is 25 mU/mL (normal, 3-20 mU/mL) and FSH is 56 mU/mL (normal, 0.8-13 mU/mL). Bone density using DXA reveals a Z-score of -2.5 at the lumbar spine and -1.7 at the hip. Which of the following is the most appropriate treatment for this patient?

Accepted Answer

Explanation: 11ec2b69_bed2_f7b1_8f63_5d32c0b0d240_MD0005_00 This patient has amenorrhea with low estrogen, elevated FSH, and hypoestrogenic symptoms. This is consistent with primary ovarian insufficiency (POI), which is a common complication of cancer treatment with chemotherapy and radiation therapy. In addition, she has low bone density as evidenced by a low (age-adjusted) Z-score on DXA. Patients with POI can rapidly lose bone mass, leading to an increased risk of fragility fractures. In the absence of specific risk factors (eg, history of breast cancer), most patients with POI should receive oral or transdermal estrogen therapy, which should be combined with a progestin in women with an intact uterus to reduce the risk of endometrial cancer (Choice B). Estrogen therapy can relieve hypoestrogenic symptoms (eg, hot flashes, vaginal dryness) and minimize bone loss. Estrogen replacement should be continued until the average age of normal menopause, around age 50. Postmenopausal estrogen/progesterone therapy is associated with significant risks (eg, venous thromboembolism, coronary heart disease), but the absolute risks are substantially lower in young patients with POI, and the benefits far outweigh the risks for most patients. (Choices A and E) Bisphosphonates (eg, risedronate) are commonly used in the management of postmenopausal osteoporosis. Calcitonin is occasionally used as a second-line agent. However, neither of these medications has been studied extensively in osteoporosis due to POI, and neither would alleviate this patient's hypoestrogenic symptoms. (Choice D) Raloxifene is a selective estrogen modulator. It stimulates estrogen receptors on bone cells to improve bone density and is used to treat postmenopausal osteoporosis. However, it has antagonistic effects on other estrogen-responsive tissues and can worsen the hypoestrogenic symptoms in this patient. Educational objective: Primary ovarian insufficiency is a common complication of cancer treatment. Patients can experience hypoestrogenic symptoms (eg, hot flashes) and rapid bone loss. Treatment includes oral or transdermal estrogen therapy, which should be combined with a progestin in women who have an intact uterus. References: Premature ovarian failure: clinical presentation and treatment. (http://www.ncbi.nlm.nih.gov/pubmed/25681846)

Question 4

A 1-week-old boy is brought to the office by his parents to establish primary care.  The infant was born at 38 weeks gestation to a 31-year-old woman, gravida 3 para 2, via scheduled repeat cesarean delivery.  The infant weighed 3.2 kg (7 lb 1 oz, 50th percentile) at birth and had an unremarkable nursery course.  The infant was discharged home at age 3 days and has been breastfeeding exclusively.  He is voiding and stooling normally.  Yesterday, the parents were notified of an abnormal result from newborn screening.  Today, the infant weighs 3.21 kg (7 lb 1 oz).  Physical examination is normal.  Laboratory studies reveal a T4 level of 6 µg/dL (normal: 10-22 for the first week after birth) and a TSH level of 46 µU/mL.  Which of the following is the most appropriate statement for this patient's parents?

Accepted Answer

Explanation: 11ec2b69_becf_9c4a_8f63_ed71ea6b8b55_MD0005_00 11ec2b69_becf_9c4b_8f63_db406516e558_MD0005_00 Congenital hypothyroidism is a common and preventable cause of intellectual disability, affecting approximately 1 in 2,500 children in the United States. The majority of cases are due to thyroid dysgenesis (agenesis, hypoplasia, or ectopy). Most infants lack clinical signs of hypothyroidism at birth as maternal T4 crosses the placenta. However, as maternal T4 disappears, the infant may demonstrate decreased physical and mental activity (eg, lethargy, poor feeding, constipation, hypotonia). T4 is critically important for normal brain development and myelination. Infants with congenital hypothyroidism may experience permanent intellectual disability if hormone replacement is not initiated by age 2 weeks. Therefore, hypothyroidism is included in newborn screening programs throughout the United States. Newborn screening programs detect abnormal thyroid hormones (low T4, high TSH, or both) to identify infants with congenital hypothyroidism before clinical signs develop, which allows prompt treatment with levothyroxine and prevents intellectual disability. (Choice A) Iodine deficiency in the mother can cause decreased fetal and neonatal production of T4. Iodine deficiency is a relatively common cause of congenital hypothyroidism in the developing world but has virtually disappeared from the United States due to iodization of salt. (Choice C) Most infants with congenital hypothyroidism identified through newborn screening are asymptomatic due to the presence of residual transplacental maternal T4. The lack of clinical findings should not preclude further investigation and treatment. (Choice D) Waiting 2-4 weeks to treat congenital hypothyroidism places the infant at risk of intellectual disability as untreated patients may develop permanent neurological injury by age 2 weeks. (Choice E) Infants with congenital hypothyroidism have excellent outcomes if levothyroxine replacement therapy is started by age 2 weeks. Educational objective: Newborn screening can identify congenital hypothyroidism before symptoms develop. Low T4 and elevated TSH levels are confirmatory. Levothyroxine should be started as soon as possible to prevent permanent neurological injury. References: Pediatric hypothyroidism: diagnosis and treatment. (http://www.ncbi.nlm.nih.gov/pubmed/28534114) Hypothyroidism. (http://www.ncbi.nlm.nih.gov/pubmed/25086165)

Question 5

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 best management for this patient?

Accepted Answer

Explanation: Amiodarone decreases the peripheral conversion of T4 to T3, with abnormalities in thyroid biomarkers (normal to high TSH, low T3, high T4) seen within the first 3 months of therapy. These abnormalities then improve over the subsequent 3-6 months. Patients are usually clinically euthyroid, and no treatment is necessary. (Choice A) The half-life of amiodarone is more than 100 days. Consequently, discontinuation will not improve thyroid dysfunction in a short period. However, amiodarone may be continued safely with close follow-up in euthyroid patients. (Choice B) Amiodarone-induced destructive thyroiditis with thyrotoxicosis is treated with glucocorticoids. (Choices C and D) Levothyroxine is the treatment of choice for amiodarone-induced hypothyroidism. Relatively high doses of levothyroxine may be required in amiodarone-induced hypothyroidism due to amiodarone's effect of decreasing the conversion of T4 to its active form, T3. Combination treatment with levothyroxine and liothyronine is not shown to be superior to levothyroxine alone. Educational objective: Amiodarone-induced biochemical abnormalities in thyroid hormone metabolism improve with time, and no treatment is necessary. References: Amiodarone and thyroid dysfunction. (http://www.ncbi.nlm.nih.gov/pubmed/20689491)

Question 6

A 22-year-old woman comes to the office to discuss initiating oral contraception. She has been sexually active with the same partner for the last year and has been using condoms but would like a more reliable method of contraception. The patient has a 4-year history of primary hypothyroidism, which has been well controlled on 125 µg/day of levothyroxine. Her most recent serum TSH was within normal limits. She has no other chronic medical conditions and no previous surgeries. The patient does not use tobacco, alcohol, or illicit drugs. Family history is significant for breast cancer in her mother diagnosed at age 52 and a sister who has type 1 diabetes mellitus. Blood pressure is 110/76 mm Hg and pulse is 78/min. BMI is 24 kg/m². There is no thyromegaly, and the remainder of the physical examination is normal. The patient states that her best friend noted an improvement in her acne after starting an oral contraceptive, and she would like to take the same type of pill. Which of the following is the most accurate statement regarding contraception in this patient?

Accepted Answer

Explanation: 11ec2b69_bed0_388c_8f63_97d0bfc56b17_MD0005_00 More than 99% of circulating thyroid hormone (T4, T3) is bound to plasma proteins, primarily thyroxine-binding globulin (TBG). Biologically active, free thyroid hormone is rapidly cleared by the kidneys, and binding proteins ensure that adequate hormone is available for delivery to the peripheral tissues. Elevated estrogen levels, as seen in pregnancy and patients taking oral contraceptives, stimulate hepatic synthesis of TBG. Patients with normal thyroid function can increase thyroid hormone production to saturate the additional protein binding sites, but those with primary hypothyroidism are unable to increase thyroid hormone synthesis; oral contraceptive use in these patients can induce a relative hypothyroid state. Most patients with hypothyroidism will require an increased dose of levothyroxine when starting oral contraceptives or becoming pregnant (Choice D). Serum TSH should be checked several weeks after initiating an oral contraceptive, with the levothyroxine dose increased as needed to maintain TSH within the normal range. Due to the risk of hypothyroid complications early in pregnancy, pregnant patients warrant even more aggressive management; the levothyroxine dose should be increased by approximately 30% (eg, 2 additional tablets a week) immediately following a positive pregnancy test and TSH checked every 4-6 weeks thereafter. (Choices A and C) There is a slightly increased risk of venous thromboembolism in women taking estrogen-containing oral contraceptives, but the risk is not further increased due to hypothyroidism. Hypothyroidism is not a contraindication to oral contraceptives (and the estrogen dose does not need to be altered) provided the dose of levothyroxine is properly adjusted. (Choice B) Progestin-only contraceptives (ie, "mini-pills") are indicated for patients with contraindications to estrogen (eg, venous thromboembolism) but are less effective in preventing pregnancy than combined oral contraceptives. Educational objective: Patients with hypothyroidism may require an increased dose of levothyroxine following initiation of estrogen-containing oral contraceptives due to an increase in thyroxine-binding globulin. Patients should have TSH measured several weeks after initiation of oral contraceptives, with the dose of levothyroxine adjusted to maintain TSH in the normal range. References: Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17ß-oestradiol in comparison to one containing levonorgestrel and ethinyl estradiol on markers of endocrine function. (http://www.ncbi.nlm.nih.gov/pubmed/21942708) Effects of the environment, chemicals and drugs on thyroid function. (http://www.ncbi.nlm.nih.gov/pubmed/25905415)

Question 7

A 40-year-old man is brought to the emergency department for sudden onset of headaches, diaphoresis, and loss of consciousness.  His wife states that he was previously in his usual state of health.  His past medical history is unremarkable.  He works as a physician assistant and does not smoke or drink alcohol.  On physical examination, the patient is diaphoretic and comatose.  His fingerstick blood glucose level is 45 mg/dL.  The patient is given 50% dextrose intravenously and then regains consciousness.  He says that he is currently dealing with a great deal of work- and relationship-related stress. Laboratory test results on the blood sample drawn prior to dextrose administration are as follows:
 Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: 11ec2b69_becb_cbb4_8f63_0b481471e18a_MD0005_00 This patient has the classic Whipple's triad of symptomatic hypoglycemia - symptoms consistent with hypoglycemia, low blood glucose, and symptom resolution after glucose administration. Elevated insulin, C-peptide, and proinsulin levels indicate hypoglycemia due to endogenous insulin secretion, either from an insulinoma or surreptitious use of oral hypoglycemic medication (rather than an insulin injection). True spontaneous hypoglycemia is uncommon and insulinoma is relatively rare. As a result, sulfonylurea and/or meglitinide use should be suspected given that the patient works in healthcare and may have access to prescription medications. The first step to differentiate insulinoma from surreptitious medication ingestion is to obtain a serum assay for oral hypoglycemic agents. If no medications are detected, insulinoma becomes more likely, and ultrasound or CT imaging can localize the tumor for subsequent surgical resection (Choice B). The following principles should guide the evaluation of hypoglycemia: Whipple's triad must be fulfilled before a hypoglycemia workup is initiated. Many normal individuals may have blood glucose in the nominal hypoglycemic range without symptoms of hypoglycemia. Low blood glucose in normal individuals will suppress production of insulin, C-peptide, and proinsulin. In the presence of significant hypoglycemia, normal levels of these hormones indicate an abnormal response. Fingerstick blood glucose measurement is unreliable in the hypoglycemic range. Low blood glucose recorded by a bedside glucometer must be confirmed by a standard laboratory assay. Blood samples for biochemical testing must be taken when the patient is hypoglycemic and before glucose administration. (Choice A) When a patient is in a normoglycemic state but is suspected to have a hypoglycemic disorder, a 72-hour fasting test is done to induce hypoglycemia. Patients with an insulinoma will continue to have high or inappropriately normal insulin levels despite a prolonged fast. However, this patient has confirmed hypoglycemia with elevated serum insulin, so prolonged fasting is unnecessary. (Choice C) C-peptide is a by-product of endogenous insulin secretion. Normal or elevated C-peptide levels confirm ongoing insulin production. Surreptitious insulin injection elevates plasma insulin but C-peptide remains low. (Choice D) The mixed-meal challenge test is used for evaluating patients with hypoglycemic symptoms that only occur after eating. Educational objective: Patients exhibiting Whipple's triad - symptoms consistent with hypoglycemia, low blood glucose, and symptom resolution following glucose administration - should be evaluated for a hypoglycemic disorder. A serum assay for oral hypoglycemic agents and serum levels of insulin, C-peptide, and proinsulin can generally determine the likely cause. The blood sample should be drawn during the hypoglycemic episode. References: Evaluation and management of adult hypoglycemic disorders: An Endocrine Society clinical practice guideline. (http://www.ncbi.nlm.nih.gov/pubmed/19088155)

Question 8

A 25-year-old man comes to the emergency department because of headache, palpitations, sweating, and irritability.  He came directly from the health club, which he joined a few weeks ago.  He states that after every exercise session during evening, before dinner, he develops similar symptoms and he gets symptomatic relief by consuming granola bars.  He was diagnosed with type 1 diabetes mellitus eight years ago.  He takes a combination of NPH and regular insulin before breakfast and supper.  He states that he is very compliant with his insulin and meals.  He does not have any other symptoms or chronic complications of diabetes.  His blood pressure is 110/80 mmHg, pulse is 100/min, temperature is 36.7C (98F) and respirations are 14/min.  He is slightly diaphoretic but completely alert and awake.  His neurological examination is nonfocal.  The rest of the examination is unremarkable.
Hypoglycemia is defined as a plasma glucose level of:

Accepted Answer

Explanation: The normal fasting blood sugar range is 70 to 100 mg/dL. Any individual with a blood sugar level less than 60 mg/dL is suspected to be hypoglycemic. The most important cause of hypoglycemia in type 1 diabetes mellitus is mismatch between insulin dose and insulin requirement. The patient in this case had hypoglycemic episodes during exercise due to a decreased requirement of insulin during exercise. The patient needs to adjust his insulin dosage or consume more carbohydrate. The target pre-meal blood sugar level in patients with diabetes is between 80 and 120 mg/dL. The action is generally necessary if the pre-meal blood sugar is consistently less than 80 or more than 140 mg/dL. Whipple's triad is characterized by a low blood glucose level, symptoms of hypoglycemia, and symptomatic relief with the administration of glucose. Whipple's triad is strongly suggestive of true hypoglycemia. (Choices A and B)Blood sugars below 90 and 120 mg/dL are not within the hypoglycemic range. (Choices D and E)In a non-diabetic normal individual, the prolonged fast blood sugar level can be as low as 45-50 mg/dL without any specific symptoms; therefore, in non-diabetic individuals being tested for hypoglycemia, a blood sugar level less than 50 mg/dL during a prolonged fast is generally considered abnormal if accompanied by hypoglycemic symptoms. Educational Objective: A plasma glucose level of less than 60 mg/dL is suggestive of hypoglycemia. In some normal individuals, the blood glucose level can reach around 45 mg/dL without symptoms. Whipple's triad is suggestive of true hypoglycemia.

Question 9

A 54-year-old postmenopausal woman comes to the office to establish care. She feels well and describes her lifestyle as "overall healthy." The patient has a history of hypertension, osteopenia, and anxiety disorder. She went through menopause at age 49, during which time she experienced hot flashes, sleep disturbances, and mood swings. The symptoms have largely resolved except for occasional episodes of anxiety. The patient did not receive any therapy for her menopausal symptoms. Her current medications include valsartan, calcium/vitamin D, and paroxetine. She is married, works as a television news reporter, and does not smoke or consume alcohol. Family history is negative for coronary heart disease, stroke, cancer, and venous thromboembolism. Blood pressure is 128/76 mm Hg and pulse is 68/min. BMI is 29 kg/m². Physical examination is normal. Laboratory results are as follows: The patient says that her friends have been telling her about the "anti-aging" effects of hormone replacement therapy, and she would like to discuss initiating treatment. She asks for advice regarding the risks and benefits of combined estrogen/progesterone menopausal hormonal therapy (MHT). Which of the following is the most appropriate response regarding MHT in this patient?

Accepted Answer

Explanation: 11ec2b69_bed2_5b70_8f63_fd6dffc52b6b_MD0005_00 Combination estrogen/progesterone menopausal hormone therapy (MHT), or estrogen alone for women who have had a hysterectomy, is the most effective treatment available for menopausal hot flashes. The use of MHT has declined following prospective trials (eg, Women's Health Initiative, Heart and Estrogen/progestin Replacement Study) that found an increased risk of stroke, coronary heart disease (CHD), breast cancer, and venous thromboembolism in women taking combination MHT. However, much of this risk is age-related; women age 50-59 have a lower risk of adverse effects, resulting in a more favorable risk-benefit profile compared with women age >60. In light of this, MHT can be safely used for a short period (3-5 years) in younger, low-risk women (ie, nonsmokers; no history of breast cancer, venous thromboembolism, or CHD). Prior to initiating therapy, patients should be advised of potential risks. In particular, the risk of ischemic stroke is increased in all age groups, although the absolute risk is small in women age <60. This increased risk is not eliminated by management of blood pressure or other traditional stroke risk factors. In addition, randomized studies have found no significant benefits of MHT on skin wrinkling. (Choice A) Combination MHT is associated with a lower risk of type 2 diabetes mellitus, possibly due to decreased insulin resistance. (Choice B) Unopposed estrogen is associated with an increased risk of endometrial cancer, an effect that is largely eliminated with combination estrogen/progesterone therapy. In contrast, the risk of breast cancer is increased with combination therapy (although it may be lower with unopposed estrogen). (Choice C) Both combined MHT and estrogen alone are associated with lower all-cause mortality in postmenopausal women age <60, a benefit that is not seen in women age >60. (Choice D) Combination MHT is associated with an increased risk of CHD in women age >60. This risk is significantly lower in women age <60 and those on unopposed estrogen. Educational objective: Combination estrogen/progesterone menopausal hormone therapy increases the risk for stroke, coronary heart disease, breast cancer, and venous thromboembolism. However, this risk is age-related, with a higher risk seen in women age >60. The risk of ischemic stroke is increased in all age groups, but the absolute risk in women age <60 is small. References: Menopausal hormone therapy for the primary prevention of chronic conditions: a systematic review to update the U.S. Preventive Services Task Force recommendations. (http://www.ncbi.nlm.nih.gov/pubmed/22786830)

Question 10

A 32-year-old woman, gravida 1 para 0, calls the office to schedule her first prenatal visit.  Her last menstrual period was 5 weeks ago and she had a positive pregnancy test 2 days ago.  The patient feels well and has no vaginal bleeding or cramping.  She was diagnosed with Hashimoto thyroiditis 4 years ago and has been on a stable dose of levothyroxine for the past 2 years.  Serum TSH 3 months ago was within normal limits.  The patient has no other chronic medical conditions or previous surgeries.  She has started taking a prenatal vitamin daily.  Family history is significant for a sister currently undergoing evaluation for recurrent miscarriages.  The patient does not use tobacco, alcohol, or illicit drugs.  She is nervous about her sister's obstetric history and asks if she needs to make any changes to her medication.  Which of the following would be the most appropriate response to this patient?

Accepted Answer

Explanation: 11ec2b69_becd_7966_8f63_edea8fb518ec_MD0005_00 Thyroid physiology changes during pregnancy to meet increased metabolic demands. During the first trimester, β-hCG binds TSH receptors on thyroid follicular cells and stimulates thyroid hormone production. The resulting elevations in T3 and T4 suppress TSH secretion. Concurrently, elevated estrogen levels cause an increase in serum thyroxine-binding globulin (TBG), which leads to higher total T3 and T4 levels. Thyroid hormone requirements increase by about 25%-50% over the prepregnancy state. Patients with normal thyroid function can increase thyroid hormone production to saturate the elevated number of thyroid hormone binding sites on TBG, but patients with primary hypothyroidism are unable to increase thyroid hormone production. In light of this, current guidelines advise that the dose of levothyroxine be empirically increased by approximately 30% (eg, 2 additional levothyroxine doses weekly) at the time the pregnancy is first detected (Choices B and E). Subsequently, TSH should be measured every 4 weeks and the dose adjusted to maintain TSH within trimester-specific norms. (Choice A) T3 is made primarily in the peripheral tissues, and circulating levels correlate poorly with thyroid status in hypothyroidism. If assessment of thyroid hormone is needed during pregnancy, free T4 (using trimester-specific norms) or total T4 can be measured. However, the dose of levothyroxine should be increased first, and TSH is usually adequate for monitoring of thyroid status. (Choice C) Levothyroxine replacement should not be discontinued during early pregnancy. The fetus is completely dependent on maternal thyroid hormone for brain development until 12 weeks gestation when the fetal thyroid gland is fully developed. Educational objective: Newly pregnant patients with hypothyroidism should increase their levothyroxine dose at the time pregnancy is detected. TSH is then checked every 4 weeks with the levothyroxine dose adjusted to trimester-specific norms. 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/22954017) Thyroid dysfunction during pregnancy and in postpartum period: treatment and latest recommendations. (http://www.ncbi.nlm.nih.gov/pubmed/24510157)

Question 11

A 10-year-old girl is brought to the office by her father due to concerns about her behavior and declining school performance over the last 6 months.  Her teachers have said that she is constantly distracted and does not pay attention in class.  The patient's grades have dropped significantly and she is failing most of her classes.  In addition, she has been irritable and moody with frequent outbursts of crying recently.  She takes no daily medications or supplements.  Temperature is 36.7 C (98 F), blood pressure is 116/58 mm Hg, and pulse is 114/min.  Weight is 27 kg (59.5 lb), decreased by 1 kg (2.2 lb) from last year.  Physical examination reveals a nervous-appearing girl who is fidgeting with her clothes.  The pupils are equally reactive to light.  The sclera is nonicteric and visible above the iris.  Cardiac examination reveals a regular rhythm and normal S1 and S2.  The abdomen is soft and nontender without hepatosplenomegaly.  Deep tendon reflexes are 3+ and symmetric in the upper and lower extremities.  The skin is warm and moist.  Without treatment, this patient is at risk of developing which of the following long-term complications?

Accepted Answer

Explanation: 11ec2b69_beca_6c22_8f63_b3885163e977_MD0005_00 This patient has behavioral changes, weight loss, lid lag, and increased cardiac output, concerning for hyperthyroidism. Graves disease (an autoimmune condition in which TSH receptor-stimulating antibodies activate the TSH receptor) is the most common etiology. Hyperstimulation of the TSH receptor causes elevated T3 and T4 levels. Excess circulating T3 and T4 hormones result in a constellation of findings related to sympathetic overactivity. Children and adolescents with hyperthyroidism often have psychological changes, such as inattention, moodiness/irritability, and poor school performance. Other calorigenic sequelae include weight loss, tachycardia with a wide pulse pressure, hyperreflexia, and warm/sweaty skin. A diffuse goiter is often present, and patients typically have lid lag, which causes the sclera to be visible above the iris. Exophthalmos (proptosis due to extraocular muscle inflammation) is common in adults. If hyperthyroidism remains untreated, increased adrenergic activity stimulates cardiac contractility, which can lead to arrhythmias (eg, atrial fibrillation) and dilated cardiomyopathy. Osteoporosis is a long-term complication due to elevated thyroid hormone stimulating calcium and phosphate release from bone. (Choice A) Mitral valve prolapse and regurgitation, not mitral valve stenosis, are associated with hyperthyroidism. (Choice B) Nephropathy is a complication of untreated diabetes mellitus, which typically presents with polydipsia, polyuria, and weight loss. Although behavioral changes may occur, lid lag and hyperreflexia would not be expected. (Choice D) Respiratory insufficiency can occur with myopathies such as myasthenia gravis. Ocular muscle weakness is typical, but a myopathy would result in hyporeflexia, not hyperreflexia as seen in this patient. (Choice E) In times of stress, untreated adrenal insufficiency can lead to hypotension and shock. Although presentation may include behavioral changes and weight loss, this disorder is unlikely to cause hyperreflexia or lid lag. Educational objective: Hyperthyroidism is characterized by sympathetic overactivity and can present with psychological changes (eg, irritability, poor academic performance) in addition to weight loss, tachycardia, hyperreflexia, and lid lag. Treatment prevents complications such as arrhythmias, cardiomyopathy, and osteoporosis. References: The influence of thyroid dysfunction on bone metabolism. (http://www.ncbi.nlm.nih.gov/pubmed/25648501) Metabolic and clinical consequences of hyperthyroidism on bone density. (http://www.ncbi.nlm.nih.gov/pubmed/23970897)

Question 12

A 47-year-old Caucasian man comes to the office for a follow-up visit.  He was recently diagnosed with diabetes mellitus type 2, and was started on a low-carbohydrate diet six months ago.  He also has obesity, hypertension and hyperlipidemia.  He is a financial advisor.  He does not use tobacco or illicit drugs, but drinks alcohol occasionally.  His medications include enalapril, simvastatin and hydrochlorothiazide. Examination shows no abnormalities.  His laboratory test results show the following:
Serum Chemistry
 LFT
 Lipid Profile
 Which of the following is the most appropriate pharmacotherapy for this patient?

Accepted Answer

Explanation: Despite a low-carbohydrate diet, this patient has uncontrolled diabetes, hypercholesterolemia and hypertriglyceridemia. He probably has non-alcoholic steatohepatitis (NASH), manifested by mild elevations of the liver enzymes (AST/ALT less than one) and alkaline phosphatase. He needs to be started on pharmacologic therapy. Metformin will be very useful in this case. It is a biguanide that is ideal for obese patients because its use is associated with some weight loss. It decreases fasting glucose levels by around 20%. It has proven to be helpful in patients with hypertriglyceridemia and hepatic steatosis by improving glycemic control and helping to stabilize obesity. (Choice A) Sulfonylureas (e.g., glyburide, glipizide or glimepiride) will aggravate the patient's obesity, and will not improve his lipid profile. (Choice C) Insulin is not recommended at this point because other alternatives have not been tried yet. (Choice D) Acarbose's efficacy is low when used alone. Its benefit will be marginal in this case. (Choice B) Although a thiazolidinediones (e.g., pioglitazone) is effective for glycemiccontrol, and can improve NASH, their use is not recommended in obese patients because of an associated weight gain, which is in part due to fluid retention. Like metformin, they decrease the triglyceride levels and increases HDL; however, they are potentially more hepatotoxic. Educational objective: Metformin is especially useful in the management of obese, diabetic patients. This drug, along with pioglitazone, decreases triglycerides, increases HDL and improves NASH. Thiazolidinediones, insulin and sulfonylureas can cause weight gain. Acarbose's action is too weak to be used as monotherapy.

Question 13

A 67-year-old woman comes to the emergency department because of severe weakness, fatigue, and non-bloody diarrhea.  She has well-controlled diabetes mellitus type 2 and bronchial asthma.  The patient used to smoke 1 pack of cigarettes daily for 25 years but quit 10 years ago.  She does not use alcohol or illicit drugs.  Her medications include glyburide, metformin, albuterol, and fluticasone metered dose inhalers.  Her temperature is 37.8 C (100 F), blood pressure is 92/61 mm Hg, pulse is 106/min, and respirations are 32/min.  Examination shows no pulmonary or cardiac abnormalities on auscultation.  The patient's laboratory tests show the following:  The patient's serum creatinine was 1.7 mg/dL 3 months ago.  Which of the following is the most appropriate immediate next step?

Accepted Answer

Explanation: 11ec2b69_bed3_6ce3_8f63_03adb65a25d8_MD0005_00 This patient's laboratory studies show acute kidney injury (AKI) with a low bicarbonate level and an increased anion gap. The anion gap is helpful in the interpretation of metabolic acidosis and is obtained using the following formula: Anion gap = Serum sodium - (Serum chloride + Serum bicarbonate) This patient's anion gap can thus be calculated as 142 - (105 + 12), which gives a result of 25, compared to a normal anion gap of around 12. The major causes of high anion gap acidosis can be recalled using the "mud piles" mnemonic (Table). In addition to AKI and likely hypovolemia, this patient's presentation is concerning for metformin-related lactic acidosis. Although lactic acidosis is rare in patients with normal renal function, patients with impaired renal function are at increased risk. Other risk factors for metformin-related lactic acidosis include hypovolemia, severe liver disease, and heart failure. Diarrhea is a common side effect of metformin and may contribute to hypovolemia. In addition to aggressive intravenous (IV) fluid support, this patient should have clarification of acid-base status with an arterial blood gas (ABG) analysis and measurement of lactate and ketone levels. (Choice A) IV insulin and high-flow IV fluids are appropriate management for diabetic ketoacidosis (DKA), which may also cause an elevated anion gap. However, DKA is rare in type 2 diabetes and is typically associated with much higher glucose levels. Subcutaneous insulin would be a more appropriate treatment for this patient's mild hyperglycemia. (Choices C and E) This patient's increased respiratory rate is due to compensatory hyperventilation in response to the metabolic acidosis, and not due to bronchial asthma or pneumonia. In light of normal findings on cardiopulmonary examination, these interventions are not needed. (Choice D) Diarrhea is a common side effect of metformin and usually improves a few days after discontinuation of this medication. Stool evaluation may be indicated if symptoms do not improve promptly. Educational objective: Lactic acidosis is a rare but serious complication of metformin. The risk of metformin-induced lactic acidosis increases with hypovolemia, severe liver disease, renal dysfunction, or heart failure. References: Metformin-associated lactic acidosis requiring hospitalization. A national 10 year survey and a systematic literature review. (http://www.ncbi.nlm.nih.gov/pubmed/23436666)

Question 14

A 65-year-old female is admitted to the intensive care unit for chest pain where she is diagnosed with a non-ST elevation myocardial infarction.  She has a history of hypertension, type 2 diabetes mellitus, hyperlipidemia, and osteoporosis.  Over the last two months, she has been getting occasional chest pain on exertion.  She also complains of some recent fatigue and mild constipation.  Cardiac catheterization is performed and shows severe triple-vessel coronary artery disease.  A coronary artery bypass graft procedure (CABG) is planned.  Her laboratory values include the following:
 Which of the following is the most appropriate next step in the management of this patient?

Accepted Answer

Explanation: This patient's morning cortisol level is at the higher end of normal and her HbA1c is only slightly above goal level, neither of which present much risk for her planned CABG. Her elevated TSH and low total T4 do however confirm the presence of previously undiagnosed hypothyroidism. There is a risk that hypothyroidism may worsen perioperative outcomes, although urgent or emergent surgeries can usually be done on patients with hypothyroidism as long as there are no symptoms of myxedema coma or other findings to suggest severe hypothyroidism. Treatment with levothyroxine can increase myocardial oxygen demand resulting in myocardial infarction, angina, or cardiac dysrhythmias. Levothyroxine generally needs to be started slowly and gradually in patients with cardiac disease, which might prolong the wait for this patient's badly needed CABG. Therefore, it is probably best to do the surgery now despite her hypothyroid state, even though it might slightly increase her risk for perioperative adverse events. (Choice A) Iodine loading before surgery can be considered in patients with hyperthyroidism, not hypothyroidism. (Choice B) Giving the patient a large loading dose of levothyroxine would be dangerous since it may lead to myocardial ischemia with subsequent dysrhythmia or recurrent myocardial infarction. (Choice D) A thyroid scan is not needed to confirm a diagnosis of hypothyroidism, although it might be helpful to determine its underlying cause. It would be unnecessary to delay the patient's CABG to perform such a study. (Choice E) Given this patient's severe coronary disease she will be at risk for recurrent myocardial infarction until revascularization is performed with CABG. It is not necessary to postpone her surgery for slow initiation of levothyroxine therapy. Educational objective: Patients with coronary artery disease are at risk of myocardial ischemia when levothyroxine is first started and the medication should be started very slowly in these patients. Hypothyroidism (in the absence of myxedema coma or other severe symptoms) usually only mildly increases the perioperative risk.

Question 15

A 38-year-old woman with a history of bipolar I disorder comes to the office due to low energy.  The patient felt well until 4 months ago when she noticed she was reacting slowly at work and was reluctant to meet with friends on weekends due to fatigue.  She is afraid she is becoming depressed again.  The patient says, "I am so discouraged.  I really felt so much better on my medication, and now I feel like I'm slipping."  She has a history of multiple hospitalizations for manic and depressive episodes since late adolescence.  She attempted suicide at age 20 by taking an overdose of aspirin.  The patient was previously treated with valproate and olanzapine and has been taking lithium for the past year.  Her other medical issues include hypertension and allergic rhinitis, for which she takes hydrochlorothiazide and loratadine, respectively.  On review of systems, the patient reports fatigue and difficulty concentrating over the past few weeks.  Mental status examination shows a tired appearance and sad affect.  She has no suicidal ideation.  Physical examination shows no abnormalities.  The patient's blood lithium level is 0.9 mEq/L (range: 0.6-1.2 mmol/L).  Other laboratory results are as follows:  Which of the following is the best next step in management of this patient?

Accepted Answer

Explanation: This patient's elevated TSH level and new onset of fatigue during treatment with lithium suggest hypothyroidism. Lithium interferes with the synthesis and release of thyroid hormone, causing a range of thyroid abnormalities that typically occur in the first 2 years of treatment. Goiter occurs in 40%-50% and hypothyroidism in 20%-30% of lithium-treated patients. Hyperthyroidism and autoimmune thyroiditis may occur infrequently. Physicians should perform a clinical examination for goiter and obtain thyroid function tests prior to initiating lithium treatment and every 6-12 months thereafter. The development of lithium-induced hypothyroidism is not an indication to stop lithium. Patients may continue lithium if necessary and receive treatment with levothyroxine. This is particularly important in those with a history of severe mood episodes, such as this patient, who respond preferentially to lithium. (Choice A) The patient's thyroid abnormality should be corrected prior to considering addition of an antidepressant. (Choice C) Thiazide diuretics, nonsteroidal anti-inflammatory drugs (except aspirin), and ACE inhibitors have been associated with increased lithium levels. However, this patient's lithium level is within the therapeutic range and the clinical picture is consistent with hypothyroidism, not lithium toxicity. These drugs are not contraindicated in patients taking lithium, but they do require frequent monitoring of lithium levels. (Choice D) Decreasing the lithium dose may result in a subtherapeutic serum level and increase the patient's risk of relapse. (Choice E) This patient has a history of multiple mood episodes and has been treated with other mood-stabilizing medications in the past, suggesting that lithium may be uniquely effective. In such cases, continuing lithium and supplementing with thyroid hormone is preferred. Educational objective: Symptoms of fatigue and depression in lithium-treated bipolar patients should prompt a workup for hypothyroidism. When lithium-induced hypothyroidism develops, it should be treated with levothyroxine and does not typically require lithium discontinuation. References: Spectrum of lithium induced thyroid abnormalities: a current perspective. (http://www.ncbi.nlm.nih.gov/pubmed/23391071) Female vulnerability for thyroid function abnormality in bipolar disorder: role of lithium treatment. (http://www.ncbi.nlm.nih.gov/pubmed/24330379) Lithium side effects and toxicity: prevalence and management strategies.. (http://www.ncbi.nlm.nih.gov/pubmed/27900734)

Question 16

A 36-year-old woman comes to the office due to type 1 diabetes mellitus.  She was initially diagnosed 20 years ago and is treated with a combination of long- and short-acting insulin analogues.  A month ago, the patient had an episode of severe hypoglycemia with near loss of consciousness that required the administration of a home glucagon kit by her husband.  Since then, she has felt normal.  Review of the patient's continuous glucose-monitoring system shows multiple glucose excursions <50 mg/dL in the past week; however, none of these episodes was associated with tremor, sweating, or altered mental status.  Hemoglobin A1c is 7.8%.  Which of the following interventions is most likely to restore hypoglycemic awareness in this patient?

Accepted Answer

Explanation: 11ec2b69_becc_67f5_8f63_f3ef2536b16a_MD0005_00 Patients with long-standing type 1 diabetes mellitus are at increased risk for insulin-induced hypoglycemia. These patients often have alpha cell failure, leading to reduced glucagon secretion in response to hypoglycemia. In addition, they commonly have a blunted autonomic response to hypoglycemia with less prominent neurogenic symptoms (eg, arousal, tremor, sweating) and therefore reduced hypoglycemic awareness. Hypoglycemic awareness is further reduced following severe hypoglycemic events. Recurrent or severe hypoglycemia reduces epinephrine-induced hepatic glucose release and suppresses the symptoms related to the catecholamine surge, increasing the risk for progressively worse hypoglycemia (ie, hypoglycemia-associated autonomic failure). Management requires strict avoidance of hypoglycemia, which can often restore awareness within 2-3 weeks. Careful timing of insulin administration, close monitoring of blood glucose, and modified carbohydrate ingestion (eg, in relation to physical activity) are necessary. hypoglycemia-associated autonomic failure (Choice A) Beta blockers can blunt hypoglycemia-induced sympathetic symptoms and further reduce hypoglycemic awareness. They increase the risk for severe hypoglycemia and therefore would not be ideal for this patient. (Choice C) Maintaining hemoglobin A1c <7% is recommended for most patients with diabetes mellitus to reduce the progression of microvascular complications (eg, neuropathy, nephropathy). However, this is associated with an increased risk for severe hypoglycemia; this patient's glycemic targets may need to be loosened until she can consistently avoid hypoglycemia. (Choice D) Exercise can induce hypoglycemia in patients on insulin therapy and may necessitate reduced dosing. In addition, high-intensity exercise may reduce hypoglycemic awareness. Although exercise is an important part of diabetes care, this patient's hypoglycemic awareness should be restored through strict avoidance of hypoglycemia before a new exercise regimen is initiated. (Choice E) Weight loss can increase insulin sensitivity and reduce dosing requirements. However, it can also increase the risk of hypoglycemia unless the insulin dose is carefully monitored. Educational objective: Recurrent or severe hypoglycemia in patients with long-standing type 1 diabetes mellitus reduces the autonomic symptoms of hypoglycemia (eg, tremor, arousal), increasing the risk for further severe hypoglycemic episodes. Strict avoidance of hypoglycemia for 2-3 weeks can restore hypoglycemic awareness.

Question 17

A 24-year-old woman has a 2.1-cm nodule in her right thyroid lobe.  She is otherwise healthy and takes no medications.  The patient has no past history of radiation exposure or family history of thyroid disease.  She does not experience pain, difficulty swallowing, or voice changes.  Physical examination is within normal limits.  Laboratory studies show normal T3, T4, and TSH levels.  An ultrasound of the thyroid gland reveals a solid nodule measuring 2.6 x 1.7 x 1.3 cm in the right lobe.  The left lobe appears to be normal in size and echotexture. Further workup of this patient confirms the diagnosis of medullary thyroid cancer.  Serum calcitonin is 300 pg/mL (normal 0-10 pg/mL).  Genetic studies show a mutation in the RET proto-oncogene.  Which of the following is the best next step in the management of this patient?

Accepted Answer

Explanation: 11ec2b69_bed1_bf2e_8f63_f589f3aa9ab5_MD0005_00 Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder caused by germline mutations involving the RET proto-oncogene located on chromosome 10. MEN 2 can be divided into 3 classifications: MEN 2A, MEN 2B, and familial medullary thyroid cancer (FMTC). MEN 2A predisposes to medullary thyroid cancer (MTC), pheochromocytoma (PCC), and hyperparathyroidism (due to parathyroid hyperplasia or multiple adenomas). MEN 2B is not accompanied by hyperparathyroidism but may be associated with marfanoid habitus, mucosal neuromas, and skeletal deformations (eg, kyphoscoliosis, lordosis). FMTC is a subset of MEN 2A associated with MTC only, without PCC or parathyroid disease. All patients with MTC require serum calcitonin and carcinoembryonic antigen, neck ultrasound (evaluation for regional metastases), genetic testing for germline RET mutations, and evaluation for coexisting tumors (hyperparathyroidism, PCCs). PCC is present in approximately 40% of patients with MEN 2, and undiagnosed PCC can cause life-threatening hemodynamic complications during and after thyroid surgery. Plasma-free metanephrines are usually elevated in PCC and confirmed with 24-hour urinary fractionated metanephrines, catecholamines, and abdominal imaging. Once PCC has been ruled out, patients with nonmetastatic MTC may proceed to thyroidectomy for definitive management (Choice B). (Choices C and D) Anticancer drugs and external beam radiation do not play a role in initial management of MTC. Radiotherapy is usually reserved for postsurgery patients with extrathyroidal disease or extensive nodal metastases not amenable to surgical resection. Chemotherapy is considered for patients with progressively metastatic MTC not responsive to surgery or radiotherapy. (Choice E) Radioactive iodine is preferentially taken up by thyroid tissue and is often used following surgery for patients with differentiated thyroid cancer (papillary or follicular) who are at risk for recurrence. Radioactive iodine is not effective for MTC as these cells do not take up iodine. Educational objective: Medullary thyroid cancer (MTC) is part of the multiple endocrine neoplasia type 2 syndromes. All patients with new MTC require serum calcitonin and carcinoembryonic antigen, neck ultrasound (evaluation for regional metastases), genetic testing for germline RET mutations, and evaluation for coexisting tumors (hyperparathyroidism, pheochromocytomas). References: Medullary thyroid cancer: management guidelines of the American Thyroid Association. (http://www.ncbi.nlm.nih.gov/pubmed/19469690)

Question 18

A 20-year-old female is referred to your office by her pediatrician.  The patient has been followed by her pediatrician for idiopathic hypoparathyroidism for the past four years.  She takes vitamin D 50,000 units with 1.5 g of elemental calcium every day.  She denies any symptoms.  The physical examination is unremarkable, including a negative Chvostek's sign.  Her calcium level is 7.8 mg/dL, and phosphorus level is of 5.2 mg/dL.  Her 24-hour urinary calcium is 680 mg.  What is the next best step in the management of this patient?

Accepted Answer

Explanation: Patients with hypoparathyroidism are treated with vitamin D (Calciferol), or its active form, 1,25-dihydroxyvitamin D (calcitriol). Patients with chronic hypoparathyroidism are usually managed by giving them high doses of vitamin D and calcium. Vitamin D is generally preferred over 1,25-dihydroxy vitamin D for chronic management in most patients because it is cheaper and effective. The usual dose of vitamin D varies from 25,000 units to 100,000 units per day. High doses of vitamin D are required in hypoparathyroid patients because of the defective conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D in the kidneys resulting from low PTH levels. The dose of vitamin D and calcium is adjusted to keep the calcium levels between 8.5 and 9 mg/dL. After starting treatment with vitamin D and calcium, majority of the patients will have an increase in their urinary calcium excretion due to low PTH levels (PTH increases renal calcium reabsorption). In patients with borderline low serum calcium and high urinary calcium, as seen in the patient described in the vignette, the addition of a thiazide diuretic will not only decrease the urinary calcium, but also increase serum calcium levels. The addition of a thiazide diuretic is therefore the next best step in the management of this patient. (Choice E) If calcium supplementation is increased in this patient, serum calcium is likely to improve; however, her urinary calcium excretion will also increase. Further increasing the urinary calcium excretion will predispose this patient to nephrocalcinosis, renal stones and renal impairment. (Choice B)Decreasing calcium supplementation will worsen this patient's hypocalcemia. (Choice A)In most patients with hypoparathyroidism, hypocalcemia and hyperphosphatemia can be effectively controlled using vitamin D and calcium supplementation. Calcitriol is used in the primary treatment of few patients. It is very useful in patients who are refractory to vitamin D. Compared to the conventional vitamin, calcitriol has a rapid onset of action that lasts for a shorter time. Due to its rapid onset of effect, it is the preferred drug of choice in the management of acute hypocalcemia during the postoperative period. (Choice D) This patient has a borderline low serum calcium and an elevated 24-hour urinary calcium. Continuing the same treatment is likely to harm this patient. Educational Objective: Understand the long-term management of patients with chronic hypoparathyroidism: in patients with borderline low serum calcium and high urinary calcium, as seen in the patient described in the vignette, the addition of a thiazide diuretic will not only decrease the urinary calcium, but also increase serum calcium levels.

Question 19

A 36-year-old woman comes to the office due to a 6-month history of lethargy and poor sleep. She has non-restorative sleep with frequent awakening throughout the night. The patient has also had a loss of appetite and decreased interest in day-to-day activities. In addition, she has had irregular menses, with infrequent, heavy, painless menstrual bleeding. There is no associated weight change, fever, cough, dyspnea, palpitations, abdominal pain, constipation, cold intolerance, or dry skin. Past medical history is unremarkable, and the patient takes no medications. She has a 10-pack-year smoking history, drinks alcohol socially, and does not use recreational drugs. Family history is positive for Graves disease in a sister and hypertension in her father. On examination, her blood pressure is 136/90 mm Hg, pulse is 78/min, and BMI is 27 kg/m². The thyroid gland is diffusely enlarged and firm on palpation. Cardiopulmonary examination is normal, with no pedal edema. No focal neurological deficits are noted. Laboratory results show TSH of 9 μU/mL (normal 0.35-4.5 μU/mL), free T4 of 1.2 ng/dL (normal 0.8-1.8 ng/dL), and anti-thyroid peroxidase antibody present in high titers. Repeat TSH level is 8.8 μU/mL. Which of the following is the best next step in this patient's care?

Accepted Answer

Explanation: 11ec2b69_becf_0009_8f63_cbb601ad9b11_MD0005_00 This patient has subclinical hypothyroidism associated with irregular menses and symptoms suggestive of depression. Subclinical hypothyroidism is a state of mild thyroid dysfunction characterized by an elevated TSH level in the presence of a normal free thyroxine (T4) level. Subclinical hypothyroidism is often asymptomatic, but it can be associated with a variety of somatic and cognitive symptoms. Patients with subclinical hypothyroidism and a TSH >10 μU/mL or elevated titers of antithyroid peroxidase antibodies have a high likelihood of progression to overt hypothyroidism and are likely to benefit from levothyroxine replacement therapy. Patients with a TSH of 4.5-10 µU/mL and typical symptoms of hypothyroidism or diffuse goiter may also benefit from treatment. In addition, women with ovulatory dysfunction/infertility or who are pregnant or planning to get pregnant should be offered levothyroxine. This patient has a diffuse goiter, symptoms suggestive of depression, and ovulatory dysfunction, along with a positive antithyroid peroxidase antibody titer suggesting early chronic lymphocytic (Hashimoto) thyroiditis. She should therefore be started on levothyroxine therapy. (Choice A) This patient should receive levothyroxine therapy. Patients who have subclinical hypothyroidism with TSH <10μU/mL and any of the additional risk factors described above can be monitored (eg, repeat thyroid function tests every 6-12 months). (Choice B) Conversion of T4 to T3 is regulated by TSH. Patients with primary hypothyroidism can have normal circulating T3 levels despite impaired thyroid function because of increased peripheral conversion due to elevated TSH levels. Serum T3 measurement is therefore of limited utility in hypothyroidism. (Choice C) Both overt and subclinical forms of depression associated with hypothyroidism may improve with treatment of hypothyroidism alone. (Choice D) T3 is the active form of thyroid hormone and is produced primarily by conversion from T4 in peripheral tissues. However, T3 has a very short half-life, and treatment with liothyronine (oral T3 supplement) produces wide fluctuations in blood levels. Therefore, liothyronine supplementation is not recommended for routine use. Educational objective: Subclinical hypothyroidism is characterized by a normal free thyroxine (T4) level with an elevated TSH. Indications for levothyroxine therapy in subclinical hypothyroidism include hypothyroid symptoms, pregnancy, infertility or ovulatory dysfunction, goiter, positive antithyroid antibody titers, and TSH >10 μU/mL. References: Subclinical hypothyroidism: an update for primary care physicians. (http://www.ncbi.nlm.nih.gov/pubmed/19121255)

Question 20

A 42-year-old female complains of occasional nagging midabdominal pain.  She describes the pain as crampy in quality and states that it is relieved by bowel movements.  Sometimes the pain wakes her from sleep.  She denies any associated nausea, vomiting, chest pain, fever or weight loss.  She is otherwise healthy.  Her blood pressure is 130/80 mmHg and her heart rate is 85/min.  Physical examination is essentially unremarkable.  Abdominal CT scan shows a right-sided adrenal mass measuring 2 cm in diameter.  Which of the following is the best next step in managing this patient?

Accepted Answer

Explanation: Based on her history, this patient's abdominal pain is most likely functional, as in irritable bowel syndrome. Still, she has undergone abdominal CT scanning to rule out an organic cause, and this investigation has incidentally revealed an adrenal mass, or "incidentaloma." Incidentally discovered (as part of the work-up for an unrelated problem) adrenal masses are common, present in up to 8% of autopsies and 4% of abdominal CT studies. Although this patient has no symptoms to suggest adrenal pathology, all adrenal masses require workup for hormone hypersecretion or malignancy. In any patient with an adrenal mass, essential laboratory studies include serum electrolytes, dexamethasone suppression testing, and 24-hour urine catecholamine, metanephrine, vanillylmandelic acid and 17-ketosteroid measurement. Surgical excision is recommended for all functional tumors, all malignant tumors (which demonstrate a characteristic heterogenous appearance on imaging), and all tumors greater than 4 cm. All other masses can be managed conservatively with serial abdominal imaging, and removed if they increase in size. (Choice A) Observation and repeat evaluation is indicated for non-functional tumors less than 4 cm in diameter with a benign appearance on CT scan. Functional studies must first be performed before deciding on observation. (Choice B)Fluorodeoxyglucose (FDG) PET scanning can identify tumors with moderate to high proliferative activity as well as other tissues with increased metabolic activity. False-positive and false-negative results are common, thus, this modality is not commonly used in the initial assessment of adrenal masses. (Choice C)17-hydroxyprogesterone is an intermediate in adrenal cortical cortisol and androstenedione production. It is elevated in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase and 11b-hydroxylase deficiency, and depressed in CAH due to 17a-hydroxylase deficiency. An intermediate product, its levels would not be elevated in an incidentally discovered unilateral adrenal mass in an adult. (Choice E)A pituitary MRI would be of little immediate relevance in this patient. The MEN IIa and IIb syndromes include pheochromocytoma but not pituitary adenomas, and MEN I includes pituitary tumors but not adrenal tumors. Educational objective: Before deciding to medically, surgically, or conservatively manage an incidentally detected unilateral adrenal mass, evaluation for hormone production should first be completed. All functional masses, masses with radiographic evidence of malignancy, or masses greater than 4 cm in size should be removed.

Exam 1: Advanced Clinical Medicine