Endocrine Flashcards

Question

Diabetes Mellitus, Type 1: Diagnosis

Answer 1

* The first three criteria should be confirmed by repeat testing (preferably with the same test) without delay, except in the setting of unequivocal hyperglycemia with acute metabolic decompensation.

Answer 2

* The International Expert Committee on Diabetes recommends that an A1c of 6.5% or greater can be used to diagnose DM with a repeat level obtained for confirmation. Confirmatory testing is not needed if a patient has the clinical symptoms of DM or if the random plasma glucose level is greater than 200 mg/dL. Of note, this test cannot be used for diagnosis in the setting of pregnancy, hemoglobinopathy, or other situations with abnormal rates of erythrocyte turnover.

Answer 3

* Another test to assess beta cell function and insulin production in a patient with T1DM is C-peptide level. Proinsulin is cleaved into insulin and C-peptide, the latter being biologically inactive. Therefore, C-peptide levels are found in amounts equal to endogenous insulin. However, exogenous insulin preparations do not include C-peptide. Thus, a patient with residual pancreatic beta cell function will have decreased but nonetheless detectable levels of C-peptide, whereas if no insulin is being produced, the levels of C-peptide will be negligible (normal fasting level = 0.51 to 2.72 ng/mL [0.17 to 0.90 mmol/L]).

Answer 4

*General Measures Refer to Endocrinology – Insulin is the mainstay of therapy with education regarding matching of mealtime insulin dose to carbohydrate intake, premeal blood glucose level, and anticipated activity. – Pre-meal blood glucose goal: 90 to 130 mg/dL – Bedtime/overnight blood glucose levels goal: 90 to 150 mg/dL – Adult A1c goal: <7% (A1c <6.5% reasonable in select individuals); less stringent A1c goals may be appropriate for elderly patients and other special populations – If using a GCM, most individuals should aim for a time in range (70-180 mg/dL) of at least 70% of readings

Answer 5

– Most treated with multiple daily injections (MDI) of prandial insulin and basal insulin, or continuous subcutaneous insulin infusion (CSII). – Flexible intensive insulin therapy is the gold standard. – MDI or CSII have equal efficacy – Total initial dose is 0.2 to 0.4 units/kg/day for insulin-naive patients – ~50% of total dose given as basal insulin, with the rest as bolus insulin. – Diabetes Mellitus, Type 1: Treatment

Answer 6

– A common occurrence in patients with T1DM and occurs for a variety of reasons: excessive exogenous insulin, missed meals or inadequate food intake, excessive exercise, alcohol ingestion, drug interactions, or decreases in liver or kidney function. – Signs and symptoms include diaphoresis, tachycardia, hunger, shakiness, altered mentation (ranging from an inability to concentrate to frank coma), slurred speech, and seizures. – The signs and symptoms exhibited by the patient are highly individual and can vary from mild to severe. – In 2017, the International Hypoglycemia Study Group of the ADA Standards of Medical Care in Diabetes classified a plasma glucose level of less than 54 mg/dL as serious, clinically significant hypoglycemia. – A blood glucose level of 70 mg/dL is considered a threshold level that requires intervention.

Answer 7

– The goal of treatment is to normalize the plasma glucose level promptly. – If the patient is conscious and able to swallow, this is best accomplished by the prompt ingestion of glucose or carbohydrate-containing food with a high glycemic index for rapid absorption. – Pure glucose is the treatment of choice according to the ADA, but any carbohydrate that can increase the blood glucose level can be given. – Blood glucose should be checked 15 minutes after treatment, and additional carbohydrates should be given if the blood glucose remains less than 70 mg/dL. – For severe hypoglycemia in a patient who is unconscious or unable to swallow, 1 mg of glucagon can be given subcutaneously to mobilize hepatic glucose stores.

Answer 8

– American Diabetes Association (ADA)diet: www.diabetes.org/food-and-fitness/food/ – Carbohydrate counting using insulin-to-carbohydrate ratio with all meals and snacks allows patient flexibility in eating. – The following formulas can be used to determine the total number of kilocalories needed to maintain current weight: – For males: 66 + 13.7 (weight in kg) + 5 (height in cm) – 6.8 (age) – For females: 65 + 9.6 (weight in kg) + 1.7 (height in cm) – 4.7 (age) – Multiply the result by 1.2 for a fairly active person and by up to 1.5 for an ill person, given increased caloric requirements.

Answer 9

– Check blood glucose before, every 30 to 60 minutes during, and after physical activity. – Avoid physical activity if fasting glucose is more than 250 mg/dL and ketosis is present or if the glucose level is more than 300 mg/dL, regardless of whether ketosis is present. – Consume additional carbohydrates if the glucose level is less than 100 mg/dL and as needed to avoid hypoglycemia. – Identify when changes in insulin dose or food intake are necessary.

Answer 10

Diabetic Ketoacidosis

Answer 11

* T2DM is characterized by the abnormal secretion of insulin, resistance to the action of insulin in the target tissues, and/or an inadequate response at the level of the insulin receptor. * T2DM is associated with two physiological abnormalities: insulin resistance and impaired insulin secretion by the beta islet cells of the pancreas. * Initially, as insulin resistance increases, insulin levels begin to rise but the glucose level remains normal, resulting in a state of hyperinsulinemia. * Insulin resistance worsens in conjunction with hyperinsulinemia, eventually resulting in the development of fasting hyperglycemia, because hepatic gluconeogenesis increases due to glucagon being produced by pancreatic alpha cells in response to the hyperinsulinemia. * As hyperglycemia is ultimately toxic to pancreatic beta cells, over time this results in relative hypoinsulinemia, which ultimately necessitates exogenous insulin in cases of advanced T2DM.

Answer 12

Family history (first-degree relative, Body mass index greater than 25 kg/m2 (lower for Asian Americans), Older than 45 years, Impaired fasting glucose or A1c greater than 5.7%, History of gestational diabetes, Hypertension, Hyperlipidemia, Females with polycystic ovarian syndrome, Race/ethnicity: African American, Latino, Native American, Asian American, Pacific Islander

Answer 13

– Usually insidious, only a minority of patients are initially symptomatic. – Polyuria, polydipsia, polyphagia, weight loss, fatigue, blurry vision, neuropathy (numbness/tingling), pruritus, and frequent infections (especially candida).

Answer 14

– Usually insidious, only a minority of patients are initially symptomatic. – Polyuria, polydipsia, polyphagia, weight loss, fatigue, blurry vision, neuropathy (numbness/tingling), pruritus, and frequent infections (especially candida).

Answer 15

– BMI, waist circumference, funduscopic exam, oral exam, cardiopulmonary exam, abdominal exam for hepatomegaly, focused neurologic exam, and diabetic foot exam. – In severe cases, patients may present with HHS, in which profound dehydration results from prolonged hyperglycemia. Formerly known as hyperosmolar hyperglycemic nonketotic coma, HHS is associated with a high mortality rate and is typically seen in older diabetic adults who have developed an infection, such as pneumonia or other illness.

Answer 16

a high mortality rate and is typically seen in older diabetic adults who have developed an infection, such as pneumonia or other illness.

Answer 17

– Glycosylated hemoglobin (A1c) of 6.5% or higher – Symptoms of diabetes (e.g., polyuria, polydipsia, weight loss) plus a random plasma glucose level of 200 mg/dL or higher – Fasting plasma glucose level of 126 mg/dL or higher (after 8 hours of no caloric intake) – Two-hour plasma glucose level of 200 mg/dL or higher during an oral glucose tolerance test (OGTT) with a 75-g glucose load

Answer 18

* *In T2DM, the C-peptide level is normal or elevated, but it is decreased in T1DM.* * Diabetes Mellitus, Type 2: Treatment * Tight glucose control prevents long-term microvascular complications, but benefits on macrovascular outcomes are less apparent. * Use patient-centered approach. * Dietary modification, regular exercise, control of cardiovascular risk factors (blood pressure and lipids)

Answer 19

– A1c <7.0: long life expectancy, no cardiovascular disease (CVD), short duration of DM, no history of hypoglycemia – A1c <8.0%: limited life expectancy, advanced micro- or macrovascular complications, extensive comorbidities, history of severe hypoglycemia or long-standing DM where lower goal is difficult to attain.

Answer 20

* Always consider side effect profile, CV benefit, renal benefit, and cost. * Diabetes Mellitus, Type 2: Treatment * First Line

Answer 21

– Reduces hepatic gluconeogenesis and multiple other mechanisms of action – Preferred due to high efficacy in lowering glucose, good safety profile, low hypoglycemia risk, low cost, and weight loss – Avoid in severe acute illnesses (e.g., liver disease, cardiogenic shock, pancreatitis, hypoxia) and for surgery due to risk of lactic acidosis. – Hold metformin when getting contrast dye due to risk of kidney injury. – Caution with acute heart failure, alcohol abuse, elderly; associated with vitamin B12 deficiency – Severe diarrhea in 10% of patients, requiring switch to another agent – In CKD for eGFR 30 to 45 reduce dose to ≤1,000 mg, stop if eGFR <30.

Answer 22

Second Line – If HbA1c is not at goal, add second/third agent. – If patient has CAD, heart failure, or CKD, consider drugs that improve outcomes with these conditions. – Consider drug-specific side effects such as weight gain or hypoglycemia. – Cost of drug is an important consideration. – GLP-1 RA – Semaglutide injection (Ozempic) and oral (Rybelsus) – Reduced risk of atherosclerotic CVD events – Low hypoglycemia risk, promotes weight loss. – Small risk of acute pancreatitis. Use cautiously in CKD ≥ stage 4. May exacerbate gastroparesis. – Contraindicated in personal/family history of medullary thyroid cancer or multiple endocrine neoplasia (MEN) type 2 – GLP-1/GIP RA – tirzepatide (Mounjaro) – clinically meaningful A1c reduction compared to placebo, superior A1c/weight reductions when compared to semaglutide and titrated insulin degludec

Answer 23

Hyperosmolar Hyperglycemic Syndrome

Answer 24

* Description – Hyperthyroidism or thyrotoxicosis is due to thyroid hormone excess. The former describes excess from the thyroid gland, whereas the latter can also be produced from another source. – Graves disease (GD) is the most common cause with autoantibodies directed at the thyroid-stimulating hormone (TSH) receptors. – Toxic multinodular goiter (TMNG) is the most common cause of hyperthyroidism in patients >65 years of age; often an insidious onset, frequent in iodine-deficient areas. 60% TSH receptor gene abnormality; 40% unknown – Drug-induced thyroiditis: amiodarone, lithium

Answer 25

– Positive family history, especially in maternal relatives – Other autoimmune disorders

Answer 26

– TSH, free T4, total T4, and T3 will establish the hyperthyroid diagnosis – 95% have suppressed TSH and elevated free T4. – T3: is elevated in T3 toxicosis or amiodarone-induced thyrotoxicosis (AIT) – Presence of TSH receptor antibody or thyroid-stimulating immunoglobulin is diagnostic of GD – Free thyroxine index (FTI): calculated from T4 and thyroid hormone–binding ratio; corrects for misleading results caused by pregnancy and estrogens – Inappropriately normal or elevated TSH with high T4 suspicious for pituitary tumor or thyroid hormone resistance

Answer 27

* GD or TMNG can be managed by either antithyroid medication, radioactive iodine therapy (RAIT), or thyroidectomy. * Medication – Antithyroid drugs: Methimazole and propylthiouracil are thioamides that inhibit iodine oxidation, organification, and iodotyrosine coupling. Propylthiouracil can block peripheral conversion of T4 to active T3. Both can be used as primary treatment for GD and prior to RAIT or surgery – The most serious side effects are hepatitis (0.1–0.2%), vasculitis, and agranulocytosis; baseline CBC recommended – Methimazole (preferred): adults – Propylthiouracil: adults (preferred in thyroid storm and 1st trimester of pregnancy) – β-Adrenergic blocker: Propranolol in high doses (>160 mg/day) inhibits T3 activation by up to 30%. Atenolol, metoprolol, and nadolol can be used and are also useful in relieving palpitations and in slowing the heart rate in patients with sinus tachycardia. – Glucocorticoids: reduce the conversion of active T4 to the more active T3 – Cholestyramine: anion exchange resin that decreases thyroid hormone reabsorption in the enterohepatic circulation – Hyperthyroidism: Ongoing Care * Refer to Endocrinology * Refer to Ophthalmology for exophthalmos

Answer 28

– It may take 4 to 6 weeks after starting medication to notice an improvement in symptoms because of the amount of stored hormone in the thyroid gland. – Daily weights and eat sufficient calories to prevent weight loss – Patients need written instructions to monitor for the signs and symptoms of thyroid storm, as well as signs of hypothyroidism once treatment is initiated. – Persons receiving radioactive iodine therapy should avoid contact with infants, children, and pregnant females for 7 days after ingestion. – Monitor for signs of depression/anxiety as hormone levels change

Answer 29

– It is a disease of various causes that lead to inadequate amounts of thyroid hormone being produced and/or secreted, resulting in a slowing of many bodily functions and metabolic processes. The typical course of the disease is gradual loss of thyroid function leading to thyroid failure.

Answer 30

– Personal or family history of autoimmune diseases – External head or neck irradiation; radioiodine therapy or thyroid surgery – Abnormal thyroid examination, presence of goiter and/or TPO Ab positivity – Treatment with amiodarone, lithium, interferon-α – Down syndrome or Turner syndrome – Hypothyroidism: Diagnosis

Answer 31

– Screening test: Order TSH levels; serum free T4 should be obtained only if TSH is abnormal and not as part of initial screening test. – Primary hypothyroidism – Elevated TSH – Decreased serum free T4

Answer 32

– Elevated serum TSH – Normal serum free T4 – Note: Serum free triiodothyronine (T3) or total T3 should not be done to diagnose hypothyroidism

Answer 33

– Assess free T4 or free T4 index – Decreased serum free T4 – Antithyroid antibodies absent – TRH stimulation test, especially if free T4 and/or TSH is low-normal and patient has hypothalamopituitary pathology – Imaging of the hypothalamus and pituitary gland – Hypothyroidism: Diagnosis

Answer 34

– Antithyroid antibodies (primarily thyroid peroxidase antibodies and antithyroglobulin antibodies) may define the cause of primary hypothyroidism but are not necessary in all settings

Answer 35

– Drugs that decrease TSH: – Thyroid supplement, glucocorticoids, dopamine agonists, octreotide

Answer 36

– Drugs that increase TSH: – Phenytoin, amiodarone, dopamine antagonist (metoclopramide/domperidone), oral cholecystographic dyes (sodium ipodate), or estrogen or androgen in excess

Answer 37

– Drugs that increase free T4: – Heparin, high intake of biotin

Answer 38

– Levothyroxine (Synthroid, Levothyroid) – 1.5 to 1.8 μg/kg/day (use ideal body weight); titrate by 12.5 to 25 μg/day every 4 to 8 weeks until TSH in normal range – Use caution when changing between capsule, tablet, and liquid because formulations may be absorbed differently – Elderly patients may require 2/3 of dose used in young adults because clearance is decreased – Levothyroxine should be taken on an empty stomach, ideally an hour before breakfast – Medications that interfere with its absorption should be taken 4 hours after the T4 dose; these include ferrous sulfate, proton pump inhibitors, calcium carbonate, bile acid sequestrants

Answer 39

Hypothyroidism: Ongoing Care * Monitor TSH and free T4 every 4 to 8 weeks after initiating treatment or after change in dose. Once stabilized, periodic TSH level should be done after 6 months and then at 12-month intervals or more frequently if clinically indicated. In central hypothyroidism, TSH is unreliable; must monitor free T4. * Monitor cardiac function in older patients * Monitor for Iatrogenic thyrotoxicosis; It can lead to AFib and osteoporosis. * Educate on signs of hypo-hyperthyroid and on Hypersensitivity to opiates * Referral to Endocrinology – Women planning conception – Presence of goiter, nodule, or other structural changes in the thyroid gland – Presence of adrenal or pituitary disorders

Answer 40

* Treatment for subclinical hypothyroidism has varied recommendations. * The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating subclinical disease when antithyroid antibodies are present, when evidence of atherosclerotic cardiovascular disease exists, when heart failure exists, or if the patient is symptomatic at the respective TSH level. * Some patients with subclinical hypothyroidism feel better when treated with levothyroxine. * Medication therapy has potentially dangerous adverse effects but may improve subtle abnormalities, prevent goitrous growth, and prevent the development of frank hypothyroidism. * Therapy is advisable especially if thyroid autoantibodies are positive, because overt hypothyroidism frequently develops in these patients. * If the decision is made not to treat these patients, they should be evaluated at 6- to 12-month intervals for evidence of more severe clinical disease or biological loss of thyroid function as reflected in worsening laboratory indices. * A lower dose (0.5 to 1.0 μg/kg) of levothyroxine may be given for the treatment of subclinical hypothyroidism.

Answer 41

– A serious, progressive, and chronic disease characterized by excess adipose tissue to the extent that health may be impaired, typically quantified in adults by body mass index (BMI) ([kg] / [m2]), ≥30 kg/m2 – Overweight: BMI 25 to 29.9 kg/m2 – Obesity is categorized into three classes: – Class 1 obesity is BMI 30 to 34.9 kg/m2 – Class 2 obesity is BMI 35 to 39.9 kg/m2 – Class 3 obesity (also called severe obesity) is BMI ≥40 kg/m2 – Obesity is preventable and associated with negative health outcomes. – Abdominal obesity increases the risk of morbidity and mortality.

Answer 42

– Parental obesity – Sedentary lifestyle and lack of regular physical activity – Poor nutrition, especially consumption of calorie-dense food, and limited access to fresh produce/foods – Stress and mental illness

Answer 43

– Multifactorial process where genetic, environmental, behavioral, and psychosocial issues lead to an imbalance between energy intake and expenditure. – Adipocytes (fat cells) produce peptides called adiponectin and leptin. Adiponectin improves insulin sensitivity, and the absence of leptin has been associated with severe obesity. – After obesity has developed, an individual's neuronal signaling is altered to decrease satiety, and adipocyte hypertrophy leads to both local and systemic inflammation.

Answer 44

– Encourage regular physical activity with a goal of at least 150 minutes of moderate-intensity activity per week (e.g., 30 minutes of exercise, 5 days per week), and a well-balanced diet with appropriate portion sizes. – Avoid calorie-dense and nutrient-poor foods such as sugar-sweetened beverages and processed foods.

Answer 45

* Coronary heart disease/congestive heart failure * Hypertension * Dyslipidemia/hyperlipidemia * Type 2 diabetes mellitus/insulin resistance * Metabolic syndrome * Sleep apnea * Restrictive lung disease * Asthma

Answer 46

– Diet and exercise habits – Reported readiness to change lifestyle, and previous attempts at weight loss – Life stressors, social support, and resources

Answer 47

– Physical Activity, Vital Signs – Assess if patient achieves minimum goal of 150 minutes of moderate-intensity physical activity per week – Waist circumference: – May be more important than BMI to assess obesity-associated health risks, especially in the elderly (sarcopenia) – Recommend measuring in patients with BMI 25-35 kg/m2 – Measure at the level of the umbilicus. Elevated: – Male: >40 inches (102 cm) – Female: >35 inches (88 cm) – Common abnormal findings: large neck habitus, acanthosis nigricans, striae

Answer 48

– Screen for underlying physiologic causes as well as associated comorbid conditions – Fasting blood glucose, A1C – Lipid Panel – Thyroid function tests – CMP (non-alcoholic fatty liver disease) – Uric Acid – Vitamin D – General laboratory tests including a complete blood count, urinalysis, and urinary microalbumin – An electrocardiogram should also be obtained to assess cardiac health. – Provider’s Guide: Caring for Patients with Obesity

Answer 49

– Assess: – Motivation to lose weight and patient-specific goals of therapy – Nutritional intake and physical activity habits – Goal: achieve and sustain loss of at least ≥5% of body weight – Weight loss is curvilinear with rapid weight loss at first, then slows until plateau – USPSTF recommendation: “Encourage clinicians to promote behavioral interventions as the primary focus of the effective interventions for weight loss in adults.” – USPSTF found that pharmacotherapy combined with behavioral interventions was associated with greater weight loss and maintenance over 12-18 months than behavioral treatment alone. – Treat obesity-related comorbidities * Guidelines suggest at least 3-6 months of nonpharmacologic treatment with comprehensive lifestyle intervention alone prior to starting medications

Answer 50

* Consider pharmacotherapy in patients with a history of failure to achieve clinically meaningful weight loss (≥5% total body weight) and to sustain lost weight in patients who meet the following criteria: – BMI ≥30 – BMI ≥27 + comorbidities (e.g., CAD, diabetes, sleep apnea, HTN, hyperlipidemia)

Answer 51

– The most common side effects are GI related (nausea, vomiting, diarrhea, abdominal pain), unless otherwise specified. – Injectables – GLP-1 agonist – Liraglutide (Saxenda, Victoza) – Semaglutide (Ozempic, Rybelsus, Wegovy)

Answer 52

Medication cont. – Oral – Phentermine/topiramate (Qysmia)—likely most effective oral medication available – Phentermine reduces appetite through increasing norepinephrine in the hypothalamus, and topiramate reduces appetite through its effect on GABA receptors. Schedule IV medication. – Adverse effects: misuse potential, tachycardia, mood disorders, and dry mouth – Orlistat (Xenical) – Inhibitor of pancreatic lipase that reduces intestinal absorption of fat and increases excretion. FDA approved for ≥12 years old – Adverse effects: GI side effects (cramps, flatus, fecal incontinence, oily spotting) often not tolerated. Should be taken with vitamin supplements because of slight decrease in fat-soluble vitamins (A, D, E, and K) – Naltrexone /bupropion (Contrave) – Naltrexone is an opioid antagonist that blocks effects of β-endorphins to reduce food intake. Bupropion reduces food intake by acting on adrenergic and dopaminergic receptors in the hypothalamus. – Adverse effects: increased blood pressure, dry mouth, headache, insomnia – Obesity: Treatment

Answer 53

– Results in additional 11.5 kg weight loss over 1 year in addition to dietary intervention alone – Aerobic vs. resistance or high intensity vs. low intensity does not seem to affect overall weight loss – Dose-response relationship between duration of physical activity and weight loss, although still some inter-individual variability – Should be individualized to patient's goals, physical capacity, exercise history, motivation, and overall health status

Answer 54

– Components: 1) prescription of a moderately reduced-calorie diet, 2) program of increased physical activity, 3) behavioral strategies to facilitate adherence to diet and activity recommendations – Most effective in-person with high intensity (≥14 sessions in 6 months) by a trained interventionist

Answer 55

– A referral for bariatric surgery is considered when other treatments have failed, BMI ≥35 + comorbidities, or BMI ≥40 – Associated with significant improvement in diabetes, sleep apnea, quality of life, depression, pain, and physical function – Obesity: Ongoing Care

Answer 56

– Long-term studies suggest net calorie reduction (~500 kcal/day) with a diet that a patient can adhere to is the best. Goal for women: 1200-1500 kcal/d, men: 1500-1800 kcal/d. – A reduction of 500 kcal/day can result in ~1 lb (0.45 kg) weight loss per week – Very low-calorie diet (200 to 800 kcal/day) – Produced significantly greater short-term weight loss but had similar long-term weight loss compared to low-calorie diets. Requires medical supervision – Mediterranean – Primarily plant-based foods, olive oil, nuts, legumes, whole grain, fruits, and vegetables. Fish and poultry multiple times per week – Meta-analysis showed decrease in bodyweight, BMI, Hemoglobin A1c, fasting glucose, and cardiovascular disease risk – Balanced-nutrient, moderate calorie – Usually 1200-1800 kcal/d; e.g., DASH diet – Based on MyPyramid food guide with emphasis on low saturated fat and ample fruits, vegetables, and fiber – Obesity: Ongoing Care * Continue to discuss weight, lifestyle modifications, and address both current and new goals. * A new treatment plan should be implemented if no clinical meaningful weight loss after 3-4 months.

Answer 57

– American Medical Society for Sports Medicine (AMSSM) website for Exercise prescriptions: https://www.sportsmedtoday.com/exercise-prescription-va-156.htm – Dietary guidelines and how to build a healthy eating routine: https://health.gov/sites/default/files/2021-08/DGA-FactSheet-2021-03-26-compressed.pdf

Answer 58

– Metabolic syndrome is a constellation of risk factors including hypertension, hyperlipidemia, insulin resistance, and overweight/obesity that significantly increases an individual’s risk of cardiovascular disease and diabetes mellitus. – The term metabolic syndrome has been imprecisely defined, the primary care practitioner should evaluate and treat all CVD risk factors without regard to whether a patient meets the criteria for diagnosis of metabolic syndrome. – Clinicians need to be cognizant of new information pertaining to this syndrome because definitions change rapidly. – The American Diabetes Association has published a statement with multiple professional societies addressing metabolic syndrome, and the Endocrine Society has a practice guideline stressing the importance of recognizing these at-risk patients.

Answer 59

– Testosterone (T) is the principle circulating androgen in males. Testosterone deficiency (TD) is characterized by low levels of T in addition to signs and symptoms. – No universally accepted threshold of T concentration to distinguish eugonadal from hypogonadal men, but the Federal Drug Administration (FDA) definition is T <300 ng/dL. – T levels correlate with overall health and may be associated with sexual dysfunction.

Answer 60

– Hypothalamus produces GnRH, which stimulates pituitary to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH). LH stimulates Leydig cells to produce T. Leydig cells are responsible for 90% of the body's T. – Primary hypogonadism: testes produce insufficient amount of T; FSH/LH levels are elevated. – Secondary hypogonadism: low T from inadequate production of LH

Answer 61

– Obesity, diabetes, COPD, depression, thyroid disorders, malnutrition, alcohol, stress – Chronic infections, inflammatory states, narcotic use – Undescended testicles, varicocele – Trauma, cancer, testicular radiation, chemotherapy, disorders of the pituitary and/or hypothalamus – Testosterone Deficiency: Diagnosis

Answer 62

– Congenital and developmental abnormalities – Infertility, loss of libido, erectile dysfunction – Depression, fatigue, difficulty with concentration – Decreased muscle strength, energy level – Increase in body fat, development of diabetes – Bone fractures from relatively minor trauma – Testicular trauma, infection, radio- or chemotherapy – Decrease in testicle size or consistency – Headaches or vision changes – Medications, narcotic use

Answer 63

– Decreased muscular development, visceral fat distribution – Presence of gynecomastia – Small and/or soft testicles – Digital rectal exam – International Prostate Symptom Score (IPSS) Calculator: International Prostate Symptom Score (IPSS) – Testosterone Deficiency: Diagnosis

Answer 64

– Morning T level is initial test. If initial morning T is low, and confirmed on repeat test, further evaluation is appropriate – Evaluation should include LH and FSH to differentiate between primary versus secondary hypogonadism. – Consider estradiol and prolactin, especially if LH is low, or if breast symptoms and gynecomastia. – If primary hypogonadism of unknown origin and physical exam reveals severe testis atrophy, consider obtaining karyotype (Klinefelter 1:500 to 1,000 risk) – Refer to Endocrinology and Genetics. – If secondary hypogonadism, consider prolactin, iron saturation, pituitary function testing, and/or MRI.

Answer 65

* Testosterone therapy (TT) recommended for symptomatic men (e.g., low libido and/or erectile dysfunction, low energy level, constitutional symptoms) with low T levels ≤300 ng/dL obtained in the morning; not recommended for older men with low T levels in absence of signs or symptom.

Answer 66

– breast or prostate cancer – palpable prostate nodules or induration – untreated obstructive sleep apnea – severe lower urinary tract symptoms with an International Prostate Symptom Score of greater than 19 – New York Heart Association class III or IV heart failure

Answer 67

– Hemoglobin and hematocrit (to determine risk of polycythemia) – Prostate-specific antigen (PSA) in men >40 years of age (to exclude prostate cancer diagnosis) – Estradiol in men with breast symptoms or gynecomastia – Testosterone Deficiency: Treatment – Topical gels/solutions: most common – Mimics normal daily circadian rhythm – Good absorption, 15–20% are non-responders Testosterone pellets (Testopel) – Minor office procedure – Long-acting formulation, 3 to 4 months – 1–2% risk of infection or pellet extrusion – Transdermal patch (Androderm) – Achieves less robust levels – High incidence of skin irritation

Answer 68

– Testosterone enanthate (Xyosted) SC weekly injection – Boxed warning for increased blood pressure – Testosterone cypionate (IM every 1–3 weeks) – Starting dose: 100 mg/week or 200 mg/2 weeks – Testosterone undecanoate (IM every 8–12 weeks) – Small risk of oil embolism, needs observation in office for 30 minutes postinjection

Answer 69

* Patient Monitoring – 3 to 6 months after treatment initiation and then every 6–12 months – Adjust dosing to achieve a total T in the middle tertile of the normal reference range. – Measure hematocrit at baseline, at 3 to 6 months, and then annually. – Stop treatment 3 to 6 months after starting in patients who experience normalization of T but fail to achieve symptom improvement. – Bone mineral density after 1 to 2 years of therapy in men with osteoporosis – Prostate exam every 6 to 12 months

Answer 70

– Lifestyle changes and weight loss may raise testosterone levels without need for T replacement .

Answer 71

– TD can be chronic and may need lifelong therapy. – T replacement comes with many risks, and it is very important to regularly monitor outcomes. – Women and children must not be allowed to come in contact with T products. – Hyperparathyroidism: Basics

Answer 72

– Excess production of parathyroid hormone (PTH)

Answer 73

– PTH is synthesized by the four parathyroid glands, which are located behind the thyroid gland, and mostly regulated by calcium levels. – PTH releases calcium from bone by osteoclastic stimulation (increasing bone resorption). – PTH increases reabsorption of calcium in the distal tubules of the kidneys. – PTH increases phosphorus excretion by decreasing reabsorption in the proximal tubules of the kidneys. – PTH stimulates the conversion of 25-hydroxycholecalciferol (25[OH]D) to 1,25-dihydroxycholecalciferol (1,25[OH]2D or active vitamin D) in the kidneys

Answer 74

intrinsic parathyroid gland dysfunction resulting in excessive secretion of PTH with a lack of response to feedback inhibition by elevated calcium

Answer 75

appropriate increased secretion of PTH in response to potential hypocalcemia and/or hyperphosphatemia. This is can be caused by vitamin D deficiency, kidney dysfunction, decreased calcium intake, decreased calcium absorption, and/or phosphate loading.

Answer 76

autonomous hyperfunction of the parathyroid gland in the setting of long-standing secondary HPT

Answer 77

– Chronic kidney disease, increasing age, poor nutrition, radiation, and/or family history

Answer 78

– Almost 80% of patients are asymptomatic. – Kidney stones (15–20%) – Osteitis fibrosa cystica (<5%) characterized by subperiosteal resorption of phalanges, tapering of distal clavicles, bone cysts, brown tumors of long bones, and “salt and pepper” appearance of the skull – Symptoms due to hypercalcemia like mental fogginess, memory impairment, polyuria, polydipsia, constipation, nausea, anorexia, bone pain, decreased concentration, altered mental status, fatigue, and muscle weakness

Answer 79

– Limited usefulness; 70–80% of patients have no obvious symptoms or signs of disease

Answer 80

* Initial Tests – Often detected by incidental hypercalcemia on routine labs – Calculate corrected calcium: [serum calcium in mg/dL + 0.8 × (4 − patient’s albumin in g/dL)]. Some patients will have mild hypercalcemia for years, and it won’t be detected as the uncorrected calcium is normal. – If hypercalcemia is confirmed, follow with intact PTH level. – PTH-dependent: High or (abnormally) normal PTH suggests primary HPT. – PTH-independent: Undetectable or low PTH suggests PTH-independent hypercalcemia. – Other findings may include low serum phosphate and high 24-hour urine calcium excretion. – In secondary HPT, an elevated phosphorus suggests chronic renal failure; a low phosphorus suggests another cause, commonly 25(OH)D deficiency. Both are common causes of elevated PTH levels while having normal corrected calcium levels

Answer 81

– A 24-hour urine calcium concentration to creatinine clearance ratio >0.02 suggests primary HPT; a ratio <0.01 may be normal or indicate FHH; an important finding because FHH does not require surgery. – Routine measurement of 25(OH)D levels is recommended in all patients with primary HPT. In case of vitamin D deficiency (<20 ng/mL or <50 nmol/L), defer management decisions until levels are maintained >20 ng/mL (50 nmol/L).

Answer 82

– Serial measurements of serum calcium, creatinine, and vitamin D – Bone density scan every 1 to 2 years

Answer 83

– In the presence of hypercalciuria or elevated 1,25(OH)2D levels, dietary calcium restriction is recommended. Otherwise, daily calcium intake should be maintained at up to 1,000 mg. – Restrict dietary phosphate in secondary HPT.

Answer 84

Operative management is curative; For those awaiting or unable to have surgery medications are available. Refer to Endocrinology.

Answer 85

Treatment is often aimed at underlying etiology

Answer 86

Medical treatment is not curative and generally not indicated

Answer 87

– Deficient or absent secretion of parathyroid hormone (PTH), a major hormone regulator of serum calcium and phosphorus levels in the body

Answer 88

– Reduced or absent PTH action results in hypocalcemia, hyperphosphatemia, and hypercalciuria

Answer 89

– Surgical: removal or damage to parathyroid glands or their blood supply/enervation during neck surgery for thyroidectomy/parathyroidectomy, or neck surgery for head and neck cancers – Autoimmune: isolated or combined with other endocrine deficiencies in polyglandular autoimmune (PGA) syndrome – Functional hypoparathyroidism: may result from hypomagnesemia or hypermagnesemia because magnesium is crucial for PTH secretion and activation of the PTH receptor. – Congenital – Infiltrative: metastatic carcinoma, hemochromatosis (iron), Wilson disease (copper), granulomas

Answer 90

– Often asymptomatic; ask about previous neck trauma or surgery or irradiation, family history of hypocalcemia, or presence of other autoimmune endocrinopathies. – Cardinal clinical feature: neuromuscular hyperexcitability from low calcium – Also may include: fatigue, circumoral or distal extremity paresthesias, muscle spasm, seizures, neuropsychiatric

Answer 91

– Chvostek sign: ipsilateral twitching of the upper lip on tapping the facial nerve on the cheek. – Trousseau sign: painful carpal spasm after 3-minute occlusion of brachial artery with BP cuff. BP cuff inflation to above systolic BP for 3 minutes leads to carpal spasm (flexion of metacarpophalangeal [MCP] joints, extension of interphalangeal [IP] joints, adduction of fingers and thumb). – Tetany, laryngo- or bronchospasm, cardiac arrhythmias, refractory heart failure, dyspnea, edema – Dry, coarse, puffy hair; brittle nails – Loss of deep tendon reflexes – Dysrhythmias (secondary hypocalcemia) – Cataracts or ectopic calcifications – Tooth enamel defects – Vitiligo

Answer 92

* Initial Tests – Calcium: low ionized and total (Correct serum calcium level for albumin.) – Corrected serum calcium = total serum calcium + 0.8 (4 − serum albumin) – Phosphorus: high – Intact or “whole” PTH: low; distinguish from pseudohypoparathyroidism or secondary causes – Magnesium: low or normal – BUN, creatinine: Monitor renal function, especially in the elderly. – 25-OH vitamin D level: Vitamin D deficiency can worsen hypoparathyroidism. – Urinary calcium: normal or high

Answer 93

– ECG: prolongation of ST and QTc intervals, nonspecific repolarization changes, dysrhythmias – Urine calcium: Creatinine ratio (normal 0.1 to 0.2) may be low before treatment but should be monitored to prevent stones due to hypercalciuria. – Hungry bone syndrome (transient hypoparathyroidism after parathyroid surgery) – Hypocalcemia due to hungry bone syndrome may persist despite recovery of PTH secretion from the remaining normal glands. Thus, serum PTH concentrations may be low, normal, or even elevated. – Osteoblastic metastasis of prostate, breast, or lung cancer; consider appropriate imaging.

Answer 94

* Hypoparathyroid with severe symptoms (tetany, seizures, cardiac failure, laryngospasm, bronchospasm) requires hospitalization with IV calcium replacement and continuous ECG monitoring. * Oral calcium carbonate: preferred due to high elemental calcium concentration; take with meals and stop PPI for better absorption. * Oral calcium citrate: preferred for patients on PPI therapy and those with constipation on calcium carbonate * Calcitriol (vitamin D 1, 25-dihydroxycholecalciferol): preferred form of vitamin D replacement; start at 0.25 μg/day; doses 0.5 to 2.0 μg/day are usually required. * For hypercalciuria, consider a thiazide diuretic. * For phosphate level well above normal (>6.5 mg/dL), use low phosphate diet or phosphate binder. * Refer to Endocrinology; Refer to nephrologist for renal impairment or recurrent stones; Refer to ophthalmologist for eye involvement

Answer 95

– Goal is a total corrected serum calcium level in low normal range (8.0 to 8.5 mg/dL). If calcium <8.0 mg/dL, then treat even if asymptomatic. – Outpatient measurement of serum calcium, phosphate, magnesium, and creatinine weekly to monthly during initial management; for changes in medication, check weekly or every other week; when stable, measure every 6 months. – 24-hour urine for calcium and Cr secretion yearly – If symptoms of renal stone disease or increasing Cr, get renal imaging every 5 years. – Annual slit-lamp and ophthalmologic evaluations are recommended. – DEXA scan: standard monitoring recommended

Answer 96

* Vitamin D is a hormone and a vitamin. * Cholecalciferol (D3) is synthesized in the skin by exposure to ultraviolet B (UV-B) radiation. Ergocalciferol (D2) and D3 are present in foods. * D2 and D3 are hydroxylated in the liver to 25 vitamin D (calcidiol), the major circulating form. * Calcidiol is further hydroxylated in the kidney to the active metabolite 1,25 vitamin D (calcitriol). * Hypocalcemia stimulates parathyroid hormone (PTH) secretion, which prompts increased conversion of 25 vitamin D to 1,25 vitamin D. * Vitamin D deficiency is associated with risk of myocardial infarction (MI) and all-cause mortality.

Answer 97

– Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish); many foods are fortified with vitamins D2 and D3. – Recommended minimum daily requirement is 600 IU/day from age 1 to 70 years and 800 IU/day for those aged >70 years. Up to 4,000 IU/day is safe in healthy adults without risk of toxicity. – For ages 51 to 70 years, minimally recommended supplementation is 800 IU/day to prevent nonvertebral fractures.

Answer 98

– Inadequate sun exposure; Latitudes higher than 38 degrees – Female; elderly; obesity; low socioeconomic status; dark skin – Institutionalized – Depression – Medications (phenobarbital, phenytoin) – Gastric bypass surgery/malabsorption syndromes

Answer 99

– 25-OH vitamin D (most sensitive measure of vitamin D status) – IOM: <20 ng/mL – Endocrine Society, National Osteoporosis Foundation (NOF), International Osteoporosis Foundation (IOF), and American Geriatrics Society (AGS) suggest a minimum level of 30 ng/mL.

Answer 100

* Vitamin D sufficient (25-OH vitamin D ≥20 ng/mL) – Vitamin D 800 to 2,000 IU/day D2/D3 – D3 (animal derived) may be slightly more effective than D2 (plant derived). – Calcium supplementation: unclear benefit and may increase some CHD risk in patients; no supplementation currently required (see below) – * Vitamin D deficiency (25-OH vitamin D <20 ng/mL) – D2 50,000 IU/week for 8 to 12 weeks, followed by 1,000 to 2,000 IU/day of vitamin D3 – * All-cause mortality: Cochrane Systematic Review found vitamin D supplementation lowers all-cause mortality. Recent long-term data shows treatment to 25 vitamin D levels >30 ng/mL lowered both MI and all-cause mortality risk.

Answer 101

– Dietary intake of ~700 mg/day leads to best outcomes; higher doses did NOT decrease risk of osteoporotic fractures. – Dietary calcium may be more beneficial than calcium supplementation. Supplementary calcium is associated with an increased risk of MI, especially in women, but this data remain controversial. – Supplementation of both vitamin D and calcium may increase risk of renal stone formation.

Endocrine Flashcards

(129 cards)