Podcast
Questions and Answers
What is the primary hypothesis that describes the pathophysiology of metabolic syndrome?
What is the primary hypothesis that describes the pathophysiology of metabolic syndrome?
How does the prevalence of metabolic syndrome change with age in the U.S. population?
How does the prevalence of metabolic syndrome change with age in the U.S. population?
Which of the following factors is NOT mentioned as contributing to the obesity epidemic?
Which of the following factors is NOT mentioned as contributing to the obesity epidemic?
Which examination finding is NOT typically associated with metabolic syndrome?
Which examination finding is NOT typically associated with metabolic syndrome?
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What might a high waist to hip ratio indicate regarding metabolic syndrome?
What might a high waist to hip ratio indicate regarding metabolic syndrome?
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What common health condition is characterized by symptoms of polyuria and polydipsia, and is important in metabolic syndrome?
What common health condition is characterized by symptoms of polyuria and polydipsia, and is important in metabolic syndrome?
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Which lifestyle factor correlates most strongly with the increased incidence of metabolic syndrome?
Which lifestyle factor correlates most strongly with the increased incidence of metabolic syndrome?
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What is a characteristic finding of xanthelasma, often observed in individuals at risk for metabolic syndrome?
What is a characteristic finding of xanthelasma, often observed in individuals at risk for metabolic syndrome?
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What is the primary mechanism of weight loss?
What is the primary mechanism of weight loss?
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What percentage of women with hirsutism are affected by PCOS?
What percentage of women with hirsutism are affected by PCOS?
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What is a potential consequence of androgen excess in females?
What is a potential consequence of androgen excess in females?
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Which of the following best describes idiopathic hirsutism?
Which of the following best describes idiopathic hirsutism?
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In which ethnic group is body hair typically less prevalent?
In which ethnic group is body hair typically less prevalent?
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What is the most common site for hirsutism hair growth in females?
What is the most common site for hirsutism hair growth in females?
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What is the functional role of androgens in hair growth?
What is the functional role of androgens in hair growth?
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Which type of hair is primarily affected by androgens?
Which type of hair is primarily affected by androgens?
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Which condition is characterized by increased hair growth in androgen-dependent areas, specifically the face and chest?
Which condition is characterized by increased hair growth in androgen-dependent areas, specifically the face and chest?
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What is the fasting glucose level classified as Type II Diabetes Mellitus?
What is the fasting glucose level classified as Type II Diabetes Mellitus?
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In the treatment of metabolic syndrome, which dietary recommendation is suggested?
In the treatment of metabolic syndrome, which dietary recommendation is suggested?
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What body mass index (BMI) classification is defined as obesity?
What body mass index (BMI) classification is defined as obesity?
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What is the recommended minimum duration of moderate exercise per week to impact metabolic syndrome positively?
What is the recommended minimum duration of moderate exercise per week to impact metabolic syndrome positively?
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Which of the following is NOT a laboratory test commonly obtained to evaluate metabolic syndrome?
Which of the following is NOT a laboratory test commonly obtained to evaluate metabolic syndrome?
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What is the minimum weekly duration of moderate-intensity aerobic physical activity recommended for adults?
What is the minimum weekly duration of moderate-intensity aerobic physical activity recommended for adults?
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Which of the following is NOT a recommended method for incorporating physical activity into daily routines?
Which of the following is NOT a recommended method for incorporating physical activity into daily routines?
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Which treatment is considered for patients with metabolic syndrome and a BMI greater than 40 kg/m²?
Which treatment is considered for patients with metabolic syndrome and a BMI greater than 40 kg/m²?
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What condition is associated with an increased risk of cognitive decline and dementia in patients with metabolic syndrome?
What condition is associated with an increased risk of cognitive decline and dementia in patients with metabolic syndrome?
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What pharmacological treatment should be considered for patients with a BMI of 27 kg/m2 who have obesity-related diseases?
What pharmacological treatment should be considered for patients with a BMI of 27 kg/m2 who have obesity-related diseases?
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What is the mechanism of action for Orlistat?
What is the mechanism of action for Orlistat?
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What pharmacological agent is used to treat insulin resistance and hyperglycemia in patients with metabolic syndrome?
What pharmacological agent is used to treat insulin resistance and hyperglycemia in patients with metabolic syndrome?
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Which of the following lifestyle changes has shown a significant impact on weight management among pediatric populations in the context of metabolic syndrome?
Which of the following lifestyle changes has shown a significant impact on weight management among pediatric populations in the context of metabolic syndrome?
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Which side effect is commonly associated with the use of Orlistat?
Which side effect is commonly associated with the use of Orlistat?
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What behavioral therapy technique is intended to help patients develop positive and realistic thoughts about themselves?
What behavioral therapy technique is intended to help patients develop positive and realistic thoughts about themselves?
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Which of the following pharmacological treatments is an appetite suppressant?
Which of the following pharmacological treatments is an appetite suppressant?
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What type of support is recommended as part of adjunctive behavioral therapy for obesity treatment?
What type of support is recommended as part of adjunctive behavioral therapy for obesity treatment?
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What is a primary characteristic of insulin resistance?
What is a primary characteristic of insulin resistance?
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Which group has a higher prevalence of insulin resistance?
Which group has a higher prevalence of insulin resistance?
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What is NOT considered a risk factor for insulin resistance?
What is NOT considered a risk factor for insulin resistance?
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Which symptom is typically NOT associated with insulin resistance?
Which symptom is typically NOT associated with insulin resistance?
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What lifestyle change is most effective in managing insulin resistance based on studies?
What lifestyle change is most effective in managing insulin resistance based on studies?
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Which component is NOT part of the metabolic syndrome definition?
Which component is NOT part of the metabolic syndrome definition?
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What is the relationship between visceral adipose tissue and insulin resistance?
What is the relationship between visceral adipose tissue and insulin resistance?
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Which of the following is a component of metabolic syndrome according to the NCEP-ATP III guidelines?
Which of the following is a component of metabolic syndrome according to the NCEP-ATP III guidelines?
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Which method is ineffective in diagnosing insulin resistance?
Which method is ineffective in diagnosing insulin resistance?
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Which of the following statements about insulin resistance is true?
Which of the following statements about insulin resistance is true?
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Which factor is an essential component of effective cognitive behavioral therapy for obesity treatment?
Which factor is an essential component of effective cognitive behavioral therapy for obesity treatment?
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What is the primary mechanism of action for appetite suppressants used in obesity treatment?
What is the primary mechanism of action for appetite suppressants used in obesity treatment?
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What is a critical consideration when advising a patient on a behavior change for obesity treatment?
What is a critical consideration when advising a patient on a behavior change for obesity treatment?
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Which of the following conditions may warrant the consideration of pharmacological treatment for weight loss?
Which of the following conditions may warrant the consideration of pharmacological treatment for weight loss?
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Which lifestyle activity is specifically mentioned as a way to incorporate physical activity into daily routines?
Which lifestyle activity is specifically mentioned as a way to incorporate physical activity into daily routines?
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Which side effect is most commonly associated with Orlistat as a pharmacological treatment?
Which side effect is most commonly associated with Orlistat as a pharmacological treatment?
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What should patients be instructed to do to effectively use stimulus control in behavioral therapy?
What should patients be instructed to do to effectively use stimulus control in behavioral therapy?
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Which of the following pharmacological agents is categorized as an appetite suppressant?
Which of the following pharmacological agents is categorized as an appetite suppressant?
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What contributes to the varying extent of terminal hair in women based on ethnic background?
What contributes to the varying extent of terminal hair in women based on ethnic background?
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What is the most common clinical presentation of hirsutism in women?
What is the most common clinical presentation of hirsutism in women?
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What is a significant challenge in maintaining weight loss after achieving it?
What is a significant challenge in maintaining weight loss after achieving it?
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How does hirsutism relate to androgen excess in females?
How does hirsutism relate to androgen excess in females?
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What is the primary source of circulating testosterone in females experiencing hirsutism?
What is the primary source of circulating testosterone in females experiencing hirsutism?
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What defines idiopathic hirsutism in women?
What defines idiopathic hirsutism in women?
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What effect do androgens have on hair follicles in androgen-sensitive areas?
What effect do androgens have on hair follicles in androgen-sensitive areas?
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Which characteristic is NOT typically associated with hirsutism due to androgen excess?
Which characteristic is NOT typically associated with hirsutism due to androgen excess?
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What is true regarding body mass index (BMI) classification for adults?
What is true regarding body mass index (BMI) classification for adults?
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Which of the following describes centripetal obesity and its associated risks?
Which of the following describes centripetal obesity and its associated risks?
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What percentage of individuals with obesity also has metabolic syndrome?
What percentage of individuals with obesity also has metabolic syndrome?
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What demographic trend has been observed concerning obesity prevalence among adults in recent decades?
What demographic trend has been observed concerning obesity prevalence among adults in recent decades?
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What are the main steps involved in evaluating a patient with obesity?
What are the main steps involved in evaluating a patient with obesity?
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Which factor is most strongly associated with developing obesity in adults?
Which factor is most strongly associated with developing obesity in adults?
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Which health complications are associated with obesity?
Which health complications are associated with obesity?
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What aspect of obesity history is important to consider for effective management?
What aspect of obesity history is important to consider for effective management?
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What is the most challenging aspect of defining metabolic syndrome?
What is the most challenging aspect of defining metabolic syndrome?
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Which risk factor is associated with a higher prevalence of insulin resistance?
Which risk factor is associated with a higher prevalence of insulin resistance?
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What percentage of the general nonobese, nondiabetic population has insulin resistance comparable to that observed in type 2 diabetes?
What percentage of the general nonobese, nondiabetic population has insulin resistance comparable to that observed in type 2 diabetes?
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Which symptom is commonly associated with elevated blood glucose levels due to insulin resistance?
Which symptom is commonly associated with elevated blood glucose levels due to insulin resistance?
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What role does visceral adipose tissue play in metabolic syndrome?
What role does visceral adipose tissue play in metabolic syndrome?
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Which condition is NOT commonly associated with insulin resistance?
Which condition is NOT commonly associated with insulin resistance?
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What is the primary method recommended for improving insulin resistance?
What is the primary method recommended for improving insulin resistance?
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Which population is at higher risk for developing metabolic syndrome?
Which population is at higher risk for developing metabolic syndrome?
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What treatment has shown effectiveness in reducing the risk of progressing to type 2 diabetes?
What treatment has shown effectiveness in reducing the risk of progressing to type 2 diabetes?
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Which of the following is NOT a component of metabolic syndrome according to NCEP-ATP III?
Which of the following is NOT a component of metabolic syndrome according to NCEP-ATP III?
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Which diagnostic criterion for polycystic ovary syndrome (PCOS) is associated with ovarian volume?
Which diagnostic criterion for polycystic ovary syndrome (PCOS) is associated with ovarian volume?
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What is the primary medical treatment for weight reduction in obese patients diagnosed with PCOS?
What is the primary medical treatment for weight reduction in obese patients diagnosed with PCOS?
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Which medication is commonly used as a first-line treatment for ovulation induction in patients desiring pregnancy?
Which medication is commonly used as a first-line treatment for ovulation induction in patients desiring pregnancy?
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What is the role of spironolactone in the treatment of hirsutism in PCOS patients?
What is the role of spironolactone in the treatment of hirsutism in PCOS patients?
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Which of the following options is a secondary treatment for patients with glucose abnormalities in PCOS?
Which of the following options is a secondary treatment for patients with glucose abnormalities in PCOS?
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In the absence of effective improvement in hirsutism after six months of first-line treatment, which additional therapy is recommended?
In the absence of effective improvement in hirsutism after six months of first-line treatment, which additional therapy is recommended?
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Which of the following assessments is NOT commonly recommended to screen for conditions associated with PCOS?
Which of the following assessments is NOT commonly recommended to screen for conditions associated with PCOS?
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Which hormonal treatment option is used for endometrial protection in women with PCOS who do not wish to become pregnant?
Which hormonal treatment option is used for endometrial protection in women with PCOS who do not wish to become pregnant?
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What is the mean weight loss observed in pivotal trials for the RESHAPE device?
What is the mean weight loss observed in pivotal trials for the RESHAPE device?
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Which of the following conditions is NOT directly linked to obesity outcomes?
Which of the following conditions is NOT directly linked to obesity outcomes?
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What percentage of individuals losing 40 lbs are able to maintain that loss for more than 2 years?
What percentage of individuals losing 40 lbs are able to maintain that loss for more than 2 years?
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What is a common digestive disorder associated with obesity?
What is a common digestive disorder associated with obesity?
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What is the primary adverse effect reported for both the RESHAPE and ORBERA devices?
What is the primary adverse effect reported for both the RESHAPE and ORBERA devices?
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What is a potential side effect of naltrexone + bupropion treatment for obesity?
What is a potential side effect of naltrexone + bupropion treatment for obesity?
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Which obesity treatment is associated with an amphetamine?
Which obesity treatment is associated with an amphetamine?
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What is a common complication of bariatric surgery?
What is a common complication of bariatric surgery?
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What mechanism of action does liraglutide use to promote weight loss?
What mechanism of action does liraglutide use to promote weight loss?
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Which is a potential outcome of using pharmacological treatments for obesity?
Which is a potential outcome of using pharmacological treatments for obesity?
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What is the primary requirement for achieving weight loss effectively?
What is the primary requirement for achieving weight loss effectively?
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What percentage of American women experience hirsutism?
What percentage of American women experience hirsutism?
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Which condition is a common cause of hirsutism in women?
Which condition is a common cause of hirsutism in women?
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In which sites does androgen excess primarily lead to increased hair growth in females?
In which sites does androgen excess primarily lead to increased hair growth in females?
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Which of the following best defines idiopathic hirsutism?
Which of the following best defines idiopathic hirsutism?
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What role do androgens play in hair growth?
What role do androgens play in hair growth?
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How does ethnic background influence the prevalence of body hair?
How does ethnic background influence the prevalence of body hair?
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Which hormonal factors contribute to the development of hirsutism in females?
Which hormonal factors contribute to the development of hirsutism in females?
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What distinguishes nonclassical adrenal hyperplasia from its classical form?
What distinguishes nonclassical adrenal hyperplasia from its classical form?
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What hormone level is primarily elevated in cases of ovarian hyperthecosis?
What hormone level is primarily elevated in cases of ovarian hyperthecosis?
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Which condition is most likely if a female presents with severe hirsutism and testosterone levels exceeding 150-200 ng/dl?
Which condition is most likely if a female presents with severe hirsutism and testosterone levels exceeding 150-200 ng/dl?
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What is the significance of measuring serum 17-hydroxyprogesterone in women suspected of having congenital adrenal hyperplasia?
What is the significance of measuring serum 17-hydroxyprogesterone in women suspected of having congenital adrenal hyperplasia?
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Which of the following is a rare cause of androgen excess in women?
Which of the following is a rare cause of androgen excess in women?
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What condition would likely present alongside hirsutism, oligomenorrhea, and obesity?
What condition would likely present alongside hirsutism, oligomenorrhea, and obesity?
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Which of the following is not typically a clinical manifestation of androgen excess?
Which of the following is not typically a clinical manifestation of androgen excess?
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What is a potential diagnostic clue indicating adrenal carcinoma in a patient with hirsutism?
What is a potential diagnostic clue indicating adrenal carcinoma in a patient with hirsutism?
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Which hormone is typically low in conditions related to premature ovarian insufficiency?
Which hormone is typically low in conditions related to premature ovarian insufficiency?
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What should be the target weight loss over a 6-month period for effective obesity treatment?
What should be the target weight loss over a 6-month period for effective obesity treatment?
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Which of the following symptoms is associated with Cushing syndrome as a sign of secondary obesity?
Which of the following symptoms is associated with Cushing syndrome as a sign of secondary obesity?
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Which of the following caloric intake guidelines is correct for women aiming to lose weight?
Which of the following caloric intake guidelines is correct for women aiming to lose weight?
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What is the combination that is deemed most effective for obesity treatment?
What is the combination that is deemed most effective for obesity treatment?
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What is the primary caloric deficit recommended per day to achieve weight loss?
What is the primary caloric deficit recommended per day to achieve weight loss?
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Which condition is NOT typically a direct contributor to obesity?
Which condition is NOT typically a direct contributor to obesity?
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What is the main goal in terms of weight loss recommended for someone weighing 200 lbs?
What is the main goal in terms of weight loss recommended for someone weighing 200 lbs?
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Which characteristic of a diet has shown to be the primary factor for successful long-term weight loss?
Which characteristic of a diet has shown to be the primary factor for successful long-term weight loss?
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Study Notes
Insulin Resistance
- Cells fail to respond normally to insulin
- Common in type 2 diabetes, obesity, dyslipidemia, and hypertension
- Is a component of metabolic syndrome
- 25% of non-obese, non-diabetic population
- Higher risk of developing type 2 diabetes
Insulin Resistance - Pathophysiology
- Insulin is a hormone released by the pancreas in response to carbohydrates
- Allows glucose to enter cells and reduces blood glucose
- Insulin resistance means normal insulin levels do not control blood glucose effectively
- Etiology poorly understood
Insulin Resistance - Risk Factors
- Obesity
- Sedentary lifestyle
- Family history of diabetes (genetic and environmental factors)
- Certain health conditions: hypertension, hyperlipidemia, PCOS, NAFLD, Hepatitis C, history of gestational diabetes, other disorders of acute or chronic inflammation
- Age older than 45
- Certain ethnicities: African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander American
- Certain medications: corticosteroids, protease inhibitors, atypical anti-psychotics
Insulin Resistance - Clinical Presentation
- Initially asymptomatic
- Signs and symptoms appear as blood glucose levels elevate, including:
- Fatigue/Malaise
- Polyuria, Polydipsia, polyphagia
- Nausea
- Difficulty concentrating
- Dizziness
- Vision problems
- Slow healing
- Skin lesions - Acanthosis Nigricans
- Paresthesias
Insulin Resistance - Treatment
- Can be improved or reversed with lifestyle changes:
- Attain and maintain a healthy body weight
- Diet
- Increase physical activity
- The Diabetes Prevention Program (DPP) showed that exercise and diet were more effective than metformin at reducing the risk of progressing to type 2 diabetes
- Pharmacologic Tx: Metformin
- More frequent monitoring for diagnosis of type 2 diabetes
Metabolic Syndrome - Definition
- Constellation of metabolic abnormalities that increase the risk of cardiovascular disease (CVD) and diabetes mellitus
- Components:
- Central obesity
- Hypertriglyceridemia
- Low levels of high-density lipoprotein (HDL) cholesterol
- Hyperglycemia/Insulin Resistance/Impaired fasting glucose
- Hypertension
Metabolic Syndrome - Epidemiology
- Prevalence in the US is 34.7%
- Prevalence increases with age
- Generally equal in women and men, but varies between populations
Metabolic Syndrome - Etiology
- Insulin resistance is the most accepted hypothesis
- Obesity epidemic:
- Over nutrition
- Atherogenic diet (high fats, sugars, salt)
- Sedentary lifestyles
- Genetic contributions
- Polycystic Ovarian Syndrome (PCOS): shares many common characteristics
Metabolic Syndrome - Principles
- Increased overweight/obese population = increased metabolic syndrome incidence
- No known common single cause
- Reflects sedentary lifestyle and over nutrition = excess adiposity
- Endothelial dysfunction and atherosclerosis = increased CVD and Type II DM
- Diagnosis: helps identify people at high-risk for CVD and Diabetes
Metabolic Syndrome - H&P
- PMHx:
- Type II DM, HTN, hyperlipidemia, insulin resistance, HIV infection
- Medications: glucocorticoids, antipsychotics, anti-viral drugs (HIV)
- Family Hx:
- CVD, type II DM, hyperlipidemia, obesity, PCOS
- Social Hx:
- Decreased exercise, increased caloric consumption, alcohol intake, smoking
- H&P:
- Symptoms: polyuria, polydipsia, weight loss, angina, PCOS, obstructive sleep apnea
- Blood pressure, BMI, waist and hip circumference, waist to hip ratio
- Cardiovascular & respiratory system exam, abdominal exam
- Corneal arcus & xanthelasma, hepatomegaly, hirsutism, acne, acanthosis nigricans
Metabolic Syndrome - Labs
- Fasting glucose:
- Normal: less than 100 mg/dL
- 101-125 mg/dL: proceed with 2 hr OGTT (75g glucose load)
- Glucose less than 140 mg/dL: normal
- Glucose greater than or equal to 200 mg/dL: Type II DM
- Glucose 141-199 mg/dL: impaired glucose tolerance
- Obtain these (in addition to fasting glucose):
- Lipid panel (fasting)
- CMP - evaluate renal & liver functions
- UA - proteinuria assess for renal damage (HTN & DM)
- TSH & free T4 - possible cause of obesity
- Uric acid - increased risk of metabolic syndrome with hyperuricemia
- Consider these in appropriate patients:
- Sleep study - Symptoms of obstructive sleep apnea
- PCOS - suspected based on clinical features & anovulation
- testosterone, luteinizing hormone, & follicle-stimulating hormone
Metabolic Syndrome - Diagnosis
- 7 different sets of criteria from various organizations
- Suggested approach:
- Treat all CVD risk factors individually and aggressively
- Achieving this removes the need for a diagnosis of metabolic syndrome
Metabolic Syndrome - Treatment
- Treat specific conditions separately (HTN, glucose, etc.)
- Goal= reduce CVD and type II DM risk, decrease excess adiposity and resultant insulin resistance
- Lifestyle Modification:
- Diet and exercise
- Low saturated fat, high complex carbohydrates & fiber, no added sugar, low sodium
- Mediterranean Diet recommended
- Eliminate sugar sweetened beverages
- Team-based, interactive approach with frequent contact and motivated patients
- Exercise:
- Regular moderate-intense physical activity is preventive
- Aerobic exercise removes abdominal fat
- Minimum 30 minutes moderate exercise daily (~150 min/week)
- Significant impact in the pediatric population
- Caloric value of 1 hour of various exercise based on body weight
- Smoking cessation
- Pharmaceuticals:
- Orlistat (Xenical, Alli) - 120 mg PO Tid
- Sibutramine (Meridia) – removed from market (increased MI, CVA)
- Phentermine – exact MOA unknown, schedule IV drug
- Bariatric surgery
Metabolic Syndrome - Treatment - Bariatric Surgery
- Patients with metabolic syndrome and a BMI greater than 40 kg/m2
- Patients with metabolic syndrome and a BMI greater than 35 kg/m2 with comorbidities
- Evolving application - patients with a BMI as low as 30 kg/m2 & type 2 diabetes
- Surgical options:
- Gastric bypass
- Vertical sleeve gastrectomy
Metabolic Syndrome - Treatment - Insulin Resistance & Hyperglycemia
- Metformin
- Pioglitazone
- Rosiglitazone
Metabolic Syndrome - Treatment - Dyslipidemia
- Statins
- Other lipid-lowering drugs
Metabolic Syndrome - Treatment - Hypertension
- Lifestyle modification
- Antihypertensive medications
Metabolic Syndrome - Treatment - Summary
- Treat all components individually
Metabolic Syndrome - Clinical Implications
- Fatty liver disease with steatosis, leading to fibrosis, and cirrhosis
- Hepatocellular carcinoma & intrahepatic cholangiocarcinoma
- Chronic kidney disease (CKD; defined as a glomerular filtration rate less than 60 mL/min per 1.73 m2)
- Polycystic ovary syndrome
- Male Hypogonadism
- Sleep-disordered breathing, including obstructive sleep apnea
- Hyperuricemia & gout
- Increased risk of cognitive decline & dementia
Obesity - Diagnosis
- Body Mass Index (BMI): Measure of excess adipose tissue
- BMI = weight (kg)/height (m)2
- BMI > 30 = Obese
- BMI classifications:
- 18.5-24.9 = Normal
- 25-29.9 = Overweight
- 30-34.9 = Class I obesity
- 35-39.9 = Class II obesity
-
40 = Extreme obesity
Obesity - Treatment - Adjunctive Behavioral Therapy
- Cognitive behavioral therapy strategies to help change & reinforce new dietary and physical activity behaviors
- Self-monitoring techniques (e.g., journaling, weighing, & measuring food & activity)
- Stress management
- Stimulus control (e.g., using smaller plates, not eating in front of the television or in the car)
- Social support
- Problem solving
- Cognitive restructuring to help patients develop more positive & realistic thoughts about themselves
Obesity - Treatment - Adjunctive Pharmacological Tx
- Should be considered for patients with:
- A BMI ≥30 kg/m2
- A BMI ≥27 kg/m2 who have concomitant obesity-related diseases & for whom dietary & physical activity therapy has not been successful
- Options:
- Gastrointestinal fat blockers - Orlistat (xenical, Alli)
- Appetite suppressants (anorexiants) - Lorcaserin (Belviq), Phentermine + topiramate, Naltrexone + bupropion, Liraglutide (Saxenda, Victoza)
Obesity - Treatment - Adjunctive Pharmacological Tx - Orlistat (xenical, Alli)
- 120 mg PO Tid with meals
- 5% body weight loss
- MOA: reduces fat absorption in the GI tract
- SE: may cause GI distress = diarrhea, cramping, flatulence
- Low fat diet reduces Sx = pt.motivator to stay on diet
Obesity - Treatment - Adjunctive Pharmacological Tx - Lorcaserin (Belviq)
- 10 mg PO Bid
- 5% body weight loss
Obesity - Summary
- To achieve weight loss: caloric expenditure > caloric intake
- Maintaining weight loss is very difficult, requires permanent behavior modification (diet and exercise)
Hirsutism - Definition
- Excessive male-pattern hair growth in women of reproductive age
- Affects 5-10% of females of reproductive age
- Most common cause: PCOS
- Clinical Presentation:
- Course, pigmented, hair on the face, chest, abdomen, back in a female
Hirsutism - Epidemiology
- 20% of American women have hirsutism
- 80% of women with androgen excess have hirsutism (not all)
- Extent of terminal hair varies by ethnic background:
- East Asian & Native American women < body hair
- Southern European women (Mediterranean) > body hair
- Hirsutism may occur with virilization:
- Male pattern alopecia, voice deepening, increased muscle bulk, clitoromegaly
- Virilization = moderate/severe androgen excess
Hirsutism - Etiology
- Idiopathic Hirsutism:
- Females with hirsutism
- Normal androgen concentrations
- No menstrual irregularities
- No identifiable cause of the hirsutism.
Androgens & Androgen Action
- Hirsutism results from the interaction of circulating serum androgens & the sensitivity of the hair follicle to those androgens, as well as local growth factors
- Androgens:
- Testosterone: usually ovarian origin
- Dehydroepiandrosterone sulfate (DHEAS): Adrenal origin
- Androstenedione: adrenal or ovarian origin
Androgens & Hair Growth
- Hair on the scalp, eyebrows, and eyelashes grow in the absence of androgens
- At other body sites (face, axilla, pubis, arms, legs, trunk, and ears) androgens increase hair growth
- This is manifested by increased follicle size, hair fiber diameter, and proportion of time terminal hairs spend in the anagen phase (growth phase)
- Androgen excess in females leads to increased hair growth in the most androgen-sensitive sites (upper lip, chin, midsternal, upper abdomen, back, and buttocks)
- However, this leads to scalp hair loss due to the time hairs spend in the anagen phase
Polycystic Ovarian Syndrome (PCOS)
- A hormonal disorder common among women of reproductive age.
- Characterized by:
- Irregular periods
- Excess androgen production
- Cysts on the ovaries.
- It can lead to:
- Obesity
- Infertility
- Hirsutism
Insulin Resistance
- Cells do not respond normally to insulin
- Contributing factor in type 2 diabetes, obesity, dyslipidemia, and hypertension
- 25% of the general, nonobese, nondiabetic population has insulin resistance similar to that seen in type 2 diabetics
- Increased risk of developing type 2 diabetes
Insulin Resistance - Pathophysiology
- Insulin is a hormone released by the pancreas that allows glucose to enter cells and lowers blood glucose levels
- Released in response to carbohydrates consumed in the diet
- Insulin resistance occurs when normal insulin levels do not effectively control blood glucose levels
Insulin Resistance - Risk Factors
- Obesity
- Sedentary lifestyle
- Family history of diabetes (genetic and environmental factors)
- Various health conditions: hypertension, hyperlipidemia, PCOS, NAFLD, hepatitis C, history of gestational diabetes, other disorders of acute and chronic inflammation
- Age > 45
- African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander American ethnicity
- Certain medications: corticosteroids, protease inhibitors, atypical anti-psychotics
Insulin Resistance - Clinical Presentation
- Initially asymptomatic
- Signs and symptoms appear as blood glucose levels elevate, which may include:
- Fatigue/Malaise
- Polyuria, Polydipsia, polyphagia
- Nausea
- Difficulty concentrating
- Dizziness
- Vision problems
- Slow healing
- Skin lesions - Acanthosis Nigricans
- Paresthesias
Insulin Resistance - Treatment
- Can be improved or reversed with lifestyle changes:
- Attain and maintain a healthy body weight
- Diet
- Increase physical activity
- The Diabetes Prevention Program (DPP) showed that exercise and diet were nearly twice as effective as metformin in reducing the risk of progressing to type 2 diabetes
- Pharmacologic treatment: Metformin
- More frequent monitoring for diagnosis of T2DM
Metabolic Syndrome
- A group of metabolic abnormalities that increase the risk of cardiovascular disease and diabetes mellitus
- Includes:
- Central obesity
- Hypertriglyceridemia
- Low levels of high-density lipoprotein (HDL) cholesterol
- Hyperglycemia/Insulin Resistance/Impaired fasting glucose
- Hypertension
Obesity - Risks
- Increased risk of various health problems:
- Hypertension
- Diabetes
- Dyslipidemia
- Obstructive sleep apnea
- Nonalcoholic fatty liver disease
- Some malignancies
Obesity - Demographics (Americans)
- Adults:
- 30.7% overweight
- 42.4% obese
- 9.2% severely obese
- 60% of individuals with obesity have metabolic syndrome
- 40-70% of obesity is attributed to genetic influences
- < 1% is secondary obesity (hypothyroid, Cushing syndrome)
Obesity - Treatment
- Adjunctive Behavioral Therapy:
- Cognitive behavioral therapy strategies to help change and reinforce new dietary and physical activity behaviors
- Self-monitoring techniques (e.g., journaling, weighing, and measuring food and activity)
- Stress management
- Stimulus control (e.g., using smaller plates, not eating in front of the television or in the car)
- Social support
- Problem-solving
- Cognitive restructuring to help patients develop more positive and realistic thoughts about themselves
- Adjunctive Pharmacological Treatment:
- Consider for patients with a BMI ≥ 30 kg/m2 or a BMI ≥ 27 kg/m2 with obesity-related diseases when dietary and physical activity therapy has not been successful.
- Options include:
- Gastrointestinal fat blockers - Orlistat (Xenical, Alli)
- Appetite suppressants (anorexiants) - Lorcaserin (Belviq), Phentermine + topiramate, Naltrexone + bupropion, Liraglutide (Saxenda, Victoza)
Hirsutism
- Definition: Excessive male-pattern hair growth in women of reproductive age
- Affects 5-10% of females of reproductive age
- Most common cause: PCOS
- Clinical presentation: Course, pigmented hair on the face, chest, abdomen, back in a female
Hirsutism - Epidemiology
- 20% of American women have hirsutism
- 80% of women with androgen excess have hirsutism
- Extent of terminal hair varies by ethnicity:
- East Asian and Native American women < body hair
- Southern European women (Mediterranean) > body hair
- Hirsutism may occur with virilization: Male pattern alopecia, voice deepening, increased muscle bulk, clitoromegaly
- Virilization = moderate/severe androgen excess
Hirsutism Etiology
- Idiopathic Hirsutism:
- Females with hirsutism
- Normal androgen concentrations
- No menstrual irregularities
- No identifiable cause of hirsutism
Androgens & Androgen Action
- Hirsutism results from the interaction of circulating serum androgens and the sensitivity of the hair follicle to those androgens, as well as local growth factors:
- Testosterone: Usually ovarian origin
- Dehydroepiandrosterone sulfate (DHEAS): Adrenal origin
- Androstenedione: Adrenal or ovarian origin
Androgens & Hair Growth
- Hair on the scalp, eyebrows, and eyelashes grow in the absence of androgens
- At other body sites (face, axilla, pubis, arms, legs, trunk, & ears), androgens increase hair growth
- Increased hair growth is manifested by increased follicle size, hair fiber diameter, and proportion of time terminal hairs spend in the anagen phase (growth phase)
- Androgen excess in females leads to increased hair growth in the most androgen-sensitive sites (upper lip, chin, midsternal, upper abdomen, back, & buttocks)
- This can lead to scalp hair loss due to the extended time hairs spend in the anagen phase
PCOS - Diagnostic Evaluation
- Pelvic ultrasound:
- ≥ 12 follicles in either ovary measuring 2-9 mm diameter or
- Ovarian volume > 10 ml
- Basal body temperature chart: absence of a biphasic pattern (anovulation) – rarely used now
PCOS - Other Considerations
- BP/BMI/Waist circumference - CVD risk
- Fasting lipid profile
- 2-hour OGTT or fasting glucose and hgbA1C
- Screen for OSA
- Liver enzymes (not recommended to use US to screen for fatty liver)
- Screen for depression and anxiety disorders
PCOS - Treatment
- Obese patients: Weight reduction and exercise are often effective in reversing metabolic defects and inducing ovulation
- Patients who do not desire pregnancy:
- Combined hormonal OCPs are first-line treatment for hyperandrogenism and menstrual irregularities
- Intermittent or continuous progestin therapy or hormonal IUD can be used for endometrial protection in women who choose not to use OCP
- Metformin therapy second line to improve menstrual function but has no benefit on hirsutism, acne, or infertility; used for glucose abnormalities
PCOS - Treatment for Hirsutism
- 6 months of combined OCP
- If not improved, add spironolactone
- Topical eflornithine (Vaniqa) cream twice daily for 6 months
- Electrolysis, laser therapy
Hirsutism
- Excessive male-pattern hair growth in women of reproductive age.
- Affects 5-10% of females of reproductive age.
- Most common cause: Polycystic Ovarian Syndrome (PCOS).
- Clinical Presentation: Course, pigmented, hair on the face, chest, abdomen, back in a female.
Hirsutism - Epidemiology
- 20% of American women have hirsutism.
- 80% of women with androgen excess have hirsutism.
- Extent of terminal hair varies by ethnicity:
- East Asian & Native American women have less body hair
- Southern European women (Mediterranean) have more body hair
- Hirsutism may occur with virilization:
- Male pattern alopecia, voice deepening, increased muscle bulk, clitoromegaly
- Virilization is moderate/severe androgen excess.
Hirsutism Etiology
-
Idiopathic Hirsutism:
- Females with hirsutism
- Normal androgen concentrations
- No menstrual irregularities
- No identifiable cause of the hirsutism.
Androgens & Androgen Action
- Hirsutism results from the interaction of circulating serum androgens and the sensitivity of the hair follicle to those androgens, as well as local growth factors.
-
Androgens:
- Testosterone: usually ovarian origin
- Dehydroepiandrosterone sulfate (DHEAS): Adrenal origin
- Androstenedione: adrenal or ovarian origin
Androgens & Hair Growth
- Hair on the scalp, eyebrows, & eyelashes grow in the absence of androgens.
- At other body sites (face, axilla, pubis, arms, legs, trunk, & ears) androgens increase hair growth.
- Androgens increase hair growth by:
- Increased follicle size
- Increased hair fiber diameter
- Increased time terminal hairs spend in the anagen phase (growth phase)
- Androgen excess in females leads to increased hair growth in the most androgen sensitive sites (upper lip, chin, midsternal, upper abdomen, back, & buttocks).
- However, this leads to scalp hair loss due to the time hairs spend in the anagen phase.
Nonclassical Adrenal Hyperplasia
- Excess androgens are a key feature of most forms of congenital adrenal hyperplasia.
- Usually recognized at birth or early infancy.
- Nonclassical forms (primary 21-hydroxylase deficiency):
- Affected females present with hirsutism around the time of puberty.
- Sometimes have menstrual irregularities, or primary amenorrhea.
- No manifestations of cortisol deficiency.
Females with Virilization or Severe Hyperandrogenemia
- Rapid Virilization: refers to acute onset of exaggerated characteristics usually in a female, often because of the adrenal glands overproducing androgens.
- Usually due to an androgen secreting tumor:
- Ovarian
- Adrenal
- Ovarian hyperthecosis: Hyperplasia of the theca interna of the ovary with clusters of thecal cells in the ovarian stroma producing excessive amounts of testosterone leading to hirsutism & virilization.
- Occurs later in life & progresses rapidly when compared to PCOS.
-
Androgen Secreting Ovarian tumors:
- About 5% of ovarian tumors.
- May be identified by pathology (biopsy/surgery) or transvaginal ultrasound.
- Most females have testosterone levels > 150-200 ng/dl & present with virilization.
Ovarian Hyperthecosis
- Nonmalignant ovarian disorder.
- Increased production of testosterone by the luteinized thecal cells in the stroma.
- Markedly increased testosterone concentrations >700ng/dl.
- Unclear if this disorder is distinct or part of PCOS spectrum.
- Primarily in postmenopausal females but can be premenopausal.
Androgen Secreting Tumors
-
Adrenal tumors:
- Rare causes of androgen excess.
- Some are adrenal adenomas & secrete testosterone.
- Most are adrenal carcinoma & secrete DHEA, DHEAS, & cortisol.
- Women may have clinical manifestations of androgen excess & Cushing Syndrome.
- Elevated DHEAS suggests adrenal carcinoma.
Differential Dx - Other
-
Cushing Disease: Adrenal overactivity due to a corticotroph adenoma secreting ACTH.
- Results in excess cortisol & excess androgens.
-
Uncommon causes of hirsutism:
- Hyperprolactinemia (pituitary adenoma).
- Acromegaly (pituitary adenoma).
- Hypothyroidism.
- Severe Insulin resistance.
- Drugs: androgen therapy (testosterone, DHEA), Danazol (used to treat endometriosis).
Hirsutism – Clinical Presentation
-
Mild to moderate hirsutism:
- Regular menses, no identifiable cause of hirsutism.
- Think - Idiopathic hirsutism
-
Hirsutism with any of the following: think - Polycystic Ovarian Syndrome (PCOS)
- Acne
- Male pattern alopecia
- Acanthosis nigricans
- Obesity
- Oligomenorrhea
-
Hirsutism with any of the following: think - Ovarian or adrenal androgen secreting tumor or ovarian hyperthecosis.
- Testosterone > 150 ng/dl: require evaluation for Ovarian or adrenal androgen secreting tumor or ovarian hyperthecosis.
PCOS Diagnostic Evaluation
-
DHEAS: Not suggested for everyone
- Measure for symptoms of severe hyperandrogenism.
- Can be extremely elevated in patients with adrenal carcinoma.
- Androstenedione: Role unclear in evaluation of PCOS (mixed results).
-
Serum 17-hydroxyprogesterone:
- Measure morning levels in early follicular phase to rule out congenital adrenal hyperplasia due to 21-hydroxylase deficiency.
-
800 ng/dl = adrenal hyperplasia.
- FSH & estradiol: high in premature ovarian insufficiency (also have low estradiol).
- Check TSH: Thyroid abnormalities cause irregular ovulation & menses.
- Increased Prolactin: Pituitary adenoma, causes irregular cycles.
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Description
This quiz explores insulin resistance, its pathophysiology, and associated risk factors. It highlights the implications for type 2 diabetes and metabolic syndrome, emphasizing the importance of understanding this condition for prevention and management. Test your knowledge on the factors influencing insulin efficacy and related health conditions.
