Weight Gain and Obesity (Case 40)

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Weight Gain and Obesity (Case 40)

Elizabeth Briggs MD

Case: The patient is a 38-year-old woman who is referred to you for evaluation of a 40-pound weight gain over 2 years. She tells you that she had weighed about 110 pounds from age 18 until age 24 years, when she gained 25 pounds over the course of a successful pregnancy. By 6 months after this pregnancy, she had lost 15 lb and had been stable at about 120 lb until the past 2 years. She says that she has tried to decrease her intake of calories and increase her exercise, but these measures haven’t been effective in slowing her weight gain. In addition, she has been noticing facial hair, as well as hair on her chest and abdomen, which is new for her. She is clearly distressed over the changes she sees physically. Her menstrual cycle, usually regular since menarche, has been less so, with eight to nine menses per year and occasional months with 5 to 8 days of menstrual bleeding, which is longer than what she was used to until 3 years ago. On further questioning, she complains of easy bruising, acne, emotional lability, and difficulty walking up stairs due to leg weakness.

On physical examination, her blood pressure is 150/102 mm Hg, weight 164 pounds, height 62 in., and BMI 30. She has an obese trunk with relatively thin extremities. She has a rounded face with ruddy cheeks and excess supraclavicular and dorsocervical fat. She has hair on her chin, upper lip, chest, abdomen, back, and upper thighs, as well as acneiform lesions on her face, chest, and upper back. She has purple-red striae, 1 cm in diameter, on her abdomen, proximal thighs, and axillae, and ecchymoses on her upper and lower extremities. She has proximal weakness in her upper and lower extremities.

Differential Diagnosis

Exogenous obesity	Cushing syndrome
Hypothyroidism	Polycystic ovarian syndrome (PCOS)

Speaking Intelligently

Weight gain is a common problem encountered in clinical practice. When I evaluate a patient for weight gain I consider what could be its cause, as well as the potential consequences of the weight gain. Weight gain and obesity are very common; about one third of American adults are classified as overweight and about one third as obese. Obesity increases the risk for several disorders, including type 2 diabetes, hypertension, obstructive sleep apnea, dyslipidemia, atherosclerosis, osteoarthritis, and several cancers. Patients are often distressed by weight gain because of societal pressures to attain thinness. Interventions for weight loss include dietary modification, exercise, medications, and weight loss surgery. As clinicians, our responsibility is to identify factors contributing to weight gain and remove them if possible, attenuate risks associated with obesity, and facilitate safe and sustainable weight loss.

PATIENT CARE

Tests for Consideration

• Testing should generally be guided by clinical suspicion generated by clues on history and physical examination.
• Obesity is common, and Cushing syndrome is rare. Screening for Cushing syndrome is thus associated with false positive and false negative test results. Specific features of Cushing syndrome, as noted in our patient case, should be identified in order to proceed with screening, which consists of three potential tests:
• Midnight salivary cortisol: In normal subjects, midnight cortisol is very low as a consequence of diurnal variation, which is lost in syndromes of endogenous hypercortisolism.	$23
• 24-hour urine free cortisol	$24
• 1 mg overnight dexamethasone suppression test	$23
• When clinical suspicion is high, two of the three above tests should be requested to increase diagnostic accuracy.
• Thyroid-stimulating hormone (TSH): Elevated in primary hypothyroidism.	$24
• Consider screening for associated metabolic disorders with fasting glucose and a fasting lipid panel.	$7, $19
• A sleep study should be requested in most obese patients if they have fatigue or hypersomnolence, since obstructive sleep apnea is often undiagnosed.	$795
• Specific genetic testing for genes that predispose patients to obesity is not widely available and has unproven clinical utility; future research may some day demonstrate that gene testing coupled with early clinical interventions is helpful for patients.

Clinical Entities

Medical Knowledge

Exogenous Obesity
Pφ	Results from relatively more energy intake than expenditure; more likely in patients with a genetic predisposition to obesity (usually polygenic).
TP	Patients have usually been overweight through adulthood, often from childhood, though weight gain can present in a previously normal-weight person who has increased caloric intake, decreased exercise, or both. Weight gain tends to be more gradual. Patients can have either truncal or gluteal-femoral obesity.
Dx	Diagnosis is made by taking a dietary and exercise history and ruling out other causes for weight gain.
Tx	• Hypocaloric diets: All compositions of diet are modestly effective; the most important factor is adherence to the diet, and weight tends to be regained after patients stop the diet. • Increased physical activity: Improves fitness and helps patients maintain weight loss. • Weight loss medications: Currently approved medications include: Sibutramine: Serotonin uptake inhibitor that suppresses appetite; approved for long-term use and is moderately effective, but patients tend to regain weight after stopping the medication. Orlistat: Reduces fat absorption by blocking pancreatic lipase activity in the gut. Available by prescription and in a reduced-dose over-the-counter (OTC) preparation. Moderately effective; main side effect is oily stool, and fecal urgency and leakage. • Bariatric surgery: Most effective intervention for obesity (effectiveness varies with surgical procedure), 0.1% to 1% operative mortality, frequent remission of type 2 diabetes, reduced long-term mortality. See Cecil Essentials 60.

Cushing Syndrome
Pφ	Excess of glucocorticoid. Most common etiology is treatment with systemic glucocorticoids. Endogenous hypercortisolism is most commonly Cushing disease, which is caused by an adrenocorticotropic hormone (ACTH)–secreting pituitary tumor. Other causes are cortisol-producing adrenal adenoma, nodular adrenal hyperplasia, and ectopic ACTH secretion.
TP	Presentation can range from subclinical to overt and rapidly progressive. The symptoms of hypercortisolism seen with any etiology are weight gain, hyperglycemia, muscle weakness, easy bruising, violaceous striae, moon facies, increased dorsocervical and supraclavicular fat pads, and facial plethora. Patients with ectopic ACTH secretion can have weight loss (due to underlying malignancy), hyperpigmentation, and hypokalemic metabolic alkalosis.
Dx	Screening tests for endogenous hypercortisolism: • Midnight salivary cortisol • 24-hour urine free cortisol • 1-mg overnight dexamethasone suppression test If positive, measure ACTH. Should be low with exogenous glucocorticoids and cortisol-producing adrenal neoplasm. If ACTH is high, request pituitary MRI to evaluate for pituitary adenoma. Invasive sampling procedures can be done in specialized centers if the diagnosis is unclear. If ectopic ACTH secretion is suspected, pursue imaging for the primary tumor.
Tx	• Exogenous glucocorticoids: Limit dose as much as possible; taper off if possible. • Pituitary Cushing: Trans-sphenoidal resection of pituitary adenoma. • Cortisol-producing adrenal adenoma: Unilateral adrenalectomy. • Micronodular adrenal hyperplasia: Bilateral adrenalectomy. • Ectopic ACTH: Resection of primary tumor if possible. If not possible, drugs to block steroid synthesis (ketoconazole, metyrapone). If necessary, bilateral adrenalectomy. See Cecil Essentials 65, 67.

Hypothyroidism
Pφ	Most commonly due to autoimmune (Hashimoto) thyroiditis. Other causes of primary hypothyroidism include prior radioactive iodine treatment for hyperthyroidism, thyroidectomy, and drugs (lithium, amiodarone, interferon). Central hypothyroidism is caused by a pituitary disorder (adenoma, infiltrative disease, pituitary surgery) or hypothalamic disorder (rare).
TP	Hypothyroidism can cause modest weight gain (generally less than 10–20 pounds). Patients may have fatigue, constipation, cold intolerance, and menorrhagia. On exam, hypothyroid patients may have coarse hair; cool, dry skin; puffy face; delayed relaxation phase on reflex testing; bradycardia; and a yellowish hue due to accumulation of carotene. Patients with subclinical hypothyroidism (normal free thyroxine with elevated TSH) should not have weight gain attributable to thyroid disease.
Dx	• TSH: The most reliable test for primary hypothyroidism. • Free thyroxine and free triiodothyronine (T3): These tests are primarily used to evaluate for hypothyroidism due to pituitary or hypothalamic disease (in which case TSH is unreliable).
Tx	Replacement with synthetic levothyroxine to target thyroid function in the normal range. Supraphysiologic doses of levothyroxine or T3 to induce weight loss are not indicated. Lean mass is lost preferentially to fat mass in the hyperthyroid state, and side effects include risk for arrhythmia and loss of bone mass. See Cecil Essentials 66.

Polycystic Ovarian Syndrome
Pφ	PCOS does not cause weight gain but is exacerbated by obesity and should be considered as a differential diagnosis in our patient. It is characterized by chronic anovulation and increased ovarian androgen production. Patients with PCOS have high rates of insulin resistance and have improvement in ovulation with weight loss and treatment with insulin sensitizers. They have increased risk of cardiovascular disease and diabetes.
TP	Women with PCOS generally have had irregular periods since menarche. They may have acne and hirsutism, reflecting hyperandrogenism.
Dx	Diagnostic criteria for PCOS include the following: chronic anovulation, clinical or biochemical hyperandrogenism, and polycystic ovaries (need two of these criteria), and exclusion of other causes for these symptoms including Cushing syndrome, congenital adrenal hyperplasia (CAH), and an androgen-secreting tumor.
Tx	Diet and exercise interventions should be undertaken to improve metabolic risk. If fertility is desired, an insulin sensitizer, such as metformin, can be tried to allow ovulation. Ovulation induction with clomiphene is also effective. If pregnancy is not desired, oral contraceptives regulate menses, reduce endometrial cancer risk, and improve acne and hirsutism. Spironolactone can also be used to treat acne and hirsutism, and patients may seek cosmetic hair removal. See Cecil Essentials 71.

a. Monogenic obesity (leptin deficiency, melanocortin 4 receptor mutations): Tend to present with severe obesity in childhood.

b. Growth hormone deficiency: Fairly common in patients with other pituitary disorders; isolated growth hormone deficiency is less common. Growth hormone deficiency results predominantly in truncal weight gain.

Practice-Based Learning and Improvement: Evidence-Based Medicine

Title
A descriptive study of individuals successful at long-term maintenance of substantial weight loss

Authors
Klem ML, Wing RR, McGuire MT, Seagle HM, Hill JO

Institution
University of Pittsburgh School of Medicine

Reference
Am J Clin Nutr 1997;66:239–246

Problem
What are the diet and exercise habits of people who have been successful at maintaining weight loss?

Intervention
This study describes the demographics, diet, and exercise habits of 784 patients (80% women) in the National Weight Control Registry (a registry of people who have maintained a greater than 30-lb weight loss for longer than 1 year).

Quality of evidence
Level II-3

Outcome/effect
These patients, who have been successful with weight control, consumed an average of 1380 kcal daily and reported 2825 kcal of exercise per week.

Historical significance/comments
Many types of interventions allow short-term weight loss, but maintaining weight loss is more difficult. This study suggests that to maintain weight loss, continued moderate caloric restriction and regular exercise are important.

Interpersonal and Communication Skills

Successful Intervention for Weight Gain Requires Getting to Know Your Patient

To establish a successful plan of care for patients with weight gain, you must take a careful history and get to know your patient’s habits. First, entertain medical disorders that could cause weight gain. Consider the psychological context of and your patient’s feelings about weight gain. Identify psychiatric and behavioral disorders, such as depression and eating disorders, that may hinder weight loss efforts. These must be addressed if interventions are to succeed. In establishing a plan for diet and exercise modification, be sure you have your patient’s input and agreement. Remember, it is the patient who will have to implement the changes. Patients should be given behavioral goals (e.g., engaging in physical activity for more than 30 minutes 5 days a week and increasing intake of fruits and vegetables). Be sure the goals are realistic and then check in regularly with your patient to provide positive reinforcement and to troubleshoot problems.

Professionalism

Be Nonjudgmental with Patients

Weight gain and obesity are exceedingly common. Obesity is an emotionally charged subject in American culture. Most patients will be distressed by significant weight gain, though often patients may not want to address it as a problem. It is important that we as physicians are honest with patients about the health risks associated with being overweight, but it’s important not to be judgmental about an individual’s inability to control his or her weight. We should target interventions that we know to improve these risks and target health rather than slenderness. A strategy of addressing obesity as a chronic disease rather than blaming the patient is most effective.

Systems-Based Practice

EMTALA: Ensuring Access to Emergency Services

Serious complications can unexpectedly occur in patients with obesity who undergo bariatric surgery, necessitating urgent care at emergency rooms of hospitals where they do not receive their usual care. If the patient lacks insurance coverage, there may be the desire to transfer the patient to his or her usual facility for provision of care. There are clear regulations, however, that govern the provision of emergency care. In 1986 Congress enacted the Emergency Medical Treatment & Labor Act (EMTALA) to ensure public access to emergency services regardless of ability to pay. The essential matter is to ensure that hospitals providing emergency services do not refuse to provide proper care to patients who lack insurance coverage. There are four fundamental EMTALA principles:

1. A hospital must provide an appropriate medical screening examination for any patient. The statute was amended in 1988 and 1989 to add more specific provisions pertaining to on-call physicians in general, as well as the practice of obstetrics.

2. If a hospital determines that a patient requires emergency medical treatment, it must provide such treatment—to the extent that it is able to do so—as is necessary to stabilize the medical condition.

3. A hospital may not transfer any patient in an unstable medical condition unless either the patient requests the transfer (after being the recipient of a specific informed consent) or a physician certifies that the risks of transfer are outweighed by the potential benefits.

4. Hospitals are precluded from inquiring about a patient’s insurance or ability to pay before providing the initial screening examination or before stabilizing any emergency condition.

(See http://emedicine.medscape.com/article/790053-overview.)