Weight Gain and Obesity (Case 40)
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.
Polycystic ovarian syndrome (PCOS)
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.
• When I evaluate a patient for weight gain, I first consider what has been the change in body composition. In most cases, patients have an increase in fat mass, but they should be examined for other causes, such as fluid retention, as might be seen with congestive heart failure.
• The pace and amount of weight gain vary with different etiologies and should be considered in the context of life and health events, such as pregnancy, change in environment, and new life stressors.
• Additionally important is medication history, as multiple medications, including antihyperglycemic agents, glucocorticoids, and antipsychotic medications, are known to be associated with weight gain.
• In reviewing the dietary history, ask patients to recall intake and, if possible, to keep a food diary. These tools often will reveal that a patient is taking in more calories than he or she recognizes and will identify components in the diet that can be eliminated or substituted.
• Assess the patient’s body habitus. Truncal obesity (apple-shaped) might reflect glucocorticoid excess, and this pattern of obesity is more commonly associated with metabolic syndrome than is gluteal-femoral obesity (pear-shaped).
• Look for potential signs of glucocorticoid excess (truncal obesity, rounded face, increase in supraclavicular and dorsocervical fat, hirsutism, red-purple wide striae, ecchymoses), hypothyroidism (puffy face; yellowish hue; delayed relaxation phase of reflexes; dry, cool skin; rough elbows), and male hypogonadism (fine wrinkles at corners of eyes, gynecomastia, soft or small testes).
• With respect to conditions exacerbated by obesity, look for signs of insulin resistance (acanthosis nigricans, skin tags), hypertension, PCOS (hirsutism), and type 2 diabetes (signs of insulin resistance, complications of diabetes–peripheral neuropathy, infections, carpal tunnel syndrome).
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Results from relatively more energy intake than expenditure; more likely in patients with a genetic predisposition to obesity (usually polygenic).
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.
Diagnosis is made by taking a dietary and exercise history and ruling out other causes for weight gain.
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.
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.
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.
Screening tests for endogenous hypercortisolism:
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.
• 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.
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).
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.
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
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.
Women with PCOS generally have had irregular periods since menarche. They may have acne and hirsutism, reflecting hyperandrogenism.
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.
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.
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.