Many patients are concerned that they have a "metabolic" or "glandular" cause for their obesity. This may be a reflection of the frustration that some of these individuals feel over the difficulties that they have had in battling a weight problem over many years. They may be looking for a "medical" explanation of why they have not succeeded in their goal of losing weight. Endocrine causes of serious obesity are not common. The three most commonly cited are hypothyroidism, Cushing's syndrome, and hypothalamic obesity. To evaluate the patient for hypothyroidism, questions can be asked about cold intolerance, constipation, irregular menses, fatigue, or depression. The presence of easy bruisability, proximal muscle weakness (difficulty getting out of a chair, trouble getting things out of a high cupboard), a change in appearance, or osteoporosis may be signs of hypercortisolism. The patient can be examined for signs of hypothyroidism including bradycardia, cool dry skin, a firm palpable thyroid, and delayed reflexes. Cushing's syndrome, though often cited as an endocrine cause of obesity, is rarely found. Central obesity, enlarged supraclavicular fat pads, and a buffalo hump are features of hypercortisolism, but they are not very specific for the condition. More specific physical findings include a recent change in habitus demonstrated from old photographs, objective evidence of proximal muscle weakness, wide (>2 cm) violaceous striae, and visible unexplained bruising. Hypothalamic obesity is exceedingly rare and is associated with headaches, visual field defects, and evidence of hypothalamic/pituitary dysfunction. A serum thyroid-stimulating hormone (TSH) is the best test to rule out the presence of hypothyroidism. A 24-h urinary free cortisol level or an overnight 1-mg dexamethasone suppression test are the most widely used screening tests for hypercortisolism, although these tests have false negative and false positive results in a significant number of cases (47,48). In particular, obese individuals, depressed persons, and chronic alcoholics may have increased cortisol on these screening tests that is not caused by any of the usual causes of Cushing's syndrome (ACTH-secreting tumor, ectopic ACTH secretion, or an adrenal tumor) (49). Some have recently advocated a nighttime salivary cortisol as a good screening test; however this assay is not as widely available as the more traditional measures. The most common cause of hypothalamic obesity is the presence of a retrochiasmatic tumor such as a craniopharyngioma. This condition is predominantly encountered in children and obesity occurs following surgical resection in 25 to 75% of those affected.
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