Poorly Controlled Diabetes Mellitus and Fatigue

Posted by • May 31st, 2013

In the latest Case Record from the Massachusetts General Hospital, a 56-year-old woman with diabetes mellitus was admitted to the hospital because of hyperglycemia and chest pain. Approximately 4 years earlier, a chest radiograph showed a solitary pulmonary nodule in the right upper lobe. 

The differential diagnosis for uncontrolled diabetes includes undertreatment or misdiagnosis of the type of diabetes, a progressive course due to weight gain or advancing beta-cell failure, or a superimposed pathological process (e.g., pancreatitis, pancreatic cancer, hemochromatosis, cystic fibrosis, acromegaly, lipodystrophy, medication use, or high levels of endogenous or exogenous glucocorticoids).

Clinical Pearls

• What characteristics of solitary pulmonary nodules are suggestive of benign conditions as opposed to cancer?   

Benign nodules typically are less than 5 mm in the greatest dimension, have smooth borders, and appear dense or solid, with a concentric, central, or homogeneous pattern of calcification. Benign nodules tend to double in size either very rapidly (in <1 month) or very slowly (in >1 year). Features of nodules that are worrisome for cancer include a size greater than 10 mm, the presence of irregular or spiculated borders, a nonsolid ground-glass appearance, the absence of calcifications or the presence of eccentric  calcifications, and a doubling time between 1 month and 1 year.  Additional clinical factors incorporated into treatment algorithms include smoking history, age, and a personal cancer history.

• What are the clinical features of Cushing’s syndrome?

Many of the clinical features of Cushing’s syndrome (e.g., obesity,  hypertension, hyperglycemia, edema, hypokalemia, fatigue, mood disorders, and insomnia) are common but nonspecific; others (e.g. easy bruising, purple striae, facial plethora, and proximal-muscle weakness) are more specific and particularly helpful in reaching a clinical diagnosis.

Morning Report Questions

Q: According to the authors, what nonpathological forms of hypercortisolism should be considered when patients present with features that are suggestive of Cushing’s syndrome?      

A: Patients with nonpathological forms of hypercortisolism (e.g.,  pregnancy, depression, alcohol abuse, morbid obesity) can present  with similar features, and these diagnoses should keep these in mind as potential causes of abnormal laboratory values during evaluation.

Q: What diagnostic assays are available for Cushing’s syndrome?

A: The most sensitive test is the measurement of the 24-hour urinary free cortisol level, which is recommended in the setting of a high clinical suspicion of Cushing’s syndrome. However, there are a number of considerations: the urine volume must be adequate (if the volume is too high, it can lead to a false positive result, and, if too low, to a false negative result), the patient must not be taking exogenous glucocorticoids that might interfere with the test, and the creatinine level should be normal. If the level of urinary free cortisol is higher than three times the upper limit of the normal range, it is diagnostic for Cushing’s syndrome. For the 1 mg overnight dexamethasone suppression test, the patient needs to take 1 mg of dexamethasone between 11 p.m. and midnight the night before the test. Then, the serum cortisol level should be measured at precisely 8 a.m. A level greater than 5 micrograms per deciliter (138 nmol per liter) is suggestive of Cushing’s syndrome. To increase the sensitivity of the test, some advocate lowering the cut-off point to 1.8 micrograms per deciliter (50 nmol per liter). The 1-mg dexamethasone suppression test has a very good negative predictive value — a cortisol level less than 1.8 micrograms per deciliter effectively rules out Cushing’s syndrome. A high-dose dexamethasone suppression test is used to screen for Cushing’s disease, since a low dose test does not typically cause suppression, but a high dose of dexamethasone will. A measurement of the salivary cortisol level is a test that can beperformed at home. The patient chews on a cotton swab and deposits the saliva in a vial that can be sent back to the laboratory. Saliva is collected between 11 p.m. and midnight.


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