Changing patterns in diagnosis and therapy of acromegaly over two decades.

BACKGROUND: The increased morbidity and mortality of acromegaly makes early diagnosis and therapy critical. However, whether the type of medical professional who first diagnoses acromegaly, the major complaint prompting medical attention, or the management paradigms used in the setting of novel medical therapies have changed over time has not been well explored. OBJECTIVES: Our objective was to identify the medical professional who first suspected acromegaly and the complaint prompting the diagnosis, and if these have changed. Additional goals were to assess the interval from symptom onset to diagnosis of acromegaly and to compare treatment trends over consecutive decades. DESIGN: This was a case-record retrospective study. SETTING: The study was performed in a neuroendocrine clinical center at a tertiary care center. SUBJECTS: A total of 100 patients (45 men and 55 women) with acromegaly referred from 1985-2005 was included in the study. RESULTS: Acral changes (24%) and headaches (20%) were most prevalent presenting symptoms prompting diagnosis. Eighteen percent reported no symptoms of acromegaly at diagnosis. The primary care physician most often initiated the evaluation (44%). Comorbidities were more prevalent in older patients (P = 0.001). The interval between symptom onset and diagnosis decreased, compared with previous reports. Radiation therapy was used less frequently in the decade after 1994 than in the prior (16 vs. 33%; P < 0.05). CONCLUSIONS: The primary care doctor plays the major role in diagnosis of acromegaly. The increased use of brain magnetic resonance imaging may contribute to the many incidentally discovered cases and to the shortened time interval to diagnosis. Presumably due to the availability of new medical therapies, the use of radiation therapy has decreased.

Skeletal Fragility in Endogenous Hypercortisolism.

Skeletal fragility is a frequent complication of endogenous hypercortisolism, and fragility fractures may be the first clinical manifestation of the disease. Fractures involve more frequently the vertebrae and may occur in 30-50% of the patients exposed to glucocorticoid excess, in close relationship with severity and duration of hypercortisolism. Although improvement of bone mineral density was reported after resolution of hypercortisolism, there are patients with persistently high fracture risk after the cure of hypercortisolism, and other patients in whom the resolution of hypercortisolism may take a long time, implying a multistep therapeutic approach. Since vertebral fractures tend to occur early during the natural history of disease, a skeletal-specific approach should be undertaken in these patients; however, the cost-effectiveness of this approach is still largely unknown since data on effectiveness and safety of bone-active drugs in endogenous hypercortisolism are scarce.

The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial.

The effect of metformin (1000 mg twice a day) on markers of endothelial activation, inflammation, and coagulation was investigated in subjects with impaired glucose tolerance (IGT) in a 16-wk, randomized, placebo-controlled, double-blind study. Soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, C-reactive protein, TNFalpha, von Willebrand factor, and tissue plasminogen activator were measured at baseline and at the end of the trial. Subjects with IGT (n = 55, 14 males and 41 females), aged 48.4 +/- 9.6 yr with a body mass index of 31.4 +/- 5.6 kg/m(2), were studied. All participants followed a 1-month stabilization period in their diet and physical activity. Afterward, 29 subjects were assigned to the treatment group and 26 to the control group. A significant reduction in weight, fasting plasma glucose, soluble intercellular adhesion molecule (306 +/- 75 vs. 268 +/- 61 ng/ml, P = 0.029), soluble vascular cell adhesion molecule (595 +/- 114 vs. 508 +/- 126 ng/ml, P = 0.006), and von Willebrand factor (124 +/- 34 vs. 94 +/- 34%, P = 0.001) was seen in the treatment group, whereas tissue plasminogen activator, TNFalpha, and C-reactive protein levels did not change. No change was seen in the control group. Thus, metformin improves the plasma levels of some markers of endothelial activation and coagulation in subjects with IGT, whereas it has no effect on markers of inflammation.