I. Patelli

Prevalence of Vertebral Fractures in Men with Acromegaly

CONTEXT Data on osteoporotic fractures in acromegaly are limited. An increased prevalence of radiological vertebral fractures was already observed in postmenopausal women with active acromegaly. It is unknown whether this observation may reflect a more general increased risk of fractures in acromegaly. DESIGN This was a cross-sectional study. SETTING The study was conducted at referral centers. PATIENTS AND CONTROL SUBJECTS Subjects included 40 males with acromegaly (25 patients with controlled disease and 15 patients with active disease) and 31 control males, with age and gonadal status comparable with the patients. INTERVENTIONS Evaluation of vertebral fractures (quantitative morphometric analysis) and bone mineral density (BMD) at lumbar spine and total hip (dual energy X-ray absorptiometry) was done. MAIN OUTCOME MEASURE Vertebral fractures were assessed. RESULTS Although BMD was not significantly different between acromegalic patients and control subjects, the prevalence of vertebral fractures was higher in acromegalic patients as compared with the control subjects (57.5 vs. 22.6%; chi(2): 8.7; P = 0.003). Fractured and nonfractured acromegalic patients showed no significant difference in age and BMD Z-score. However, acromegalic patients with fractures had serum IGF-I values significantly higher and duration of active disease significantly longer with respect to patients without fractures. Moreover, patients with fractures showed significantly longer untreated hypogonadism as compared with patients without fractures. In a multivariate logistic regression analysis, the duration of active acromegaly was the only risk factor significantly correlated with the occurrence of fractures (odds ratio 1.1, confidence interval 1.04-1.6). CONCLUSIONS This study reports for the first time a high prevalence of osteoporotic vertebral fractures in an unselected acromegalic male population generally considered at low risk of osteoporosis, suggesting that complicated osteoporosis is an important comorbidity of acromegaly.

Serum TSH values and risk of vertebral fractures in euthyroid post-menopausal women with low bone mineral density

INTRODUCTION There is evidence that variations of thyrotropin (TSH) even in its reference range may influence bone mineral density (BMD). In fact, low-normal TSH values have been associated with high prevalence of osteoporosis in post-menopausal women. However, data associating TSH and risk of fractures are scanty and limited to subjects with subclinical thyrotoxicosis. MATERIALS AND METHODS In this observational study, we investigated the correlation between serum TSH and prevalence of radiological vertebral fractures in a cohort of 130 post-menopausal women with normal thyroid function. RESULTS Osteoporosis was observed in 80 women (61.5%), whereas 49 women (37.7%) had osteopenia. Vertebral fractures were found in 49 women (37.7%), who were significantly older, with higher prevalence of osteoporosis and with lower serum TSH values as compared with women who did not fracture. Stratifying the patients according to serum TSH values, vertebral fractures were found to be significantly (p=0.004) more prevalent in first tertile (56.8%) of TSH values as compared with the second (23.3%) and third tertiles (32.6%). Multivariate logistic regression analysis demonstrated that low serum TSH maintained a significant correlation with vertebral fractures (odds ratio 2.8, C.I. 95% 1.20-6.79) even after correction for age, BMD, BMI and serum free-thyroxine values. DISCUSSION Low-normal TSH values are associated with high prevalence of vertebral fractures in women with post-menopausal osteoporosis or osteopenia, independently of thyroid hormones, age and BMD.

Glucocorticoid replacement therapy and vertebral fractures in hypopituitary adult males with GH deficiency

OBJECTIVE GH deficiency (GHD) and glucocorticoid excess are associated with increased risk of fragility fractures. We aimed to evaluate whether the prevalence of vertebral fractures may be influenced by glucocorticoid over-replacement in hypopituitary males with GHD. DESIGN Cross-sectional study. METHODS Fifty-one adult hypopituitary patients (all males; mean age 55 years, range: 23-81) with severe adult-onset GHD (replaced in 21 patients and untreated in 30 patients) and glucocorticoid deficiency on replacement treatment were studied for vertebral fractures using a radiological and morphometric approach. RESULTS Vertebral fractures were observed in 31 patients (60.8%) in correlation with untreated GHD, urinary cortisol values, and cortisone doses. Patients were stratified according to treatment of GHD, and current and cumulative cortisone doses. In untreated GHD, vertebral fractures occurred more frequently in patients who had received higher (greater than median) cumulative and current doses of cortisone compared with patients who had received lower (less than median) drug doses (95.2 vs 50.0%, P=0.009 and 90.5 vs 55.6%, P=0.04 respectively). In untreated GHD, fractured patients had significantly higher urinary cortisol values compared with patients without vertebral fractures (84 microg/24 h, range: 24-135 vs 49 microg/24 h, range: 30-96; P=0.04). In treated GHD patients, by contrast, the prevalence of vertebral fractures was not influenced by cumulative and current cortisone doses and urinary cortisol values. CONCLUSIONS Glucocorticoid over-replacement may increase the prevalence of vertebral fractures in patients with untreated GHD. However, treatment of GHD seems to protect the skeleton from the deleterious effects of glucocorticoid overtreatment in hypopituitary patients.

Biochemical Evaluation of Patients with Active Acromegaly and Type 2 Diabetes Mellitus: Efficacy and Safety of the Galanin Test

The oral glucose tolerance test, which is considered the gold standard for the diagnosis of active acromegaly, should not be performed in the presence of basal hyperglycemia. Moreover, false-positive responses may occur in patients with diabetes mellitus. Galanin has previously been demonstrated to induce paradoxical inhibition of growth hormone (GH) secretion in most patients with active acromegaly. In this study, we assessed GH response to galanin infusion in a series of 17 consecutive patients with active acromegaly, 7 of whom had coexistent type 2 diabetes mellitus and 10 were without either diabetes mellitus or impaired tolerance to glucose. 6 acromegalic patients with diabetes mellitus (85.7%) and 7 without diabetes (70.0%) showed a decrease in serum GH values during galanin infusion (χ2 0.9; p = 0.6). The GH nadir occurred at a comparable time in the two groups of acromegalic patients. Moreover, the two groups showed no significant difference (p = 0.45) in ΔGH during galanin infusion. Galanin infusion did not induce any significant change in plasma glucose levels in both diabetic and non-diabetic patients with acromegaly. The results of our study provide evidence that the galanin test may be of value for the diagnosis of acromegaly in patients with type 2 diabetes mellitus.

Contents Vol. 88, 2008

D.H. Abbott, Madison, Wisc. H. Ahlman, Gothenburg E. Arzt, Buenos Aires T. Bartness, Atlanta, Ga. C.L. Bethea, Beaverton, Oreg. D.W. Brann, Augusta, Ga. B. Canny, Monash M. Caplin, London K. Catt, Bethesda, Md. A. Chodobski, Providence, R.I. C. Coen, London W. de Herder, Rotterdam S.L. Dickson, Gothenburg J. Drouin, Montreal W. Farrell, Keele M. Freeman, Tallahasse, Fla. R.C. Gaillard, Lausanne A.C. Gore, Austin, Tex. K. Grove, Portland, Oreg. T. Harmar, Edinburgh A. Herbison, Dunedin J. Herman, Cincinnati, Ohio J.J. Hirst, Callaghan T. Hökfelt, Stockholm D. Jezová, Bratislava U. Kaiser, Boston, Mass. A. Kauff man, Seattle, Wash. K. Kim, Seoul J.Z. Kiss, Geneva G. Leng, Edinburgh J. Levine, Evanston, Ill. C. Libertun, Buenos Aires C. Llorens-Cortes, Paris A. Loudon, Manchester Z.-L. Lu, Edinburgh G. Martinez de la Escalera, Querétaro R. Melcangi, Milano Z. Naor, Tel Aviv S.R. Ojeda, Beaverton, Oreg. M. Palkovits, Budapest I. Parhar, Kuala Lumpur D.W. Pfaff , New York, N.Y. J. Reul, Bristol G. Rindi, Parma J.L. Roberts, San Antonio, Tex. I. Robinson, London P. Ruszniewski, Clichy W. Schlegel, Geneva A.J. Silverman, New York, N.Y. D. Skinner, Laramie, Wyo. E. Spinedi, La Plata R. Steiner, Seattle, Wash. E. Terasawa, Madison, Wisc. A. Tilbrook, Clayton W. Vale, La Jolla, Calif. B. Walker, Edinburgh H. Watanobe, Tokyo M. Wierman, Denver, Colo. J. Wingfi eld, Seattle, Wash. S. Wray, Bethesda, Md. International Journal for Basic and Clinical Studies on Neuroendocrine Relationships