We examined pituitary tumor volumes in patients treated with pegvisomant for 18 months or longer, and in whom the tumors were monitored for at least 3 years. We present details on 9 of 304 patients in clinical trials with pegvisomant who experienced tumor growth within the first year of treatment.Magnetic resonance images prior to start of pegvisomant and at last follow-up were examined in 43 patients (14% of participating patients). Twenty-nine had received prior radiation therapy (18% of irradiated patients) and all but five received somatostatin analogs between periods of pegvisomant treatment.At follow-up, the median tumor volume was 0.6 cc (range 0.0-19.7 cc), in comparison with 1.6 cc (0.0-19.7 cc) at baseline (P<0.001). Twenty-five patients, of which 23 received radiation therapy, had tumor volume reduction. Seventeen patients had no significant change. One patient, who had not received radiation therapy, had an increase in tumor volume from 1.61 to 1.93 cc. Of the nine patients with tumor growth, six had progressive growth before initiating pegvisomant. Two patients with stable tumors while on octreotide experienced enlargement after octreotide discontinuation but remained stable on long-term pegvisomant therapy.The present data indicate that pegvisomant does not promote tumor growth and suggest that the nine observed cases of tumor progression, which occurred within 8 months after commencing pegvisomant, are likely rebound expansions after discontinuation of somatostatin analogs and/or the natural history of aggressively growing pituitary tumors. Continued long-term surveillance of tumor volume, particularly in non-irradiated patients, is recommended.
GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients.Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values <0.05 were considered statistically significant.PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference.GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures.
OBJECTIVE: This open label, multicentre study was designed to evaluate the efficacy and tolerability of lanreotide Autogel (L-Autogel) in acromegalic patients over a 24-week period. The outcome of treatment with this new, long-acting, aqueous formulation of lanreotide was also compared with the patients' previous treatment with octreotide long acting repeatable (LAR). DESIGN AND METHODS: Twenty-five acromegalic patients (13 males, mean age 51+/-12 years) were switched from octreotide LAR (20-40 mg/4 weeks for at least 6 months) to L-Autogel, given deep subcutaneously at a fixed dose of 90 mg/4 weeks. After 12 weeks, the dose of L-Autogel was titrated according to patients' mean GH and IGF-I levels at week 8. It was increased to 120 mg/4 weeks if GH>2.5 microg/l or if IGF-I was above the age-adjusted normal range. It was reduced to 60 mg/4 weeks if mean GH<1 microg/l and IGF-I was within the normal range. If the values did not fall within these ranges, the dose remained unchanged at 90 mg. RESULTS: After 24 weeks of treatment with L-Autogel (final doses 60 mg in 3 patients, 90 mg in 4 patients and 120 mg in 18 patients), mean serum GH (2.9+/-2.4 microg/l) and IGF-I concentrations (332+/-193 microg/l) remained statistically unchanged when compared with baseline values under octreotide LAR (GH 2.4+/-1.8 microg/l and IGF-I 337+/-201 microg/l, non significant (NS)). There was a significant improvement of the acromegalic symptom score over the study period, from 4.8+/-3.4 to 2.8+/-2.5 (P<0.001) and a small but significant reduction in the residual pituitary tumour volume (P<0.05). Local side-effects were observed less frequently and no technical problems were encountered with the L-Autogel injections, as opposed to treatment with octreotide LAR (60 difficult injections/150 (P<0.001)). CONCLUSIONS: L-Autogel appears to be as effective as octreotide LAR in lowering GH and IGF-I concentrations in acromegalic patients. This treatment was also well tolerated by the patients, giving fewer local side-effects and technical problems with injections. These advantages may improve the long-term acceptability of medical treatment in acromegaly.
A 29-year-old female patient with Graves' disease who developed thyroid hormone autoantibodies (THAA) under treatment with methimazole is presented. THAA were identified as IgG-ĸ. During a first pregnancy that ended by miscarriage in the 3rd month, the titer of anti-thyroxine autoantibodies decreased by about 30%. Relapse of Graves' disease occurred 2 months later and an increase in serum THAA concentration to the initial titer was observed. THAA titer remained unchanged during treatment with methimazole and afterwards during thyroxine supplementation for radioiodine-induced hypothyroidism. During a second pregnancy, a decrease in anti-thyroxine autoantibody titer reached 45% at the time of delivery and an increase by 20% was noted 5 months later. A similar decline in THAA concentration was shown during a third pregnancy. The changes in THAA concentrations observed during pregnancy suggest an immunological influence of pregnancy on the THAA production, as previously demonstrated in other autoimmune diseases, like Hashimoto's thyroiditis.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by nodular proliferation of the parathyroid glands and tumors of the anterior pituitary gland, the endocrine pancreas, and the neuroendocrine cell system of the gut. Loss of the putative tumor suppressor effect of the MEN1 gene is probably responsible for the development of MEN1-associated tumors. We report here a genetic study of a female MEN1 patient with the association of nodular hyperplasia of two parathyroid glands, an insulinoma, multiple duodenal gastrinomas, a prolactinoma, and a gastric carcinoid. We performed loss of heterozygosity (LOH) studies of chromosome 11 on all affected tissues except the insulinoma. Allelic losses of chromosome 11 were detected in several tumors, but the chromosomal regions of LOH were different, suggesting that different somatic mutational events are involved in the pathogenesis of these tumors. LOH of chromosome 11 was also detected in the prolactinoma of this patient, which indicates that the MEN1 gene has a tumor suppressor effect in the pituitary.
