AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.

The posttreatment basal GH concentration less than 2.5 microg/liter in acromegalic patients is associated with a normal lifespan. Excess mortality is confined to poorly controlled patients and possibly those who have received conventional radiotherapy.

Our results support the previous finding that germline CDKN1B/p27(Kip1) mutations predispose to a human MEN1-like condition. However, such mutations appear uncommon in suspected MEN1 cases and rare or nonexistent in familial or sporadic acromegaly/pituitary adenoma patients.

Pituitary adenomas are common neoplasms of the anterior pituitary gland. Germ-line mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene cause pituitary adenoma predisposition (PAP), a recent discovery based on genetic studies in Northern Finland. In this population, a founder mutation explained a significant proportion of all acromegaly cases. Typically, PAP patients were of a young age at diagnosis but did not display a strong family history of pituitary adenomas. To evaluate the role of AIP in pituitary adenoma susceptibility in other populations and to gain insight into patient selection for molecular screening of the condition, we investigated the possible contribution of AIP mutations in pituitary tumorigenesis in patients from Europe and the United States. A total of 460 patients were investigated by AIP sequencing: young acromegaly patients, unselected acromegaly patients, unselected pituitary adenoma patients, and endocrine neoplasia-predisposition patients who were negative for MEN1 mutations. Nine AIP mutations were identified. Because many of the patients displayed no family history of pituitary adenomas, detection of the condition appears challenging. Feasibility of AIP immunohistochemistry (IHC) as a prescreening tool was tested in 50 adenomas: 12 AIP mutation-positive versus 38 mutation-negative pituitary tumors. AIP IHC staining levels proved to be a useful predictor of AIP status, with 75% sensitivity and 95% specificity for germ-line mutations. AIP contributes to PAP in all studied populations. AIP IHC, followed by genetic counseling and possible AIP mutation analysis in IHC-negative cases, a procedure similar to the diagnostics of the Lynch syndrome, appears feasible in identification of PAP.immunohistochemistry ͉ growth hormone/prolacting-secreting adenomas ͉ acromegaly

KAUKUA, JARMO, TUULA PEKKARINEN, TIMO SANE, AND PERTTI MUSTAJOKI. Sex hormones and sexual function in obese men losing weight. Obes Res. 2003;11:689-694. Objective: To study the impact of a weight-loss program on sex hormones and sexual function among 38 middle-aged obese men (BMI Ն35 kg/m 2 ). Research Methods and Procedures: A randomized controlled clinical trial was conducted. The treatment group (n ϭ 19) participated in a 4-month weight-loss program including 10 weeks on a very-low-energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n ϭ 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time-points during follow-up. Results: The mean weight loss in the treatment group was 21 kg at the end of the 10-week VLED. At the end of follow-up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormonebinding globulin, testosterone, and high-density lipoproteincholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow-up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group. Discussion: We conclude that obese men lose weight and increase their serum testosterone level on a weight-loss program with VLED and behavior modification. However, they do not change their sexual function scores.

OBJECTIVE:To study health-related quality of life (HRQL) in a clinically selected sample obese outpatients. DESIGN: A single-strand before and after study with 2-y follow-up after treatment comprising 10 weeks on very-low-energy diet (VLED) and 4 months of behaviour modification in groups. SUBJECTS: A total of 126 patients (mean (s.d.) age 48.2 (11.1) y and body mass index (BMI) 42.8 (6.2) kg/m 2 (63% women)) referred for treatment in an obesity clinic. MEASUREMENTS: Weight and HRQL using questionnaires (RAND 36-Item Health Survey 1.0 and Obesity-related Psychosocial problems-scale). RESULTS: In all, 100 patients (61% women) completed the treatment and 67 (71% women) completed the 2-y follow-up. The mean (s.d.) weight loss was 12.5 (5.6)% at the end of group therapy, 6.0 (7.1)% at 1 y, and 2.6 (7.5)% at 2 y. At baseline, the mean (s.d.) score for OP-scale was 61.9 (24.6). The mean scores on every RAND-36 scale were markedly lower than in the Finns without chronic conditions. All the scales in HRQL improved markedly during the treatment. During the follow-up, all the scales started to return back towards baseline levels and at 2 y, only obesity-related psychosocial problems and physical functioning were still improved relative to baseline. In categories of weight change at 2 y (Z10% weight loss, 0-9.9% weight loss, weight gain), obesity-related psychosocial functioning, physical functioning, and general health showed dose-response improvement with increasing weight loss. A Z10% weight loss at 2 y after treatment was associated with clear improvement in obesity-related psychosocial problems, physical functioning, physical role functioning, bodily pain, general health, mental health, and vitality. A 0-9.9% weight loss was associated with improvement in obesity-related psychosocial problems and physical functioning. Weight gain was associated with improvement in obesity-related psychosocial problems and social functioning. The study population was too small to examine possible gender differences. CONCLUSIONS: Treatment with VLED and behaviour modification produces marked short-term weight loss and clear improvement in all aspects of HRQL. At 2 y after treatment, the average maintained weight loss is modest. However, one-third of patients maintain Z5% weight loss. Improvement in obesity-related psychosocial problems and physical functioning is associated even with o10% of maintained weight loss. Since the pattern of HRQL changes did only partly follow the pattern of weight change as expected, other factors, such as the therapeutic effect of participating in the weight loss programme or increase in physical activity, may affect HRQL responses.

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HRQoL is reduced in treated patients with acromegaly. The best HRQoL may be achieved by normalization of IGF-I and by targeting the GHOGTT nadir to levels between 0.3 and 1.0 microg/liter. Radiotherapy is associated with adverse HRQoL.