Obesity-associated hypogonadism is very prevalent in males with morbid obesity and is mostly reversed after sustained weight loss by bariatric surgery.

Objective: Most cases of familial isolated pituitary adenomas with mutated aryl hydrocarbon receptorinteracting protein (AIP:HGNC:358) gene develop somatotropinomas. They are characterised by an aggressive clinical phenotype including early age at diagnosis, large tumours and frequent invasiveness. There is little information on AIP gene mutations' prevalence in isolated somatotropinomas characterised by poor response to somatostatin analogue treatment. The aim of this study was to investigate the prevalence of AIP mutations in non-familial cases of somatotropinomas with poor response to conventional treatment. Design and methods: Fifty patients with acromegaly (22 males/28 females, age 51G18 years) and 60 controls were included in this study performed at eight University Hospitals in Spain. None had family history of pituitary adenomas or other endocrine tumors. All patients failed to respond to conventional treatment including surgery and somatostatin analogues. Some patients received adjuvant radiotherapy and most cases required pegvisomant (PEG) treatment for normalisation of IGF1. AIP analysis was performed in DNA extracted from peripheral leucocytes, using standardised PCR protocol in which the coding regions of exons 1, 2, 3, 4, 5 and 6 were amplified. Possible deletions/duplications were studied using multiplex ligation-dependent probe amplification. Results: Sequence changes of potential different significance that could be considered as mutations or variations of unknown significance (VUS) of the AIP gene were found in four patients (8%). In two cases, two different mutations previously described were found: p.Arg9Gln and p.Phe269Phe. Two other VUS were also found: c.787C24COT in intron 5 and c.100-18COT in intron 1. Age at diagnosis ranged from 21 to 50 years old, and in all patients, the tumor was a macroadenoma depicting IGF1 normalisation under PEG treatment. Conclusions: AIP germline mutations show a low, but non-negligible, prevalence in non-familial acromegaly patients with tumors resistant to treatment with somatostatin analogues.European Journal of Endocrinology 168 9-13

Leptin is an independent predictor of TSH concentration variations only in euthyroid smoker subjects of both sexes at all ranges of BMI, but not in nonsmokers. Age, smoking status, and positive thyroid autoimmunity also influenced TSH variability.

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