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P H Kann, D Ivan, A Pfützner, Th Forst, P Langer and S Schaefer

Objective: Endoscopic ultrasound (EUS) is a highly reliable procedure to localize insulinomas preoperatively. It has been considered to be important in planning surgical strategy, especially considering a minimal invasive approach. However, even under ideal conditions experienced examiners miss about 10–20% of insulinomas by EUS imaging.

Design and methods: This retrospective study aimed to identify factors associated with negative EUS imaging. Twenty-nine consecutive patients (24 benign and 5 malignant) with sporadic pancreatic insulinomas confirmed by successful surgery and positive histopathology were included. All EUS examinations were performed by one single experienced examiner over a period of one decade.

Results: Three of the tumors were not detected by preoperative EUS as they were isoechoic to the surrounding healthy pancreatic tissue; 25 could be detected as hypoechoic lesions, (including all malignant tumors), and one lesion was hyperechoic. Low body mass index (P=0.053) and young age (P=0.037) were associated with negative EUS imaging. All patients with negative imaging were females. The position on the examiner’s learning curve, the diameter and location of insulinoma, and endocrine parameters (insulin concentrations and insulin–glucose ratios in the prolonged fasting test) had no influence on the success of EUS imaging.

Conclusions: Some insulinomas are missed by preoperative EUS imaging as they are completely isoechoic. A low body mass index, female gender, and young age might be risk factors for negative imaging.

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S Schaefer, N Boegershausen, S Meyer, D Ivan, K Schepelmann and P H Kann

Objective

Hypothalamic–pituitary insufficiency may have diverse causes. The aim of this study was to determine the incidence of hypothalamic–pituitary insufficiency in patients with previous infectious diseases of the central nervous system (CNS) of different etiologies and mild-to-moderate clinical course.

Design

Patient series. Basal and stimulated (insulin tolerance test) pituitary function testing was performed in 19 patients with previous neuroborreliosis, encephalitis, or meningitis following an interval of between 10 and 56 months (mean 26.1±13.1 months) after the acute event.

Results

Four patients (21%; two males, two females) showed an isolated corticotropic insufficiency (peak cortisol <181.25 μg/l during the insulin tolerance test). Two patients (11%, males) showed borderline gonadotropic insufficiency (basal testosterone between 2.4 and 3.0 μg/l). No patient had somatotropic or thyrotropic insufficiency or evidence for diabetes insipidus; all had prolactin concentrations within the reference range.

Conclusions

Hypothalamic–pituitary dysfunction and especially isolated corticotropic insufficiency may develop in a relevant proportion of patients after infectious diseases of the CNS.

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S Schaefer, M Shipotko, S Meyer, D Ivan, K J Klose, J Waldmann, P Langer and P H Kann

Objective

Adrenal lesion is one of the features of multiple endocrine neoplasia type 1 (MEN1). This study aimed to assess prevalence, natural course and clinical relevance of small adrenal lesions without clinical symptoms, endocrine activity, or mechanical problems and thus without clear indication for surgical therapy by endoscopic ultrasound (EUS).

Design and methods

Forty-nine patients with familial MEN1 were studied. Twenty-seven of these with adrenal lesions were detected by EUS and at least two performed EUS examinations were included into a subgroup where changes in adrenal morphology were studied by measuring changes in the largest diameter of the dominant adrenal tumour.

Results

EUS detected adrenal lesions in 36 (73%) patients: 6 (12%) plump adrenals, 17 (35%) nodular hyperplasia, 12 (24%) adenomas and 1 (2%) cyst. Bilateral adrenal lesions were detected in 17 patients and unilateral in 19 patients. A change in the largest tumour diameter was found to be for nodular hyperplasia −0.02±1.41% per month (range −2.56 to 4.58%) and for adenomas −0.61±1.95% per month (range −6.25 to 1.15%). One patient had an adrenal cyst with significant growth. There was no evidence of carcinoma or metastatic disease during the study.

Conclusions

The prevalence of adrenal lesions in MEN1 is higher than that reported earlier. Except one cystic lesion, no significant change in the tumour size was observed over a mean observation period of more than 2 years. In a typical situation, small adrenal lesions in MEN1 seem to be constant in their morphology.

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Marco Bonomi, Valeria Vezzoli, Csilla Krausz, Fabiana Guizzardi, Silvia Vezzani, Manuela Simoni, Ivan Bassi, Paolo Duminuco, Natascia Di Iorgi, Claudia Giavoli, Alessandro Pizzocaro, Gianni Russo, Mirella Moro, Letizia Fatti, Alberto Ferlin, Laura Mazzanti, Maria Chiara Zatelli, Salvo Cannavò, Andrea M Isidori, Angela Ida Pincelli, Flavia Prodam, Antonio Mancini, Paolo Limone, Maria Laura Tanda, Rossella Gaudino, Mariacarolina Salerno, Pregnolato Francesca, Mohamad Maghnie, Mario Maggi, Luca Persani and Italian Network on Central Hypogonadism

Objective

Isolated hypogonadotropic hypogonadism (IHH) is a rare disorder with pubertal delay, normal (normoosmic-IHH, nIHH) or defective sense of smell (Kallmann syndrome, KS). Other reproductive and non-reproductive anomalies might be present although information on their frequency are scanty, particularly according to the age of presentation.

Design

Observational cohort study carried out between January 2008 and June 2016 within a national network of academic or general hospitals.

Methods

We performed a detailed phenotyping of 503 IHH patients with: (1) manifestations of hypogonadism with low sex steroid hormone and low/normal gonadotropins; (2) absence of expansive hypothalamic/pituitary lesions or multiple pituitary hormone defects. Cohort was divided on IHH onset (PPO, pre-pubertal onset or AO, adult onset) and olfactory function: PPO-nIHH (n = 275), KS (n = 184), AO-nIHH (n = 36) and AO-doIHH (AO-IHH with defective olfaction, n = 8).

Results

90% of patients were classified as PPO and 10% as AO. Typical midline and olfactory defects, bimanual synkinesis and familiarity for pubertal delay were also found among the AO-IHH. Mean age at diagnosis was significantly earlier and more frequently associated with congenital hypogonadism stigmata in patients with Kallmann’s syndrome (KS). Synkinesis, renal and male genital tract anomalies were enriched in KS. Overweight/obesity are significantly associated with AO-IHH rather than PPO-IHH.

Conclusions

Patients with KS are more prone to develop a severe and complex phenotype than nIHH. The presence of typical extra-gonadal defects and familiarity for PPO-IHH among the AO-IHH patients indicates a common predisposition with variable clinical expression. Overall, these findings improve the understanding of IHH and may have a positive impact on the management of patients and their families.