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Peter Wiesli, Beat Schwegler, Beat Schmid, Giatgen A Spinas, and Christoph Schmid

Objective: To determine whether systematic evaluation of cognitive function by the Mini-Mental State Examination (MMSE) allows the objective detection and documentation of cognitive deterioration in patients referred for evaluation of suspected hypoglycaemic disorders by the 72-h fast.

Design: Prospective case series.

Methods: In 50 patients referred for evaluation of suspected hypoglycaemic disorders, the MMSE score (maximum 30 points) was assessed at the start and at the end of the fast.

Results: The fast was terminated before 72 h in 14 patients because they developed neuroglycopenic symptoms due to hypoglycaemic disorders. Their MMSE score fell from a median of 29 points (range 20–30) at the beginning to 17 points (range 0–24) at the termination of the fast. The score dropped by ≥6 points in all patients with hypoglycaemic disorders. Median (range) plasma glucose concentration at the end of the fast was 2.1 (1.1–2.5) mmol/l. Thirty-six individuals developed no neuroglycopenic symptoms throughout the 72-h fast, their MMSE score remained between 27 and 30 throughout the fast and their median plasma glucose concentration dropped to 2.9 (2–3.6) mmol/l.

Conclusions: Systematic evaluation of cognitive function by the MMSE at the beginning and at the termination of the fast allows objective determination and documentation of the deterioration of the cognitive state in patients with hypoglycaemic disorders. A decline in the cognitive performance by ≥6 points in the MMSE score rather than a distinct plasma glucose concentration should be used as the criterion to terminate the prolonged fast before 72 h.

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Thomas Münzer, Andrea Hegglin, Tobias Stannek, Otto D Schoch, Wolfgang Korte, Daniel Büche, Christoph Schmid, and Christoph Hürny


To investigate the long-term effects of nasal continuous positive airway pressure (CPAP) ventilation in patients with obstructive sleep apnea syndrome (OSAS) on body composition (BC) and IGF1.


Observational study.


Seventy-eight (11 females and 67 males) OSAS patients who were compliant with CPAP (age 51±1.1 years) participated in the study. We assessed body mass index (BMI), total body mass (TBM), total body fat (TBF; kg) and lean body mass (LBM; kg), abdominal subcutaneous (SC) and visceral (V) fat (cm2), and waist circumference (WC; cm) by magnetic resonance imaging, and IGF1 (ng/ml) before and after 7.8±1.3 months of CPAP use of an average of 5.9±1.2 h.


Women had a higher BMI, WC; TBM, TBF, and more SC fat. Men had a higher LBM and more V fat. CPAP increased WC (+2.8±9.6 cm, P=0.02) and LBM (2.2±0.5 kg, P=0.006), but not IGF1. In men, CPAP increased BMI (0.5±0.2 kg/m2, P=0.02), WC (1.7±6.9 cm, P=0.002), TBM (1.7±0.4 kg, P=0.0001), LBM (1.5±0.4 kg, P=0.0003), SC fat (12.9±5.1 cm2, P=0.02), and IGF1 (13.6±4.2 ng/ml, P=0.002).

Compliance with CPAP increased LBM in men aged <60 years, but not in those aged >60 years, and IGF1 increased in men aged 40–60 years only.


Long-term CPAP increased LBM in both sexes and IGF1 in men, while fat mass remained unchanged, suggesting a sexually dimorphic response of IGF1 to CPAP. The role of the GH axis activity and age to this response is unclear. The metabolic consequences of changes in LBM are still to be determined. Future studies on the effects of CPAP on BC should include LBM as an outcome.

Free access

Lisa Sze, Christoph Schmid, Konrad E Bloch, René Bernays, and Michael Brändle

Objective: Sleep apnoea syndrome (SAS) is common in acromegaly and both diseases are independently associated with hypertension and insulin resistance contributing to increased morbidity and mortality. Pituitary surgery remains the principal treatment modality in acromegaly. The aim of this study was to assess the prevalence and risk factors of SAS in acromegaly and to analyze the effect of transsphenoidal adenomectomy on SAS and cardiovascular risk factors.

Subjects and methods: Thirteen consecutive patients (seven women and six men, aged 25–77 years) with newly diagnosed acromegaly were prospectively studied. Biochemical assessment (IGF-I, GH, acid labile subunit, fasting blood glucose (FBG), insulin), overnight respiratory polygraphy, and an Epworth Sleepiness scale score (ESS) were obtained before and 12 weeks after surgery. SAS was defined by an ESS ≥ 10 and ≥ 5 apnoeas/hypopnoeas (central or obstructive) per hour.

Results: Six of the thirteen (46%) patients had SAS. Risk factors were male gender (83.3 vs 14.3% without SAS) and long disease duration until diagnosis of acromegaly (10.2 ± 3.2 vs 4.6 ± 3.6 years, mean ± s.d.). Ten patients had a homeostasis assessment model score ≥ 4 indicating insulin resistance and one had diabetes mellitus requiring insulin. Seven patients had hypertension (≥ 140/90 mmHg). Postoperatively, GH and IGF-I levels decreased, but only five patients were cured. However, SAS resolved in all patients irrespective of whether acromegaly was cured or not. FBG (5.5 ± 1.2 vs 4.8 ± 0.4 mmol/l) and systolic blood pressure (150.8 ± 18.5 vs 130.8 ± 17.5 mmHg) decreased in all SAS patients.

Conclusion: We found a high prevalence of SAS in acromegaly patients, in particular, in men and those with long duration of disease. Importantly, a marked reduction of GH excess by transsphenoidal adenomectomy may cure SAS and improve insulin resistance and hypertension.

Free access

Diane L Möller-Goede, Michael Brändle, Klara Landau, Rene L Bernays, and Christoph Schmid


To assess frequency, symptoms and outcome of pituitary apoplexy (PA) among pituitary adenoma patients, to gain better insight into risk factors for bleeding into pituitary adenoma and to estimate the sequelae of PA by means of a matched control group.


By reviewing charts of 574 patients with pituitary adenoma, we analysed incidence, symptoms and outcome of PA and potential risk factors for developing PA by means of a control group (patients with pituitary adenoma without PA).


In total, 42 suffered from PA, all had macroadenomas; 30/217 male (14%) and 12/179 female (7%) macroadenoma patients, 32/194 patients with clinically non-functioning (16.5%) and 10/202 with clinically active (5.0%) macroadenoma were affected. Antithrombotic therapy predisposed patients to PA (P=0.026), diabetes mellitus and hypertension did not (P=1.00). Patients with PA and pituitary adenoma patients without PA had similar frequencies of hypopituitarism (45 vs 48%, P>0.05) and visual field defects (38 vs 55%, P>0.05), but ophthalmoplegia was significantly more common (76 vs 5%, P<0.001) in patients with PA. Nearly all patients were treated by surgery; most recovered from ophthalmoplegia, whereas visual function improved only moderately. Endocrine outcome was worse in patients with PA than in patients without PA.


Male sex and characteristics of the adenoma itself (especially tumour size and tumour type) rather than patient's cardiovascular risk factors such as diabetes and hypertension seem to predispose to PA; antithrombotic therapy may also be important.

Free access

Marian Christoph Neidert, Lisa Sze, Cornelia Zwimpfer, Johannes Sarnthein, Burkhardt Seifert, Karl Frei, Henning Leske, Elisabeth Jane Rushing, Christoph Schmid, and René-Ludwig Bernays


Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study, we present baseline αKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery.


Prospective controlled study.


We measured soluble αKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples.


Soluble αKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812–6623 pg/ml) and declined after surgery during early follow-up (2–6 days; median 645 pg/ml, IQR 550–1303 pg/ml) (P<0.001) and during late follow-up (2–3 months post-operatively; median 902 pg/ml, IQR 497–1340 pg/ml; P<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400–677 pg/ml; P<0.001). Following surgery, soluble αKL remained low during early and late follow-up – changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls.


High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).