GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases

Zoicas, Flavius; Droste, Michael; Mayr, B; Buchfelder, Michael; Schöfl, Christof

doi:10.1530/eje-12-0997

Cited by 99 publications

(84 citation statements)

References 52 publications

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“…22,51,70,80,94,102 Unfortunately, we did not record patients' body mass index, but rather we recorded their weight. In 13 (76.5%) of 17 patients with a postoperative severe weight gain (> 20 kg), the lesion was involving and/or compressing the third ventricle.…”

Section: Quality Of Lifementioning

confidence: 99%

The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients

Cavallo

Günther

Cappabianca

et al. 2014

JNS

190

198

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Object Despite their benign histological appearance, craniopharyngiomas can be considered a challenge for the neurosurgeon and a possible source of poor prognosis for the patient. With the widespread use of the endoscope in endonasal surgery, this route has been proposed over the past decade as an alternative technique for the removal of craniopharyngiomas. Methods The authors retrospectively analyzed data from a series of 103 patients who underwent the endoscopic endonasal approach at two institutions (Division of Neurosurgery of the Università degli Studi di Napoli Federico II, Naples, Italy, and Division of Neurosurgery of the Bellaria Hospital, Bologna, Italy), between January 1997 and December 2012, for the removal of infra- and/or supradiaphragmatic craniopharyngiomas. Twenty-nine patients (28.2%) had previously been surgically treated. Results The authors achieved overall gross-total removal in 68.9% of the cases: 78.9% in purely infradiaphragmatic lesions and 66.3% in lesions involving the supradiaphragmatic space. Among lesions previously treated surgically, the gross-total removal rate was 62.1%. The overall improvement rate in visual disturbances was 74.7%, whereas worsening occurred in 2.5%. No new postoperative defect was noted. Worsening of the anterior pituitary function was reported in 46.2% of patients overall, and there were 38 new cases (48.1% of 79) of postoperative diabetes insipidus. The most common complication was postoperative CSF leakage; the overall rate was 14.6%, and it diminished to 4% in the last 25 procedures, thanks to improvement in reconstruction techniques. The mortality rate was 1.9%, with a mean follow-up duration of 48 months (range 3–246 months). Conclusions The endoscopic endonasal approach has become a valid surgical technique for the management of craniopharyngiomas. It provides an excellent corridor to infra- and supradiaphragmatic midline craniopharyngiomas, including the management of lesions extending into the third ventricle chamber. Even though indications for this approach are rigorously lesion based, the data in this study confirm its effectiveness in a large patient series.

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Section: Quality Of Lifementioning

confidence: 99%

The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients

Cavallo

Günther

Cappabianca

et al. 2014

JNS

190

198

View full text Add to dashboard Cite

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“…f/f mice were generated by crossing Glp1r f/f mice (Smith et al, 2014) with Sim1-Cre mice (Balthasar et al, 2005), a kind gift from Dr. J. Elmquist (University of Texas Southwestern Medical Center, Dallas). To generate litters that contained both genotypes (Sim1-Cre, Glp1r f/f and Glp1r f/f ), the dams were Glp1r f/f and the sires were Glp1r f/f mice heterozygous for the Sim1-Cre transgene.…”

Section: Animals Sim-1-cre; Glp1rmentioning

confidence: 99%

“…RNA extraction and real-time PCR were performed as previously described (Smith et al, 2014). Briefly, mice (n ϭ 4 or 5 per group) were rapidly decapitated and the brains removed and flash-frozen in dry ice-chilled isopentane.…”

Section: Animals Sim-1-cre; Glp1rmentioning

confidence: 99%

“…Although originally identified as a gastrointestinal hormone (Varndell et al, 1985), GLP-1 is also produced in the brain by neurons largely confined to the caudal division of the nucleus of the solitary tract (NTS) and the ventral medulla (Merchenthaler et al, 1999). Importantly, the GLP-1 receptor (Glp1r) is abundantly expressed in the PVN (Merchenthaler et al, 1999), and GLP-1-immunoreactive fibers derived from the NTS innervate both neuroendocrine and preautonomic PVN neurons (Vrang et al, 2007;Tauchi et al, 2008), suggesting possible involvement in stress reactivity. Indeed, pharmacological studies demonstrate that GLP-1 receptor antagonism reduces HPA axis responses to both reactive (physical) and anticipatory (emotional) stressors (Kinzig et al, 2003), and central administration of GLP-1 receptor agonists activates hypothalamic and brainstem neurons innervating sympathetic preganglionic neurons (Yamamoto et al, 2002(Yamamoto et al, , 2003.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the GLP-1 receptor (Glp1r) is abundantly expressed in the PVN (Merchenthaler et al, 1999), and GLP-1-immunoreactive fibers derived from the NTS innervate both neuroendocrine and preautonomic PVN neurons (Vrang et al, 2007;Tauchi et al, 2008), suggesting possible involvement in stress reactivity. Indeed, pharmacological studies demonstrate that GLP-1 receptor antagonism reduces HPA axis responses to both reactive (physical) and anticipatory (emotional) stressors (Kinzig et al, 2003), and central administration of GLP-1 receptor agonists activates hypothalamic and brainstem neurons innervating sympathetic preganglionic neurons (Yamamoto et al, 2002(Yamamoto et al, , 2003. The clear interaction between HPA-and sympatho-excitatory NTS GLP-1 projections and putative PVN stress effector neurons led us to hypothesize that endogenous GLP-1 neurons form a dedicated neurocircuit coordinating different modalities of stress responses at the level of the PVN.…”

Section: Introductionmentioning

confidence: 99%

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Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress

Ghosal¹,

Packard²,

Mahbod³

et al. 2017

J. Neurosci.

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Organismal stress initiates a tightly orchestrated set of responses involving complex physiological and neurocognitive systems. Here, we present evidence for glucagon-like peptide 1 (GLP-1)-mediated paraventricular hypothalamic circuit coordinating the global stress response. The GLP-1 receptor (Glp1r) in mice was knocked down in neurons expressing single-minded 1, a transcription factor abundantly expressed in the paraventricular nucleus (PVN) of the hypothalamus. Mice with single-minded 1-mediated Glp1r knockdown had reduced hypothalamic-pituitary-adrenal axis responses to both acute and chronic stress and were protected against weight loss associated with chronic stress. In addition, regional Glp1r knockdown attenuated stress-induced cardiovascular responses accompanied by decreased sympathetic drive to the heart. Finally, Glp1r knockdown reduced anxiety-like behavior, implicating PVN GLP-1 signaling in behavioral stress reactivity. Collectively, these findings support a circuit whereby brainstem GLP-1 activates PVN signaling to mount an appropriate whole-organism response to stress. These results raise the possibility that dysfunction of this system may contribute to stress-related pathologies, and thereby provide a novel target for intervention.

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A 52‐week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity

Lomenick

Buchowski

Shoemaker

2016

Obesity

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Background/Objectives Hypothalamic obesity (HO) is a common complication of hypothalamic tumors and effective therapies are lacking. The objective of this pilot study was to investigate changes in body weight before and during treatment with exenatide. Subjects/Methods This was a prospective, open-label 52-week pilot study of exenatide (10 mcg b.i.d.) in adults with HO. Ten patients enrolled and 8 completed the study. Study measures included indirect calorimetry, body composition, buffet meals, diet recall, actigraphy and hormone assays. Results Participants were obese with a baseline weight of 137.2 ± 37.6 kg. Exenatide therapy was well tolerated. Change in weight with exenatide therapy was not significant (−1.4 ± 4.3 kg [95% CI −2.2 to 4.9], p=0.40) but 6 of 8 completers lost weight (−6.2 to −0.2 kg). Participants reported significantly lower intake on food recall during treatment compared with baseline (7837.8 ± 2796.6 vs. 6258.4 ± 1970.7 kJ [95% CI −2915.8 to −242.6], p= 0.027) but there was no change in intake during buffet meals. Conclusions We did not observe significant weight loss in patients with HO treated with exenatide but 75% of completers had stable or decreasing weight. Further studies are needed to evaluate weight loss efficacy in patients with HO.

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GLP-1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases

Cited by 99 publications

References 52 publications

The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients

The endoscopic endonasal approach for the management of craniopharyngiomas: a series of 103 patients

Disruption of Glucagon-Like Peptide 1 Signaling in Sim1 Neurons Reduces Physiological and Behavioral Reactivity to Acute and Chronic Stress

A 52‐week pilot study of the effects of exenatide on body weight in patients with hypothalamic obesity

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