The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia

Dastamani, Antonia; Güemes, María; Pitfield, Catherine; Morgan, Kate; Rajab, Mansoor H.; Rottenburger, Christof; Bomanji, Jamshed; Coppi, Paolo De; Dattani, Mehul; Shah, Pratik

doi:10.1159/000491101

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…Lanreotide and Long-acting release octreotide (LAR-Octreotide) are two formulations used in few numbers of patients with HH [131][132][133][134][135][136] reported not only to be useful in the management of HH in children, but potentially displaying a more stable glycemic control than octreotide [134]. Lanreotide has also been proven useful in managing inoperable F-CHH [137].…”

Section: Long-acting Somatostatin Analoguesmentioning

confidence: 99%

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Güemes

Rahman

Kapoor

et al. 2020

Rev Endocr Metab Disord

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Hyperinsulinemic hypoglycemia (HH) is characterized by unregulated insulin release, leading to persistently low blood glucose concentrations with lack of alternative fuels, which increases the risk of neurological damage in these patients. It is the most common cause of persistent and recurrent hypoglycemia in the neonatal period. HH may be primary, Congenital HH (CHH), when it is associated with variants in a number of genes implicated in pancreatic development and function. Alterations in fifteen genes have been recognized to date, being some of the most recently identified mutations in genes HK1, PGM1, PMM2, CACNA1D, FOXA2 and EIF2S3. Alternatively, HH can be secondary when associated with syndromes, intra-uterine growth restriction, maternal diabetes, birth asphyxia, following gastrointestinal surgery, amongst other causes. CHH can be histologically characterized into three groups: diffuse, focal or atypical. Diffuse and focal forms can be determined by scanning using fluorine-18 dihydroxyphenylalanine-positron emission tomography. Newer and improved isotopes are currently in development to provide increased diagnostic accuracy in identifying lesions and performing successful surgical resection with the ultimate aim of curing the condition. Rapid diagnostics and innovative methods of management, including a wider range of treatment options, have resulted in a reduction in co-morbidities associated with HH with improved quality of life and long-term outcomes. Potential future developments in the management of this condition as well as pathways to transition of the care of these highly vulnerable children into adulthood will also be discussed.

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Section: Long-acting Somatostatin Analoguesmentioning

confidence: 99%

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Güemes

Rahman

Kapoor

et al. 2020

Rev Endocr Metab Disord

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“… 73 Many studies document the use of SST analogues for treating childhood HH, dating back to 1977. 14 , 27 , 67 …”

Section: The Role Of Sst Analogues In Treatment Of Hhmentioning

confidence: 99%

Somatostatin analogues for the treatment of hyperinsulinaemic hypoglycaemia

Haris

Saraswathi

Hussain

2020

Therapeutic Advances in Endocrinology

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Hyperinsulinaemic hypoglycaemia (HH) is a biochemical finding of low blood glucose levels due to the dysregulation of insulin secretion from pancreatic β-cells. Under normal physiological conditions, glucose metabolism is coupled to β-cell insulin secretion so that blood glucose levels are maintained within the physiological range of 3.5–5.5 mmol/L. However, in HH this coupling of glucose metabolism to insulin secretion is perturbed so that insulin secretion becomes unregulated. HH typically occurs in the neonatal, infancy and childhood periods and can be due to many different causes. Adults can also present with HH but the causes in adults tend to be different. Somatostatin (SST) is a peptide hormone that is released by the delta cells (δ-cells) in the pancreas. It binds to G protein-coupled SST receptors to regulate a variety of location-specific and selective functions such as hormone inhibition, neurotransmission and cell proliferation. SST plays a potent role in the regulation of both insulin and glucagon secretion in response to changes in glucose levels by negative feedback mechanism. The half-life of SST is only 1–3 min due to quick degradation by peptidases in plasma and tissues. Thus, a direct continuous intravenous or subcutaneous infusion is required to achieve the therapeutic effect. These limitations prompted the discovery of SST analogues such as octreotide and lanreotide, which have longer half-lives and therefore can be administered as injections. SST analogues are used to treat different forms of HH in children and adults and therapeutic effect is achieved by suppressing insulin secretion from pancreatic β-cells by complex mechanisms. These treatments are associated with several side effects, especially in the newborn period, with necrotizing enterocolitis being the most serious side effect and hence SS analogues should be used with extreme caution in this age group.

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“…Infants respond well to initial doses of octreotide, but tachyphylaxis after a few doses makes it not suitable for the long-term treatment. Long-acting somatostatin analogues (octreotide-LAR and lanreotide) have similar effects as octreotide but have the advantage that they are given once every 4 weeks, which improves therapy compliance and quality of life (21,109,110). However, due to a similar mechanism of action as octreotide, long-acting somatostatin analogues show similar side effects (111).…”

Section: Possible K Atp Channel-independent Strategies To Treat Chimentioning

confidence: 99%

Possible New Strategies for the Treatment of Congenital Hyperinsulinism

et al. 2020

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Objective: Congenital hyperinsulinism (CHI) is a rare disease characterized by persistent hypoglycemia as a result of inappropriate insulin secretion, which can lead to irreversible neurological defects in infants. Poor efficacy and strong adverse effects of the current medications impede successful treatment. The aim of the study was to investigate new approaches to silence b-cells and thus attenuate insulin secretion. Research Design and Methods: In the scope of our research, we tested substances more selective and more potent than the gold standard diazoxide that also interact with neuroendocrine ATP-sensitive K + (K ATP) channels. Additionally, K ATP channel-independent targets as Ca 2+-activated K + channels of intermediate conductance (K Ca 3.1) and L-type Ca 2+ channels were investigated. Experiments were performed using human islet cell clusters isolated from tissue of CHI patients (histologically classified as pathological) and islet cell clusters obtained from C57BL/6N (WT) or SUR1 knockout (SUR1-/-) mice. The cytosolic Ca 2+ concentration ([Ca 2+ ] c) was used as a parameter for the pathway regulated by electrical activity and was determined by fura-2 fluorescence. The mitochondrial membrane potential (DY) was determined by rhodamine 123 fluorescence and single channel currents were measured by the patch-clamp technique. Results: The selective K ATP channel opener NN414 (5 µM) diminished [Ca 2+ ] c in isolated human CHI islet cell clusters and WT mouse islet cell clusters stimulated with 10 mM glucose. In islet cell clusters lacking functional K ATP channels (SUR1-/-) the drug was without effect. VU0071063 (30 µM), another K ATP channel opener considered to be selective, lowered [Ca 2+ ] c in human CHI islet cell clusters. The compound was also effective in islet cell clusters from SUR1-/mice, showing that [Ca 2+ ] c is influenced by additional effects besides K ATP channels. Contrasting to NN414, the drug depolarized DY in murine islet cell clusters pointing to severe interference with mitochondrial metabolism. An opener of K Ca 3.1 channels, DCEBIO (100 µM), significantly decreased [Ca 2+ ] c in SUR1-/and human CHI islet cell clusters. To target L-type Ca 2+ channels we tested two

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The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia

Cited by 12 publications

References 23 publications

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Hyperinsulinemic hypoglycemia in children and adolescents: Recent advances in understanding of pathophysiology and management

Somatostatin analogues for the treatment of hyperinsulinaemic hypoglycaemia

Possible New Strategies for the Treatment of Congenital Hyperinsulinism

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