Hepatoblastoma and Wilms’ tumour in an infant with Beckwith–Wiedemann syndrome and diazoxide resistant congenital hyperinsulinism

Summary Beckwith–Wiedemann syndrome (BWS) can be associated with embryonal tumours and congenital hyperinsulinism (CHI). We present an infant with BWS who developed congenital hepatoblastoma and Wilms’ tumour during infancy. The infant presented with recurrent hypoglycaemia requiring high intravenous glucose infusion and was biochemically confirmed to have CHI. He was resistant to diazoxide but responded well to octreotide and was switched to Lanreotide at 1 year of age. Genetic analysis for mutations of ABCC8 and KCNJ11 were negative. He had clinical features suggestive of BWS. Methylation-sensitive multiplex ligation-dependent probe amplification revealed hypomethylation at KCNQ1OT1:TSS-DMR and hypermethylation at H19 /IGF2:IG-DMR consistent with mosaic UPD(11p15). Hepatoblastoma was detected on day 4 of life, which was resistant to chemotherapy, requiring surgical resection. He developed Wilms’ tumour at 3 months of age, which also showed poor response to induction chemotherapy with vincristine and actinomycin D. Surgical resection of Wilms’ tumour was followed by post-operative chemotherapy intensified with cycles containing cyclophosphamide, doxorubicin, carboplatin and etoposide, in addition to receiving flank radiotherapy. We report, for the first time, an uncommon association of hepatoblastoma and Wilms’ tumour in BWS in early infancy. Early onset tumours may show resistance to chemotherapy. UPD(11p15) is likely associated with persistent CHI in BWS. Learning points: Long-acting somatostatin analogues are effective in managing persistent CHI in BWS. UPD(11)pat genotype may be a pointer to persistent and severe CHI. Hepatoblastoma and Wilms’ tumour may have an onset within early infancy and early tumour surveillance is essential. Tumours associated with earlier onset may be resistant to recognised first-line chemotherapy.

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The Dose of Somatostatin Analogues during Pre-Surgical Treatment Is a Key Factor to Achieve Surgical Remission in Acromegaly

Endocrines ◽

10.3390/endocrines2030023 ◽

2021 ◽

Vol 2 (3) ◽

pp. 241-250

Author(s):

Marta Araujo-Castro ◽

Eider Pascual-Corrales ◽

Héctor Pian ◽

Ignacio Ruz-Caracuel ◽

Alberto Acitores Cancela ◽

...

Keyword(s):

Retrospective Study ◽

Surgical Treatment ◽

Surgical Outcomes ◽

Pituitary Adenomas ◽

Somatostatin Analogues ◽

Beneficial Effects ◽

Key Factor ◽

Long Acting ◽

First Time ◽

Endocrine Complications

Purpose: to determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: most patients, 83.3% (n = 40), harbored macroadenomas and 31.3% (n = 15) invasive pituitary adenomas. In this case, 14 patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60–120] and 20 [range 20–30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and untreated patients (p > 0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanreotide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR = 4.64, p = 0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR = 0.65, p = 0.570), independently of the doses and the duration of SSA treatment (p > 0.05). Conclusions: the dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

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007–Long Acting Somatostatin Analogues: Early Experience in the Treatment of 5 patients with Congenital Hyperinsulinism

Journal of Pediatric Nursing ◽

10.1016/j.pedn.2015.01.006 ◽

2015 ◽

Vol 30 (2) ◽

pp. 428-429

Author(s):

Lisa Truong ◽

Paul Thornton

Keyword(s):

Early Experience ◽

Somatostatin Analogues ◽

Congenital Hyperinsulinism ◽

Long Acting

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The Dose of Somatostatin Analogues During Pre-Surgical Treatment is a Key Factor to Achieve Surgical Remission in Acromegaly

10.20944/preprints202107.0065.v1 ◽

2021 ◽

Author(s):

Marta Araujo-Castro ◽

Eider Pascual-Corrales ◽

Héctor Pian ◽

Ignacio Ruz-Caracuel ◽

Alberto Acitores Cancela ◽

...

Keyword(s):

Retrospective Study ◽

Surgical Treatment ◽

Surgical Outcomes ◽

Somatostatin Analogues ◽

Transsphenoidal Approach ◽

Beneficial Effects ◽

Key Factor ◽

Long Acting ◽

First Time ◽

Endocrine Complications

Purpose: To determine whether pre-surgical treatment using long-acting somatostatin analogues (SSAs) may improve surgical outcomes in acromegaly. Methods: Retrospective study of 48 patients with acromegaly operated by endoscopic transsphenoidal approach and for first time. Surgical remission was evaluated based on the 2010 criteria. Results: Most patients, 83.3% (n=40), harboured macroadenomas and 31.3% (n=15) invasive pitu-itary adenomas. Fourteen patients were treated with lanreotide LAR and 6 with octreotide LAR, median monthly doses of 97.5 [range 60-120] and 20 [range 20-30] mg, respectively, for at least 3 months preoperatively. Presurgical variables were comparable between pre-treated and un-treatred patients (P>0.05). Surgical remission was more frequent in those pre-treated with monthly doses ≥90 mg of lanre-otide or ≥30 mg of octreotide than in untreated or pre-treated with lower doses (OR=4.64, P=0.025). However, no differences were found between pre-treated and untreated patients when lower doses were included or between those treated for longer than 6 months compared to those untreated or pre-treated for shorter than 6 months. Similarly, no differences were found either in terms of surgical or endocrine complications (OR=0.65, P=0.570)), independently of the doses and the duration of SSA treatment (P>0.05). Conclusions: The dose of SSAs is a key factor during pre-surgical treatment, since the beneficial effects in surgical remission were observed with monthly doses equal or higher than 90 mg of lanreotide and 30 mg of octreotide, but not with lower doses.

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Long-acting somatostatin analogues in the treatment of children with congenital hyperinsulinism. Literature review

Pharmateca ◽

10.18565/pharmateca.2020.9.38-41 ◽

2020 ◽

Vol 9_2020 ◽

pp. 38-41

Author(s):

A.R. Savkina Savkina ◽

M.A. Kareva Kareva ◽

M.A. Melikyan Melikyan ◽

◽

Keyword(s):

Literature Review ◽

Somatostatin Analogues ◽

Congenital Hyperinsulinism ◽

Long Acting

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A Multicenter Experience with Long-Acting Somatostatin Analogues in Patients with Congenital Hyperinsulinism

Hormone Research in Paediatrics ◽

10.1159/000485184 ◽

2017 ◽

Vol 89 (2) ◽

pp. 82-89 ◽

Cited By ~ 16

Author(s):

Ivo van der Steen ◽

Mirjam E. van Albada ◽

Klaus Mohnike ◽

Henrik Thybo Christesen ◽

Susann Empting ◽

...

Keyword(s):

Adverse Effect ◽

Side Effects ◽

Liver Enzymes ◽

Blood Glucose Control ◽

Severe Hypoglycemia ◽

Somatostatin Analogues ◽

Somatostatin Analogue ◽

Congenital Hyperinsulinism ◽

Elevated Liver Enzymes ◽

Long Acting

Background/Aims: Congenital hyperinsulinism (CHI) is a rare disease characterized by recurrent severe hypoglycemia. In the diffuse form of CHI, pharmacotherapy is the preferred choice of treatment. Long-acting somatostatin analogues have been used in children as off-label medication. However, the efficacy, outcomes, and adverse effect profiles of long-acting somatostatin analogues have not been described in multicentered studies. The aim of this retrospective study is to summarize the experience with long-acting somatostatin analogues in a large group of children with CHI. Methods: Data were obtained retrospectively from 27 patients with CHI who received long-acting somatostatin analogues in 6 different centers in Europe. These included information on glycemic stability, auxology, and adverse effect profile in clinical follow-up assessments. Results: Blood glucose control improved in most patients (89%). No life-threatening side effects occurred. Thirteen patients (48%) experienced side effects; in 3 patients (11%), the side effects were the main reason for discontinuation of the treatment. The most frequent side effect was elevated liver enzymes (n = 10, 37%). Conclusion: Long-acting somatostatin analogues are effective in glycemic control of patients with CHI. However, in 37% of all patients increased liver enzymes were observed. It is important to monitor liver function in all patients receiving long-acting somatostatin analogue therapy.

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SPECIAL PROBLEMS IN TOXICITY TESTING OF LONG ACTING DEPOT CONTRACEPTIVES

Acta Endocrinologica ◽

10.1530/acta.0.075s315 ◽

1974 ◽

Vol 77 (1_Suppla) ◽

pp. S315-S354 ◽

Cited By ~ 4

Author(s):

F. Neumann ◽

R. von Berswordt-Wallrabe ◽

W. Elger ◽

K.-J. Gräf ◽

S. H. Hasan ◽

...

Keyword(s):

Biological Effects ◽

Histological Finding ◽

Toxicity Testing ◽

Prolactin Secretion ◽

List Type ◽

Human Species ◽

Prolactin Plasma Level ◽

Human Use ◽

Long Acting ◽

Reproductive Processes

ABSTRACT Two types of so-called "depot contraceptives", long-acting steroids which are of interest for human use, were studied in animals. Norethisterone oenanthate, mainly gestagenic in the human and other species, turned out to be predominantly oestrogenic in rats. This oestrogenicity caused indirectly, via an enhanced hypophysial prolactin secretion, the well-known hypophysial and mammary tumours in rats. Another synthetic gestagen, 4,6-dichloro- 17- acetoxy- 16α-methyl-4,6-pregnadiene-3,20-dione, which might be considered in its biological actions similar to preparations containing chlormadinone acetate or medroxy-progesterone acetate, induced no signs of oestrogenicity in dogs. It is surmised that its gestagenic influence indirectly, and probaby, via an enhanced hypophysial prolactin secretion caused "mammary nodules" in this "non-rodent" species. These studies have born out mainly two facts: A synthetic steroid, norethisterone oenanthate, exerted different biological effects in different species: it was a gestagen in the rabbit, whereas in rats, its predominant influence was oestrogenic. The hypophysial prolactin secretion was enhanced in various species by different mechanisms: in rats, the oestrogenicity caused an increased prolactin plasma level, whereas in dogs, a gestagen with obviously no inherent oestrogenicity, 4,6-dichloro-17-acetoxy-16α-methyl-4,6-pregnadiene-3,20-dione, converted the histological appearance of the anterior pituitary into a condition with a greatly increased number of eosinophils. This histological finding was interpreted as an indicator for a hypersecretion of prolactin. Hence, animal work with "gestagens" has only limited predictive value with respect to their possible effects in the human species. Therefore, inflexible recommendations are not helpful in solving the safety problem of long-acting steroids which affect primarily reproductive processes.

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