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164 Basic and Clinical Endocrinology Up-to-Date

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The diagnosis of nesidioblastosis is made in patients with definite biological evidence of hypoglycaemia related to endogenous hyperinsulinism (as in insulinoma patients, see biological diagnosis) in the absence of insulin secretagogues, autoimmune hypoglycaemia, and detectable pancreatic tumour. There is neither clinical nor biological basis to make a distinction between insulinoma and nesidioblastosis. Patients with nesidioblastosis may have a positive fast test (as in all our patients), though patients with NIPHS have negative fast tests and only reactive insulin-mediated hypoglycaemia; on the other hand, very rare insulinoma patients may present with a negative fast test, and some of them have only reactive insulin-mediated hypoglycaemia. The diagnostic specificity of multi-site insulin stimulation by intra-arterial calcium injection is not fully established: such insulin stimulation after intraarterial calcium injection was found in normal pancreatic areas for unknown reasons (Wiesli et al. 2004a; Guettier et al. 2009), and has been reported in patients with factitious hypoglycaemia related to insulin secretagogues (Hirshberg et al. 2001). In addition, intra-arterial calcium stimulation may provide a pseudo-insulinoma response pattern in patients with adult nesidioblastosis, maybe because nesidioblastosis is not evenly distributed in the pancreas. One must also be reminded that nesidioblastosis has been found in patients who had concurrent insulinoma (Bright et al. 2008) (Service et al. 1999). Slight focal pancreatic abnormalities have

The natural course of adult-onset nesidioblastosis is not well established. Most patients require a medical and/or surgical treatment. In an obese patient with idiopathic nesidioblastosis who had been treated by left-sided pancreatectomy and high doses of octreotide, hypoglycaemia finally subsided during the perimenopausal years, and changed to mild type-2 diabetes mellitus. No similar change was observed in other patients with nesidioblastosis, though the dose of diazoxide could be decreased in one patient during the

A medical treatment is the first-line therapeutic approach for nesidioblastosis, but it may not be sufficient to control the hypoglycaemia, and pancreatic surgery must often be performed. Diazoxide remains the reference medication for nesidioblastosis, and is often effective to control the hypoglycaemia, at least after partial pancreatectomy (Arao et al. 2006). Longterm treatment with somatostatin analogues has also been reported to be effective, without the side effects of diazoxide (Vezzosi et al. 2008). One of our patients was treated with continuous subcutaneous administration of a high dose of octreotide throughout her pregnancy, without any detectable maternal or foetal adverse effect (Boulanger et al. 2004). Calcium channel blockers have been employed (Witteles et al. 2001) (Vella & Service 2007). Pancreatic surgery, guided by the results of transhepatic venous sampling or those of insulin stimulation after selective intraarterial calcium injection, is often performed. The extent of surgery is controversial, in order to achieve a total control or a significant improvement of hypoglycaemia, without pancreatic insufficiency (Raffel et al. 2007). Selective intra-arterial calcium injection usually helps in choosing the extent of pancreatectomy (Toyomasu et al. 2009). Total pancreatectomy cannot be recommended, since complete or acceptable control of the hypoglycaemia can be achieved in most patients by partial pancreatectomy followed if necessary by a medical treatment. Spleen-preserving distal pancreatectomy is often performed unless the results suggest a proximal pancreatic

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*Endocrinology* 162(5): 1001-1008.

*Academy of Sciences* 615: 125-127.

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1623-1627.

918-920.

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272.

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*Laboratory* 49(3-4): 113-121.

462.

1152.

1589.

711-719.

*Metabolism* 85(11): 3973-3974.

*Sciences* 304(3): 164-167.

*Surgery* 30(5): 670-679.

*Roentgenology* 176(2): 471-474.

*Endocrinology and Metabolism* 74(1): 204-210.

132(6): 976-982; discussion 982-973.


**Part 5** 

**Aging and Endocrinology** 

