A mysterious case of normalising blood sugar: insulinoma in a long-standing diabetic patient
Department of Medicine for the Elderly, Woodend Hospital, Eday Road, Aberdeen, AB15 6XS, UK
Address correspondence to: M. F. Hameed. Email: fhameed{at}nhs.net
Abstract
We report a case of recurrent hypoglycaemia in a long-standing type 2 diabetic patient, despite dramatic reduction in her anti-diabetic therapy. Subsequent investigations revealed an insulinoma as the cause. This patient was treated medically with diazoxide therapy, as multiple co-morbidities were felt to preclude surgical intervention. Although insulinoma is rare in the elderly and exceedingly rare in the context of type 2 diabetes, it should be given due consideration when no other exacerbating factor is found.
Keywords: hypoglycaemia, insulinoma, diabetic, impaired cognition, elderly
A 70-year-old woman was admitted in an acute confusional state on a background of recent urinary frequency. She had a 17-year history of type 2 diabetes mellitus and had been controlled on once-daily long-acting insulin for 11 years. She was almost completely blind secondary to severe diabetic maculopathy and was additionally profoundly deaf.
Four months earlier, she had been admitted (again with confusional state) to another local hospital. Over the course of that admission, her blood glucose measurements had consistently been low, such that her dose of glargine insulin had been reduced from 58 units on admission to 0 by the time of discharge. It was also noted during this admission that she had significant cognitive impairment, although assessment was limited by communication difficulties. She had been discharged home, where she stayed with her son.
On this admission, a midstream specimen of urine grew coliform. Routine blood screen was unremarkable other than a low venous glucose of 2.9 mmol/l, despite not receiving any diabetic medication. She was commenced on an intravenous 5% dextrose infusion, and the urinary tract infection was treated with ciprofloxacin.
On discontinuation of the dextrose infusion, she had frequent episodes of hypoglycaemia. Pituitary hormones and cortisol axis (short synacthen test) were measured and found to be normal for her age. She had no access to exogenous insulin or to oral hypoglycaemics.
As part of further evaluation of her hypoglycaemia, during an overnight fast, two paired venous glucose and insulin/C-peptide levels were taken. These showed the following results:
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The above-mentioned results consistently showed inappropriately elevated insulin and C-peptide levels, despite significant hypoglycaemia. On the basis of these results, it was felt that an insulin-secreting tumour was likely and a CT abdomen was carried out. This demonstrated a small nodule just superior to the body of the pancreas with characteristics consistent with an islet cell tumour (Figure 1).
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Because of co-morbidity, cognitive impairment and communication difficulties, it was felt that surgical intervention was inappropriate. We therefore elected to treat her with diazoxide 100 mg three times daily.
The subsequent improvement of her blood sugar did not, unfortunately, result in any improvement of cognitive function or agitation. It did, however, lessen her frequent demands for Mars bars, which we assumed to be a reflection of hypoglycaemia.
Insulinomas are the commonest pancreatic islet cell tumours, but are rare, occurring in four per million per year [1]. They are usually benign, small and solitary tumours, although up to 16% are malignant [2]. Highest incidence is in the 40- to 60-year age bracket. Multiple endocrine neoplasia type 1 is present in up to 16% of patients [1].
Diagnosis depends on the exclusion of the more common causes of hypoglycaemia (e.g. factitious insulin or sulphonylurea administration) and on the demonstration of raised plasma insulin and C-peptide levels in the presence of hypoglycaemia [2]. In our patient, blood levels were taken during the overnight fast, as she became symptomatically hypoglycaemic; guidelines however recommend fasting up to 72 h to increase the diagnostic yield. CT and ultrasound are used to localise the tumour, but this can be problematic (e.g. diagnostic yield from ultrasonography can vary from 25 to 75%) [3]. The removal of the tumour is curative in the great majority of cases but is less successful in the context of metastases or MEN1 [1]. Medical treatment with diazoxide (which inhibits insulin secretion from beta cells) or octreotide is an alternative in cases where curative removal is not possible [1].
Insulinoma in the elderly is rare and may present atypically, e.g. with recurrent falls [4]. Insulinoma in patients with pre-existing diabetes is also extremely rare; indeed, the incidence of diabetes amongst patients with insulinoma is much lower than that in the whole population (only 1 in 313 patients with insulinoma at one institution also had diabetes) [5]. There are sporadic case reports of insulinoma presenting in both type 1 and 2 diabetics [2, 5–7]. Interestingly, there is possibly an association between insulinoma and a family history of diabetes [2].
References
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- Svartberg J, Stridsberg M, Wilander E, Andersson DEH, Eriksson B. Tumor-induced hypoglycaemia in a patient with insulin-dependent diabetes mellitus. J Intern Med 1996; 239: 181–5.[Medline]
- Fedorak IJ, Ko TC, Gordon D, Flisak M, Prinz RA. Localisation of islet cell tumors of the pancreas: a review of current techniques. Surgery 1993; 113: 242–9.[Medline]
- Beauchet O, Kressig RW, Vischer UM, de Perrot T, de Saussure P. Insulinoma revealed by recurrent falls in old age. J Am Geriatr Soc 2005; 53: 552–3.[Medline]
- Levine RA, Sobel BE. Insulinoma, type 2 diabetes and plasminogen activator inhibitor type-I. Coron Artery Dis 2001; 12: 333–6.[Medline]
- Sapountzi P, Charnogursky G, Emanuele MA, Murphy D, Nabhan F, Emanuele NV. Case study: diagnosis of insulinoma using continuous glucose monitoring system in a patient with diabetes. Clin Diabetes 2005; 23: 140–3.
[Free Full Text] - Ravnik-Oblak M, Janez A, Kocijanicic A. Insulinoma induced hypoglycaemia in a type 2 diabetic patient. Wien Klin Wochenschr 2001; 113: 339–41.[Medline]
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