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Special Features: Partha Kar, Paul Price, Stewart Sawers, Satya Bhattacharya, Rodney H. Reznek, and Ashley B. Grossman Insulinomas May Present with Normoglycemia after Prolonged Fasting but Glucose-Stimulated Hypoglycemia J Clin Endocrinol Metab 2006; 91: 4733-4736 [Abstract] [Full text] [PDF]

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Re: Glucose-Stimulated Hypoglycemia

Ashley B. Grossman   (22 February 2007)

Glucose-Stimulated Hypoglycemia

Adrian Vella, F. John Service   (13 February 2007)

Re: Markedly elevated insulin levels in patients presenting with hypoglycemia

Ashley B Grossman   (6 February 2007)

Markedly elevated insulin levels in patients presenting with hypoglycemia

Teck-Kim Khoo   (18 January 2007)

Re: Glucose-Stimulated Hypoglycemia 22 February 2007
Ashley B. Grossman, Physician St. Bartholomew's Hospital Send letter to journal: Re: Re: Glucose-Stimulated Hypoglycemia a.b.grossman{at}qmul.ac.uk Ashley B. Grossman	Vella and Service consider that the 72-hour fast is commonly negative in patients with confirmed insulinomas. Nevertheless, for 75 years, the 72-hour fast has been, in words of authors from the NIH, the “cornerstone for the diagnosis” of insulinomas (1). They found that approximately 95% of patients were diagnosed at even 48 hours of fasting, and retrospectively, 100% were hypoglycemic at that time. More confusing is Vella and Service’s claim that that the oral glucose tolerance test (OGTT) is “universally discredited.” First, they define nadir glucose as less than 50 mg/dL, whereas we defined significant hypoglycemia as a minimum glucose of less than 40 mg/dL. Second, most units will have considerable experience in the use of a standard 0GTT and very little of a standard mixed meal. While the latter may be more reliable in diagnosing reactive hypoglycemia, we maintain that it is unnecessary in the diagnosis of an insulinoma. Whatever the merits of either the classic OGTT or a standard meal, the essential point of our both our paper and Service’s earlier review (2) is that there may be important false negatives with the most commonly recommended test procedure, the 72-hour fast. References 1. Hirshberg B, Livi A, Bartlett DL, Libutti SK, Alexander HR, Doppman JL, Skarulis MC, Gorden P. 2000. Forty-eight-hour fast: the diagnostic test for insulinoma. J Clin Endocrinol Metab 85:3222–3226 2. Service FJ. 1995. Hypoglycemic disorders. N Engl J Med 332:1144-1152
Glucose-Stimulated Hypoglycemia 13 February 2007
Adrian Vella Mayo Clinic College of Medicine, F. John Service Send letter to journal: Re: Glucose-Stimulated Hypoglycemia vella.adrian{at}mayo.edu Adrian Vella, et al.	The report by Kar et al (1) of two patients who experienced postprandial hypoglycemia and had a negative 72-hr fast is a not uncommon phenomenon in insulinoma patients. Indeed, this prompted abandonment of the classical classification of hypoglycemic disorders (reactive vs. fasting) more than a decade ago (2). Their use of the universally discredited oral glucose tolerance test (OGTT) in lieu of a standard mixed meal test to confirm the postprandial occurrence of hypoglycemia is puzzling (3, 4). At least 10% of healthy persons will have a plasma glucose nadir <50 mg/dL during an OGTT (3). Furthermore, there is no correlation between the nadir of plasma glucose and autonomic symptoms in these circumstances (4). In addition, the OGTT has relatively poor reproducibility (5). Comparison of plasma glucose responses to a mixed meal with those following an OGTT demonstrated that none of the subjects who had a hypoglycemic nadir after OGTT experienced hypoglycemia after a mixed meal. In that study, there was no electroencephalogram (EEG) evidence of hypoglycemia despite the occurrence of symptoms during both tests (6). References 1. Kar P, Price P, Sawers S, Bhattacharya S, Reznek RH, Grossman AB. 2006. Insulinomas may present with normoglycemia after prolonged fasting but glucose-stimulated hypoglycemia. J Clin Endocrinol Metab 91:4733-4736 2. Service FJ. 1995. Hypoglycemic disorders. N Engl J Med 332:1144-1152 3. Lev-Ran A, Anderson RW. 1981. The diagnosis of postprandial hypoglycemia. Diabetes 30:996-999 4. Johnson DD, Dorr KE, Swenson WM, Service FJ. 1980. Reactive hypoglycemia. JAMA 243:1151-1155 5. Davidson MB. 2002. Counterpoint: the oral glucose tolerance test is superfluous. Diabetes Care 25:1883-1885 6. Hogan MJ, Service FJ, Sharbrough FW, Gerich JE. 1983. Oral glucose tolerance test compared with a mixed meal in the diagnosis of reactive hypoglycemia: A caveat on stimulation. Mayo Clin Proc 58:491-496
Re: Markedly elevated insulin levels in patients presenting with hypoglycemia 6 February 2007
Ashley B Grossman, Physician St. Bartholomew's Hospital, London EC1A 7BE, UK Send letter to journal: Re: Re: Markedly elevated insulin levels in patients presenting with hypoglycemia a.b.grossman{at}qmul.ac.uk Ashley B Grossman	Dr. Khoo brings our attention to a rare but very interesting etiology of hypoglycemia, which is that secondary to the insulin autoimmune syndrome. As he rightly points out, this is usually reported as a common problem only in Japan, but scattered case reports have been published from other parts of the world. While this was clearly not the cause of the hypoglycemia in our two patients, the problem remitting with removal of pathologically-confirmed insulinomas, we agree that it would certainly be prudent to consider this diagnosis in patients with hypoglycemia secondary to inappropriate insulin secretion.
Markedly elevated insulin levels in patients presenting with hypoglycemia 18 January 2007
Teck-Kim Khoo, Fellow, Endocrinology, Diabetes and Metabolism Mayo Clinic, Rochester Send letter to journal: Re: Markedly elevated insulin levels in patients presenting with hypoglycemia khoo.teckkim{at}mayo.edu Teck-Kim Khoo	I read with interest the clinical case seminar by Kar et al. (1) regarding the two insulinoma patients having glucose-stimulated hypoglycemia by oral glucose tolerance testing, but negative after prolonged fasting. It is noteworthy that Patient 1 had an insulin level of 1500 mU/liter at 30 minutes of the study, 60 times above their normal limit. However, there was no mention of testing for insulin autoantibodies. Given the impressive levels of insulin, even during normoglycemia, it would be prudent to screen for autoantibody-mediated hypoglycemia. Although this entity, referred to as Hirata's disease, is rare and has been mostly reported in Japanese patients (2), it can also be seen in Caucasian patients (3). The hypoglycemia may occur in both fasting and postprandial states. One important clue to this disorder is a dramatically increased level of serum insulin. Given that this condition is usually not treated surgically, screening patients with hypoglycemia for insulin antibodies would be important, and even more so for those with very high insulin levels. References 1. Kar P, Price P, Sawers S, Bhattacharya S, Reznek RH, Grossman AB. 2006. Insulinomas May Present with Normoglycemia after Prolonged Fasting but Glucose-Stimulated Hypoglycemia. J Clin Endocrin Metab 91:4733-4736 2. Uchigata Y, Hirata Y. 1999. Insulin Autoimmune Syndrome (IAS, Hirata disease). Ann Med Interne 150:245-253 3. Basu A, Service FJ, Yu L, Heser D, Ferries LM, Eisenbarth G. 2005. Insulin Autoimmunity in Seven White Patients. Endocr Prac 11:97-103