TREATMENT
There is no consensus on treatment of NIPHS in postbariatric surgery patients, and no “gold standard” exists. Pharmacologic treatment is recommended prior to surgical intervention in patients who present with symptomatic hypoglycemia without loss of consciousness or seizures.1
Pharmacologic treatments include calcium channel blockers (eg, verapamil or nifedipine), the b-cell inhibitor diazoxide, the secretory inhibitor octreotide, and a-glucosidase inhibitors.1 In one hospital group, patients were initially treated with verapamil ER 100 mg/d.5 If patients did not respond to this therapy or developed adverse effects, diazoxide was added (starting dose, 25 mg tid, titrated to 75 mg tid).5 If this combination did not produce results, octreotide (dose ranging from 25 mg/d to 50 mg tid, subcutaneously) was added. Acarbose can also be added, with the typical starting dose of 50 mg tid.1
Distal or subtotal pancreatectomy to debulk the hypertrophic islets is the most common surgical method used in patients with severe hypoglycemia that is refractory to medical management.2,5 The extent of pancreatic resection is guided by calcium angiography and typically ranges from 80% to 95%.7 Smaller pancreatic resection is associated with higher risk for persistent postoperative hypoglycemia.5 Complications associated with pancreatectomy include insulin-dependent diabetes and exocrine insufficiency.5
It is not uncommon for patients to experience recurrent symptoms after subtotal pancreatectomy, but the symptoms are typically easier to manage pharmacologically than they were pre-operatively. Occasionally, a second surgery with 95% to complete pancreatectomy is employed if recurrent hypoglycemia develops that is refractory to medical management.5
Reversal of Roux-en-Y bypass surgery has been described as an attempted treatment method in several case reports of patients with NIPHS. In at least one patient, hyperinsulinemic hypoglycemia persisted after Roux-en-Y gastric bypass reversal.2 Adjustable gastric band placement was recently reported to reverse hypoglycemic symptoms and maintain weight loss, due to restricted gastric emptying.2 Conversion of Roux-en-Y gastric banding to gastric sleeve may also be employed to restore normal gastrointestinal continuity and resolve hypoglycemia, though limited data is available regarding the efficacy of this procedure.2
Close monitoring is necessary in patients treated with pharmacologic therapy to ensure that symptoms are well controlled and that surgery is not necessary.1
SUMMARY AND CONCLUSION
Symptomatic hypoglycemia is a potential complication associated with gastric bypass surgery and is most commonly caused by dumping syndrome. It is important to consider other causes of postprandial hypoglycemia, such as insulinoma and NIPHS, in patients who continue to experience hypoglycemia despite making dietary modifications.1,4
NIPHS is a rare and poorly understood complication of gastric bypass surgery involving pathologic b-cell overgrowth, leading to hyperinsulinemia and potentially severe hypoglycemia.6 Some patients may present with complete relief of symptoms with pharmacologic treatment, while others will need surgical treatment with subtotal pancreatectomy.1
The findings of increased levels of GLP-1 hormone in patients who have received gastric bypass surgery and the fact that only a very small subset of gastric bypass patients develop NIPHS with histologic features of nesidioblastosis are subjects for further research. Further understanding of the hormonal factors involved in the pathogenesis of NIPHS and adult-onset nesidioblastosis following gastric bypass surgery could lead to novel drug development to treat diabetes.6
REFERENCES
1. Moreira RO, Moreira RBM, Machado NAM, et al. Post-prandial hypoglycemia after bariatric surgery: pharmacological treatment with verapamil and acarbose. Obes Surg. 2008;18:1618-1621.
2. Cui Y, Elahi D, Andersen D. Advances in the etiology and management of hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass. J Gastrointest Surg. 2011;15:1879-1888.
3. Sarwar H, Chapman III WH, Pender JR, et al. Hypoglycemia after Roux-en-Y gastric bypass: the BOLD experience. Obes Surg. 2014; 24(7):1120-1124.
4. Service GJ, Thompson GB, Service FJ, et al. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery. N Engl J Med. 2005;353(3):249-254.
5. Mathavan VK, Arregui M, Davis C, et al. Management of postgastric bypass noninsulinoma pancreatogenous hypoglycemia. Surg Endosc. 2010;24:2547-2555.
6. Cummings D. Gastric bypass and nesidioblastosis—too much of a good thing for islets? N Engl J Med. 2005;353(3):300-302.
7. Clancy TE, Moore FD, Zinner MJ. Post-gastric bypass hyperinsulinism with nesidioblastosis: subtotal or total pancreatectomy may be needed to prevent recurrent hypoglycemia. J Gastrointest Surg. 2006;10(8):1116-1119.
8. Kaczirek K, Niederle B. Nesidioblastosis: an old term and a new understanding. World J Surg. 2004;28:1227-1230.
9. Salehi M, Gastaldelli A, D’Alessio DA. Altered islet function and insulin clearance cause hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia. J Clin Endocrinol Metab. 2014;99(6): 2008-2017.