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Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: a Case Report and Brief Literature Review

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Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: a Case Report and Brief Literature Review Case Report J Endocrinol Metab. 2019;9(6):199-202 Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: A Case Report and Brief Literature Review Vania Gomesa, b, Florbela Ferreiraa Abstract ders, characterized by inappropriate insulin secretion from the pancreatic β cells in the presence of low blood glucose (BG) Hyperinsulinemic hypoglycemia is characterized by inappropriate in- levels [1]. In adults, 0.5-5% of hypoglycemias are due to HH sulin secretion from the pancreatic β cells causing low blood glucose [1]. The diagnosis of hypoglycemia is based on Whipple’s triad levels. Nesidioblastosis is a very rare cause of hyperinsulinemic hypo- (symptoms, signs or both consistent with hypoglycemia; a low glycemia in adults. Medical therapy can effectively improve disease reliably measured plasma glucose concentration (< 55 mg/dL) symptoms. In 2014, a 45-year-old man presented with recurrent severe at the time of suspected hypoglycemia; resolution of symp- fasting and postprandial symptomatic hypoglycemia. The symptoms toms or signs when hypoglycemia is corrected) [2]. Hypogly- resolved after glucose ingestion. Fasting test was positive after only 4 cemia may have multiple etiologies: insulinoma, post-bariatric h but imaging methods (abdominal computerized tomography, mag- surgery, adult-onset nesidioblastosis, autoimmunity, medica- netic resonance imaging, endoscopic ultrasonography and octreotide tions, non-islet cell tumors, hormonal deficiencies, critical ill- scintigraphy) failed to identify pancreatic lesions. Hypoglycemia in ness and factitious hypoglycemia [3]. Insulinoma is the most face of endogenous hyperinsulinemia and lack of focal lesions in the common cause of endogenous HH in adults. On the contrary, pancreas in multiple imaging exams suggested the diagnosis of adult nesidioblastosis is a very rare cause of HH in this age group nesidioblastosis. The patient preferred conservative medical treatment and the etiology is still not fully understood [4]. This condi- in association with dietary recommendations. Nifedipine (30 mg/day) tion is a functional and anatomical disorder of non-neoplastic did not improve the glycemic profile and was poorly tolerated by the β cells characterized by hyperplasia, diffuse proliferation and patient. Diazoxide 150 mg/day was started, with progressive increase hypertrophy of islet cells [5]. to 400 mg/day over 6 weeks. Patient has been successfully treated with The majority of cases of adult-onset nesidioblastosis oc- medical treatment for 5 years, with no events of severe hypoglycemia, curred after Roux-en-Y gastric bypass surgery and potential no significant side effects and with marked improvement in quality of implicated mechanisms include: increased levels of incretins life. This clinical case demonstrates that adult hyperinsulinemic hypo- (glucagon-like peptide-1 (GLP-1) and gastric inhibitory pep- glycemia can be effectively controlled with medical treatment, which tide); improved β-cell sensitivity to GLP-1; absence of post- is a viable alternative to pancreatic surgery. surgery reduction of islet cell mass/function; increased insu- lin sensitivity secondary to weight loss; inappropriate insulin Keywords: Nesidioblastosis; Hyperinsulinemic hypoglycemia; Med- hypersecretion and anomalous counter-regulatory hormonal ical treatment; Diazoxide response to hypoglycemia [6]. Nesidioblastosis is a possible cause of HH in individuals without previous history of bariatric surgery and negative lo- calizing imaging studies. In this condition hypoglycemia usu- ally arises in the postprandial period [3]. Treatment of nesidio- Introduction blastosis includes the acute management of hypoglycemia and surgical or chronic medical treatment. Surgical treatment is the Hyperinsulinemic hypoglycemia (HH) comprises a group of choice in patients with severe or refractory hypoglycemia. Pri- clinically, genetically and histologically heterogeneous disor- or to surgery, selective arterial calcium stimulation (SACST) should be done to determine whether the increased insulin se- cretion is focal or diffuse [7]. In cases where the imaging and Manuscript submitted October 14, 2019, accepted October 25, 2019 functional tests fail to fully characterize the condition or the patient presents any contraindication to surgery, medical treat- aEndocrinology, Diabetes and Metabolism Department, Santa Maria Hospital, ment can be considered. Long-term medical therapy comprises Lisbon, Portugal dietetic measures, alpha-glucosidase inhibitors, calcium chan- bCorresponding Author: Vania Gomes, Endocrinology, Diabetes and Metabo- lism Department, Santa Maria Hospital, Avenida Professor Egas Moniz, Lis- nel blockers, diazoxide, and somatostatin analogues [1]. Di- bon 1649-035, Portugal. Email: [email protected] etary modifications might be sufficient to manage patients with mild postprandial hypoglycemic episodes [7, 8]. Treatment de- doi: https://doi.org/10.14740/jem617 pends on the severity of hypoglycemic episodes. When medi- Articles © The authors | Journal compilation © J Endocrinol Metab and Elmer Press Inc™ | www.jofem.org This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits 199 unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited Hyperinsulinemic Hypoglycemia in the Adult J Endocrinol Metab. 2019;9(6):199-202 Table 1. Laboratory Tests Parameter Patient’s 72-h fasting test Endogenous hyperinsulinism [2] Insulin (µU/mL) 6.4 ≥ 3 Proinsulin (pmol/L) 5.6 ≥ 5 C-peptide (nmol/L) 0.6 ≥ 0.2 Beta-hydroxybutyrate (mmol/L) ≤ 2.7 ≤ 2.7 cation is needed, diazoxide is the first-line medical therapy for and lack of focal lesions in the pancreas in multiple imaging long-term management [1]. exams suggested the diagnosis of adult nesidioblastosis. The We report a case of a 45-year-old man with HH, probably patient was hesitant toward any further invasive procedure as nesidioblastosis, successfully treated with medical therapy. SACST and surgery. He opted for conservative medical treat- ment in association with dietary recommendations. A short trial with nifedipine 30 mg per day resulted in no amelioration Case Report of hypoglycemia and intolerable side effects of headache and peripheral edema. Treatment with diazoxide 150 mg/day was We report the case of a 45-year-old man, referenced to the en- started, with progressive increase to 400 mg/day over 6 weeks. docrinology department of a tertiary hospital in 2014 for inves- Patient now presents fasting glycemia of 78 - 86 mg/dL and 90 - tigation of severe and recurrent hypoglycemia. The patient was 115 mg/dL postprandially. Blood pressure levels remain within a construction worker, so these hypoglycemic episodes were normal range and the patient reports no diazoxide-related side life-threatening. He reported fasting and postprandial symp- effects. Patient has been successfully treated with diazoxide for toms of dizziness, impaired concentration, profuse sweating, 5 years with marked improvement in quality of life. and peripheral tremor. After food ingestion, symptoms re- verted. In one of such episodes capillary BG was confirmed to be below 40 mg/dL. Nevertheless, in routine blood analy- Discussion sis 2 years prior, he presented BG levels under 60 mg/dL, but no further investigation was conducted then. He denied recent Distinction between adult nesidioblastosis and an occult insu- significant weight gain. Medical history was notable for pul- linoma can be difficult, due to the similarity of the biochemi- monary tuberculosis in 2011, cured after a prolonged course of cal profile and some overlap in clinical presentation. The main combined tuberculostatic drugs, as well as vena cava throm- clinical feature of nesidioblastosis is postprandial hypoglyce- bosis, diagnosed in the same year and treated with acenocou- mia, although fasting hypoglycemia has also been reported, as marol 4 mg/day since then. The patient denied previous sur- is typical in patients with insulinoma [9, 10]. The definitive gical interventions, particularly bariatric or gastric procedures diagnosis relies on anatomical localization and histological ex- and previous diagnosis of diabetes or surreptitious intake of in- amination of the pancreatic tissue [10, 11]. sulin or oral hypoglycemic agents. He admitted having regular Nesidioblastosis is suspected in patients with HH and moderate consumption of alcoholic beverages (48 g of alcohol negative imaging studies, as we presented in this clinical case. per day). Physical examination was unremarkable. Localization imaging studies comprise CT, MRI, transabdomi- Laboratory tests showed normal thyroid, adrenal and nal ultrasonography and somatostatin receptor scintigraphy, liver function. Liver ultrasonography was also normal. Gly- as well as more invasive studies (endoscopic ultrasonography cated hemoglobin was 4.0% and ambulatory self-monitoring and SACST) [3]. Besides, emerging GLP-1 receptor-based of capillary glucose confirmed low BG levels in fasting state imaging with 68Ga-DOTA-exendin-4 positron emission to- (30 - 60 mg/dL) and postprandially (55 - 90 mg/dL), even mography-computed tomography (PET-CT) has been used for after implementation of a low carbohydrate seven-meal diet insulinoma localization in a few studies [12]. plan. The 72-h fasting test led to the fulfillment of Whipple’s When these methods fail to identify a focal lesion, SACST triad after only 4 h (BG of 45 mg/dL).
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