Autoimmune hypoglycemia syndrome associated with α lipoic acid consumption

Michalopoulou Alevras, Theodora; Guerrero Gual, Mireia; Villabona Artero, Carles; Pérez-Maraver, Manuel
doi:10.1016/j.medcle.2014.02.004
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    "titulo" => "Autoimmune hypoglycemia syndrome associated with <span class="elsevierStyleBold">&#945;</span> lipoic acid consumption"
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      "es" => array:1 [
        "titulo" => "S&#237;ndrome de hipoglucemia autoinmune asociado al consumo de &#225;cido <span class="elsevierStyleBold">&#945;</span> lipoico"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The insulin autoimmune syndrome &#40;IAS&#41; is a rare cause of endogenous hyperinsulinism&#44; characterised by fasting hypoglycaemia&#44; postprandial hypoglycaemia or both&#44; by very high levels of insulin and by positive anti-insulin autoantibodies &#40;IAA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> It can be induced by certain drugs&#44; especially those with sulfhydryl groups&#44; which have been related to up to 50&#37; of the cases&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> In particular&#44; its onset can be triggered by the &#945; lipoic acid &#40;ALA&#41;&#44; increasingly used during the last years as nutritional supplement&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The case of a Caucasian 55 year-old female referred for hypoglycaemia examination is presented&#46; Allergy to iodinated contrast was the only relevant history&#59; no use of habitual medication was reported&#46; She had a 2-month case history characterised by adrenergic and neuroglycopenic symptoms&#44; both in fasting and postprandial states&#44; that resolved after food intake&#44; and a 2<span class="elsevierStyleHsp" style=""></span>kg weight gain &#40;weight 53<span class="elsevierStyleHsp" style=""></span>kg&#44; body mass index &#91;BMI&#93; 21<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&#41;&#46; The physical examination using devices was anodyne&#46; The general laboratory tests showed blood sugar levels of 3&#46;2<span class="elsevierStyleHsp" style=""></span>mmol&#47;L &#40;4&#46;1&#8211;6&#46;9&#41; and haemoglobin &#40;HbA&#41;<span class="elsevierStyleInf">1c</span> of 5&#46;6&#37;&#46; A fasting test was performed and it was positive at 3<span class="elsevierStyleHsp" style=""></span>h with blood sugar levels of 2&#46;4<span class="elsevierStyleHsp" style=""></span>mmol&#47;L &#40;4&#46;1&#8211;6&#46;9&#41;&#59; insulinemia&#58; 1&#46;033<span class="elsevierStyleHsp" style=""></span>pmol&#47;L &#40;21&#8211;174&#41;&#59; C peptide&#58; 4&#46;10<span class="elsevierStyleHsp" style=""></span>nmol&#47;L &#40;0&#46;26&#8211;1&#46;44&#41;&#59; and cortisol 419<span class="elsevierStyleHsp" style=""></span>nmol&#47;L &#40;155&#8211;678&#41;&#46; The determination of urine sulfonylurea was negative&#46; IAA determination was done&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A treatment with fractionated diet and 200<span class="elsevierStyleHsp" style=""></span>g of iv glucose was established&#44; with recurrence of hypoglycaemia and occasional postprandial hyperglycaemia episodes&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Complementary examinations were required to rule out insulinoma as the most frequent cause of endogenous hyperinsulinism&#46; Given her history&#44; 3 bolus of 50<span class="elsevierStyleHsp" style=""></span>mg&#47;day of prednisone i&#46;v&#46; were administered prior to the computed tomography with contrast&#44; which was normal&#46; The echoendoscopy described a 3<span class="elsevierStyleHsp" style=""></span>mm nodule in the pancreatic head&#44; whose citological analysis &#40;fine-needle aspiration &#91;FNA&#93;&#41; was consistent with normal pancreas&#46; <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the results of the selective angiography with calcium stimulation&#46; Finally&#44; a diagnostic laparotomy was performed&#46; Manual examination and intraoperative ultrasound scan of the pancreas were normal&#59; thus&#44; only an extended biopsy was performed&#46; After the intervention&#44; the blood sugar levels were normalised and gave place to the progressive withdrawal of i&#46;v&#46; glucose contribution&#46; The received results of the IAAs &#40;RIA&#41; were 85&#46;8&#37; &#40;normal&#58; &#60;8&#46;20&#37;&#41;&#46; In a new targeted history&#44; ALA intake &#40;200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; as nutritional supplement &#40;to prevent hair loss&#41; during 15 days was discovered&#46; The histological result showed hyperplasia of the pancreatic islets affecting approximately 10&#37; of them and with insulin predominant expression&#46; At the moment of discharge&#44; the patient did not show new episodes of hypoglycaemia and insulinema was normalised&#46; After one year&#44; the IAA levels have decreased without reaching normalisation&#46; Corticosteroids as preparation for the radiological techniques were the only immunomodulator treatment administered&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The IAS&#44; first described by Hirata in 1970&#44; is a rare cause of hypoglycaemia&#44; except in Japan where it constitutes the third cause&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">3&#44;4</span></a> The cases described in Caucasian population are scarce&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> It affects patients aged between 40 and 80 years old&#44; with no difference in gender&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> It is associated to autoimmune diseases<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> &#40;related to HLA-DRB1&#42;0406 and HLA-DRB1&#42;0403<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a>&#41; such as systemic lupus erithematosus &#40;SLE&#41;&#44; among others<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a>&#44; and to the use of drugs with sulfhydryl groups<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> &#40;e&#46;g&#46;&#44; methimazole&#41;&#46; The physiopathology is barely known&#59; the hypothesis is that the activity reducing the sulfhydryl group causes the rupture of the insulin disulphide bridges&#44; exposing it to the cells that carry the antigen&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Hypoglycaemia is the consequence of the dissociation of insulin and the IAAs&#44; which occurs asynchronously with blood sugar levels&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Insulinemia is higher than expected for an insulinoma&#44; generally over 1000<span class="elsevierStyleHsp" style=""></span>pmol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a> Little data has been reported about the histology of these cases&#44; and they are about cells hyperplasia &#946;&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> In 80&#37; of the cases&#44; the symptoms are resolved in weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> The treatment includes a diet fractionated in carbohydrates as first line&#44; discontinuation of any medication associated to IAS and glucocorticoids &#40;prednisone 30&#8211;60<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Plasmapheresis and other treatments have demonstrated different results&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The ALA is an antioxidant with sulfhydryl groups&#46; In 2004&#44; it was approved as nutritional supplement and it is widely used nowadays&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> Seventeen cases of IAS related to the ALA have been described in Japan&#44; and recently 7 cases were reported in the Caucasian population&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;9</span></a> IAS was our definitive diagnosis considering the presence of hypoglycaemia with occasional episodes of postprandial hyperglycaemia&#44; very high levels of insulinemia and positive IAAs&#44; selective arteriography with increased levels of insulin in the entire gland without a gradient&#44; histology with hyperplasia of the pancreatic islets and symptoms resolution after the administration of corticosteroids&#44; in the context of previous administration of ALA&#46; The application of the modified Karch and Lasagna causality algorithm<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a> allowed the categorisation of our case as possible IAS related to the administration of ALA&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">It is the first case of IAS associated to the use of ALA in Spain&#46; The use of ALA must be included in the habitual history of patients under examination for endogenous hyperinsulinism&#46;</p></span>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">90<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">120<span class="elsevierStyleHsp" style=""></span>min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="5" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Insulin &#40;pmol&#47;L&#41;</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Common hepatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">936&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1058&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1080&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Gastroduodenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1041&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">976&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1008&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1040&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Proximal splenic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1092&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1168&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1081&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1065&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Superior mesenteric&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1042&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1042&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1066&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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