Cases Of Hyperinsulinism Research Articles

The Rising Incidence of Hyperinsulinemic Hypoglycemia: Connection With Maternal Health

ObjectiveDue to a perceived rise in hyperinsulinemic hypoglycemia (HH) cases over time, notably during the COVID-19 pandemic, institutional experiences between 2013 and 2021 were reviewed to evaluate trends, characteristics, and outcomes in children with HH. MethodsCharts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology were reviewed. HH was defined per Pediatric Endocrine Society guidelines. Regression analysis compared rates of change in HH cases and maternal risk factors over time. ResultsThe incidence of HH began to rise in April 2016 and became significant in March 2017 (P < .001), with a more rapid rate of rise during the first year of the COVID-19 pandemic (P < .001). Seventy-four children with HH were identified over 9 years; 43% (n = 32) were diagnosed in 2020-2021. Maternal hypertensive disorders demonstrated longitudinal association with hyperinsulinism cases (P < .001). ConclusionWhile HH diagnoses were on the rise for much of the 9-year study period, nearly half of all infants were diagnosed during the COVID-19 pandemic in 2020 to 21. The trends in HH diagnoses correlated with maternal hypertensive disorders. More studies exploring the roles of maternal health, hypertension, and stress and development of HH in offspring are needed.

Audit of acute hypoglycaemia in children: re-audit of procedures for diagnosis

A protocol exists for the collection of samples to investigate unexplained hypoglycaemia, termed the 'hypopack'. These packs are kept in Accident and Emergency departments and neonatal special care baby units throughout Northern Ireland and most wards of the Regional Children's Hospital. A retrospective audit of 107 hypopacks received between July 2001 and December 2003 highlighted a number of problems: samples collected when the patient was receiving dextrose, incomplete clinical history provided, insufficient and haemolysed samples received and poor filing of reports in charts. These were addressed by re-designing the request form, updating the protocol and introducing a summative report. The new protocol was introduced in April 2006. The aim of this study is to assess whether the revised protocol improved utility of the hypopack. A retrospective re-audit of 100 hypopacks received between April 2006 and May 2007 was performed. Forty-nine percent of patients were hypoglycaemic (<2.6 mmol/L) compared with 35% in the original audit. In both audits, 33% of laboratory reports were missing from patients' charts. One case of medium-chain acyl-CoA dehydrogenase deficiency, three cases of hyperinsulinism and two endocrine-related cases were identified. The new hypopack protocol has increased the number of appropriately performed investigations. Provision of information concerning dextrose infusion has assisted the interpretation of the hypopack results.

A case of hyperinsulinism/hyperammonaemia syndrome: usefulness of the oral protein tolerance for the evaluation of treatment

Hyperinsulinism/hyperammonaemia (HI/HA) syndrome (OMIM 606762) was first reported by Zammarchi et al. [7] and Weinzimer et al. [6] in the late 1990 s as cases of hyperinsulinism with hypoglycaemia having persistently high plasma ammonium levels. In 1998, Stanley et al. [4] reported that HI/HA syndrome is caused by mutations in the glutamate dehydrogenase (GDH) gene [4]. It is known that the occurrence of HI/HA is as follows [3]. As the result of the overactivity of GDH, a mitochondrial matrix enzyme, there is an increase in the ATP/ADP ratio and a reduction in glutamate using NAD or NADP as a coenzyme. Leucine acts as an activator of GDH resulting in hyperinsulinism. Hyperammonaemia results from the decrease in glutamate which in turn decreases the level of N-acetylglutamate, an activator of carbamoyl-phosphate synthetase, the first step in ammonia metabolism. HI/HA syndrome is considered to be an autosomal dominant inherited disorder, although a de novo mutation is often observed. Administration of diazoxide, which inhibits insulin secretion, is considered to be an effective treatment for HI/HA syndrome [2,5]. The present study reports our experience of a case of HI/ HA syndrome in which the oral protein tolerance test was useful in evaluation of treatment. The patient was a girl aged 6 years and 3 months. At the age of 4 years and 1 month, when she had an episode of diarrhoea, her family noticed that she was unsteady and could not articulate. At a local hospital, intravenous glucose infusion resulted in a rapid improvement. As blood glucose was 23 mg/dl and urinary ketones were demonstrated (4+), a diagnosis of ‘‘ketotic hypoglycaemia’’ was made. Thereafter, during occasional upper respiratory tract infections, blood glucose levels often dropped below 50 mg/dl. At the age of 6 years, symptoms such as abnormal eye movements and body sway after lunch became increasingly frequent. At this stage, the patient who was thought to be experiencing hypoglycaemic episodes, was referred to our medical centre. In terms of family history, her mother (34 years old) had hypoglycaemia when she was young. The patient’s physical development had been normal, but she had always been restless. On examination, height was 113.2 cm (-0.34 SD) and weight was 23.0 kg (obesity index 14%), and the physical examination was unremarkable, with neither hepatomegaly nor splenomegaly observed. Clinical laboratory tests on admission revealed hypoglycaemia (blood glucose 44 mg/dl) and hyperammonaemia (NH3 212 lg/dl) with no other abnormalities. Blood ketone bodies and free fatty acids were within the appropriate reference ranges. Plasma insulin level (IRI) was normal (3.1 lU/ml), and levels of pituitary hormones, cortisol, thyroid hormones, and glucagon were unremarkable. Venous blood gas analysis and urinalysis revealed no abnormality. Prior to the current admission, she had been brought straight from kindergarten to the emergency department of our hospital at the age of 5 years. At that time, blood biochemistry showed the following results: glucose 23 mg/dl; IRI 19.2 lU/ml; and NH3 184 lg/dl. On recovery, she had been followed up on an outpatient basis and fasting biochemistry revealed the following: glucose 52 mg/dl; IRI 2.1 lU/ml; NH3 183 lg/dl, and ketone bodies 99 nmol/ml. Analysis of urinary organic acids demonstrated only a mild to moderate increase in ketone bodies during hypoglycaemic attacks. Acylcartinine analysis by tandem mass spectrometry showed no particular abnormality. Moreover, analysis of blood amino acids during a hypoglycaemic attack was unremarkable. In terms of diagnostic imaging, ultrasound and CT revealed no abnormality of the liver, pancreas, or portal vein. The level of insulin was high (19.2 lU/ml) Y. Toriumi (&) AE K. Murata AE T. Taketani AE A. Uchiyama T. Ohie AE S. Yamaguchi Department of Paediatrics, Shimane University School of Medicine, Izumo, Japan E-mail: toriumi@r3.dion.ne.jp Tel.: +81-852-278111 Fax: +81-852-278119

Diagnostic value of sodium tolbutamide test in hypoglycemia.

The intravenous Na-tolbutamide test was done on various types of hypoglyce-mia and the following conclusions were obtained: (1) Though very useful in the screening of hypoglycemia, the test is not always satisfactory for the differential diagnosis of various types of hypoglycemia. (2) The diagnosis of hypoglycemia by means of the Na-tolbutamide test is con-sidered practically established when the recovering ability from hypoglycemic levels is absent or insufficient, so as to give a value of the recovery index mostly 0.5 or less, and the stationary value is not higher than 55mg/100ml. (3) Pronounced hypoglycemia occasionally persists in some cases of functional hypoglycemia. Temporary rise in the blood sugar levels is observed in some cases of pancreatic hyperinsulinism. Differential diagnosis between the two types of hypoglycemia is impossible when only the Na-tolbutamide test is employed. (4) In a patient with diabetes complicated with hypoglycemia, the blood sugar level 20 and 30 minutes after intravenous tolbutamide injection showed an obvious decrease in the decline rate. (5) Biphasic fluctuations of blood sugar levels after intravenous tolbutamide injection were observed in three cases of hyperinsulinism.

INSULIN HYPOGLYCEMIA IN EPILEPSY

In this study epileptic patients were given injections of insulin for the purpose of determining the role of hypoglycemia in precipitating seizures. Reports of many studies have appeared in the literature suggesting that epileptic attacks may be due to hypoglycemia. On the whole, the evidence has been indirect and not conclusive. Recent clinical knowledge of hyperinsulinism and other types of hypoglycemia has aroused attention anew to this problem. Harris 1 reported three cases of hyperinsulinism and collected reports of twelve others (twelve of fifty recorded cases) in which convulsions were the predominant symptom. In several of these cases a diagnosis of epilepsy was made at first. The injection of insulin is known to induce convulsions in several species of animals. In fact, insulin was formerly assayed in rabbits by this method. Convulsions resulting from an overdose of insulin are of infrequent occurrence in adult human beings. Still, if hypoglycemia bears

Gastro-intestinal manifestation of hyperinsulinism

1. Reports of cases of hyperinsulinism by clinicians in many countries show that the gastro-intestinal manifestations of this new disease entity are protean and important.

Hyperinsulinism: Three Cases Relieved by Radiation

THE disease entity hyperinsulinism, accompanied and characterized by certain symptoms, the result of hypoglycemia, was first brought to the attention of the profession by Harris (1), in 1924. Shortly after the discovery of insulin by Banting in 1922, reports of cases receiving overdoses began to appear. The symptomatology noted in these cases resembled so closely symptom-complexes frequently observed in certain patients in whom pancreatic disease had not been suspected and in whom insulin had not been given, that a relationship as to cause was the logical conclusion in Harris' mind. In his first communication, he reported two cases—non-diabetic patients who had not received insulin—in which the symptoms observed were identical with certain other cases which were known to have received an over-dose of insulin. Both of these cases had low blood sugar, and in each the symptoms were controlled by carbohydrate diet. If a certain group of cases, receiving an over-dose of insulin, showed the same symptom-complex as another group that had not received insulin, Harris reasoned that there must be existing in this latter group, spontaneously, an excess of insulin. Hence the term hyperinsulinism, an over-secretion of the islets of Langerhans which Harris considers a disease analogous to hyperthyroidism, hyperpituitarism, hyperadren-alism, etc. Incidentally he argues that “hypoinsulinism” would be a preferable term to describe diabetes or hyperglycemia. The symptoms of hyperinsulinism, while protean, are generally familiar to the profession to-day; the procedures in arriving at a diagnosis and the methods of treatment are somewhat standardized, but the etiology in many cases remains unsettled and unexplained. Hyperinsulinism is a disease of the pancreas, although hypoglycemia, its distinctive and constantly accompanying condition, may be due to disease of other organs or secreting glands. The first case of unconsciousness and convulsions, proven to be due to hyperinsulinism, was reported by Allen (2) in 1928. Autopsy in this case showed carcinoma of the pancreas with metastasis to the liver, the metastatic areas in the liver showing islet cells with insulin production. Allen (3), in 1928, reported two other cases of hyperinsulinism with recurring attacks of convulsions. In 1929, Howland (4) reported the first case of hyperinsulinism, showing convulsions and coma, which was cured by surgical removal of an adenoma of the pancreas. In 1931, Car (5) reported a case, a boy 18 years of age, diagnosed as adenoma of the pancreas, who was cured by operative removal of the adenoma. This patient was having convulsions and marked hypoglycemia. In 1932, Womack, Grogi, and Graham (6) reported the removal from the pancreas of a small adenoma, with cure of hypoglycemia and relief of mental confusions and unconsciousness.