OBJECTIVE: Hyperinsulinemic hypoglycaemia (HH) presents significant management challenges, especially in cases refractory to standard therapies. This case series aims to report the efficacy and safety of sirolimus, an mTOR inhibitor, as an adjunctive therapy in persistent HH, noting that current clinical guidelines caution its use outside of research.
METHODS: We report a case series from two paediatric endocrinology centres across Australia, describing use of sirolimus in four infants with persistent HH refractory to conventional treatments or post near-total pancreatectomy. Retrospective chart reviews provided clinical and biochemical data, documenting each patient\'s sirolimus dosing, treatment responses, and adverse events.
CONCLUSIONS: Sirolimus emerged as a useful and safe adjunct, enabling hospital discharge, and demonstrating efficacy even at lower serum trough levels. Despite safety concerns, including recurrent viral infections in one patient, sirolimus was generally well-tolerated. We advocate for implementing risk mitigation strategies, including a multidisciplinary approach, and maintaining lower sirolimus trough levels than previously recommended. Careful consideration of sirolimus is warranted in select cases of severe diffuse HH, emphasising ongoing monitoring for adverse effects and further research to refine treatment guidelines.

Hypoglycaemic unawareness (HU) is more frequently described in relation to diabetics in the literature. We have noted that there is also an increasing reporting of HU in insulinoma cases. We report a hospital presentation for an incidental finding of hypoglycaemic unawareness in a gentleman in his fifties who was eventually diagnosed with insulinoma following biochemical studies, radiologic evaluation and histologic evaluation of an excised lesion between the pancreas and the spleen. We have reviewed existing literature evidence regarding the possible aetiologies and management options for this occurrence. More research studies to identify the epidemiology of this association and the determination of a protocol for increased detection of patients with insulinoma who display HU will need to be done.

Insulin autoimmune syndrome (IAS) is a rare cause of spontaneous hypoglycaemia. We discuss a 91-year-old Caucasian lady who presented with syncope and episodic adrenergic and neuroglycopenic symptoms. Despite significantly elevated insulin, C-peptide, and proinsulin levels with the presence of anti-insulin antibodies, a pancreatic mass was not identified. Serum immunoelectrophoresis demonstrated monoclonal gammopathy of undetermined significance (MGUS). Treatment involved high-dose steroids, diazoxide, corn starch and acarbose, however the patient passed away four months later due to worsening co-morbidities. The management of IAS in the setting of MGUS is challenging.

Noonan syndrome (NS) is a dominantly inherited genetic disorder with mutations in genes encoding components or regulators of the Rat sarcoma virus/mitogen-activated protein kinase pathway. Its diagnosis is based on characteristic features, including typical facial features, a short stature, congenital heart disease, mild developmental delay, and cryptorchidism. Patients with NS sometimes develop autoimmune diseases, such as Hashimoto\'s thyroiditis and, rarely, systemic lupus erythematosus (SLE). We herein present a 29-year-old Japanese female with NS complicated by SLE and repeated severe hypoglycaemia. The patient was diagnosed with SLE based on thrombocytopenia, nephritis, a positive antinuclear antibody titre (1:640), and a positive anti-dsDNA antibody. The patient was treated with a glucocorticoid, mycophenolate mofetil, and tacrolimus, which attenuated both SLE and hypoglycaemia. Since insulin receptor antibody levels were higher to the upper normal range and decreased after treatment, hypoglycaemia probably appeared to be attributed to type B insulin resistance syndrome. We herein present the first case of SLE in NS complicated by type B insulin resistance syndrome. Although NS is a rare disease, we need to consider the complication of autoimmune diseases, including SLE.

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A 78-year-old diabetic patient was admitted with unexplained refractory hypoglycaemia. He was taking gliclazide and metformin and had good glycaemic control. He was suspected to have a sulfonylurea overdose, and intravenous 10% dextrose failed to correct hypoglycaemia. He was then treated with octreotide (a specific antidote to sulfonylurea), which corrected his low blood sugar level. Intravenous dextrose and octreotide are often the drugs of choice for treating hypoglycaemia from sulfonylurea toxicity. A high index of suspicion is needed for early diagnosis of sulfonylurea overdose.

Costus igneus, commonly known as the \'Insulin plant\' has been traditionally used in India to lower blood sugar levels. Its method of action is through a protein peculiar to itself, which has hypoglycaemic action. It therefore may prove harmful if used in excess, or together with other hypoglycaemic agents.

The pathogenesis of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia is not yet fully clarified. Recent studies suggest an up-regulation of the intestinal glucose transporter SGLT-1 aimed to prevent carbohydrate malabsorption. The overexpression of SGLT-1 could therefore represents one of the mechanisms underlying the wide glycemic excursions found in patients after gastrectomy, but studies investigating the use of SGLT-1/SGLT-2 inhibitors in patients with post-gastrectomy reactive hyperinsulinemic hypoglycaemia are very scant in the literature. We report the case of a 37-year-old non diabetic man who frequently presented symptoms of hypoglycaemia in the postprandial period. In 2012, he underwent Roux en-Y gastric bypass (RYGB) and after two years, he started to experience typical symptoms of reactive hyperinsulinaemic hypoglycaemia. We suggested healthy modifications of dietary habits and periodic follow-up visits with a dietitian. After three months, the patient still presented symptoms of reactive hypoglycaemia; we provided him with Flash Glucose Monitoring (FGM) to assess trend of glucose levels in interstitial fluid during the day and we decided to introduce canagliflozin 300 mg/day before the main meal. Hypoglycaemic events previously referred by the patient and clearly recorded by FGM completely disappeared taking canagliflozin. We found a reduction of time spent in hypoglycaemia, an improvement of glycemic variability and an increase of time in target range. It was also noted a reduction of time spent in hyperglicemia with consequent improvement of average glucose values and of glucose main indicator. This is the first report with FGM supporting a role of canagliflozin in the management of post-gastrectomy reactive hyperinsulinaemic hypoglycaemia. Our preliminary results are very limited but in line with those of the literature and showed for the first time a reduction of hypoglycaemic events and an improvement of glycemic variability through a flash glucose monitoring system. Further studies are mandatory to confirm this therapeutic opportunity.

BACKGROUND: Insulinomas are an uncommon occurrence, with an annual incidence of approximately 4 per million. These functional pancreatic neuroendocrine tumours can present with a myriad of nonspecific symptoms leading to frequent misdiagnoses.
METHODS: In this case report is presented a 55-year-old man who was misdiagnosed and managed for a seizure disorder with escalating antiepileptic treatments for 11 months. A thorough history after an attack was the main tool in solving the mystery of his refractory seizures, leading to the discovery of a pancreatic insulinoma. Biochemical tests revealed fasting hypoglycaemia and a relative hyperinsulinemia, and a distal pancreatic lesion measuring approximately 1.8 cm × 1.3 cm was detected on CT, MRI and endoscopic ultrasound. Successful laparoscopic pancreatic left resection led to complete resolution of symptoms and restoration of quality of life to pre-illness levels.
CONCLUSIONS: Insulinomas have historically been difficult to diagnose because their symptoms mimic neurologic and psychiatric conditions. Patterns of symptom occurrence obtained from a carefully-taken history is the single most important tool in assessing patients with insulinomas, who usually present with unusual and refractory neuropsychiatric conditions.

Dumping syndrome after bariatric surgery is common. However, it is rarely seen during pregnancy because patients are usually advised to avoid pregnancy immediately after surgery. This case highlights the importance of avoidance of pregnancy after bariatric surgery. We report a case of unplanned pregnancy in a 35-year-old woman with a history of subfertility for 8 years who conceived spontaneously 3 months after gastric bypass surgery. This occurred because there was no contraception offered to her after the procedure. The pregnancy was complicated with recurrent episodes of hypoglycaemia secondary to dumping syndrome. Primary care providers need to be vigilant and have a high index of suspicion for dumping syndrome in pregnant obese women who have undergone bariatric surgery.