Diagnosis and Treatment > Signs and Symptoms
Search for other papers by A Veltroni in
Google Scholar
PubMed
Search for other papers by G Zambon in
Google Scholar
PubMed
Search for other papers by S Cingarlini in
Google Scholar
PubMed
Search for other papers by M V Davì in
Google Scholar
PubMed
Summary
Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Moreover, several recent reports showed a direct association between the onset of IAS and the consumption of dietary supplements containing alpha-lipoic acid (LA). Insulinoma remains the most prevalent cause of hypersulinaemic hypoglycaemia in Caucasians. Consequently, primary investigation in these patients is generally focused on localisation of the pancreatic tumour, often with invasive procedures followed by surgery. We described a case of an Italian woman presenting to us with severe recurrent hypoglycaemia associated with high insulin and C-peptide levels and no evidence of pancreatic lesions at imaging diagnostic procedures. She had taken LA until 2 weeks before hospitalisation. After an evaluation of her drug history, an autoimmune form of hypoglycaemia was suspected and the titre of insulin autoantibodies was found to be markedly elevated. This allowed us to diagnose LA-related IAS, thus preventing any unnecessary surgery and avoiding invasive diagnostic interventions.
Learning points:
-
IAS is a rare cause of hyperinsulinaemic hypoglycaemia that typically affects Asian population, but it has been increasingly recognised in Caucasian patients.
-
It should be considered among the differential diagnosis of hyperinsulinaemic hypoglycaemia to avoid unnecessary diagnostic investigations and surgery.
-
It should be suspected in the presence of very high serum insulin levels (100–10 000 μU/mL) associated with high C-peptide levels.
-
There is a strong association with administration of drugs containing sulphydryl groups included LA, a dietary supplement commonly used in Western countries to treat peripheral neuropathy.
Search for other papers by Sarah Y Qian in
Google Scholar
PubMed
Search for other papers by Matthew J L Hare in
Google Scholar
PubMed
Search for other papers by Alan Pham in
Google Scholar
PubMed
Department of Medicine, Monash University, Melbourne, Australia
Search for other papers by Duncan J Topliss in
Google Scholar
PubMed
Summary
Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.
Learning points:
-
Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.
-
Although uncommon, insulinomas can present with post-prandial hypoglycaemia.
-
In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.
-
Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.
-
Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.
Search for other papers by Catarina Roque in
Google Scholar
PubMed
Search for other papers by Ricardo Fonseca in
Google Scholar
PubMed
Search for other papers by Carlos Tavares Bello in
Google Scholar
PubMed
Search for other papers by Carlos Vasconcelos in
Google Scholar
PubMed
Search for other papers by António Galzerano in
Google Scholar
PubMed
Search for other papers by Sância Ramos in
Google Scholar
PubMed
Summary
Primary adrenal lymphoma is a rare malignancy. It frequently presents bilaterally and with symptoms of adrenal insufficiency. Amiodarone may induce secondary organ dysfunction, and thyrotoxicosis develops in 15% of cases. The symptomatology of both conditions is nonspecific, especially in the elderly, and a high suspicion index is necessary for appropriate diagnosis. A 78-year-old female presented to the emergency department with confusion, nausea and vomiting. She had recently been to the emergency department with urinary tract infection, vomiting and acute hypochloremic hyponatremia. Upon re-evaluation, the leukocyturia persisted and because of TSH 0.01 µU/mL and free-T4 68 (10–18) pmol/L, she was admitted to the Endocrinology ward. Further evaluation supported amiodarone-induced thyroiditis type 2. Sepsis ensued, in the setting of nosocomial pneumonia. Hemodynamic instability, hyponatremia, hypoglycemia and vomiting raised the suspicion of adrenocortical insufficiency. Fluid resuscitation and hydrocortisone led to clinical improvement, and adrenal insufficiency was admitted. The thoracoabdominal tomography suggested an endobronchic primary lesion with hepatic and adrenal secondary deposits (6.6 and 7 cm), but this was confirmed neither on pleural effusion nor on bronchofibroscopic fluid analyses. The adrenals were not accessible for biopsy. Despite high-dose hydrocortisone maintenance, the patient died before definite diagnosis. The autopsy confirmed primary non-Hodgkin lymphoma.
Learning points:
-
Primary adrenal lymphoma is a rare cause of adrenal insufficiency, but progression can be fast and fatal.
-
Hyperpigmentation is frequently absent.
-
The presenting symptoms are nonspecific and might mimic infection. Disproportion of the general state with signs of specific organ symptomatology is a diagnostic clue.
-
Infection may precipitate adrenal crisis and worsen thyroid function with further adrenal insufficiency exacerbation.
-
In the context of thyrotoxicosis, there may be little clinical response to a therapeutic trial with standard dose glucocorticoids.
-
High-dose glucocorticoid substitution may be required to achieve clinical stability in thyrotoxic patients.
Search for other papers by Adriana de Sousa Lages in
Google Scholar
PubMed
Search for other papers by Isabel Paiva in
Google Scholar
PubMed
Search for other papers by Patrícia Oliveira in
Google Scholar
PubMed
Search for other papers by Francisco Portela in
Google Scholar
PubMed
Search for other papers by Francisco Carrilho in
Google Scholar
PubMed
Summary
Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia. Although surgical enucleation is the standard treatment, a few other options are available to high-risk patients who are elderly or present with co-morbidities. We present a case report of an 89-year-old female patient who was admitted to the emergency department due to recurrent hypoglycaemia, especially during fasting. Laboratory work-up raised the suspicion of hyperinsulinaemic hypoglycaemia, and abdominal CT scan revealed a 12 mm nodular hypervascular lesion of the pancreatic body suggestive of neuroendocrine tumour. The patient was not considered a suitable candidate for surgery, and medical therapy with diazoxide was poorly tolerated. Endoscopic ultrasound-guided ethanol ablation therapy was performed and a total of 0.6 mL of 95% ethanol was injected into the lesion by a transgastric approach; no complications were reported after the procedure. At 5 months of follow-up, no episodes of hypoglycaemia were reported, no diazoxide therapy was necessary, and revaluation abdominal CT scan revealed a pancreatic nodular lesion with a size involution of about half of its original volume. The patient is regularly followed-up at the endocrinology clinic and shows a significant improvement in her wellbeing and quality of life.
Learning points:
-
Insulinomas are the most frequent cause of hyperinsulinaemic hypoglycaemia.
-
Surgical enucleation is the standard treatment with a few other options available to high-risk patients.
-
Endoscopic ultrasound-guided ethanol ablation therapy is one feasible option in high-risk patients with satisfactory clinical outcomes, significant positive impact on quality of life and low complication rates related to the procedure.
Search for other papers by Katia Regina Marchetti in
Google Scholar
PubMed
Search for other papers by Maria Adelaide Albergaria Pereira in
Google Scholar
PubMed
Search for other papers by Arnaldo Lichtenstein in
Google Scholar
PubMed
Search for other papers by Edison Ferreira Paiva in
Google Scholar
PubMed
Summary
Adrenacarcinomas are rare, and hypoglycemic syndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by these tumors have been described infrequently. This study describes the case of a young woman with severe persistent hypoglycemia and a large adrenal tumor and discusses the physiopathological mechanisms involved in hypoglycemia. The case is described as a 21-year-old woman who presented with 8 months of general symptoms and, in the preceding 3 months, with episodes of mental confusion and visual blurring secondary to hypoglycemia. A functional assessment of the adrenal cortex revealed ACTH-independent hypercortisolism and hyperandrogenism. Hypoglycemia, hypoinsulinemia, low C-peptide and no ketones were also detected. An evaluation of the GH–IGF axis revealed GH blockade (0.03; reference: up to 4.4 ng/mL), greatly reduced IGF-I levels (9.0 ng/mL; reference: 180–780 ng/mL), slightly reduced IGF-II levels (197 ng/mL; reference: 267–616 ng/mL) and an elevated IGF-II/IGF-I ratio (21.9; reference: ~3). CT scan revealed a large expansive mass in the right adrenal gland and pulmonary and liver metastases. During hospitalization, the patient experienced frequent difficult-to-control hypoglycemia and hypokalemia episodes. Octreotide was ineffective in controlling hypoglycemia. Due to unresectability, chemotherapy was tried, but after 3 months, the patient’s condition worsened and progressed to death. In conclusion, our patient presented with a functional adrenal cortical carcinoma, with hyperandrogenism associated with hypoinsulinemic hypoglycemia and blockage of the GH–IGF-I axis. Patient’s data suggested a diagnosis of hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor (low levels of GH, greatly decreased IGF-I, slightly decreased IGF-II and an elevated IGF-II/IGF-I ratio).
Learning points:
-
Hypoglycemyndrome resulting from the secretion of insulin-like growth factor II (IGF-II) by adrenal tumors is a rare condition.
-
Hypoinsulinemic hypoglycemia associated with hyperandrogenism and blockage of the GH–IGF-I axis suggests hypoglycemia induced by an IGF-II or a large IGF-II-producing tumor.
-
Hypoglycemia in cases of NICTH should be treated with glucocorticoids, glucagon, somatostatin analogs and hGH.
Search for other papers by Pooja Sahni in
Google Scholar
PubMed
Search for other papers by Nitin Trivedi in
Google Scholar
PubMed
Search for other papers by Abdulkadir Omer in
Google Scholar
PubMed
Summary
A 65-year-old obese Caucasian woman presented with symptomatic postprandial hypoglycemic episodes, resolution of symptoms with carbohydrate intake and significantly elevated anti-insulin antibody levels. She did not have any evidence for the use of oral antidiabetic medications, insulin, herbal substances, performing strenuous exercise or history of bariatric surgery. Fingerstick blood glucose readings revealed blood sugar of 35 mg/dL and 48 mg/dL, when she had these symptoms. Her medical history was significant for morbid obesity, hypothyroidism and gastro esophageal reflux disease. Her home medications included levothyroxine, propranolol and omeprazole. A blood sample obtained during the symptoms revealed the following: fingerstick blood sugar 38 mg/dL, venous blood glucose 60 mg/dL (normal (n): 70–99 mg/dL), serum insulin 202 IU/mL (n: <21), proinsulin 31.3 pmol/L (n: <28.9), C-peptide 8 ng/mL (n: 0.9–7), beta-hydroxybutyrate 0.12 mmol/L (n: 0.02–0.27) anti-insulin antibody >45.4 U/mL (n: <0.4). The result obtained while screening for serum sulfonylurea and meglitinides was negative. The repeated episodes of postprandial hypoglycemia associated with significantly elevated anti-insulin antibodies led to a diagnosis of insulin antibody syndrome (IAS). Significant improvement of hypoglycemic symptoms and lower anti-insulin antibody levels (33 U/mL) was noted on nutritional management during the following 6 months. Based on a report of pantoprazole-related IAS cases, her omeprazole was switched to a H2 receptor blocker. She reported only two episodes of hypoglycemia, and anti-insulin antibody levels were significantly lower at 10 U/mL after the following 12-month follow-up.
Learning points:
Initial assessment of the Whipple criteria is critical to establish the clinical diagnosis of hypoglycemia accurately.
Blood sugar monitoring with fingerstick blood glucose method can provide important information during hypoglycemia workup.
Autoimmune hypoglycemia is a rare cause of hypoglycemia, which can be diagnosed on high index of clinical suspicion and systematic evaluation.
