Browse
Search for other papers by Rikako Nakajima in
Google Scholar
PubMed
Search for other papers by Daisuke Sato in
Google Scholar
PubMed
Search for other papers by Ichirota Togashi in
Google Scholar
PubMed
Search for other papers by Hiroto Idesawa in
Google Scholar
PubMed
Search for other papers by Jun Ito in
Google Scholar
PubMed
Search for other papers by Kei Ito in
Google Scholar
PubMed
Search for other papers by Masanao Fujii in
Google Scholar
PubMed
Search for other papers by Hiroaki Yagyu in
Google Scholar
PubMed
Summary
An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies.
Learning points
-
Insulinoma presenting with concomitant anti-insulin antibodies appears rare.
-
Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome.
-
Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.
Search for other papers by Takashi Kurihara in
Google Scholar
PubMed
Search for other papers by Kanta Fujimoto in
Google Scholar
PubMed
Search for other papers by Toshio Iwakura in
Google Scholar
PubMed
Search for other papers by Yuji Hataya in
Google Scholar
PubMed
Search for other papers by Daisuke Yamashita in
Google Scholar
PubMed
Search for other papers by Naoki Matsuoka in
Google Scholar
PubMed
Summary
An 82-year-old woman with a 60-year history of a lung tumor presented with hypoglycemia. Non-islet cell tumor hypoglycemia (NICTH) was suspected; however, her hypoglycemia stabilized with supplemental food. She was discharged, based on her wishes, and planned to undergo surgery later. After discharge, the hypoglycemia worsened rapidly and required immediate resection. Postoperatively, the hypoglycemia resolved. Western immunoblot analysis confirmed the presence of big insulin-like growth factor 2, confirming NICTH. This patient experienced the rapid progression of symptoms after an unprecedentedly long-term asymptomatic state. Therefore, when NICTH is suspected, early intervention is recommended regardless of the presence of asymptomatic state.
Learning points
-
In patients with NICTH, the onset of hypoglycemia is usually within a year of tumor detection, and few reports regarding long-term asymptomatic NICTH have been documented.
-
NICTH can cause rapidly progressive symptoms after a long-term asymptomatic state, as in this case, and an asymptomatic state does not preclude the necessity for intervention, especially when patients are at risk for malnutrition.
-
Tumor resection is the only curative treatment for patients with NICTH, but there is no consensus regarding the timing of surgery. However, considering the possibility of rapid symptom progression, patients should be examined and treated in a timely manner.
Search for other papers by Saohoine Inthasot in
Google Scholar
PubMed
Search for other papers by Julien Vanderhulst in
Google Scholar
PubMed
Search for other papers by Peter Janssens in
Google Scholar
PubMed
Search for other papers by Sien Van Daele in
Google Scholar
PubMed
Search for other papers by Evelien Van Hoof in
Google Scholar
PubMed
Search for other papers by Cyrielle Kint in
Google Scholar
PubMed
Search for other papers by Laura Iconaru in
Google Scholar
PubMed
Search for other papers by Jeroen de Filette in
Google Scholar
PubMed
Summary
Familial renal glucosuria (FRG) is a rare renal tubular disorder characterized by increased urinary glucose excretion despite normoglycemia. It is most commonly caused by pathogenic variants in the solute carrier family V member 2 (SLC5A2) gene. This gene encodes the sodium–glucose cotransporter 2, crucial for glucose reabsorption. We report the case of a 44-year-old male referred to the endocrinology outpatient clinic for unexplained glucosuria despite well-controlled diabetes mellitus with metformin and gliclazide therapy. His main complaints were nocturia and an unintentional 5 kg weight loss in 1 year. A 24-h urinary collection revealed overt glucosuria (23.3 g/1.73 m2/24 h), generalized aminoaciduria, and increased uric acid excretion (fractional excretion: 6.4%). Whole-exome sequencing revealed a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene. Specific analysis of the maturity-onset diabetes of the young type (MODY) gene panel showed no pathogenic variants in the hepatocyte nuclear factor-1A (HNF-1A; MODY3) nor in other MODY-associated genes. We assume that the association of glucosuria, aminoaciduria, and increased uric acid excretion can be explained by the combination of diabetes and the likely pathogenic SLC5A2 variant in this patient. In conclusion, we describe a well-controlled diabetic patient with FRG, associated with a novel heterozygous c.469-1G>A likely pathogenic variant in the SLC5A2 gene.
Learning points
-
The diagnosis of a renal tubular disorder should be considered in patients with unexplained glucosuria and diabetes mellitus, especially if the latter is well controlled.
-
FRG usually presents with glucosuria but may be associated with generalized aminoaciduria and hyperuricosuria.
-
Genetic analysis should be considered in patients with young-onset diabetes and glucosuria, particularly with a positive family history.
Search for other papers by F Stringer in
Google Scholar
PubMed
Western Health, Melbourne, Victoria, Australia
Search for other papers by C Preston in
Google Scholar
PubMed
Australian Centre for Accelerating Diabetes Innovations, University of Melbourne, Victoria, Australia
Search for other papers by R MacIsaac in
Google Scholar
PubMed
Search for other papers by F Inchley in
Google Scholar
PubMed
Search for other papers by L Rivera-Woll in
Google Scholar
PubMed
Search for other papers by S Farrell in
Google Scholar
PubMed
Search for other papers by N Sachithanandan in
Google Scholar
PubMed
Summary
Congenital hyperinsulinism is the leading cause of persistent hypoglycaemia in infants and children; however, it is uncommon to be diagnosed in adulthood. We describe the cases of two sisters who presented with hyperinsulinaemic hypoglycaemia aged 47 and 57 years old, who were subsequently diagnosed with compound heterozygous likely pathogenic variants in the ABCC8 gene, a known cause of monogenic congenital hyperinsulinism. We discuss the typical presenting features, investigation findings, and treatment strategies for patients with this condition.
Learning Points
-
Congenital hyperinsulinism is a rare cause of hyperinsulinaemic hypoglycaemia diagnosed in adulthood.
-
Clinical presentation is similar to an insulinoma, and imaging modalities may assist in differentiation.
-
There are minimal medical therapies currently available for patients non-responsive to diazoxide (such as those with ABCC8 and KCNJ11 variants).
-
Continuous glucose monitoring can be helpful in giving patients autonomy in managing their disease, as well as relieving anxiety and fear associated with hypoglycaemia.
Search for other papers by M L Cheneler in
Google Scholar
PubMed
Search for other papers by K Qureshi in
Google Scholar
PubMed
Search for other papers by C Bahrami in
Google Scholar
PubMed
Summary
Hemichorea–hemiballismus (HCHB) syndrome is a syndrome characterized by choreic movements which are irregular, nonrepetitive, and random movements, and ballismus which are spontaneous and violent movements. HCHB syndrome with a metabolic cause is a rare presentation that can be precipitated by uncontrolled diabetes. Presented here is a case of HCHB syndrome with right-sided neuroimaging findings and contralateral chorea due to uncontrolled type 2 diabetes mellitus. This patient was found to be obtunded with a blood glucose of greater than 500 mg/dL by EMS. After the administration of insulin, she was able to answer clarifying questions of noncompliance with her antihyperglycemic medications. She had a computed tomography without contrast of the head which showed hyperdense lesions in the right caudate nucleus and putamen consistent with HCHB syndrome. She was started on treatment for nonketotic hyperglycemia with insulin. As her mentation improved, she was able to cooperate with physical examination, which revealed irregular and violent movements in the left upper and lower extremities. Her hemichorea and hemiballismus improved with strict glycemic control, and she was able to be discharged to a skilled nursing facility for further rehabilitation. She would later have repeated hospitalizations for poor glycemic control, and repeat neuroimaging would reveal the resolution of hyperdensities after 4 months. HCHB syndrome due to uncontrolled diabetes has been termed diabetic striatopathy and is characterized by poor glycemic control, unilateral striatal hyperdensity on CT imaging, and contralateral choreic movements. Diabetic striatopathy remains a poorly understood disease, and the exact pathophysiologic mechanism has not been definitively elucidated.
Learning points
-
Diabetic striatopathy is a relatively new term for metabolic etiology of hemichorea–hemiballismus syndrome and was coined in 2009.
-
The triad for diabetic striatopathy is poor glycemic control, unilateral striatal hyperdensity on CT imaging, and contralateral choreic movements.
-
Multiple etiologies have been suggested for the cause of diabetic striatopathy including petechial hemorrhage, mineral deposition, myelin destruction, and infarction with reactive astrocytosis; however, the exact mechanism has yet to be determined.
-
Antidopaminergic medications may be used to control the choreic movements of diabetic striatopathy; however, the mainstay of treatment is glycemic control, often with insulin therapy.
Search for other papers by S Chew Sue Mei in
Google Scholar
PubMed
Search for other papers by N Pritchard in
Google Scholar
PubMed
Search for other papers by H Grayton in
Google Scholar
PubMed
Search for other papers by I Simonicova in
Google Scholar
PubMed
Search for other papers by S M Park in
Google Scholar
PubMed
University of Oxford Diabetes Trials Unit, Oxford, UK
Search for other papers by A I Adler in
Google Scholar
PubMed
Summary
Kabuki syndrome is a genetic disorder characterised by distinctive facial features, developmental delays, and multisystem congenital anomalies. Endocrine complications such as premature thelarche and short stature are common, whereas disorders of glycaemic control are less frequent. We describe a 23-year-old white female referred to the diabetes clinic for hyperglycaemia during haemodialysis. She was subsequently diagnosed with Kabuki syndrome based on characteristic clinical features, confirmed by detecting a heterozygous pathogenic variant in KMT2D. She was known to have had multiple congenital anomalies at birth, including complex congenital heart disease and a single dysplastic ectopic kidney, and received a cadaveric transplanted kidney at the age of 13. She had hyperglycaemia consistent with post-transplant diabetes mellitus (DM) and was started on insulin. Examination at the time revealed truncal obesity. She developed acute graft rejection and graft failure 14 months post-transplant and she was started on haemodialysis. Her blood glucose levels normalised post-graft explant, but she was hyperglycaemic again during haemodialysis at the age of 23. Given her clinical phenotype, negative diabetes antibodies and normal pancreas on ultrasound, she was assumed to have type 2 DM and achieved good glycaemic control with gliclazide.
Learning points
-
Involve clinical genetics early in the investigative pathway of sick neonates born with multiple congenital anomalies to establish a diagnosis to direct medical care.
-
Consider the possibility of Kabuki syndrome (KS) in the differential diagnoses in any neonate with normal karyotyping or microarray analysis and with multiple congenital anomalies (especially cardiac, renal, or skeletal), dysmorphic facial features, transient neonatal hypoglycaemia and failure to thrive.
-
Consider the possibility of diabetes as an endocrine complication in KS patients who are obese or who have autoimmune disorders.
Search for other papers by Presoon Kuruvilla in
Google Scholar
PubMed
Search for other papers by Angel John in
Google Scholar
PubMed
Search for other papers by Ashith Murali in
Google Scholar
PubMed
Summary
Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes. Insulin autoantibodies are diagnostic for the condition. Hirata’s disease has been seen to be associated with other autoimmune conditions. Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology. Although autoimmunity plays a role in the pathogenesis of both the diseases, association between the two has not been reported till date. In our case, a 72-year-old Indian woman with vitiligo for the past 30 years presented with recurrent episodes of fasting hypoglycaemia. She was found to have very high levels of fasting insulin, C-peptide, and insulin antibody and was diagnosed with IAS. Thus, we conclude that the clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.
Learning points
-
Insulin autoantibody syndrome (IAS) or Hirata’s disease is a rare condition characterized by recurrent fasting hypoglycaemic and postprandial hyperglycaemic episodes in which insulin plays a major role.
-
Insulin autoantibodies are diagnostic for IAS. The endocrine insulin and its autoantibodies play a major role in the pathogenesis of the disease.
-
Vitiligo is a common depigmentation disorder whose exact cause is unknown but thought to have an autoimmune aetiology.
-
IAS and vitiligo are two diseases with autoimmune aetiology which has been seen to be associated with each other (the first case to be reported).
-
The clinical spectrum of Hirata’s disease has to be taken as more heterogenous than previously assumed.
-
On dealing with autoimmune diseases, we should also keep in mind about other diseases with autoimmune pathogenesis.
Search for other papers by Omayma Elshafie in
Google Scholar
PubMed
Search for other papers by Anjali Jain in
Google Scholar
PubMed
Search for other papers by Summit Bichpuria in
Google Scholar
PubMed
Search for other papers by Yamina Rassou in
Google Scholar
PubMed
Search for other papers by Syed Furqan Hashmi in
Google Scholar
PubMed
Search for other papers by Abir Bou Khalil in
Google Scholar
PubMed
Summary
A 60-year-old woman presented to our clinic with an acute onset 3 months history of right ankle pain. The patient had a history of poorly differentiated thyroid cancer, which was treated with total thyroidectomy, left lateral neck dissection levels II–V and central neck dissection levels VI–VII followed by postoperative I-131 radioactive iodine (131I) ablation therapy 3.7 GBq 6 months ago. The post-131I WBS showed residual iodine-avid thyroid tissue with no other iodine-avid disease or metastasis. SPECT/CT of the neck and chest showed nonavid bilateral pulmonary nodules, discrete nodal masses in mediastinum and nonavid bone lesions. FDG-PET CT scan showed FDG-avid mediastinal lymph nodes (LN), innumerable non-FDG-avid subcentimetric pulmonary nodules and few FDG-avid lytic lesions in the skeleton. X-ray and MRI of the right ankle showed a well-marginated lytic lesion in the posterior body of calcaneus and 5 × 6 cm soft tissue mass lesion, respectively. The histopathology of the calcaneus mass confirmed a positive immunostaining for thyroid origin which includes thyroglobulin and TTF-1 with PAX-8. Endobronchial mediastinal and bronchial LN biopsy confirmed thyroid cancer metastasis. Gene mutation showed HRAS and GNA13 with a high tumor mutational burden. We describe a rare case of poorly differentiated thyroid cancer in a patient who presented with right ankle pain; we confirmed the cause to be a calcaneus metastasis from the thyroid cancer, with calcaneus being an extremely rare site for bone metastases. Gene mutations points toward treatment with immune checkpoint inhibitors.
Learning points
-
Poorly differentiated thyroid carcinoma (PDTC) usually metastasizes to lung and bone but can rarely occur in the calcaneus.
-
Patients with distant metastases have significantly worse long-term prognosis.
-
Radiotherapy is effective in reducing the metastatic pains as well as reducing the size of the metastasis.
-
PAX-8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas.
-
The importance of searching for gene mutations to decide the treatment of PDTC.
Search for other papers by Dave Duggan in
Google Scholar
PubMed
Search for other papers by Cinthia Minatel Riguetto in
Google Scholar
PubMed
Summary
There is a scarcity of literature relating to post-bariatric hypoglycaemia (PBH) in pregnancy. Recurrent hyperglycaemia and hypoglycaemia can have significant consequences for both the mother and the developing fetus. We describe a case of a young pregnant woman who was diagnosed with symptomatic PBH in the second trimester of pregnancy using continuous glucose monitoring (CGM) 3 years after Roux-en-Y gastric bypass (RYGB) surgery. Instigating a low glycaemic index and complex carbohydrate diet significantly improved the patient’s glycaemic excursions. Given that this condition is likely underdiagnosed as a complication of RYGB surgery, a greater awareness of this complication is needed. Patients should be adequately consented pre-operatively for this relatively frequent late surgical complication to enable patients to identify symptoms of this condition at an early stage and seek medical treatment.
Learning points
-
PBH is an important diagnosis in patients post-RYGB surgery, particularly in women of childbearing age when consequences of both hyperglycaemia and hypoglycaemia during pregnancy can adversely affect both mother and the fetus.
-
Adverse outcomes of recurrent hypoglycaemia to the fetus can include small for gestational age, intrauterine growth restriction and possible impairment of beta cell function.
-
Providing adequate carbohydrate intake to allow growth of the fetus during pregnancy while also attempting to resolve both hyperglycaemia and hypoglycaemia associated with PBH by reducing the intake of simple carbohydrates and high glycaemic index foods can prove challenging.
-
Patients should be adequately consented for late complications of RYGB surgery such as PBH in order to allow early recognition of symptoms and enable prompt treatment.
Search for other papers by Ishara Ranathunga in
Google Scholar
PubMed
Search for other papers by Chandima Idampitiya in
Google Scholar
PubMed
Summary
Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the destruction of the pancreatic beta cells, which produce insulin. Individuals with T1DM usually require at least 3-5 years to develop microvascular complications in comparison to people with type 2 diabetes (T2DM), who may develop complications even before the diagnosis of diabetes. We discuss a patient who presented with proliferative diabetic retinopathy subsequently diagnosed with T1DM and diabetic neuropathy following investigations. Diabetic retinopathy or other microvascular complications as the presenting feature of T1DM is rarely known or reported in the literature. A 33-year-old healthcare worker had been seen by the opticians due to 1-week history of blurred vision. The ophthalmology assessment had confirmed proliferative retinopathy in the right eye and severe non-proliferative retinopathy in the left eye with bilateral clinically significant macular oedema. His BMI was 24.9 kg/m2. The nervous system examination revealed bilateral stocking type peripheral neuropathy. The random venous glucose was 24.9 mmol/L. Plasma ketones were 0.7 mmol/L and HbA1c was 137 mmol/mol. On further evaluation, the anti-glutamic acid decarboxylase (GAD) antibody was positive, confirming the diagnosis of T1DM. He was started on aflibercept injections in both eyes, followed by panretinal photocoagulation. Subsequent nerve conduction studies confirmed the presence of symmetrical polyneuropathy. The pathogenesis of the development of microvascular complications in T1DM is multifactorial. Usually, the development of complications is seen at least a few years following the diagnosis. The occurrence of microvascular complications at presentation is rare. This makes the management challenging and extremely important in preventing the progression of the disease.
Learning points
-
The pathogenesis of the development of microvascular complications in type 1 diabetes mellitus is multifactorial.
-
The development of complications is seen at least a few years following the diagnosis.
-
Occurrence of microvascular complications at presentation is rare.
-
This makes the management challenging and extremely important to prevent the progression of the disease.
