Endocrinology, Diabetes and Metabolism Case Reports最新文献

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.

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.

Summary: Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for cardiovascular disease. Very low HDL-C levels (less than 20 mg/dL), however, were uncommonly seen and can be due to genetic defects involving the metabolic pathway of high-density lipoprotein (HDL). We encountered a 50-year-old Chinese man who was only noticed to have extremely low HDL-C levels after surviving recurrent episodes of myocardial infarction. Further workup revealed the undetectable level of apolipoprotein A-I, the absence of HDL on gel electrophoresis, and a novel heterozygous splicing variant in the ABCA1 gene, which was predicted to be pathogenic by in silico analysis. To the best of our knowledge, this is the first reported Hong Kong Chinese with ABCA1 deficiency and probable Tangier disease. The association of ABCA1 deficiency/Tangier disease and accelerated atherosclerosis is discussed.

Learning points: Clinicians should be aware of the differential diagnoses of very low HDL-C, which could be divided into genetic and acquired causes. Genetic low HDL syndromes include apoA-I deficiency, Tangier disease, and familial LCAT deficiency, each of which has characteristic clinical features and can be differentiated from the other further by apoA-I measurement, lipoprotein analysis, and genetic testing. Patients with ABCA1 deficiency and Tangier disease are at risk of premature coronary artery disease and should be aggressively screened and treated for cardiovascular risk factors and established cardiovascular diseases. Revascularization strategy and indications for coronary artery bypass grafting in patients with Tangier disease and coronary artery disease follow that as for patients without Tangier disease.

Summary: Maturity-onset diabetes of the young (MODY) is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with dominant inheritance of beta-cell dysfunction. There are few reports of the coinheritance of glucokinase (GCK) and hepatocyte nuclear factor 1 alpha gene (HNF1A) variants underlying MODY in patients. Herein, we describe a case involving combinations of monoallelic GCK and HNF1A variants associated with MODY. A 10-year-old Japanese girl with a three-generation family history of diabetes without obesity showed high levels of urinary glucose during a school screening test. Her glucose metabolism profile revealed 124 mg/dL of fasting glucose, 6.9% glycated hemoglobin (HbA1c), and 2.78 ng/mL of C-peptide immunoreactivity levels. In a 75-g oral glucose tolerance test, her base glucose, peak glucose, insulin resistance, and homeostasis model assessment of beta cell function levels were 124 mg/dL, 210 mg/dL (120 min), 1.71, and 33%, respectively. Based on the clinical phenotype of GCK-MODY, alimentary and exercise therapy without oral hypoglycemic agents were used to maintain her fasting glucose and HbA1c levels. We explored the coinheritance of MODY with GCK and HNF1A variants in this and past cases and found that careful clinical follow-up is required to firmly establish phenotypic features. Moreover, the accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.

Learning points: MODY is a group of monogenic forms of diabetes mellitus characterized by early-onset diabetes with the dominant inheritance of beta-cell dysfunction. MODY2 and MODY3 caused by heterozygous loss-of-function variants in the glucokinase (GCK) and hepatocyte nuclear factor 1 alpha (HNF1A) genes, respectively, are the most common forms of the disease. Few cases of MODY have previously been reported as being associated with the coinheritance of GCK and HNF1A variants. Careful clinical follow-up is required to firmly establish phenotypic features in the coinheritance of MODY with GCK and HNF1A variants. The accumulation of data on genetically confirmed MODY associated with the coinheritance of GCK and HNF1A variants will be useful for understanding genotype-phenotype correlations.

Summary: Congenital adrenal hyperplasia (CAH) is one of the most common inherited rare endocrine disorders. This case report presents two female siblings with delayed diagnosis of non-classical CAH 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2D/HSD3B2) despite early hospital admission and apparent CAH manifestations such as infections, hirsutism, menstrual disturbances, and PCOS phenotype. Initially, sister 1 was misdiagnosed with PCOS and then 11-hydroxylase deficiency (CYP11B1), based on ultrasound, biochemical findings, and negative genetic testing for 21-hydroxylase deficiency (CYP21A2). Additional diagnostic workup was performed when sister 2also presented with symptoms of androgen excess. Genetic testing for CAH/steroid disorders finally revealed that both siblings were compound heterozygous for two variants in the HSD3B2 gene: a frameshift variant, c.558dup, p.(Thr187Hisfs*17) and a novel missense variant, c.65T>C, p.(Leu22Ser). A Synacthen test showed an insufficient cortisol increase. In vitro studies of the variants in a cell model revealed loss of function for the p.(Thr187Hisfs*17) and partial activity for p.(Leu22Ser) confirming non-classic CAH. Overlapping symptomatology and lack of specialized knowledge on steroid biosynthesis and associated rarest forms of CAH may explain the delayed diagnosis. However, with newer diagnostic methods comprising a less biased approach, very rare forms of non-classical CAH may no longer be overlooked in the future.

Learning points: Non-classic 3βHSD2 is likely underdiagnosed. Late diagnosis of mild non-classic 3βHSD2 does occur and one should be aware of this diagnosis. Early diagnosis of NCCAH may prevent many consequences such as severe hirsutism, prolonged menstrual irregularities, infertility, or even adrenal crisis with severe infections. Comprehensive steroid profiling and genetic testing should be used earlier, especially when in doubt about a diagnosis.

Summary: We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum. Fine needle aspiration (FNA) of the thyroid nodule confirmed the diagnosis of MTC. An 18F-fluorodopa positron emission tomography/computed tomography (PET/CT) scan revealed the presence of distant metastases in ribs, vertebrae, in the right iliac wing and the liver. Since surgery was not feasible, the patient was started on cabozantinib 40 mg/dL. After 16 months the patient is still on cabozantinib at the same dose, he reports complete autonomy in daily life activities, and serum Ct is still elevated; however, the imaging evaluation does not show signs of disease progression.

Learning points: High procalcitonin serum values despite the absence of infection are suggestive of MTC. Advanced MTC with multiple metastases can have an indolent course and can go unrecognized for years. Cabozantinib is a valuable option for the treatment of advanced MTC.

Summary: Menstrual cycle abnormalities are common in premenopausal females with Cushing's syndrome, although the underlying mechanism is poorly understood. Signs and symptoms found in Cushing's syndrome overlap with polycystic ovarian syndrome (PCOS). The patient is a 33-year-old female previously diagnosed by a gynecologist with PCOS and treated with oral contraceptive pills (OCPs) for 2 years. She then discontinued her OCPs without consulting a clinician, resulting in amenorrhea for 6 months, for which she presented. She also had symptoms of depression and anxiety but had no other signs and symptoms of Cushing's syndrome, except a plethoric face. Initial lab work showed evidence of central hypogonadism (low luteinizing hormone, follicle-stimulating hormone, and estrogen), so a complete anterior pituitary hormone workup was done. Her thyroid-stimulating hormone was also low with a low free T4 level. Prolactin level was normal, but surprisingly, her AM cortisol level was high. The Cushing's syndrome workup revealed non-suppressed cortisol after a 1 mg dexamethasone suppression test and positive 24-h urine cortisol with suppressed adrenocorticotrophic hormone. A CT scan of her adrenal glands revealed a left adrenal adenoma. She underwent a left adrenalectomy, after which her menstrual cycles became regular again, and pituitary function has recovered.

Learning points: In Cushing's syndrome, female patients can have menstrual abnormalities due to the high cortisol levels, which can affect gonadotrophin levels. We encourage clinicians to include Cushing's syndrome in the differential diagnosis of patients with central hypogonadism.

Summary: Riedel's thyroiditis is the rarest form of thyroiditis, occasionally resulting in rapid thyroid enlargement and potential tracheal obstruction. Here, we detail the case of an 81-year-old woman with a medical history including Hodgkin lymphoma, Hashimoto's thyroiditis, and multinodular goiter. She presented to the emergency room with stridor, cervical swelling, and breathing difficulties for over 2 days. CT scans revealed substantial thyroid enlargement causing significant glottal and tracheal compression, to a minimum tracheal diameter of 7 mm. Due to the severity of the compressive symptoms, orotracheal intubation and mechanical ventilation were deemed necessary. Surprisingly, despite the initial suspicion of malignancy given the rapid growth in the elderly, subsequent cytological and histological evaluations indicated a benign form of invasive fibrous thyroiditis - Riedel's thyroiditis. Although surgical intervention was advised, the patient declined and opted for endobronchial treatment with a prosthetic stent and subsequent treatment with systemic glucocorticoids. Following successful treatment, she was discharged within a week and resumed normal activities without respiratory distress. This case is noteworthy for its rapid benign mass growth, rare emergent presentation, and the patient's advanced age.

Learning points: The rapid enlargement of the thyroid gland in elderly patients poses a diagnostic challenge, stemming from the higher occurrence of aggressive thyroid carcinomas. Despite the clinical presentation, a comprehensive diagnostic workup, including fine-needle aspiration and core-needle biopsy, is crucial for accurately distinguishing between benign and malignant causes of thyroid nodule enlargement. This case report illustrates diverse treatment options for Riedel's thyroiditis, and the importance of individualized treatment plans based on the degree of airway obstruction, patient preferences, and response to initial interventions. Clinicians should contemplate the inclusion of glucocorticoids in the therapeutic regimen for Riedel's thyroiditis, particularly in cases where surgical intervention is not feasible or declined by the patient.

Summary: Bariatric surgery is increasingly being accepted as a viable treatment for managing the growing obesity epidemic. Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures. Perforated duodenal ulcer following RYGB is a rare condition with a low incidence. We report a case of a patient with a perforated duodenal ulcer post RYGB, and the surgical approach. A 66-year-old man with hypertension and a history of laparoscopic RYGB for class III obesity was admitted to the emergency department with severe epigastric pain radiating to the right side of his abdomen and right shoulder, associated with nausea and vomiting. Computed tomography (CT) showed intraperitoneal free fluid, a thickened wall of the duodenum and free air, duodenal perforation was suspected. The patient underwent exploratory laparoscopy that revealed a perforated duodenal ulcer that was closed with an absorbable barbed suture and omental patch. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis, and clinicians should be aware of and have a low threshold for diagnostic laparoscopy.

Learning points: Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed procedures in bariatric surgery. Perforated ulcers in excluded segments after RYGB are a rare entity with a challenging diagnosis. The pathophysiology of this perforation is not clear, but several mechanisms have been proposed. Helicobacter pylori has been implicated. Clinicians should be aware and have a low threshold for diagnostic laparoscopy for a patient who has acute abdominal pain after RYGB, despite negative diagnostic measures.

Summary: Hypoglycemia is one of the paraneoplastic syndrome manifestations that arise from primary and secondary liver cancer. Hypoglycemia usually presents in the late stage of the disease and indicates a poor prognosis. This case series displays the characteristics profile of patients with primary and secondary liver cancer who are presented with hypoglycemia in a tertiary referral hospital in Indonesia. The study included 41 liver cancer patients who were presented with hypoglycemia. Hepatocellular carcinoma was diagnosed in 51.2% of patients, metastatic liver disease in 14.6% of patients, and undiagnosed liver cancer in 34.1% of patients. The mean age was 47.7 years with male predominance (65.9%). Jaundice was found in 58.5% and hepatomegaly in 70.7% of patients. The mean (± S.D.) initial blood glucose was 42.15 ± 17.11 mg/dL and the Child-Pugh score was 9.93 ± 2.11. Based on imaging, tumor diameter was 12.6 ± 6.9 cm, multiple (61%), and involving both lobes (61%). Treatments for hypoglycemia included oral/enteral feeding, intravenous dextrose, and steroids. No treatment was given for the cancer because all patients were in an advanced stage. The treatment resulted in 41.5% blood glucose being controlled, 56.1% refractory, and 2.4% persistent. Mortality was 70.7% and in average occurred 5.76 ± 4.99 days after hypoglycemia. The mainstay of treatment in these cases is treating the tumor with cytoreduction. However, it was difficult to do cytoreduction because the tumor was already in an advanced stage. Beneficial supportive treatments for maintaining normal blood glucose are frequent meals, dextrose infusion, steroids, and glucagon.

Learning points: Hypoglycemia in liver cancer occurs due to the failure of the liver to fulfill body glucose demand because the liver parenchyma has been largely replaced by the tumor, in addition to the high production of insulin growth factor (IGF). Hypoglycemia is often caused by islet cell and non-islet cell tumors, with a higher occurrence in non-islet cell tumors due to paraneoplastic syndrome and the high metabolic requirements of the tumor. The mainstay of NICTH treatment is treating the tumor with cytoreduction. However, in an advanced stage, cytoreduction therapy is often challenging to conduct. Beneficial supportive treatments for controlling blood glucose are frequent meals, dextrose infusion, and the injection of steroids and glucagon. Steroids play a beneficial role in the treatment of persistent hypoglycemia in hepatocellular carcinoma by stimulating gluconeogenesis and increasing lipolysis. Steroids also have roles in the inhibition of peripheral glucose intake, suppression of big IGF-2 production, and modulation of the GH-IGF axis.