JCEM case reports最新文献

Predicting the onset of type 1 diabetes mellitus (T1D) in patients treated with immune checkpoint inhibitors (ICI) remains challenging. ICI-induced T1D (ICI-T1D) is a rare but serious complication that leads to complete insulin depletion. While diabetes-associated autoantibodies, such as glutamic acid decarboxylase antibodies (GADA), are typically absent in non-ICI-related fulminant T1D, they are relatively common in ICI-T1D. However, it is unclear whether these autoantibodies are detectable before the development of ICI-T1D. We present the case of a 61-year-old man with diabetes who had strongly positive GADA and preserved insulin secretion prior to initiating ICI therapy. Following treatment with durvalumab, he developed ICI-T1D, characterized by complete insulin depletion. Notably, the onset of ICI-T1D was precisely tracked on a daily basis, facilitating the timely initiation of insulin therapy and preventing diabetic ketoacidosis. Although the cost-effectiveness of pretreatment GADA screening and intensive monitoring remains a concern, early detection of diabetes-associated autoantibodies and vigilant glucose monitoring after ICI administration may help predict ICI-T1D and enable early therapeutic intervention.

Cushing syndrome due to ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) is rare and may progress rapidly, making treatment very challenging. We report a 27-year-old woman with metastatic neuroendocrine tumor (NET) who presented with sudden onset and rapidly progressing fatigue, muscle weakness, and weight gain. Laboratory findings confirmed severe EAS with new onset hypocalcemia, hypokalemia, and hyperglycemia. The patient was hospitalized and initiated on high-dose osilodrostat. Cortisol levels rapidly decreased in response to osilodrostat. During treatment, she developed glucocorticoid withdrawal symptoms for which hydrocortisone treatment was started. Due to her ineligibility for bilateral adrenalectomy, bilateral adrenal arterial embolization was attempted but ultimately converted to right-only embolization due to hypertensive urgency and difficulty in catheterization. With significant improvement of cortisol levels, her hypocalcemia, hyperglycemia, and hypokalemia resolved. Her osilodrostat dose was gradually lowered during follow-up. Glucocorticoid replacement continued as part of the ongoing block-and-replace regimen.

Cataracts secondary to type 1 or type 2 diabetes are not uncommon in adults; however, they are a rare finding in pediatric patients with type 1 diabetes. A 15-year-old girl presented with progressively worsened bilateral vision for 6 months. Her vision rapidly deteriorated over the previous month, prompting further evaluation that found bilateral cataracts with haziness in all layers and swollen lenses. Labs were done due to the findings and were significant for elevated serum glucose and hemoglobin A1c and mild diabetic ketoacidosis. Further testing confirmed type 1 diabetes. She had bilateral cataract surgery and has had a successful return of 20/20 vision in both eyes. The prevalence of early diabetic cataracts in the pediatric population is rare. Pathophysiology includes a defect in the polyol pathway, combined with oxidative stress, leading to increased fluid retention. Treatment involves cataract surgery and improved glycemic control. Current International Society for Pediatric and Adolescent Diabetes guidelines recommend initial evaluation for cataracts and subsequent surveillance concomitant with diabetic retinopathy monitoring biennially with those with good glycemic control. Given the rapid formation and severity of onset of bilateral cataracts for this patient, we propose continual screening for visual symptoms at each visit and emphasize the importance of ophthalmologic referrals.

3β-Hydroxysteroid dehydrogenase 2 deficiency (3βHSD2D) is a rare form of congenital adrenal hyperplasia (CAH) with variable clinical presentation. We describe a 46, XY child with ambiguous genitalia and CAH without apparent adrenal insufficiency due to 2 novel heterozygous variants in the HSD3B2 gene (c.779C > T/p.Pro260Leu and c.307 + 1G > A/p.Gly103Asp,fs29X). The disease-causing effect of the novel variants was assessed by genetic and functional studies informing on positive genotype-phenotype correlation. Sex registration was female, and no gender dysphoria has been noted until the present age of 7 years, but psychological assessments have been difficult with a concomitant diagnosis of autism spectrum disorder. Virilization that already progresses prepubertally through peripheral conversion of androgen precursors by 3β-hydroxysteroid dehydrogenase 1 will pose an increasing challenge during puberty.

Hypercalcemia of malignancy (HCM) is the most common cause of hypercalcemia in hospitalized patients. The pathogenesis of HCM is often multifactorial. One of the rare causes of HCM is extra-renal production of 1,25-dihydroxyvitamin D (or calcitriol), which is often seen in patients with lymphoproliferative malignancies. Here we report an interesting case of a 77-year-old female with severe hypercalcemia and renal mass. Initially, she was presumed to have humoral hypercalcemia of malignancy. However, her renal mass turned out to be diffuse large B cell lymphoma upon removal. Her severe hypercalcemia was attributed to a combination of ectopic calcitriol production from the tumor and probable iatrogenic vitamin D intoxication. This case highlights the need to consider multiple concurrent etiologies in patients with severe hypercalcemia.

Hypoparathyroidism (hypoPTH), sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant condition with approximately 200 cases published. HDR syndrome is caused by variants of GATA binding protein 3 gene (GATA3), which encodes a transcription factor, with multiple types of GATA3 variants reported. We present the case of a 76-year-old woman who was diagnosed with hypoPTH when she was aged 40 years and transferred care to our institution. Further history elucidated presence of deafness at age 1 year and chronic kidney disease with a left atrophic kidney diagnosed in her 60 seconds. Genetic testing identified a novel GATA3 missense variant of unknown significance (c.791G > A, p.Cys264Tyr). There was no family history of hypoPTH, deafness, or renal disease, which might indicate incomplete penetrance or de novo mutation. Advanced modeling of protein sequence and biophysical properties predicts abnormal protein function, suggesting possible pathogenicity. In addition, a likely pathogenic variant in the same amino acid was previously described in a patient with HDR, supporting the in silico prediction of pathogenicity in our patient's variant. Syndromic hypoPTH should be considered in patients even if presenting later in life with presumed chronic isolated conditions. Genetic testing can guide further disease screening and family testing when appropriate.

Congenital hypogonadotropic hypogonadism (CHH) can cause delayed secondary sexual characteristics and contribute to juvenile osteoporosis, with multiple causative genes having been reported. We treated a 27-year-old man diagnosed with central hypogonadism, presenting with delayed secondary sexual characteristics and juvenile osteoporosis, using bone resorption inhibitors and testosterone therapy. Genetic testing revealed missense variants both in the fibroblast growth factor receptor 1 (FGFR1) and gonadotropin-releasing hormone receptor (GNRHR) genes, a combination that has not been previously reported. This case represents a CHH caused by a novel combination of gene variants not registered in the human genome mutation database.

We report a 31-year-old man with diarrhea and tachycardia. Diagnostic workup confirmed raised free thyroid hormones with unsuppressed thyroid stimulating hormone (TSH). Laboratory assay and medication interference were excluded. Consistent with a high glycoprotein hormone α-subunit (α-GSU), the α-GSU:TSH molar ratio was increased. However, anterior pituitary panel testing also confirmed an isolated, raised follicle stimulating hormone (FSH) (17.3 IU/L; reference range, 1.7-8.0). Therefore, interpretation of α-GSU was limited given the co-existent elevated FSH. There was no pituitary lesion on magnetic resonance imaging (MRI) and stimulated TSH was 232% of baseline levels following thyrotropin-releasing hormone (TRH) stimulation, making a diagnosis of TSH-oma less likely. Genetic analysis revealed no pathogenic variants in the thyroid hormone receptor β gene. Due to the persistently elevated FSH, a follow-up pituitary MRI was arranged, which identified a nasopharyngeal mass on the floor of the sphenoid sinus, raising the possibility of ectopic pituitary tissue. The patient underwent endoscopic resection of this lesion, with subsequent normalization of free T4, TSH, and FSH within a few weeks. Histology confirmed a plurihormonal pituitary adenoma with staining for TSH, growth hormone, luteinizing hormone, and FSH. This case highlights the biochemical and radiological challenges of diagnosing ectopic TSH-secreting pituitary tumors.

A male neonate exhibited hallmark features of Beckwith-Wiedemann syndrome (BWS) including large for gestational age, macroglossia, multiple ear pits, and umbilical hernia. He had neonatal hypoglycemia, requiring a glucose infusion rate of 9.7 mg/kg/min. Over time, he demonstrated persistent hypoglycemia with point-of-care glucose <60 mg/dL (<3.3 mmol/L) (70-140 mg/dL, 3.9-7.8 mmol/L) prompting a critical sample. A diagnostic fast of 13 hours revealed no hypoglycemia <50 mg/dL. However, he was found to have postprandial hypoglycemia after 2 hours to 58 mg/dL (3.2 mmol/L) (70-140 mg/dL, 3.9-7.8 mmol/L) with low β-hydroxybutyrate of <1.8 mg/dL (<0.17 mmol/L) (>3.6 mg/dL, >1.8 mmol/L) and increased insulin 3.9 μIU/mL (27 pmol/L) (2-13 μIU/mL; 14-90 pmol/L). Low-dose diazoxide (6 mg/kg/day) and chlorothiazide (10 mg/kg/day) were initiated. After 48 hours on diazoxide, all episodes of postprandial hypoglycemia resolved. A safety fast on diazoxide sustained blood glucose >70 mg/dL with a rise in serum β-hydroxybutyrate at 13 and 19 hours. Our case highlights the heterogeneity of hypoglycemia in BWS, either fasting or postprandial. This emphasizes the importance of appropriate screening for both forms of hypoglycemia in patients with BWS and that diazoxide is an effective treatment.