JCEM case reports最新文献

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.

A 75-year-old female presented with fasting hypoglycemic episodes. A supervised fast ended at 72 hours fulfilling Whipple triad, with suppressed insulin and C-peptide levels, but discordantly suppressed serum β-hydroxybutyrate levels. After 21 months of recurring symptoms, a repeat fast ended at 48 hours with Whipple triad, suppressed serum β-hydroxybutyrate level, and borderline nonsuppressed C-peptide level, suggesting endogenous hyperinsulinism. Serum insulin levels were discordantly suppressed. Computed tomography (CT) of the abdomen demonstrated an enhancing 1.36 × 0.93-cm nodule in the head of the pancreas. Endoscopic ultrasound (EUS)-guided fine-needle aspirate of the lesion derived cytology consistent with a neuroendocrine tumor, but fine-needle core biopsy returned normal pancreatic tissue. Because the results were equivocal, functional imaging with ⁶⁸Gallium-DOTA-exendin-4 positron emission tomography CT was performed, which confirmed the diagnosis of a single head-of-pancreas insulinoma. The patient declined surgical resection. Oral diazoxide therapy resulted in significant peripheral edema. Hence, EUS-guided radiofrequency ablation of the lesion was performed, and the patient remains symptom free 10 months postprocedure. This case illustrates that (1) exendin-4-based positron emission tomography may help one confidently diagnose and localize insulinoma when prior biochemical or endoscopic biopsy results are ambiguous; and (2) EUS-guided radiofrequency ablation is an efficacious alternative option to surgical resection in the frail, elderly patient with insulinoma.

A 37-year-old man presented with symptoms of polyuria and weight loss over the past year. Initial laboratory examination showed elevated blood glucose level (468 mg/dL [25.9 mmol/L]; normal reference range [RR], 75-109 mg/dL [4.1-6.0 mmol/L]), high glycated hemoglobin A1c (13.2% [120 mmol/mol]; RR, 4.6-6.2% [26-44 mmol/mol]), low urinary C-peptide excretion (17.4 μg/day [5.76 nmol/day]; RR, 18.3-124.4 μg/day [6.0-41.1 nmol/day]), and ketosis, leading to a diagnosis of insulin-dependent diabetes mellitus. Subsequent investigations identified medullary thyroid carcinoma and bilateral pheochromocytomas. Given the detected RET gene variant and the patient's family history of multiple endocrine neoplasia type 2A (MEN2A), the diagnosis of MEN2A was confirmed. Upon hospital admission, intensive insulin therapy was commenced, which resolved the symptoms and normalized blood glucose levels. Subsequently, laparoscopic bilateral adrenalectomy was performed, after which the patient's glucose tolerance normalized, eliminating the need for diabetes treatment and avoiding hypoglycemia. This case highlights the potential for catecholamine-induced suppression of insulin secretion via α2 action on pancreatic β-cells to be remission and rapidly improved by adrenalectomy in individuals with MEN2A experiencing insulin-dependent diabetes mellitus.

[This corrects the article DOI: 10.1210/jcemcr/luae207.].