JCEM case reports最新文献

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.].

A defect in the canonical Wnt-β-catenin pathway may lead to reduced bone strength and increased fracture risk. Sclerostin is a key inhibitor of this pathway by binding to low-density lipoprotein (LDL) receptor-related protein (LRP)-5/6, thereby reducing bone formation. The effectiveness of romosozumab, a human monoclonal antibody that binds sclerostin and prevents this inhibitory effect, has been questioned in patients with inactivating genetic variants in LRP5 or LRP6. We present a 67-year-old woman with severe osteoporosis with 4 grade 2 vertebral fractures due to a heterozygous pathogenic variant in LRP5. She was treated with romosozumab for 1 year, after which a routine follow-up spine x-ray revealed 5 new vertebral fractures, despite a strong increase in bone mineral density (BMD) (lumbar spine [LS] + 58%; femur neck [FN] + 23%), although overestimated at LS because of the vertebral fractures. This suggests that in patients with loss-of-function LRP5 variants, romosozumab is able to increase BMD. However, it is unclear whether the progressive vertebral fractures are due to the severe osteoporosis in relation to the start of romosozumab or a diminished responsiveness related to her LRP5 variant. Further evaluation is needed on the effect of romosozumab on BMD and fracture outcomes in patients with a likely defective LRP5/6 receptor.

Lymphocytic infundibuloneurohypophysitis (LINH) is a disease with an etiology involving an autoimmune mechanism, characterized by lymphocytic inflammation of the posterior pituitary and infundibular stalk, resulting in arginine vasopressin deficiency. It is difficult to distinguish from pituitary neoplasm or infiltrative diseases, and biopsy is necessary for a definitive diagnosis, but this is highly invasive. In children, it is especially important to distinguish LINH from tumors such as germ cell tumors. Recently, the usefulness of anti-rabphilin-3A antibody as a serum marker for LINH has been reported. To date, only a limited number of pediatric cases have been reported. We present a 4-year-old boy with arginine vasopressin deficiency. Magnetic resonance imaging of the head showed thickening of the pituitary stalk without a posterior pituitary bright spot, and anti-rabphilin-3A antibody was positive. Consequently, pituitary biopsy was not performed because of the strong suspicion of LINH. Five months after symptom onset, the pituitary stalk thickening had resolved. This case represents the first report of probable or definitive LINH with anti-rabphilin-3A antibody positivity in a 4-year-old child, making it the youngest positive case reported to date. Our case highlights the importance of noninvasive approaches and careful follow-up to avoid invasive interventions for children with LINH.

46,XY sex reversal 11 (SRXY11) is a rare and recently identified form of 46,XY difference in sexual development (DSD), caused by variants in the DEAH-Box Helicase 37 gene (DHX37). DHX37 is crucial for ribosome biogenesis, but its specific role in gonadal development remains unclear. The genital phenotype varies widely, ranging from typical female to typical male. We present a 46,XY infant with prenatal ultrasound findings of atypical genitalia. Amniotic fluid gene analysis revealed a known heterozygous pathogenic variant in DHX37, p.R308Q (c.923G>A), confirmed postnatally. The patient was born with markedly undervirilized genitalia with posteriorly fused labioscrotal folds, a single introitus, no clitoromegaly, and nonpalpable gonads. Laboratory evaluation at multiple points showed undetectable anti-Müllerian hormone (AMH) and inhibin B levels, elevated gonadotropin levels, and negligible testosterone levels. Clinical course was complicated by urine retention in the vagina and uterus and hydronephrosis requiring catheterization. Endoscopy revealed a urogenital sinus with separate urethral and vaginal openings and 2 cervices leading into 2 separate uteri suggestive of a bicornuate bicollis uterus. Laparoscopy revealed 2 intra-abdominal gonads adjacent to the fallopian tubes. Evidence for inheritance, penetrance, genotype-phenotype correlation, and risk of malignancy in SRXY11 is limited to case reports.

Routine serum studies in a female patient with sustained prediabetic glycated hemoglobin A_1c (HbA_1c) levels, controlled on metformin, yielded an unexpected finding: an elevated HbA_1c value of ≥14.9% (≥139 mmol/mol) (normal reference range, <5.7% to <39 mmol/mol). Estimated average glucose (EAG) (normal reference range, <126 mg/dL to <7 mmol/L) is a linearly corresponding blood glucose value calculated from HbA_1c measurements that reflects the average glycemic status over the preceding 3 months. Caution must be used when the EAG provided by the HbA_1c does not align with blood glucose values obtained around the same period. Our patient carries a rare heterozygous pathogenic variant affecting the β subunit called hemoglobin Graz (Hb Graz), characterized by a histidine for leucine substitution, resulting in clinically silent Hb abnormalities. Individuals without diabetes carrying the Hb Graz pathogenic variant exhibit significantly higher HbA_1c values when analyzed by high-performance liquid chromatography. Alternative methods of quantifying glycemic control are suggested if the possibility of a confounding variable exists, such as when a HbA_1c-blood glucose mismatch occurs or unexplainable HbA_1c levels are detected.