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PurposeBilateral inferior petrosal sinus sampling (BIPSS) is useful for differential diagnosis of adult Cushing’s disease (CD) but may not be so reliable in pediatric cases. The purpose of this study was to evaluate the sensitivity of BIPSS before and after desmopressin stimulation in pediatric CD, and to explore related factors of false-negative results and meanings of sampling lateralization.MethodsWe retrospectively analyzed 16 pediatric CD patients who underwent 17 BIPSS procedures from 2006 to 2017. CD was diagnosed if inferior petrosal sinus (IPS) to peripheral adrenocorticotropic hormone (ACTH) ratio was >2 at baseline or >3 after desmopressin stimulation. Sampling lateralization was yielded if interpetrosal sinus gradient was >1.4. Magnetic resonance imaging (MRI) was conducted. All the patients underwent surgery and the diagnosis was confirmed.ResultsThe sensitivity was 64.7% (11/17) at baseline and 83.3% (10/12) after desmopressin stimulation. After stimulation, BIPSS reached its best sensitivity at 3 min. Sampling lateralization rate was 62.5% and 63.6% before and after stimulation, and the accordant rate with actual tumor lateralization was 50.0% and 42.9%, respectively. The accuracy of MRI in predicting the tumor lateralization was 80.0%. Sampling lateralization rate (81.8% in true-positive, 20.0% in false-negative, p = 0.036) and ACTH at dominant IPS (p = 0.001) was lower among false-negative patients.ConclusionsThe sensitivity of BIPSS in pediatric CD was low at baseline, but increased after desmopressin stimulation. Sampling lateralization cannot accurately indicate the tumor lateralization, but the absence of sampling lateralization with low ACTH at IPS is a hint of false-negative cases in BIPSS.

Contexts Bilateral inferior petrosal sinus sampling (BIPSS) can differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS). The traditional cutoff of inferior petrosal sinus to peripheral (IPS:P) ACTH gradient was 2 before stimulation and 3 after stimulation, which yielded unsatisfactory sensitivity in some studies. Objectives To determine the optimal cutoff in BIPSS before or after desmopressin stimulation and to evaluate the necessity of stimulation. Design and Setting Single-center retrospective study (2011–2018) along with meta-analysis. Patients 226 CD and 24 EAS patients with confirmed diagnosis who underwent BIPSS with desmopressin stimulation. Results In the meta-analysis of 25 studies with 1249 CD and 152 EAS patients, the traditional cutoff yielded sensitivity of 86% and 97% and specificity of 98% and 100% before and after stimulation, respectively. We then analyzed the data from our center. With the traditional cutoff, the sensitivity was 87.2% (197/226) and 96.5% (218/226) before and after stimulation, and specificity was both 100% (25/25), which were close to the results of meta-analysis. Receiver operating characteristic analysis revealed that the optimal cutoff was 1.4 before stimulation and 2.8 after stimulation. With the new cutoff, the sensitivity was 94.7% (214/226) and 97.8% (221/226) while the specificity remained 100% (25/25) before and after stimulation. Among the 7 CD patients (7/226; 3.1%) for whom stimulation was necessary to get correct diagnosis, none has a pituitary lesion >6 mm by magnetic resonance imaging, and their sampling lateralization rate (P = .007) and peak ACTH level at dominant inferior petrosal sinus (P = .011) were lower than those among CD patients with IPS:P >1.4 before stimulation. Conclusions The optimal cutoff for IPS:P in BIPSS is different from the commonly-used one. The optimal cutoff value can yield satisfactory accuracy even without stimulation, and stimulation may be unnecessary for those with pituitary adenoma >6 mm.

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Liddle syndrome is a rare autosomal dominant monogenic form of hypertension. The authors analyzed clinical and genetic features of 12 cases of Liddle syndrome, the largest sample size ever reported. Clinical data were studied retrospectively. The exon 13 of the β and γ subunits of the epithelial sodium channel were amplified and sequenced in the peripheral blood leukocytes of the patients. The onset age of the 12 patients was 15.5±3.3 years. Their blood pressures were poorly controlled, and serum potassium levels in most patients were <3.0 mmol/L. Upright plasma renin activity and plasma aldosterone concentration were suppressed in all patients. All patients were treated with triamterene, and blood pressures were well controlled and serum potassium levels returned to normal. The serum creatinine level rose to 124 and 161 μmol/L, respectively, in two patients upon triamterene treatment, and returned to normal soon after treatment was discontinued. Eight mutation alleles were identified, and three mutations were newly identified.

Pheochromocytoma/paraganglioma (PPGL) has a high genetic heterogeneity with 40% germline variants in known pathogenic genes. Data in Chinese on this aspect are scanty. To detect the genetic and clinical profile of Chinese PPGL patients, we examined the variants of 12 known germline pathogenic genes (SDHA, SDHB, SDHC, SDHD, SDHAF2, FH, VHL, RET, NF1, MAX, TMEM127, and KIF1B) by next-generation sequencing and Sanger sequencing in 314 Chinese PPGL subjects. Twenty nine percent of Chinese PPGL patients had germline variants and SDHB was the most frequently mutated (14.6%). The most frequent SDHB variants were in exon 2, exon 7, and IVS 7. Pathogenic variants were more likely to occur in metastatic PPGL patients, paragangliomas, and patients under 30, with the ratio being 50.7% (35/69), 35.9% (56/156), and 49.5% (52/105), respectively. Our cohort included 314 patients from a single setting. The genetic and clinical features of Chinese PPGL patients were unique in some aspects compared to their non-Chinese counterparts. Identification of genotype-phenotype relation can serve as an effective tool for genetic prioritization and clinical decision-making.

This study was conducted to investigate the effects of urotensin-II (UII) on the proliferation of pheochromocytoma cells and the mRNA expression of UII and its receptor G protein-coupled receptor 14 (GPR14) in normal adrenal and human pheochromocytoma tissues. The effects on the cell proliferation by different UII concentrations and at different time were observed with the MTT method in both rat pheochromocytoma cell line (PC12 cell) and human pheochromocytoma cells. The mRNA expression of UII and GPR14 was evaluated by RT-PCR. UII had no significant effect on the proliferation in PC12 cells, but promoted the proliferation of human pheochromocytoma cells. The mRNA expression of UII and GPR14 in pheochromocytoma was lower than that in normal adrenal tissues. But mRNA expression of UII and GPR14 in adrenal pheochromocytomas was lower than that in extra-adrenal pheochromocytomas. Thus, UII and its receptor GPR14 exert a possible effect in the pathogenesis of pheochromocytoma.

Ectopic TSH-secreting tumors are extremely rare. In terms of hormone secretion profile, histological characteristics, and response to octreotide, they are similar to pituitary TSH-secreting adenomas, suggesting that they are of identical cell origin.