Paediatric Cushing's disease: Epidemiology, pathogenesis, clinical management and outcome.

Cushing's disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing's syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70-100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.

Testicular ultrasonographic features predict future risk for bilateral testicular germ cell tumour: A long-term single centre follow-up study.

BACKGROUND: Bilateral testicular germ cell tumours (B-GCT) are rare, with an incidence of 2-5%, and can be classified as synchronous (sB-GCT) or metachronous (mB-GCT). Our study aimed to identify clinical, biochemical, and radiological risk factors for mB-GCT in a cohort of patients with GCT at a single tertiary referral centre. METHODS: This retrospective case-control study included patients with GCT referred to Policlinico Umberto I-Sapienza University of Rome, from 2005 to 2023. We evaluated clinical history, testicular ultrasound features, hormone levels, semen analysis, histological characteristics, staging, and treatments. mB-GCTs were compared with unilateral GCT patients with a follow-up longer than the median time-to-onset of the second tumour. RESULTS: Of 319 patients, 52 experienced B-GCT, with a median time-to-onset of the second tumour of 62 months (range: 8-229). The mB-GCT group showed higher gonadotropin levels (FSH 13.6mUI/mL vs. 7.4mUI/mL, p < 0.001; LH 6.6mUI/mL vs. 3.9mUI/mL, p = 0.004), lower sperm concentration (27 × 106/ejaculate vs. 78 × 106/ejaculate, p = 0.009), smaller residual testis volume (10.4 mL vs. 16.3 mL, p < 0.001), more inhomogeneous echotexture [57.5% vs. 14%, p < 0.001], and presence of microlithiasis (75% vs. 19.5%, p < 0.001). Kaplan-Meier curves confirmed that ultrasound features of the residual testis increased the cumulative risk of developing a second tumour. Microlithiasis was a strong independent predictor (OR 30.712, 95% CI 3.357-280.942, p = 0.002). CONCLUSIONS: Histological features of the first tumour or its treatment do not influence the onset of a second tumour. However, low residual testis volume, inhomogeneous echotexture, and microlithiasis significantly increase this risk. A comprehensive evaluation of the residual testis at baseline is essential for developing a personalised surveillance programme in GCT survivors, with regular ultrasound follow-up recommended beyond the conventional 5-year limit.

Use of contrast enhanced ultrasound in testicular diseases: A comprehensive review.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) is a sonographic technique that increases the diagnostic accuracy of ultrasound and color Doppler ultrasound (CDUS) when studying testicular abnormalities. However, its role in clinical practice is still debatable because there are no accepted standards regarding how and when this technique should be used for patients with testicular disease. OBJECTIVES: To perform a nonsystematic review of the current literature to highlight the strength and flaws of performing CEUS and to provide a critical overview of current research evidence on this topic. MATERIALS AND METHODS: A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. RESULTS: Strong enhancement of neoplastic lesions (both benign and malignant) during CEUS aids in differential diagnosis with non-neoplastic lesions, which usually appears either nonenhanced or enhanced in a manner similar to that of the surrounding parenchyma. CEUS enhancement has a high predictive value in the identification of neoplastic lesions, whereas a similar or complete absence of enhancement may be interpreted as strong evidence of benignity, although there are exceptions. Literature on quantitative analysis is still scarce, though promising, particularly in distinguishing benign from malignant neoplasms. Furthermore, CEUS may be useful in many emergency situations, such as acute scrotum, blunt scrotal trauma, and focal infarction of the testis. Finally, CEUS can help increase the probability of sperm recovery in azoospermic males. DISCUSSION AND CONCLUSION: CEUS is a safe, easy-to-perform, and cost-effective diagnostic tool that can provide a more accurate diagnosis in testicular lesions and acute scrotal disease. However, further studies with larger cohorts are required to refine the differential diagnosis between benign and malignant neoplasms. Finally, these preliminary results can instigate the development of innovative research on pre-testicular sperm extraction to increase the chances of sperm recovery.

Therapeutic use of pulsed electromagnetic field therapy reduces prostate volume and lower urinary tract symptoms in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) etiology remains poorly understood, but chronic low-grade inflammation plays a role. Pulsed electromagnetic field therapy (PEMF) (1-50 Hz) is effective in reducing tissue inflammation. OBJECTIVES: We designed a pilot study to evaluate the effects of PEMF on prostate volume (PV) in BPH. MATERIALS AND METHODS: This is a prospective interventional trial on 27 naive patients with BPH and lower urinary tract symptoms (LUTS). At baseline (V0 ), all patients had blood tests, transrectal ultrasound, and questionnaires (IPSS, IIEF-15) and received a perineal PEMF device (Magcell® Microcirc, Physiomed Elektromedizin). PEMF was delivered on perineal area 5 minutes twice daily for 28 days, then (V1 ) all baseline evaluations were repeated. Afterward, nine patients continued therapy for 3 more months (PT group) and 15 discontinued (FU group). A 4-month evaluation (V2 ) was performed in both groups. RESULTS: A reduction was observed both at V1 and at V2 in PV: PVV0 44.5 mL (38.0;61.6) vs PVV1 42.1 mL (33.7;61.5, P = .039) vs PVV2 41.7mL (32.7;62.8, P = .045). IPSS was reduced both at V1 and at V2 : IPSSV0 11 (5.7;23.2) vs IPSSV1 10 (6;16, P = .045) vs IPSSV2 9 (6;14, P = .015). Baseline IPSS was related to IPSS reduction both at V1 (rs  = 0.313;P = .003) and at V2 (rs  = 0.664;P < .001). PV reduction in patients without metabolic syndrome (ΔPVV1nMetS -4.7 mL, 95%CI -7.3;-2.0) was greater than in affected patients (ΔPVV1MetS 1.7 mL, 95%CI -2.69;6.1)(P = .017, Relative RiskMetS  = 6). No changes were found in gonadal hormones or sexual function. DISCUSSION: PEMF was able to reduce PV after 28 days of therapy. Symptoms improved in a short time, with high compliance and no effects on hormonal and sexual function or any side effects. Patients with moderate-severe LUTS and without MetS seem to benefit more from this treatment. CONCLUSION: PEMF reduces PV and improves LUTS in a relative short time, in BPH patients. These benefits seem greater in those patients with moderate-severe LUTS but without MetS.

Combined intravitreal ranibizumab and verteporfin photodynamic therapy versus ranibizumab alone for the treatment of age-related macular degeneration.

PURPOSE: To compare same-day combined therapy of photodynamic therapy with verteporfin (PDT-V) and intravitreal ranibizumab versus monotherapy with ranibizumab for the treatment of choroidal neovascularization. METHODS: IN THIS PROSPECTIVE STUDY, THE TOTAL NUMBER OF EYES WAS RANDOMIZED INTO TWO GROUPS: in the first, treatment consisted of a combined therapy of PDT-V and ranibizumab 0.5 mg on the same day; in the second, ranibizumab 0.5 mg in 3 monthly injections. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) on optical coherence tomography (OCT) were recorded before and 6 months after treatment. RESULTS: A total of 47 eyes of 47 subjects were enrolled in the study. In the combined-therapy group (group 1), the mean baseline BCVA ± standard deviation (SD) was 32.65 ± 11.09 letters (Snellen equivalent, 20/59); in the ranibizumab-alone group (group 2), 29.13 ± 9.03 letters (20/70). At 6 months' follow-up, in group 1 the mean baseline BCVA was 39.06 ± 10.12 letters (20/42); in group 2, 33.87 ± 12.06 letters (20/57). Improvement was significant in both group 1 (P = 0.03) and group 2 (P = 0.002). In group 1, the mean CMT at baseline ± SD was 315 ± 95.49 µm; in group 2, 306.33 ± 71.61 µm. At 6 months' follow-up, in group 1 it was 202 ± 52.02 µm; in group 2, 226 ± 65.58 µm. Reduction was significant in both group 1 (P = 0.0007) and group 2 (P = 0.00001). After 6-months, the rate of retreated eyes was 29.4% in group 1 and 43.3% in group 2. The need for retreatment did not depend on the treatment protocol (P = 0.34). CONCLUSIONS: From a functional and anatomic point of view, the two treatments showed equivalent efficacy, with fewer retreatments in group 1. No serious adverse events, such as retinal detachment, endophthalmitis, or ocular hypertension occurred in either group.