Acromegaly caused by a GHRH-producing pancreatic neuroendocrine tumor: a rare manifestation of MEN1 syndrome.

SUMMARY: Multiple endocrine neoplasia type 1 NM_001370259.2(MEN1):c.466G>C(p.Gly156Arg) is characterized by tumors of various endocrine organs. We report on a rare, growth hormone-releasing hormone (GHRH)-releasing pancreatic tumor in a MEN1 patient with a long-term follow-up after surgery. A 22-year-old male with MEN1 syndrome, primary hyperparathyroidism and an acromegalic habitus was observed to have a pancreatic tumor on abdominal CT scanning, growth hormone (GH) and insulin-like growth factor 1 (IGF1) were elevated and plasma GHRH was exceptionally high. GHRH and GH were measured before the treatment and were followed during the study. During octreotide treatment, IGF1 normalized and the GH curve was near normal. After surgical treatment of primary hyperparathyroidism, a pancreatic tail tumor was enucleated. The tumor cells were positive for GHRH antibody staining. After the operation, acromegaly was cured as judged by laboratory tests. No reactivation of acromegaly has been seen during a 20-year follow-up. In conclusion, an ectopic GHRH-producing, pancreatic endocrine neoplasia may represent a rare manifestation of MEN1 syndrome. LEARNING POINTS: Clinical suspicion is in a key position in detecting acromegaly. Remember genetic disorders with young individuals having primary hyperparathyroidism. Consider multiple endocrine neoplasia type 1 syndrome when a person has several endocrine neoplasia. Acromegaly may be of ectopic origin with patients showing no abnormalities in radiological imaging of the pituitary gland.

Translation, cross-cultural adaptation, and validation of the sino-nasal outcome test (snot)-22 for Finnish patients.

PURPOSE: The Sino-Nasal Outcome Test-22 (SNOT-22) is the most commonly used disease-specific quality of life questionnaire in rhinology. The purpose of this prospective study was to translate and validate SNOT-22 into Finnish. METHODS: The validation process followed the guidelines proposed for cross-cultural adaptation of health-related measures of quality of life. The study consisted of three groups: rhinologic out-patients (N = 96), FESS patients (N = 49) and healthy controls (N = 79). Out-patient and FESS groups completed the questionnaire twice (answers A and B), out-patients after two weeks and FESS patients after 3 months. Validity, reliability and responsiveness were evaluated. RESULTS: The mean SNOT-22 sum score of the out-patient questionnaires were 35.3 points (answer A) and 32.4 points (answer B). ICC in out-patient group was 0.879. For the FESS patients, the mean pre- and postoperative (answer A and B) SNOT-22 sum scores were 46.8 and 21.9 points, respectively (p < 0.0001). The mean SNOT-22 of healthy controls was 8.9 points. The out-patients (answer A) and healthy controls had statistically significant difference in SNOT-22 scores (p < 0.0001). CONCLUSIONS: The results of our study show that the validated Finnish version of the SNOT-22 questionnaire demonstrates good validity, reliability and responsiveness.

Noise Equally Degrades Central Auditory Processing in 2- and 4-Year-Old Children.

Purpose: The aim of this study was to investigate developmental and noise-induced changes in central auditory processing indexed by event-related potentials in typically developing children. Method: P1, N2, and N4 responses as well as mismatch negativities (MMNs) were recorded for standard syllables and consonants, frequency, intensity, vowel, and vowel duration changes in silent and noisy conditions in the same 14 children at the ages of 2 and 4 years. Results: The P1 and N2 latencies decreased and the N2, N4, and MMN amplitudes increased with development of the children. The amplitude changes were strongest at frontal electrodes. At both ages, background noise decreased the P1 amplitude, increased the N2 amplitude, and shortened the N4 latency. The noise-induced amplitude changes of P1, N2, and N4 were strongest frontally. Furthermore, background noise degraded the MMN. At both ages, MMN was significantly elicited only by the consonant change, and at the age of 4 years, also by the vowel duration change during noise. Conclusions: Developmental changes indexing maturation of central auditory processing were found from every response studied. Noise degraded sound encoding and echoic memory and impaired auditory discrimination at both ages. The older children were as vulnerable to the impact of noise as the younger children. Supplemental materials: https://doi.org/10.23641/asha.5233939.

Factors Affecting the Visual Outcome of Pituitary Adenoma Patients Treated with Endoscopic Transsphenoidal Surgery.

OBJECTIVE: To evaluate visual acuity (VA) and visual fields (VF) quantitatively before and after endoscopic transsphenoidal surgery (ETS), with special attention to prognostic factors such as the pituitary adenoma (PA) suprasellar extension (SSE), volume and the patients' age. METHODS: Medical records of 47 patients with PA undergoing ETS were evaluated. VA, VF, preoperative visual impairment score (VISpre) and postoperative visual impairment score (VISpost) were determined. The PA SSE, volume, chiasmal contact, and their correlation with visual function were assessed preoperatively and postoperatively. RESULTS: The final cohort included 47 patients. VA improved in 54 of 76 eyes (71.0%) after ETS, and 69 of 76 eyes (90.7%) gained normal VA. Postoperative VF recovery occurred in 32 of 37 eyes (86.5%). The mean change in VIS was 12.0 (95% confidence interval [CI], 7.7-16.3) and improved in all patients with tumor-related visual impairment (n = 25). However, visual outcome was poorer when VISpre was greater than 40. When VISpre was 21-40, age linearly correlated with VIS improvement (P = 0.03); younger patients had satisfactory and older poorer visual outcome. The mean SSE in patients with VF defects (n = 20) was 16.6 mm (95% CI, 13.3-19.9). Mean SSE in patients with no VF defects (n = 23) was 6.6 mm (95% CI, 4.9-8.3; P < 0.001), and the cutoff value for visual perturbations was 9.5 mm for SSE and 8.6 mL for PA volume (P < 0.001 for both). CONCLUSIONS: The visual outcome after ETS for PAs was excellent, and serious complications were rare. Severe preoperative visual impairment resulted in poorer postoperative visual outcomes. The SSE of the PA was the most important predictor of visual outcome after ETS.

The feasibility of NBI in patients with suspected upper airway lesions: A multicenter study.

OBJECTIVE: Narrow band imaging (NBI) improves diagnosis of laryngopharyngeal cancer, but most reported NBI studies are from experienced centers. Feasibility reports on use at everyday outpatient departments are needed. STUDY DESIGN: Researcher-initiated, prospective, multicenter. METHODS: Participating physicians were instructed in NBI technique during a 4-hour meeting. Patients underwent an examination that included endoscopy with white light (WL) high-definition (HD) TV and NBI filter in the selected time period. All suspicious lesions were biopsied. The medical records of patients with NBI negative findings were evaluated 6 months after the visit to detect all possible malignant lesions coming into view at mucosal sites. These were considered as false-negative cases, enabling long-term assess to the positive predictive value (NPV) of the protocol. RESULTS: We enrolled 125 patients. Of those, 84 (67.2%) were males and the median age was 65 years (range, 35-91). In analysis of the accuracy of WL HD TV and NBI against biopsy, the sensitivity and specificity of WL HD TV were 62% and 81%, respectively; and the sensitivity and specificity of NBI were 100% and 84%, respectively. The diagnostic accuracy of NBI was significantly better (P < 0.05). When analyzing medical records 6 months after the initial examination, we found three patients who had been diagnosed with a malignant lesion (NPV of NBI of 96.8%). CONCLUSION: Narrow band imaging is readily implemented in an everyday outpatient practice, and there seems to be better detection rates of dysplastic/carcinoma lesions with HD NBI compared to HD WL. LEVEL OF EVIDENCE: 2b. Laryngoscope, 127:1821-1825, 2017.

Long-term influence of recurrent acute otitis media on neural involuntary attention switching in 2-year-old children.

BACKGROUND: A large group of young children are exposed to repetitive middle ear infections but the effects of the fluctuating hearing sensations on immature central auditory system are not fully understood. The present study investigated the consequences of early childhood recurrent acute otitis media (RAOM) on involuntary auditory attention switching. METHODS: By utilizing auditory event-related potentials, neural mechanisms of involuntary attention were studied in 22-26 month-old children (N = 18) who had had an early childhood RAOM and healthy controls (N = 19). The earlier and later phase of the P3a (eP3a and lP3a) and the late negativity (LN) were measured for embedded novel sounds in the passive multi-feature paradigm with repeating standard and deviant syllable stimuli. The children with RAOM had tympanostomy tubes inserted and all the children in both study groups had to have clinically healthy ears at the time of the measurement assessed by an otolaryngologist. RESULTS: The results showed that lP3a amplitude diminished less from frontal to central and parietal areas in the children with RAOM than the controls. This might reflect an immature control of involuntary attention switch. Furthermore, the LN latency was longer in children with RAOM than in the controls, which suggests delayed reorientation of attention in RAOM. CONCLUSIONS: The lP3a and LN responses are affected in toddlers who have had a RAOM even when their ears are healthy. This suggests detrimental long-term effects of RAOM on the neural mechanisms of involuntary attention.

Effects of recurrent acute otitis media on cortical speech-sound processing in 2-year old children.

OBJECTIVES: To investigate at the age of 2 years the effects of childhood recurrent acute otitis media (RAOM) on central auditory processing by using cortical event-related potentials elicited by syllable stimuli. DESIGN: During a 1-year period, 22- to 26-month-old children fulfilling the criteria for tympanostomy tube insertion in Oulu University Hospital, Oulu, Finland, were recruited to the RAOM group (N = 20). The control group (N = 19) was matched by age, sex, and mother's educational level. In both groups, children were typically developing and had no family history of language disorder or developmental language problems. Finnish syllables /ke:/ and /pi:/ as standards and their variants with changes in frequency, intensity, vowel, consonant, and vowel duration as deviants were used to record P1, N2, and mismatch negativity (MMN) responses in the multifeature paradigm. The clinically healthy ears at the time of registration were a prerequisite for the participation. RESULTS: Children with RAOM and their controls showed the age-typical P1 and N2 responses with no differences in the amplitudes or latencies between the groups, which suggests unaffected basic encoding of sound features and sound representation formation. However, the groups showed different auditory discrimination profiles. In children with RAOM, frequency and vowel MMN amplitudes were increased. Furthermore, the MMN latency for the frequency change was shorter and the frequency MMN amplitude lateralized to the left hemisphere in the RAOM group instead of an adult-like right-hemispheric lateralization observed in the controls. The children with RAOM had a more anterior MMN amplitude scalp distribution for the intensity change than control children. In addition, the MMN amplitude elicited by consonant change was evenly distributed unlike in controls, who had a left-side preponderant lateralization. Taken together, these results suggest an elevated responsiveness for frequency, vowel, and intensity changes, and an immature pattern of discriminating small speech sound contrasts in children with RAOM. CONCLUSIONS: The results suggest that childhood RAOM does not affect the central auditory pathway integrity or sound encoding. However, RAOM may lead to aberrant preattentive discrimination of sound features even when the peripheral auditory input is normal. These results are clinically significant because even transient problems with auditory processing may delay language development.

Clinical characteristics and therapeutic responses in patients with germ-line AIP mutations and pituitary adenomas: an international collaborative study.

CONTEXT: AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. OBJECTIVE: The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. DESIGN: This study was an international, multicenter, retrospective case collection/database analysis. SETTING: The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. PATIENTS: Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. RESULTS: The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P < 0.00001) vs. controls. AIPmut prolactinomas occurred generally in young males and frequently required surgery or radiotherapy. CONCLUSIONS: AIPmut pituitary adenomas have clinical features that may negatively impact treatment efficacy. Predisposition for aggressive disease in young patients, often in a familial setting, suggests that earlier diagnosis of AIPmut pituitary adenomas may have clinical utility.

Incidence of pituitary adenomas in Northern Finland in 1992-2007.

CONTEXT: Data on the incidence of pituitary adenomas (PAs) are scant and outdated. A population-based regional cohort with thorough case identification was used to evaluate the incidence of clinically detected PAs in the era of magnetic resonance imaging. OBJECTIVE: The objective of the study was to describe the age- and sex-specific incidence of all PA subgroups, with data on incidentally found PAs, pituitary apoplexies, and time trends. DESIGN, SETTINGS, AND PATIENTS: This was a retrospective descriptive analysis of PA patients diagnosed during 1992-2007 in Northern Finland (NFi). MAIN OUTCOME MEASURE: World Health Organization 2000-standardized incidence rates (SIRs) of PAs per 100,000 were measured. RESULTS AND CONCLUSION: The final cohort consisted of 355 PAs. The incidence rates of the Oulu University Hospital regional district were used as a reference to assess the applicability of our case finding over the rest of NFi. Incidence rates of all PA subgroups except microprolactinomas were statistically equal between these areas; thus, all presented SIRs are based on the NFi's cohort except Oulu University Hospital regional district-based prolactinomas and PAs overall. Overall SIR of PAs was higher (4.0 per 100,000) than in previous reports. Prolactinomas had the highest SIR: 2.2 per 100,000, followed by clinically nonfunctioning PAs (1.0) and GH-secreting (0.34), ACTH-secreting (0.17), and TSH-secreting (0.03) PAs. The gender-specific SIR was 2.2 per 100,000 in males and 5.9 per 100,000 in females. Pituitary apoplexy occurred as a presenting symptom in 11% of clinically nonfunctioning PA patients. The SIR of incidentally discovered PAs increased significantly from 1992-1999 to 2000-2007 (0.59 to 1.6, respectively; P < 0.01), which accounted for the perceived increasing trend in the overall SIR of PAs (3.8 to 4.2; P > 0.05).

3D modeling-based surgical planning in transsphenoidal pituitary surgery--preliminary results.

CONCLUSION: The preoperative three-dimensional (3D) modeling of the pituitary adenoma together with pituitary gland, optic nerves, carotid arteries, and the sphenoid sinuses was adopted for routine use in our institution for all pituitary surgery patients. It gave the surgeon a more profound orientation to the individual surgical field compared with the use of conventional 2D images only. OBJECTIVE: To demonstrate the feasibility of 3D surgical planning for pituitary adenoma surgery using readily available resources. SUBJECTS AND METHODS: The computed tomography (CT) and magnetic resonance imaging (MRI) data of 40 consecutive patients with pituitary adenoma were used to construct 3D models to be used in preoperative planning and during the surgery. A freely available, open source program (3D Slicer) downloaded to a conventional personal computer (PC) was applied. RESULTS: The authors present a brief description of the 3D reconstruction-based surgical planning workflow. In addition to the preoperative planning the 3D model was used as a 'road map' during the operation. With the 3D model the surgeon was more confident when opening the sellar wall and when evacuating the tumor from areas in contact with vital structures than when using only conventional 2D images.