Antti Raappana

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CONTEXT Data on the incidence of pituitary adenomas (PAs) are scant and outdated.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 NFis 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).

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.

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.

Long-Term Health-Related Quality of Life of Surgically Treated Pituitary Adenoma Patients: A Descriptive Study

Context. The literature concerning the health-related quality of life (HRQoL) of patients with surgically treated PA is controversial. Objective. To describe the long-term HRQoL of surgically treated patients in all PA classes. Design and subjects. The 15D, a generic HRQoL instrument producing a 15-dimensional profile and a single 15D index score (a difference ≥0.03 on a 0-1 scale is considered clinically important), was used to assess the HRQoL of a 13-year surgical cohort of PA patients in Northern Finland. Results and Conclusion. Nighty-eight eligible consecutive patients with surgically treated PA were studied at an average of 6.3 years after their latest pituitary operation. The average postoperative 15D profiles in patients with non-functioning PA and in acromegalics without GH-suppressive medical treatment were similar to those of the age-standardized general population. However, after this rather long followup, the mean 15D score and the number of statistically significant 15D dimension impairments, compared with those of their reference population, were 0.11 and 9/15, 0.10 and 3/15, and 0.08 and 7/15 for Cushings disease, acromegalics needing somatostatin analog, and prolactinoma patients, respectively. Hypopituitarism with replacement medication was not associated with impaired HRQoL. The somatostatin-analog-associated HRQoL finding warrants further clinical research.

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

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.

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.

Restricted consonant inventories of 2-year-old Finnish children with a history of recurrent acute otitis media

Many children experience recurrent acute otitis media (RAOM) in early childhood. In a previous study, 2-year-old children with RAOM were shown to have immature neural patterns for speech sound discrimination. The present study further investigated the consonant inventories of these same children using natural speech samples. The results showed that 2-year-old children with RAOM (N = 19) produced fewer words and had smaller consonant inventories compared to the healthy controls (N = 21). In particular, the number of consonants produced in the medial position of words was restricted. For places and manners of articulation, the most notable difference between the groups was observed for fricatives, which were produced less often by the children with RAOM than by the controls. These results further support the assumption that early and recurrent middle ear infections should be considered a risk factor for language development.