Retro-and orthonasal olfactory function in relation to olfactory bulb volume in patients with hypogonadotrophic hypogonadism / Função olfativa retro e ortonasal em relação ao volume do bulbo olfatório em pacientes com hipogonadismo hipogonadotrófico

Abstract Introduction: Idiopathic hypogonadotrophic hypogonadism with an olfactory deficit is defined as Kallmann syndrome and is distinct from normosmic idiopathic hypogonadotrophic hypogonadism. Objective: Because olfactory perception not only consists of orthonasally gained impressions but also involves retronasal olfactory function, in this study we decided to comprehensively evaluate both retronasal and orthonasal olfaction in patients with idiopathic hypogonadotrophic hypogonadism. Methods: This case-control study included 31 controls and 45 idiopathic hypogonadotrophic hypogonadism patients. All participants whose olfactory and taste functions were evaluated with orthonasal olfaction (discrimination, identification and threshold), retronasal olfaction, taste function and olfactory bulb volume measurement. The patients were separated into three groups according to orthonasal olfaction: anosmic idiopathic hypogonadotrophic hypogonadism, hyposmic idiopathic hypogonadotrophic hypogonadism and normosmic idiopathic hypogonadotrophic hypogonadism. Results: Discrimination, identification and threshold scores of patients with Kallmann syndrome were significantly lower than controls. Threshold scores of patients with normosmic idiopathic hypogonadotrophic hypogonadism. were significantly lower than those of controls, but discrimination and identification scores were not significantly different. Retronasal olfaction was reduced only in the anosmic idiopathic hypogonadotrophic hypogonadism group compared to controls. Identification of bitter, sweet, sour, and salty tastes was not significantly different when compared between the anosmic, hyposmic, and normosmic idiopathic hypogonadotrophic hypogonadism groups and controls. Olfactory bulb volume was lower bilaterally in all patient groups when compared with controls. The olfactory bulb volume of both sides was found to be significantly correlated with threshold, discrimination and identification scores in idiopathic hypogonadotrophic hypogonadism patients. Conclusion: 1) There were no significant differences in gustatory function between controls and idiopathic hypogonadotrophic hypogonadism patients; 2) retronasal olfaction was reduced only in anosmic patients but not in orthonasally hyposmic participants, possibly indicating presence of effective compensatory mechanisms; 3) olfactory bulb volumes were highly correlated with olfaction scores in the hypogonadotrophic hypogonadism group. The current results indicate a continuum from anosmia to normosmia in idiopathic hypogonadotrophic hypogonadism patients.

Resumo Introdução: O hipogonadismo hipogonadotrófico idiopático com déficit olfatório é definido como síndrome de Kallmann e é distinto de hipogonadismo hipogonadotrófico idiopático normósmico. Objetivo: Pelo fato de a percepção olfativa não apenas consistir em impressões obtidas ortonasalmente, mas também envolver a função olfativa retronasal, neste estudo decidimos avaliar de maneira abrangente o olfato retronasal e ortonasal em pacientes com hipogonadismo hipogonadotrófico idiopático. Método: Este estudo caso-controle incluiu 31 controles e 45 pacientes com hipogonadismo hipogonadotrófico idiopático. Todos os participantes tiveram as funções olfativas e de paladar avaliadas com olfação ortonasal (discriminação, identificação e limiar), olfação retronasal, função do paladar e medida do volume do bulbo olfatório. Os pacientes foram separados em três grupos de acordo com a olfação ortonasal: hipogonadismo hipogonadotrófico idiopático anósmico, hipogonadismo hipogonadotrófico idiopático hipósmico e hipogonadismo hipogonadotrófico idiopático normósmico. Resultados: Os escores de discriminação, identificação e limiar de pacientes com síndrome de Kallmann foram significativamente menores do que os controles. Os escores dos limiares de pacientes com hipogonadismo hipogonadotrófico idiopático normósmico foram significativamente menores do que os dos controles, mas os escores de discriminação e identificação não foram significativamente diferentes. A olfação retronasal foi reduzida apenas no grupo hipogonadismo hipogonadotrófico idiopático anósmico em comparação com os controles. A identificação de gostos amargos, doces, azedos e salgados não foi significativamente diferente quando comparada entre os grupos e controles de hipogonadismo hipogonadotrófico idiopático anósmicos, hipósmicos e normósmicos. O volume do bulbo olfatório foi menor bilateralmente em todos os grupos de pacientes quando comparado com os controles. O volume do bulbo olfatório de ambos os lados foi significativamente correlacionado com os escores de limiar, discriminação, identificação em pacientes com hipogonadismo hipogonadotrófico idiopático. Conclusão: 1) Não houve diferenças significativas na função gustativa entre controles e pacientes com hipogonadismo hipogonadotrófico idiopático; 2) A olfação retronasal foi reduzida apenas em pacientes anosmáticos, mas não em participantes ortonasalmente hipósmicos, possivelmente indicou presença de mecanismos compensatórios efetivos; 3) Os volumes do bulbo olfatório foram altamente correlacionados com os escores de olfação no grupo hipogonadismo hipogonadotrófico. Os resultados atuais indicam um contínuo da anosmia à normosmia em pacientes com hipogonadismo hipogonadotrófico idiopático.

Olfactory and gustatory functions in patients with non-complicated type 1 diabetes mellitus.

The aim of this study was to evaluate any possible relationship between diabetic state and olfactory and gustatory functions in patients with non-complicated diabetes mellitus type 1 (T1D), and also to present evidence of the association between olfactory and gustatory scores and HbA1c values and disease durations. The study included 39 patients with non-complicated T1D and 31 healthy controls. Clinical characteristics such as age, gender, duration of disease, education levels and biochemical analyses (fasting blood glucose, urea, creatinine, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein (HDL-C), triglyceride, HbA1c, C-peptide, postprandial blood glucose) were measured. Subjective olfactory and gustatory tests were performed for all participants. There were no significant differences in olfactory tests between the two groups (odor thresholds 8.63 ± 0.91 vs. 8.55 ± 0.57, p = 0.66; odor discrimination 12.97 ± 0.80 vs. 12.74 ± 0.79, p = 0.24; odor identification 13.81 ± 0.98 vs. 13.72 ± 0.89, p = 0.69; TDI score 35.34 ± 1.94 vs. 34.97 ± 1.4, p = 0.37). There were also no significant differences in gustatory tests between the two groups (bitter 3.45 ± 0.51 vs. 3.44 ± 0.50, p = 0.90; sweet 3.32 ± 0.48 vs. 3.38 ± 0.49, p = 0.60; salty 3.13 ± 0.72 vs. 3.10 ± 0.72, p = 0.88; total score of taste 13.16 ± 1.61 vs. 13.13 ± 1.22, p = 0.92). Comparison of gustatory and olfactory scores according to disease duration of type 1 diabetes mellitus patients revealed that there were no differences between groups (all p > 0.05). T1D without complications may not be associated with olfactory and gustatory dysfunction according to subjective testing. We also found that gustatory and olfactory functions may not be related with HbA1c values and disease duration in non-complicated T1D.

Mitotane-induced hyperlipidemia: a retrospective cohort study.

Limited data are available about mitotane-nduced hyperlipidemia. We retrospectively analyzed lipid data in 38 patients with adrenocortical carcinoma (ACC) who received mitotane therapy with emphasis on HDL cholesterol (HDL-c) and clinical predictors of lipid changes. At baseline, the mean levels of HDL-c, LDL-c, and triglycerides were 53.3 mg/dL, 114.4 mg/dL, and 149 mg/dL, respectively. HDL-c, LDL-c, and triglyceride concentrations significantly increased with mitotane therapy to a mean HDL peak (HDL-P) of 86.3 mg/dL (P < 0.001), a mean LDL peak of 160.1 mg/dL (P < 0.001), and a mean triglyceride peak (Tg-P) of 216.7 mg/dL (P = 0.042). HDL-P positively correlated with mitotane concentration (r = 0.52, P < 0.001), while LDL-P levels and Tg-P did not. Gender, body mass index, cortisol overproduction, baseline levels of HDL-c, and triglyceride did not predict change in HDL-c. Similar changes were noticed in subgroup analysis after excluding patients who were using lipid-lowering agents. In conclusion, in ACC patients, mitotane caused significant increases in HDL-c that may counteract the deleterious atherosclerotic effects of LDL-c and Tg rise. Understanding the mechanism of HDL change may lead to the discovery of novel HDL-c-elevating drugs.

Adrenocortical carcinoma: clinical outcomes and prognosis of 330 patients at a tertiary care center.

OBJECTIVE: Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. Herein, we describe the clinical features and outcomes for a large series of ACC patients. DESIGN AND METHODS: Retrospective review of ACC patients seen at The University of Texas MD Anderson Cancer Center from 1998 through 2011. RESULTS: A total of 330 patients with median age at diagnosis of 48.5 years; 12 (3.6%) patients were under 18 years. Hormonally functioning tumors represented 41.8% (n=138) of all cases. Surgical resection for the primary tumor was done in 275 (83.3%) patients (45 at MD Anderson (16.4%)). For those who had surgical resection, the median local-recurrence-free time was 1.04 years. Factors associated with local recurrence included positive surgical margins (P=0.007) and advanced disease stage (P=0.026). Median overall survival time for all patients was 3.21 years. Median survival times were 24.1, 6.08, 3.47, and 0.89 years for stages I, II, III, and IV respectively. In multivariable analysis, older age, functioning tumors, and higher disease stage remained significant prognostic factors associated with poor survival. CONCLUSION: ACC prognosis remains poor with the use of currently available treatments. Older age, functioning tumors, and incomplete resections are clinical factors associated with poor survival. Surgical expertise is important to achieve complete resections and to improve outcome.

A retrospective cohort analysis of the efficacy of adjuvant radiotherapy after primary surgical resection in patients with adrenocortical carcinoma.

CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with high recurrence and mortality rates. The role of adjuvant radiation therapy (RT) to improve outcome remains unclear. OBJECTIVE: The aim of this study was to evaluate the impact of adjuvant RT on overall survival and recurrence rates of ACC patients. DESIGN: We conducted a retrospective cohort study of select ACC patients who were seen at The University of Texas MD Anderson Cancer Center (MDACC) between 1998 and 2011. All patients in this study underwent primary tumor resection and received adjuvant RT within 3 months of primary surgical resection prior to referral to the MDACC. We compared patients who had surgery and adjuvant RT with patients who had surgery alone. RESULTS: Baseline characteristics and adjuvant mitotane use were not significantly different between the adjuvant RT group (n = 16) and the non-RT group (n = 32). Local recurrence occurred in seven patients (43.8%) who received RT and 10 patients (31.3%) in the control group. At 5 yr, the estimated local recurrence-free rate (95% confidence interval) was 53% (32-87%) in the RT group and 67% (52-86%) in the non-RT group (P = 0.53). The distributions of time to distant recurrence and recurrence-free survival were not significantly different between the two groups. Using a multivariate Cox proportional hazards model for overall survival, the hazard ratio for RT use was 1.593 (95% confidence interval, 0.707-3.589; P = 0.26) after adjusting for stage and adjuvant mitotane therapy. CONCLUSIONS: ACC has high rates of recurrence. In our study, RT did not improve clinical outcomes in patients who received their initial care in the community. We believe there is a need for a collaborative, multicenter, prospective randomized trial to evaluate the role of adjuvant treatments (both mitotane and RT) to assess their impact on recurrence patterns and survival.