Recovery of hypothalamus-pituitary-gonadal dysfunction after the treatment of suprasellar germ cell tumors.

OBJECTIVE: To investigate the incidence of hypothalamus-pituitary-gonadal (HPG) axis initiation/recovery after treatment and to identify predictive risk factors for noninitiation/recovery. METHODS: A total of 127 consecutive suprasellar germ cell tumor (GCT) patients managed at Peking Union Medical College Hospital (2006-2019) were retrospectively analyzed. Prepubertal patients (followed up until 13 years of age for girls and 14 years of age for boys) and patients with HPG dysfunction (followed up for 2 years) were divided into the initiation/recovery and noninitiation/recovery groups. RESULTS: Of the 127 suprasellar GCT patients, 75 met the follow-up criteria, 28 (37.3%) of whom experienced HPG axis initiation/recovery. Compared to the noninitiation/recovery group, the initiation/recovery group included more males and had shorter delayed diagnosis times, smaller tumor sizes, lower panhypopituitarism rates, thinner pituitary stalk widths, lower visual deficit rates, and higher serum testosterone and estradiol levels. The cutoff values of pituitary stalk width, tumor size, and delayed diagnosis time used to predict noninitiation/recovery were 6.9 mm, 6.9 mm and 1.7 years, respectively. Tumor size ≥6.9 mm (odds ratio (OR) = 7.5, 95% CI: 2.2-25.8, P = 0.001), panhypopituitarism (OR = 5.0, 95% CI: 1.4-17.6, P = 0.013), and delayed diagnosis time ≥1.7 years (OR = 5.7, 95% CI: 1.5-20.7, P = 0.009) were risk factors for noninitiation/recovery. CONCLUSIONS: Among suprasellar GCT patients, nearly one-third of prepubertal patients and patients with HPG dysfunction experience HPG axis initiation/recovery after treatment. Tumor size ≥6.9 mm, panhypopituitarism, and delayed diagnosis time ≥1.7 years were identified as predictive risk factors for noninitiation/recovery.

Autonomic Dysfunction is Associated with Increased Cardiometabolic Risk in Patients with Childhood-Onset Craniopharyngioma.

Patients with craniopharyngioma are susceptible to autonomic dysfunction as a result of hypothalamic damage. We evaluated indices of heart rate variability (HRV) in patients with childhood-onset craniopharyngioma to investigate autonomic function and its relationship with components of the metabolic syndrome (MetS). This cross-sectional, case-only study included 53 patients (10-30 years of age). We measured the standard deviation of all normal R-R intervals (SDNN) and total power indicating overall HRV, the root-mean square of the difference of successive R-R intervals (RMSSD) and high frequency indicating parasympathetic modulation, and low frequency. These indices were compared according to the presence of the MetS. During the mean 10.8 years of follow-up, 25% of patients were diagnosed with the MetS. Patients with the MetS showed significantly lower levels of SDNN (29.0 vs. 40.6 ms), total power (416.1 vs. 1129.6 ms2), RMSSD (20.1 vs. 34.5 ms), high frequency (94.7 vs. 338.5 ms2), and low frequency (94.5 vs. 289.4 ms2) than those without (p <0.05, for all). Individual components of the MetS including insulin resistance, serum triglycerides levels, and systolic blood pressure were inversely associated with SDNN, total power, RMSSD and high frequency. Higher overall variability and parasympathetic modulation were related to decreased odds ratios for having the MetS (OR 0.91, p=0.029 for SDNN; OR 0.91, p=0.032 for total power). In conclusion, autonomic dysfunction, as evidenced by reduced HRV indices, is associated with increased cardiometabolic risk in patients with childhood-onset craniopharyngioma.

[Childhood craniopharyngioma with hypothalamic obesity - no long-term weight reduction due to rehabilitation programs]. / Kraniopharyngeom mit hypothalamischer Adipositas - Stationäre Rehabilitation ohne Einfluss auf die Gewichtszunahme bei Kindern und Jugendlichen.

BACKGROUND: Severe obesity due to hypothalamic involvement has major impact on prognosis in long-term survivors of childhood craniopharyngioma. The long-term effects of rehabilitation efforts on weight development and obesity in these patients are not analyzed up to now. PATIENTS AND METHODS: 108 patients with childhood craniopharyngioma recruited in HIT Endo before 2001 were included in the study. Long-term weight development (BMI SDS after >10 yrs follow-up) was analyzed in regard to rehabilitation, which was performed in 31 of 108 (29%) patients (one rehabilitation in 4 patients (13%), more than one in 21 patients (68%), 6 patients unknown) in 13 German rehabilitation -clinics. RESULTS: 84% of patients underwent rehabilitation in order to reduce hypothalamic obesity (BMI>+ 2 SD), whereas 12% of patients were normal weight. Childhood craniopharyngioma pa-tients with rehabilitation presented with higher BMI at diagnosis (median BMI: +1.32 SD; range: -1.08 to + 7.00 SD) and at last evaluation (median BMI: +4.93 SD; range: -0.20 to + 13.13 SD) when compared with patients without rehabilitation (median BMI at diagnosis: +0.24 SD; range: -2.67 to + 6.98 SD; BMI at evaluation: +2.09 SD; range: -1.48 to + 10.23 SD). A long-term weight reducing effect of rehabilitation was no detectable regardless of degree of obesity, frequency of rehabilitation, and hospital of rehabilitation. CONCLUSION: Treatment options for hypothalamic obesity in terms of rehabilitation are limited. Accordingly, strategies for prevention of hypothalamic lesions and psychosocial effects of rehabilitation are currently in focus for improvement of prognosis in childhood craniopharyngioma patients.

Coping strategies in patients after treatment for functioning or nonfunctioning pituitary adenomas.

CONTEXT AND OBJECTIVE: Coping strategies may affect quality of life, which is decreased in patients after treatment for Cushing's disease, acromegaly, or nonfunctioning pituitary macroadenomas (NFMA). We aimed to explore coping strategies in these patients because this has never been done before. DESIGN: We conducted a cross-sectional study. SUBJECTS: We included patients treated for Cushing's disease (n = 42), for acromegaly (n = 80), and for NFMA (n = 61). These patients were compared with three reference populations: an a-select sample from the Dutch population (n = 712), patients with chronic pain (n = 59), and patients receiving primary care psychology services (n = 525). Furthermore, the three patient groups were compared with each other. Coping strategies were assessed by the Utrecht Coping List. RESULTS: Compared with the a-select sample, patients with pituitary adenomas reported less active coping (P < 0.0001), sought less social support (P < 0.0001), and reported more avoidant coping (P = 0.008). In contrast, patients treated for pituitary adenomas reported somewhat better coping strategies than patients with chronic pain and those with psychological disease. When patients with different pituitary adenomas were compared, patients treated for Cushing's disease sought more social support than patients treated for NFMA (P = 0.035). CONCLUSIONS: Patients treated for pituitary adenomas display different and less effective coping strategies compared with healthy controls. A targeted intervention might help to stimulate patients to use a more active coping strategy and to seek social support instead of an avoiding coping strategy. This might, in turn, improve their quality of life.

Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

CONTEXT AND OBJECTIVE: Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. DESIGN: Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). PATIENTS AND CONTROL SUBJECTS: We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. RESULTS: Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P < 0.001), irritability (P < 0.001), anxiety (P < 0.001), negative affect and lack of positive affect (P < 0.001 on both scales), somatic arousal (P < 0.001), and 11 of 18 subscales of the Dimensional Assessment of Personality Pathology short-form (P < 0.05). CONCLUSIONS: Patients with long-term cured CD show an increased prevalence of psychopathology and maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women.

CONTEXT: Few data are available on pregnancy outcomes in women with acromegaly. STUDY DESIGN: This was a retrospective multicenter study. PATIENTS: The study included 46 women with GH-secreting pituitary microadenomas (n = 7) or macroadenomas (n = 39). Their mean age was 31.7 yr (±4.5 yr). Incomplete transsphenoidal surgical resection (n = 39) and pituitary radiation (n = 14) had been performed, respectively, 2.9 ± 2.6 and 7.3 ± 4.2 yr before pregnancy. The patients were receiving dopamine agonists (n = 25) and/or somatostatin analogs (n = 14), and GH/IGF-I hypersecretion was controlled and uncontrolled in, respectively, 23 and 34 cases. Five pregnancies followed the fertility treatment. RESULTS: Fifty-nine pregnancies resulted in 64 healthy babies. Gestational diabetes and gravid hypertension occurred in four (6.8%) and eight (13.6%) pregnancies, respectively, and both were more frequent when GH/IGF-I hypersecretion was not controlled before pregnancy. Visual field defects were diagnosed during pregnancy in four women, three of whom were diagnosed with acromegaly during the pregnancy. Seven women had isolated headache. Magnetic resonance imaging performed 3.9 ± 0.3 months after delivery showed that the size of the adenoma had increased in three cases, decreased in two cases, and remained stable in 22 cases. Seventeen women breast-fed with no complications. Four women gave birth to a small-for-gestational-age infant; all had received somatostatin analogs, alone or in combination with dopamine agonists, during pregnancy. The mean IGF-I level fell significantly during the first trimester in 12 cases (before conception 588 ± 207 ng/ml, first trimester 319 ± 126 ng/ml, P = 0.002), whereas the GH concentration did not change significantly. CONCLUSION: The following conclusions were reached: 1) pregnancy in women with active or uncontrolled acromegaly may be associated with an increased risk of gestational diabetes and gravid hypertension; 2) pregnancy is occasionally associated with symptomatic enlargement of GH-secreting pituitary macroadenomas; 3) changes in serum GH and IGF-I concentrations are variable during pregnancy, indicating that routine monitoring is not mandatory if the pregnancy is uneventful; and 4) GH-suppressive treatment can be safely withdrawn after conception in most acromegalic women.

Disease-specific impairments in quality of life during long-term follow-up of patients with different pituitary adenomas.

OBJECTIVE: Quality of life (QoL) is impaired in patients treated for pituitary adenomas. However, differences in age and gender distributions hamper a proper comparison of QoL. Therefore, we compared age- and gender-specific standard deviations (SD) scores (Z-scores) of QoL parameters in patients treated for pituitary adenomas. PATIENTS AND METHODS: We determined Z-scores for health-related questionnaires [the Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI)-20, Nottingham Health Profile (NHP), and Short Form Health Survey (SF-36)] in patients during long-term follow-up (13 +/- 8 years) after treatment for pituitary adenomas. Z-scores were calculated by comparing the data for 403 patients with acromegaly (n = 118), Cushing's disease (CD; n = 58), prolactinoma (n = 128), and nonfunctioning macroadenoma (n = 99) with a control population (n = 440) for each subscale of the questionnaires and for total QoL score. RESULTS: All subscales of the questionnaires and the total QoL score were negatively affected in patients compared to controls. Comparing the Z-scores, patients treated for acromegaly reported more impairment in physical ability and functioning and more bodily pain compared to patients treated for nonfunctioning macroadenoma and those treated for prolactinoma. Patients with CD reported impairment in physical functioning compared to patients treated for nonfunctioning macroadenoma. Linear regression analysis, with correction for age and gender, confirmed these findings. Additionally, CD was associated with increased anxiety. Hypopituitarism negatively influenced multiple aspects of QoL. CONCLUSION: QoL is impaired in patients during long-term follow-up after treatment of pituitary adenomas. Patients with pituitary adenomas should be informed of these persistent adverse effects of their disease on QoL to prevent inappropriate expectations with respect to the long-term results of treatment.

Patients cured from craniopharyngioma or nonfunctioning pituitary macroadenoma (NFMA) suffer similarly from increased daytime somnolence despite normal sleep patterns compared to healthy controls.

OBJECTIVE: Adults patients previously treated for craniopharyngioma have increased general and physical fatigue compared to healthy controls. This could be related to disturbed sleep patterns. The aim of this study was to compare sleepiness and sleep patterns in those patients to healthy controls and to patients treated for nonfunctioning macroadenomas (NFMA) of the pituitary. DESIGN: Case-control study. PATIENTS AND METHODS: Sleepiness and sleep patterns were assessed in 27 adult patients [14 men, 8 patients diagnosed at childhood age, mean age of 53 years (range 27-80 year)] after long-term follow-up and compared to 50 healthy controls and 38 age-, gender- and BMI-matched patients with NFMA. We used two validated questionnaires for sleep parameters (Epworth sleepiness score and Münchener Chronotype Questionnaire). RESULTS: Sleep patterns (onset, sleep timing, duration and rise time) were not statistically different between the three groups. However, daytime sleepiness scores were increased in patients treated for craniopharyngioma compared to healthy controls, but not different from patients with NFMA. Thirty-three percent of patients with craniopharyngiomas had ESS scores above 10 compared to 8% of healthy controls (P = 0.005), indicating severe daytime hypersomnolence. Neither type of surgery, previous radiotherapy, or age at diagnosis influenced the sleepiness scores in patients with craniopharyngioma. CONCLUSION: Patients treated for craniopharyngioma or NFMA have increased daytime somnolence despite normal sleep patterns, compared to healthy subjects. The results indicate that increased daytime somnolence is a general consequence of large tumours, and/or their treatment, in the hypothalamic/pituitary region, rather than a specific feature of craniopharyngiomas per se.

Assessment of quality of life in patients with uncontrolled vs. controlled acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL).

OBJECTIVE: Acromegaly is a chronic disease with an important impact on quality of life. An acromegaly disease-generated quality of life questionnaire (AcroQoL) has recently been developed. We aimed to confirm reliability, construct validity and disease-specificity of the AcroQoL questionnaire. Second, we investigated the effect of remission status on health-related quality of life (HRQoL) in patients with acromegaly. DESIGN AND PATIENTS: Using a prospective, cross-sectional design, 33 patients with treated acromegaly and 22 patients with treated hormone-inactive pituitary adenoma under stable replacement therapy completed the German version of the AcroQoL questionnaire. MEASUREMENTS AND RESULTS: Cronbach's alpha analysis showed high reliability of the total score and the different scales and subscales in patients with acromegaly (alpha ranging from 0.83 to 0.93, item-total correlation 0.41-0.84). Patients with hormone-inactive pituitary adenoma showed lower reliability (alpha ranging from 0.17 to 0.75). Exploratory factor analysis in patients with acromegaly suggested a two-factorial solution with item distribution largely matching the scaling of the original Spanish questionnaire. Multiple regression analysis revealed significantly lower results of the total score and the different scales and subscales (indicating worse HRQoL) in patients with persistent acromegalic activity compared to patients with acromegaly in remission or discordant remission status. Consistently, IGF-I was an independent negative predictor of the different scores of the questionnaire. CONCLUSIONS: The AcroQoL questionnaire represents a reliable, construct valid and disease-specific tool for assessing health-related quality of life in patients with acromegaly. Patients with biochemically uncontrolled acromegaly showed significantly lower HRQoL than patients with acromegaly in remission or discordant remission status.

[Rehabilitation of young craniopharyngioma patients]. / Rehabilitation jugendlicher Kraniopharyngeom-Patienten.

The course of rehabilitation in 11 young patients with craniopharyngeoma was investigated. With intelligence well-preserved, neuropsychological diagnosis revealed impairments in rate and persistence in virtually all patients; behaviour disorders were present in 8 of the 11 patients, with efforts to distinguish psychoorganic from psychoreactive causality however not always successful. The neuropsychological deficits and behavioural deviations mentioned, rather than complications of a medical nature (1 of 11), resulted in only 2 patients having been able to maintain their premorbid educational/vocational status. The rehabilitative outcomes obtained in patients with clear-cut indications of diencephalic lesion (among them variations in vigilance, polyphagia, adipsia) had been unsatisfactory, whereas, in the other behaviourally disordered patients, successful outcomes were achieved by a therapeutic approach tailored to the specific needs of the individual condition.

[Results of psychological examinations for the optimization of rehabilitation following neurosurgical therapeutic measures in cerebral lesions of adults]. / Psychologische Untersuchungsergebnisse zur Rehabilitationsoptimierung nach neurochirurgischen Therapiemassnahmen bei zerebralen Läsionen im Erwachsenenalter.

On the basis of statistical data on neurosurgical therapy measures carried out in two five-year periods in adult patients with cerebral lesions, the need of rehabilitation, psychic peculiarities, and problems of social integration are discussed. The results of the neuropsychological examinations demonstrate the multifactorial dependence of inter-individual and environmental factors in postoperative problems. Aspects of psychological consultation, of special pedagogical therapy measures and of forms of communication are presented as promising possibilities of an optimisation of rehabilitation.