Time to recovery of adrenal function after curative surgery for Cushing's syndrome depends on etiology.

CONTEXT: Successful tumor resection in endogenous Cushing's syndrome (CS) results in tertiary adrenal insufficiency requiring hydrocortisone replacement therapy. OBJECTIVE: The aim was to analyze the postsurgical duration of adrenal insufficiency of patients with Cushing's disease (CD), adrenal CS, and ectopic CS. DESIGN: We performed a retrospective analysis based on the case records of 230 patients with CS in our tertiary referral center treated from 1983-2014. The mean follow-up time was 8 years. PATIENTS: We included 91 patients of the three subtypes of CS undergoing curative intended surgery and documented followup after excluding cases with persistent disease, pituitary radiation, concurrent adrenostatic or somatostatin analog treatment, and malignant adrenal disease. RESULTS: The probability of recovering adrenal function within a 5 years followup differed significantly between subtypes (P = .001). It was 82% in ectopic CS, 58% in CD and 38% in adrenal CS. In the total cohort with restored adrenal function (n = 52) the median time to recovery differed between subtypes: 0.6 years (interquartile range [IQR], 0.03-1.1 y) in ectopic CS, 1.4 years (IQR, 0.9-3.4 y) in CD, and 2.5 years (IQR, 1.6-5.4 y) in adrenal CS (P = .002). In CD the Cox proportional-hazards model showed that the probability of recovery was associated with younger age (hazard ratio, 0.896; 95% confidence interval, 0.822-0.976; P = .012), independently of sex, body mass index, duration of symptoms, and basal ACTH and cortisol levels. There was no correlation with length and extend of hypercortisolism or postoperative glucocorticoid replacement doses. CONCLUSIONS: Time to recovery of adrenal function is dependent on the underlying etiology of CS.

Quality of life is impaired in association with the need for prolonged postoperative therapy by somatostatin analogs in patients with acromegaly.

OBJECTIVE: To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly. DESIGN: This is a cross-sectional study in two tertiary referral centers in The Netherlands. PATIENTS AND METHODS: One hundred and eight patients with acromegaly, in whom transsphenoidal (n=101, 94%) or transcranial (n=7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS. RESULTS: IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85±1.52 vs 0.25±1.21, P=0.026), but the percentage of patients with insufficient control (IGF1 SDS >2) was not different (17 vs 9%, P=0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTA+, n=26, IGF1 SDS 0.44±0.72 vs SSTA-, n=44, IGF1 SDS 0.41±0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA. CONCLUSION: QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

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.