Jitske Tiemensma

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 Cushings 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.

Subtle Cognitive Impairments in Patients with Long-Term Cure of Cushing’s Disease

CONTEXT AND OBJECTIVE Active Cushings disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushings disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushings disease. DESIGN Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning. PATIENTS AND CONTROL SUBJECTS We included 74 patients cured of Cushings disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education. RESULTS Compared with NFMA patients, patients cured from Cushings disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushings disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushings disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushings disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients. CONCLUSIONS Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushings disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.

Neuropsychiatric Disorders in Cushing’s Syndrome

Glucocorticoids are crucial in the initiation and consolidation of the stress response. Patients with active Cushing’s syndrome (CS) are exposed to excessive endogenous glucocorticoid levels. In these patients, psychopathology is often being observed. The most common co-morbid disorder is major depression, but to a lesser extent mania and anxiety disorders have also been reported. A severe clinical presentation of CS often also includes depression. Reduction of glucocorticoid synthesis or action, either with metyrapone, ketoconazole, or mifepristone, rather than treatment with antidepressant drugs, is generally successful in relieving depressive symptoms, as well as other disabling symptoms. Following successful surgical treatment of hypercortisolism, both physical and psychiatric signs and symptoms improve substantially. However, it appears that patients do not completely return to their premorbid level of functioning and persistent impairment of quality of life and cognitive function has been reported despite long-term cure. At present, it is not clear whether, and to which extent, psychopathology still affects general well-being after long-term cure of CS.

Negative illness perceptions are associated with impaired quality of life in patients after long-term remission of Cushing's syndrome

OBJECTIVE Illness perceptions pertain to the pattern of beliefs patients develop about their illness. Illness perceptions are determinants of quality of life (QoL). Factors contributing to persisting impaired QoL after Cushings syndrome (CS) remain largely unknown. Therefore, the objective of this study was to explore illness perceptions, as potentially modifiable psychological factors, in relation to QoL in patients with long-term remission of CS. DESIGN Cross-sectional study. METHODS We included patients with long-term remission of CS (n=52). Illness perceptions were evaluated using the Illness Perception Questionnaire (IPQ)-Revised, and QoL was measured using the physical symptom checklist, EuroQoL-5D (EQ-5D), and the CushingQoL. Reference data were derived from recent studies and included patients with vestibular schwannoma (n=80), acute (n=35) or chronic (n=63) pain, and chronic obstructive pulmonary disease (COPD; n=171). RESULTS Illness perceptions showed a strong correlation with QoL. Patients with CS scored distinctively more negative on the IPQ compared with patients with vestibular schwannoma and patients with acute pain, and also reported more illness-related complaints (all P<0.01). There were also some differences in illness perceptions between patients with CS and patients with chronic pain and patients with COPD, but there was no distinct pattern. CONCLUSIONS Patients after long-term remission of CS report more negative illness perceptions compared with patients with other acute or chronic conditions. Further research is needed to assess whether QoL in CS can be improved by addressing these illness perceptions, for example, by a self-management intervention program.

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 Cushings 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 Cushings 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 Cushings 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.

Affected Illness Perceptions and the Association with Impaired Quality of Life in Patients with Long-Term Remission of Acromegaly

CONTEXT AND OBJECTIVE Illness perceptions pertain to the beliefs patients develop about their illness, and these views are determinants of behavior directed at the illness. Illness perceptions are determinants of quality of life (QoL). QoL remains impaired in patients with biochemical control of acromegaly, but illness perceptions were never studied in these patients. AIM The aim of the current study was to explore illness perceptions and their association with QoL in patients with long-term biochemical control of acromegaly. DESIGN This was a cross-sectional study. SUBJECTS We included patients with long-term biochemical control of acromegaly (n = 81), and compared them with Dutch reference populations: patients with acute pain (n=35) or chronic pain (n = 63), Cushings syndrome (n = 52), chronic obstructive pulmonary disease (n = 171), and vestibular schwannoma (n = 80). Illness perceptions were evaluated using the Illness Perception Questionnaire Revised, and QoL was assessed with the Physical Symptoms Checklist, EuroQoL-5D, and AcroQoL. RESULTS Illness perceptions showed strong correlations with QoL. Patients after remission of acromegaly have a good understanding of their disease, but they experience a lack of personal control and are not likely to seek medical care compared with patients with acute disease (all P < 0.01). CONCLUSION Illness perceptions of patients after long-term remission of acromegaly are affected and strongly related to QoL. Patients reported more negative illness perceptions than patients with acute illness but more positive illness perceptions than patients with chronic diseases. Additional research is necessary to assess whether a self-management intervention might help in improving affected illness perceptions and thereby improve QoL.

Smaller grey matter volumes in the anterior cingulate cortex and greater cerebellar volumes in patients with long-term remission of Cushing's disease: a case-control study

OBJECTIVE Patients with long-term remission of Cushings disease (CD) have persistent psychological and cognitive impairments. It is unknown whether, and to what extent, these impairments are accompanied by structural abnormalities in the brain. We aim to investigate structural changes in the brain in patients with predominantly long-term remission of CD and to examine whether these changes are associated with psychological and cognitive dysfunction and clinical severity. DESIGN A cross-sectional, case-control study. METHODS In 25 patients with predominantly long-term remission of CD and 25 matched healthy controls, grey matter volumes in the regions of interest (hippocampus, amygdala, and anterior cingulate cortex (ACC)) and in the whole brain were examined, using 3T magnetic resonance imaging and a voxel-based morphometry approach. Psychological and cognitive functioning were assessed using validated questionnaires and clinical severity was assessed using the Cushings syndrome severity index. RESULTS Compared with controls, patients had smaller grey matter volumes of areas in the ACC (on average 14%, P<0.05) and greater volume of the left posterior lobe of the cerebellum (on average 34%, P<0.05). As expected, patients with remitted CD reported more depressive symptoms (P=0.005), more anxiety (P=0.003), more social phobia (P=0.034), more apathy (P=0.002), and more cognitive failure (P=0.023) compared with controls, but the differences in grey matter volumes were not associated with psychological or cognitive measures, nor with clinical severity. CONCLUSION Patients with predominantly long-term remission of CD showed specific structural brain abnormalities, in the presence of psychological dysfunction. Our data form a basis for future work aimed at elucidating the relation of the structural brain abnormalities and the sustained psychological deficits after long-term exposure to high cortisol levels.

Increased Psychopathology and Maladaptive Personality Traits, But Normal Cognitive Functioning, In Patients after Long-Term Cure of Acromegaly

OBJECTIVE Active acromegaly is associated with psychopathology, personality changes, and cognitive dysfunction. It is unknown whether, and to what extent, these effects are present after long-term cure of acromegaly. AIM The aim of the study was to assess psychopathology, personality traits, and cognitive function in patients after long-term cure of acromegaly. DESIGN This was a cross-sectional study. PATIENTS AND METHODS We studied 68 patients after long-term cure (13±1 yr) of acromegaly and 68 matched controls. We compared these data with 60 patients treated for nonfunctioning pituitary macroadenomas (NFMAs) and 60 matched controls. Psychopathology was assessed using the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form, and personality was assessed by the Dimensional Assessment of Personality Pathology short-form (DAPPs). Cognitive function was assessed by 11 tests. RESULTS Compared with matched controls, patients cured from acromegaly scored significantly worse on virtually all psychopathology questionnaires and on several subscales of the DAPPs. Compared with NFMA patients, patients cured from acromegaly scored worse on negative affect (P=0.050) and somatic arousal (P=0.009) and seven of 18 subscales of the DAPPs (P<0.05). Cognitive function in patients cured from acromegaly did not differ from matched controls or patients treated for NFMA. CONCLUSION Patients with long-term cure of acromegaly show a higher prevalence of psychopathology and maladaptive personality traits but not cognitive dysfunction, compared with matched controls and patients treated for NFMA. These results suggest irreversible effects of previous GH excess, rather than effects of pituitary adenomas per se and/or their treatment, on the central nervous system.

Psychological morbidity and impaired quality of life in patients with stable treatment for primary adrenal insufficiency: cross-sectional study and review of the literature.

CONTEXT A high prevalence of psychological morbidity and maladaptive personality as well as impaired quality of life (QoL) is observed in patients with and without hydrocortisone dependency following (cured) Cushings syndrome. However, it is currently unclear whether a similar pattern is present in patients with chronic glucocorticoid replacement for primary adrenal insufficiency (PAI). OBJECTIVE To evaluate psychological functioning, personality traits, and QoL in patients with PAI. DESIGN AND SUBJECTS A cross-sectional study including 54 patients with stable treatment for PAI and 54 healthy matched controls. Both patients and controls completed questionnaires on psychological functioning (Apathy Scale, Irritability Scale, Mood and Anxiety Symptoms Questionnaire short form, and Hospital Anxiety and Depression Scale), personality traits (Dimensional Assessment of Personality Pathology short form), and QoL (Multidimensional Fatigue Inventory, Short Form 36, EuroQoL-5D, Nottingham Health Profile, and Physical Symptom Checklist). RESULTS Patients with PAI suffered from more psychological morbidity (i.e. irritability and somatic arousal) and QoL impairments compared with controls (all P<0.01). There were no differences regarding maladaptive personality traits between patients and controls. However, there was a strong and consistent positive association between the daily hydrocortisone dose and prevalence of maladaptive personality traits (i.e. identity problems, cognitive distortion, compulsivity, restricted expression, callousness, oppositionality, rejection, conduct problems, social avoidance, narcissism, and insecure attachment, all P<0.05). There was also a strong relation between the mean daily hydrocortisone dose and both psychological morbidity (i.e. depression, P<0.05) and QoL impairments (i.e. general health perception, several measures of physical functioning, and vitality, all P<0.05). CONCLUSION Patients on stable glucocorticoid replacement therapy for PAI report psychological morbidity and impaired QoL. Psychological morbidity, impaired QoL, and maladaptive personality traits were all associated with higher dosages of hydrocortisone.

Clinical osteoarthritis predicts physical and psychological QoL in acromegaly patients

OBJECTIVE Quality of life is decreased in patients with long-term control of acromegaly. In addition, these patients suffer from irreversible osteoarthritis. The aim of this study was to assess the impact of joint-specific complaints, clinical and radiological signs of arthropathy on different aspects of quality of life (QoL) in patients with acromegaly after long-term disease control. DESIGN Cross-sectional study. METHODS We studied 58 patients (31 males), mean age 60 years (range 32-81 years), with strict biochemical control of acromegaly for a mean duration of 15 years. QoL was assessed by four health-related QoL questionnaires (HADS, MFI-20, NHP, SF-36) and one disease specific QoL questionnaire (AcroQoL). The outcomes of these questionnaires were compared with joint-specific self-reported complaints of pain/stiffness, clinical osteoarthritis based on American College of Rheumatology (ACR) and radiological osteoarthritis based on the Kellgren-Lawrence (KL) scoring method. RESULTS Long-term cured acromegaly patients had high pain scores of the spine, knee, and hip which limited physical functioning (mean difference -27.0, 95%-CI -9.5, -41.0) and psychological well-being (mean difference -44.4, 95%-CI -26.1, -60.9) (SF-36). Clinical osteoarthritis of the spine was associated mostly with impaired QoL scores, on physical, social, and emotional functioning, and on anxiety and depression. Remarkably, radiological osteoarthritis was not associated with impaired QoL. CONCLUSION These findings accentuate the importance of recognition of the clinical manifestations of arthropathy in patients with acromegaly despite long-term disease control.