Search Results

You are looking at 1 - 10 of 21 items for

  • Author: Nienke R Biermasz x
Clear All Modify Search
Free access

Nienke R Biermasz, Neveen A T Hamdy, Alberto M Pereira, Johannes A Romijn and Ferdinand Roelfsema

Introduction: The anabolic actions of growth hormone (GH) are well documented. In acromegaly, the skeletal effects of chronic GH excess have been mainly addressed by evaluating bone mineral density (BMD). Most data were obtained in patients with active acromegaly, and apparently high or normal BMD was observed in the absence of hypogonadism. Data on BMD are not available after successful treatment of acromegaly. Whether the positive effect of GH excess on bone mass is maintained in the long term after clinical and biochemical cure of acromegaly remains to be established.

Patients and methods: In a cross-sectional study design, lumbar spine and femoral neck BMD was measured in 79 acromegalic patients cured or well controlled on octreotide treatment (45 male and 34 female patients; mean age 57±1 years). Successful treatment (by surgery, radiotherapy and/or use of octreotide) was defined as normal age-adjusted IGF-I. Mean time after biochemical remission was 10.2±7 years.

Results: Normal or increased BMD was observed at the femoral neck and lumbar spine in both men and women in remission after treatment for acromegaly. Similar results were obtained in patients in remission for 5 years or longer. Osteoporosis was present in 15% of the patients, with similar prevalence in men and women. There was no relationship between BMD and duration or severity of GH excess before treatment, gonadal status and presence of pituitary hormone deficiencies. Pituitary irradiation was a strong negative predictor of bone mass at the femoral neck. Long-term bone loss was observed only at the femoral neck.

Conclusion: Our data suggest that the anabolic effect of GH on trabecular and cortical bone remains demonstrable after remission of acromegaly, although it may not be maintained at cortical sites in the long term. In the present study, the lack of effect of gonadal status on BMD may be explained by the presence of only mild hypogonadism and by our policy of prompt hormonal replacement therapy for severe hypogonadism. The negative effect of pituitary irradiation on femoral neck BMD remains intriguing, although it is probably related to some degree of the diminished GH secretion frequently observed after this form of treatment.

Free access

John M Felt Jr, Sarah A Depaoli, Alberto M Pereira, Nienke R Biermasz and Jitske Tiemensma

Context

Impaired quality of life (QoL) is common in patients after long-term remission of acromegaly. The acromegaly QoL (AcroQoL) is a disease-specific QoL questionnaire for patients diagnosed with acromegaly. The summed total score is the most frequently used scoring method of the AcroQoL. However, the total score does not capture all of the aspects of QoL that are outlined by the World Health Organization (WHO).

Objective

The aim of the present study was to use novel and sophisticated confirmatory methods to identify the optimal number of subscales for the AcroQoL.

Design and patients

Patients in remission from acromegaly were recruited from the Leiden University Medical Center and were asked to complete the AcroQoL (Dutch version) questionnaire (n=72).

Results

The three-subscale version of the AcroQoL consisted of subscales reflecting Physical Complaints, Appearance Issues, and Personal Relations Issues related to QoL. Model fit indices (i.e., comparative fit index and root mean square error of approximation) indicated that the three-subscale version represented the data better than the total score and two-subscale models did. A χ 2 difference test indicated that the three-subscale model was a significantly better fit than the total score and two-subscale models were (P<0.05).

Conclusion

Model fit and comparison statistics indicate that the three-subscale model is a better scoring method than the total score and two-subscale versions of the AcroQoL are. The three-subscale version also better reflected the WHO's recommendation of using a multidimensional measure of QoL than the total score and two-subscale methods did. Therefore, it is recommended that values from the three-subscales of the AcroQoL be reported in future research.

Free access

Jitske Tiemensma, Alberto M Pereira, Johannes A Romijn, Elizabeth Broadbent, Nienke R Biermasz and Adrian A Kaptein

Context and objective

Patients with acromegaly have persistent complaints despite long-term biochemical control. Drawings can be used to assess patients' perceptions about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions and quality of life (QoL) in patients after long-term remission of acromegaly.

Design

A cross-sectional study was conducted to evaluate the utility of the drawing test.

Methods

A total of 50 patients after long-term remission (mean±s.e.m., 16±1.2 years) of acromegaly were included in this study. Patients completed the drawing test (two retrospective drawings of their body perception before acromegaly and during the active phase of acromegaly, and one drawing on the current condition after long-term remission), Illness Perception Questionnaire-Revised, Physical Symptom Checklist, EuroQoL-5D, and AcroQoL.

Results

Patients perceived a dramatic change in body size during the active state of the disease compared with the healthy state before the awareness of acromegaly. Patients reported that their body did not completely return to the original proportions after long-term remission. In addition, larger drawings indicated more negative consequences (P<0.05), a higher score on emotional representations (P<0.05), and more perceived symptoms that were attributed to acromegaly (P<0.01). Larger drawings also indicated more impaired QoL, especially disease-specific QoL (all P<0.05).

Conclusion

There are strong correlations among the drawing test, illness perceptions, and QoL. The drawing test appears to be a novel and relatively easy tool to assess the perception of patients after long-term remission of acromegaly. The assessment of drawings may enable health care providers to appreciate the perceptions of patients with long-term remission of acromegaly, and enable discussion of symptoms and remission.

Free access

Natasha M Appelman-Dijkstra, Marnick Rijndorp, Nienke R Biermasz, Olaf M Dekkers and Alberto M Pereira

Background

Recombinant human growth hormone (rhGH) replacement is advocated in adult growth hormone-deficient (GHD) patients to increase bone mass and improve lipid profile, body composition, and quality of life. The long-term effects of discontinuation of rhGh replacement are unknown.

Methods

This cohort study and systematic review aim to evaluate the long-term metabolic effects of discontinuation of rhGh replacement in adult GHD patients, with a subgroup analyses according to age (< or > 60 years). Data on anthropometry, lipids, glucose, and bone mass density (BMD) were assessed for 3 years after discontinuation.

Results

Cohort study included 64 patients who had discontinued rhGh replacement for >12 months. Fat percentage increased from 31.5±9.5% to 33.8±9.0% (mean difference 2.3, P=0.003). BMI decreased only in subjects <60 years (P=0.014). Glucose, total cholesterol, and LDL-cholesterol levels did not change; however, the percentage of patients on statins increased slightly from 39% to 44%. HDL-C concentration increased only in patients <60 years (mean difference 0.2, P=0.043). Lumbar spine BMD did not change; however, femoral neck BMD and bone turnover markers decreased in subjects <60 years (P=0.001). Systematic review included eight studies (n=166 patients) with a follow-up duration of 6–18 months. Of the eight studies, three qualified as low risk of bias and five as having an intermediate risk of bias. None of the studies reported handling of statins, bisphosphonates, and glucose-lowering medication or excluded patients using these medications.

Conclusions

In this study, discontinuation of rhGh replacement resulted in metabolic changes only in patients <60 years after 3 years. Further research warrants to determine the optimal strategies for (dis)continuation of rhGh replacement in adult patients with GHD.

Free access

Nieke E Kokshoorn, Nienke R Biermasz, Ferdinand Roelfsema, Johannes W A Smit, Alberto M Pereira and Johannes A Romijn

Context

Recombinant human GH (rhGH) is prescribed for the treatment of adults with GH deficiency (GHD). However, conflicting data are available on the efficacy of rhGH treatment in elderly GHD patients.

Objective

To assess the efficacy of rhGH treatment in elderly GHD subjects.

Methods

We searched the available literature in PubMed, Cochrane Library, Web of Science and EMBASE.

Study selection

Studies on GHD patients, aged >60 years, treated with rhGH were eligible for inclusion. Data extraction was performed by two reviewers independently.

Results

We found 11 eligible studies with a total of 534 patients. Only two studies had prospective, randomized, placebo-controlled study designs of rhGH treatment with a duration of 6 (n=15) and 12 months (n=62), respectively. Treatment with rhGH decreased total and low density lipoprotein (LDL) cholesterol levels by 4–8 and 11–16%, respectively, but did not alter high density lipoprotein or triglyceride levels. RhGH did not affect body mass index, but decreased waist circumference (by ∼3 cm) and waist/hip ratio. RhGh did not consistently affect blood pressure or bone mineral density. RhGH increased lean body mass by 2–5% and decreased total fat mass by 7–10% in four studies, but did not affect body composition in two other studies. RhGH consistently improved quality of life (QoL) parameters reflected in AGHDA-scores. There were no explicit data on elderly GHD patients aged >80 years.

Conclusion

RhGH replacement in elderly subjects with GHD decreases LDL cholesterol levels and improves QoL, but the effects on other parameters are not unequivocal. There were no data on the efficacy and safety of rhGH treatment in octogenarians with GHD.

Free access

Natasha M Appelman-Dijkstra, Kim M J A Claessen, Ferdinand Roelfsema, Alberto M Pereira and Nienke R Biermasz

Background

The beneficial effects of recombinant human GH (rhGH) therapy in GH deficient (GHD) adults are well-established in the short term. However, data documenting the effects during prolonged follow-up are relatively scarce.

Objective

To evaluate the reported effects of rhGH replacement (≥5 years) in GHD adults on biochemical and anthropometric parameters, quality of life (QoL), bone metabolism, muscle strength, serious adverse events and mortality.

Methods

We conducted a systematic literature search. Quality assessment of retrieved papers was performed using a quality assessment based on the modified STROBE statement.

Results

We included 23 prospective studies with a rhGH treatment duration ranging from 5 to 15 years. Overall, beneficial effects were reported on QoL, body composition, lipid profile, carotid intima media thickness and bone mineral density. In contrast, the prevalence of the metabolic syndrome, glucose levels, BMI and muscle strength were not, or negatively, influenced. Most of the studies were uncontrolled, lacked the presence of a control group (of non-treated GHD patients), and reported no data on lipid-lowering and anti-diabetic medication. Overall mortality was not increased.

Conclusion

rhGH treatment in adult GHD patients is well-tolerated and positively affects QoL in the long term. However, the metabolic and cardiovascular effects during long-term treatment are variable. The low numbers of long-term studies and studied patients and lack of control data hamper definite statements on the efficacy of prolonged treatment. Therefore continuous monitoring of the effects of rhGH replacement to enable an adequate risk-benefit analysis that may justify prolonged, potentially life-long, treatment is advisable.

Free access

Jitske Tiemensma, Adrian A Kaptein, Alberto M Pereira, Johannes W A Smit, Johannes A Romijn and Nienke R Biermasz

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 Cushing's 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.

Free access

Ferdinand Roelfsema, Alberto M Pereira, Nienke R Biermasz, Marijke Frolich, Daniel M Keenan, Johannes D Veldhuis and Johannes A Romijn

Context

The hypothalamus–pituitary–thyroid axis in Cushing's syndrome may be altered. Previous reports have shown diminished serum TSH concentration and decreased response to TRH.

Objective

We analyzed serum TSH profiles in relation to cortisol profiles in patients with hypercortisolism of pituitary (n=16) or primary-adrenal origin (n=11) and after remission by pituitary surgery (n=7) in order to delineate aberrations in the hypothalamus–pituitary–thyroid system.

Intervention

Patients and controls (n=27) underwent a 24-h blood sampling study. Serum TSH and cortisol were measured with precise methods, and data were analyzed with a deconvolution program, approximate entropy (ApEn), and cosinor regression.

Results

Pulsatile TSH secretion and mean TSH pulse mass were diminished during hypercortisolism, independently of etiology (P<0.001). TSH secretion was increased in patients in remission only during daytime due to increased basal secretion (P<0.01). Pulse frequency and half life of TSH were similar in patients and controls. TSH ApEn (irregularity) was increased in patients with hypercortisolism (P<0.01), but was normal in cured patients. Cross-ApEn between TSH and cortisol, a measure of pattern synchrony loss, was increased in active disease, indicating (partial) loss of secretory synchrony. The TSH rhythm was phase delayed in hypercortisolemic patients, but normal in cured patients (P<0.01). Free thyroxine levels were decreased only in pituitary-dependent hypercortisolism compared with controls (P=0.003). Total 24-h TSH correlated negatively and linearly with log-transformed cortisol secretion (R=0.43, P=0.001).

Conclusion

Cortisol excess decreases TSH secretion by diminishing pulsatile release, whereas surgically cured patients have elevated nonpulsatile TSH release. Diminished TSH secretory regularity in active disease suggests glucocorticoid-induced dysregulation of TRH or somatostatinergic/annexin-1 control.

Free access

Kai Hang Yiu, Nina Ajmone Marsan, Victoria Delgado, Nienke R Biermasz, Eduard R Holman, Johannes W A Smit, Richard A Feelders, Jeroen J Bax and Alberto M Pereira

Objective

Active Cushing's syndrome (CS) is associated with cardiomyopathy, characterized by myocardial structural, and ultrastructural abnormalities. The extent of myocardial fibrosis in patients with CS has not been previously evaluated. Therefore, the objective of this study was to assess myocardial fibrosis in CS patients, its relationship with left ventricular (LV) hypertrophy and function, and its reversibility after surgical treatment.

Design and methods

Fifteen consecutive CS patients (41±12 years) were studied together with 30 hypertensive (HT) patients (matched for LV hypertrophy) and 30 healthy subjects. Echocardiography was performed in all patients including i) LV systolic function assessment by conventional measures and by speckle tracking-derived global longitudinal strain, ii) LV diastolic function assessment using E/E′, and iii) myocardial fibrosis assessment using calibrated integrated backscatter (IBS). Echocardiography was repeated after normalization of cortisol secretion (14±3 months).

Results

CS patients showed the highest value of calibrated IBS (−15.1±2.5 dB) compared with HT patients (−20.0±2.6 dB, P<0.01) and controls (−23.8±2.4 dB, P<0.01), indicating increased myocardial fibrosis independent of LV hypertrophy. Moreover, calibrated IBS in CS patients was significantly related to both diastolic function (E/E′, r=0.79, P<0.01) and systolic function (global longitudinal strain, r=0.60, P=0.02). After successful surgical treatment, calibrated IBS normalized (−21.0±3.8 vs −15.1±2.5 dB, P<0.01), suggestive of regression of myocardial fibrosis.

Conclusions

Patients with CS have increased myocardial fibrosis, which is related to LV systolic and diastolic dysfunction. Successful treatment of CS normalizes the extent of myocardial fibrosis. Therefore, myocardial fibrosis appears to be an important factor in the development and potential regression of CS cardiomyopathy.

Free access

Jitske Tiemensma, Cornelie D Andela, Ad A Kaptein, Johannes A Romijn, Roos C van der Mast, Nienke R Biermasz and Alberto M Pereira

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) Cushing's 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.