A. A. van der Klaauw

High prevalence of arthropathy, according to the definitions of radiological and clinical osteoarthritis, in patients with long- term cure of acromegaly: a case-control study

OBJECTIVE To evaluate the prevalence and rheumatological and radiological characteristics of arthropathy in patients after long-term cure of acromegaly in comparison with age-matched controls. DESIGN Case-control study. PATIENTS We compared 89 patients with adequate biochemical control of acromegaly (mean 14 years) and 67 age-matched controls. MEASUREMENTS Study parameters were the results of symptom questionnaires, structured physical examination and radiographs of the spine, hip, knee and hand. The diagnosis of osteoarthritis was based on a) radiological osteoarthritis determined by Kellgren and Lawrence and b) clinical osteoarthritis determined by the American College of Rheumatology (ACR) criteria. For the radiological comparison with controls, a Dutch reference group was used. RESULTS Pain/stiffness at > or =1 joint site was reported by 72% of patients, most frequently in the spine and hands. Radiological osteoarthritis at > or =1 joint site was present in 99% of patients, most frequently in the spine and hip, and increased at all joint sites in comparison with controls (odds ratios: 2-20). Despite long-term cure of acromegaly, the characteristic widening of joint spaces was still present. In addition, severe osteophytosis was present. Representative radiographs of these typical features are included in the manuscript. According to the ACR criteria, clinical osteoarthritis at > or =1 joint site was present in 63% of patients, most frequently in the spine and hand. Patients had a higher prevalence of osteoarthritis than controls at all joint sites according to all scoring methods and at a younger age. CONCLUSIONS Prior GH excess has irreversible, deleterious late effects on the clinical and radiological aspects of joints in patients with long-term cure of acromegaly.

Patients Previously Treated for Nonfunctioning Pituitary Macroadenomas Have Disturbed Sleep Characteristics, Circadian Movement Rhythm, and Subjective Sleep Quality

CONTEXT AND OBJECTIVE Fatigue and excessive sleepiness have been reported after treatment of nonfunctioning pituitary macroadenomas (NFMA). Because these complaints may be caused by disturbed nocturnal sleep, we evaluated objective sleep characteristics in patients treated for NFMA. DESIGN We conducted a controlled cross-sectional study. SUBJECTS AND METHODS We studied 17 patients (8 women; mean age, 54 yr) in remission of NFMA during long-term follow-up (8 yr; range, 1-18 yr) after surgery (n = 17) and additional radiotherapy (n = 5) without comorbidity except for hypopituitarism and 17 controls matched for age, gender, and body mass index. Sleep was assessed by nocturnal polysomnography, sleep and diurnal movement patterns by actigraphy, and quality of life and subjective sleep characteristics by questionnaires. RESULTS Compared to controls, patients had reduced sleep efficiency, less rapid eye movement sleep, more N1 sleep, and more awakenings in the absence of excessive apnea or periodic limb movements. Actigraphy revealed a longer sleep duration and profound disturbances in diurnal movement patterns, with more awakenings at night and less activity during the day. Patients scored higher on fatigue and reported impaired quality of life. CONCLUSION Patients previously treated for NFMA suffer from decreased subjective sleep quality, disturbed distribution of sleep stages, and disturbed circadian movement rhythm. These observations indicate that altered sleep characteristics may be a factor contributing to impaired quality of life and increased fatigue in patients treated for NFMA.

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.

The exon-3 deleted growth hormone receptor polymorphism predisposes to long-term complications of acromegaly

OBJECTIVE The aim of the study was to evaluate the impact of the genomic deletion of exon 3 of the GH receptor (d3GHR) on long-term clinical outcome of acromegaly in a well-characterized cohort of patients with long-term remission of acromegaly. DESIGN We conducted a cross-sectional study. METHODS The presence of the d3GHR polymorphism was assessed in 86 acromegalic patients with long-term disease control and related to anthropometric parameters, cardiovascular risk factors, osteoarthritis, bone mineral density, colonic polyps and diverticulae, and dolichocolon. RESULTS Fifty-one patients had two wild-type alleles (59%), whereas 29 patients (34%) had one allele and six patients (7%) had two alleles encoding for the d3GHR isoform. Carriers of the d3GHR isoform showed increased prevalence of osteoarthritis, especially of the hip [adjusted odds ratio (OR), 5.2; 95% confidence interval (CI), 3.2-7.1], of adenomatous polyps (adjusted OR, 4.1; 95% CI, 2.4-5.6), and dolichocolon (adjusted OR, 3.2; 95% CI, 1.8-4.6). Anthropometric parameters, cardiovascular risk factors, bone mineral density, and (non)vertebral fractures were not significantly different between patients with and without the d3GHR allele. CONCLUSION In patients with long-term cured acromegaly, the d3GHR polymorphism is associated with an increased prevalence of irreversible comorbidities such as osteoarthritis, dolichocolon, and adenomatous colonic polyps, but not with other comorbidities such as cardiovascular risk factors.

Pretreatment insulin-like growth factor-I concentrations predict radiographic osteoarthritis in acromegalic patients with long-term cured disease.

OBJECTIVE The aim of the study was to identify factors influencing the development of osteoarthritis during long-term control of acromegaly, focusing on disease-specific parameters, GH and IGF-I concentrations, and duration of disease, adjusted for the well-known determinants of primary osteoarthritis. DESIGN We conducted a follow-up study. METHODS We studied 67 patients with adequate biochemical control of acromegaly for a mean of almost 13 yr. Study parameters were the results of radiological assessment of the spine, hip, knee, and hand. Osteoarthritis was defined as radiological osteoarthritis using the scoring system developed by Kellgren and Lawrence. Correlations between potential factors of influence and osteoarthritis were performed by analysis of covariance and adjusted for age, gender, and body mass index. RESULTS Patients with pretreatment IGF-I sd scores in the highest tertile had an almost 4-fold increased risk for radiological osteoarthritis of the hip when compared with patients in the lowest tertile. After adjustment for age, gender, BMI, and disease duration, pretreatment IGF-I sd scores predicted radiographic osteoarthritis in all joint sites. Osteoarthritis was not predicted by other factors, including pretreatment GH levels, type of treatment, and duration of follow-up. CONCLUSION This is the first study to document pretreatment IGF-I concentration as a predictor of radiographic osteoarthritis in acromegalic patients with long-term disease control.

Pheochromocytomas and extra-adrenal paragangliomas detected by screening in patients with SDHD-associated head-and-neck paragangliomas

Patients with SDHD-associated head-and-neck paragangliomas (HNP) are at risk for developing pheochromocytomas for which screening has been advised. To assess clinical, biochemical, and radiological outcomes of screening in a large single-center cohort of SDHD-positive patients with HNP and to address the necessity for repetitive follow-up, we evaluated 93 patients with SDHD-associated HNP (p.Asp92Tyr, p.Leu139Pro). Screening consisted of measurement of 24 h urinary excretion of catecholamines and/or their metabolites in duplicate, which was repeated with intervals of 2 years if initial biochemical screening was negative. In patients, in whom urinary excretion was above the reference limit, imaging studies with (123)I-MIBG (metaiodobenzylguanidine) scintigraphy and magnetic resonance imaging (MRI) and/or computed tomography (CT) were performed. Pheochromocytomas and extra-adrenal paragangliomas were treated surgically after appropriate blockade. Median follow-up was 4.5 years (range 0.5-19.5 years). Twenty-eight out of the 93 patients were included in our study and underwent additional imaging for pheochromocytomas/extra-adrenal paragangliomas. In 11 out of the 28 patients intra-adrenal pheochromocytomas were found. Extra-adrenal paragangliomas were discovered in eight patients. These tumors were detected during initial screening in 63% of cases, whereas 37% were detected after repeated biochemical screening. One patient was diagnosed with a biochemically silent pheochromocytoma. The high prevalence of pheochromocytomas/extra-adrenal paragangliomas in patients with SDHD-associated HNP warrants regular screening for tumors in these patients. Paragangliomas that do not secrete catecholamines might be more prevalent than previously reported. Future studies will have to establish whether routine imaging studies should be included in the screening of SDHD mutation carriers, irrespective of biochemical screening.

Attenuated pulse size, disorderly growth hormone and prolactin secretion with preserved nyctohemeral rhythm distinguish irradiated from surgically treated acromegaly patients.

Background  Radiation induces time‐dependent loss of anterior pituitary function, attributed to damage of the pituitary gland and hypothalamic centres. The development of growth hormone deficiency (GHD) in irradiated acromegaly patients is not well defined.

Short‐term overt hypothyroidism induces discrete diastolic dysfunction in patients treated for differentiated thyroid carcinoma

Background  Thyroid hormone has important effects on the cardiovascular system. The consequences of episodes of acute hypothyroidism on cardiac function have been investigated in only a few studies, and their results are inconclusive. Our objective was to investigate the effects of acute hypothyroidism on cardiac function in patients with iatrogenically induced subclinical hyperthyroidism after treatment for differentiated thyroid carcinoma.

Effects of octreotide therapy in progressive head and neck paragangliomas: Case series

Octreotide, a somatostatin analog, may be beneficial in the treatment of head and neck paragangliomas (HNPGLs).

Quality of life is decreased after treatment for nonfunctioning pituitary macroadenoma

Pituitary gland diseases are, in general, accompanied by an impaired quality of life (QoL). Hypopituitarism is associated with macroadenomas, and QoL is lessened even if there is optimal endocrine replacement. Because most studies of QoL have included both functioning and nonfunctioning tumors, the present study aimed to assess QoL in adults whose nonfunctioning pituitary macroadenomas (NFMAs) were removed by transsphenoidal surgery. The 99 participants, who were in remission following surgery for NFMA and, in some instances, radiotherapy, and whose age averaged 62 years, were compared with 125 age-matched control patients from this and other studies. The four validated health-related questionnaires used were the Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Index (MFI), Nottingham Health Profile (NHP), and Short Form-36 (SF-36). The mean postoperative follow-up was nearly 10 years. All but six of the 99 study patients were pituitary-deficient in at least one axis, and almost half had panhypopituitarism of the anterior pituitary. QoL was impaired in the NFMA group compared with control subjects. All elements of the MFI, which evaluates energy/fatigue, were affected, as were a majority of functions assessed by the NHP and SF-36, which assess general health and well-being. Study patients did less well than controls on all subscales of the HADS. Compared with age-adjusted reference values, deficits were found in social functioning, physical problems, emotional problems, perceived general health, lack of energy, and emotional reactivity. Stepwise univariate linear regression analysis showed age to be an independent predictor of reduced physical ability. The presence of multiple hormonal deficiencies independently predicted role limitations due to physical problems, impaired social functioning, sleep problems, and increased general fatigue. Gonadotropin deficiency predicted increased physical fatigue and reduced activity. Neither radiotherapy nor visual field defects were independent predictors of reduced QoL. Even patients with NFMA who are successfully treated tend to have a considerably impaired quality of life. In the present study, multiple pituitary deficiencies were the strongest predictor of reduced QoL.