Physical activity, sports participation and exercise-related constraints in adult women with primary hypothyroidism treated with thyroid hormone replacement therapy.

Awareness of physical activity (PA) constraints in patients with primary hypothyroidism on thyroid hormone replacement therapy (THR) is important. Hence, this cross-sectional matched case-control study aimed to determine PA and sports participation (SP) in patients with hypothyroidism on THR in comparison to control subjects. Accordingly, survey questions were selected from the National Survey on Injuries and Physical Activity in the Netherlands (IPAN), supplemented with questions related to self-reported clinical characteristics and exercise-related constraints (ERC) of patients. In total, 1,724 female patients (mean age 53.0 years ±11.6) and 1,802 controls (mean age 52.6 ± 13.2) were included. Compared to controls, patients were less likely to comply with the moderate-intensity PA guideline (OR 0.70; 95% CI: 0.611-0.803), although patients were more actively participating in sports (OR 1.40; 95% CI: 1.156-1.706). Two-thirds of patients reported that hypothyroidism was limiting their PA performance. These limitations were more pronounced in patients with autoimmune thyroiditis (AIT) than in patients with hypothyroidism from other aetiology (OR 1.93; 95% CI: 1.518-2.457), representing disease-specific exercise intolerance. In order to establish effective intervention programmes to encourage regular PA in hypothyroid patients on THR with exercise intolerance, further research is warranted to better understand PA barriers.

Management of glucocorticoid replacement in adrenal insufficiency shows notable heterogeneity - data from the EU-AIR.

CONTEXT AND OBJECTIVE: Treatment for adrenal insufficiency (AI) remains suboptimal. Despite glucocorticoid replacement, patients with AI have reduced life expectancy and quality of life. This study aimed to describe the spectrum of management of glucocorticoid replacement in patients with AI enrolled in the European Adrenal Insufficiency Registry (EU-AIR). DESIGN, SETTING AND PATIENTS: EU-AIR is a prospective, multinational, multicentre, observational study initiated in August 2012 to monitor the long-term safety of glucocorticoid replacement in routine clinical practice in Germany, the Netherlands, Sweden and the UK (ClinicalTrials.gov identifier: NCT01661387). This analysis included 1166 patients with primary and secondary AI (mean disease duration 16·1 ± 11·6 years) receiving long-term glucocorticoid replacement therapy. MAIN OUTCOME MEASURE: Glucocorticoid type, dose, frequency and treatment regimen were examined. RESULTS: Most patients (87·4%) were receiving hydrocortisone. The most common dose range, taken by 42·2% of patients, was 20 to <25 mg/day; however, 12·6% were receiving doses of ≥30 mg/day. Hydrocortisone was being taken once daily by 5·5%, twice daily by 48·7%, three times daily by 43·6% and four times daily by 2·1%. Patients with primary AI received higher replacement doses than those with secondary AI (23·4 ± 8·9 and 19·6 ± 5·9 mg/day, respectively). Twenty-five different regimens were being used to deliver a daily hydrocortisone dose of 20 mg. CONCLUSIONS: We have shown significant heterogeneity in the type, dose, frequency and timing of glucocorticoid replacement in real-world clinical practice. This reflects dose individualization based on patient symptoms and lifestyle in the absence of data supporting the optimal regimen.

Incidence of adrenal crisis in patients with adrenal insufficiency.

BACKGROUND: An adrenal crisis (AC) is a potential life-threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes, and risk factors of AC in AI. METHODS: Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified, and all medical records were assessed by two independent investigators. The observed frequency of AC was determined as incidence rate, calculated as the number of AC divided by person-years (PY). In addition, precipitating factors and risk factors were assessed. RESULTS: We observed an incidence rate of 5·2 AC (95% CI 4·3-6·3) per 100 PY in primary adrenal insufficiency (PAI, a total of 111 patients), and 3·6 AC (95% CI 3·1-4·1) per 100 PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients with an established diagnosis of tertiary (glucocorticoid-induced) adrenal insufficiency (a total of 28 patients) had 15·1 AC (95% CI 11·0-19·9) per 100 PY. The most important risk factor was the existence of comorbidity. Gastro-enteritis and other infections were the most common precipitating factors for AC. CONCLUSION: AC still occurs relatively frequent in patients with AI, mostly precipitated by infections and particularly in patients with high comorbidity. This should be taken into account in the education and follow-up of patients with AI.

Self-management support in patients with adrenal insufficiency.

OBJECTIVE: Patient education is an important intervention to prevent an adrenal crisis in patients with adrenal insufficiency. The objective of this study was to assess the knowledge of adjusting the dose of glucocorticoids in special circumstances in patients with adrenal insufficiency who had previously been educated on this topic. In patients with insufficient knowledge, we tried to identify the underlying causes and care needs. DESIGN: Quantitative and qualitative study. METHODS: Adult patients with chronic primary and secondary adrenal insufficiency who received glucocorticoid stress management education were invited to participate in a telephone interview in which we tested their knowledge using hypothetical situations of physical and mental stress. In respondents with insufficient knowledge, we conducted a qualitative semistructured interview to elicit the underlying reasons from patients' perspective for their lack of knowledge and determine their care needs. RESULTS: Forty-three of the 83 patients who previously received education had insufficient knowledge about how to act during stressful situations. We found a significant association between education level and level of knowledge after the educational consult. The following underlying factors were identified: unawareness of the seriousness of their condition, ineffective coping strategies, the lack of experience with self-management skills and misconceptions. The most important care needs were repetition of education, the use of guidelines, learning from experience and optimizing social support. CONCLUSION: One or two educational consults are not effective to achieve adequate self-management skills. There is a need for structural follow-up where education is repeated and practical implementation of this knowledge is tested in order to identify the potential inadequate action.

Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. METHODS: In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. RESULTS: A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. CONCLUSION: Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue.

High resolution pituitary gland MRI at 7.0 tesla: a clinical evaluation in Cushing's disease.

OBJECTIVE: To evaluate the detection of pituitary lesions at 7.0 T compared to 1.5 T MRI in 16 patients with clinically and biochemically proven Cushing's disease. METHODS: In seven patients, no lesion was detected on the initial 1.5 T MRI, and in nine patients it was uncertain whether there was a lesion. Firstly, two readers assessed both 1.5 T and 7.0 T MRI examinations unpaired in a random order for the presence of lesions. Consensus reading with a third neuroradiologist was used to define final lesions in all MRIs. Secondly, surgical outcome was evaluated. A comparison was made between the lesions visualized with MRI and the lesions found during surgery in 9/16 patients. RESULTS: The interobserver agreement for lesion detection was good at 1.5 T MRI (κ = 0.69) and 7.0 T MRI (κ = 0.62). In five patients, both the 1.5 T and 7.0 T MRI enabled visualization of a lesion on the correct side of the pituitary gland. In three patients, 7.0 T MRI detected a lesion on the correct side of the pituitary gland, while no lesion was visible at 1.5 T MRI. CONCLUSION: The interobserver agreement of image assessment for 7.0 T MRI in patients with Cushing's disease was good, and lesions were detected more accurately with 7.0 T MRI. KEY POINTS: Interobserver agreement for lesion detection on 1.5 T MRI was good; Interobserver agreement for lesion detection on 7.0 T MRI was good; 7.0 T enabled confirmation of unclear lesions at 1.5 T; 7.0 T enabled visualization of lesions not visible at 1.5 T.

Feasibility of high-resolution pituitary MRI at 7.0 tesla.

OBJECTIVES: Since the pituitary gland measures 3-8 mm, imaging with the highest possible spatial resolution is important for the detection of even smaller lesions such as those seen in Cushing's disease. In the current feasibility study, we tested a multi-sequence MRI protocol to visualize the pituitary gland in high resolution at 7.0 Tesla (7.0 T). METHODS: Ten healthy volunteers were examined with a 7.0 T pituitary gland protocol. The protocol consisted of a T1-weighted magnetization-prepared inversion recovery (MPIR) turbo spin-echo (TSE) sequence and a T2-weighted TSE sequence. Additionally, this protocol was tested in five patients with clinical and biochemical suspicion of a microadenoma. RESULTS: The dedicated protocol was successful in visualizing normal pituitary anatomy. At 7.0 T compared to 1.5 T, four times as many slices covered the pituitary gland in sagittal and coronal direction. In three patients, a lesion was diagnosed at 7.0 T, and was confirmed by histopathology to be a microadenoma. CONCLUSION: Head-to-head comparisons of 7.0 T with 1.5 T and 3.0 T are needed with larger samples of patients and with imaging times feasible for clinical settings. However, the current study suggests that high-resolution 7.0 T MRI of the pituitary gland may provide new perspectives when used as a second-line diagnostic examination in the specific context of Cushing's disease. KEY POINTS: • 7.0 T MRI enables ultra-high-resolution imaging of the pituitary gland. • 7.0 T MRI is appropriate to visualize normal pituitary gland anatomy. • The pituitary protocol consists of a T 1 -MPIR-TSE and a T 2 -TSE sequence. • In four patients, a suspected ACTH-producing microadenoma was visualized at 7.0 T. • Histopathology confirmed three of four lesions to be ACTH-producing microadenomas.

European Adrenal Insufficiency Registry (EU-AIR): a comparative observational study of glucocorticoid replacement therapy.

BACKGROUND: Increased morbidity and mortality associated with conventional glucocorticoid replacement therapy for primary adrenal insufficiency (primary AI; estimated prevalence 93-140/million), secondary AI (estimated prevalence, 150-280/million, respectively) or congenital adrenal hyperplasia (estimated prevalence, approximately 65/million) may be due to the inability of typical glucocorticoid treatment regimens to reproduce the normal circadian profile of plasma cortisol. A once-daily modified-release formulation of hydrocortisone has been developed to provide a plasma cortisol profile that better mimics the daytime endogenous profile of cortisol. Here, we describe the protocol for the European Adrenal Insufficiency Registry (EU-AIR), an observational study to assess the long-term safety of modified-release hydrocortisone compared with conventional glucocorticoid replacement therapies in routine clinical practice (ClinicalTrials.gov identifier: NCT01661387). METHODS: Patients enrolled in EU-AIR have primary or secondary AI and are receiving either modified-release or conventional glucocorticoid replacement therapy. The primary endpoints of EU-AIR are the incidence of intercurrent illness, adrenal crisis and serious adverse events (SAEs), as well as the duration of SAEs and dose changes related to SAEs. Data relating to morbidity, mortality, adverse drug reactions, dosing and concomitant therapies will be collected. Patient diaries will record illness-related dose changes between visits. All decisions concerning medical care are made by the registry physician and patient. Enrolment is targeted at achieving 3600 patient-years of treatment (1800 patient-years per group) for the primary analysis, which is focused on determining the non-inferiority of once-daily modified-release replacement therapy compared with conventional glucocorticoid therapy. RESULTS: Recruitment began in August 2012 and, as of March 2014, 801 patients have been enrolled. Fifteen centres are participating in Germany, the UK and Sweden, with recruitment soon to be initiated in the Netherlands. CONCLUSIONS: EU-AIR will provide a unique opportunity not only to collect long-term safety data on a modified-release preparation of glucocorticoid but also to evaluate baseline data on conventional glucocorticoid replacement. Such data should help to improve the treatment of AI.

Does recovery of adrenal function occur in patients with autoimmune Addison's disease?

OBJECTIVE: We earlier discovered partial recovery in a patient with autoimmune Addison's disease. The aim of this study was to assess the occurrence of adrenocortical recovery in patients with autoimmune adrenalitis. DESIGN: Cross-sectional study. PATIENTS: Twenty-seven adult patients with autoimmune Addison's disease on stable glucocorticoid and mineralocorticoid replacement therapy (RT) attending the Department of Endocrinology of a university teaching hospital were included in this study. METHODS: Adrenocortical function was assessed by performing an adrenocorticotrophic hormone (ACTH) (250 µg Synacthen) stimulation test (SST) after interruption of current glucocorticoid and mineralocorticoid RT. A normal adrenal response was defined as a serum cortisol concentration ≥500 nm 30 or 60 min after stimulation. Partial recovery was defined as a cortisol concentration ≥100 and ≤500 nm after stimulation. RESULTS: In 17 patients (63%), serum cortisol concentrations remained undetectable 30 and 60 min after the administration of ACTH. None of the remaining 10 participants had a normal response. Only one patient reached a cortisol concentration of 100 nm after 60 min, but this could not be confirmed during a second SST. CONCLUSIONS: In this cross-sectional study among 27 patients with autoimmune adrenalitis, no new cases of adrenocortical recovery were found.

A multiplex immunoassay for human adipokine profiling.

BACKGROUND: Adipose tissue secretory proteins, called adipokines, play pivotal roles in the pathophysiology of obesity and its associated disorders such as metabolic syndrome, type 2 diabetes, and cardiovascular disease. Because methods for comprehensive adipokine profiling in patient plasma and other biological samples are currently limited, we developed a multiplex immunoassay for rapid and high-throughput measurement of 25 adipokines in only 50 microL of sample. METHODS: (Pre)adipocyte and ex vivo cultured adipose tissue supernatants were generated and together with plasma from 5 morbidly obese patients and 5 healthy and normal weight controls used to develop the adipokine multiplex immunoassay and test its usefulness in biological samples. We assessed adipokine dynamic ranges, lower limits of detection and quantification, cross-reactivity, intra- and interassay variation, and correlation with adipokine ELISAs. RESULTS: The limits of quantification and broad dynamic ranges enabled measurement of all 25 adipokines in supernatants and patient plasmas, with the exception of TNF-alpha in plasma samples. Intraassay variation was <10% for all adipokines; interassay variation was < 15%. The multiplex immunoassay results correlated significantly with ELISA measurements. Plasma adipokine profiling showed significantly higher concentrations of the novel adipokines cathepsin S (5.1 x 10(4) vs 4.3 x 10(4) ng/L, P = 0.003) and chemerin (4.1 x 10(5) vs 2.7 x 10(5) ng/L, P = 0.0008) in morbidly obese patients than normal weight controls, besides the established differences in adiponectin and leptin concentrations. CONCLUSIONS: Our findings underscore the relevance of the novel adipokines cathepsin S and chemerin, but foremost the potential of this novel method for both comprehensive adipokine profiling in large patient cohorts and for biological discovery.

Is Diagnosis and Subclassification of Adrenal Insufficiency as Easy as It Looks?

The diagnosis of adrenal insufficiency (AI) is a challenge. Most signs and symptoms are nonspecific and vary considerably depending upon the underlying cause and degree of AI. Identification of AI is crucial because the disease may be life-threatening if left unrecognized. The diagnostic evaluation consists of three steps. The first step is establishing the presence of hypocortisolism. The second step is establishing the level of hypothalamus-pituitary-adrenal axis dysfunction. The third and final step is searching for the exact cause of AI by additional laboratory and imaging techniques. Each diagnostic step can have its own uncertainties. The optimal test in case of intermediate basal cortisol measurements is still a matter of debate. Furthermore, interpretation of the results of the tests is complicated by arbitrary definitions of normal cutoff responses, variability in the analytical accuracy of the cortisol assays used and factors influencing cortisol-binding globulin. This chapter aims to provide a concise stepwise approach for the diagnostic evaluation of AI, taking into account the possible pitfalls associated with the different tests.

Successful treatment of a prolactinoma with the antipsychotic drug aripiprazole.

UNLABELLED: In this report, we describe a female patient with both prolactinoma and psychotic disorder who was successfully treated with aripiprazole, a partial dopamine 2 receptor agonist. During the follow-up of more than 10 years, her psychotic symptoms improved considerably, prolactin levels normalised and the size of the prolactinoma decreased. This observation may be of clinical relevance in similar patients who often are difficult to treat with the regular dopaminergic drugs. LEARNING POINTS: Prolactinoma coinciding with psychosis can represent a therapeutic challenge.In contrast to many other antipsychotic drugs, aripiprazole is associated with a decrease in prolactin levels.Aripiprazole can be a valuable pharmaceutical tool to treat both prolactinoma and psychosis.

Adrenal Crisis: Still a Deadly Event in the 21st Century.

Adrenal crisis is a life-threatening medical emergency, associated with a high mortality unless it is appropriately recognized and early treatment is rendered. Despite it being a treatable condition for almost 70 years, failure of adequate preventive measures or delayed treatment has often led to unnecessary deaths. Gastrointestinal illness is the most common precipitant for an adrenal crisis. Although most patients are educated about "sick day rules," patients, and physicians too, are often reluctant to increase their glucocorticoid doses or switch to parenteral injections, and thereby fail to avert the rapid deterioration of the patients' condition. Therefore, more can be done to prevent an adrenal crisis, as well as to ensure that adequate acute medical care is instituted after a crisis has occurred. There is generally a paucity of studies on adrenal crisis. Hence, we will review the current literature, while also focusing on the incidence, presentation, treatment, prevention strategies, and latest recommendations in terms of steroid dosing in stress situations.

Prognostic significance of successful ablation with radioiodine of differentiated thyroid cancer patients.

OBJECTIVES: Currently, little is known about the prognostic significance of achieving successful ablation with the first dosage of I-131 in patients with differentiated thyroid cancer. This study aimed to assess the following: (i) whether successful or unsuccessful ablation at post-ablation follow-up has prognostic consequences; (ii) possible factors predicting success of ablation in a patient. METHODS: In order to do this, we retrospectively studied 180 patients with a median follow-up of 55 months. Ablation was considered to be successful if 1 year after the initial dosage of I-131 patients fulfilled all of the following criteria: not dead from thyroid cancer, no additional therapy needed for any kind for thyroid cancer within the first year, undetectable thyroglobulin (Tg) levels under TSH stimulation, and negative I-131 scintigraphy. Tg levels at the time of ablation (P < 0.001), lymph node metastasis (P = 0.04) and distant metastasis (P < 0.001) have a significant influence on the success of ablation. P values were calculated by Mann-Whitney U test and Chi-square test, respectively. RESULTS: Patients with successful ablation had a better prognosis than those with unsuccessful ablation: disease-free survival was 87% versus 49% after 10 years; additionally, thyroid-cancer related survival was 93% versus 78%. CONCLUSION: We conclude that the extent of the remaining normal or neoplastic thyroid tissue influences the outcome of ablation, and that successful ablation leads to a better prognosis. It seems that it is very important to achieve complete ablation as soon as possible in order to ensure the best possible prognosis for a patient.

Obesity-related beliefs predict weight loss after an 8-week low-calorie diet.

The objective of this study was to examine whether beliefs about the cause, consequences, time line, and control of obesity are predictors of the amount of weight loss after an 8-week, low-calorie diet consisting of meal replacements. Forty-eight women and 18 men, mean age=45.9 (range=23 to 73 years) years and body mass index between 30 and 50 participated in a weight-loss program. Beliefs were measured at baseline by the Obesity Cognition Questionnaire and by an eating behavior self-efficacy scale. Correlational and regression analyses were performed to examine whether beliefs predicted weight change. Changes in body mass index, waist circumference, and blood pressure were significant (P <.001). Less weight reduction was associated with poor self-efficacy (r =-0.34, P <.01) and the beliefs that obesity had a physical origin (r =0.27, P =.04) and was not under behavioral control (r =-0.25, P =.04). Self-efficacy remained a significant predictor in regression analysis. The results suggest that the outcome of dietary interventions may be improved when adjusting beliefs, especially self-efficacy.

Impact of overt and subclinical hypothyroidism on exercise tolerance: a systematic review.

PURPOSE: This systematic review describes the state of the art of the impact of hypothyroidism on exercise tolerance and physical performance capacity in untreated and treated patients with hypothyroidism. METHOD: A systematic computer-aided search was conducted using biomedical databases. Relevant studies in English, German, and Dutch, published from the earliest date of each database up to December 2012, were identified. RESULTS: Out of 116 studies, a total of 38 studies with 1,379 patients fulfilled the inclusion criteria. These studies emphasize the multifactorial causes of exercise intolerance in untreated patients by the impact of limitations in different functional systems, with cardiovascular, cardiopulmonary, musculoskeletal, neuromuscular, and cellular metabolic systems acting in concert. Moreover, the studies affirm that exercise intolerance in patients is not always reversible during adequate hormone replacement therapy. As a consequence, despite a defined euthyroid status, there remains a significant group of treated patients with persistent complaints related to exercise intolerance who are suffering from limitations in daily and sport activities, as well as an impaired quality of life. An explanation for this phenomenon is lacking. Only 2 studies investigated the effects of a physical training program, and they showed inconsistent effects on the performance capacity in untreated patients with subclinical hypothyroidism. CONCLUSIONS: A limited body of knowledge exists concerning exercise tolerance in treated patients with hypothyroidism, and there is an insufficient amount of quantitative studies on the effects of a physical training program. To enhance exercise and sports participation for this specific group, more research in this forgotten area is warranted.

Increased use of antimicrobial agents and hospital admission for infections in patients with primary adrenal insufficiency: a cohort study.

BACKGROUND: Previous studies have suggested that infections are an important cause of death in patients with Addison's disease, but epidemiological studies on the frequency of infections in this population are lacking. OBJECTIVE: To assess and compare the incidence risk of infections in patients with primary adrenal insufficiency with controls. DESIGN AND SETTING: We conducted a cohort study, using data from the Dutch PHARMO record linkage system, that links patients' demographics and medication histories to hospital admissions. PATIENTS: From a cohort of oral glucocorticoid users, 390 patients with primary adrenal insufficiency were identified by assessing concurrent use of glucocorticoids and mineralocorticoids using pharmacy dispensing records. A reference cohort (n=1933) with the same age and sex distribution was sampled from patients not using glucocorticoids. OUTCOME MEASURE: Incidence rates and incidence rate ratios (IRR) were calculated of infections, defined by use of antimicrobial agents, as well as hospital admissions for infection. RESULTS: The incidence of infectious episodes, defined by usage of antimicrobial agents, among patients with primary adrenal insufficiency (incidence rate 59.2/100 person-years) was 1.5 times higher compared with controls, yielding a crude IRR OF 1.61 (95% CI 1.51-1.72). The IRR decreased slightly to 1.58 (95% CI 1.47-1.70) After adjustment for co-medication and co-morbidity also associated with infection risk. Also with respect to hospital admissions for infection, the incidence rates observed for patients with primary adrenal insufficiency was higher compared with controls (3.8/100 vs 0.8/100 person-years): crude IRR 5.02 (3.66-6.87) and adjusted IRR 4.34 (95% CI 3.04-6.22). CONCLUSION: Patients with primary adrenal insufficiency had an increased use of antimicrobial agents and hospital admissions related to infection.

High failure rates after (131)I therapy in Graves hyperthyroidism patients with large thyroid volumes, high iodine uptake, and high iodine turnover.

PURPOSE: The objective of this study was to identify patient characteristics positively and independently associated with I-iodide treatment failure in a large cohort of patients with Graves hyperthyroidism treated with either a calculated "standard" activity of 3.7 MBq/mL (0.1 mCi) or 7.4 MBq/mL (0.2 mCi) of thyroid volume. METHODS: Data on 385 consecutive patients were prospectively collected. Clinical treatment outcome up to 1 year in relation to thyroid volume, 5- and 24-hour I uptake, 5/24-hour I uptake ratio, and the administered activity of radioiodine were analyzed. RESULTS: Overall treatment results were hypothyroidism in 46%, euthyroidism in 29%, and recurrent hyperthyroidism in 26% of patients. Thyroid volume (P = 0.000), 5/24-hour uptake ratio (P = 0.000), and 5- and 24-hour uptake alone (respectively, P = 0.000 and P = 0.002) were significantly associated with therapy outcome. Patients with a combination of a thyroid volume greater than 50 mL and a 5/24-hour uptake ratio 0.8 or greater showed treatment failure in 70% and 42% (respectively, 3.7 MBq/mL, n = 20; and 7.4 MBq/mL, n = 41).Thyroid volume and 5/24-hour uptake ratio were positively and independently associated with recurrent hyperthyroidism (respectively, odds ratio [OR], 5.3; 95% confidence interval [CI], 2.39-11.76; and OR, 2.97; 95% CI, 1.59-5.59). Higher activities of 7.4 MBq/mL I were associated with a lower risk of treatment failure (OR, 0.34; 95% CI, 0.18-0.62). CONCLUSIONS: Large thyroid volumes and high 5/24-hour uptake ratios are positively and independently associated with recurrent hyperthyroidism following I therapy in Graves hyperthyroidism. Higher success rates can be achieved when account is taken of these poor prognostic factors. In consequence, these patients should be treated with activities greater than 7.4 MBq/mL.

Atypical hypocortisolism.

OBJECTIVE: To report a patient who had developed reversible hypocortisolism during the use of quetiapine. METHODS: Early morning cortisol levels were measured on two separate days. In addition, the patient underwent testing with intravenous synthetic adrenocorticotropic hormone (1 mcg tetracosactide) before and after tapering of quetiapine. Pituitary function was assessed and magnetic resonance imaging (MRI) was performed. RESULTS: The patient had low early morning cortisol levels at presentation when using quetiapine. Tetracosactide testing indicated hypocortisolism. A MRI of the pituitary was unremarkable. The patient was treated temporarily with hydrocortisone and quetiapine was tapered. After quetiapine had been discontinued, the patient's cortisol production had returned to normal. CONCLUSION: Although lowering cortisol levels has been previously reported, this is the first report of hypocortisolism associated with the use of quetiapine. It is possible symptoms of malaise in patients who use quetiapine could be attributed to quetiapine-related hypocortisolism.

[Thomas Addison and the adrenal gland]. / Thomas Addison en de bijnier.

The famous and beautifully illustrated monograph "On the Constitutional and Local Effects of Disease of the Suprarenal Capsules" was published by Thomas Addison in 1855. This was the first description of the disease that now bears his name. Thomas Addison provided the first real contribution to the knowledge of adrenal function after three centuries of non-productive speculation and is one of the founders of modern endocrinology.