Radiofrequency ablation for autonomously functioning nodules as treatment for hyperthyroidism: subgroup analysis of toxic adenoma and multinodular goitre and predictors for treatment success.

PURPOSE: Treatment of hyperthyroidism caused by autonomously functioning thyroid nodules (AFTN) with 131I often leads to undesirable hypothyroidism. Radiofrequency ablation (RFA) has emerged as a promising alternative. This retrospective analysis aimed to examine the efficacy of, and postprocedural hypothyroidism after, RFA for AFTN. METHODS: Patients with hyperthyroidism caused by AFTN and treated with RFA were included if follow-up of at least 1 year was available. Cure was defined as thyroid medication-free biochemical euthyroidism. To predict cure, patient and treatment factors were analysed. A distinction was made between solitary toxic adenoma (STA) and toxic multinodular goitre (TMG). RESULTS: Forty-eight patients (36 STA, 12 TMG) were included. One year post-RFA cure rate was 72% in STA versus 25% in TMG (p = 0.004). One patient developed hypothyroidism. In 11 patients that remained hyperthyroid, a second RFA was successful in 83% of STA and 40% of TMG patients. At last available follow-up, this amounted to a total cure rate of 81% in STA and 33% in TMG (p = 0.002). In STA, cured patients had a higher baseline TSH and a lower FT3 than non-cured patients (p = 0.026 and 0.031). Cure was observed in 91% of patients when > 2.1 kJ/mL was delivered during RFA, compared to 44% when less energy was administered. CONCLUSION: The efficacy of RFA was nearly 3 times higher in STA patients compared to TMG. Severity of hyperthyroidism and kJ/mL delivered during RFA predicts cure. Direct comparison to the current standard of care is needed to implement RFA in treatment of hyperthyroidism caused by AFTN.

The effect of treatment on quality of life in patients with acromegaly: a prospective study.

OBJECTIVE: Acromegaly has a negative influence on health-related quality of life (HRQoL). Previous studies provide limited information on the course of HRQoL during treatment. This study aims to assess the effect of treatment on the course of HRQoL at six predefined time points. DESIGN: This prospective study examines HRQoL in treatment-naive patients before and during the first 2.5 years of acromegaly treatment. METHODS: Therapy-naive acromegaly patients completed three validated questionnaires (RAND-36, AcroQoL, and the Appearance Self-Esteem (ASE)) at six predetermined time points before, during, and after treatment. Outcomes were correlated to IGF1 levels and disease control status. RESULTS: Twenty-seven acromegaly patients completed the questionnaires at all time points. After treatment, all patients had controlled acromegaly. Scores of RAND-36 domains General health, Vitality and Health change, and all AcroQoL dimensions (except for Relations) improved during treatment (P ≤ 0.003); the largest changes were detected during the first year. Gender influenced HRQoL scores, since AcroQoL scores significantly improved in males but not in females. Over time, IGF1 levels were negatively correlated with HRQoL. After 2.5 years of follow-up, HRQoL of controlled patients was still lower than in the general population. CONCLUSION: HRQoL of acromegaly patients was considerably reduced at diagnosis. Disease control was associated with an improvement of HRQoL scores. Males showed a more pronounced improvement than females. The largest changes were detected in the first year of treatment. However, HRQoL during and after treatment remained impaired in acromegaly patients, emphasizing the need of additional support.

Conditioning cortisol in humans: design and pilot study of a randomized controlled trial.

BACKGROUND: Conditioning of physiological responses can be achieved by repeatedly pairing a previously neutral conditioned stimulus with the administration of a pharmacologically salient unconditioned stimulus. This type of conditioning has been effective for specific immune and endocrine responses, but results with regard to conditioning of cortisol, a key stress-regulatory parameter, are currently unclear. This paper describes a pharmacological conditioning design, optimized for the examination of effects of cortisol conditioning under both basal conditions and in response to stress. METHODS: A double-blind randomized controlled conditioning paradigm aimed at conditioning of cortisol is conducted in 48 healthy female volunteers. During the acquisition phase, a gustatory stimulus (conditioned stimulus) is paired with hydrocortisone (100 mg, capsulated, unconditioned stimulus) three times before being administered together with placebo during three evocation sessions. To investigate possible effects of cortisol conditioning in response to stress, participants are exposed to the Trier Social Stress Test during the third evocation session. Primary outcome measure of this study is the mean area under the curve of salivary cortisol during the first two evocation sessions. As secondary outcomes, self-reported affect and stress as well as alpha-amylase are investigated. A pilot study was conducted to ensure that this design is feasible to be used in a larger study. DISCUSSION: This study design provides an innovative opportunity to examine the conditioning of cortisol under basal conditions and in response to stress. Also, the possible effect of cortisol conditioning on secondary outcomes of self-reported affect and alpha-amylase can be investigated. If cortisol could successfully be conditioned, this would be of conceptual relevance, showing that hypothalamic pituitary adrenal (HPA) axis regulation can be influenced by associative learning processes. Eventually, this could also have important clinical implications for understanding and treating stress-related disorders in which HPA axis dysregulation might play a role. TRIAL REGISTRATION: Nederlands Trial Register, NTR4651. Registered on 29 July 2014.

Three-dimensional soft tissue analysis of the hand: a novel method to investigate effects of acromegaly.

BACKGROUND: Acral overgrowth is a highly common clinical sign in patients with active acromegaly. To what extent this overgrowth persists after long-term remission of acromegaly is largely unknown. Using the new imaging technique of three-dimensional (3D) stereophotogrammetry, it is possible to accurately investigate soft tissue changes of the hand. The aim of the recent study was to compare the 3D soft tissue characteristics of the hands of patients in long-term remission of acromegaly to those of a healthy pair matched control group. METHODS: A case-control study was performed at a tertiary referral center. Twelve patients in remission of acromegaly (58 % male, mean age 58.3 years, mean BMI 29.6 kg/m2) were compared to twelve age-, gender-, ethnicity-, and BMI-matched control subjects. Of each individual, 3D photographs of both hands were acquired and analyzed using a 3D computer software program. RESULTS: The patients in long-term remission of acromegaly have overgrowth of soft tissue of the hand compared to matched control subjects, with a larger length and width of the hand (p = 0.0025, p = 0.0017, respectively). Furthermore, the diameters measured at the proximal interphalangeal (PIP) joints of the individual fingers are larger in the acromegaly patients. CONCLUSIONS: Significant soft tissue overgrowth of the hand persists in former acromegaly patients, even after long-term remission. Analysis of 3D hand photographs is an accurate and easy tool to evaluate the acral soft tissue patterns in acromegaly. Level of Evidence: Level III, diagnostic study.

[Acromegaly: recognition of a rare disease in psychiatric practice]. / Acromegalie, herkenning van een zeldzame ziekte in de psychiatrie.

BACKGROUND: Acromegaly is a rare disease which is caused by a tumour in the anterior lobe of the pituitary gland. The tumour stimulates excessive production of the growth hormone. As a result, all the organs and tissues in the body are induced to grow. This growth is responsible for a wide range of symptoms, some of which can be neuro-psychiatric.
AIM: To promote the early detection of acromegaly so that treatment can be started as soon as possible and further damage can be prevented.
METHOD: We searched PubMed for articles relating to quality of life and cognitive, psychological and psychiatric symptoms and personality changes associated with acromegaly.
RESULTS: We describe the pathophysiology and epidemiology of acromegaly. Then we present the characteristic, external changes, neuro-cognitive complications, psychiatric disorders, personality changes and relevant comorbid somatic symptoms. Acromegaly is a disease in which patients, long before being diagnosed, present with cognitive and affective disorders. Before patients are diagnosed, they have often visited several consultants in connection with their nonspecific symptoms.
CONCLUSION: We believe that in everyday practice patients with acromegaly are frequently misdiagnosed. If patients present with extensive somatic co-morbidity and treatment-resistant depression and particularly if these symptoms are combined with the typical external features of acromegaly, then acromegaly can be suspected and further investigation should proceed without delay.

Vascular Health in Patients in Remission of Cushing's Syndrome Is Comparable With That in BMI-Matched Controls.

CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant because this topic relates to future development of cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether micro- and macrovascular health is impaired after long-term remission of CS in patients with no or adequately treated comorbidities. DESIGN AND SETTING: This was a cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: Sixty-three patients (remission of CS for ≥ 4 y) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls), serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity, and pulse wave analysis were studied. In group B (14 patients and 14 controls), endothelium-dependent and -independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intraarterial acetylcholine, sodium-nitroprusside, and NG-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in groups A and B. CONCLUSION: The vascular health of patients in long-term remission of CS seems to be comparable with that of healthy gender-, age-, and body mass index-matched controls, provided that the patients have no, or adequately controlled, comorbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for the stringent treatment of metabolic comorbidities in these patients.

Spontaneous remission of acromegaly and Cushing's disease following pituitary apoplexy: Two case reports.

In this double case report, we present two special cases of pituitary apoplexy. First, we describe a patient with growth hormone deficiency despite clinical suspicion of acromegaly. Imaging showed evidence of a recent pituitary apoplexy, which might have caused spontaneous remission of the acromegaly before presentation at our outpatient clinic. Second, we describe a patient who presented with spontaneous remission of Cushing's disease after pituitary apoplexy, followed by a spontaneous remission of a relapse of the Cushing's disease due to a second pituitary apoplexy. These cases show that patients in spontaneous remission of hormonally active pituitary adenomas should be suspected of a pituitary apoplexy. Furthermore, even after spontaneous remission following pituitary apoplexy, careful long-term follow-up of these patients is mandatory, as relapses of hormonal hypersecretion can occur.

Three-dimensional facial analysis in acromegaly: a novel tool to quantify craniofacial characteristics after long-term remission.

PURPOSE: The exact quantification of craniofacial characteristics in patients with acromegaly is important because it provides insight in the pathophysiology of the disease and offers a tool to evaluate the effects of treatment on tissue specific endpoints. However, until recently this was not feasible due to limitations of available cephalometric methods. The new technique of three-dimensional (3D) cephalometry enables the accurate quantification of facial anatomical characteristics of both soft tissue and bone. This is the first study that uses 3D cephalometry to analyze craniofacial disproportions in patients in long-term remission of acromegaly. METHODS: Sixteen patients in remission of acromegaly for over 24 months (50% male, mean age 56.0 ± 10.7 years, mean body mass index 29.3 ± 5.5 kg/m(2)) were compared to 16 matched control subjects. A 3D cone beam computed tomography scan and 3D stereophotograph of each individual were acquired and analyzed using 3D cephalometry. RESULTS: In addition to an accurate quantification of the classical craniofacial characteristics, 3D cephalometry, shows that many typical soft tissue deformities persist, even after long-term remission. Furthermore, we found that, compared to controls, the patients in remission of acromegaly have a wider face at the level of the zygoma and longer maxilla (p < 0.05). CONCLUSIONS: 3D cephalometry is an attractive novel imaging modality to accurately investigate craniofacial disproportions of both soft tissue and bony parts of the face in patients with acromegaly, which makes it a promising technique for future research purposes and clinical practice.

Persistent self-consciousness about facial appearance, measured with the Derriford appearance scale 59, in patients after long-term biochemical remission of acromegaly.

CONTEXT: Acromegaly is associated with impaired quality of life (QoL) and causes anatomical disproportions, which may contribute to the decreased QoL after successful treatment. The Derriford appearance scale 59 (DAS59) is a questionnaire measuring psychological distress and disruptions to everyday life associated with self-consciousness of appearance. OBJECTIVE: Investigate the psychological distress and dysfunction related to self-consciousness about appearance and its effect on QoL in patients in long-term remission of acromegaly. PATIENTS, DESIGN AND METHODS: Patients (>18 years old) treated for acromegaly at the Department of Endocrinology of the Radboud University Medical Center Nijmegen were invited to participate. A gender-, age- and body mass index matched control group was provided by the patients themselves. Participants were asked to complete the modified DAS59-, research and development 36- (RAND-36), acromegaly quality of life questionnaire (AcroQoL) and a sociodemographic questionnaire. Differences between patient- and control groups and correlations between questionnaire scores and clinical characteristics collected from medical records were analyzed. MAIN OUTCOME MEASURES: Questionnaire scores. RESULTS: Of the 120 respondents, 73 agreed to participate [all cured or under biochemical control, median remission time 10.5 years (range 2.3-43.6 years)]. Of these, 34 (46.6%) reported self-consciousness about their appearance. Twenty-nine of these patients (85.3%) pointed out their face to be a prominent source of self-consciousness. Fifty-seven matched control subjects were included as well. Significant correlations were found between the scores of the DAS59 and the AcroQoL, RAND-36 and VAS in patients. CONCLUSIONS: Even after long-term remission of acromegaly, a large number of patients are self-conscious about their appearance, leading to psychological distress and disruptions to everyday life and decreased QoL. Facial features were the most important source of self-consciousness. This stresses the importance of addressing self-consciousness of appearance and the need for additional support in this regard during follow-up in these patients.

Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas.

CONTEXT: Although the endoscopic technique of transsphenoidal pituitary surgery (TS) has been widely adopted, reports on its results in Cushing's disease (CD) are still scarce and no studies have investigated long-term recurrence rates. This is the largest endoscopic series published till now. OBJECTIVE: To gain insight into the role of endoscopic TS as a primary treatment option for CD, especially in patients with magnetic resonance imaging (MRI)-negative CD and (invasive) macroadenomas. DESIGN: Retrospective cohort study. PATIENTS AND METHODS: The medical records of 86 patients with CD who underwent endoscopic TS were examined. Data on preoperative and postoperative evaluation, perioperative complications, and follow-up were collected. Remission was defined as disappearance of clinical symptoms with a fasting plasma cortisol level ≤ 50 nmol/l either basal or after 1 mg dexamethasone. RESULTS: The remission rate in different adenoma subclasses varied significantly: 60% in MRI-negative CD (n=20), 83% in microadenomas (n=35), 94% in noninvasive macroadenomas (n=16), and 40% in macroadenomas that invaded the cavernous sinus (n=15). The recurrence rate was 16% after 71 ± 39 months of follow-up (mean ± S.D., range 10-165 months). CONCLUSIONS: Endoscopic TS is a safe and effective treatment for all patients with CD. Recurrence rates after endoscopic TS are comparable with those reported for microscopic TS. Our data suggest that in patients with noninvasive and invasive macroadenomas, the endoscopic technique of TS should be the treatment of choice as remission rates seem to be higher than those reported for microscopic TS, although no comparative study has been performed.