Predictors of autoimmune thyroid disease.

This case-control study sought to investigate whether thyroid autoimmunity is significantly associated with identifiable and potentially modifiable environmental factors. A total of 324 individuals were recruited: 164 cases (with positive thyroid peroxidase antibodies [TPO-Ab] and/or thyroid-stimulating hormone receptor antibodies [TSH-R Ab]) and 160 controls (negative antibodies) who had been screened for thyroid autoimmunity within the previous 12 months. A questionnaire sought information on drug, social, and reproductive history, stress, and iodine intake, while blood specimens were collected to measure glycosylated hemoglobin, thyroid function, TPO-Ab/TSH-R Ab status, 25-hydroxyvitamin D level, and hepatitis C antibody status. Both TPO-Ab-positive and TSH-R Ab-positive individuals were exposed to a higher amount of smoking pack-years (P = 0.038 and 0.037, respectively). No significant predictors of TSH-R Ab positivity were identified on multivariate regression analysis. The odds for TPO-Ab positivity was increased by female gender (odds ratio [OR] 2.815, 95% confidence interval [CI], 1.387, 5.714; P = 0.004) and discontinuation of smoking (OR 2.367, 95% CI, 1.213, 4.621; P = 0.012), while birth in winter (OR 0.470, 95% CI, 0.253, 0.871; P = 0.017) and higher intake of iodine-rich foods (OR 0.864, 95% CI, 0.761, 0.981; P = 0.024) decreased the odds for TPO-Ab development. Therefore, avoidance of ever starting smoking and correction of iodine deficiency may help protect against TPO-Ab development.

Clinical outcomes following unilateral adrenalectomy in patients with primary aldosteronism.

BACKGROUND: In approximately half of cases of primary aldosteronism (PA), the cause is a surgically-resectable unilateral aldosterone-producing adrenal adenoma. However, long-term data on surgical outcomes are sparse. AIM: We report on clinical outcomes post-adrenalectomy in a cohort of patients with PA who underwent surgery. DESIGN: Retrospective review of patients treated for PA in a single UK tertiary centre. METHODS: Of 120 consecutive patients investigated for PA, 52 (30 male, median age 54, range 30-74) underwent unilateral complete adrenalectomy. Blood pressure, number of antihypertensive medications, and serum potassium were recorded before adrenalectomy, and after a median follow-up period of 50 months (range 7-115). Recumbent renin and aldosterone were measured, in the absence of interfering antihypertensive medication, ≥3months after surgery, to determine if PA had been biochemically cured. RESULTS: Overall, blood pressure improved from a median (range) 160/95 mmHg (120/80-250/150) pre-operatively to 130/80 mmHg (110/70-160/93), P < 0.0001. 24/52 patients (46.2%) had cured hypertension, with a normal blood pressure post-operatively on no medication. 26/52 (50%) had improved hypertension. 2/52 patients (3.8%) showed no improvement in blood pressure post-operatively. Median (range) serum potassium level increased from 3.2 (2.3-4.7) mmol/l pre-operatively to 4.4 mmol/l (3.3-5.3) post-operatively, P < 0.0001). Median (range) number of antihypertensive medications used fell from 3 (0-6) pre- to 1 post-operatively (range 0-4), P < 0.0001. CONCLUSIONS: Unilateral adrenalectomy provides excellent long-term improvements in blood pressure control, polypharmacy and hypokalaemia in patients with lateralizing PA. These data may help inform discussions with patients contemplating surgery.

Stereotactic radiosurgery XX: ocular neuromyotonia in association with gamma knife radiosurgery.

UNLABELLED: We report three patients who developed symptoms and signs of ocular neuromyotonia (ONM) 3-6 months after receiving gamma knife radiosurgery (GKS) for functioning pituitary tumours. All three patients were complex, requiring multi-modality therapy and all had received prior external irradiation to the sellar region. Although direct causality cannot be attributed, the timing of the development of the symptoms would suggest that the GKS played a contributory role in the development of this rare problem, which we suggest clinicians should be aware of as a potential complication. LEARNING POINTS: GKS can cause ONM, presenting as intermittent diplopia.ONM can occur quite rapidly after treatment with GKS.Treatment with carbamazepine is effective and improve patient's quality of life.

Sequelae and survivorship in patients treated with (131)I-MIBG therapy.

BACKGROUND: (131)I-meta-iodobenzylguanidine ((131)I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae. METHODS: Fifty-eight patients with metastatic NETs and CCTs who had received (131)I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated. RESULTS: In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of (131)I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of (131)I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function. CONCLUSION: Long follow up of (131)I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.

FGF signalling through Fgfr2 isoform IIIb regulates adrenal cortex development.

Developmental signalling pathways are implicated in the formation and maintenance of the adrenal gland, but their roles are currently not well defined. In recent years it has emerged that Sonic hedgehog (Shh) and Wnt/ß catenin signalling are crucial for the growth and development of the adrenal cortex. Here we demonstrate that Fibroblast growth factor receptor (Fgfr) 2 isoforms IIIb and IIIc are expressed mainly in the adrenal subcapsule during embryogenesis and that specific deletion of the Fgfr2 IIIb isoform impairs adrenal development, causing reduced adrenal growth and impaired expression of SF1 and steroidogenic enzymes. The hypoplastic adrenals also have thicker, disorganised capsules which retain Gli1 expression but no longer express Dlk1. Fgfr2 ligands were detected in both the capsule and the cortex, suggesting the importance of signalling between the capsule and the cortex in adrenal development.

A prospective evaluation of postural stimulation testing, computed tomography and adrenal vein sampling in the differential diagnosis of primary aldosteronism.

CONTEXT: In primary aldosteronism (PA), discriminating unilateral from bilateral disease is crucial because adrenalectomy is frequently curative in the former case but rarely helps in the latter. Various series have reported the utility of postural stimulation testing (PST), cross-sectional imaging and adrenal vein sampling (AVS) in the assessment of PA, but most of these studies were retrospective. OBJECTIVE: To prospectively determine the diagnostic utility of PST, AVS and computed tomography (CT) using a radiological scoring system in the assessment of PA in a tertiary centre, as well as to document the incidence of autonomous cortisol cosecretion. DESIGN AND SETTING: Fifty consecutive patients with PA underwent PST, CT, AVS and a low-dose dexamethasone suppression test with measurement of serum cortisol at 48 h. For patients who underwent surgery, histological confirmation, and a normal postoperative serum aldosterone concentration and plasma renin activity were taken as evidence for unilateral disease. For other patients, results from successful adrenal vein sampling were the diagnostic evidence against which CT and PST were assessed. RESULTS: Postural stimulation testing had a sensitivity and specificity of 44-56% and 71-75%, respectively. CT had an overall sensitivity and specificity of 77% and 80%, respectively, rising to 100% sensitivity and specificity if there was a single, discrete macronodule with an unequivocally normal contralateral gland. Evidence of cosecretion of cortisol occurred in 14% of patients. CONCLUSIONS: Preliminary experience is presented of an objective radiological scoring system for selecting patients with PA for AVS. PST provides little, if any, useful additional information. A significant minority of patients with PA exhibit evidence of cortisol cosecretion, which may have implications for perioperative management.