Immunohistochemical staining seems mandatory for individualizing and shortening follow-up in unilateral primary aldosteronism.

OBJECTIVE: The clinical significance of immunohistochemistry (IHC) for unilateral primary aldosteronism (PA) has been unclear. Individualized follow-up of PA patients could be in sight. Long-term outcomes of patients, classified based on IHC, need further investigation. We aimed to assess long-term clinical outcomes for unilateral PA, classifying patients based on IHC. DESIGN: A nationwide observational study, with up to 16 years follow-up, executed in 2007-2016 at Landspitali University Hospital, tertiary referral center. Patients were diagnosed and treated in line with the current guidelines. Haematoxylin and eosin (H&E) tissue slides were stained using CYP11B1 and -B2 antibodies. All cases were re-evaluated and classified according to the HISTALDO consensus. Outcomes were assessed using the PASO criteria. PATIENTS: All unilateral PA patients diagnosed in 2007-2016 in Iceland, 26 patients aged 28-73 years, who underwent adrenalectomy, were included. MEASUREMENTS: Aldosterone, renin, and cortisol values, use and dosage of antihypertensives, potassium supplementation, blood pressure and serum potassium pre-intervention and throughout follow-up, and histopathology results post-adrenalectomy. RESULTS: Following IHC, an aldosterone-producing nodule was seen in 12 adrenals, an aldosterone-producing adenoma in 10 and multiple aldosterone-producing micronodules in four. IHC altered histopathology from previous H&E diagnosis in 23% (6/26) of the patients. In total, 81% (21/26) of the patients had partial clinical success. Eight percent (2/26) of the patients needed potassium supplementation during follow-up. In the classical group, the AVS results were more determinative with significantly higher lateralization index (median 10.1 vs. 5.3, p = .04) and more contralateral suppression (median nondominant ratio 0.4 vs. 1.0, p = .03). One out of five patients with complete clinical success at 12 months post-op had severe relapse later, the other four were normotensive without antihypertensives for up to 10 years. CONCLUSIONS: We found IHC mandatory for accurate histopathologic diagnosis of PA. Our results support the importance of contralateral suppression when interpreting AVS results. Also, the study highlights the complicated assessment of clinical outcome and importance of aldosterone and renin measurements during follow-up.

Towards defining biomarkers to evaluate concussions using virtual reality and a moving platform (BioVRSea).

Current diagnosis of concussion relies on self-reported symptoms and medical records rather than objective biomarkers. This work uses a novel measurement setup called BioVRSea to quantify concussion status. The paradigm is based on brain and muscle signals (EEG, EMG), heart rate and center of pressure (CoP) measurements during a postural control task triggered by a moving platform and a virtual reality environment. Measurements were performed on 54 professional athletes who self-reported their history of concussion or non-concussion. Both groups completed a concussion symptom scale (SCAT5) before the measurement. We analyzed biosignals and CoP parameters before and after the platform movements, to compare the net response of individual postural control. The results showed that BioVRSea discriminated between the concussion and non-concussion groups. Particularly, EEG power spectral density in delta and theta bands showed significant changes in the concussion group and right soleus median frequency from the EMG signal differentiated concussed individuals with balance problems from the other groups. Anterior-posterior CoP frequency-based parameters discriminated concussed individuals with balance problems. Finally, we used machine learning to classify concussion and non-concussion, demonstrating that combining SCAT5 and BioVRSea parameters gives an accuracy up to 95.5%. This study is a step towards quantitative assessment of concussion.

Self-reported concussion history among Icelandic female athletes with and without a definition of concussion.

OBJECTIVE: This study examined whether Icelandic female athletes in contact sports, based their self-reported concussion history on adequate medical definitions, by assessing self-reported concussion history with and without a definition of concussion. Another aim was to examine whether currently active athletes were more knowledgeable of concussions than retired athletes. METHODS: Participants (age = 26.9, SD = 7.1) were 508 former (34.5%) and current (65.5%) elite female athletes in soccer (41%), handball (30.6%), basketball (19.1%), ice hockey (4.5%) and combat sports (4.7%). An online questionnaire (QuestionPro) was distributed to females in contact sports (snowball sampling). Participants later came for an in-person interview where the authenticity of previous responses was confirmed. In the questionnaire, participants answered background questions and questions about concussion history. First, they reported the total number of sustained concussions without a prompt. They reported the number of sustained concussions again after reading a definition of concussion. Participants could not correct their previous answers. Pearson's Chi-square was used for group comparisons. RESULTS: The prevalence of reported concussions increased from 40.2% to 64.8% following a definition. There was no significant difference in how many participants changed their answer when asked about sustaining SRCs before and after reading the definition based on whether the participants were still competitive or retired X2(1) = 0.69, p = 0.41. CONCLUSIONS: Our data suggest that understanding of concussions is inadequate among female athletes. Self-report will continue to be an essential source of clinical information and prompting with a definition can increase the reliability of self-reported concussions.

Adrenal lesions in patients with extra-adrenal malignancy - benign or malignant?

BACKGROUND: Adrenal lesions in patients with extra-adrenal malignancy can be part of disseminated tumour disease, but may also be incidental, benign finding. Strict characterisation is therefore crucial, and may have profound effects on patient management. PURPOSE: To prospectively characterise and follow-up adrenal lesions in patients with extra-adrenal malignancy, stratified into those with past or concurrent malignancy, with or without metastases. MATERIAL AND METHODS: All incidentally detected adrenal lesions identified at cross-sectional imaging during 18 months in a defined geographical region were prospectively reported. All adult oncologic patients with adrenal lesions were subjected to biochemical work-up and dedicated adrenal imaging for lesion characterisation, including a two year follow-up. RESULTS: Benign adrenal lesions were found in 74% (29/39) of patients who had a history of extra-adrenal malignancy, in 53% (57/108) of those with concurrent extra-adrenal malignancy without metastatic disease and in 25% (27/109) in those with signs of metastatic disease. CONCLUSION: An adrenal lesion occurring in a patient with past malignancy has a high likelihood of representing a benign lesion, and even in patients with present signs of malignant disease at least one fourth to one half of such lesions are benign. Dedicated adrenal imaging including computed tomography attenuation measurements with wash-out characteristics, in addition to biochemical testing for adrenal dysfunction, is highly recommended in these cases, especially in patients without any other signs of metastatic spread.

Adrenal lesion frequency: A prospective, cross-sectional CT study in a defined region, including systematic re-evaluation.

BACKGROUND: incidentally detected adrenal lesions have become a growing clinical problem. PURPOSE: to prospectively estimate and validate the prevalence of incidentally detected adrenal lesions (adrenal incidentaloma) in patients with or without malignant disease undergoing CT. MATERIAL AND METHODS: during 18 months all adult patients with incidentally discovered adrenal lesions detected at CT were prospectively reported from the radiology departments of all hospitals in Western Sweden (1.66 million inhabitants). Frequencies of adrenal lesions initially reported at CT and at a systematic re-evaluation were compared. The interobserver variation in blindly assessing adrenal lesions was also analyzed. RESULTS: adrenal lesions were reported and verified in 339 patients (193 females; mean age 69 years, range 30-94 years). Mean lesion size was 25.8 mm (range 8-94 mm). The mean frequency of originally reported adrenal lesions was 0.9% (range 0-2.4% between hospitals). The systematic re-evaluation of 3801 randomly selected cases showed a mean frequency of 4.5% (range 1.8-7.1% between hospitals). The re-evaluation revealed 177 cases with adrenal lesions, 30% of these were submitted by the local radiologist in accordance with the study design, 23% were described in the local radiology report but not submitted to the study center, while 47% were neither locally reported nor submitted. CONCLUSION: adrenal lesions are under-reported in clinical practice. Prevalence figures for adrenal incidentalomas should therefore be interpreted with caution, especially in multi-center settings.

Lack of regulation of 11beta-hydroxysteroid dehydrogenase type 1 during short-term manipulation of GH in patients with hypopituitarism.

OBJECTIVE: Evidence from long-term clinical studies measuring urinary steroid ratios, and from in vitro studies, suggests that GH administered for longer than 2 months down-regulates 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11beta-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer. DESIGN: Observational studies of GH withdrawal and reintroduction in patients with hypopituitarism. METHODS: Twelve men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were reintroduced for another 3 weeks. We measured cortisol kinetics during 9,11,12,12-(2)H(4)-cortisol (d4-cortisol) infusion, urinary cortisol/cortisone metabolite ratios, liver 11beta-HSD1 by appearance of plasma cortisol after oral cortisone, and 11beta-HSD1 mRNA levels in subcutaneous adipose biopsies. RESULTS: GH withdrawal and reintroduction had no effect on 9,12,12-[(2)H](3)-cortisol (d3-cortisol) appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11beta-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 min after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5alpha-reduced cortisol metabolites. CONCLUSIONS: In this setting, GH did not regulate 11beta-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11beta-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11beta-HSD1 activity, although dose adjustment may be required in the longer term.

The liquorice effect on the RAAS differs between the genders.

OBJECTIVE: Liquorice-induced increase in blood pressure (BP) is more profound in subjects with essential hypertension (HT) than in healthy individuals. Liquorice induces pseudohyperaldosteronism by inhibiting the 11beta-hydroxysteroid dehydrogenase type 2 and is also known to inhibit the renin-angiotensin-aldosterone system (RAAS). We explored the difference in response in BP, considering the RAAS and the genders. DESIGN: Patients with HT (eight men and three women, mean age 40.7 years) and healthy controls (13 men and 12 women, mean age 31.2 years) consumed 100 g of liquorice (150 mg glycyrrhetinic acid) daily for 4 weeks. METHODS: Blood, urine samples and BP were evaluated before and after 4 weeks of liquorice consumption and 4 weeks after cessation of liquorice consumption. RESULTS: The relative change in serum aldosterone levels differed between the genders (p < 0.02), men being more responsive than women, but not between patients with HT and healthy subjects. CONCLUSION: The liquorice-induced inhibition of aldosterone secretion differs between the genders and is not influenced by the BP levels. This difference between the genders has not been exposed before.

GH effect on enzyme activity of 11betaHSD in abdominal obesity is dependent on treatment duration.

OBJECTIVE: In the past years the interaction of GH and 11beta hydroxysteroid dehydrogenase (11betaHSD) in the pathogenesis of central obesity has been suggested. DESIGN: We studied the effects of 9 months of GH treatment on 11betaHSD activity and its relationship with body composition and insulin sensitivity in 30 men with abdominal obesity, aged 48-66 years, in a randomised, double-blind, placebo-controlled trial. METHODS: Urinary steroid profile was used to estimate 11betaHSD type 1 and 2 (11betaHSD1 and 11betaHSD2) activities. Abdominal s.c. and visceral adipose tissues were measured using computed tomography. Glucose disposal rate (GDR) obtained during a euglycaemic-hyperinsulinaemic glucose clamp was used to assess insulin sensitivity. RESULTS: In the GH-treated group the 11betaHSD1 activity decreased transiently after 6 weeks (P < 0.01) whereas 11betaHSD2 increased after 9 months of treatment (P < 0.05). Between 6 weeks and 9 months, GDR increased and visceral fat mass decreased. Changes in 11betaHSD1 correlated with changes in visceral fat mass between baseline and 6 weeks. There were no significant correlations between 11betaHSD1 and 11betaHSD 2 and changes in GDR. DISCUSSION: The study demonstrates that short- and long-term GH treatment has different effects on 11betaHSD1 and 11betaHSD2 activity. Moreover, the data do not support that long-term metabolic effects of GH are mediated through its action on 11betaHSD.