Quality of life in primary aldosteronism: A prospective observational study.

BACKGROUND: Previous studies suggested that patients affected by primary aldosteronism (PA) have impaired quality of life (QOL) compared to the general population, but a direct comparison with patients affected by essential hypertension (EH) has never been performed. The aim of the study was to compare the QOL of patients affected by PA to the QOL of patients affected by EH. MATERIAL AND METHODS: We designed a prospective observational study comparing the QOL of patients with PA and carefully matched patients with EH before and after treatment. We recruited 70 patients with PA and 70 patients with EH, matched for age, sex, blood pressure levels and intensity of antihypertensive treatment. We assessed QOL at baseline and after specific treatment for PA or after optimization of medical therapy for patients with EH. RESULTS: Patients with PA displayed impaired QOL compared with the general healthy population, but similar to patients with EH. Both laparoscopic adrenalectomy and treatment with mineralocorticoid receptor antagonist allowed an improvement of QOL in patients with PA, that was more pronounced after surgical treatment. Optimization of blood pressure control by implementation of antihypertensive treatment (without MR antagonists) allowed a minimal improvement in only one of eight domains in patients with EH. CONCLUSIONS: Patients with PA have impaired QOL, which is likely caused by uncontrolled hypertension and the effects of intensive antihypertensive treatment. Surgical and medical treatment of PA allows a significant improvement of QOL, by amelioration of blood pressure control and, after surgical treatment, by reduction of antihypertensive treatment.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

Psychological Symptoms and Well-Being After Treatment for Primary Aldosteronism.

Primary aldosteronism (PA) is an increasingly identified cause of secondary hypertension. PA can be caused by an aldosterone-producing adenoma or by bilateral adrenal hyperplasia, generally treated by adrenalectomy or mineralocorticoid receptor antagonists, respectively. Recent studies suggest that PA is associated with more psychological symptoms and lower levels of well-being. The purpose of this study was to investigate the associations between subtype of PA and psychological symptoms and well-being after specific treatment. We analyzed the outcomes of the Mental Health Continuum-Short Form and the Symptom Checklist in 160 patients (mean age 57 years; 74.3% males) with PA, comparing the scores for psychological symptoms and well-being between both subtypes of PA. Additionally, we performed subgroup analyses based on gender, age, time since initiation of treatment, and co-morbidity. Moreover, we compared the results with published norm scores. Mean follow-up after adrenalectomy or start of medication was four years and two months. Depressive symptoms, anxiety and obsessive-compulsive thoughts and well-being did not differ between subtypes of PA. Subgroup analysis did not reveal any differences, except for women with bilateral adrenal hyperplasia who scored higher on the anxiety subscale than women after adrenalectomy. Compared to the general population, patients with treated PA reported more psychological symptoms. In contrast, well-being did not differ significantly from norm scores. Subtype and treatment of PA were no important determinants of psychological symptoms and well-being on the long-term. We suggest that physicians should be alert for psychological symptoms, as these were more frequently present in patients with PA.

Health-Related Quality of Life and Mental Health in Primary Aldosteronism: A Systematic Review.

The aim of this review was to determine the impact of primary aldosteronism on health-related quality of life (HRQoL) and mental health. We performed a systematic literature search up to July 2017 in six electronic databases. First, we screened the articles derived from this search based on title and abstract. Second, the selected studies were systematically reviewed and checked for our predefined inclusion criteria. The search yielded 753 articles, of which 15 studies met our inclusion criteria. Untreated patients with primary aldosteronism showed an impaired physical and mental HRQoL as compared to the general population. Multiple domains of HRQoL were affected. This applied to patients with both an aldosterone-producing adenoma and bilateral adrenal hyperplasia. Adrenalectomy improves HRQoL. Conflicting results have been reported on the extent of this improvement, the improvement after initiation of medical treatment, and whether there is a difference in HRQoL after both treatments. Similarly, psychopathological symptoms of anxiety, demoralization, stress, depression and nervousness were more frequently reported in untreated patients with primary aldosteronism than in the general population and patients with hypertension. Also an impaired sleep quality has been reported. Improvement of these symptoms was observed after treatment with both adrenalectomy and mineralocorticoid receptor antagonists. This review shows that HRQoL is impaired and psychopathology is more frequently reported in patients with primary aldosteronism. This seems to be at least partly reversible after treatment but the extent of improvement remains unknown. To assess HRQoL in these patients more precisely a primary aldosteronism-specific HRQoL questionnaire is required.

Mood Disorders in Uncontrolled Hypertension Despite Multiple Anti-Hypertensive Medications: Searching for a Link.

INTRODUCTION: Resistant hypertension is a clinical condition in which blood pressure (BP) control is not achieved under a pharmacological therapy including a diuretic and at least two additional antihypertensive drug classes. AIM: To discuss an unusual presentation of uncontrolled hypertension despite multiple anti-hypertensive medications. METHODS AND RESULTS: A 46-year-old woman presented with resistant hypertension (HT) and with a long history of polydipsia, polyuria, weight loss and psychiatric symptoms (sudden onset of personality disorder with free anxiety, negativism and asthenia) unsuccessfully treated with antidepressant drugs. Tests for secondary HT showed a marked increase of serum renin and aldosterone both in clinostatic (342 pg/ml and 907 pmol/l, respectively) and orthostatic posture (351 pg/ml and 2845 pmol/l, respectively), hypokalemia (2.9 mmol/l) and macroalbuminuria (431 mg/day). Diagnostic examinations also revealed a focal stenosis of approximately 70 % of the proximal right renal artery with post-stenotic dilation. After percutaneous balloon angioplasty and stent implantation, BP was normalized with 5 mg/day amlodipine and psychiatric symptoms suddenly disappeared. CONCLUSIONS: Psychopathological symptoms are rare at the onset of hyperaldosteronism, and their aetiology is not well defined. A proper diagnostic and therapeutic process is mandatory in order to get the recommended therapeutic targets in short-midterm improving long-term prognosis. We also suggest not considering depressed or treat with antidepressant agents a young hypertensive subject with uncontrolled hypertension despite multiple anti-hypertensive medications without having ruled out a secondary form of hypertension.

Quality of life in patients with primary aldosteronism: gender differences in untreated and long-term treated patients and associations with treatment and aldosterone.

Psychopathological symptoms in patients with primary aldosteronism (PA) have been reported. In a cross-sectional design the self-reported physical and mental condition among patients with PA of the German Conn's Registry differently treated during the course of the disease were analysed. 27 patients were investigated before initiation of specific therapy (U), 56 patients were on chronic mineralocorticoid antagonist treatment (MRA) and 49 patients had undergone adrenalectomy (ADX). Patient's quality of life was analysed with the SF-12 for a Physical (PCS) and a Mental Component (MCS). Statistically significant lower scores for PCS were found for female PA patients treated with MRA in comparison to ADX patients and the German reference population (36.4 ± 11.1 vs. 49.1 ± 10.9 (p = 0.024) vs. 47.9 ± 9.7 (p = 0.001)), respectively. Concerning MCS, untreated female patients scored significantly lower (36.5 ± 7.4) than females from the German population (51.3 ± 8.4, p = 0.000). Furthermore, untreated females appear to differ significantly from MRA and ADX females, scoring the lowest reading (U vs. MRA: p = 0.029; U vs. ADX: p = 0.005). Significant correlations were found between plasma aldosterone (r = -0.819, p = 0.013) and the MCS and between plasma renin concentration and MCS (r = -0.938, p = 0.001) in female MRA patients. In summary, PA patients report a worse physical and mental condition than the one reported for the German reference population. Untreated and mineralocorticoid antagonist treated patients report the lowest readings. Females were found to be more impaired than males in QoL. MRA treatment seems to affect the MCS of female patients.

Psychopathological symptoms in patients with primary hyperaldosteronism--possible pathways.

A close comorbidity between endocrine diseases and psychopathological symptoms has been described in the literature. Until now only a few studies have reported about an increased anxiety and depressive symptoms in patients with primary hyperaldosteronism (PHA). The exact pathways of psychiatric comorbidities have not been totally clarified yet, although the renin-angiotensin-aldosterone-system has gained more attention in research on anxiety and depression. There are several structures and factors, which could mediate anxiety or a depressive symptomatology. Additionally a possible influence of the standardised treatment with a mineralocorticoidreceptor (MR) antagonist or adrenalectomy should be investigated as they have been shown to affect mood. Psychiatric comorbidities are not only an additional burden in these patients, but as depression and anxiety are additional risk factors in patients with cardiovascular diseases. Possible pathomechanisms in the relation between PHA and psychiatric symptoms should be more closely investigated. For the clinical practice a regular screening for psychiatric comorbidities and an adequate treatment are required.

Quality of life in patients with bilateral primary aldosteronism before and during treatment with spironolactone and/or amiloride, including a comparison with our previously published results in those with unilateral disease treated surgically.

BACKGROUND: Measurement of quality of life (QOL) allows assessment of the impact of a disease or treatment from the patient's perspective, including need for social, emotional, or physical support. We are not aware of any published QOL assessment in patients with bilateral primary aldosteronism (BPA), before or after commencing medical treatment (MT) with spironolactone and/or amiloride. METHODS: Using the internationally validated Medical Outcomes Study Short Form 36 General Health Survey (SF-36), QOL was assessed in 21 patients with BPA at baseline (time of diagnosis), and at 3 and 6 months after commencing MT. QOL scores at baseline were compared with published normative values for the Australian population. The results of the current study were compared with those from our previous study showing reduced QOL in patients with unilateral primary aldosteronism (UPA) with normalization by 3 months after unilateral laparoscopic adrenalectomy. RESULTS: Compared with the general population, patients with BPA showed significant reduction (P < 0.01) in four QOL domains--physical functioning, role limitations due to physical health problems, general health perceptions, and vitality. After 6 months (but not 3 months) of MT, statistically significant (P < 0.05) improvements were detected in all these domains of QOL. When compared with patients with UPA treated surgically, scores were significantly (P < 0.05) lower at 3 months for five domains (role limitations due to physical health, general health, role limitations due to emotional health, mental health, and vitality) but at 6 months for only one domain (role limitations due to emotional problems). CONCLUSION: Subnormal QOL scores were improved after 6 months of MT in 21 patients with BPA, but more slowly and to a lesser degree than surgical treatment had previously been shown to improve QOL scores in 22 patients with UPA.

Psychological assessment of primary aldosteronism: a controlled study.

OBJECTIVE: Our objective was to investigate psychological correlates in a population with primary aldosteronism (PA) using methods found to be sensitive and reliable in psychosomatic research. METHODS: Twenty-three PA patients (12 male, 11 female; mean age 50 ± 9 yr) were compared with 23 patients with essential hypertension (EH) (15 male, eight female; mean age 47 ± 8 yr) and 23 matched normotensive subjects. A modified version of the Structural Clinical Interview for DSM-IV, a shortened version of the structured interview for the Diagnostic Criteria for Psychosomatic Research, and two self-rating questionnaires, the Psychosocial Index and the Symptom Questionnaire, were administered. RESULTS: Twelve of 23 patients with PA (52.2%) suffered from an anxiety disorder compared with four of 23 with EH (17.4%) and one control (4.3%) (P < 0.001). Generalized anxiety disorder was more frequent in PA than in EH patients and controls (P < 0.05). As assessed by Diagnostic Criteria for Psychosomatic Research, irritable mood was more frequent in PA and EH compared with controls (P < 0.05) but did not differentiate PA from EH. According to Psychosocial Index results, patients with PA had higher levels of stress (P < 0.01) and psychological distress (P < 0.01) and lower level of well-being (P < 0.05) than controls. Compared with EH patients, PA patients had higher scores in stress subscale (P < 0.05). The Symptom Questionnaire showed higher levels of anxiety (P < 0.01), depression (P < 0.01) and somatization (P < 0.01) and lower physical well-being (P < 0.05) in PA than controls. CONCLUSION: A role of mineralocorticoid regulatory mechanisms in clinical situations concerned with anxiety and stress is suggested.

Psychological aspects of primary aldosteronism.

BACKGROUND: Except for 3 case reports of Conn's syndrome presenting as depression, psychosocial factors have not been explored in primary aldosteronism. We investigated psychological correlates in primary aldosteronism using methods that were found to be sensitive and reliable in psychosomatic research. METHOD: Ten consecutive newly diagnosed patients with primary aldosteronism were studied: 5 males/5 females; mean age (+/-SD) 45.5 +/- 6.6 years, age range 34-54 years; 4 with an aldosterone-producing adenoma and 6 with idiopathic aldosteronism; systolic/diastolic blood pressure 189 +/- 20/111 +/- 7.7 mm Hg; upright plasma aldosterone 40.0 +/- 18.3 ng/dl; upright plasma renin activity (PRA) 0.2 +/- 0.1 ng/ml/h; aldosterone/PRA ratio 229.2 +/- 191.0; serum K(+) 3.5 +/- 0.5 mmol/l. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for eliciting psychiatric diagnoses, and a shortened version of the structured interview for subclinical psychological syndromes, the Diagnostic Criteria for Psychosomatic Research (DCPR), were administered. RESULTS: Seven patients (2 with aldosterone-producing adenoma and 5 with idiopathic hyperaldosteronism) received both DSM-IV and DCPR diagnoses, while 3 had neither. As to DSM-IV, generalized anxiety disorder was detected in 6 cases (in 1 it was associated with panic disorder and in 1 with major depression) and obsessive-compulsive disorder in 1. The most frequent DCPR cluster was demoralization (5 cases), while persistent somatization occurred in 2 cases (associated with demoralization in 1) and irritable mood in 1. CONCLUSIONS: The occurrence of anxiety disorders in patients with primary aldosteronism was much higher than that found in the general population and in primary care. Since an association between hyperaldosteronism and anxiety has also been suggested in previous animal studies, it seems worthwhile to gain further knowledge on clinical aspects by larger population studies.

Number impairments following hypokalemia: a case study.

A case study is reported of a 55 year old female (B.B.) who complained of significant difficulty manipulating and remembering numbers. Twenty-four years prior to the present complaint, B.B. had been hospitalized for idiopathic hypokalemia and secondary hyperaldosteronism. The present study examined the nature and extent of B.B.'s cognitive impairments. On standardized and experimental tests of intelligence and general cognitive ability, she scored quite well. However, she demonstrated significant impairments in digit span, number processing and calculation, memory for biographical details involving numbers and general number knowledge. The implications of such a constellation of impairments are discussed from both cognitive and neurological perspectives.