International multicenter survey on screening and confirmatory testing in primary aldosteronism.

OBJECTIVE: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. DESIGN: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. RESULTS: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. CONCLUSIONS: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA.

[A woman in her twenties with paranoid delusions] / En kvinne i 20-årene med paranoide vrangforestillinger.

BACKGROUND: A woman in her twenties was admitted to the psychiatric ward with suspected psychosis. Routine tests revealed a rare and potentially dangerous cause of her symptoms. CASE PRESENTATION: The patient had a history of bipolar II disorder, recurrent depressive disorder and hypothyroidism, and presented to the psychiatric emergency department with a one-week history of delusions of persecutory character and increasing insomnia. She had given birth four months prior to admission. Clinical examination was otherwise unremarkable. Bipolar psychosis was considered the most likely diagnosis, and she was started on antipsychotic medication with quetiapine 100 mg × 2. Routine blood tests revealed severe hypothyroidism with thyroid stimulating hormone (TSH) of 151,00 mIU/L and free T4 (fT4) of <3,0 pmol/L (9,5-22,0), and the patient was treated with a high dose of oral levothyroxine. After a few days the patient's psychiatric symptoms resolved completely, and her fT4 increased to 10,8 pmol/L. Upon further questioning, the patient admitted to increasing fatigue and constantly feeling cold over the previous few months, which she attributed to being a parent. She was discharged after a week without any psychiatric symptoms. INTERPRETATION: This case report highlights the importance of a broad somatic differential diagnostic approach to patients with psychosis.

The natural history of 21-hydroxylase autoantibodies in autoimmune Addison's disease.

BACKGROUND: The most common cause of primary adrenal failure (Addison's disease) in the Western world is autoimmunity characterized by autoantibodies against the steroidogenic enzyme 21-hydroxylase (CYP21A2, 21OH). Detection of 21OH-autoantibodies is currently used for aetiological diagnosis, but how levels of 21OH-autoantibodies vary over time is not known. SETTING: Samples from the national Norwegian Addison's Registry and Biobank established in 1996 (n = 711). Multi-parameter modelling of the course of 21OH-autoantibody indices over time. RESULTS: 21OH-autoantibody positivity is remarkably stable, and >90% of the patients are still positive 30 years after diagnosis. Even though the antibody levels decline with disease duration, it is only rarely that this downturn reaches negativity. 21OH-autoantibody indices are affected by age at diagnosis, sex, type of Addison's disease (isolated vs autoimmune polyendocrine syndrome type I or II) and HLA genotype. CONCLUSION: 21OH-autoantibodies are reliable and robust markers for autoimmune Addison's disease, linked to HLA risk genotype. However, a negative test in patients with long disease duration does not exclude autoimmune aetiology.

GWAS for autoimmune Addison's disease identifies multiple risk loci and highlights AIRE in disease susceptibility.

Autoimmune Addison's disease (AAD) is characterized by the autoimmune destruction of the adrenal cortex. Low prevalence and complex inheritance have long hindered successful genetic studies. We here report the first genome-wide association study on AAD, which identifies nine independent risk loci (P < 5 × 10-8). In addition to loci implicated in lymphocyte function and development shared with other autoimmune diseases such as HLA, BACH2, PTPN22 and CTLA4, we associate two protein-coding alterations in Autoimmune Regulator (AIRE) with AAD. The strongest, p.R471C (rs74203920, OR = 3.4 (2.7-4.3), P = 9.0 × 10-25) introduces an additional cysteine residue in the zinc-finger motif of the second PHD domain of the AIRE protein. This unbiased elucidation of the genetic contribution to development of AAD points to the importance of central immunological tolerance, and explains 35-41% of heritability (h2).