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Context Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis. Objective To determine frequencies and clinical features of residual corticosteroid production in patients with AAD. Design Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography–tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test. Results Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = –0.487; P < 0.001). Conclusion In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.

The most consistent biochemical finding of untreated AAD was low sodium independent of the degree of glucocorticoid deficiency. Half of the patients had elevated TSH levels. Only a minority presented with marked hyperkalaemia or other nonhormonal abnormalities. Thus, unexplained low sodium and/or elevated TSH should prompt consideration of an undiagnosed AAD, and on clinical suspicion bring about assay of cortisol and ACTH. Presence of 21-hydroxylase autoantibodies confirms autoimmune aetiology. Anticipating additional abnormalities in routine blood tests may delay diagnosis.

ObjectiveRathke's cleft cysts are benign, embryological remnants in the pituitary gland. The majority of them are small and asymptomatic but a few may become large, and cause mass effects, pituitary hormone deficiencies and visual impairment. Recommendations for the follow‐up of Rathke's cleft cysts vary since data on the natural history are sparse.Patients and DesignData at diagnosis and at 1, 5 and 10 years for patients with a Rathke's cleft cyst (434 at diagnosis, 317 females) were retrieved from the Swedish Pituitary Registry. Cysts ≤3 mm in diameter were excluded from the study.MeasurementsData included demographics, cyst size, pituitary function, visual defects and surgery.ResultsThe mean age at diagnosis was 45 years. In patients with cysts <10 mm in diameter (n = 204) 2.9% had pituitary hormone deficiencies and 2% had visual field impairments. Cyst size did not progress during the 5 years. Cysts with a diameter of ≥10 mm that were not operated (n = 174) decreased in size over the years (p < .01). Pituitary hormone deficiencies and visual impairments were more frequent (18% and 5.7%, respectively) but were stable over time. Transphenoidal surgery was performed in 56 patients of whom 51 underwent surgery before the 1‐year follow‐up. The mean cyst diameter at diagnosis was 18 mm (range: 9─30 mm), 36% had pituitary hormone deficiency, 45% had visual field defects and 20% had impaired visual acuity. One year after surgery 60% had no cyst remnants, 50% had a pituitary deficiency, 26% had visual field defects and 12% had impaired visual acuity. No major changes were observed after 5 years. Twelve of the operated patients had a follow‐up at 10 years, in eight the cyst remnants or recurrences increased in size over time (p < .05).ConclusionsRathke's cleft cysts with a size less than 10 mm rarely grow and our results indicate that radiological follow‐up can be restricted to 5 years. In contrast, progression of postoperative remnants or recurrent cysts is more likely and require long‐term follow‐up.

Objective Autoimmune Addison’s disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. The aim of this study was to investigate the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. Design and methods Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and co-morbidities, focusing on the pre-vaccine phase. Results Among the 615 included patients with AAD, COVID-19 was reported by 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients 85% increased their glucocorticoid dosage during sickness. Older age (p=0.002) and hypertension (p=0.014) were associated with an increased risk of hospital care while younger age (p&lt;0.001) and less worry about infection (p=0.030) correlated with a higher risk of COVID-19. Conclusions In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one fifth of the cohort contracted COVID-19 few patients required hospital care. A majority of the patients applied general recommended sick-rules despite reporting limited communication with healthcare during the pandemic.

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Background: Patients with Cushing´s disease (CD) in remission have increased mortality compared to the general population. To date, large cohort studies, performed to assess long-term comorbidities in patients with CD, are lacking. Objective: To study the incidence of cardiovascular disease, sepsis, fractures and cancer in an unselected nationwide cohort of patients with CD. Methods: Patients with CD, diagnosed between 1987 and 2013, were identified in the Swedish National Patient Registry. Medical records were systematically reviewed to verify the diagnosis and remission status. Standardized incidence ratios (SIRs) for comorbidities after CD was diagnosed, with 95% confidence intervals (CI), were calculated by using the Swedish general population as the reference. Patients: A total of 502 patients had confirmed diagnosis of CD. Of these, 419 (83%) patients [325 (78%) women] were in remission at the last follow-up, and thereby eligible for the analysis. The mean±SD age at diagnosis was 41±15 years and median (interquartile range) time in remission was 10 years (4-21). Out of 419 patients in remission, 315 (75%) had been treated with pituitary surgery, 116 (28%) with radiotherapy and 102 (25%) with bilateral adrenalectomy. Results: SIR in patients in remission was 2.6 (1.9-3.4) for stroke, 1.8 (1.1-2.6) for myocardial infarction, 4.4 (2.5-7.1) for pulmonary embolism and 3.4 (1.8-6.0) for deep vein thrombosis. The risk for sepsis was markedly elevated with a SIR of 5.8 (3.8-8.4). SIR for all fractures was 1.7 (1.3-2.1), 2.6 (1.4-4.6) for wrist fracture and 1.6 (0.9-2.6) for hip fracture. The overall incidence of cancer was not increased [SIR 1.2 (0.9-1.5)] in comparison with the background population. Conclusions This large nationwide study shows that patients with CD in remission have an increased risk for cardiovascular disease, thromboembolism, fractures and severe infections. The excess morbidity in these patients illustrate the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.

Purpose To describe the clinical presentation and treatment outcomes in a nationwide cohort of patients with giant prolactinomas. Methods Register-based study of patients with giant prolactinomas (serum prolactin [PRL] &gt;1000 µg/L, tumor diameter ≥40 mm) identified in the Swedish Pituitary Register 1991-2018. Results Eighty-four patients (mean age 47 [SD ±16] years, 89% men) were included in the study. At diagnosis, the median PRL was 6305 µg/L (range 1450-253000), the median tumor diameter was 47 mm (range 40-85), 84% of the patients had hypogonadotropic hypogonadism, and 71% visual field defects. All patients were treated with a dopamine agonist (DA) at some point. Twenty-three (27%) received one or more additional therapies, including surgery (n=19), radiotherapy (n=6), other medical treatments (n=4), and chemotherapy (n=2). Ki-67 was ≥10% in 4/14 tumors. At the last follow-up (median 9 years [IQR 4-15]), the median PRL was 12 µg/L (IQR 4-126), and the median tumor diameter was 22 mm (IQR 3-40). Normalized PRL was achieved in 55%, significant tumor reduction in 69%, and combined response (normalized PRL and significant tumor reduction) in 43%. In the primary DA-treated patients (n=79), the reduction in PRL or tumor size after the first year predicted the combined response at the last follow-up (p&lt;0.001 and p=0.012 respectively). Conclusion DAs effectively reduced PRL and tumor size, but approximately one patient out of four needed multimodal treatment. Our results suggest that the response to DA after one year is useful for identifying patients who need more careful monitoring and, in some cases, additional treatment.