Paal Methlie

• MD, PhD
• Consultant at Haukeland University Hospital

Primary aldosteronism (PA) affects 5–20% of the hypertensive population and is associated with increased cardiovascular and metabolic risks compared with primary hypertension. PA is significantly underdiagnosed partly due to our inability to capture the pulsatile variability of aldosterone over 24 hours in clinical settings. To gain insight into st...

Cortisol is released upon activation of the hypothalamic–pituitary–adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based...

Objective Previous studies indicate a possible bidirectional stimulatory relationship between parathyroid hormone (PTH) and adrenocortical hormones, but the pattern of adrenocortical secretion in hypoparathyroidism is unknown. We aimed to characterize the adrenocortical secretion in patients with postsurgical hypoparathyroidism, and whether continu...

Background: Salivary cortisol (sa-cortisol) and salivary cortisone (sa-cortisone) correlate well with serum cortisol (s-cortisol) but validated reference ranges for healthy individuals are lacking. Objective: To establish cutoff levels for sa-cortisol and cortisone following cosyntropin testing, and assess their diagnostic utility in adrenal ins...

Purpose Thyroid eye disease (TED) is the most common extrathyroidal manifestation of Graves disease. Patients may be severely affected with eyelid retraction, exophthalmos, diplopia, pain, and threatened vision. Autoantibodies against thyroid-stimulating hormone receptor and insulin-like growth factor 1 receptor have shown associations with pathoph...

Objective Increased prevalence of cardiovascular disease has been reported in autoimmune Addison’s disease (AAD), but pathomechanisms are poorly understood. Design Cross-sectional study. Methods We compared serum levels of 177 cardiovascular and inflammatory biomarkers in 43 patients with AAD at > 18-hour glucocorticoid withdrawal and 43 matched...

Disclosure: M.A. Grytaas: None. P. Methlie: None. I. Marinelli: None. E. Zavala: None. M. Øksnes: None. T. Upton: None. K. Simunkova: None. D.A. Vassiliadi: None. K. Løvås: None. S. Bensing: None. I. Botusan: None. K. Berinder: None. G.M. Russell: None. G. Ueland: None. O. Kampe: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. B...

Disclosure: Å.B. Sævik: None. G. Ueland: None. A. Åkerman: None. P. Methlie: None. M. Quinkler: None. A. Jørgensen: None. C. Höybye: None. A.W. Debowska: None. B. Nedrebø: None. A. Dahle: None. S. Carlsen: None. A.E. Tomkowicz: None. S.T. Sollid: None. I. Nermoen: None. K. Grønning: None. P.M. Dahlqvist: None. G. Grimnes: None. J. Skov: None. T. Fi...

Disclosure: I. Botusan: None. K. Berinder: None. P. Methlie: None. T. Upton: None. E. Zavala: None. K. Simunkova: None. D.A. Vassiliadi: None. I. Marinelli: None. G.M. Russell: None. M.A. Grytaas: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. O. Kampe: None. M. Oksnes: None. S. Bensing: None. Background: The autoimmune attack...

Disclosure: T. Upton: None. E. Zavala: None. P. Methlie: None. M. Oksnes: None. M.A. Grytaas: None. K. Simunkova: None. S. Bensing: None. I. Botusan: None. K. Berinder: None. D.A. Vassiliadi: None. O. Kampe: None. S. Tsagarakis: None. E.S. Husebye: None. G.M. Russell: None. S.L. Lightman: None. Background: Rhythms are intrinsic to endocrine systems...

Hovedbudskap Hos fedmepasienter synes metabolsk syndrom å være en mulig risikofaktor for utvikling av alvorlig periodontitt I et utvalg med få pasienter var det ikke mulig å påvise en negativ effekt ved bruk av kalsiumantagonister på periodontal status Tidlig diagnostisering av periodontitt synes å være særlig viktig ved behandling av fedmepasiente...

Objective Atypical Graves disease (GD) is a common complication in multiple sclerosis (MS) patients treated with alemtuzumab. We present epidemiological, clinical, and biochemical characteristics of alemtuzumab-induced GD. Methods Retrospective follow-up study of MS patients treated with alemtuzumab from 2014 to 2020, including clinical course of...

Objective To map inflammatory biomarkers in patients with autonomous cortisol secretion (ACS), and overt Cushing syndrome (CS). Method Observational study including serum from prospectively included patients with ACS (n = 63), adrenal CS (n = 2), pituitary CS (n = 8), and healthy subjects (n = 120). Serum samples were analysed for 92 inflammatory...

Background Epidemiological studies support an association between obesity, metabolic syndrome (MetS), and periodontitis. Still, understanding of the effects of low-grade inflammation in obese subjects on periodontitis and influence of MetS remains incomplete. The aims of this cross-sectional study were to explore the association between obesity rel...

Rhythms are intrinsic to endocrine systems, and disruption of these hormone oscillations occurs at very early stages of the disease. Because adrenal hormones are secreted with both circadian and ultradian periods, conventional single-time point measurements provide limited information about rhythmicity and, crucially, do not provide information dur...

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI due to the non-physiological patte...

Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison's disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 p...

Pulsatile endogenous cortisol secretion is critical for physiological glucocorticoid gene signaling. Conventional glucocorticoid replacement therapy does not mimic endogenous cortisol pulsing in primary adrenal insufficiency. In an open-labelled, two-week, non randomized cross-over study of five patients with adrenal insufficiency (Addison’s diseas...

Objective: To define liquid chromatography tandem mass spectrometry (LC-MS/MS)-based cutoff levels and panels of steroid hormones, to improve diagnosis of nonclassic congenital adrenal hyperplasia (NCCAH) and other partial enzyme defects in the adrenals. Design: Prospective cohort analysis. Setting: University hospital-based tertiary endocrine...

Feminizing estrogen-secreting adrenocortical carcinomas (ACCs) are exceedingly rare and carry a poor prognosis. The most common presenting trait is gynecomastia, but enlarged breasts are also a frequent clinical finding in healthy men. Biochemical evaluation may be challenging. As such, there is a high risk of delayed diagnosis and treatment opport...

Objective: Deciding the optimal doses of glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD) is impeded by the lack of reliable biomarkers. This frequently results in over-treatment, with alarming and persistent side-effects, or under-replacement, which could be fatal. There is a need to think new in the quest for robust...

Background Diagnosing Cushing syndrome (CS) can be challenging. 24-hour urine free cortisol (UFC) measurement is considered gold standard. This is a laborious test, dependent on correct urine collection. Late-night salivary cortisol is easier, and used as a screening test for CS in adults, but has not been validated for use in children. Objective...

Background No reliable biomarkers exist to guide glucocorticoid (GC) replacement treatment in autoimmune Addison’s disease (AAD), leading to overtreatment with alarming and persistent side-effects or undertreatment, which could be fatal. Objective To explore changes in gene expression following different GC replacement doses as a means of identify...

Objective: Autonomous cortisol secretion (ACS) is a condition with ACTH-independent cortisol overproduction from adrenal incidentalomas (AI) or adrenal hyperplasia. The hypercortisolism is often mild, and most patients lack typical clinical features of overt Cushing's syndrome (CS). ACS is not well defined and diagnostic tests lack validation. Me...

Context Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison’s disease (AAD) produce corticosteroids even years after diagnosis. Objective Determine frequencies and clinical features of residual corticosteroid production in patients with AAD. Design Two-staged, cross-sectional clinical study in 17 center...

Background: Underlying causes of adrenal insufficiency include congenital adrenal hyperplasia (CAH) and autoimmune adrenocortical destruction leading to autoimmune Addison's disease (AAD). Here, we report a patient with a homozygous stop-gain mutation in 3β-hydroxysteroid dehydrogenase type 2 (3βHSD2), in addition to impaired steroidogenesis due to...

Context Autonomous cortisol secretion (ACS) can be uni- or bilateral irrespectively of the presence of an adrenal tumor. A reliable method to discriminate between uni- and bilateral ACS is lacking. Objective Evaluate the use of adrenal venous sampling (AVS) to distinguish between uni- and bilateral ACS. Design and Methods Prospective study of AVS...

Background The cosyntropin test is used to diagnose adrenal insufficiency (AI) and non-classical congenital adrenal hyperplasia (NCCAH). Current cutoffs for cortisol and 17-hydroxyprogesterone (17-OHP) are derived from non-standardized immunoassays. Liquid chromatography tandem mass spectrometry (LCMSMS) offers direct measurement of steroids, promp...

Objectives: The overnight dexamethasone (DXM)-suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative...

Pituitary and adrenal gland assessment, is one of the most important aspects of the management of a pituitary and adrenal adenoma. Clinical practice varies widely with regard to assessment of pituitary and adrenal status pre- and post-operative. Pre-operative testing includes dynamic testing to assess function which is not practical in the immediat...

Background: 1-mg overnight dexamethasone-suppression test (DST) is commonly used to screen for hypercortisolism. Sensitivity is high (95%), but specificity is low (80%), leading to false positive results. Identifying individuals with abnormal dexamethasone absorption or metabolism could enhance diagnostic accuracy. Aim: Use serum dexamethasone (s-D...

Objective: Many patients with primary adrenal insufficiency (Addison's disease) take extra doses of glucocorticoids during stressful events, but a benefit has not been demonstrated in controlled trials. Here, we investigated the effects of a pre-exercise hydrocortisone dose on cardiorespiratory, hormonal, and metabolic parameters in response to sh...

Many patients with primary adrenal insufficiency (Addison’s disease) take extra doses of glucocorticoids before or during stressful events, but benefit has not been demonstrated. We aimed to test the effect of an extra dose of glucocorticoids on cardiorespiratory, hormonal and metabolic parameters in response to physical activity in a randomised pl...

ContextConventional glucocorticoid replacement therapy in patients with Addison's disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. The diurnal cortisol profile can likely be restored by continuous subcutaneous hydrocortisone infusion (CSHI).Objective The aim of this study was to compare circ...

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is suggested as a pathophysiological factor in bipolar disorder and schizophrenia. Increased clearance of cortisol was recently indicated as a component in the HPA axis hyperdrive. The aim of the present study was to test the model of increased cortisol metabolism in a new replication sam...

Background: Conventional glucocorticoid replacement therapy in patients with Addison’s disease (AD) is unphysiological with possible adverse effects on mortality, morbidity and quality of life. Physiological amounts of glucocorticoids are required for normal GH production and release and a chronically raised cortisol level, suppresses the secretion...

About 95% of the cases of congenital adrenal hyperplasia (CAH) are caused by mutations in CYP21A2 encoding 21-hydroxylase (21OH). Recently we reported four novel CYP21A2 variants in the Norwegian population of patients with CAH, of which p.L388R and p.E140K were associated with salt-wasting (SW), p.P45L with simple virilising (SV) and p.V211M + p.V...

Context: Conventional glucocorticoid replacement therapy fails to mimic the physiological cortisol rhythm, which may have implications for morbidity and mortality in patients with Addison's disease. Objective: The objective of the study was to compare the effects of continuous sc hydrocortisone infusion (CSHI) with conventional oral hydrocortiso...

Objectives: Increased intra-adipose cortisol is thought to promote obesity, but few human studies have investigated intra-adipose glucocorticoid hormones and none have demonstrated prospective changes with fat loss. Design and methods: Subcutaneous adipose tissue (SAT) was obtained from obese subjects before and 1-year after surgery-induced fat...

Liquid chromatography-mass spectrometry (LC-MS/MS) offers superior analytical specificity compared to immunoassays, but is not available in many regions and hospital due to expensive instrumentation and tedious sample preparation. Thus, we developed an automated, high-throughput LC-MS/MS assay for simultaneous quantification of 10 endogenous and sy...

Failure to mirror the diurnal cortisol profile could contribute to the impaired subjective health status in Addison's disease (AD). Some patients report benefit from the use of various nutritional compounds. The objective of this study was to investigate the impact of licorice and grapefruit juice (GFJ) on the absorption and metabolism of cortisone...

The hypothalamic-pituitary-adrenal (HPA) axis seems dysregulated and part of the pathophysiology in bipolar disorder and schizophrenia, but the underlying mechanisms are unknown. Recent evidence indicates that systemic cortisol metabolism influences blood cortisol levels and HPA axis functioning. Our objective was to estimate systemic cortisol meta...

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is documented in bipolar disorder and schizophrenia, but the mechanism is unclear; recently, increased activity of cortisol metabolizing enzymes was indicated in these disorders. We investigated whether five genes involved in cortisol metabolism were associated with altered activity of co...

Because we found higher serum 25-hydroxyvitamin D (25(OH)D) levels among smokers than among non-smokers with analyses using an electrochemiluminescence immunoassay (ECLIA) from Roche, the purpose of the present study was to examine whether this difference between smokers and non-smokers was maintained using other serum 25(OH)D assays. A cross-secti...

Limited knowledge is available on to what extent doctors and nurses know the correct use of various inhalation devices. We wanted to examine this skill among 25 doctors and 25 nurses randomly selected from the departments of pulmonology, internal medicine and surgery at a university hospital. Two technicians asked them to demonstrate the correct us...