Papers by Ulla Feldt-rasmussen
PLOS ONE
Background Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 ... more Background Single-nucleotide polymorphisms (SNPs) of the glucocorticoid receptor (GR) gene NR3C1 have been associated with an altered sensitivity to glucocorticoids, and thus may alter the therapeutic effects of glucocorticoids. We investigated the prevalence of adrenal suppression after treatment with glucocorticoids and evaluated whether GR SNPs were associated with altered risks of adrenal suppression and metabolic disorders in patients with chronic obstructive pulmonary disease (COPD). Methods In an observational prospective cohort study, we recruited 78 patients with severe COPD receiving 5 days glucocorticoid treatment for an exacerbation of COPD. In total, 55% of these patients were also receiving regular inhaled corticosteroids (ICS). Adrenal function was evaluated with a corticotropin test 30 days after the exacerbation. Patients were genotyped for Bcl1, N363S, ER22/23EK, and 9β SNPs. Results The prevalence of adrenal suppression (corticotropin-stimulated plasma-cortisol ≤ ...
The Journal of Clinical Endocrinology & Metabolism
Context Interpretation of thyroid function tests during pregnancy is limited by the generalizabil... more Context Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody–positive participants led to...
European Journal of Endocrinology, 2022
Context Hypothalamic injury often leads to rapid, intractable weight gain causing hypothalamic ob... more Context Hypothalamic injury often leads to rapid, intractable weight gain causing hypothalamic obesity, which is associated with increased risk of cardiovascular and metabolic morbidity and mortality. There are no approved or effective pharmacological treatments for hypothalamic obesity, and conventional lifestyle management remains ineffective. Objective To investigate the safety and efficacy of Tesomet (0.5 mg tesofensine/50 mg metoprolol) in adults with hypothalamic obesity. Methods Twenty-one adults with hypothalamic obesity (16 females) were randomized to Tesomet (0.5 mg/50 mg) or placebo for 24 weeks. Patients also received diet/lifestyle counselling. The primary endpoint was safety; secondary endpoints included measures of body weight, appetite scores, quality of life, and metabolic profile. Results Eighteen patients completed 24 weeks. Consent withdrawal, eligibility, and serious adverse events (SAE) unrelated to treatment resulted in dropouts. One patient experienced a Teso...
Hormones, 2022
Background Autoimmune disease, including autoimmune thyroid disease, with uncharacteristic sympto... more Background Autoimmune disease, including autoimmune thyroid disease, with uncharacteristic symptoms can be due to additional severe disease. We report a life-threatening debut of autoimmune polyglandular syndrome type II (APS II) defined as Addison’s disease combined with autoimmune diabetes and/or thyroid disease. Patient findings A 33-year-old male with newly diagnosed hypothyroidism was referred to a tertiary center due to fatigue and 20-kg rapid weight loss. Malignancy was excluded. After a gastroscopy, he developed Addison’s crisis; he was admitted to our hospital and stabilized. Final diagnoses included Hashimoto’s thyroiditis, Addison’s disease, vitiligo, and pernicious anemia. Whole genome sequencing found no genetic variants associated with component diseases. Human leukocyte antigen typing revealed DR3/DR4 and DQ8/DQ2 heterozygosity associated with APS II. Summary A patient with Hashimoto’s thyroiditis and weight loss presented with Addison’s crisis and was diagnosed with ...
eLife, 2021
Background:Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarke... more Background:Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.Methods:In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.Results:We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA...
The Journal of Clinical Endocrinology & Metabolism, 2020
Context Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack o... more Context Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; ...
Frontiers in Endocrinology, 2017
European Journal of Endocrinology, 2017
Objective Patients receiving long-term glucocorticoid treatment are at risk of developing adrenal... more Objective Patients receiving long-term glucocorticoid treatment are at risk of developing adrenal insufficiency during treatment. We investigated the prevalence of prednisolone-induced adrenal insufficiency in the particular clinical situation where patients receive ongoing low-dose (5 mg/day) prednisolone treatment, a dose by itself too low to cover glucocorticoid needs during stress. Design and methods Cross-sectional study in 42 patients with rheumatoid arthritis (29 women, aged 36–86 years) treated with 5 mg prednisolone/day, who had received prednisolone for ≥6 months (median: 66, range: 6–444 months). Adrenal function was evaluated by a 250 μg Synacthen test performed after mean 48.7 h prednisolone pause. Local assay-specific cut-off for normal adrenal function was P-cortisol ≥420 nmol/L 30 min after Synacthen injection. Results Overall, 20 of the 42 patients (48%, 95% CI: 33–62%) had an insufficient adrenal response to the Synacthen test. Including only patients who had not r...
Frontiers in Endocrinology
Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathe... more Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests ...
Pituitary, 2021
Purpose Pasireotide is an effective treatment for acromegaly and Cushing’s disease, although trea... more Purpose Pasireotide is an effective treatment for acromegaly and Cushing’s disease, although treatment-emergent hyperglycemia can occur. The objective of this study was to assess incretin-based therapy versus insulin for managing pasireotide-associated hyperglycemia uncontrolled by metformin/other permitted oral antidiabetic drugs. Methods Multicenter, randomized, open-label, Phase IV study comprising a core phase (≤ 16-week pre-randomization period followed by 16-week randomized treatment period) and optional extension (ClinicalTrials.gov ID: NCT02060383). Adults with acromegaly (n = 190) or Cushing’s disease (n = 59) received long-acting (starting 40 mg IM/28 days) or subcutaneous pasireotide (starting 600 µg bid), respectively. Patients with increased fasting plasma glucose (≥ 126 mg/dL on three consecutive days) during the 16-week pre-randomization period despite metformin/other oral antidiabetic drugs were randomized 1:1 to open-label incretin-based therapy (sitagliptin followe...
Clinical Thyroidology, 2021
Gastrointestinal Tumors, 2021
Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worl... more Introduction: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer mortality worldwide. Recent animal studies suggest that thyroid hormone treatment improves HCC prognosis. The aim of this study was to describe the association between thyroid disease and HCC prognosis in humans. Methods: We performed a nationwide cohort study including all persons with an HCC diagnosis from 2000 to 2018. Patients’ age, sex, HCC treatment, and diagnoses of thyrotoxicosis, nontoxic goiter, and myxedema were obtained from Danish national healthcare registries. We used regression models to examine the association between thyroid disease and mortality hazard and restricted mean survival time after HCC diagnosis, adjusting for confounding by sex and age. Results: We included 4,812 patients with HCC and 107 patients with thyroid disease. Median follow-up time was 5 months (total 5,985 person-years). The adjusted mortality hazard ratio was 0.68 (95% CI: 0.47–0.96) for thyrotoxicosis and 0.60...
Journal of the Endocrine Society, 2020
Hypothyroidism due to non-compliance with levothyroxine (LT4) treatment is not infrequent (pseudo... more Hypothyroidism due to non-compliance with levothyroxine (LT4) treatment is not infrequent (pseudomalabsorption). It should be considered in patients with persistent severe clinical and biochemical hypothyroidism even after excessive LT4 dose. The diagnosis can be confirmed by LT4 Absorption Test. We present 4 female patients (age range 21-44 years) with suspicion of (pseudo)malabsorption who underwent absorption test (3 patients with autoimmune hypothyroidism and one patient with hypothyroidism after total thyroidectomy due to Graves’ disease). They presented with persistent hypothyroidism (TSH 30 to >100 mU/L) even after gradual increase to excessive LT4 dose (400-700 μg daily). All denied non-compliance; drug and dietary interference with LT4 absorption and nephrotic syndrome were excluded. Two patients with autoimmune hypothyroidism underwent absorption test with their last daily LT4 dose as loading dose (700 and 200 μg) followed by hourly free T4 (fT4) determination for 6 hou...
Endocrine Connections, 2018
A recent study proposed new TNM groupings for better survival discrimination among stage groups f... more A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38–4.57) vs 3.04 (95% CI: 1.38–6.67) for stage II, 2.06 (95% C...
F1000 - Post-publication peer review of the biomedical literature, 2017
Endocrine Abstracts, 2015
Endocrine
Purpose To provide an overview of consequences of undertreatment with levothyroxine (LT4) in the ... more Purpose To provide an overview of consequences of undertreatment with levothyroxine (LT4) in the common non-communicable disease, hypothyroidism. Methods Narrative review of the literature. Results Hypothyroidism is globally very prevalent at all age groups and represents a non-communicable disease in which the risks and consequences are preventable. In children and adolescents, the most devastating consequences of undertreatment are poor growth and development. Lack of early treatment in congenital hypothyroidism can lead to permanent damage of brain function. In young to middle-aged adults, consequences are often overlooked, and treatment delayed by many years. The resulting consequences are also at this age group compromised brain and physical functioning but less severe and partly reversible with treatment. The undertreated condition often results in a higher risk of several secondary devastating diseases such as increased cardiovascular disease burden, obesity, hypertension, po...
Uploads
Papers by Ulla Feldt-rasmussen