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...
ObjectiveActive acromegaly is subject to sex differences in growth hormone (GH) and Insulin like ... more ObjectiveActive acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF‐I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear.DesignIn a cross‐sectional, multi‐centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined.MethodsSerum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF‐I and completion of two HR‐Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient‐assessed Acromegaly Symptom Questionnaire [PASQ]).ResultsThe mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF‐I standard deviation sc...
Objective To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in... more Objective To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and −0.5 (−1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (−1.5 to...
ObjectivesTriclosan is an antibacterial agent suspected to disrupt the endocrine system. The aim ... more ObjectivesTriclosan is an antibacterial agent suspected to disrupt the endocrine system. The aim of this study was to investigate the influence of triclosan on the human thyroid system through a systematic literature review of human studies.MethodsEligibility criteria and method of analysis were registered at Prospero (registration number: CRD42019120984) before a systematic search was conducted in Pubmed and Embase in October 2020. Seventeen articles were found eligible for inclusion. Thirteen studies were observational, while four had a triclosan intervention. Participants consisted of pregnant women in eight studies, of men and non-pregnant women in seven studies and of chord samples/newborns/children/adolescents in six studies. The outcomes were peripheral thyroid hormones and thyroid-stimulating hormone (TSH) in blood samples.ResultsSeveral studies found a negative association between triclosan and triiodothyronine and thyroxine, and a positive association with TSH; however, th...
ObjectiveData on sex differences in acromegaly at the time of diagnosis vary considerably between... more ObjectiveData on sex differences in acromegaly at the time of diagnosis vary considerably between studies.DesignA nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed.MethodSex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated.ResultsThe cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma s...
OBJECTIVE: Several biomarkers for glucocorticoid (GC) sensitivity have been proposed relevant for... more OBJECTIVE: Several biomarkers for glucocorticoid (GC) sensitivity have been proposed relevant for the inter-individual variation seen in treatment response and side effects to GC treatment. Four single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene have been associated with increased (Bcl1 and N363S) or decreased (9β and ER23/23EK) GC sensitivity. We investigated the influence of these proposed biomarkers for GC sensitivity on GC-induced adrenal insufficiency. SUBJECTS AND METHODS: We included 239 patients receiving long-term prednisolone treatment for rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) / giant cell arteritis (GCA), or after renal transplantation (RTx). Four GR gene SNPs (Bcl1 rs41423247; 9β rs6198; N363S rs56149945; ER22/23EK rs6189 + rs6190) were sequenced by Sanger sequencing. Adrenal function was evaluated by a 250 µg corticotropin stimulation test. To compare allele frequencies with background population, two control groups were generated from...
Objective Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) hav... more Objective Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during three study periods (1994–1999 (P1), 2000–2004 (P2), and 2005–2012 (P3)) using the KIMS (Pfizer’s International Metabolic) database. Methods Data were retrieved for a total of 6069 patients with adult-onset GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment decreased by 2.9 years over the entry year periods. IGF-1 incr...
In recent years, there has been a growing interest in nutraceuticals, which may be considered as ... more In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology—these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol—some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims...
Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and ... more Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. Objective To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. Patients and Methods 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. Main outcome measures GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). Results IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P < 0.01). SA dose increase was performed in 20 patients in the...
Objective Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are rel... more Objective Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are released from the pituitary gland and stimulate Leydig cells to produce testosterone and initiates spermatogenesis. Little is known about how and when the deterioration of semen quality occurs in patients with adult-onset gonadotropin insufficiency. Design and methods A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of young healthy men (n = 340). Results Thirteen of 20 patients (65%) and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (P = 0.05). For the individual semen variables, there were no significant differences in semen volume (median (intraquartile range) 3.0 (1.3–6.8) vs 3.2 (2.3–4.3) mL, P = 0.47), sperm concent...
Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed f... more Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Methods Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment sa...
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...
ObjectiveActive acromegaly is subject to sex differences in growth hormone (GH) and Insulin like ... more ObjectiveActive acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF‐I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear.DesignIn a cross‐sectional, multi‐centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined.MethodsSerum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF‐I and completion of two HR‐Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient‐assessed Acromegaly Symptom Questionnaire [PASQ]).ResultsThe mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF‐I standard deviation sc...
Objective To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in... more Objective To analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database). Patients and methods Patients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis. Results At baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and −0.5 (−1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (−1.5 to...
ObjectivesTriclosan is an antibacterial agent suspected to disrupt the endocrine system. The aim ... more ObjectivesTriclosan is an antibacterial agent suspected to disrupt the endocrine system. The aim of this study was to investigate the influence of triclosan on the human thyroid system through a systematic literature review of human studies.MethodsEligibility criteria and method of analysis were registered at Prospero (registration number: CRD42019120984) before a systematic search was conducted in Pubmed and Embase in October 2020. Seventeen articles were found eligible for inclusion. Thirteen studies were observational, while four had a triclosan intervention. Participants consisted of pregnant women in eight studies, of men and non-pregnant women in seven studies and of chord samples/newborns/children/adolescents in six studies. The outcomes were peripheral thyroid hormones and thyroid-stimulating hormone (TSH) in blood samples.ResultsSeveral studies found a negative association between triclosan and triiodothyronine and thyroxine, and a positive association with TSH; however, th...
ObjectiveData on sex differences in acromegaly at the time of diagnosis vary considerably between... more ObjectiveData on sex differences in acromegaly at the time of diagnosis vary considerably between studies.DesignA nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed.MethodSex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated.ResultsThe cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma s...
OBJECTIVE: Several biomarkers for glucocorticoid (GC) sensitivity have been proposed relevant for... more OBJECTIVE: Several biomarkers for glucocorticoid (GC) sensitivity have been proposed relevant for the inter-individual variation seen in treatment response and side effects to GC treatment. Four single nucleotide polymorphisms (SNPs) of the GC receptor (GR) gene have been associated with increased (Bcl1 and N363S) or decreased (9β and ER23/23EK) GC sensitivity. We investigated the influence of these proposed biomarkers for GC sensitivity on GC-induced adrenal insufficiency. SUBJECTS AND METHODS: We included 239 patients receiving long-term prednisolone treatment for rheumatoid arthritis (RA), polymyalgia rheumatica (PMR) / giant cell arteritis (GCA), or after renal transplantation (RTx). Four GR gene SNPs (Bcl1 rs41423247; 9β rs6198; N363S rs56149945; ER22/23EK rs6189 + rs6190) were sequenced by Sanger sequencing. Adrenal function was evaluated by a 250 µg corticotropin stimulation test. To compare allele frequencies with background population, two control groups were generated from...
Objective Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) hav... more Objective Clinical observations over time of adults with growth hormone (GH) deficiency (GHD) have indicated a shift in patient characteristics at diagnosis. The objective of this study was to compare baseline characteristics of patients diagnosed with adult-onset GHD naive to GH replacement during three study periods (1994–1999 (P1), 2000–2004 (P2), and 2005–2012 (P3)) using the KIMS (Pfizer’s International Metabolic) database. Methods Data were retrieved for a total of 6069 patients with adult-onset GHD from six countries (Belgium, Germany, Netherlands, Spain, Sweden, and UK): P1 (n = 1705), P2 (n = 2397), and P3 (n = 1967). Results The proportions of patients with pituitary/hypothalamic tumors and patients with multiple pituitary hormone deficiencies decreased per entry year period, while the proportions with hypertension and diabetes increased. The lag time from diagnosis of pituitary disease to start of GH treatment decreased by 2.9 years over the entry year periods. IGF-1 incr...
In recent years, there has been a growing interest in nutraceuticals, which may be considered as ... more In recent years, there has been a growing interest in nutraceuticals, which may be considered as an efficient, preventive, and therapeutic tool in facing different pathological conditions, including thyroid diseases. Although iodine remains the major nutrient required for the functioning of the thyroid gland, other dietary components play important roles in clinical thyroidology—these include selenium, l-carnitine, myo-inositol, melatonin, and resveratrol—some of which have antioxidant properties. The main concern regarding the appropriate and effective use of nutraceuticals in prevention and treatment is due to the lack of clinical data supporting their efficacy. Another limitation is the discrepancy between the concentration claimed by the label and the real concentration. This paper provides a detailed critical review on the health benefits, beyond basic nutrition, of some popular nutraceutical supplements, with a special focus on their effects on thyroid pathophysiology and aims...
Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and ... more Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. Objective To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. Patients and Methods 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. Main outcome measures GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). Results IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P < 0.01). SA dose increase was performed in 20 patients in the...
Objective Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are rel... more Objective Gonadotropins (luteinizing hormone (LH) and follicle-stimulating hormone (FSH)) are released from the pituitary gland and stimulate Leydig cells to produce testosterone and initiates spermatogenesis. Little is known about how and when the deterioration of semen quality occurs in patients with adult-onset gonadotropin insufficiency. Design and methods A retrospective study comprising 20 testosterone-deficient men (median age, 29 years) with acquired pituitary disease who delivered semen for cryopreservation before initiation of testosterone therapy. Semen variables and hormone concentrations were compared to those of young healthy men (n = 340). Results Thirteen of 20 patients (65%) and 82% of controls had total sperm counts above 39 million and progressive motile spermatozoa above 32% (P = 0.05). For the individual semen variables, there were no significant differences in semen volume (median (intraquartile range) 3.0 (1.3–6.8) vs 3.2 (2.3–4.3) mL, P = 0.47), sperm concent...
Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed f... more Objective Somapacitan is a reversible albumin-binding growth hormone (GH) derivative, developed for once-weekly administration. This study aimed to evaluate the safety of once-weekly somapacitan vs once-daily Norditropin®. Local tolerability and treatment satisfaction were also assessed. Design 26-week randomized, controlled phase 3 safety and tolerability trial in six countries (Nbib2382939). Methods Male or female patients aged 18–79 years with adult GH deficiency (AGHD), treated with once-daily GH for ≥6 months, were randomized to once-weekly somapacitan (n = 61) or once-daily Norditropin (n = 31) administered subcutaneously by pen. Both treatments were dose titrated for 8 weeks to achieve insulin-like growth factor I (IGF-I) standard deviation score (SDS) levels within the normal range, and then administered at a fixed dose. Outcome measures were adverse events (AEs), including injection site reactions; occurrence of anti-somapacitan/anti-GH antibodies and change in treatment sa...
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Papers by Ulla Feldt-rasmussen