| 1. |
- Barbosa, Edna J L, 1961, et al.
(författare)
-
Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
- 2014
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
-
Tidskriftsartikel (refereegranskat)abstract
- Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
|
|
| 2. |
- Barbosa, Edna J L, 1961, et al.
(författare)
-
Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
- 2012
-
Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
-
Tidskriftsartikel (refereegranskat)abstract
- bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
|
|
| 3. |
- Barbosa, Edna J L, 1961, et al.
(författare)
-
Influence of the Exon 3-deleted/full-length Growth Hormone Receptor Polymorphism on the Response to Growth Hormone Replacement Therapy in Adults with Severe Growth Hormone Deficiency. : d3-GHR isoform in GHD adults
- 2009
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 639-644
-
Tidskriftsartikel (refereegranskat)abstract
- Context: There is considerable individual variation in the clinical response to growth hormone (GH) replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: To assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design, Patients: 124 adult GHD patients (79 men, median age 50 years) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (Group 1) and those bearing at least one d3-GHR allele (Group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as Group 1, while 52 (42%) had at least one d3-GHR allele and were classified as Group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.
|
|
| 4. |
|
|
| 5. |
- Filipsson, Helena, 1966, et al.
(författare)
-
Exploring the use of recombinant human TSH in the diagnosis of central hypothyroidism.
- 2008
-
Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 159:2, s. 153-60
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The diagnosis of central hypothyroidism (CH) is often difficult to establish as serum TSH levels may be low, normal, or slightly increased. OBJECTIVE: To explore the use of recombinant human TSH (rhTSH) in the diagnosis of CH. DESIGN: Randomized single-blind clinical trial. SETTING: Outpatient clinic of a tertiary care referral center. INTERVENTION: A single intramuscular injection of 0.1 and 0.9 mg rhTSH in random order with 1-week interval. PARTICIPANTS: Eighteen adult patients with pituitary insufficiency and six healthy age-, sex-, and body mass index-matched controls. Six patients had untreated CH (newCH), six had treated CH (CH), and six patients were TSH sufficient (nonCH). Five weeks before TSH stimulation, levothyroxine was replaced with tri-iodothyronine (T(3)) for 4 weeks. One week before stimulation, treatment was withdrawn. MAIN OUTCOME MEASURES: Thyroid hormones and thyroglobulin (Tg) before and 2, 3(1/2), 7, 24, 48, and 72 h after each injection. RESULTS: In the newCH group, basal free thyroxine (FT(4)) levels were lower than in controls (P<0.05). After 0.9 mg rhTSH, the increases in FT(4) and reverse T(3) (rT(3)) were less marked in the newCH group than in controls (FT(4)+/-s.e.m. 9.2+/-0.5 to 19.7+/-1.2 vs 11.3+/-0.5 to 27.8.2+/-2.4 pmol/l, P<0.05). The CH group exhibited reduced basal and stimulated FT(4) compared with the TSH-sufficient groups. Tg increased similarly among all study groups after rhTSH injection. CONCLUSION: In this pilot study, patients with untreated CH had lower response to 0.9 mg rhTSH in FT(4) and rT(3) than controls. An rhTSH test may be useful in the diagnosis of CH, but further studies are required.
|
|
| 6. |
- Filipsson, Helena, 1966, et al.
(författare)
-
GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies.
- 2009
-
Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 161 Suppl 1
-
Tidskriftsartikel (refereegranskat)abstract
- Severe GH deficiency (GHD) in adults has been described as a clinical entity. However, some of the features associated with GHD could be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult. Moreover, oral estrogen replacement therapy decreases IGF1 levels compared with the transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral estrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism. Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement.
|
|
| 7. |
- Filipsson, Helena, 1966, et al.
(författare)
-
The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients.
- 2006
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:10, s. 3954-61
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features. OBJECTIVE: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age. RESULTS: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
|
|
| 8. |
- Glad, Camilla A M, 1981, et al.
(författare)
-
SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.
- 2014
-
Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:1, s. 101-7
-
Tidskriftsartikel (refereegranskat)abstract
- GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.
|
|
| 9. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
-
Long-acting hydrocortisone for glucocorticoid replacement therapy.
- 2007
-
Ingår i: Hormone research. - : S. Karger AG. - 1423-0046 .- 0301-0163. ; 68 Suppl 5, s. 182-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Glucocorticoid (GC) deficiency is a consequence of various disorders that are by themselves rare. Because of this low prevalence, the low cost of GC replacement therapy and the belief that existing outcomes are good, there has been little interest in development of new and improved pharmaceutical products for treatment of GC deficiency. However, GC replacement therapy is complex: diurnal variation of endogenous cortisol must be replicated, GC needs may change during times of physical and psychological stress and there is no biomarker of its action that can be used to monitor individual dose response. CURRENT LIMITATIONS: Recent data suggest that the outcome of established long-term GC replacement therapy may not be as good as previously believed. Short-acting GCs such as hydrocortisone (HC) and cortisone acetate for replacement therapy require 2 to 3 administrations per day. DEVELOPING ALTERNATIVES: Drug delivery system technologies are now available that could permit design and manufacture of a formulation that could accommodate once-daily administration of HC. Such a formulation would enable more physiological serum cortisol-time profiles than are possible with currently available formulations. This short review provides some background on GC replacement therapy, along with recent data on the outcome of patient groups with GC insufficiency, and briefly discusses some general principles for a controlled-release ('long-acting') HC formulation.
|
|
| 10. |
- Nyström, Helena Filipsson, 1966, et al.
(författare)
-
Detection of genetic hypopituitarism in an adult population of idiopathic pituitary insufficiency patients with growth hormone deficiency.
- 2011
-
Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1573-7403 .- 1386-341X. ; 14:3, s. 208-216
-
Tidskriftsartikel (refereegranskat)abstract
- Idiopathic pituitary insufficiency (IPI) is diagnosed in 10% of all hypopituitary patients. There are several known and unknown aetiologies within the IPI group. The aim of this study was to investigate an adult IPI population for genetic cause according a screening schedule. From files of 373 GH deficient (GHD) patients on GH replacement 50 cases with IPI were identified. Of the 39 patients that approved to the study, 25 patients were selected for genetic investigation according to phenotype and 14 patients were not further tested, as sporadic isolated GHD (n=9) and GHD with diabetes insipidus (n=5) have low probability for a known genetic cause. Genotyping of all coding exons of HESX1, LHX4, PROP1, POU1F1 and GH1 genes were performed according to a diagnostic algorithm based on clinical, hormonal and neuroradiological phenotype. Among the 25 patients, an overall rate of 8% of mutations was found, and a 50% rate in familial cases. Among two sibling pairs, one pair that presented with complete anterior pituitary insufficiency, had a compound heterozygous PROP1 gene mutation (codons 117 and 120: exon 3 p Phe 117 Ile (c349 T>A) and p Arg 120 Cys (c358 C>T)) with a phenotype of very late onset ACTH-insufficiency. In the other sibling pair and in the sporadic cases no mutation was identified. This study suggests that currently known genetic causes are rare in sporadic adult IPI patients, and that systematic genetic screening is not needed in adult-onset sporadic cases of IPI. Conversely, familial cases are highly suspect for genetic causes.
|
|
