| 31. |
- Götherström, Galina, 1962, et al.
(författare)
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Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency.
- 2007
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - : Oxford University Press (OUP). - 0804-4643. ; 156:1, s. 55-64
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Tidskriftsartikel (refereegranskat)abstract
- There are few studies that have determined the effects of long-term GH replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD adults using dual energy X-ray absorptiometry (DEXA). The results show that GH replacement induced a sustained increase in BMD at all the skeletal sites measured. INTRODUCTION: Little is known of the effect of more than 5 years of GH replacement therapy on bone metabolism in GHD adults. PATIENTS AND METHODS: In this prospective, open-label, single-center study, which included 87 consecutive adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood onset GHD, the effect of 10 years of GH replacement on BMD was determined. RESULTS: The mean initial dose of GH was 0.98 mg/day. The dose was gradually lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end. The GH replacement induced a sustained increase in total, lumbar (L2-L4) and femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment response in IGF-I SDS was more marked in men, whereas women had a more marked increase in the total body BMC and the total body z-score. There was a tendency for women on estrogen treatment to have a larger increase in bone mass and density compared with women without estrogen replacement. CONCLUSIONS: Ten years of GH replacement in hypopituitary adults induced a sustained, and in some variables even a progressive, increase in bone mass and bone density. The study results also suggest that adequate estrogen replacement is needed in order to have an optimal response in BMD in GHD women.
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| 32. |
- Götherström, Galina, 1962, et al.
(författare)
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Ten years of growth hormone (GH) replacement normalizes muscle strength in GH-deficient adults.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 809-16
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: GH replacement for 1-5 yr improves, but does not fully normalize, muscle strength. OBJECTIVE, DESIGN, AND PATIENTS: In this single-center, open-labeled, prospective study, the effects of 10 yr of GH replacement on muscle strength and neuromuscular function were followed in 109 consecutive adults (61 men; mean age 50.0 yr; range 22-74 yr) with adult-onset GH deficiency. RESULTS: The mean initial GH dose of 0.88 mg/d was gradually lowered to 0.47 mg/d. The mean IGF-I sd score increased from -1.54 at baseline to 1.12 at study end. GH replacement induced a sustained increase in lean mass and isometric knee flexor strength (60 degrees). In most other measures of upper leg and handgrip strength, there were transient increases during the first half of the study (0-5 yr), whereas during the second half (5-10 yr), the absolute values of muscle strength decreased and returned to or even below the baseline values. However, after correction for age and gender using observed/predicted value ratios, there were sustained and, until 7 yr, even progressive increases in the measures of muscle strength. At study end, knee flexor strength had increased to 104-110% of predicted, knee extensor strength to 93-108%, and handgrip strength to 88-93%. Measurements of neuromuscular function showed reduced voluntary motor unit activation after 10 yr. CONCLUSIONS: Ten years of GH replacement therapy increased muscle strength during the first half of the study and thereafter partly protected against the normal age-related decline in muscle strength and neuromuscular function, resulting in approximately normalized muscle strength after 10 yr.
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| 33. |
- Götherström, Galina, 1962, et al.
(författare)
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The effects of five-year growth hormone replacement therapy on muscle strength in elderly hypopituitary patients.
- 2005
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Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 62:1, s. 105-13
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Little is known of the long-term effects of GH replacement therapy on muscle strength in elderly adults with adult onset GH deficiency (GHD). In this study, the effects of 5 years of GH replacement therapy on muscle function were determined in adults over 60 years of age with adult onset GHD. DESIGN: A prospective, open-label, single-centre study. Patients Twenty-six (12 male and 14 female) consecutive hypopituitary adults with adult onset GHD, mean age 65.0 (range 61-74) years. MEASUREMENTS: Upper leg muscle strength was measured using a Kin-Com dynamometer. Right and left handgrip strength were measured using an electronic grip force instrument. RESULTS: The mean insulin-like growth factor-I (IGF-I) SD score increased from -1.10 at baseline to 1.21 at end of the study. Body weight was unchanged during the 5-year study. A sustained increase in lean body mass and a sustained reduction of body fat was observed as measured using dual-energy X-ray absorptiometry (DEXA). The GH replacement therapy induced a sustained increase in isometric (60 degrees ) knee flexor strength. After statistical correction for age and sex variables using observed/predicted value ratios, a sustained increase was also observed in concentric knee flexor strength at an angular velocity of 60 degrees /s, concentric knee extensor strength at 60 degrees /s and 180 degrees /s, and peak right handgrip strength. At baseline, knee flexor strength was 90-96% of predicted, knee extensor strength was 85-87% of predicted, and hand-grip strength was 74-80% of predicted values. At study end, knee flexor strength was 98-106% of predicted, knee extensor strength was 90-100% of predicted, and hand-grip strength was 80-87% of predicted values. CONCLUSION: Elderly patients with adult onset GH deficiency had decreased baseline muscle strength also after correction for age and sex. The 5-year GH replacement therapy normalized knee flexor strength and improved, but did not fully normalize, knee extensor strength and handgrip strength.
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| 34. |
- Holmer, Helene, et al.
(författare)
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Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone
- 2007
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:9, s. 3560-3567
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Tidskriftsartikel (refereegranskat)abstract
- Context: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. Objective: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus ( T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. Design and Participants: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. Results: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. Conclusions: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.
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| 35. |
- Isaksson, Olle, 1943, et al.
(författare)
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GH and bone--experimental and clinical studies.
- 2000
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Ingår i: Endocrine journal. - 0918-8959. ; 47 Suppl, s. S9-16
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Tidskriftsartikel (refereegranskat)abstract
- GH increases bone formation both via a direct interaction with GH receptors on osteoblasts and via locally produced IGF-I (autocrine/paracrine action). GH deficiency results in decreased bone mass in both man and laboratory animals and treatment of GHD patients with GH for several months results in increased bone mass. GH treatment also increases bone mass and the total mechanical strength of bones in rats with normal GH secretion. Because of the short duration of GH-treatment in man with normal GH secretion, the effect on bone mass is still inconclusive. The action of GH on bone metabolism in GHD adults is twofold: It stimulates both bone resorption and bone formation. A "Biphasic model" of GH action in bone remodeling has recently been proposed [1] (Fig. 2). According to this model the net effect of GH first results in a loss of bone mass, followed by a net increase in bone mass. The transition point occurs when bone formation proceeds at a higher rate than bone resorption. Taking all clinical studies of GH-treatment of GHD adults into account, it appears that the "transition point" occurs after approximately six months and that a net increase in bone mass usually is seen after 12-18 months of GH treatment. It should be emphasized that the "Biphasic model" of GH action in bone remodeling is proposed based on findings in GHD adults, and it remains to be clarified whether or not it is valid for subjects with normal GH secretion.
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| 36. |
- Janson, Per-Olof, 1940, et al.
(författare)
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Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.
- 1998
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Ingår i: Clinical endocrinology. - 0300-0664. ; 48:2, s. 243-50
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Tidskriftsartikel (refereegranskat)abstract
- A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.
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| 37. |
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| 38. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:5, s. 2046-52
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Tidskriftsartikel (refereegranskat)abstract
- Thirty-eight women, aged 25-65 yr, with androgen deficiency due to hypopituitarism were treated with oral dehydroepiandrosterone (DHEA; 30 mg/d if <45 yr of age and 20 mg if > or =45 yr of age) for 6 months in a randomized, placebo-controlled, double blind study, followed by a 6-month open treatment period. The administration of DHEA raised the serum levels of DHEAS to normal age-related reference ranges and increased androstenedione and T to subnormal levels. Androgen effects on skin and/or pubic and/or axillary hair were observed in 84% (32 of 38) of the women after all received 6 months of DHEA treatment. No such effects were observed after the placebo treatment. These effects after 6 months were correlated with the serum levels of DHEAS (r = 0.37; P = 0.03), androstenedione (r = 0.42; P = 0.01), and T (r = 0.37; P = 0.03). The percentages of partners who reported improved alertness, stamina, and initiative by their spouses were 70%, 64%, and 55%, respectively, in the DHEA group and 11%, 6%, and 11%, respectively, in the placebo group (P < 0.05). According to the partners, sexual relations tended to improve compared with placebo (P = 0.06). After 6 months of treatment, increased sexual interest or activity was reported by 50% of the women taking 30 mg DHEA, by none taking 20 mg DHEA, and by two women taking placebo (P = NS). Compared with levels after placebo administration, high density lipoprotein cholesterol and apolipoprotein A-1 levels decreased after DHEA. Serum concentrations of IGF-I, serum markers of bone metabolism, and bone density did not change. In conclusion, oral administration of a low dose of DHEA to adult hypopituitary women induced androgen effects on skin and axillary and pubic hair as well as changes in behavior, with only minor effects on metabolism.
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| 39. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Two years of growth hormone (GH) treatment increases bone mineral content and density in hypopituitary patients with adult-onset GH deficiency.
- 1996
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 81:8, s. 2865-73
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Tidskriftsartikel (refereegranskat)abstract
- The main purpose of this trial was to determine the effects of 2 yr of GH treatment on bone mineral density (BMD) and bone metabolism in patients with adult-onset GH deficiency. Forty-four patients (24 men and 20 women; aged 23-66 yr) participated in a 2-yr open treatment trial with recombinant human GH. BMD was assessed with dual energy x-ray absorptiometry, and serum concentrations of osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), and carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) were measured. After 2 yr of GH treatment, the BMD increased in the lumbar spine L2-L4 by 3.8% [95% confidence interval (CI), 2.1-5.5], in the femoral neck by 4.1% (CI, 2.1-6.1) in the femoral trochanter by 5.6% (CI, 3.8-7.4) and in Ward's triangle by 4.9% (CI, 2.2-7.6) compared with baseline. Patients with a z-score (difference in SD from the mean of age- and sex-matched subjects) below -1 SD responded with the most marked BMD increment. The serum concentrations of osteocalcin, PICP, and ICTP remained higher throughout the 2 yr of treatment. Women demonstrated a more marked increase in total body BMD and a less pronounced initial increment in osteocalcin, PICP, and ICTP than men. Two years of GH treatment induced a sustained increase in overall bone remodeling activity, which resulted in a net gain in BMD that was more marked in those subjects with a low pretreatment z-score.
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| 40. |
- Karimi, Mahssa, et al.
(författare)
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Increased neck soft tissue mass and worsening of obstructive sleep apnoea after growth hormone treatment in men with abdominal obesity : Growth hormone and obstructive sleep apnoea in abdominally obese men
- 2010
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Ingår i: Journal of Clinical Sleep Medicine. - 1550-9389. ; 6:3, s. 256-263
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Tidskriftsartikel (refereegranskat)abstract
- Background Risk factors for obstructive sleep apnea (OSA) are male gender, obesity and abnormalities in neck soft tissue mass. OSA is associated with both growth hormone (GH) excess and severe GH deficiency in adults. Adults with abdominal obesity have markedly suppressed GH secretion. Aim To study the effect of GH treatment on OSA in abdominally obese men with impaired glucose tolerance. Patients and Methods Forty men with abdominal obesity and glucose intolerance were randomized in a prospective, 12-month, double-blind trial to receive either GH or placebo. The treatment groups had similar BMI and waist circumference. Overnight polysomnography and computed tomography to assess muscle and fat distribution in the neck and abdomen were performed at baseline and after 12 months. Results GH treatment increased insulin-like growth-factor-1 from (mean (SD)) 168(17) to 292(28) μg/L, the apnea-hypopnea index from (n/h) 31(20) to 43(25) and oxygen-desaturation index from (n/h) 18(14) to 29(21) (p=0.0001, 0.001, 0.002). Neck transverse diameter, circumference and total cross-sectional area (p=0.007, 0.01, 0.02) increased while abdominal visceral adipose tissue (p=0.007) was reduced. No between-group differences in total sleep time, REM sleep, non-REM sleep and time spent in supine position were found. The Epworth sleepiness scale score was unchanged. Conclusions GH treatment increased the severity of OSA in abdominally obese men. The possible mechanism appears to be reflected by the GH-induced increase of measures of neck volume. The present results, to some extent, argue against that low GH/IGF-I activity is a primary cause of OSA in abdominally obese men.
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