Increased Serum Growth Hormone Research Articles

Effect of cysteamine hydrochloride supplementation on the milk performance of dairy cow

Cysteamine (CS) can increase serum growth hormone concentrations and the growth performance of broiler, sheep, and pigs. However, information of CS supplementation on the milk performance of dairy cows is limited. An experiment was conducted to investigate the effect of dietary cysteamine hydrochloride (CSH) supplementation on lactation performance of dairy cows. Forty-eight multiparous mid-lactation Holsteins were fed a control diet or supplemented with 15, 30, or 45g/d CSH preparation (cysteamine HCl 20%) for 63d, including 7d for adaptation. The base diet was formulated to meet the nutrient requirements of lactating dairy cows according to the Chinese feeding standard (China Standard NY/T 34,Feeding standard of dairy cattle 2004 Issued by Ministry of Agriculture of People's Republic of ChinaBeijing) and the DMI, milk yield, milk composition, and plasma parameters were measured. Milk yield was 7.1% and 6.3% higher for the two higher supplementation amounts (SEM=0.50, P<0.05), and milk protein content was 7.7%, 8.7%, and 8.1% higher for the three supplemented groups (SEM=0.077, P<0.05), respectively, than the control. Plasma urea N were lower for the 30 and 45g/d CSH groups than for the control. Level of plasma somatostation was reduced and plasma growth hormone was enhanced in CSH groups compared with that of control (P<0.01). Supplementation of CSH preparation at 30g/d increased milk production of dairy cows while 15g/d has no positive effect on milk yield or milk efficiency.

The effects of ovariectomy on meat performance and expression of GH/IGF-I in young goats

Zhang, L., Wang, Y.-y., Fu, M.-z., Li, G., An, N., Li, S.-y. and Zhou, Z.-q. 2014. The effects of ovariectomy on meat performance and expression of GH/IGF-I in young goats. Can. J. Anim. Sci. 94: 619–626. Experiments were carried out to investigate the effects of ovariectomy on meat production efficiency and to explore the expression of GH/IGF-I in young goats. Animal performance, meat quality, levels of serum growth hormone (GH) and insulin-like growth factor 1 (IGF-I), and mRNA levels of three key genes [GH Receptor (GHR), IGF-I and IGF-I Receptor (IGF-IR)] in longissimus dorsi and biceps femoris muscles were measured. The results show that carcass weight, net meat mass, fat weight and loin eye area of ovariectomized goats were higher than those of the controls, and ovariectomized goats lost 0.40 kg of bone weight (P&lt;0.05). There was no statistically valid difference for the color, pH, water-holding capacity, or cooking rate of meat (P&gt;0.05) between the two groups, except for the shear value, which was significantly lower in the Ovx group than in the control group (P&lt;0.05). The results of this research show for the first time a significant trend (P&lt;0.05) for serum GH and IGF-I in the direction of increasing in ovariectomized goats. Furthermore, the mRNA levels of GHR, IGF-I and IGF-IR in muscle were all up-regulated, except for the IGF-I gene in biceps femoris, by ovariectomy. In summary, ovariectomy showed a beneficial promotion in animal performance, but did not reduce meat quality, and increased serum GH and IGF-I and mRNA expression levels of GHR, IGF-I and IGF-IR in young female goats.

The aging suppressor klotho: a potential regulator of growth hormone secretion.

Klotho is a transmembranal protein highly expressed in the kidneys, choroid plexus, and anterior pituitary. Klotho can also be cleaved and shed and acts as a circulating hormone. Klotho-deficient mice (kl/kl mice) develop a phenotype resembling early aging. Several lines of evidence suggest a role for klotho in the regulation of growth hormone (GH) secretion. The kl/kl mice are smaller compared with their wild-type counterparts, and their somatotropes show reduced numbers of secretory granules. Moreover, klotho is a potent inhibitor of the IGF-I pathway, a negative regulator of GH secretion. Therefore, we hypothesized that klotho may enhance GH secretion. The effect of klotho on GH secretion was examined in GH3 rat somatotrophs, cultured rat pituitaries, and cultured human GH-secreting adenomas. In all three models, klotho treatment increased GH secretion. Prolonged treatment of mice with intraperitoneal klotho injections increased mRNA levels of IGF-I and IGF-I-binding protein-3 mRNA in the liver, reflecting increased serum GH levels. In accord with its ability to inhibit the IGF-I pathway, klotho partially restored the inhibitory effect of IGF-I on GH secretion. Klotho is known to be a positive regulator of basic bFGF signaling. We studied rat pituitaries and human adenoma cultures and noted that bFGF increased GH secretion and stimulated ERK1/2 phosphorylation. Both effects were augmented following treatment with klotho. Taken together, our data indicate for the first time that klotho is a positive regulator of GH secretion and suggest the IGF-I and bFGF pathways as potential mediators of this effect.

A Crucial Role of Activin A-Mediated Growth Hormone Suppression in Mouse and Human Heart Failure

Infusion of bone marrow-derived mononuclear cells (BMMNC) has been reported to ameliorate cardiac dysfunction after acute myocardial infarction. In this study, we investigated whether infusion of BMMNC is also effective for non-ischemic heart failure model mice and the underlying mechanisms. Intravenous infusion of BMMNC showed transient cardioprotective effects on animal models with dilated cardiomyopathy (DCM) without their engraftment in heart, suggesting that BMMNC infusion improves cardiac function via humoral factors rather than their differentiation into cardiomyocytes. Using conditioned media from sorted BMMNC, we found that the cardioprotective effects were mediated by growth hormone (GH) secreted from myeloid (Gr-1(+)) cells and the effects was partially mediated by signal transducer and activator of transcription 3 in cardiomyocytes. On the other hand, the GH expression in Gr-1(+) cells was significantly downregulated in DCM mice compared with that in healthy control, suggesting that the environmental cue in heart failure might suppress the Gr-1(+) cells function. Activin A was upregulated in the serum of DCM models and induced downregulation of GH levels in Gr-1(+) cells and serum. Furthermore, humoral factors upregulated in heart failure including angiotensin II upregulated activin A in peripheral blood mononuclear cells (PBMNC) via activation of NFκB. Similarly, serum activin A levels were also significantly higher in DCM patients with heart failure than in healthy subjects and the GH levels in conditioned medium from PBMNC of DCM patients were lower than that in healthy subjects. Inhibition of activin A increased serum GH levels and improved cardiac function of DCM model mice. These results suggest that activin A causes heart failure by suppressing GH activity and that inhibition of activin A might become a novel strategy for the treatment of heart failure.

Pharmacological Characteristics of KP-102 (GHRP-2), a Potent Growth Hormone-Releasing Peptide

KP-102 (D-alanyl-3-(2-naphthyl)-D-alanyl-L-alanyl-L-tryptophyl-D-phenylalanyl-L-lysinamide dihydrochloride, growth hormone-releasing peptide-2, GHRP-2, pralmorelin, CAS 158861-67-7), is a potent synthetic growth hormone (GH) secretagogue. In the present study, the pharmacological characteristics of the GH-releasing property of KP-102 were investigated by means of in vivo and in vitro experiments. In conscious rats, the GH-releasing activity of KP-102 was more potent than that of exogenously injected GH-releasing hormone (GHRH). Under pentobarbital anesthesia in which endogenous somatostatin secretion is known to be decreased, KP-102 and GHRH, both showed an almost equivalent GH-releasing potency, which was also similar to that of KP-102 in conscious rats. Besides, KP-102 showed GH-releasing activity in conscious dogs as well, while GHRH failed to increase serum GH levels in conscious dogs. These findings suggest that the GH-releasing activity of KP-102 was less sensitive to GH suppression by endogenous somatostatin as compared with that of GHRH. The GH-releasing activity of KP-102 was completely absent in hypophysectomized rats, but present in median eminence-lesioned rats in which secreted GH amounts were significantly less than those normal rats, indicating necessity of the median eminence (endogenous GHRH) to exert the full activity of KP-102 in GH stimulation. KP-102 directly stimulated GH secretion from cultured rat anterior pituitary cells, although the GH-releasing potency of KP-102 was significantly weaker than that of GHRH in vitro. In conscious rats, KP-102 stimulated the secretion of both adrenocorticotrophic hormone (ACTH) and corticosterone, but not of prolactin. Three weeks administration of KP-102 showed growth-accelerating effect, a slight increase of body weight and wet weight of some organs in both normal and monosodium glutamate (MSG)-treated rats. These results suggest that KP-102 showed specific GH-releasing activity apart from slight ACTH secretion, and that the GH-releasing activity was stable in comparison with that of exogenously injected GHRH.

Octreotide for the treatment of systemic lupus erythematosus: Clinical effects and an in vitro study on its therapeutic mechanism

Increased serum growth hormone (GH), together with high expression of growth hormone receptor on peripheral blood mononuclear cells (PBMCs), correlates with systemic lupus erythematosus (SLE) activity, suggesting that modulation of GH signaling may affect SLE activity. We explored the effects of octreotide (OCT), an analog of somatostatin that suppresses the release of GH, in SLE. The objectives of the study were to investigate effects of OCT on the proliferative capacity and cytokine expression of PBMCs from patients with SLE and to investigate therapeutic effects of OCT in patients with SLE. PBMCs from 13 active/inactive SLE patients and 11 controls were pretreated with or without GH and cultured with OCT. The proliferation of PBMCs was assessed by MTT assay and cytokines were quantified by ELISA. We compared the clinical response of 12 patients with SLE treated with OCT (100 µg twice daily) with 12 patients treated with prednisone over three months. OCT inhibited PBMC proliferation in a dose-dependent manner and decreased the secretion of interleukin-6 (IL-6), interleukin-10 (IL-10), and interferon-gamma (IFN-γ). Patients treated with OCT demonstrated improvements in SLEDAI, dsDNA titer, complement levels, and erythrocyte sedimentation rate (ESR). OCT inhibited PBMC proliferation and PBMC secretion of IL-6, IL-10 and IFN-γ stimulated by GH. Treatment of patients with OCT resulted in clinical improvement in SLE.

Thyroïde et calcium

Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40–130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy.

Changes in the Somatotrophic Axis in Genetically Identical Dogs

Because cloned dogs are genetically identical, variations among these animals can be a useful tool to elucidate mechanisms underlying phenotypic differences. To estimate the influence of genetic factors on phenotypic variation, changes in concentration patterns of growth hormone (GH), insulin like growth factor-1 (IGF-1), and IGF binding protein 3 (IGFBP-3) were compared among cloned and age-matched control dogs. In addition, the concentrations of GH and IGF-1 following administration of growth hormone releasing hormone (GHRH) and somatostatin (SRIF) were measured in both groups. In comparing hormone profiles, the control dogs had larger standard deviations from the means for GH, IGF-1, and IGFBP-3 than the clones. Also, the mean concentration of IGFBP-3 in clones was significantly lower than in the controls between 7 to 12 months of age, whereas the IGFBP-3 changes in clones and controls followed the same pattern. GHRH induced increased serum growth hormone concentration both in clones and controls. However, the concentration of IGF-1 was lower in clones than in controls, and larger standard variations were noted in the control group. In conclusion, the measured traits were more homogeneous in cloned animals than in controls, so cloned animals could be valuable for assessing effects of genotype and environment interactions.

Increase in serum growth hormone induced by electrical stimulation of muscle combined with blood flow restriction

The purpose of this study was to investigate the role of muscle metaboreflex on exercise-induced growth hormone (GH) secretion. In order to accumulate metabolites within exercised muscle with minimized central motor activity, electromyostimulation (EMS) was performed combined with blood flow restriction (BFR). Seven men performed one-legged isometric knee extension evoked by EMS (frequency, 20Hz; pulse duration, 400μs; on-off ratio, 3-1s). Just before the exercise, proximal portion of either a stimulated thigh (ST) or a non-stimulated thigh (NT) was compressed at 150mmHg with an air-pressure cuff for the purpose of BFR. The compression was kept throughout the exercise session, and was released 2min after the end of the exercise. Two exercise sessions (ST(BFR), BFR for ST; NT(BFR), BFR for NT) were separated by 1week. ST(BFR) was aimed to accumulate metabolites within exercised muscle, whereas NT(BFR) was aimed to match mechanical stress with ST(BFR) without accumulating metabolites. Blood samples for hormonal measurements were taken from the antecubital vein before and after the exercise. Blood lactate increased immediately after the exercise in the NT(BFR), whereas it increased after the cuff deflation in the ST(BFR), suggesting that locally produced metabolites were retained and accumulated within the exercised muscle in the ST(BFR). Although serum cortisol and plasma noradrenaline increased in a similar manner in two conditions, serum immunoreactive GH (irGH) increased only in the ST(BFR). These results suggest that muscle metaboreflex plays an important role in the exercise-induced GH secretion, at least in terms of irGH secretion.

A Blend of Chlorophytum Borivilianum and Velvet Bean Increases Serum Growth Hormone in Exercise-Trained Men

Background:Several isolated ingredients have been proposed to increase growth hormone (GH) release, including Chlorophytum borivilianum and Velvet bean. A combination of these two ingredients has been packaged within an investigational dietary supplement. It was the purpose of the present investigation to determine the impact of acute ingestion of this supplement on circulating GH in healthy, exercise-trained men.Methods:Fifteen men ingested the dietary supplement on two different days, separated by one week. Blood was collected from subjects before ingestion of the supplement and at 20, 40, 60, 80, 100, and 120 minutes post ingestion. GH was analyzed in serum samples using an ELISA method. Values for GH for each subject, at each collection time, were averaged over both test days and used in the main analysis.Results:Serum GH increased over time, with higher values at 60 minutes (1.56 ± 0.65 ng · mL−1; P = 0.04; +767%), 80 minutes (1.76 ± 0.69 ng · mL−1; P = 0.02; +878%), and 100 minutes (1.48 ± 0.62 ng · mL−1; P = 0.05; +722%) compared to pre ingestion (0.18 ± 0.04 ng · mL−1). A great deal of subject variability existed in the area under the curve (AUC) for GH, with pooled values ranging from 0.49 to 61.2 ng · mL−1 · 2 hr−1Conclusion:Acute ingestion of an investigational dietary supplement containing the active ingredients Chlorophytum borivilianum and Velvet bean results in an increase in circulating GH in exercise-trained men. Additional placebo controlled investigations are needed to extend these findings. Moreover, studies are needed to determine if chronic use of such supplementation leads to favorable changes in health-related parameters associated with increased circulating GH.

Effect of exercise performed at anaerobic threshold on serum growth hormone and body fat distribution in obese patients with type 2 diabetes

The mechanism by which exercise reduces visceral fat is not fully understood. We have reported that increase in serum growth hormone (GH) level by mild exercise is associated with increase in lipolysis in type 2 diabetes (T2D), and that GH stimulates lipolysis in rat visceral adipose tissue. The aim of this study was to investigate the effect of GH secretion in response to exercise on visceral fat in obese subjects with T2D. Subjects were divided into exercise (n = 11) and non-exercise (n = 8) groups. Exercise was performed at anaerobic threshold (AT). Blood samples were obtained at weeks 0 and 4. To evaluate the secretion of GH and catecholamines in response to exercise, serum GH and catecholamines levels were measured before and after a bout of exercise on day 1. Visceral fat area (VFA) reduction tended to be greater in exercise group compared to non-exercise group (p = 0.067), whereas subcutaneous fat area (SFA) reduction was not different between two groups. In exercise group, serum GH level tended to increase during exercise, while catecholamines showed no significant changes. The change in serum GH level correlated negatively with the change in VFA during this study, but did not correlate with SFA. The increase in serum insulin-like growth factor-I level in exercise group was 10-fold higher than that in non-exercise group. These results suggest that in obese patients with T2D, exercise performed at AT may reduce visceral fat and the reduction appears to be associated with GH secretion but not with catecholamine in response to exercise.:

Growth hormone stimulates the collagen synthesis in human tendon and skeletal muscle without affecting myofibrillar protein synthesis

In skeletal muscle and tendon the extracellular matrix confers important tensile properties and is crucially important for tissue regeneration after injury. Musculoskeletal tissue adaptation is influenced by mechanical loading, which modulates the availability of growth factors, including growth hormone (GH) and insulin-like growth factor-I (IGF-I), which may be of key importance. To test the hypothesis that GH promotes matrix collagen synthesis in musculotendinous tissue, we investigated the effects of 14 day administration of 33-50 microg kg(-1) day(-1) recombinant human GH (rhGH) in healthy young individuals. rhGH administration caused an increase in serum GH, serum IGF-I, and IGF-I mRNA expression in tendon and muscle. Tendon collagen I mRNA expression and tendon collagen protein synthesis increased by 3.9-fold and 1.3-fold, respectively (P < 0.01 and P = 0.02), and muscle collagen I mRNA expression and muscle collagen protein synthesis increased by 2.3-fold and 5.8-fold, respectively (P < 0.01 and P = 0.06). Myofibrillar protein synthesis was unaffected by elevation of GH and IGF-I. Moderate exercise did not enhance the effects of GH manipulation. Thus, increased GH availability stimulates matrix collagen synthesis in skeletal muscle and tendon, but without any effect upon myofibrillar protein synthesis. The results suggest that GH is more important in strengthening the matrix tissue than for muscle cell hypertrophy in adult human musculotendinous tissue.

Acromegaly

Excessive production of the growth hormone (GH) is responsible for acromegaly. It is related to a pituitary GH-secreting adenoma in most cases. Prevalence is estimated 40-130 per million inhabitants. It is characterised by slowly progressive acquired somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The rheumatologic, cardiovascular, respiratory and metabolic consequences determine its prognosis. The diagnosis is confirmed by an increased serum GH concentration, unsuppressible by an oral glucose load and by detection of increased levels of insulin-like growth factor-I (IGF-I). Treatment is aimed at correcting (or preventing) tumour compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. When surgery, the usual first-line treatment, fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogues and/or radiotherapy can be used. The GH-receptor antagonist (pegvisomant) is helpful in patients who are resistant to somatostatin analogues. Thanks to this multistep therapeutic strategy, adequate hormonal disease control is achieved in most cases, allowing a normal life expectancy.

Inhaled Growth Hormone (GH) Compared with Subcutaneous GH in Children with GH Deficiency: Pharmacokinetics, Pharmacodynamics, and Safety

Delivery of GH via inhalation is a potential alternative to injection. Previous studies of inhaled GH in adults have demonstrated safety and tolerability. We sought to assess safety and tolerability of inhaled GH in children and to estimate relative bioavailability and biopotency between inhaled GH and sc GH. This pediatric multicenter, randomized, double-blind, placebo-controlled, crossover trial had two 7-d treatment phases. Patients received inhaled GH and sc GH in the alternate phase. Placebo was administered by the route opposite from active drug. GH and IGF-I levels were measured at multiple time points. Pharmacokinetics were assessed using noncompartmental methods. Twenty-two GH-deficient children aged 6-16 yr were treated. Absorption of GH appeared to be faster after inhalation with maximum serum concentrations measured at 1-4 h compared with 2-8 h for sc GH. Mean relative bioavailability for inhaled GH was 3.5% (90% confidence interval 2.7-4.4%). Mean relative biopotency, based on IGF-I response, was 5.5% (confidence interval 5.2-5.8%). Similar dose-dependent increases in mean serum GH area under the curve and IGF-I changes from baseline were seen after inhaled and sc GH doses. Inhaled GH was well tolerated and preferred to injection. No significant changes in pulmonary function tests were seen. In this first pediatric trial of GH delivered by inhalation, it was well tolerated and resulted in dose-dependent increases in serum GH and IGF-I levels. This study establishes that delivery of GH via the deep lung is feasible in children.

Ultra Dynamised and Undynamised Dilutions of Alloxan at Micro-doses Influence Selective Pancreatic Beta Cell and Hormonal Profile: An Experimental Approach

Dynamised and Undynamised preparations of Alloxan 6x, 30x, 200x, and 1000x were examined for its anti-diabetic activities in Alloxan induced diabetes mellitus albino rats. Oral administration of dynamised potencies of Alloxan 6x, 30x, 200x, and 1000x at dose level of 50μ μμ μμ1/100 g.b.w. daily for 30 days regularly exhibited slow and steady fall in blood sugar level accompanied with perceptible increase in serum growth hormone (GH) i.e. p < 0.01 (less significant) and p < 0.001 (significant) respectively when compared to dynamised and Undynamised control as well as Undynamised Alloxan fed groups under identical conditions. Histological and histo-morphometric studies also revealed reactivation of Pancreatic β-cells. Dynamised dilutions of Alloxan acts steadily through hypothalamo-hypophysial- pancreatic β-cells axis producing selective reactivation of βcells at micro-doses, steadily viz 6x < 30x < 200x < 1000x. The drug may indirectly release Releasing factors (RF) from hypothalamic neurons, stimulating the secretion of growth hormone which in turn triggers optimum insulin secretion from β-cells. The therapeutic action of the test drug in dynamised dilutions at micro dose and relatively high dilutions on pancreatic β-cells confirms the phenomenon of “Potentization” & “Similia Similibus Curentur” and lack of acute and sub-acute toxicity at fairly large dosage may open up new prospects in the treatment of diabetes mellitus and throw light in elucidating the mechanism of action at higher dilutions. It was noticed that the dynamised dilutions of alcohol fed control group is more toxic and lethal to animals than the dynamised and Undynamised dilutions of Alloxan and Undynamised alcohol fed control groups. Furthermore, it was also discernible that blood sugar and growth hormone levels were stabilized even after withdrawal of test drug in its 30x, 200x and 1000x potencies.

Acromégalie

Acromegaly is a rare disease usually caused by growth hormone (GH) hypersecretion, due to a pituitary adenoma; in very rare cases, acromegaly is due to ectopic secretion of GHRH, responsible for pituitary hyperplasia. Owing to its insidious onset, acromegaly is often diagnosed late (4 to > 10 years after onset), at an average age of about 40 years, in front of an acquired, slowly progressing disfigurement mainly involving the face and extremities. Acromegaly has also rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. The diagnosis is based on an increased serum GH concentration unsuppressed following an oral glucose load (oral glucose tolerance test -OGTT-) and an increased insulin-like growth factor-I (IGF-I); according to a 2000 Consensus statement, if the basal serum GH is above 0,4microg/L (1.2mIU/L) and/or if the IGF-I is elevated, an OGTT must be performed. If the lowest GH value (nadir) during OGTT remains above 1microg/L (3mIU/L), acromegaly is confirmed. With the generalized use of very sensitive assays nowadays, it has recently been considered that this cutoff should be decreased to 0,3microg/L (0.9mIU/L). Treatment is aimed at correcting (or preventing) tumor compression by excising the culprit lesion, and at reducing GH and IGF-I levels to normal values (or at least to a "safe" GH level of < 2microg/L or < 6mIU/L). A stepwise therapeutic strategy is used: transsphenoidal surgery is often the first-line treatment; when surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used, somatostatin analogs being generally preferred; the GH antagonist (pegvisomant) is used in patients that are resistant or intolerant to somatostatin analogs. Prognosis of acromegaly has improved in the recent years: adequate hormonal disease control is achieved in most cases, allowing life expectancy similar to that of the general population.

Acromegaly

Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000–250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain.

Acromegaly with Normal IGF-1 Levels Probably due to Poorly Controlled Diabetes Mellitus

Acromegaly is characterized by the somatic disfigurement and excessive production of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Here we report a patient with aromegaly and diabetes mellitus, who showed normal IGF-1 levels in spite of elevated GH levels. The patient was a 52-year-old woman with acromegalic manifestations. Serum GH level was elevated (32.4 ng/mL) with hyperglycemia (fasting plasma glucose, 277 mg/dL) and an extremely high level of glycosylated hemoglobin (HbA1c 17.7%), whereas serum IGF-1 level was within normal range (110 ng/mL, normal range 37-266). Brain magnetic resonance imaging detected a pituitary tumor, with involvement of the right cavernous sinus. Oral glucose tolerance test (OGTT) showed no suppression of serum GH. Thyrotropin-releasing hormone test showed paradoxical increases in serum GH. We therefore diagnosed acromegaly accompanied with diabetes mellitus. A large amount of insulin (34 units/day) was required to control the blood glucose level. The patient was treated with octreotide, a somatostatin analogue, followed by transsphenoidal surgery. After the surgery, serum GH levels were suppressed by OGTT, although basal serum GH levels remained to be high. Basal serum GH levels, however, were normalized 5 months later. Blood glucose became well controlled by the diet alone. In contrast, serum IGF-1 increased to the range of 219-233 ng/mL. Pre-operative serum IGF-1 levels were low probably due to poorly controlled diabetes mellitus. In conclusion, the presence of normal serum IGF-1 levels cannot exclude the diagnosis of acromegaly especially when the patient is accompanied by diabetes mellitus.

Comparison between voluntary and stimulated contractions of the quadriceps femoris for growth hormone response and muscle damage

This study aimed to compare voluntary and stimulated exercise for changes in muscle strength, growth hormone (GH), blood lactate, and markers of muscle damage. Nine healthy men had two leg press exercise bouts separated by 2 wk. In the first bout, the quadriceps muscles were stimulated by biphasic rectangular pulses (75 Hz, duration 400 mus, on-off ratio 6.25-20 s) with current amplitude being consistently increased throughout 40 contractions at maximal tolerable level. In the second bout, 40 voluntary isometric contractions were performed at the same leg press force output as the first bout. Maximal voluntary isometric strength was measured before and after the bouts, and serum GH and blood lactate concentrations were measured before, during, and after exercise. Serum creatine kinase (CK) activity and muscle soreness were assessed before, immediately after, and 24, 48, and 72 h after exercise. Maximal voluntary strength decreased significantly (P < 0.05) after both bouts, but the magnitude of the decrease was significantly (P < 0.05) greater for the stimulated contractions (-22%) compared with the voluntary contractions (-9%). Increases in serum GH and lactate concentrations were significantly (P < 0.05) larger after the stimulation compared with the voluntary exercise. Increases in serum CK activity and muscle soreness were also significantly (P < 0.05) greater for the stimulation than voluntary exercise. It was concluded that a single bout of electrical stimulation exercise resulted in greater GH response and muscle damage than voluntary exercise.

Growth hormone producing prolactinoma in juvenile cystinosis: a simple coincidence?

Juvenile cystinosis was diagnosed in a patient who presented with severe headache attacks and photophobia. Treatment with oral cysteamine and topical cysteamine eye drops was started. One-and-a-half years later, he developed unilateral gynecomastia and elevated prolactin and growth hormone levels. A pituitary macroprolactinoma was discovered and successfully treated with the dopamine agonist cabergoline. Increased serum growth hormone levels were attributed to enhanced growth hormone production by the prolactinoma and somatostatin inhibition by cysteamine. Although the occurrence of prolactinoma in this patient could be a simple coincidence, it might also be a rare yet unrecognised complication of cystinosis.