Elevated Growth Hormone Research Articles

Abstract CN07-02: Disrupting insulin-like growth factor signaling with monoclonal antibodies

Abstract The insulin-like growth factor (IGF) system is composed of a network of ligands, receptors, and binding proteins. The type I IGF receptor (IGF1R) is a transmembrane tyrosine kinase receptor and shares a high degree of homology with the insulin receptor (InsR). Data from many sources implicate the IGF system in cancer biology. Because of the role for InsR in glucose homeostasis, specific targeting of IGF1R with monoclonal antibodies has been deemed desirable. Numerous monoclonal antibodies have been developed against this receptor and share similar properties in preclinical model systems. To date, all of the antibodies have been shown to bind IGF1R and cause its internalization and downregulation. Early clinical studies have shown that IGF1R antibodies have activity as single agents in some diseases (sarcoma) and have activity in combination with cytotoxic chemotherapy. These early promising results suggest that inhibition of this receptor will emerge as a new cancer therapy. In addition, these early clinical results raise additional questions regarding optimizing their use in cancer treatment. In a xenograft model, monoclonal antibodies to IGF1R do not suppress tumor growth of the MDA-435/LCC6 cell line yet inhibit tumor metastasis. These data suggest that a commonly measured clinical phenotype, tumor growth, may not be detected in early phase II clinical trials. Clinical trials have also shown that IGF1R monoclonal antibody therapy results in elevation of growth hormone, IGF-I, and insulin levels. Since InsR may also mediate signaling in the IGF system, it is possible that InsR is also a target for cancer therapy. To address this issue, we have used shRNA to downregulate InsR expression while leaving IGF1R levels intact. In the MDA-435/LCC6 cells, disruption of InsR decreases tumor growth and inhibits pulmonary metastases. We have also selected cells in increasing concentrations of IGF1R antibodies. Finally, long term incubation of cells with IGF1R monoclonal antibodies results in cells with low levels of receptor expression, yet the receptor remains biochemically functional and can be inhibited by IGF1R tyrosine kinase inhibitors. Thus, disruption of IGF1R signaling has promise as a new cancer therapy. Future consideration of the role of the ligands, the InsR, and combination therapies with other signaling disruptors will allow us to optimize this therapeutic strategy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):CN07-02.

Oligomenorrhoea in Exercising Women

To date, the predominant mechanism underlying menstrual disturbances in exercising women supports an underlying energy deficiency-related aetiology, in which a failure to compensate dietary intake for the energy cost of exercise suppresses reproductive function. Increasing evidence demonstrates that energy deficiency plays a causal role in the induction of amenorrhoea in exercising women, and consistent with this mechanism are findings of glucoregulatory perturbations such as low triiodothyronine, reduced insulin secretion and elevated cortisol, growth hormone and ghrelin levels. The menstrual disturbance that may differ in its energetic characteristics and, perhaps in its androgenic and ovarian steroid environment, is oligomenorrhoea. We conducted a systematic review of the literature to begin to understand whether oligomenorrhoea in exercising women is a mild subclinical phenotype of polycystic ovarian syndrome (PCOS) in which exercise is conferring beneficial effects in protecting women from the classic PCOS phenotype, or whether oligomenorrhoea is part of the spectrum of menstrual disturbances caused by an energy deficiency that is often reported in exercising women with menstrual disturbances. We included observational, randomized controlled trials and cross-sectional studies that reported clinical, hormonal and metabolic profiles in exercising women with amenorrhoea or oligomenorrhoea and in women with PCOS. Previous studies examining the underlying mechanisms and consequences of exercise-associated menstrual disturbances have grouped exercising amenorrhoeic and oligomenorrhoeic women into a single group, and have relied primarily on self-reported menstrual history. Although scarce, the data available to date suggest that hyperandrogenism, such as that observed in PCOS, may likely be associated with oligomenorrhoea in exercising women, and may not always represent hypothalamic inhibition secondary to an energy deficiency. It is critical to closely examine the metabolic and endocrine status of women with menstrual disturbances because the treatment strategies for energy deficiency-related menstrual disturbances differ from that of disturbances traceable to hyperandrogenaemia. Further investigation is necessary to explore whether different endocrine aetiologies underly menstrual disturbances, particularly oligomenorrhoea, in physically active women.

Pegvisomant: current and potential novel therapeutic applications

Background: Pegvisomant is a genetically engineered molecule, which exhibits specific growth hormone (GH) antagonism by directly interacting with the GH receptor. It is currently licensed for the treatment of acromegaly where surgery and medical therapy with somatostatin analogues have failed. Objective: To delineate the role of pegvisomant in the treatment of acromegaly and its novel application in other areas of clinical medicine where suppression of GH action may be of therapeutic benefit. Methods: A literature review from PubMed- and EMBASE-listed publications and the web-sites of licensing organisations for medicinal products. Conclusion: Pegvisomant is currently used as a second line therapy in the management of acromegaly. It is highly effective in suppressing the metabolic effects of elevated GH levels when used alone or in combination with somatostatin analogues. However, its long term efficacy and safety for this indication has yet to be established. Preliminary data indicate that pegvisomant may have a role in management of type 1 diabetes with beneficial effects on insulin sensitivity and in preventing the progression of microvascular complications. Additional roles as an adjunct to cancer chemotherapy regimens and for the diagnosis of GH deficiency have been proposed, but have yet to be confirmed.

Elevations in ostensibly anabolic hormones with resistance exercise enhance neither training-induced muscle hypertrophy nor strength of the elbow flexors.

The aim of our study was to determine whether resistance exercise-induced elevations in endogenous hormones enhance muscle strength and hypertrophy with training. Twelve healthy young men (21.8 +/- 1.2 yr, body mass index = 23.1 +/- 0.6 kg/m(2)) trained their elbow flexors independently for 15 wk on separate days and under different hormonal milieu. In one training condition, participants performed isolated arm curl exercise designed to maintain basal hormone concentrations (low hormone, LH); in the other training condition, participants performed identical arm exercise to the LH condition followed immediately by a high volume of leg resistance exercise to elicit a large increase in endogenous hormones (high hormone, HH). There was no elevation in serum growth hormone (GH), insulin-like growth factor (IGF-1), or testosterone after the LH protocol but significant (P < 0.001) elevations in these hormones immediately and 15 and 30 min after the HH protocol. The hormone responses elicited by each respective exercise protocol late in the training period were similar to the response elicited early in the training period, indicating that a divergent postexercise hormone response was maintained over the training period. Muscle cross-sectional area (CSA) increased by 12% in LH and 10% in HH (P < 0.001) with no difference between conditions (condition x training interaction, P = 0.25). Similarly, type I (P < 0.01) and type II (P < 0.001) muscle fiber CSA increased with training with no effect of hormone elevation in the HH condition. Strength increased in both arms, but the increase was not different between the LH and HH conditions. We conclude that exposure of loaded muscle to acute exercise-induced elevations in endogenous anabolic hormones enhances neither muscle hypertrophy nor strength with resistance training in young men.

Preoperative Elevated Serum Growth Hormone is Preventive of Osteopenia in Postsurgical Patients With Pituitary Somatotroph Adenomas

To investigate the influence of preoperatively elevated growth hormone to bone mass in acromegalic patients, bone mineral density (BMD), and urinary type I collagen N-telopeptide were analyzed in postoperative patients with somatotroph adenomas (SA), in comparison with patients with clinically nonfunctioning adenomas (NF). The mean T and z scores of BMD in the radius of postoperative patients with SA were significantly higher than those of postoperative patients with NF. There was no significant difference in the mean T and z scores of BMD in the lumbar spine between postoperative patients with SA and those with NF. Thus, BMD in the radius is preferentially maintained in postoperative patients with SA. This result suggests that the preoperative elevation of growth hormone and insulin-like growth factor-1 are beneficial in the maintenance of bone mass in acromegalic patients.

Changes in Growth Hormone and Insulin-like Growth Factor-I Levels in the Acute Stage after Open Heart Surgery and at the Time of Discharge

Stress conditions are known to disturb the axis of growth hormone (GH)/insulin-like growth factor-I (IGF-I), but there is little data on this topic after open heart surgery. This study aimed to investigate changes in GH/IGF-I axis in adults undergoing open heart surgery. A total of 162 adult patients admitted for elective major cardiac surgery were studied in a prospective setting. Serum concentrations of GH and IGF-I were measured at four time points: before operation as a baseline, 4 and 12 hours after operation in ICU, and at the time of discharge. Two to 4 venous blood samples were obtained from each patient. To study the changes of GH and IGF-I levels over time, general linear model for repeated measures was applied. Mean age of patients was 51.2+/-14.3 years. Compared with preoperative values (median 0.8, range 0.05-19.4 ng/mL), GH levels rose significantly at four (median 3.3, range 0.1-55 ng/mL) and twelve hours after surgery (median 5.45, range 0.55-61.2 ng/mL), and continued to remain high at the time of discharge (median 2.1, range 0.02-22.7 ng/mL) (p<0.05). Conversely, compared with preoperative levels (173.5+/-89.9 ng/mL), IGF-I decreased at four (140.9+/-66.9 ng/mL) and twelve hours after operation (135.9+/-59.9 ng/mL) and reached its nadir on the day of discharge (114.8+/-43.8 ng/mL) (p<0.01). The patterns of changes in GH and IGF-I over time were significantly different (p<0.01). Adult patients undergoing open heart surgery go through a state of GH resistance characterized by elevated GH and decreased IGF-I levels from the initial hours after operation.

Endoscopic Sellar Floor Reconstruction with Concha Bullosa Bone Autograft and Nasal Septal Flap: Technical Case Report

A novel method is introduced for sellar floor reconstruction after expanded endoscopic endonasal transsphenoidal surgery using concha bullosa bone autograft and vascularized, posteriorly based flaps of septal mucoperichondrium. A 62-year-old woman presented to her primary care physician with the insidious onset of enlarging hands and feet, coarsening of facial features, and bilateral carpal tunnel syndrome. Endocrine studies revealed elevated growth hormone (22 ng/mL) and somatomedian-C (810 ng/mL) levels. Brain magnetic resonance imaging displayed a 1.2-cm pituitary adenoma. The patient was diagnosed with acromegaly secondary to a pituitary adenoma and underwent expanded endoscopic endonasal transsphenoidal surgery for tumor resection. Preoperatively, the patient was noted to have abnormal right middle turbinate pneumatization (concha bullosa). Following adenoma resection, the sellar floor was reconstructed using concha bullosa bone autograft resected during the endonasal approach. Bilateral vascularized nasoseptal mucosal flaps were then placed over the sellar floor. In patients with concha bullosa, conchal bone provides a useful substrate for sellar reconstruction after endoscopic endonasal transsphenoidal surgery.

Neuroendocrine Disturbances in Huntington's Disease

BackgroundHuntington's disease (HD) is a severe inherited neurodegenerative disorder characterized, in addition to neurological impairment, by weight loss suggesting endocrine disturbances. The aims of this study were to look for neuroendocrine disturbances in patients with Huntington's disease (HD) and to determine the relationship with weight loss seen in HDMethods and FindingWe compared plasma levels of hormones from the five pituitary axes in 219 patients with genetically documented HD and in 71 sex- and age-matched controls. Relationships between hormone levels and disease severity, including weight-loss severity, were evaluated. Growth hormone (GH) and standard deviation score of insulin-like growth factor 1 (SDS IGF-1) were significantly higher in patients than in controls (0.25 (0.01–5.89) vs. 0.15 (0.005–4.89) ng/ml, p = 0.013 and 0.16±1.02 vs. 0.06±0.91, p = 0.039; respectively). Cortisol was higher (p = 0.002) in patients (399.14±160.5 nmol/L vs. 279.8±130.1 nmol/L), whereas no differences were found for other hormone axes. In patients, elevations in GH and IGF-1 and decreases in thyroid-stimulating hormone, free triiodothyronine and testosterone (in men) were associated with severity of impairments (Independence scale, Functional score, Total Functional Capacity, Total Motor score, Behavioral score). Only GH was independently associated with body mass index (β = −0.26, p = 0.001).ConclusionOur data suggest that the thyrotropic and in men gonadotropic axes are altered in HD according to the severity of the disease. The somatotropic axis is overactive even in patients with early disease, and could be related to the weight loss seen in HD patients.

Somatotropic axis components and nutrient partitioning in genetically diverse dairy cows managed under different feed allowances in a pasture system

The somatotropic axis [including growth hormone (GH), GH receptor, and insulin-like growth factor (IGF)-I] is uncoupled in high-producing cows in early lactation so that the liver fails to respond to GH and produces less IGF-I. This uncoupling was implicated in the process of nutrient partitioning, enabling high milk production. Different genetic selection goals may affect functional components of the somatotropic axis. Thus, the somatotropic axis was examined in diverse genetic strains of dairy cows [North American Holstein 1990 (NA90), New Zealand Holstein-Friesian 1990 (NZ90), and New Zealand Holstein-Friesian 1970 (NZ70)] that were managed similarly within a pasture-based system but were offered feed allowances commensurate with their genetic ability to produce milk. The NA90 cows produced more milk (26.2±0.3, 24.1±0.3, and 20.1±0.4kg/d, for NA90, NZ90, and NZ70, respectively), but had lower milk fat percentages (4.28±0.03, 4.69±0.03, and 4.58±0.04kg/d for NA90, NZ90, and NZ70, respectively) compared with both NZ strains. Milk protein percentages (3.38±0.02, 3.52±0.02, and 3.29±0.03kg/d for NA90, NZ90, and NZ70, respectively) were greater for NZ90 cows. During early lactation (wk 2 to 6), the total net energy produced in milk was greater in NA90 compared with NZ90 or NZ70 cows, but total net energy in milk after wk 6 was equivalent for NA90 and NZ90 cows. The greater milk production in early lactation in NA90 cows was associated with lower body condition scores (BCS; 1 to 10 scale; 4.0±0.1) elevated blood GH concentrations (1.6±0.1ng/mL), and low blood IGF-I concentrations (14.8±1.1ng/mL), indicating an uncoupled somatotropic axis. In comparison, the NZ70 cows retained a coupled somatotropic axis during early lactation, maintaining greater BCS (4.6±0.1), lower blood GH (0.7±0.1ng/mL), and greater blood IGF-I (21.9±1.2ng/mL). The degree of uncoupling in NZ90 cows was intermediate between the other 2 strains. Additional feed allowance failed to change blood IGF-I concentrations in NA90 cows but increased IGF-I concentrations in NZ90 cows (20.9±1.4 and 13.2±1.4ng/mL for the high and low feed allowance, respectively). Furthermore, additional feed allowance in NZ90 cows lessened BCS loss in early lactation, but did not affect BCS loss in NA90 cows. Functional components of the somatotropic axis differed for the respective strains and were consistent with strain differences in milk production, BCS, and feed allowance.

Effects of obesity on anastrozole response in a mouse model of postmenopausal breast cancer.

Abstract Abstract #1146 Background: The prevalence of obesity, an established breast cancer risk factor for postmenopausal women, has risen rapidly in the US in recent decades. The majority of postmenopausal breast tumors are estrogen receptor-α positive (ER-α+) and responsive to the mitogenic effects of estrogen. Tamoxifen, a selective estrogen receptor modulator, has been the endocrine agent of choice for the treatment and prevention of ER-α+ breast cancer. Unfortunately, resistance to tamoxifen develops in the majority of cases. Akt activation in breast tumors is associated with poor prognosis and resistance to tamoxifen and other forms of endocrine therapy. Akt activation in the mammary epithelium is also enhanced by obesity, possibly due to elevated growth factor and hormone levels known to activate the PI3K/Akt/mTOR pathway. Aromatase inhibitors, such as anastrozole, are emerging as the treatment of choice for the postmenopausal patient, yet little is known as to how obesity may modulate response to these agents. In this study we examined the effect of obesity on tumor growth response to anastrozole and local tumor aromatase expression. We also assessed the correlation between obesity, Akt activation and tumor growth.&amp;#x2028; Methods: To mimic postmenopausal obesity, ovariectomized C57BL/6 mice (n=80) were randomized to a control diet (10 Kcal% fat; ∼10.2 kcal/day) or a diet-induced obesity (DIO) regimen (60 Kcal% fat; ∼14.4 kcal/day). After 14 wk on the diets mice were injected with isogenic MMTV-Wnt-1 mammary tumor cells (5x104 cells/mouse) in the 4th mammary fat pad. After tumors became palpable mice were injected with the AI anastrozole (10 μg/day s.c.) or vehicle control (0.3% hydroxypropylcellulose) for 4 wk. Serum leptin and resistin were measured at the end of the study, RT-PCR and western blot analyses were used to determine aromatase gene expression and total and phosphorylated protein levels in the tumors.&amp;#x2028; Results: Mice on the DIO regimens were significantly heavier (39.2 g ±0.7) than controls (29.7 g ±1.23), with significantly higher circulating levels of the obesity-related adipokines leptin and resistin. Tumors from DIO mice, relative to controls, displayed increased aromatase expression. Anastrozole had no effect on food consumption or body weight but intriguingly increased aromatase expression in tumors from both control and DIO mice. Importantly, DIO mice, relative to controls, were much less responsive to the tumor inhibitory effect of anastrozole. Akt protein expression correlated positively with tumor weight, regardless of dietary or hormonal treatment.&amp;#x2028; Conclusion: In the context of postmenopausal breast cancer, our results suggest that obese mice compared to controls are less responsive to the effects of anastrozole on tumor growth and that aromatase expression in tumors is higher in obese mice regardless of anastrozole treatment. We also found a strong correlation between Akt activation and tumor growth, irrespective of diet or hormonal treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1146.

Duration and nature of altered pituitary function in the male rat after a single large dose of estrogen.

The effects of a single large dose (10 and 20 mg) of diethylstilbestrol dipropionate on the pituitary gland of the mature male rat were investigated at intervals up to 312 days. The initial rise in pituitary weight and serum radioimmunoassayable growth hormone and fall in pituitary growth hormone concentration were followed by gradual recovery to normal extending over 5 to 6 months. Testicular weight was diminished until day 136 and adrenal weight was raised until day 114. The early pituitary mitotic activity had subsided to normal by day 69. Pituitary prolactin concentrations as indicated by starch gel electrophoresis were raised on day 28. Enlarged pituitary glands during the period 69 to 140 days also contained increased prolactin concentrations. The individual variations among the rats killed during the latter period included greatly elevated serum growth hormone either with or without increased pituitary weight.

Short Stature, Celiac Disease and Growth Hormone Deficiency

Celiac disease (CD) is a prevalent, genetically determined, autoimmune, chronic inflammatory state caused by intolerance to gluten that results mainly in gastrointestinal manifestations. One of the most common extra-intestinal manifestations of CD is short stature, and in some patients, short stature may be the presenting and only symptom of the disease, making the diagnosis of CD challenging. Impaired growth in children with CD results mainly from nutritional deficits, and withdrawal of gluten from the diet is frequently associated with a marked improvement of linear growth. In some patients, CD may be characterized by growth hormone (GH) resistance, as suggested by normal or elevated GH levels and low insulin-like growth factor-I (IGF-I) levels. Rarely, it has been shown that poor catch-up growth and/or IGF-I response to gluten-free diet may be due to the coexistence of celiac disease and GH deficiency. We present two children with coexisting CD and GH deficiency. One patient had MRI findings suggesting congenital isolated GH deficiency, and a possibility of developing multiple pituitary hormone deficiencies later in life.

Response to Comment on: Klöting et al. (2008) Autocrine IGF-1 Action in Adipocytes Controls Systemic IGF-1 Concentrations and Growth: Diabetes 57:2074–2082

We thank Bartke and Kopchick (1) for their interest in our study (2) and the important comment that elevated IGF-1 serum concentrations in mice with a conditional inactivation of the IGF-1 receptor in adipose tissue (IGF-1RaP2Cre mice) might be due to elevated growth hormone secretion despite the reported unaltered growth hormone levels in IGF-1RaP2Cre mice at the age of 24 weeks. Indeed, we …

Ghrelin-induced growth hormone release from goldfish pituitary cells involves voltage-sensitive calcium channels

Ghrelin (GRL) is a stimulator of growth hormone (GH) release in many organisms, including goldfish. As a first study to examine the signalling mechanisms mediating GRL action on GH release in goldfish, we tested the hypothesis that GLR induces GH release from goldfish pituitary cells by enhancing Ca 2+ entry through L-type voltage-sensitive Ca 2+ channels (LVSCCs) using perifusion GH release and fura-2/AM Ca 2+-imaging experiments. Goldfish (g)GRL 19 at 1 nM elicited reversible and repeatable GH responses from dispersed goldfish mixed pituitary cultures. However, the lack of a dose-response relationship in sequential treatments with decreasing concentrations of gGRL 19 (ranging from 10 to 0.01 nM) implicated rapid desensitization of the GH response. Sequential applications of gGRL 19 (1 nM) and salmon GnRH (100 nM), a known Ca 2+-dependent stimulator of GH release, increased intracellular free Ca 2+ levels ([Ca 2+] i) from the same identified somatotropes, suggesting co-expression of GRL and GnRH receptors on single cells. In contrast, 1 nM gGRL 19 failed to elicit GH release and elevation in [Ca 2+] i when the cells are incubated with nominally Ca 2+-free media. When GH release and [Ca 2+] i increases were already stimulated by the LVSCC agonist Bay K8644 (10 μM), addition of 1 nM gGRL 19 did not further elevate these responses. Finally, the LVSCC inhibitors nifedipine (1 μM) and verapamil (1 μM) abolished 1 nM gGRL 19-induced GH release responses while nifedipine eliminated gGRL 19-induced [Ca 2+] i increase. Taken together, the results of this study provide evidence that entry of extracellular Ca 2+ through LVSCCs is a key component of the GRL signalling pathway leading to GH release in the goldfish pituitary.

Cardiac changes induced by excess exogenous growth hormone in juvenile miniature poodles

The transient elevated plasma growth hormone (GH) levels that occur at a young age in giant breed dogs may have consequences in adult life. The aim of this study was to investigate whether excess juvenile GH has consequences for cardiac function and morphology. To simulate the naturally occurring juvenile hypersomatotropism in giant breed dogs, elevated plasma GH and insulin-like growth factor-I (IGF-I) concentrations were induced in six miniature poodles (GH dogs) by daily administration of supraphysiological doses of GH starting at 12 weeks of age. Eight miniature poodles of the same age that received vehicle only served as controls. Cardiac anatomy and function were evaluated by echocardiography. After euthanasia at 21 weeks of age, the hearts were examined for weight, myocyte dimensions and collagen fraction. The hearts of the GH dogs had larger atria (+22%), a thicker left ventricular wall (+21%), greater weight (+84%), and their cardiomyocytes were 15% longer, 25% thicker, and 92% greater in volume than those of control dogs. The mean collagen fraction was also higher in the GH dogs (5.6%) than in the controls (3.1%). In conclusion, excess GH in juvenile miniature poodles resulted in myocardial hypertrophy and increased collagen content. These findings are consistent with observations in acromegalic human patients and in rats treated with GH.

Serum IGF-I levels and IGF-I gene splicing in muscle of healthy young males receiving rhGH

Objective Elevated growth hormone (GH) levels lead to increased circulating insulin-like growth factor-I (IGF-I), but the effects on localised muscle IGF-I splice variant expression is not known. The effects of rhGH administration, with or without an acute bout of high resistance exercise, were measured on serum IGF-I and on the mRNA levels of IGF-I splice variants in the vastus lateralis muscle of healthy young men. Design The study was a randomised double blind trial with a crossover design. Seven subjects were randomly assigned to a group receiving daily injections of rhGH (0.075 IU kg −1 day −1) or placebo for a two week period. Following a one month washout, the groups were reversed. Results Administration of rhGH increased circulating IGF-I from 31.8 ± 3.2 to 109 ± 5.4 nmol/L ( p < 0.05). There was no effect of the exercise bout. RNA was extracted from muscle biopsies obtained from exercised and non-exercised legs 2.5 h after the cessation of the exercise. Transcript expression was measured using Real-time QPCR. There was no effect of either exercise or rhGH administration on IGF-I 5′ (Class 1 or Class 2) or 3′ (IGF-IEa, or MGF) transcripts. Conclusion Although rhGH administration has an effect on liver IGF-I expression, as shown by increase in circulating IGF-I, muscle IGF-I expression is unaffected in young healthy subjects with normal GH profile. The findings contrast with those of a previous study in which GH deficient elderly men showed higher muscle IGF-I 3′ splice variant levels following rhGH administration with and without resistance training. Unlike in the liver, muscle Class1 and 2 IGF-I expression do not change significantly following administration of rhGH.

An Unusual Etiology of Dysphagia in a Patient with Acromegaly

Purpose: 58 year-old women with history of diabetes mellitus and high blood pressure presented to our clinics with complaints of intermittent dysphagia to solids for four years. She states that since 5 months ago, these episodes have become more frequent, usually occurring less than one second after swallowing with associated regurgitation of intact meals. There was no history of odynophagia, heartburn, vomiting, retrosternal chest pain or weight loss. She denied smoking or alcohol abuse. Physical examination revealed a protuberant mandible and puffy hands. No halithosis or signs of malnourishment were present. A barium swallow showed a stricture of the esophagus at the level of the aortic knob. A subsequent upper endoscopy revealed no mucosal lesion supporting an extraluminal etiology of dysphagia. A right aberrant subclavian artery causing thoracic esophagus compression was identified by CT scan. A diagnosis of acromegaly was entertained by the presence of an elevated insulin-like growth hormone levels and physical exam findings. Further imaging studies identified a pituitary mass and patient is on scheduled for transphenoidal resection. Dysphagia lusoria is a rare disorder in adults. The worsening of dysphagia in this patient led to a diagnosis of acromegaly. Oropharyngeal dysphagia in patients with acromegaly secondary to macroglossia has been previously described. To our knowledge, dysphagia lusoria associated to acromegaly has not been previously reported.

Modulation of fish growth hormone levels by salinity, temperature, pollutants and aquaculture related stress: a review

The focus of this review is on the importance and regulation of fish growth hormone (GH), during exposure to stress. Alterations in environmental salinity impose osmoregulatory stress on fish and upon exposure to increased salinities GH has been shown to be important in maintaining hypoosmoregulatory function. Whilst studies mainly on salmonids, demonstrate that GH essentially performs a role as a seawater adapting hormone a clear correlation of elevated GH with growth and isoosmotic salinity exposure has been identified from studies on sparids. Variations in water temperature have been shown to modulate fish GH with the overall consensus of highest levels of GH during the warmer seasons of the year, suggesting an important role for GH during the temperature acclimatization process, but whether this relates to growth is unclear. Environmentally important pollutants, including xenoestrogens and heavy metals have been shown to affect GH mediated mechanisms, in fish, possibly via interference with the GH receptor and/or GH transcription, whereas aquacultural related stressors such as handling, confinement/overcrowding and nutritional stress have also been shown to affect GH levels. In addition the impact of aquacultural related stressors can also pre-dispose fish to disease leading to chronic suppression of GH. Finally, GH has been recently demonstrated to exert an anti-apoptotic effect in fish cells, when exposed to chemical stress, providing evidence that GH can also serve as a protective agent.

Insulin-like growth factor-1 is essential to the increased mortality caused by excess growth hormone: a case of thyroid cancer and non-Hodgkin’s lymphoma in a patient with pituitary acromegaly

The effects of growth hormone are mediated in part by stimulating the production of insulin-like growth factor-1. Insulin-like growth factor-1 has significant effects on cell proliferation and differentiation, it is a potent mitogen, and it is a powerful inhibitor of programmed cell death (apoptosis). Insulin-like growth factor-1 also has a well-established role in the transformation of normal cells to malignant cells. Case reports on a possible association between elevated growth hormone and cancer risk in a variety of patient groups have been published. Here, we describe clinical and laboratory findings for a patient with acromegaly who first developed thyroid cancer, and then, in the follow up period, probably due to poorly controlled insulin-like growth factor-1 levels, developed a large cell non-Hodgkin's lymphoma. A search revealed that a case with these peculiarities had not previously been reported.

Hormonal control of aging in rodents: The somatotropic axis

There is a growing body of literature focusing on the somatotropic axis and regulation of aging and longevity. Many of these reports derive data from multiple endocrine mutants, those that exhibit both elevated growth hormone (GH) and insulin-like growth factor I (IGF-1) or deficiencies in one or both of these hormones. In general, both spontaneous and genetically engineered GH and IGF-1 deficiencies have lead to small body size, delayed development of sexual maturation and age-related pathology, and life span extension. In contrast, characteristics of high circulating GH included larger body sizes, early puberty and reproductive senescence, increased cancer incidence and reduced life span when compared to wild-type animals with normal plasma hormone concentrations. This information, along with that found in multiple other species, implicates this anabolic pathway as the major regulator of longevity in animals.