How to Grow Taller
Growth hormone (GH) is essential for skeletal growth. Acromegaly and gigantism caused by excessive GH secretion sometimes accompany OPLL, and skeletal abnormalities in DISH patients resemble those in acro-megalic patients 2 . Most of the actions of GH in bone and cartilage are mediated by insulin-like growth factor (IGF-I), and an increase in GH secretion is associated with an elevation in systemic and local concentrations of IGF-I in bone and cartilage. Based on these observations, it has been postulated that changes in GH secre
Each child has a different rate of maturation, or what Boas termed tempo of growth (Tanner, 1986). Persons with short stature are more than 2 standard deviations (SD) below the Box 23-3 Causes of Short Stature and Relationship to Bone Age and Growth Rate Constitutional growth delay Growth rate decreased Endocrine disorders Cushing's syndrome Growth hormone deficiency Chronic systemic disease Crohn's disease Heart failure Renal failure Severe malnutrition Severe psychosocial deprivation Familial short stature Skeletal dysplasias Rickets mean in height and constitute approximately 2.5 of children (Miller and Zimmerman, 2004). If a child's growth falls outside the range of normal, it is useful to obtain a bone-age radiograph, usually of the left hand and wrist, and compare it to age-specific standards. Children must be at least 2 years of age to reliably identify epiphyseal ossification centers. Box 23-3 lists some causes of retarded or accelerated bone age. Calculation of mean predicted...
A new avenue toward treating GH hypersecretion from soma-totroph adenomas may lie with pegvisomant, a genetically engineered growth hormone-receptor antagonist. It functions as an analogue of human growth hormone and prevents the correct dimerization of the receptor. A 12-week, double-blind, placebo-controlled clinical trial recently demonstrated the amelioration of the biochemical and clinical manifestations of acromegaly with pegvisomant therapy.14 The onset of efficacy was rapid, with maximal reduction of GH occurring within the first 2 weeks. Pegvisomant was also well tolerated.
Intake of growth hormone (GH) has been used for years in the belief that it has an anabolic effect on skeletal muscle. It has been demonstrated that GH administration in GH-deficient individuals can improve fat-free body mass and thus muscle, and animal studies have documented a GH-mediated stimulation of muscle hypertrophy. In spite of this, there have been no studies robustly documenting any muscle mass-increasing effect of GH in addition to strength training in either untrained or well-trained individuals 11 . What has been shown is an enhancing effect of GH on lipid oxidation and thus on body composition. Growth hormone administration results in several side-effects, in both the short and long term. Immediate side-effects are fluid accumulation in the legs and carpal tunnel syndrome, whereas impaired glucose metabolism (glucose intolerance), hyperlipidemia and car-diomegaly can develop with long-term misuse. IGF-I has become used as a doping substance but no good experiments have...
The effect of testosterone on epiphysial closure may be used to treat boys who are dissatisfied with their prospective final overtall body height (for review Drop etal. 1998). Treatment has to start before the age of 14. Doses of 500 mg testosterone enanthate have to be administered every two weeks for at least a year to produce effects (Bettendorf etal. 1997). This treatment should be reserved for special cases since tall stature is not a disease but rather a cosmetic and psychological problem. However, social and psychological conflicts caused by this condition should not be underestimated. It should also be remembered that testosterone is not registered for this treatment, which has therefore to be considered experimental . Combining ethinylestradiol with testosterone injections has no additional height-reducing effect (Decker etal. 2002). An additional reservation comes from the possible effects of such high-dose testosterone treatment at this early age on fertility, the prostate,...
Human growth hormone (HGH) has been approved for treatment of persons with endogenous HGH deficiency or short stature secondary to chronic renal failure. Additionally, HGH is used off label for patients with Turner's syndrome and children born small for gestational age who have not had sufficient catchup growth.118 However, because of its success in treating these conditions, the abuse of HGH as an ergogenic aid has become widespread as well. In a survey of high school sophomores, Rickert et al119 found 5 of respondents had used HGH, with a significant association with AAS use as well. In addition to the negative health effects of HGH abuse by athletes, Conrad and Potter121 excellently summarize the ethical dilemma of HGH use for purported antiaging effects and for idiopathic short stature. Consider the potential impact of using HGH for otherwise healthy pediatric patients at the third per-centile for growth, resulting in a vicious cycle as the third per-centile would then shift...
In trained individuals, the hormonal responses to exercise are generally decreased. This is true for the increases in norepinephrine, epinephrine, growth hormone, ACTH and glucagon, as well as for the decrease in insulin. This adaptation is especially marked with regard to the sympathoadrenal activation with exercise and occurs rapidly, within the first 2 weeks of training 51 . The mechanism behind this change is not fully established, but hormonal activation secondary to
It had been supposed that there might be a molecular weight limit on drug entry into brain from blood, uptake of drugs above about 800 kDa being small (25). However, drugs Levin studied, such as doxorubicin, vincristine, and etopside, are now known to be substrates for a potent mechanism that restricts brain entry of a wide range of drugs. Thus P-glycoprotein is sited in the apical (blood-facing) plasma membrane of the endothelium and is able to utilize ATP in pumping certain drugs from endothelial cells into blood, thus reducing brain entry, as reviewed by Borst and Schinkel (26) and in this volume by Begley et al. (23) and by Mayer (27). Substrates include vinblastine, ivermectin, digoxin, and cyclosporine. Molecules transported are often lipo-
Previous brain surgery (to identify possible recipients of dura mater grafts), growth hormone use before the mid-1980s (after which artificially synthesised growth hormone came into use), and close family members who might have had CJD (to identify those at risk of familial CJD). For patients who are identified as being at risk, any surgery involving the brain, spinal cord or eye should be undertaken using disposable instruments that are' subsequently incinerated. Surgery involving other tissues in such patients is ideally also undertaken with disposable instruments and, if non-disposable instruments are used, they must pass through a stringent decontamination process, separately from other instruments. This involves two washing cycles and a total of 18 min in a porous load (vacuum) autoclave.
Hereditability estimates for a given trait can range from 0.00 to 1.00. The higher values mean there is a stronger genetic influence on a particular trait. Height is estimated at .90, meaning your height is highly dictated by how tall your parents are and the heights of their genetic lineages.
The drugs that have made it into the transdermal market include sco-polamine, nitroglycerine, nicotine, clonidine, fantanyl, estradiol, testosterone, lidocaine, and oxybutinin (Langer, 2004). Recent additions to this list include lidocaine-tetracaine, selegiline, methyl phenidate, and rotigotine. However, the future focus is production of transdermal systems capable of delivering peptides and proteins including insulin, growth hormone, and vaccine across the skin.
Nevertheless, the development of somatic nuclear transfer techniques that facilitate targeted genetic modifications has driven transgenic research over the past 5 years. Small interfering RNA techniques and lentiviral vectors have also contributed to this cause, as have modified episomal vectors designed to promote high levels of expression of therapeutic genes (Manzini et al, 2006). The use of transgenic animals as bioreactors to synthesize valuable proteins in large quantities is probably the major application for new transgenic animals. Goats and rabbits are the most popular target species, in addition to the cow, for producing a range of proteins including enzymes such as alpha-glucosidase, hormones such as human growth hormone and large proteins such as lactoferrin, albumin, collagen and vaccines (e.g. for malaria). The development of a recombinant human antithrombin III expressed in goat's milk is the closest of these products to commercial release (Niemannn and Kues, 2007).
Reported to correlate with life history of aggression in a sample of personality-disordered subjects, covariance analyses revealed that most of this relationship could be statistically accounted for by reductions in CSF 5-HIAA (Brown et al., 1979). One study investigating the effects of the noradrenergic alpha-2 receptor agonist clonidine on the release of hypothalamic growth hormone release revealed a relationship with self-reported irritability in both personality-disordered patients and healthy volunteers (Coccaro et al., 1991), but this effect remains to be replicated.
This gangliocytoma of the pituitary is composed of randomly oriented, dysmorphic neurons embedded in a fibrillary matrix without an intervening astrocytic proliferation. The majority of neoplastic neurons are well-differentiated ganglionic cells, many with an aberrant cytoarchitec-ture, including multiple nuclei (inset). The gangliocytoma in this case is intimately adjacent to a growth-hormone-producing pituitary adenoma. SMI-33 (phosphoryla-tion-independent NF H M epitope)-avidin-biotin complex linked immunoperoxidase technique.
Some effects of testosterone on bone tissue maybe facilitated indirectly by growth hormone (GH) and, consequently, insulin-like growth factor type 1 (IGF-1) levels. These hormones have an intrinsic effect on bone tissue, increasing bone mass and density (Baum et al. 1996 Grinspoon et al. 1995 Monson 2003). Administration of androgens to hypogonadal men enhances GH secretion, mediated at the hypothalamic level primarily by promoting GHRH shedding (Bondenelli et al. 2003). Elevation of testosterone levels increases exercise- or GHRH-stimulated GH pulsatility in hypo- and eugonadal men consecutively, these effects were also observed for IGF-1 concentrations (Fryburg et al. 1997). This appears to be an important issue for assessing the role of the somatotropic axis is important when androgen effects on bone metabolism are investigated.
Activating mutations of the alpha subunit of the G protein that enhances cellular cAMP were first demonstrated in growth hormone-secreting pituitary tumors by Vallar and coworkers in 1987.20 Further investigations by Landis21 and Masters22 and their colleagues biochemically identified and characterized the effect of these stimulating mutations that inhibit G protein-specific guanosine triphosphatase (GTPase) activity. The mutated stimulating G protein (Gs) has a much lower GTPase activity than wild-type Gs. The reduced susceptibility of GTP to hydrolysis may increase the period of Gs in the GTP-bound state. Because Gs-GTP
The final distinction to draw is between genetic technologies used as a form of medical therapy and those same techniques used to enhance the abilities and characteristics that persons already have. For example, gene therapy might be used to increase the height of children with growth hormone deficiency to that of the norm in the population. This would count as therapy. But the same (or similar) techniques could be used to increase the height of a normal child so that they were of above average height. This wouldbe enhancement of characteristics. These possibilities have raised fears of ''designer babies'' and are felt to produce some of the strongest arguments against gene therapy, or specifically, germ-line gene therapy, since the general view is that effective enhancement treatment would have to act on the germ cells.
Fetuses with IUGR are those that fall below the 10th percentile for weight for a given gestational age. IUGR occurs when a fetus does not meet its growth potential (Vandenbosche and Kirchner, 1998). Some below-10th-percentile fetuses are not growth-restricted but constitutionally small, have reached their growth potential, and are healthy. Often, it is difficult to differentiate the two states. Although mild growth abnormalities are generally tolerated well by the fetus, more severe growth abnormalities can be associated with poor outcome, including fetal distress, fetal demise, and postnatal developmental abnormalities (Botero and Lifshitz, 1999). The growth-restricted fetus should be identified so that appropriate management can be instituted to ensure the best outcome. Factors that influence fetal growth can be divided into the following three categories
Short stature Constitutional growth delay Familial (genetic) short stature Growth hormone deficiency, congenital or acquired Tall stature* Familial Constitutional acceleration of growth Familial tall stature *Data from Bell J. Tall stature. In Finberg L (ed). Saunders Manual of Pediatric Practice. Philadelphia, Saunders, 1998, pp 728-730.
Several studies have been published on the effects of epidural and intrathecal opioid administration on the surgical stress response. The main conclusion has been that, despite acceptable postoperative pain relief, these techniques have no major effect on the overall postoperative stress response.13 13 Thus, the modifying effect is not comparable with that observed during epidural local anesthesia. However, long-term intrathecal opioids may lead to hypogonadism, hypocorticism, and growth hormone deficiency.113
The Mantel-Haenszel methods (Mantel 1959, Greenland 1985) are the default fixed-effect methods of meta-analysis programmed in RevMan. When data are sparse, either in terms of event rates being low or study size being small, the estimates of the standard errors of the effect estimates that are used in the inverse variance methods may be poor. Mantel-Haenszel methods use a different weighting scheme that depends upon which effect measure (e.g. risk ratio, odds ratio, risk difference) is being used. They have been shown to have better statistical properties when there are few events. As this is a common situation in Cochrane reviews, the Mantel-Haenszel method is generally preferable to the inverse variance method. In other situations the two methods give similar estimates.
No specific type of physical constitution or occupation was reported for the patients. It remains unclear, however, if obesity and diabetes mellitus influence the incidence of OPLL. Several systemic metabolic backgrounds (e.g., growth hormone, sex hormone) have been proposed to play a causative role in OPLL. For example, patients with OPLL have a higher incidence of diabetes than the overall population and may have coexisting hypoparathyroidism, acromegaly, vitamin D-resistant rickets, spondyloepiphyseal dysplasia, and myotonic muscular dystrophy.
At present, there is not sufficient evidence to implicate hormonal dysfunction as a direct cause of OCD. However, some intriguing data build a circumstantial case for an association between OCD and growth hormone abnormalities, perhaps through the serotonergic system. In the epidemiological study of OCD among high school students, described earlier, males with OCD were noted to be smaller and lighter than the community of normal controls (Flament et al., 1988). This was also shown to be true of males with other anxiety disorders (Hamburger et al., 1989). There were no reductions in the height or weight of the adolescent girls with OCD. The small size of the OCD males could be due to an effective lack of growth hormone, or to a delay in the pubertal growth spurt, although, of course, no causality is demonstrated by the relationship. To address the issue of causality, future research might employ direct assays, hormonal challenges, or therapeutic interventions.
Now if all five girls had been at the top of the rankings their total would have been 5 x 0 0 (as they would have had no boys above any of them) and the boys would have scored 5 x 5 25 (as all five of them would have had five girls above them). If the boys had all been at the top then the totals would have been reversed. With the researcher's one-tailed test we are focusing on the girls' total being small, indicating their ranks are at the top. If the girls score 0 then it seems reasonable to conclude that there is a genuine difference between the girls' and boys' ratings. If the girls scored 25 then clearly they are not ranked higher than the boys. When the score is midway between the two (12 or 13) then the two groups are mixed in their
A P value is the probability of obtaining the observed effect (or larger) under a 'null hypothesis', which in the context of Cochrane reviews is either an assumption of 'no effect of the intervention' or 'no differences in the effect of intervention between studies' (no heterogeneity). Thus, a P value that is very small indicates that the observed effect is very unlikely to have arisen purely by chance, and therefore provides evidence against the null hypothesis. It has been common practice to interpret a P value by examining whether it is smaller than particular threshold values. In particular, P values less than 0.05 are often reported as statistically significant , and interpreted as being small enough to justify rejection of the null hypothesis. However, the 0.05 threshold is an arbitrary one that became commonly used in medical and psychological research largely because P values were determined by comparing the test statistic against tabulations of specific percentage points of...
The hormonal secretions of the anterior pituitary (the adenohypophysis) are regulated by a number of hypothalamic releasing hormones and inhibitory molecules. These factors reach the pituitary through the portal circulation and, on interaction with specific receptors, either stimulate or inhibit the secretion of the anterior pituitary hormones. The main releasing hormones include thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), cortico-tropin-releasing hormone (CRH), and growth hormone-releasing hormone (GHRH). The two major inhibitory factors are dopamine, which principally inhibits prolactin release, and somatostatin, a potent inhibitor of growth
With advanced renal disease, patients may undergo dramatic changes in physical appearance, as a result of either the disease process itself or adverse effects of treatment. Short stature and delayed puberty are common, along with long-term psychological effects that accompany these deficits (Grooten-huis et al. 2006 Rosenkranz et al. 2005). Bone deformity may be a result of ESRD. Scarring from catheter and port placements for dialysis, as well as gastrostomy tubes, may be a source of embarrassment and impaired body image. Corticosteroids and immunosuppressants commonly cause cosmetic Impaired growth hormone and insulin-like growth factor, anemia, secondary hyperparathyroidism Short stature Growth hormone supplementation, optimization of nutrition
The increase of SHBG concentrations in elderly men is remarkable as it occurs in the face of increased fat mass and insulin levels, factors known to be inversely correlated to SHBG levels, but the cause of this increase of SHBG levels remains unclear. It is unlikely that the decreased testosterone levels per se are responsible, as the increase in SHBG levels is observed at an earlier age than the decrease of testosterone levels estradiol serum levels are rather similar in young and elderly men (Vermeulen etal. 1996). Serum SHBG and testosterone levels have been reported to be inversely correlated to 24-hour growth hormone and to IGF-I levels (Erfurth etal. 1996 Pfeilschifter etal. 1996 Vermeulen etal. 1996) and it has been proposed that decreased activity of the somatotropic axis may play a role in the age-associated increase of SHBG levels and ensuing decrease of free testosterone levels (Vermeulen etal. 1996).
In a majority of controlled trials of several months duration with administration of androgens to elderly men with low or (low) normal serum (bio-available) testosterone, treatment resulted in a modest decrease of total and or abdominal fat mass (Gruenewald and Matsumoto 2003). These findings were confirmed in recent controlled studies in elderly men with transdermal administration of testosterone (Steidle etal. 2003) or DHT (Ly etal. 2001), although in this context growth hormone may have a greater effect than testosterone (Mtinzer etal. 2001).
The sequelae of radiation therapy in the developing nervous system can be profound, and have become increasingly important as the survival of patients with medulloblastoma has improved. Cognitive impairment, growth retardation, and leukoencephalopathy are all associated with the use of radiation therapy in children. The vast majority of children with medulloblastoma treated with adjuvant radiation therapy have a decrease in intelligence quotient (IQ).39 Furthermore, the hypothalamic-pituitary axis is often depressed following posterior fossa irradiation, as evidenced by the high incidence of growth hormone deficiency in patients and an average height in the 25th percentile.39
Children with retarded or advanced bone ages may be short or tall for their age. Children with advanced bone age may undergo premature fusion of the epiphyses and be short in adult life. A predicted adult height can be obtained from standard tables, which require an assessment of current height and bone age. Image of a hand in a child of 6 years and 10 months with growth hormone deficiency and a dissociated bone age. The phalangeal bone age is 5 years and the carpal bone age is 2 years (G&P)
One of the first animal projects involved producing GM pigs expressing human growth hormone genes, which were designed to grow more rapidly than normal pigs and produce leaner meat. However, these so-called ''Beltsville pigs'' suffered greatly reduced welfare and provided a warning of the dire consequences which could result from this approach. GM fish are perhaps the animals closest to commercial use, with growth stimulation the principal objective. In some GM salmon, blood concentrations of growth hormone are 40 times the normal level, resulting in 5-to 11-fold increases in weight after one year of growth. Concerns for animal welfare arise from the observation that body composition and conformation can be affected, resulting, for example, in an excessive and deleterious deposition of cartilage, a pathological condition analogous to acromegaly in mammals. Other ethical concerns relate to environmental risks (specifically, effects on biodiversity and sustainability). Unlike farm...
Normal anterior pituitary comprises five histologically and functionally distinct cell types. These are lactotrophs, soma-totrophs, corticotrophs, thyrotrophs, and gonadotrophs, which are distinguished functionally by their secretion of prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), and the gonadotropins (luteinizing hormone LH and follicle-stimulating hormone FSH ), respectively. Although susceptibilities vary, each of these cell types is subject to neoplastic transformation, giving rise to tumors that retain the morphologic characteristics, secretory capacity, and nomenclature of the cell of origin. From an endocrine standpoint, the vascular supply to the ade-nohypophysis is via a confluence of capillary networks forming the portal system, which is crucial for the transfer of trophic hypothalamic hormones to the adenohypophysis.
Patients with prolactin-secreting adenomas mostly have growth arrest, in the form of short stature, and pubertal arrest.6,9 Specifically, females are at risk for menstrual dysfunction and galac-torrea, whereas males have hypogonadism. All patients harboring prolactinomas in a Mayo Clinic study had a raised level of serum prolactin.6 Hyperprolactinemia may also occur as a result of the stalk section effect. If the pituitary stalk is compressed, so that the delivery of the prolactin inhibitor (dopamine) to the adenohypophysis is interfered with, then hyperprolactinemia may occur. Thus hyperprolactinemia occurring as a result of a prolactinoma versus the stalk section effect must be distinguished. The most common hormone deficiency associated with prolactinomas is GH.15
Skin and connective tissues, and the musculoskeletal, cardiovascular, and respiratory systems. Some of the classic characteristics of acromegaly are coarse facial features, soft-tissue thickening, and enlargement of hands and feet. Thus the excess GH production that occurs with somatotroph adenomas in children is manifested by rapid linear growth, acromegalic features, and menstrual irregularities.9 With respect to the laboratory diagnosis of GH excess, the basal levels of GH should be measured and are often high in patients with somatotroph adenomas. Because growth hormone is secreted in a pulsatile fashion, a single elevated random GH level is insufficient to either secure or exclude a diagnosis of hypersomatotropism. Instead, one needs to demonstrate failure of GH suppressibility during an oral glucose tolerance test, as well as an elevated age- and sex-appropriate insulin-like growth factor 1 (IGF-1) level (somatomedin-C).
Monal abnormalities occur in 43 to 90 of patients at diagnosis.48 All of the adenohypophyseal hormones can be affected, including growth hormone luteinizing hormone (LH) or follicle-stimulating hormone (FSH) adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone. Deficiencies in LH and FSH lead to delayed or arrested puberty in adolescents, loss of libido, or secondary amenorrhea in adults. Low growth-hormone levels will result in growth retardation and delayed bone age. Hypothyroidism leads to poor growth, weight gain, cold intolerance, and fatigability. Forty percent of children demonstrate decreased height velocity or short stature at diagnosis, either from growth-hormone deficiency, central hypothy-roidism, delayed puberty, or a combination of these three. Impingement on the pituitary stalk leads to decreased amounts of prolactin inhibitory factors such as dopamine. This stalk effect results in hyperprolactinemia. In Fahlbusch's reported data, pre-operative endocrine...
Pancreatectomy Pancreatitis from many causes Viral infections Coxsackie viruses, measles Beta cytotoxic drugs Diabetogenic hormones (exogenous or endogenous) Growth hormone Epinephrine ACTH or glucocorticoids Hemochromatosis Disorders of insulin receptors Factors of immunity and autoimmunity Human leukocyte antigens (HLA)
In addition to general physical attractiveness, there are specific physical appearance factors, often related to attractiveness, that have been shown to be related to occupational success. At least two surveys have shown a relationship of height and weight to occupational success. Quinn (1978) used data from national surveys at the University of Michigan and found that taller men earned more money and held more prestigious jobs than shorter men. Also, men and women who were underweight and overweight earned less than those who were average in weight. Frieze, Olson, and Good (1990) surveyed 859 male MBAs and 355 female MB As who graduated from the University of Pittsburgh between 1973 and 1982. Weight and height were particularly important correlates of salary for the male MBAs, with the salary differences between overweight and normal weight employees increasing over time.
The adenohypophysis is derived from the invagination of the hypophyseal-pharyngeal duct known as Rathke's pouch. The adenohypophysis constitutes approximately 80 of the entire pituitary and is divided into the pars distalis (anterior lobe), pars intermedia (intermediate lobe), and the pars tuber-alis (pars infundibularis). The pars distalis is the largest and the functional part of the adenohypophysis. The pars intermedia in the human pituitary is a poorly developed, rudimentary structure lying between the anterior and posterior lobes. It often degenerates into a pars intermedia cyst (less than 5 mm) filled with colloid material. The pars tuberalis is an upward extension of the anterior lobe along the pituitary stalk and may be a source of suprasellar anterior-lobe pathology. The anterior lobe is the source of prolactin (PRL), growth hormone (GH), thyroid-stimulating hormone (TSH), gonadotropic hormones (follicle-stimulating hormone FSH and luteinizing hormone LH ), and...
Conditions to exclude include other mitochondrial diseases, primarily MERRF and MELAS any disease causing ophthalmoplegia when that is the sole presenting symptom, especially myasthenia gravis other diseases that cause multisystem involvement, such as collagen vascular diseases, particularly systemic lupus erythematosus and in the appropriate setting, Lyme disease (caused by infection with Borrelia burgdorferi) or Whipple's disease. The ultimate diagnosis is made by muscle biopsy and mtDNA analysis. There is no proven specific treatment, although coenzyme Q10 and carnitine have been used. Implanted cardiac pacemakers can be used for conduction defects. Associated endocrine abnormalities--growth hormone deficiency, diabetes mellitus, or hypoparathyroidism--can be treated medically. Although these conditions are considered chronic, complete heart block may result in sudden death.
Chronic obstructive pulmonary disease (COPD) is a chronic debilitating disease for which there are few effective therapies. Muscle wasting and dysfunction are recognized as correctable causes of exercise intolerance in these patients. It has been speculated that low levels of anabolic hormones such as testosterone, growth hormone and insulin-like growth factor-1 may contribute to muscle atrophy and dysfunction (Casaburi et al. 1996). Human growth hormone increases nitrogen
Fifty of the 72 patients diagnosed between 1960 and 1970 were thoroughly studied (Table 1). Forty-three (86 ) had panhypopituitarism, whereas seven (14 ) displayed selective pituitary deficiencies. Of the latter group, one had isolated thyroid stimulating hormone (TSH) deficiency, one had selective human growth hormone (HGH) and gonadotropin deficiency, two lacked HGH and ACTH and three had combined HGH, ACTH, and gonadotropin deficiency. Human growth hormone reserve was studied in all the patients. In the basal state, HGH was undetectable. With estrogen-priming and challenging with either insulin-induced hypo-glycemia or arginine infusion, only the patient with selective TSH deficiency had HGH reserve, as shown by an increase to 20 ng ml upon arginine infusion.
In adult patients, the most common type of SE is secondary generalized convulsive SE (GCSE). Generalized convulsive SE is characterized by intermittent or continuous overt convulsive activity accompanied by coma and epileptiform activity on EEG. The manifestations change over time such that discrete convulsions give way to increasingly subtle clinical manifestations, which is a condition known as subtle SE. Eventually, electrical status without clinical manifestations is all that remains. Occasionally, subtle SE occurs without prior convulsive activity in patients with severe diffuse cerebral dysfunction. Generalized convulsive activity produces various systemic effects including hypoxia, hyperpyrexia, blood pressure instability, and cerebral dysautoregulation. Metabolic derangements including respiratory and metabolic acidosis hyperazotemia hypokalemia hyponatremia hyperglycemia followed by hypoglycemia and marked elevations of plasma prolactin, glucagon, growth hormone, and...
Prolactin, growth hormone, and estradiol appear to be important accessory regulators for prostatic tissue permeability, receptor binding, and testosterone synthesis. FIGURE 92-2. Hormonal regulation of the prostate gland. ACTH, adrenocorticotropic hormone DHT, dihydrotestosterone FSH, follicle-stimulating hormone GH, growth hormone LH, luteinizing hormone LHRH, luteinizing hormone-releasing hormone PROL, prolactin R, receptor. (From DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy A Pathophysiologic Approach, 6th ed. New York McGraw-Hill, 2005 1856.) FIGURE 92-2. Hormonal regulation of the prostate gland. ACTH, adrenocorticotropic hormone DHT, dihydrotestosterone FSH, follicle-stimulating hormone GH, growth hormone LH, luteinizing hormone LHRH, luteinizing hormone-releasing hormone PROL, prolactin R, receptor. (From DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy A Pathophysiologic Approach, 6th ed. New York McGraw-Hill, 2005 1856.)
Growth hormone effects on, 803 serum, 229-248 Lipid emulsion, intravenous, 1683-1685, 1684 , 1690, 1695 caloric value of, 1683 coalescence of, 1683 complications and safety of, 1684 creaming of, 1683 oiling out of, 1683 Lipolysis, 756 Lipophilic drugs, 544-545 Lipoprotein(s). See also specific types metabolism of, 230-232, 231f 232f structure of, 230, 230f Lipoprotein(a), 240 Lipoprotein lipase, 230, 231, 1684 Lipram products, 409 Liquid dosage forms, administration through
Thyroid tumors vary markedly in prognosis, and the natural history of differentiated tumors is long. The control of thyroid cell growth is complex and is influenced by many hormones and growth factors operating through distinctly different cell signal transduction systems. Classically, TSH is considered the major thyroid growth hormone, and, although there is no dispute about its role in stimulating thyroid gland function, its effects on thyroid growth and particularly abnormal growth are in question. TSH stimulates differentiated thyroid functions, most notably iodine uptake and organification as well as thyroglobulin synthesis, by activating a membrane-bound adenylate cyclase system and increasing intracellular cyclic adenosine monophosphate this results in cytoplasmic protein phosphorylation and increased nuclear transcription.177 In general, follicular thyroid neoplasms have enhanced adenylate cyclase activity in response to TSH stimulation and tend to have an inverse correlation...
Aortic rupture or dissection in Turner syndrome was mentioned earlier (see Fig. 8-9).7,64,80,129,218,219,241 The typical XO Turner phenotypic female (see Fig. 8-10) is of short stature with webbing of the neck, absent or scanty auxiliary and pubic hair (ovarian dysgenesis), broad chest with widely spaced hypoplastic or inverted nipples, low anterior and posterior hairlines, small chin, prominent ears because Thirteen-year-old girl with 45XO Turner syndrome and coarctation of the aorta. Physical appearance is characterized by short stature, webbing of the neck, absent pubic hair, wide-set nipples, and small chin. Bangs obscure a low anterior hair line. Thirteen-year-old girl with 45XO Turner syndrome and coarctation of the aorta. Physical appearance is characterized by short stature, webbing of the neck, absent pubic hair, wide-set nipples, and small chin. Bangs obscure a low anterior hair line.
In summary then, there is evidence that partial and total penectomy adversely affects sexual function, with the greatest degree of dysfunction occurring in men who undergo more radical surgery and therefore lose more penile length. A general rule is that a residual postoperative penile length of 4 cm or more can still allow patients to achieve an adequate erection as well as ejaculate. Attempts at conservative therapy appear to be oncologically safe, but the evidence that they provide better sexual outcomes is at this time limited. Indeed, the quality of the evidence is relatively poor, with most publications being small and retrospective in nature.
Often they are mildly to moderately mentally retarded. They may be of short stature, with small hands, feet, and gonads. Behavioral problems are common and include obsessive-compulsive symptoms, compulsive food-related behaviors, temper tantrums, and aggression.
There is a tendency toward disc herniation in some families, such as those with congenital spinal anomalies, including fused and malformed vertebrae and lumbar spinal stenosis due to short pedicles. Patients with increased weight and tall stature are at increased risk for this condition. Also, acquired spinal disorders, such as common degenerative arthritis and ankylosing spondylitis, predispose to disc degeneration. Various behaviors that increase risk include sedentary occupations, physical inactivity, motor vehicle use, vibration, and smoking. In younger women, pregnancy and delivery are associated with lumbosacral herniation, and new symptoms of cervical disc herniation may occur in part because of the bending and lifting involved in child rearing.
Although androgens are the clearest regulators of human hair growth, unlike in most mammals (Ebling etal. 1991), various other circulating factors (reviewed in Randall 1994a) have an effect. These include adequate nutritional supplies, due to the follicles' high metabolic demands (Bradfield 1971), the hormones of pregnancy, which cause a prolonged anagen resulting in a synchronised shedding of a proportion of scalp hairs post-partum (Lynfield 1960), and lack of thyroid hormone which restricts hair growth (Jackson et al. 1972). Growth hormone is also necessary in combination with androgens for normal body hair development in
Frieboes et al. (1999) noted a number of alterations to sleep-endocrine relationships months to years following TBI. These included reduction in non-REM stage 2 sleep in the first half of the night and increased REM sleep in the second sleep cycle. With regard to endocrine functioning the nocturnal growth hormone peak was blunted and the maximal prolactin secretion was increased but the cortisol levels were unchanged.
Hormonal changes also seem to play an essential role with regard to the pathomechanisms involved in OTS, where peripheral and central mechanisms seem to have a synergetic effect. The various (supra)hypo-thalamopituitary-target gland axes are influenced by peripheral stimuli and at the same time they modulate peripheral functions 48,60 . This may even include the synthesis of Na+ K+-ATPase and thus the maintenance of the membrane potential which depends on glucocorticoid action (Fig. 2.1.5) 61 . In support of an impaired central regulation theory, a significantly decreased maximum exercise-induced rise of pituitary hormones such as adrenocorticotrophic (ACTH) and growth hormone, and cortisol during OTS in comparison to the normal state has been shown 49 . These re Fig. 2.1.5 Impaired maximal exercise-induced increase of adrenocorticotrophic hormone (ACTH), growth hormone (GH) (P 0.01), cortisol and insulin (P o. i) after exhaustive short-endurance cycle ergometer test with an intensity...
It must be pointed out that during pubertal initiation, testosterone also stimulates growth hormone secretion and growth hormone-dependent growth factor levels. Whereas no evidence points to a role of GH in adult spermatogenesis (Sjogren et al. 1999), this is less clear for the developing testis. In GH-deficient and IGF-I II-deficient animal models, testes - and body and organ size in general - are smaller. However, spermatogenesis is complete in these small testes, suggesting no direct involvement of GH and growth factors in initiation of spermatogenesis. For the GH-deficient dwarf rat it has been reported that spermatogenesis is also quantitatively normal (Bartlett etal. 1990b).
For example, patients followed for 2 to 10 months following TBI demonstrated elevated morning levels of cortisol, absence of diurnal cortisol variation, and non-suppression to dexamethasone challenge (Cohen, Oksenberg, Snir, Stern, & Grosswasser, 1992). Glucose loading in acute TBI patients was associated with increase in growth hormone (King, Knowles, McLaurin et al., 1981), prolactin secretion was noted to be elevated at various stages following severe TBI (Valenta & De Feo, 1980) and it is postulated that this latter disturbance may be attributable to the hypothalamic mechanism that controls the hormone's secretion (Molitch, 1992). Disturbances in the metabolism of thyroidal, gonadal, glucagon glucose, and antidiuretic
When visual loss due to a sellar process is suspected, pituitary and hypothalamic function should be evaluated. The basic outpatient endocrinological panel should include serum prolactin, growth hormone (GH) (after a 75-g oral glucose load), insulin-like growth factor-I, adrenocorticotropic hormone (ACTH), cortisol (serum morning sample or 24-hour urine free cortisol), thyroid-stimulating hormone (TSH), T3, T4, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and testosterone level. Low values, and even normal ones in some instances, are consistent with hypopituitarism. High values imply pituitary hypersecretion by a pituitary adenoma.
Several structures of ligand-binding domains of RTKs have been reported in the last 10 years, providing a basis for understanding dimerization mechanisms and ligand-receptor specificity (Table 4.1). The structures include receptors for cytokines such as growth hormone, prolactin, and eryth-ropoietin, as well as receptors for growth factors such as insulin-like growth factor I, fibroblast growth factor, nerve growth factor, and vascular endothelial growth factor. In general, only a subset Growth hormone (GH) GH FIGURE 4.3 Growth hormone receptor. Monomeric GH associates with two receptor monomers. Activated JAK2 kinases trans-phosphorylate JAK2 and GH receptors, and STAT transcription factors are phosphorylated by JAK2. FIGURE 4.3 Growth hormone receptor. Monomeric GH associates with two receptor monomers. Activated JAK2 kinases trans-phosphorylate JAK2 and GH receptors, and STAT transcription factors are phosphorylated by JAK2.
The incidence of this abnormal sex chromosomal karyotype is about 1 in 1000 live male births. These patients have a normal male phenotype, although cryptorchidism and hypogonadism have been known to occur. Tall stature and acneiform eruptions are common characteristics. Although earlier studies suggested that affected patients had inordinately aggressive, impulsive behavior, this finding has not been reliably substantiated. Most patients have normal behavior, and their intelligence tends to be low normal. Delayed acquisition of speech and language skills may also be present. Other minor neurological findings include postural tremor and motor incoordination. Turner's syndrome, a form of gonadal dysgenesis resulting from a 45,X karyotype (X-chromosomal monosomy), is characterized by female phenotype, short stature, a shieldlike chest, a short and sometimes webbed neck, low- set ears, high-arched palate, small mandible, and sexual infantilism. y The frequency of 45,X in female live...
Mothers of infants with the Prader-Willi syndrome note decreased in utero fetal activity, and often these neonates are born in breech presentation. The affected individuals are of short stature and have small hands and feet and a narrowed cranial bifrontal diameter. y Their eyes are almond-shaped, and they often have strabismus. The face is long, and nearly 50 percent of patients have hypopigmentation of the skin. Other common features include a small phallus, cryptorchidism, and hypogonadism with a small flat scrotum. Affected infants have a feeble suck and severe hypotonia, which commonly requires the use of a feeding tube. Near the end of the first year of life, however, the hypotonia may become less severe. The degree of mental retardation may seem more prominent in early life and may be correlated with the severity of the hypotonia. At 1 to 3 years of age the patients gain considerable weight and become obese because of hyperphagia. As the hypotonia becomes less severe, they also...
In patients with MEN 1, primary hyperparathyroidism is the most common clinical condition, occurring in approximately 95 of individuals.14 Functional pancreatic neuroendocrine tumors are the next most common condition, occurring in approximately 80 of patients.14 Finally, approximately 35 of individuals with MEN 1 develop a pituitary adenoma, most commonly a prolactinoma.14 Gastrinoma and insulinoma are the most common functional neuroendocrine pancreatic tumors in MEN 1 patients, accounting for approximately 50 and 20 of the neuroendocrine tumor syndromes, respectively.25 Nonfunctional pancreatic endocrine tumors and pancreatic polypeptide (PP)-producing tumors (PPomas) may be the most common pancreatic neuroendocrine tumors in MEN 1 patients because these tumors are almost always identified on careful histologic studies of the pancreas.26'27 Of the rare pancreatic neuroendocrine tumors, MEN 1 is present in approximately 3 of patients with glucagonoma, 1 of patients with VIPoma, 33...
Between muscles and the area of primary motor cortex (M1) that connects to those muscles is not fixed, but flexible (Graham Brown and Sherrington, 1912 Leyton and Sherrington, 1917 Lashley, 1923). The M1 contains a topography of movement representations which can be differentiated by brief (50 ms) electrical stimulation. Focal stimulation of distant regions of the motor cortex surface or deep in layer V near cortical spinal neurons reveals an organization in which contralateral face, arm and leg movements can be elicited from distinct regions, although the internal organization of each of these areas may be complex. The overall somatotopy has been described as the little man in the brain, the homunculus (Penfield and Boldrey, 1937). Penfield described both a motor and a somatosensory homunculus. An homunculus lays on each hemisphere, the foot and leg regions most medial (toes touching deep in the longitudinal cerebral fissure), and the arm and hand and face regions progressively more...
Hill et al. (31) failed to find any differences in the postoperative IL-6 level following laparoscopic and conventional inguinal hernia repair, which could be because the surgical insult caused by open hernia repair is not sufficient to generate increased levels of these markers. In a similar study, no difference in plasma cortisol, growth hormone, prolactin, and serum IL-6 levels was found following laparoscopic and open surgery for inguinal hernia, but a rise in C-reactive protein concentration and suppression of endotoxin-induced tumor necrosis factor-a production was recorded in both groups with greater changes after open hernia repair (32).
Other hormones show less consistent postictal changes. Serum Cortisol is elevated after both bona fide and simulated generalized seizures.39 The Cortisol rise follows that of corticotropin, beta-endorphin, and beta-lipotropin, all products of a common precursor molecule, proopiomelanocortin.6 Elevated vasopressin after seizures has also been reported.60 Because all these hormones are secreted in response to stress, their postictal elevation may not be specific to epileptic seizures. Inconsistent findings of postictal changes in LH and FSH have been revealed by different authors.33-34 60 No consistent significant postictal change has been seen in serum levels of growth hormone or TSH.34,60 Thus, postictal testing of hormones other than prolactin is at present not clinically useful.
Central obesity suggests increased visceral fat deposits, likely caused by increased production of peptides and other metabolic messengers. Hormonal influences most likely play a role in the distribution of fat. Central obesity is believed to result partly from increased androgenic effects, which is why men have a greater tendency for central obesity. Central obesity is also associated with hyperandrogenic states in women, such as polycystic ovary syndrome (PCOS). The increase in visceral deposition of fat that can occur after menopause in women may be related to a decrease in growth hormone and estrogen production (see Chapter 35).
Of subclinical Cushing's syndrome is established. Another suggested test is the growth hormone response to growth hormone-releasing hormone. A blunted growth hormone release might prove a sensitive and early sign of subclinical Cushing's syndrome.8 As already discussed, glucose tolerance is altered in patients with clinically inapparent adrenal masses (with and without subclinical Cushing), and a glucose tolerance test is recommended in patients with clinically inapparent adrenal masses.1012'38 Finally, bone mineral density of the spine should be performed to detect reduced bone mass in patients with subclinical Cushing's syndrome.14
Acromegaly gigantism, elevated growth hormone levels A. Growth Hormone C. Growth Hormone-Prolactin ACTH, Adrenocorticotropic hormone CRH, corticotropin-releasing hormone FSH, follicle-stimulating hormone GH, growth hormone GHRH, growth hormone-releasing hormone LH, luteinizing hormone PRL, prolactin TSH, thyroid-stimulating hormone. Somatotropic adenomas are responsible for the manifestations of gigantism in children and adolescents and acromegaly in adults. The clinical characteristics of these conditions are due to an excess of growth hormone. Acromegaly is characterized by extensive soft-tissue swelling, particularly in the hands, feet, and tongue. This pathophysiology is responsible for the typical body habitus as well as complaints of excessive snoring, sleep apnea, and carpal tunnel syndrome. In addition, acromegaly is associated with cardiomyopathies, hyperlipidemia, and abnormal serum glucose regulation, which pose significant health risks and morbidity if growth hormone...
During exercise, several hormonal systems are activated and increases are seen in plasma concentrations of adrenaline noradrenaline (epinephrine norepinephrine), adrenocorticotrophic hormone (ACTH), cortisol, b-endorphin, growth hormone, renin, testosterone, thyroid hormone and several gastrointestinal hormones (Fig. 1.2.4). Arterial levels of glucagon are unchanged or only marginally increased
Insulin stimulates glycogen synthesis in the liver and also promotes liver glucose uptake, but only at an elevated portal vein glucose concentration. Glycogen synthesis in the liver is also directly stimulated by increased vagal nerve activity. Glucagon, on the other hand, stimulates hepatic glycogenolysis as well as lipolysis in adipose tissue. In addition, glucagon stimulates the liver capacity for gluconeogenesis. The effect of glucagon on adipose tissue lipolysis is, however, secondary to the more powerful stimulation by the sympathetic nervous system, cortisol and growth hormone. Several other factors may stimulate hepatic glycogenolysis, including a- and b-adrenergic stimulation and vasoactive intestinal polypeptide, whereas hepatic gluconeogenesis is stimulated by increased precursor (lactate, pyruvate, amino acids, glycerol) availability, secondary to skeletal muscle glycolysis, skeletal muscle proteolysis and adipose tissue lipolysis. During exercise all these processes are...
The first step in diagnosing a patient with hypercortisolemia (Cushing's syndrome) is to find the etiology. In the subset of causes of Cushing's syndrome in the pediatric population, 85 of cases resulted from Cushing's disease.8 Patients diagnosed with Cushing's disease, thus having ACTH-releasing corti-cotroph adenomas, exhibit cushingoid features. Most often, these features in children are short stature, rapid weight gain, menstrual irregularities, skin striae, and mental status changes.9 To demonstrate that hypersecretion of cortisol is present, tests such as the 24-hour urinary free cortisol, 17-hydroxycorticosteroid, and creatinine excretion tests are performed.8 The normal diurnal variation in secretion of cortisol is also lost in Cushing's disease. The high- and low-dose dexamethasone suppression tests are also administered, with the dose of dexamethasone given according to body weight, and these tests have important diagnostic implications. These dynamic tests measure cortisol...
Androgen replacement therapy in male adolescents with constitutional delay of growth and adolescence has been shown to be beneficial psychologically as well as physiologically, and should be initiated promptly on diagnosis (Albanese and Stanhope 1995 de Lange etal. 1979 Kaplan et al. 1973 Rosenfeld et al. 1982). Boys with delayed puberty are at risk for not obtaining adequate peak bone mass and for having deficiencies in developing social skills, an impaired body image, and low self-esteem. Younger boys with short stature, delayed bone age (at least 10.5 years), and delayed pubertal development in the absence of other endocrinological abnormalities can be treated with 50-100 mg of testosterone enanthate or cypionate im, every four weeks for three months, whereas boys 13 years old maybe treated with 250 mg (im, every four weeks for three months). After a three-month wait and see period, another course of treatment may be offered if pubertal development does not continue. An increase in...
Increasing androgenic steroid secretion from the adrenals is defined as adrenarche and precedes puberty. Adrenarche is associated with increased growth of pubic and axillary hair independent of gonadal androgen secretion. Adrenal androgens include mainly dehydroepiandrostendione, its sulfate, and androstendione, but also other adrenal steroids have androgenic potential. Adrenocorticotropic hormone (ACTH) is a potent stimulator of adrenal androgen secretion however, its potency relative to cortisol secretion is much less. Also, substances other than ACTH may modulate adrenal androgen secretion. These include estrogens, prolactin, growth hormone, gonadotropins and lipotropin. None of these appear to be the usual physiological
Androgen therapy for HIV AIDS has been mainly investigated for its effects on disease-associated morbidity (weight loss, weakness, quality of life) rather than to influence the underlying disease natural history. Indeed, randomised placebo-controlled studies have consistently reported no androgen effect on CD4 count or viral load (Bhasin etal. 1998 Bhasin etal. 2001 Coodley and Coodley 1997 Dobs etal. 1999 Grinspoon etal. 1998 Rabkin etal. 1999 Sattler etal. 1999 Strawford etal. 1999) with two exceptions (Berger etal. 1996 Grinspoon etal. 2000), neither of which showed a consistent decrease in both CD4 count and viral load. One rationale for androgen therapy stems from the observation that body weight loss is an important terminal determinant of survival in AIDS and other fatal diseases (Grunfeld and Feingold 1992). It has been estimated that death occurs when lean body mass reaches 66 of ideal (Kotler et al. 1989) leading to the proposition that if androgens (or other agents...
For example, the osteoclast-inhibitor alendronate exerts beneficial effects onbone tissue in men with osteoporosis (Orwoll etal. 2000). Also injections of a fragment of PTH, teriparatide (rhPTH1-34), has stimulatory effects on bone formation in men, resulting in significant increase of bone mass (Orwoll et al. 2003). Men suffering from growth hormone deficiency may profit from respective supplementation in regard to maintenance of bone tissue (Baum et al. 1996 Grinspoon et al. 1995 Monson 2003 Ahmad etal. 2003).
Ghrelin, an endogenous ligand for the growth hormone (GH) secretagogue receptor, has been primarily linked to the central neuroendocrine regulation of GH secretion and food intake. Further, its actions on reproductive organs have also been reported, for example, steroidogenic dysfunction is associated with increased ghre-lin expression in human testes 121 . Recently, ghrelin has been suggested to be an endogenous antioxidant that functions as a free radical scavenger 122 . Ghrelin inhibits apoptosis by increasing the Bcl-2 Bax ratio, preventing release of cyto-chrome c, inhibiting ROS generation, stabilizing mitochondrial transmembrane potential, and inhibiting the activation of caspase 3 123 . Moreover, ghrelin was able to promote antioxidant enzyme activity (particularly that of GPx) and reduce lipid peroxidation in the testis. Taken together with the finding that luteinizing hormone human choriogonadotropic hormone (LH hCG) induces an enzymatic system with known antioxidant...
Hypothalamic-pituitary-target-organ axis. The hypothalamic hormones regulate the biosynthesis and release of eight pituitary hormones. Stimulation of each of these pituitary hormones produces and releases trophic hormones from their associated target organs to exert their principal effects. These trophic hormones regulate the activity of endocrine glands. Subsequently, increased serum concentration of the trophic hormones released from the target organs can inhibit both the hypothalamus and the anterior pituitary gland to maintain homeostasis (negative feedback). Inhibin is produced by the testes in the male and ovaries in the female during pregnancy. In-hibin directly inhibits pituitary production of follicle-stimulating hormone (FSH) through a negative feedback mechanism. Melanocyte-stimulating hormone (MSH) produced by the anterior pituitary is not illustrated in the figure (-), inhibit (+), stimulate ACTH, adrenocorticotropic hormone (corticotropin) ADH, antidiuretic...
Damage and destruction of the pituitary gland may result in secondary hypo-thyroidism, hypogonadism, adrenal insufficiency, growth hormone (GH) deficiency, hypopro-lactinemia, or insufficiency or absence of all anterior pituitary hormones (i.e., panhypopituitarism). A tumor (adenoma) located in the pituitary gland may result in excess secretion of a hormone or may physically compress the gland and suppress adequate hormone release. The type, location, and size of a pituitary tumor often determine a patient's clinical presentation. This chapter discusses the pathophysiology and role of pharmacotherapy in the treatment of acromegaly, GH deficiency, and hyperprolactinemia. The following hormones are discussed elsewhere in this textbook adrenocorticotropic hormone (ACTH or corticotropin), thyroid-stimu
May continue GH replacement therapy until child reaches satisfactory adult height, achieves documented epiphyseal closure, or fails to respond to treatment. 8. Review and retest the child using adult GH deficiency diagnostic criteria once the child reaches final adult height.
Exercise may act in synergy with hormones like growth hormone (GH) and IGFs for example, exercise amplifies periosteal bone formation induced by GH 39 . Exercise also seems to interact with estrogen effects on bone 40 . The changes in bone mass and turnover only occur in the strained parts of the skeleton. No effects in non-weight-bearing parts have been demonstrable 41 .
In 1921, Holger Scheuermann associated the disorder with avascular necrosis of the vertebral body ring apophysis. Abnormal growth plate cartilage, mechanical decompensation after endplate disc herniation (Schmorl's nodes), hormonal variation (increased growth hormone), osteoporosis, and malabsorption have been proposed as possible causes. Associations with Legg-Calve-Perthes disease, hypovitaminosis, dystonia, dural cysts, and endocrine disorders have been described. There appears to be a familial tendency. Evidence suggests that Scheuermann's disease is autosomal dominant with high penetrance and variable expressivity. However, the genetics of this disorder are not well defined.
Longitudinal studies of puberty were informative on the effects of endogenous sex hormones on cardiovascular risk factors in children and adolescents. Prepubertal boys and girls do not differ significantly in their serum lipid and lipoprotein levels. In contrast to girls, in whom levels of HDL-C and LDL-C change little with puberty, sexually maturingboys experience a decrease in HDL-C and increases in LDL-C and triglycerides (Bagatell and Bremner 1995). However, these changes may not reflect effects of sex hormones only since they are confounded by other endocrine changes, for example in the growth hormone-IGF1 axis, which also regulates lipoprotein metabolism.
The treatment of endogenous Cushing's syndrome depends on the underlying etiology. Growth Hormone Disorders Growth hormone (GH somatotropin) is secreted by the anterior pituitary in response to hypothalamic GH-releasing hormone (GHRH). GH promotes linear growth and has both anabolic and catabolic effects. Hypersecretion of GH causes gigantism when it occurs before epiphyseal closure and acromegaly when it begins afterward. Hyposecretion causes short stature in childhood and possibly a chronic fatigue-like syndrome in adults. GH acts indirectly through insulin-like growth factors (IGFs, somatomedins), with IGF-1 (formerly somatomedin C) being the most important for growth. Prolonged exposure to elevated levels of GH and IGF-1 results in the insidious onset of skeletal and soft tissue overgrowth, the latter of which is most pronounced in tissues containing large amounts of cartilage proteoglycans. 109 Cortical bone density is increased and trabecular bone (e.g., vertebral) density is...
Skeletal dysplasia with compressive neurological signs (severe in A, mild in B). No or little mental retardation. Corneal clouding 50 percent and organomegaly less prominent compared to other MPS. Survival to middle age Patients with Hurler-Scheie disease (type 2) have severe joint involvement, short stature, small thoraces, hepatosplenomegaly, coarse facial features, and corneal clouding. They may have near-normal mental abilities. The small thorax and cardiac involvement in this disease often reflect mitral valve insufficiency.
The clinical presentation of holoprosencephaly is dependent on the degree of CNS involvement. Infants with severe alobar forms often die shortly after birth. Survivors frequently present with severe mental retardation, seizures (infantile spasms occur early), severe motor impairments, poikolothermia, and endocrine insufficiencies. In the milder forms of holoprosencephaly, longer survival with various degrees of psychomotor retardation is possible. Endocrine dysfunction may become apparent, with diabetes insipidus and growth hormone deficiency having been reported in a number of cases. It should be re-emphasized that only the classic facial phenotypes are predictive of the severe alobar holoprosencephaly with its associated very poor prognosis but that a number of partial facial phenotypes, such as midline cleft lip or midface hypoplasia, are not necessarily associated with the most severe malformations in the spectrum.
Symptomatic hypoglycemias and diabetes insipidus later, growth hormone deficiency may become apparent. These endocrine insufficiencies can and should be treated by standard endocrine replacement protocols. Although retardation of cognitive development occurs especially in patients with obvious concomitant cortical anomalies, a number of cases with normal cognitive development are on record. Most cases of septo-optic dysplasia have been sporadic however, there are two observations in sibs and in cousins suggesting the existence of a form with autosomal recessive inheritance. It is an important consideration in the differential diagnosis in children presenting with optic hypoplasia. y
Animal studies with rats have suggested that during sleep deprivation, energy expenditure increases while temperature and weight drop until body systems begin to fail, beginning with the endocrine and immune systems.y This and other studies have led to the proposal that sleep conserves energy loss through thermoregulation When core body temperature decreases during sleep, heat loss to the environment is minimized. Similar studies have understandably not been performed in humans, but humans also show lowered body temperature during sleep. A different interpretation of temperature changes begins with the observation that sleep in general and deeper NREM sleep in particular are increased when the body is heated y therefore it is suggested that sleep functions to allow the shedding of excess accumulated heat.y This approach emphasizes not the decreased rate of heat loss in sleep due to decreased core temperature but the reduced rate of heat production due to slowed metabolism. Sleep may...
Proptosis or periorbital fullness suggests an orbital process such as Graves' disease, orbital meningioma, or orbital pseudotumor. The patient's general appearance may suggest an underlying chromosomal, endocrinological, or metabolic disorder. For instance, the disfiguring frontal bossing and enlargement of the mandible and hands are characteristic of acromegaly associated with a growth hormone-secreting pituitary adenoma. The heart rate, blood pressure, and carotid and cardiac examinations are important in any patient with a possible ischemic event. Patients with pseudotumor cerebri tend to be young females with obesity or a history of recent weight gain. Skin lesions such as erythema migrans (Lyme disease) or malar rash (systemic lupus erythematosus), and abnormal discolorations, such as cafe(c)-au-lait spots and axillary freckling (neurofibromatosis), or hypopigmented ash-leaf spots (tuberous sclerosis) also may be helpful in guiding the evaluation of patients with visual...
Linear growth in infants has been shown to occur in incremental bursts rather than continuously (Lampl et al., 1992). A growth curve constructed by a series of heights and weights taken over time allows the physician to compare current growth with the child's previous pattern. The linear growth velocity, or rate of gain in height, decreases from 25 cm per year during the first year of life to a prepubertal rate of 5 to 6 cm yr by age 6 or 7 years (Miller and Zimmerman, 2004). The rate accelerates during puberty. A child whose growth curve parallels the normal curve regardless of the child's absolute percentile has a normal rate of growth for that particular child. In comparison, a child whose height or weight crosses multiple percentile lines or whose linear growth rate drops below 4 cm yr requires further evaluation for nutritional, psychosocial, or organic problems that could impede or accelerate growth (Lipsky and Horner, 1988). Children with genetic short stature have normal...
A high incidence of OPLL has been reported in patients with metabolic and endocrinological disorders. Such disorders include calcium metabolic abnormality, hypoparathyroidism, vitamin D-resistant hypophos-phatemic rickets, disturbances in glucose metabolism, and growth hormone secretion or action. Acromegaly is sometimes reported to accompany OPLL. It is possible that changes in growth hormone secretion or its actions influence the development of OPLL 19 .
Receptors for hormones are present on the muscle membrane and contribute to plasticity. Fiber features are altered by thyroid and growth hormones, testosterone, and other anabolic steroids,206 and beta-2 agonists.207 Each may stimulate muscle fiber growth or prevent disuse atrophy. For example, experimental animal models show that hypothyroidism can prevent the loss of slow MHC mRNA in the nonweight bearing soleus, whereas hyperthyroidism prevented the switch of fast MHC protein types.208 Growth hormone with exercise may have a synergistic effect on limiting muscle atrophy and increasing muscle mass and strength in the elderly subject,209 but can cause adverse side effects. Indeed, all hormone replacement strategies include some risk for medical complications (see Chapter 12). The beta-2 adren-ergic agonists metaproterenol and clenbuterol have increased muscle mass and strength in patients with atrophy from a chronic SCI.210 Al-buterol had modest effects in patients with a muscular...
The most common site of germ cell tumors is the pineal followed by the suprasellar region (Figures 42-6 and 42-7). Occasionally they are found in the basal ganglia and thalamus (Figure 42-8). There is magnetic resonance imaging (MRI) and autopsy evidence that suprasellar region tumors originate from the neurohypophysis they grow intramedullarly along a line from the hypothalamus, pituitary stalk, and posterior pituitary lobe (neurohypophysis).7 Pituitary function studies revealed decreased levels of anterior pituitary hormones (especially growth hormone GH , follicle-stimulating hormone FSH , and luteinizing hormone LH ) and vasopressin and elevated prolactin titers, anomalies that manifest as panhypopituitarism because of neurohypophyseal dysfunction.21 These anatomic and functional features of suprasellar germ cell tumors have led to the adoption of the term neurohypophyseal tumor.
They encourage tissue degradation to provide energy for activity, in particular, protein degradation occurs in muscle. Growth hormone is secreted from the anterior pituitary during sleep. Lee and Stotts (1990) have reviewed the role of growth hormone in wound healing. It stimulates protein synthesis and the proliferation of a variety of cells including fibroblasts and endothelial cells.
Transgenesis involves the insertion of genes from one species to another, e.g. a human gene into a pig. As the genetic code is universal the transferred gene will work in its new environment. The new animal is described as transgenic. The first transgenic animals were mice produced in 1980. Pigs and sheep were produced to manufacture human growth hormone in 1985. The technique is mainly used in disease research. Another use is in the production of human polypep-tides for use in pharmaceuticals. Financial and ethical considerations may limit the use of this technique.
Recent advances in somatostatin analogues and growth hormone receptor antagonists have made medical treatment of acromegaly a viable option for patients with persistent disease postoperatively. Long-acting somatostatin analogues such as octreotide are used to reduce elevated growth hormone levels in acromegaly. Octreotide has been shown to reduce insulinlike growth factor 1 (IGF-1) to normal levels in approximately 60 of patients with persistent acromegaly following surgery as well as in de novo patients.4 Pegvisomant, a growth hormone receptor antagonist, has shown promising initial results in normalization of IGF-1 levels.15 There are relatively few clinical studies regarding the use of somatostatin analogues as primary therapy, and surgery remains the initial procedure of choice for most patients with acromegaly.
Studies have reported between 60 and 70 rates of early remission following surgery for patients with growth hormone-secreting adenomas.8 A long-term follow-up study in the Netherlands showed 40 of patients still in remission without adjuvant medical therapy 16 years after surgery.2 Recurrence seems to increase with time, as evidenced by two large clinical studies showing recurrence rates of 1.1 and 19 at mean follow-up periods of 33 months and 16 years, respectively.2,8
The incidence of OPLL is high in patients with metabolic and endocrinological disorders, including disrupted mineral metabolism by conditions such as hypoparathyroidism and vitamin D-resistant hypo-parathyroidism rickets osteomalacia, disturbed glucose metabolism, and altered sex hormones and growth hormone secretion or action 19,20 . Although none of the metabolic or endocrinological disturbances play a causative role in the development of OPLL, accumulating evidence indicates that disturbed bone and mineral metabolism that alters the actions of systemic hormones might underlie the progression of OPLL.
Then he said, Penises can hurt sometimes. He talked about taking a bath and about the penis being small versus big. Themes of hurting again were mentioned. (I think he was talking about erections and how it is big when he plays with it or takes a bath, and either it hurts him or he feels it is vulnerable to being hurt.) The themes continued to have something that sticks out, something that hurts or can be hurt, and something that can get small and big.
If the insulin deficiency is allowed to become profound, the disorder in FFA metabolism results in ketonuria, which accentuates the osmotic diuresis. The stress of illness can increase counterregulatory hormones (epinephrine, cortisol, growth hormone) that antagonize the effects of already-reduced insulin. The result is increasing hyperglycemia and further osmotic diuresis. Progressive hyperglycemia causes intravascular and intracellular dehydration, which reduces beta-cell
Becomes manifest with severe continuous motor activity and muscle stiffness, particularly in the face and thighs. Patients have an unusual masklike face with blepharospasm and continuous motor activity of the chin and lips. Hypertrophy of the thigh muscles also occurs. Patients may also have a variety of skeletal malformations including contractures and short stature. y
Studies characterizing human growth reserve in adult hypopituitarism have dealt mainly with pituitary neoplasms. Only eight among a total of 79 cases included in the largest series17-20 have been cases of Sheehan's syndrome. Of these 79, only four had significant levels of HGH, none of whom had Sheehan's syndrome. In this series of 50 patients, only one had HGH reserve and this patient also had isolated TSH deficiency. Of all pituitary functions evaluated, that of growth hormone secretion was the most consistently abnormal. Thus, a deficient output of growth hormone represents a sensitive and early index of pituitary failure.
Pseudohypoparathyroidism is a rare phenomenon representative of several congenital endocrinologic disorders in which tissue resistance to PTH is present. The classic form of this disorder is Albright's hereditary osteodystrophy (AHO). The AHO patient has short stature, mental retardation, brachydactyly, and PTH resistance (elevated PTH levels). Another form of AHO does not involve PTH dysfunction, called pseudo-pseudohypoparathyroidism. Although the clinical course of these diseases may vary and in some cases is protracted, AHO usually is associated with a shortened life expectancy. Treatment is primarily supportive (Levine, 2006).
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