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الرحيمDone by : Khaled Abd Ul-Karim Daif

ID : 432

Head of department : Dr. Maha Gamal

Supervised By: Dr Maged

Haron

Growth Hormone

TABLE OF CONTENT

Historical Note

Molecular level of GH

Development of Pituitary Gland

Histology of the Pituitary Gland

Hormones secreted from Pituitary Gland.

Parts of Pituitary Gland.

Pituitary Gland.

Diseases found in Pituitary Gland.

Diagrams.

Functions of Pituitary Gland.

The History of the Pituitary Gland.

•The earliest history of the pituitary gland dates back to Ancient Egypt (around 1365 BC) where a portrait, of the Pharaoh at the time (Akhenaton), shows signs of acromegaly. Galen, in 150 AD, was the first to describe the pituitary, and he proposed that its role was to drain the phlegm from the brain to the nasopharynx.•In the early 18th century, They pituitary-portal blood system was dicovered.• In 1772, Acromegaly was discribed. In 1794, Diabetes Insipidus was differentiated from diabetes mellitus. In 1887, Minkowski was the first to link the expansion of the pituitary gland to a number of clinical symptoms. Within a few years it was accepted that it was the anatomical growth of the gland that produced the symptoms.

5-6 wks

Development of Pituitary Gland

• From 6-8 weeks :• the neurohypophyseal bud grows inferiorly from the hypothalamus• the hypophyseal pouch grows superiorly from the roof of the mouth (Rathke’s pouch)• Neurohypophyseal bud becomes the posterior lobe (neurohypophysis)• Hypophyseal pouch becomes the anterior pituitary (adenohypophysis)

Histology of Pituitary Gland

Growth Hormone (GH)

Name : Growth hormone (also called somatotropin) Source of production : Adenohypophysis (Acidophilic cells in pars distalis known as somatotrophs).Chemical structure : peptide hormone composed of 191 a.a. presenting in many forms in plasma:-1) Normal human GH (known as hGH n) M.W. 22000.2) Variant human GH (known as hGH v) M.W. 20000.3) Desamino forms : less active.

GH Functions

1. Stimulates division and multiplication of chondrocytes of cartilage.

2. Increasing height in children and adolescents.3. Increases calcium retention, and strengthens and

increases the mineralization of bone.4. Increases muscle mass through sarcomere hyperplasia.5. Promotes lipolysis.6. Increases protein synthesis.7. Stimulates the growth of all internal organs excluding

the brain.8. Plays a role in fuel homeostasis.9. Reduces liver uptake of glucose.10. Promotes gluconeogenesis in the liver.11. Contributes to the maintenance and function of

pancreatic islets.12. Stimulates the immune system.

• Production of growth hormone is modulated by many factors, including stress, exercise, nutrition, sleep and growth hormone itself. However, its primary controllers are two hypothalamic hormones and one hormone from the stomach.

• Growth hormone-releasing hormone (GHRH) is a hypothalamic peptide that stimulates both the synthesis and secretion of growth hormone.

• Somatostatin (SS) produced by several tissues in the body, including the hypothalamus, inhibits GH release.

• Ghrelin secreted from the stomach binds to receptors on somatotrophs and potently stimulates secretion of growth hormone.

Regulation of GH Secretion

GH levels

• Plasma GH level: in children (5-8 ng/ml) and in adults (2-4 ng/ml)

• Some factors may elevate the level temporarily as decrease in blood glucose and FFA levels - Fasting and starvation conditions - physical stress - sleep - sex hormones.

• Other factors may depress it as obesity- aging - cortisol - somatostatin.

mechanism of release

• requires specific signal transduction systems (cAMP and/or calcium influx and/or mobilization of intracellular calcium) and/ or tyrosine kinase(s) and/or nitric oxide (NO)/cGMP

mechanism of action

• GH binding to two GHRs causes dimerization of GHR, activation of the GHR-associated JAK2 tyrosine kinase, and tyrosyl phosphorylation of both. These events recruit or activate a variety of signaling molecules

Growth hormone usesAgricultural Applications of Growth Hormone: In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, but it is not legal to use GH in raising cows for beef, cattle feeding, dairy farming and the beef hormone controversy. Use in poultry farming is illegal in the United States. Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin ) approved by the FDA but all applications have been withdrawn.

Replacement therapy: Treatment with exogenous GH is indicated only in limited circumstances, and needs regular monitoring due to the frequency and severity of side-effects. GH is used as replacement therapy in adults with GH deficiency of either childhood-onset (after completing growth phase) or adult-onset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being.

Performance enhancement: Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional

ACROMEGALY

andGIGANTISM

ACROMEGALY

DEFINITION

Chronic metabolic disorder

in which there is too much

growth hormone and the

body tissue gradually

enlarge

PATHOPHYSIOLOGY

Acromegaly is characterized by hypersecretion of growth hormone (GH),

which is caused by the existence of a secreting pituitary tumor in more

than 95% of acromegaly cases. Pituitary tumors are benign adenomas

and can be classified according to size (microadenomas being less than

10 mm in diameter and macroadenomas being greater than 10 mm in

diameter).3,4 In rare instances, elevated GH levels are caused by extra

pituitary disorders. In either situation, hypersecretion of GH in turn

causes subsequent hepatic stimulation of insulin-like growth factor-1

(IGF-1).1

SYMPTOMSBody odor

Carpal tunnel syndrome

Decrease muscle strength ( weakness )

Easy fatigue

Enlarge feet

Enlarge hands

Enlarge glands in the skin ( sebaceous

glands )

Enlarge jaw and tongue

Excessive height

Excessive sweating

Headache

Hoarseness

Joint pain

Limited joint movement

Sleep apnea

Swelling of bony areas around a joint

Thickening of skin, skin tags

Widely spaced teeth

Excess hair growth in females

Weight gain

DIFFERENTIAL DIAGNOSIS

Pseudoacromegaly

Presence of similar acromegaloid features in the absence of elevated GH or IGF-I levels

Physiologic growth spurt during puberty

Familial tall stature or large hands and feet

Myxedema

INVESTIGATION

Visual field tests

Assessment of other pituitary hormones: prolactin, adrenal, thyroid, and gonadal hormones

MRI scan of pituitary and hypothalamus: more sensitive than CT scan

CT scan: for lung, pancreatic, adrenal or ovarian tumours that may secrete ectopic growth hormone or GHRH

Total body scintigraphy with radio-labelled OctreoScan® (somatostatin) to aid localisation of the tumour

Cardiac assessment: electrocardiogram, echocardiogram

PROGNOSIS

Pituitary surgery is successful in most patient, depending on the size of the tumor and the experience of the surgeon

Without treatment the symptoms will get worse,and the risk of cardiovascular disease increase

COMPLICATIONS

Arthritis

Cardiovascular disease

Carpal tunnel syndrome

Colonic polyps

Glucose intolerance or diabetes

High blood pressure

Sleep apnea

Spinal cord compression

Uterine fibroids

Vision abnormalities

GIGANTISM

DEFINITION

Abnormally large growth due to

an excess of growth hormone

during childhood, before the

bone growth plates have closed.

CAUSES

The most common cause of too much growth hormone release is a noncancerous (benign) tumor of the pituitary gland. Other causes include:

Carney complex

McCune-Albright syndrome (MAS)

Multiple endocrine neoplasia type 1 (MEN-1)

Neurofibromatosis

If excess growth hormone occurs after normal bone growth has stopped, the condition is known as acromegaly.

SYMPTOMS

Delayed puberty

Double vision or difficulty with side (peripheral) vision

Frontal bossing and a prominent jaw

Headache

Increased sweating

Irregular periods (menstruation)

Large hands and feet with thick fingers and toes

Release of breast milk

Thickening of the facial features

Weakness

COMPLICATIONS

Delayed puberty

Difficulty functioning in everyday life due to large size and unusual features

Diminished vision or total vision loss

Embarrassment, isolation, difficulties with relationships, and other social problems

Hypothyroidism

Severe chronic headaches

Sleep apnea

PROGNOSISPituitary surgery is usually successful in limiting growth hormone production.

EXAMS & TESTSCT or MRI scan of the head showing pituitary tumor

Failure to suppress serum growth hormone (GH) levels after an oral glucose challenge (maximum 75g)

High prolactin levels

Increased insulin growth factor-I (IGF-I) levels

Damage to the pituitary may lead to low levels of other hormones, including:

Cortisol

Estradiol (girls)

Testosterone (boys)

Thyroid hormone

TREATMENT

Medications may be used to reduce GH release, block the effects of GH, or prevent growth in stature. They include:

Dopamine agonists, such as bromocriptine mesylate (Cycloset, Parlodel) and cabergoline (Dostinex), which reduce GH release

GH antagonist, pegvisomant (Somavert), which blocks the effects of GH

Sex hormone therapy, such as estrogen and testosterone, which may inhibit the growth of long bones

Somatostatin analogs, such as octreotide (Sandostatin) and long-acting lanreotide (Somatuline Depot), which reduce GH release

Radiation of the pituitary gland to regulate GH. This is generally considered the least desirable treatment option because of its limited effectiveness and side effects that can include obesity, emotional impairment, and learning disabilities.

Surgery to remove a pituitary tumor, which is the treatment of choice for well-defined pituitary tumors.

Other treatments of gigantism

Annu Rev Physiol. 1996;58:187-207,Molecular mechanism of growth hormone action,Carter-Su C, Schwartz J, Smit LS,Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622, USA.

Exp Biol Med (Maywood). 2004 Apr;229(4):291-302,Growth hormone secretion: molecular and cellular mechanisms and in vivo approaches,Anderson LL, Jeftinija S, Scanes CG,Department of Animal Science, Iowa State University, Ames, Iowa 50011, USA. llanders@iastate.edu

GIRARD J, VEST M, ROTH N. Growth hormone content of serum in infants, children, adults and hypopituitary dwarfs. Nature. 1961 Dec 16;192:1051–1053.

ROTH J, GLICK SM, YALOW RS, BERSONSA Hypoglycemia: a potent stimulus to secretion of growth hormone. Science. 1963 May 31;140(3570):987–988.

Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Shalet SM, Vance ML; Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J.

Clin. Endocrino. Metab. 91 (5): 1621–34.

"Center for Veterinary Medicine Master" www.fda.gov. 2011-04-06

"Growth Promoters in Animal Production" 2006. Retrieved 2011-08-28.

Endocrine Society's Clinical Guidelines Subcommittee, Stephens PA (May 2006). "Evaluation and treatment of adult growth hormone deficiency: an Endocrine Society Clinical Practice Guideline". J. Clin. Endocrino. Metab. 91 (5): 1621–34.

Gaffney G (2008-03-17). "Steroid Nation: Review from Stanford says HGH no benefit as PED". Steroid Nation. Retrieved 2011-08-28.

Randall T (2008-03-17). "Athletes Don't Benefit From Human Growth Hormone, Study Finds". Bloomberg. Retrieved 2011-08-28.

Liu H, Bravata DM, Olkin I, Friedlander A, Liu V, Roberts B, Bendavid E, Saynina O, Salpeter SR, Garber AM, Hoffman AR (May 2008). "Systematic review: the effects of growth hormone on athletic performance". Ann. Intern. Med. 148 (10): 747–58. PMID.

References

http://www.news-medical.net http://www.tev-tropin.com http://www.hypertropin.com http://www.youtube.com/user/ghdirect1 http://www.jintropin.cn http://www.vivo.colostate.edu

http://www.ncbi.nlm.nih.gov http://annals.org www.wikipedia.org

Thank You So Much..