Jims Problem

Group members : Clara Chua Yi Xin KhinNyein Thant Li Yawen Nisha

POSSIBLE CAUSE
(1) Precocious Puberty
-Appearance of physical and hormonal signs of pubertal development at an earlier age than consider normal. -The early development is triggered by a disease such as a tumor or injury brain.

(2) Gigantism
- Overproduction of growth hormones and due to an excess in release of GRF from hypothalamus. - A massive increase in height of the child and make him extremely large for his age.

TREATMENT
(1) Surgery for removal of tumors
- Somatostatin analogs: reduce the growth hormone release. (Such as Octreotide and Lanreotide) - Dopamine agonists: reduce growth hormones but less effective.

(2) Radiation therapy

Bringing the increased levels of growth hormones down to normal.

(3) Pegnisomant
Blocks the effect of growth hormone.

CONSEQUENCES OF IGNORANCE??
McCune Albright Syndrome
(1) It is caused by mutations in the GNASI gene.
1.

It results in abnormalities in the development of bone and skin pigmentation.

(2) Symptoms: - Autonomous endocrine hyperfunction such as precious puberty. - Polyostotic fibrous dysplasia: is a form of fibrous dysplasia affecting more than one bone. - Unilateral caf-au-lait spots: irregular, light brown color spots, especially on the back.

IF CONDITION UNTREATED
- Repeated episodes of broken bones. - Cosmetic problems resulting from facial bone abnormalities. - Blindness. - Deafness. - Premature puberty leading to short stature. - Osteitisfibrosacystica. (replacement of calcified bone by fibrous tissue) - Tumors: malignancies are rare and are usually sarcomas of the bone. (other malignancies: thyroid, testicular) - Shortens the lifespan of a person.

FURTHER INVESTIGATION
Under physical examination: Tall Well-proportioned Markedly muscular Others Mild facial acne Fine pubic hair Very large penis (for his age) Normal Testes size (3ml volume) Normal neurological signs (IQ & school performance)

EARLY DIAGNOSIS Precious Puberty

Premature appearance (2 characteristic, young children) Increase growth rate & premature skeletal mauturation Loss of synchronization (between physical maturation & emotional) 2-types Central (gonadotropin-dependent ) Peripheral (gonadotropin-independent )

EARLY DIAGONSIS

Hyperthyroidism Overproduction of thyroid hormones by overactive thyroid Increasing metabolism Several forms of hyperthyroidism :

Graves disease (diffuse toxic goiter) Toxic nodular goiter (multinodular goiter) Thyroiditis

SYMPTOMS MATCHING
Precious Puberty Growth of penis Jims Symptoms Large penis Hyperthyroidism Delayed puberty

Rapid height growth

Acne

Tall

Short stature

Mild facial acne

A puffy appearance to the face. Poor growth

Mature Body odor Muscle growth

Well-proportioned Markedly muscular Poor muscle tone

FINAL DIAGNOSIS

Precious Puberty Reason: Match with Jims symptoms

Sex-enhancing action of the disorder

Congenital adrenal hyperplasia
Genetic disorder Deficiency in the hormone control of aldosterone Overproduction of the hormone androgen (problems with normal growth & development in child sexual)

WHAT ARE THE NORMAL HORMONAL LEVELS FOR CORTISOL, TESTOSTERONE AND 17-OH-PROGESTERONE UNDER BASAL AND STIMULATED CONDITIONS?

Hormone

Normal levels

Patient's levels

Cortisol

Basal: 3-10ug/dl Stimulated: 3-21ug/dl 30

5-10ug/dl

Testosterone

172ng/dl

17-OH-progesterone

Basal: 100 Stimulated: 100

Basal: 12000ng/dl Stimulated: 22000ng/dl

ADRENAL HORMONAL IMBALANCE

A condition where production and release of hormones are at abnormal amounts. When a particular hormone is secreted at higher amounts than another. Adrenal medulla secretes: Epinephrine Norepinephrine

Adrenal cortex secretes:

Mineralcorticoids Glucocorticoids Sex steroids

ADRENAL HORMONAL IMBALANCE

There is a wide variety of possible causes of adrenal hormone imbalance. They can be both caused by environmental factors or genetic.

Unhealthy dietary practices Hormonal/ Antibiotic treatment Medication Pain relievers Family history Sedentary lifestyle

Enlargement of adrenal gland due to hyperplasia

ADRENAL HORMONAL IMBALANCE

Cortisol secretion the A.P gland is not subject to feedback control Secretes abnormally high amount of ACTH Increase uptake of cholesterol by the adrenal cortex Enlargement of the adrenal cortex causing hyperplasia Most common causes a deficiency in cortisol resulting in Addison

disease
The excess cholesterol is metabolized to produce androgens such as

testosterone
In the male this condition may results in precocious puberty but it

may cause virilisation of females

INITIAL THERAPY
Replacement hormone medication In this case, cortisol is lacking so hydrocortisone or dexamethesone can be taken daily to replace cortisol.

CONGENITAL ADRENAL HYPERPLASIA

1.

Deficiency in enzyme 21-hydroxylase

2.

This is an enzyme responsible for production of cortisol and aldosterone.

CYP21A2 gene is needed for the making of the enzyme

3.

4. Mutation in this gene causes deficiency of the enzyme 5. Lack of enzyme 21-hydroxylase leads to the formation of the substance used to synthesize cortisol and aldosterone 6. The substances are then converted to androgens, thus leading to an overproduction of androgens.

Androgen excess Simple Virilisation

SaltWasting

SALT-WASTING
Adrenal

gland unable to synthesize adequate amounts of aldosterone

Cortisol deficiency worsens condition GFR decreases leading to the hyponatremia Lose large amounts of sodium in urine
Symptoms:

poor appetite, vomiting, lethargy and failure to gain

weight

SIMPLE VIRILISATION
Often

results in ambiguous genitalia

in masculinization of the reproductive

Results

tract
Child

appears tall in childhood but have a shorter stature in adulthood

VIRILISIN G

SALT WASTING

TREATMENT FOR SALT WASTING

Fludrocortisone, Replaces Increases Dose

a mineralocorticoid

the missing aldosterone the sodium levels and blood volume

of Fludrocortisone :

0.10.2 mg

TREATMENT FOR SALT WASTING

Sodium chloride

supplements of 1-2g daily

An intravenous (IV) bolus

of isotonic sodium chloride of 20 ml/kg or 450ml/m2

If patient is hypoglycemic,

dextrose must be given after this dose

TREATMENT FOR VIRILIISING

Fludrocortisone

aid in adrenocortical suppression

Surgery can be recommended to females to correct the genital abnormalities However, problems may arise deciding the true sex of the patient

OTHER TREATMENTS?
2/15/12

Gene therapy

Experiments done on mice were successful

Problems were faced when trying to suppress adrenal androgens in humans

OR

Precocious Puberty due of Adrenal Hyperplasia

REFERENCES

A.S,Ekman (2009). Gigantism. Available: http://www.nlm.nih.gov/medlineplus/ency/article/001174.htm Eugster, E. (2009). Gigantism. Available: http://www.endotext.org/pediatrics/pediatrics1/pediatrics1b/pediatricsf rame1b.htm H.E,Chad (2010). Congenital AdrenalHyperplasia. Available: http://www.nlm.nih.gov/medlineplus/ency/article/000411.htm Paul, G, 1998. Human Endocrinology. 1st ed. United Kingdom: Taylor and Francis. S.J,McPhee, G.D, Hammer (2010). Pathophysiology of Disease. 6th ed. U.S.A: McGraw Hill. p44-444.