IN THE NAME OF GOD Delayed puberty - PowerPoint Presentation

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IN THE NAME OF GOD

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Delayed puberty

Ms,Hosseini,Associate

Prof Of

Endocrinology,Baqiatallah

University of Medical Science

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Agenda

Definition

Etiology

Evaluation

History

Physical Examination

Laboratory tests

Therapy

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N

Engl

J Med 2012;366:443-53

.

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Definition

Delayed puberty is defined as the absence of testicular enlargement in boys or

breast

development in girls at an age that is 2 to 2.5 SD later than

the

population

mean (traditionally, the age of 14 years in boys and 13 years in girls

)

B

ecause

of a downward trend in pubertal timing in the United

States and

other

countries

and differences in pubertal timing among racial and ethnic groups,

some

observers have advocated for updated definitions with younger

age

cutoffs

for the general population or perhaps for particular

countries or racial

or ethnic group

Sun SS,

Pediatrics

2002;110,

911-9

Pediatrics 2002;110:752-7

Pediatrics

2009;123(5

):

e932-e939

J

Clin

Endocrinol

Metab;2010;95:263-70

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Definition……

Development of pubic hair is usually not considered in the definition because

pubarche

may result from maturation of the adrenal

glands and

the onset

ofpubic hair can be independent of HPG-axis activation

N

Engl

J Med 2012;366:443-53

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Etiology

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Etiology….

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Idiopathic or Constitutional Delay in Growth

and Puberty

Otherwise

healthy girls who spontaneously enter

puberty after

the age of 13 years and boys

who

begin after 14 years

Affected individual usually

are short

at

evaluation and have been shorter

than

their classmates for years, although growth velocity

and height

are usually appropriate for bone age

Family

history in as many as 77% of

cases

reveals a mother who had delayed menarche or a father (

or sibling

) who entered puberty

late

Adrenarche

and

gonadarch

occure

later

Bone

age is

delayed at

presentation

There is no

impairment

of olfaction, as in

Kallmann’s

syndrome, and

undescended testes

are

uncommon

J

Clin

Endocrinol

Metab

.

2002;87:1613-1620

Clin

Endocrinol

Metab

.

2002;87:5581-5586

.

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J Clin Endocrinol Metab

97: 3056–3067, 2012

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Diagnostic tests

Basal gonadotropin

levels

GnRH

and

GnRH agonist (GnRHa

) stimulation testsHuman chorionic gonadotropin test

Genetic tests

Inhibin

B

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Conclusion

Distinguishing

IHH from CDGP is an important clinical issue. Basal

inhibin

B may

offer a simple, discriminatory test if results from recent

studies are replicated Current literature does not allow for recommendation of any diagnostic test for routine clinical use, making

this an

important area for future

investigation

J

Clin Endocrinol Metab

97: 3056–3067, 2012

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Distinguishing Constitutional Delay of Growth

and

Puberty from Isolated

Hypogonadotropic

Hypogonadism Is an Important Clinical Issue

The presence of

endogenouse

,progressive pubertal development by age 18

Yr

is the gold standard for differentiating

J Clin Endocrinol Metab

97: 3056–3067,

2012

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Evaluation

History

:

all symptoms of chronic or intermittent illnesses ,

all details

pertaining to growth and development, the

patient’s

sense of

smell,puberty

course, abnormality of labor and

delivery,family

history,history

of consanguinity

physical examination

:

height ,

weight,U

/L

ratio,BMI

, signs of puberty, height velocity over a period of at least 6

months, preferably 12

months,neurologic

examination, including examination of the optic discs and

visual field ,determination of

olfaction,stigma

of gonadal

dysgenesis,compelet

physical examination including

lung,heart,kidney

and GI is important in the search for a chronic disorders that may delay puberty

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Body Segment Ratio

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Evaluation….

Laboratory tests

:

Plasma

testosterone or estradiol

Plasma FSH and LH

Plasma thyroxine (and prolactin)

Radiographic

examination:

Bone age and lateral skull

roentgenograph

MRI with contrast enhancement

Pelvic

ultrasonography

karyotype

:

For all short

girls, even in the absence of somatic signs of

Turne

syndrome and for boys with

suspected

Klinefelter’s

syndrome stigma or behavior

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Evaluation

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Evaluation….

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Flow chart for the evaluation of delayed puberty in boys

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Flow chart for the evaluation of delayed puberty in

girls

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Treatment

Objective:

Determine

site and etiology of abnormality

Induce and maintain secondary sexual characteristics

Induce pubertal growth spurt

Prevent the potential short-term and long-term psychological, personality,

and

social handicaps of delayed puberty

Ensure normal libido and potency

Attain

fertility

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Treatment…..

Concerned But Not Anxious or Socially Handicapped Adolescent

Reassurance

and follow-up

Repeat

evaluation (including serum testosterone or estradiol) in 6

mo

Psychosocial Handicaps, Anxiety, Highly Concerned

Therapy for 4

mo

Boys:

testosterone

enanthate

100 mg IM q4wk at 14-14.5

yr

of age, or

overnight

transdermal testosterone patch

Girls:

ethinyl

estradiol 5-10

µg/day

PO or conjugated estrogens

0.3

mg/day PO or overnight

ethinyl

estradiol patch at 13

yr

of age

No therapy for 4-6

mo

; reevaluate status including serum testosterone

or

estradiol; if indicated repeat treatment

regimen

Clin

Endocrinol

(

Oxf

)

.

2003;58:267-272

Horm

Res

.

2003;59:270-275

J

Clin Endocrinol Metab

. 2001;86:3039-3044

.

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Treatment…..

If during the 3 to 6 months after discontinuing gonadal steroid therapy spontaneous puberty does not ensue or the concentrations of plasma gonadotropins and plasma testosterone in boys or plasma estradiol in girls do not

increase

, the treatment may be repeated

Only

one or two courses of therapy usually are necessary

When treatment is discontinued after bone age has

advanced(

to 12 to 13 years in girls or 13 or 14 years in boys

),patients with constitutional delay usually continue pubertal development

on their own, whereas those with

gonadotropin deficiency

do not

progress

Horm

Res 2003 ;60(

suppl

):74-77

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Treatment: Functional

hypogonadotropic

hypogonadism

Functional

hypogonadotropic hypogonadism associated with chronic disease is treated by alleviating

the

underlying problem

Delayed

puberty in this situation

is usually

a result of inadequate nutrition and low weight

or

excessive energy expenditure

When

weight returns to normal values, puberty usually

occurs spontaneously

Treatment

with T4 allows normal pubertal development in hypothyroid patients with delayed puberty

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Treatment:permanent

hypogonadism

Boys

Goal: to approximate normal adolescent development

when diagnosis

is established

Initial

therapy: at 13

yr

of age, testosterone

enanthate

50

mg IM every month for

about 9

mo

(6-12

mo

)

Over

the next 3-4

yr

: gradually increase dose to adult replacement

dose of

200 mg q2-3

wk

To

induce fertility

at appropriate time in

hypogonadotropic

hypogonadism

:

pulsatile

GnRH

or FSH and

hCG

therapy

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Girls

Goal

: to approximate normal adolescent

development when diagnosis is

stablished

Initial therapy

: at 12-13 Yr of age: ethinyl

estradiol 5

µg

by mouth or conjugated

estrogen 0.3

mg (or less) by mouth daily for 4-6

mo

or preferably

estradiol

transdermally

After

6

mo

of therapy (or sooner if breakthrough bleeding occurs),

begin cyclic

therapy:

Estrogen

: first 21 days of month

Progestagen

:

12th

to21st day

of month

Gradually

increase dose of estrogen over next 2-3

yr

to

conjugated estrogen 0.6-

1.25

mg or

ethinyl

estradiol 10-20µ

g

daily for first 21days of month or estradiol patch

In

hypogonadotropic

hypogonadism

,

to induce ovulation at

appropriate time

: pulsatile

GnRH

or FSH and

hCG

therapy

Treatment:permanent

hypogonadism

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Treatment with GH

Although the Food and Drug

Administration has

approved the use of

growth hormone

for the treatment of idiopathic short

and height is 2-2.5 SD below average for

age

,

this therapy

has at best a modest effect on adult

height

in adolescents with CDGP, and its use

in CDGP

is not recommended

N

Engl

J Med 2012;366:443-53

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Treatment with aromatase inhibitor

Aromatase inhibitors

,

can prolong

linear growth and

potentially increase adult height

In controlled trials in boys with short stature or delayed puberty,

aromatase inhibitors

delayed bone maturation and appeared to increase adult

height

However

, the

amount

of height gained as well as the optimal

timing dose

, and duration of therapy with

aromatase inhibitors

remain uncertain

Moreover

,

potentially

adverse

effects must

be

considered

This treatment requires further study before it should be incorporated into routine practice

J Clin Endocrinol Metab

2005;90:

6396-402

Lancet

2001;357:1743-8

Pediatrics 2008;121(4):e975-e983

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Medications used for the treatment of constitutional delay of growth and puberty and permanent

hypogonadism

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European Journal

of Endocrinology

(2014) 170, R229–R239

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Areas of

Uncertainty

Further research is needed to

establish:

Appropriate age

cutoffs for delayed puberty in different

racial and ethnic groups The psychosocial distress among children with delayed

puberty, whether

this

distress has

long term

sequelae

, and what effect sex-steroid

supplementation

has on these outcomes

whether

adult bone mass is

adversely affected

by pubertal

delay

J

Clin

Endocrinol

Metab

2006

J

Pediatr

2010;156:308-12

J

Pediatr

2011

;

158:100-5

.

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Areas of

Uncertainty…..

Distinguishing between CDGP

and IHH remains

difficult in many cases

The role of

inhibin B or other markers for this purpose is neededTo

compare different estrogen formulations

,

routes of administration

and

drug regimens to

determine

optimal therapy for

girls

To

identify genes that

cause CDGP

, which would also elucidate factors that

regulate

the timing of puberty

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Conclusions

and Recommendations

The patient in the vignette has delayed puberty. Given that he is male and has a family history

of

late pubertal development, CDGP is the most

likely

Before

making this diagnosis, a

careful

evaluation is required to rule out other causes

In

CDGP, in which pubertal delay is transient, the decision regarding whether to treat

should

be made by the

patient

If spontaneous puberty has not

occurred after

1 year, other diagnoses,

should be considered

and MRI of the brain is indicated

N

Engl

J Med 2012;366:443-53

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با تشكر از توجه شما

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