ms-k21 pituitary disorders

8/18/2019 MS-K21 Pituitary Disorders

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Pituitary disorders

Mardianto

Division of Endocrine and Metabolism

Department of Internal Medicine

Haji Adam Malik General Hospital

Medan


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Pituitary disorders

Anterior pituitary disordersPituitary Hypersecretion

Hipersecretion of PRL Hyperprolactinemia

Hipersecretion of GH Acrome!aly Hypersecretion of A"#H "us$in!%s disease

Pituitary Insufficiency Hypopituitarism Gonadotropin& GH& #'H& A"#H&or

Prolactin deficiency

Posterior pituitary disordersPosterior pituitary insufficiency "entral diabetes

insipidus


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Anterior pituitary

disorders


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Acrome!aly

Acrome!aly is t$e clinical syndrome t$at resultsfrom e(cessive secretion of !ro)t$ $ormone

*GH+

Its annual incidence is t$ree to four per millionpeople

#$e mean a!e at dia!nosis is ,- to ,. years/

Gro)t$ $ormone e(cess t$at occurs before

fusion of t$e epip$yseal !ro)t$ plates in a c$ild

or adolescent is called pituitary !i!antism


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Acrome!aly

"linical Manifestations#$e onset of acrome!aly is insidious& and its

pro!ression is usually very slo)/#$e interval from t$e onset of symptoms until

dia!nosis is about 01 years At dia!nosis& about 2. percent of patients $avemacroadenomas *tumor diameter 0- mm or !reater+

#$e clinical features $i!$ serum concentrations ofbot$ GH and insulin3like !ro)t$ factor3I *IG43I+&

)$ic$ is GH3dependent/ E(cess GH and IG43I $ave bot$ somatic and metabolic

effects *s$o) table+/


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Dia!nosis of acrome!aly

Documentin! E(cess GH 'ecretion 'erum IG43I concentration

#$e best sin!le test for t$e dia!nosis of acrome!aly 'erum IG43I concentrations do not vary from $our to $our

accordin! to food intake& e(ercise or sleep 'erum GH concentration

GH secretion in normal subjects is pulsatile& diurnal& andstimulated by a variety of factors& includin! s$ort3term fastin!&e(ercise& stress& and sleep

#$e most specific dynamic test for establis$in! t$e dia!nosisof acrome!aly is an oral !lucose tolerance test/

In normal subjects& serum GH concentrations fall to 0 n!5mLor less )it$in t)o $ours after in!estion of 2. ! !lucose/

In contrast& t$e post3!lucose values are !reater t$an 1 n!5mLin over 6. percent of patients )it$ acrome!aly


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Dia!nosis of acrome!aly

Determinin! #$e 'ource 7f E(cess GHMRI

7nce GH $ypersecretion $as been confirmed& t$e

ne(t step is ma!netic resonance ima!in! *MRI+ oft$e pituitary

2. 8 of patients )it$ somatotrop$ adenomas*macroadenoma 9 tumor diameter 0- mm or more+

It is important to remember t$at MRI does notdistin!uis$ bet)een functionin! and nonfunctionin!tumors

Ectopic GHRH secretion accounts for only -/.percent of cases of acrome!aly


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#reatment of acrome!aly

#$e !oals of t$erapy in acrome!aly are to lo)ert$e serum IG43I concentration

#o ac$ieve t$ese !oals& t$e adenoma secretin!GH must be identified/

:$en effective control of GH $ypersecretion isac$ieved& serum GH and IG43I concentrationsdecline to normal

#$e c$aracteristic tissue over!ro)t$ and relatedsymptoms !radually recede& and t$e metabolicabnormalities improve/


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#reatment of acrome!aly #ranssp$enoidal 'ur!ery t$e treatment of c$oice for patients )it$

somatotrop$ adenomas

after transsp$enoidal sur!ery& serum GH⇓ *0

to 1 $r+& and serum IG43I *2 to 0- days+

'ide effect

Deficiency of one or more pituitary $ormones&central diabetes insipidus& cerebrospinal fluid

r$inorr$ea& menin!itis/


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#reatment of acrome!aly Medical t$erapy'omatostatin Analo!s

7ctreotide *analo! of somatostatin+ in$ibits GH

secretion by bindin! to specific receptors forsomatostatin and its analo!s

#$e initial dose of t$e s$ort3actin! form of octreotide is

0-- ;! subcutaneously every 6 $ours

#$e s$ort3actin! form of octreotide ⇓ IG430 to normal

in .< percent of 00. patients& )$o received 0-- ;!

every ei!$t $ours for si( mont$s and in =6 percent of

t$ose )$o received >at& '& 'nyder& P?& @oun!& :4& et al/ 7ctreotide treatment of acrome!aly A randomi>ed& multicenter study

Ann Intern Med 01B 002200/


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#reatment of acrome!aly

Dopamine a!onists Dopamine a!onists& bromocriptine and caber!oline&

may in$ibit GH secretion

In a study of =, patients& caber!oline decreasedserum GH concentrations to C1/- n!5mL in ,=

percent and serum IG43I concentrations to C


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Mortality in acrome!aly

'everal retrospective studies mortality inpatients acrome!aly of bet)een 13< times t$atof an a!e and se( matc$ed

"auses of deat$ Deat$ from cardiovascular and cerebrovascular

diasease appear to be predominate in most majorepidemiolo!ic surveys/

Mortality and morbidity pro!nostic factors tumour si>e& suprasella e(tension& preoperativeGH levels& duration onset to dia!nosis& andoverall duration of t$e disorders/


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Hypopituitarism

Hypopituitarism is a clinical syndrome of deficiency inpituitary $ormone production/

Pan$ypopituitarism refers to involvement of all pituitary

$ormonesB $o)ever& only one or more pituitary$ormones are often involved& resultin! in partial$ypopituitarism/

#$e clinical manifestations depend upon t$e cause as)ell as t$e type and de!ree of $ormonal insufficiency/

Patients may be asymptomatic or present )it$symptoms related to $ormone deficiency& or a masslesion& or nonspecific symptoms suc$ as fati!ue/


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"linical manifestations

Dama!e to t$e anterior pituitary suddenly or slo)ly& can be mild or severe& and can affect t$esecretion of one& several& or all of its $ormones/

A"#H deficiency secondary adrenal insufficiency

#'H deficiency t$yro(ine deficiency

Gonadotropin deficiency 4'H ⇓ and LH⇓ causes$ypo!onadism

Gro)t$ $ormone deficiency s$ort stature *c$ildren+& inadult

Diminis$ed muscle mass and increased fat mass /

Increased risk of cardiovascular disease Decreased bone mineral density Diminis$ed sense of )ell bein!

Prolactin deficiency #$e only kno)n presentation of prolactindeficiency is t$e inability to lactate after delivery/


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Dia!nosis of $ypopituitarism

Hormonal studies s$ould be performed in pairs of tar!et!land and t$eir respective stimulatory pituitary $ormonefor proper interpretation/

A"#H and "ortrosyn stimulation test #'H and t$yro(ine 4'H& LH& and eit$er estradiol or testosterone *as appropriate for

se(+ Prolactin

GH provocative testin! Imaging Studies:

MRI or computed a(ial tomo!rap$y of t$e pituitary


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#reatment of $ypopituitarism

Glucocorticoids are reFuired if t$e A"#H3adrenal a(is isimpaired/

#$is is particularly important in sudden collapse due to pituitary apople(y oracute obstetric $emorr$a!e )it$ pituitary insufficiency/

Do not delay initiation of a possibly life3savin! treatment pendin! a definitivedia!nosis/

#reat secondary $ypot$yroidism )it$ t$yroid $ormonereplacement/

#reat !onadotropin deficiency )it$ se(3appropriate $ormones/ In men& testosterone replacement is used and modified if t$e patient desires

fertility/ In )omen& estro!en replacement is used )it$ or )it$out pro!esterone as

appropriate/ GH is replaced in c$ildren as appropriate/

GH is not routinely replaced in adults unless t$e patient is symptomatic/


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Posterior pituitary

disorders


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Diabetes Insipidus

"entral diabetes insipidus "entral DI is

associated )it$ deficient secretion of

antidiuretic $ormone *ADH+

ep$ro!enic diabetes insipidus

ep$ro!enic DI is c$aracteri>ed by

normal ADH secretion but varyin! de!rees

of renal resistance to its )ater3retainin!effect/


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Antidiuretic Hormone *ADHB

asopressin+ #$e major renal effect of ADH is to increase t$e

)ater permeability of t$e luminal membrane oft$e collectin! duct epit$elium via t$e ADH3sensitive )ater c$annels

:$en ADH is present& epit$elial permeabilityincreases markedly& and )ater is reabsorbed

In t$e absence of ADH& permeability of t$eepit$elium is very lo) and reabsorption of )aterdecreases& leadin! to polyuria/


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"entral Diabetes Insipidus

"entral diabetes insipidus *DI+ is c$aracteri>ed bydecreased release of antidiuretic $ormone *ADH+&resultin! in a variable de!ree of polyuria

Polyuria can be arbitrarily defined as a urine outpute(ceedin! < L5day in adults

Lack of ADH can be caused by disorders t$at act at oneor more of t$e sites involved in ADH secretion t$e$ypot$alamic osmoreceptorsB t$e supraoptic orparaventricular nucleiB or t$e superior portion of t$esupraoptico$ypop$yseal tract


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7nset of polyuria #$e onset is usually abrupt in central DI and almost al)ays

!radual in nep$ro!enic DI or primary polydipsia/ #$e ne) onset of nocturia in absence of ot$er causes of

nocturia is often a first clue to DI/ 4amily $istory

#$ere are familial forms of bot$ central and nep$ro!enic DI/

Plasma sodium concentration Lo) plasma sodium concentration at presentation *less t$an

0


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Dia!nosis and Differential

Dia!nosis of Polyuria :ater restriction test

:e !enerally recommend t$at t$e patient stop drinkin! t)o tot$ree $ours *administration of $ypertonic saline -/-. mL5k! per

min for no more t$an t)o $ours+ before comin! to t$e office orclinic #$e measurement of t$e urine volume and osmolality every $our

and plasma sodium concentration and osmolality every t)o $ours/ #$e $ealt$y individual )ill soon reduce urine flo) to -/. mL5min at a

concentration !reater t$an t$at of plasma&

#$e patient )it$ complete diabetes insipidus )ill maintain a $i!$urine flo) at a specific !ravity less t$an 0/--. *1-- mosm5k! of)ater+/

#$e test s$ould be terminated if t$e body )ei!$t falls by more t$an


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Dia!nosis and Differential

Dia!nosis of Polyuria asopressin #est

#$e ADH3insensitive *nep$ro!enic+ disease must be

distin!uis$ed from t$e ADH3sensitive *central+ form

#$is is done follo)in! )ater deprivation by injection of

aFueous vasopressin or desmopressin acetate/

Give . units of aFueous vasopressin subcutaneously and

measure urine osmolality after 0 $ourB patients )it$ complete

central diabetes insipidus )ill s$o) an increase of .-8 in

urine osmolality& )$ile patients )it$ nep$ro!enic diabetesinsipidus do not respond/


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Etiolo!y

Idiopat$ic DI


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#reatment of central diabetes

insipidus #reatment of t$is disorder is primarily aimed at

decreasin! t$e urine output& usually by increasin!

ADH *e!& ar!inine vasopressin or AP+ activity/ Replacement of previous and on!oin! fluid losses

is also important/Most patients )it$ central DI $ave a normal or only

mildly elevated plasma sodium concentration

"orrection of t$e $ypernatremia reFuires repair of )ater

deficit/


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#reatment of central diabetes

insipidus Desmopressin

a t)o3amino acid substitute of ADH t$at $as potent antidiuretic butno vasopressor activity

It is usually administered intranasally and in an oral tablet form #$e intranasal preparation B initial dose of . ;! at bedtime can be

titrated up)ard in . ;! increments dependin! upon t$e responseof t$e nocturia and t$en additional daytime doses added/

#$e daily maintenance dose is about . to 1- ;! once or t)ice aday/

7t$er dru!s "$lorpropamide "arbama>epine or clofibrate #$ia>ide diuretic or 'AID


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#$ank you

ms-k21 pituitary disorders

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