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 Table 5.5 Treatments of acromegaly

Advantages

Transsphenoidal surgery - common first-line Rapid effect

Can restore vis ion in optic nerve

compression

Might be curative if complete resection

Disadvantages

Invasive and requires general anaesthetic

Non-curative for large, extrasellar tumours

May cause hypopituitarism by damage to other cell types

omatostatin analogue drugs - lo!er gro!th hormone "#$%

Non-invasive

May shrin& large extrasellar tumours

'ecreases #$ in ∼()* of patients

Radiotherapy - a good second or third line Non-

invasive

+i&ely to shrin& tumour and reduce #$levels

Might be curative

Case history 5.2

Monthly intramuscular inection "most commonly%

xpensive, may lo!er chance of curative surgery for intrapituitary

lesions

#astrointestinal side-effects "commonly diarrhoea%

.nli&ely to be curative, i/e/ continuous therapy needed

lo! to act - may ta&e up to 0) years

+i&ely to cause hypopituitarism by destroying other pituitary cell types

Mildly increases ris& of cerebrovascular disease

 1 2)-year-old !oman had attended her family doctor for a cervical smear/ he sa! a ne!

doctor, her previous doctor having &no!n her since childhood/ The ne! doctor !as concerned by the patient3s

coarse facial appearance and as&ed some questions/ The !oman !as

surprised to be as&ed about her shoe si4e but confirmed that most of her shoes !ere no! a si4e larger than 0)

years ago/

5hat diagnosis is being considered6

5hat other questions should be as&ed6

5hat specific features of the examination should be sought6 5hat tests !ould

confirm the doctor3s suspicion6

 1ns!ers, see p/ 78

tary hormone defciencies ollowing surgeryor radiotherapy to the anterior pituitary (Box5.6).

 Any pituitary space-occupying lesion cancauseloss o somatotrophs and G defciency. !nchild-hood" this may #e a craniopharyngioma$ inadults"

most li%ely a non-unctioning adenoma. &therchildhood causes include congenitaldefciency

('igure .$ re*iew Box .6) or cranialirradiationor +, tumours or haematological malignancy.!nadults" loss o G secretion is part o physiological

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82 9 Chapter :; The hypothalamus and pituitary gland

07)

0)

00)

0))

7)

787)8::)

>:0):

#ro!thhormone

= 2 : ( 8 < 70)000>0=020:0(080

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ous in1ection o recom#inant G (oralpeptideswould #e degraded in the intestine). !nchildrenwith true G defciency" this results in aspectacular

clinical e2ect" with a small child growingslowlyinto a normally si3ed adult. !t is alsoused #ypaediatric endocrinologists to treat shortstatureo other causes (e.g. /urnersyndrome405"&).

 Administration o G in adeuate dosewill ma%eany child grow more uic%ly in the shortterm" #utdoes not necessarily increase fnal

height./he #eneft o treatment in adulthood

remainscontentious amongst clinicians asimpro*ementsor indi*idual patients can #e minimal./reatment

is also relati*ely expensi*e andin*asi*e$ thus" itis important to demonstrate clearpatient #eneftrom G replacement. At present" 78 guidelines

include a uality-o-lie uestionnairegeneratingan Assessment o Growth ormone9efciency in

 Adults (AG9A) score and clear#iochemical e*i-dence o G defciency (see /a#le 5.0).'rom theclinician:s perspecti*e" impro*ement inasting lipidanalysis would also #e persuasi*e orcontinuingreplacement therapy. !n clinical trials"

studies ha*ereported extensi*e #enefts;

< !mpro*ements in at mass< 9ecreased waist-to-hip ratio and lower

 *isceral at< !ncreased lean #ody mass< !ncreased #one mineral density

   #

   i  r   l  s   h  e   i  g   h   t   "  c  m   %

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Chapter :; The hypothalamus and pituitary gland 9 8'

< !ncreased muscle mass and strength< !ncreased maximal exerciseperormance

< !ncreased =&>max" maximum poweroutput" maximum heart rate andanaero#ic threshold< !ncreased let *entricular mass"stro%e *olume" cardiac output andresting heart rate with decreaseddiastolic #lood pressure< !ncreased red cell mass< !ncreased emotional reaction andimpro*ed social isolation scores< !ncreased percei*ed uality o lie< !ncreased sel-esteem< 9ecreased sleep reuirement

(rola#tin

uman prolactin (?@A) is secreted #ythe lac-totroph cells in the anterior pituitary andcomprises amino acids with threedisulphide #onds. By weight" outside o pregnancy or #reast-eeding" the ?@content o the normal human pituitarygland is ∼C that o G.

)*e#ts and me#hanism o a#tion?rolactin plays some role in stimulatinggrowth othe al*eolar component o #reast tissueduring ado-lescence. owe*er" its ma1or action is tostimulate#reast mil% production (lactation)('igure 5.D$ alsosee the endocrinology o pregnancy in+hapter "Box .6). 'ollowing child#irth and the

conseuentdecrease in maternal serum oestrogenand proges-terone" ?@ in the presence o cortisolinitiates andmaintains lactation. !ts loss results in theimmediatecessation o mil% secretion. ?@ alsoinhi#its syn-thesis and release o A and ' #y the

anteriorpituitary gonadotrophs. /his causes aphysiologicalsecondary amenorrhoea (see Box .)that acts as

a natural contracepti*e in the post-partum period.!n #irds" the hormone stimulatesnest-#uildingacti*ity and crop-mil% production$ inreptiles"amphi#ians and some fsh" it acts as anosmoregula-tor. /hese wider unctions and theconser*ation o?@-li%e molecules across species ha*eled to otheractions #eing attri#uted to ?@A in #oth

male andemale humans. owe*er" or many o these pro-posed unctions" the physiologicalsignifcanceremains unclear ('igure 5.D). Ai%eG" ?@A

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signals through specifc receptors thatdimeri3e and recruit tyrosine %inasesignalling pathways (re*iew +hapter and 'igure .E).

+eg%lation o prod%#tion

/he principles and eatures o ?@regulation aresimilar to those o G. ?@ romlactotrophs isunder tonic inhi#ition #y dopamine" with/@pro*iding a stimulatory input ('igure5.D). tressincreases serum ?@. Although the pea%s

are not asdiscrete as or G" ?@ is also releasedepisodicallywith highest le*els during sleep. /he mostprooundchanges in serum ?@ occur duringpregnancy andlactation. /he concentration increasesprogressi*ely"up to D-old" through pregnancy"possi#ly in part#ecause o rising oestrogen le*els. !tremains ele*ated

during lactation under the stimulus o suc%ling" anexample o a positi*e eed#ac% loop;prolactin stimu-lates mil% production" consumed #ysuc%ling" whichin turn #y a neural reFex stimulatesurther prolactin

release. /he loop is only #ro%en once the#a#y stopssuc%ling.

Clini#al disorders

$yperprolactinaemiaymptoms and signs!ncreased serum ?@ causesoligomenorrhoea or secondaryamenorrhoea (see Box .)" or su#-ertility in women o reproducti*e age #yinhi#iting the normal pulsatile secretiono and '" and the mid-cycle surge" leading to ano*ulation. henpresent" inappropriate #reast mil% produc-tion (galactorrhoea) is stri%ing.

yperprolactinaemia occurs withsu2icient reuency to #e rele*ant tothe primary care physician. /heunderlying cause is commonly amicroprolactinoma. &ther causes arelisted in Box 5. (+ase history 5.).

!n contrast" men and post-menopausalwomentend to present later when the underlyingpathologyis more li%ely to #e a largermacroadenoma" andpresenting symptoms and signs may

reFect the con-seuences o a space-occupying lesion(see Box 5.).Hen with hyperprolactinaemia may alsopresentwith gynaecomastia or eatures o secondary hypog-onadism (see Box .D).