45.the Parathyroid and Adrenal Glands

7/27/2019 45.the Parathyroid and Adrenal Glands

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45 The parathyroid and adrenal glands ANTHONY W GOODE

Parathyroid glandsAnatomy. The parathyroid glands, four in numer, are small, o!al in shape,

"ommonly aout #.$ "m in si%e, soft, moile, yello&ish ro&n in "olour and arranged

in pairs ' most often "losely applied to the thyroid gland, either &ithin or "losely

applied to its "apsule. The upper pair is more "onstant in position than the lo&er( )#

per "ent are found on the posterolateral aspe"t of the thyroid, immediately ao!e the

termination of the inferior thyroid artery, "lose to the "ri"othyroid arti"ulation. *ost

of the remaining +# per "ent are posterolateral to the upper pole of the thyroid loe.

The lo&er pair is more !ariale in position( # per "ent are found at the lo&er pole of

the thyroid and # per "ent are &ithin the thymi" tongue -ig. $./0. The remaining +#

per "ent are !ariale in site, most often some distan"e lateral to the thyroid, and less

often in the mediastinal thymus a fe& "entimeters elo& the sternal not"h or, !eryo""asionally, e"topi"all! situated near the "arotid sheath, sometimes as high as the

"arotid ifur"ation. On rare o""asions, a parathyroid, usually the upper gland, may e

retropharyngeal, retro1oesophageal or a"tually &ithin the thyroid sustan"e and, in /

'+ per "ent of indi!iduals, there is one or more supernumerary glands usually

asso"iated &ith a loule of thymi" tissue. Ea"h gland has a deli"ate "apsule and is

supplied y a single leash of lood !essels "learly seen running in the su"apsular

plane -ig. $.+0. 2ery often, parathyroid glands are asso"iated &ith or emedded

&ithin a pad of fat, &hi"h gi!es a useful "lue to identifi"ation.

Histology. The stroma "onsists of a ri"h sinusoidal "apillary net&or3 &ith islands of

se"retory "ells interspersed &ith fat "ells. The glandular "ells are of t&o types. The

4"hief5 or 4prin"ipal5 "ells are small &ith !esi"ular nu"lei and poorly staining

"ytoplasm. 4Water1"lear5 "ells, deri!ed from the "hief "ells, are found in hyperplasti"

and neoplasti" glands. The 4o6yphil5 "ells are less numerous and larger, &ith granular

"ytoplasm and deeply staining nu"lei.

Physiology. The "hief "ells of the parathyroids produ"e parathormone, the hormone

eing released dire"tly into the loodstream. The "ir"ulating le!el of parathormone

"an e measured y radioimmunoassay, &hi"h is suffi"iently reliale to distinguish

et&een high and lo& le!els. a"ilities for otaining the estimation are &idely

a!ailale.

Parathormone(

7stimulates osteo"lasti" a"ti!ity, therey in"reasing one resorption y moili%ing"al"ium and phosphate8

7in"reases the reasorption of "al"ium y the renal tuules, thus redu"ing the urinary

e6"retion of "al"ium8

7augments the asorption of "al"ium from the gut8

7redu"es the renal tuular reasorption of phosphate, thus promoting phosphaturia.

Parathyroid hormone is an ) amino a"id peptide &hi"h has a short half1life efore

degradation into amino1terminal and "aro6y1terminal fragments, &ith the amino1

terminal fragment ha!ing iologi"al a"ti!ity. The amino1terminal fragment retains

iologi"al a"ti!ity &ith a half1life of minutes and the "aro6y1terminal fragment a

half1life of hours. A!ailale assays measure either the inta"t hormone, the amino1 or

"aro6y1terminal or 4mid1portion5 fragments.


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9al"itonin-9opp0 is se"reted y the parafolli"ular "ells of the thyroid

-thyro"al"itonin0. :t lo&ers the serum "al"ium and affe"ts "al"ium storage in ones8

;uite the opposite a"tion of parathormone.

Parathyroid hormone1related protein -PTH1rP0

is a hyper"al"aemi" fa"tor &ith similar ioa"ti!ity to that of parathyroid hormone.

e"tion of /#'+# ml of a /# per "ent solution of "al"ium glu"onate. This may e

repeated until the patient5s "ir"ulating "al"ium le!el has een stailised. or longer1

term management, the asorption of "al"ium is enhan"ed y oral administration of the

most a"ti!e metaolite of !itamin D ' /,+$1dihydro6y"hole"al"iferol

/,+$-OH0+D?B. :ts ma>or a"tion is on the gut, promoting a"ti!e asorption of "al"ium

and phosphorus, raising "al"ium le!els to normal &ithin a &ee3. *agnesium

supplements may o""asionally e needed. usted as appropriate.

Hyperparathyroidism


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Hyperparathyroidism is a more "ommon "ondition than had een pre!iously elie!ed

7The symptomati" presentation may !ary ut the in"reased use of auto analysers has

resulted in 4asymptomati"5 hyper"al"aemi" patients eing the largest group.

7 A "orre"ted serum "al"ium "on"entration ao!e the upper limit of normal and a

simultaneous ele!ation of serum parathyroid hormone le!el are mandatory for the

diagnosis.7


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Patients &ith nausea, !omiting and anore6ia are relati!ely "ommon. Pepti" ul"er and

pan"reatitis are not infre;uently found in asso"iation &ith hyperparathyroidism, ut

the relationship is not as yet fully understood.

Psy"hiatri" "ases

Psy"hiatri" "ases are not un"ommon8 &omen, "omplaining of tiredness, listlessness

and &ith o!ious personality "hanges, are often &rongly laelled 4neuroti"5 or4menopausal5. Patients ha!e een admitted to mental institutions e"ause of irrational

eha!iour.

A"ute hyperparathyroidism

This diagnosis is diffi"ult and only too often made after death. Nausea and adominal

pain is follo&ed y se!ere !omiting, dehydration, oliguria and finally "oma. The

serum "al"ium is !ery high. Treatment is urgent after rehydration, &hi"h is !ital.

Ciphosphonates -disodium etidronate and pamidronate0 are spe"ifi" inhiitors of one

resorption. They are highly effe"ti!e gi!en parenterally and may also e used in the

preoperati!e, short1term medi"al management of se!ere hyper"al"aemia in primary

hyperparathyroidism.

9lini"al e6amination and in!estigation9lini"al e6amination may e unre&arding ut the "ause of dehydration or "onfusion

may e found in the eyes. 9orneal "al"ifi"ation may e dete"ted. :t egins on the

lateral and medial orders of the limus -&hi"h distinguishes it from ar"us senilis0

and is est seen through a hand lens y the light of a right tor"h refle"ted off the iris.

@ess "ommon is and 3eratopathy in &hi"h a trans!erse and of "al"ifi"ation forms

a"ross the front of the "ornea, and "on>un"ti!al "al"ifi"ation &here redness of the eye

also o""urs. Hypertension may e present in up to $# per "ent of "ases. There may e

ele"tro"ardiographi" "hanges &ith a shortened FT inter!al, primarily y an effe"t on

the length of the


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&hen the initial operation has failed, ut may also e helpful to less e6perien"ed

surgeons.

7The simplest lo"alisation test is an ultrasoni" s"an ut results !ary a""ording to the

s3ill and e6perien"e of the in!estigator.

7 9omputerised tomography is of most !alue in lo"alising a lesion in the

mediastinum rather than the ne"3.7Thallium'te"hnetium isotope sutra"tion imaging may lo"ate up to K# per "ent of

parathyroid adenomas efore surgery -ig. $.=0.@i3e ultrasonography, sutra"tion

s"intigraphy is more a""urate the larger the adenoma, and is ina""urate in parathyroid

hyperplasia.

7*: is impro!ing rapidly &ith some "entres reporting up to = per "ent dete"tion

prospe"ti!ely. A lo& signal is otained from the parathyroid glands on a T/1&eighted

image &hile a T+1&eighted image appears in early studies to produ"e good "ontrast

resolution from the surrounding tissues.

7:n!asi!e te"hni;ues su"h as sele"ti!e angiography and sele"ti!e !enous sampling

may e helpful in lo"ating an anormally situated gland after a failed initial

e6ploration.Differential diagnosis

Other "auses of hyper"al"aemia must e rememered and e6"luded. They are(

7se"ondary "an"er in one -reast, prostate, ron"hus, 3idney and thyroid08

7"ar"inoma &ith endo"rine se"retion -ron"hus, 3idney and o!ary08

7multiple myeloma8

7!itamin D into6i"ation8

7sar"oidosis8

7thyroto6i"osis8

7immoilisation8

7medi"ation( thia%ide diureti"s, lithium.

The differential diagnosis presents no prolem if the parathormone le!el is estimated.

:n none of the ao!e1mentioned "onditions &ill parathormone e dete"tale in the

lood.

Treatment

The only "orre"ti!e treatment is surgi"al remo!al of the o!era"ti!e gland or glands. :n

symptomati" patients, the indi"ations for operation are "lear"ut. *any patients,

ho&e!er, in &hom hyper"al"aemia has een dis"o!ered in"identally, are not o!ertly

symptomati" and a de"ision in fa!our of operation is more diffi"ult.

Preoperati!e treatment is not usually ne"essary e6"ept in a"ute "ases, &hen rapid

"orre"tion of dehydration and ele"trolyte imalan"e is ne"essary, &ith a "areful daily

"he"3 on the serum "al"ium. Drugs used &ould ha!e een dis"ussed earlier.A re"ent international sur!ey of operati!e strategy sho&s that the approa"h is

"hanging. emo!al of the adenoma &ith iopsy of the other glands has een

supplanted y remo!al of the adenoma, a peroperati!e histologi"al diagnosis and then

iopsy of one normal gland. :f the peroperati!e iopsy is that of a hyperplasti" gland,

then remo!al of all four glands &ith auto transplantation is indi"ated. Appro6imately

K# per "ent of "ases of primary hyperparathyroidisrn are asso"iated &ith single1gland

disease -adenoma0. Ten per "ent of "ases are asso"iated &ith multiple1gland disease,

either hyperplasia or more than one adenoma. Adenomas, single or multiple, are

remo!ed.

:n appro6imately /# per "ent of "ases e!en the most e6perien"ed surgeon in this field

may find diffi"ulty in lo"ating a parathyroid adenoma.


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Parathyroid tissue "an e su""essfully autotransplanted into the arm, a useful

te"hni;ue to a!oid repeated potentially diffi"ult e6plorations of the ne"3. The

indi"ations are tertiary hyperparathyroidism in patients undergoing "hroni" renal

dialysis, and re"urrent hyperparathyroidism. The te"hni;ue is to e6"ise all of the

parathyroid tissue from the ne"3 and to implant eight /1mm? fragments into a po"3et

in the forearm mus"le mass, mar3ing the site &ith nonasorale sutures.Postoperati!e !itamin D and "al"ium repla"ement therapy is re;uired for !arying

periods. e"urrent hyper"al"aemia is an indi"ation for e6ploration of the implantation

site and to e6"ise further parathyroid tissue.

Prognosis

With su""essful surgery in se!ere "ases, ones &ill re"al"ify and pseudotumours

resol!e. enal stones &ill not disappear, ut the in"iden"e of re"urren"e after surgi"al

remo!al is redu"ed and deterioration in renal fun"tion is pre!ented. Psy"hiatri"

patients sho& an early and often remar3ale re"o!ery. *any patients &ho are not

o!ertly symptomati"

eforehand are a&are of an impro!ement in &ell1eing after "orre"tion of

hyper"al"aemia. :n a small minority of "ases, hyperparathyroidism re"urs after se!eralyears and may &arrant further surgery. :n some of these, autotransplantation -ao!e0

offers reasonale prospe"ts of "ontrol8 Wells has reported e6"ellent results &hen auto

transplantation has een used for re"urrent and familial hyperparathyroidism.

Hypertension asso"iated &ith hyperparathyroidism is "ommon, ut the me"hanism is

un"lear.

@ong1term sur!i!al has een studied in K## patients in ury is seen in aout = per

"ent.

Parathyroid "ar"inoma

Parathyroid "ar"inoma is a rare "ondition to e "onsidered &hen a high serum "al"ium

is asso"iated &ith a palpale lump in the ne"3. At operation it has a "hara"teristi" grey

'&hite "olour and is adherent e"ause of lo"al in!asion of ad>a"ent soft tissue. The

est results are otained y early re"ognition, a!oiding rupture of the tumour "apsule,

and aggressi!e surgi"al management in"luding ipsilateral thyroid loe"tomy.


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"hemi"al "hara"teristi"s of amine pre"ursor upta3e and de"aro6ylation and are thus

3no&n as APLD "ells. The disorder is inherited as an autosomal dominant, the

manifestations in any one family tend to e similar and all memers of the family

should e in!estigated.

Type :

This most "ommon !ariant in!ol!es the parathyroid glands -K# per "ent0, pan"reati"islets -)# per "ent0, pituitary -=$per "ent0, thyroid and adrenal "orte6. There is

hyperplasia of the parathyroid glands and a "hromophoe adenoma of the pituitary

&hi"h may result in in"reased prola"tin produ"tion or a"romegaly. The pan"reati"

tumour may produ"e gastrin -the Mollinger'Ellison syndrome0 or insulin, glu"agon,

somatostatin or !asoa"ti!e intestinal peptide -2:P0 "ausing &atery diarrhoea.

Treatment is surgi"al e6"ision.

Type ::a

A geneti" anormality lo"ated on "hromosome /# has een identified in *EN type ha

syndrome. ifty per "ent ha!e parathyroid hyperplasia. The asso"iated lesions may e

a medullary "ar"inoma of thyroid, &hi"h produ"es "al"itonin, and a

phaeo"hromo"ytoma. The latter should e e6"luded or e the first priority fortreatment efore e6ploration of the ne"3 -see also 9hapter 0.

Type ::

This is differentiated from type ::a e"ause of additional neurologi"al anormalities.

*u"osal neuromas produ"e 4lumpy and umpy5 lips -ig. .+0 or eyelids, and there

is a "hara"teristi" *arfanoid fa"ial appearan"e. *ega"olon and ganglioneuromatosis

are also 1 found -see also 9hapter 0.

Adrenal glands


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A radiograph or 9T s"an of the pituitary fossa sho&ing an enlarged pituitary fossa is

suggesti!e of a asophil adenomas of the pituitary gland &ith e6"ess

adreno"orti"otrophi" hormone -A9TH0 pituitary se"retion.

Adrenal gland s"intigraphy using NP1$K /?//1=-1iodomethyl1/KNor"hest1$-/#0EN1

?eta1olB is of !alue in addition to 9T. :n a enign fun"tioning adrenal tumour there is

upta3e &ith suppression of the "ontra lateral gland. Cy "ontrast adreno"orti"al"ar"inoma does not usually "on"entrate the isotope and, as a result of "ontra lateral

gland suppression, there is little upta3e. Cilateral adrenal hyperplasia produ"es the

opposite result &ith a prominent ilateral image.

*: is of !alue parti"ularly for small lesions.

Adrenal "orte6

The adrenal "orte6 is made up -if the follo&ing layers from &ithout in&ards( the %ona

glomerulosa, the %ona fas"i"ulata and the %ona reti"ularis.

Physiology. At least $# steroid "ompounds ha!e een isolated from the adrenal

"orte6. These hormones e6hiit !arious types tif a"ti!ity &hi"h, for pra"ti"al

purposes, "an e arranged in three groups.

*ineralo"orti"oidsare "on"erned in the maintenan"e of &ater and ele"trolyti" alan"e.A defi"ien"y of these hormones produ"es sodium diuresis, potassium retention and

dehydration8 an e6"ess results in hypertension, oedema, "ardia" dilatation and

hypo3alaemia. Aldosteroneis the most important of these salt1regulating5 hormones

-see 9onn5s syndrome later0.

Glu"o"orti"oidsare "on"erned &ith the metaolism of proteins and "arohydrates,

fa!ouring the formation of the latter from the ody5s storehouse of the former. This

"on!ersion is 3no&n as glu"oneogenesis.The est 3no&n of these are

hydro"ortisone-also 3no&n as "ortisol0 and "ortisone -&hi"h is "on!erted in the ody

to hydro"ortisone0. The therapeuti" appli"ation of these hormones falls under t&o

headings.

7 :n endo"rine defi"ien"ies. Hydro"ortisone is the logi"al need in adreno"orti"al

insuffi"ien"y and after ilateral adrenale"tomy.

7 :n nonendo"rine disease. Hydro"ortisone or syntheti" analogues, su"h as prednisone

and etamethasone, are used in the treatment of a di!ersity of diseases, in"luding

allergi" "onditions, granulomatous disorders, lood diseases and the "ollagenoses.

Hydro"ortisone is used in the treatment of hypo"orti"ism and sho"3 -9hapter 0 and is

an effe"ti!e antiallergi" agent in a numer of s3in diseases and eye "onditions.


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Plasma "ortisol le!els. Diurnal !ariation &ith a ma6imum !alue at ).## am. may e

lost oth in 9ushing5s syndrome, &here all le!els are high, and in insuffi"ien"y &hen

le!els are lo&.

Plasma A9TH le!els. @o& plasma le!els are found &ith adrenal tumours and high

le!els &ith a pituitary lesion or e"topi" A9TH produ"tion. The ratio of A9TH to

related peptides su"h as eta1lipotrophin may fa"ilitate the distin"tion et&eenpituitary 9ushing5s and e"topi" A9TH produ"tion.

Plasma aldosterone le!els. The "on"entration of aldosterone is only one1thousandth

that of "ortisol, and oth dietary sodium and posture may "hange the !alue. Plasma

renin le!els should e measured along &ith aldosterone to differentiate et&een

primary and se"ondary hyperaldosteronism.

Lrinary steroid e6"retion. 9ortisol se"retion rate. The daily output of "ortisol is a

pre"ise measure of adreno"orti"al a"ti!ity, ut is routinely performed in only a fe&

"entres. Adult le!els are rea"hed y /) years of age and after # years fall gradually,

to e hal!ed y J# years of age. The a!erage e6"retion is higher in 9au"asian males.

The daily output may e determined y the administration of a small amount of

radioa"ti!e1laelled "ortisol, &hi"h is metaolised and e6"reted, and the urinaryradioa"ti!ity measured. The normal range is $'+) mg per + hours, &ith high le!els

in 9ushing5s syndrome and lo& le!els in adrenal insuffi"ien"y.

Lrinary "ortisol e6"retion. The "ortisol e6"retion in a +1hour urine sample is

proaly the est s"reening test for adreno"orti"al o!er se"retion.

: J1O6osteroids or 3etosteroids. These refle"t androgen output, and e6"retion is

in"reased in many &omen &ith !irilising syndromes.

De6amethasone suppression test. De6amethasone is +$ times more potent than

"ortisol. De6amethasone #.$ mg is administered =1hourly for + days and "auses a

mar3ed de"rease in urinary steroid e6"retion y inhiiting A9TH produ"tion, and thus

"ortisol, &ithout "ontriuting greatly to the total urinary steroid output. :n 9ushing5s

syndrome, no effe"t is produ"ed y the dose. @arger doses of up to + mg =1hourly

&ill, o!er se!eral days, redu"e urinary steroid e6"retion if the o!era"ti!ity is

se"ondary to ilateral adrenal hyperplasia, ut not &ith an adrenal tumour, &hi"h is

autonomous. *easurement of the plasma "ortisol at K.## a.m. after the administration

of + mg de6amethasone the pre!ious midnight ser!es as a "on!enient s"reening test

for 9ushing5s syndrome.

*etyrapone test. This differentiates et&een e6"ess A9TH produ"tion and a lesion in

the adrenal "orte6 "ausing 9ushing5s syndrome. *etyrapone inhiits the iosynthesis

of "ortisol so plasma le!els fall. :f the pituitary'adrenal a6is is inta"t, this results in

an in"rease in A9TH produ"tion and stimulation of the adrenal "orte6. The asal

le!els of /J1o6osteroids and 3etosteroids in the urine are measured for + days, J$# mgof metyrapone is gi!en per hours and a +1hour urine "olle"tion "ompleted. A

normal response is a t&o to fourfold in"rease in the urinary steroids o!er asal le!els.

A diminished response in 9ushing5s syndrome indi"ates a primary adrenal lesion.

e"ts the asal plasma "ortisol

should e greater than =# pglitre and e at least J# pglitre after stimulation. :n

Addison5s disease the response is impaired.

Disorders of adreno"orti"al fun"tion

A"ute hypo"orti"ism. Adrenal apople6y in the ne&orn. E6tensi!e haemorrhage into

one or oth adrenals may e a "ause of death in infants &ithin the first fe& days of

irth. The "ondition may o""ur after a long and diffi"ult laour, and parti"ularly &henresus"itati!e pro"edures ha!e to e employed to "omat asphy6ia neonatorum. The


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haemorrhage into the adrenals follo&s ne"rosis of the innermost layer of the "orte6,

&hi"h al&ays o""urs at irth, possily as a result of sudden &ithdra&al of the female

se6 hormone -oestrogen0. Adrenal "risis in the ne&orn produ"es signs of profound

sho"3. A mass may e palpale in one or hoth renal regions. :ntra!enous fluid therapy

&ith hydro"ortisone, or failing the latter, "ortisone intramus"ularly, offers the only

hope.Waterhouse'rideri"hsen syndrome. *assi!e ilateral adrenal "orti"al haemorrhage

o""urs in eases of fulminating meningo"o""al septi"aemia and in some "ases of

strepto"o""al, staphylo"o""al or pneumo"o""al septi"aemia. *ost "ases o""ur in

infants and young "hildren, ut it "an happen in adults &ith se!ere haemorrhage or

urns. The onset is "atastrophi", &ith rigors, hyperpyre6ia, "yanosis and !omiting.

Pete"hial haemorrhages into the s3in &hi"h "oales"e rapidly into purpuri" lot"hes

are a "onstant feature. Profound sho"3 follo&s, and efore long the patient passes into

"oma. The "ondition is one of o!er&helming sepsis that pursues a galloping "ourse,

death o""urring in most eases &ithin ) hours of the onset of symptoms unless "orre"t

treatment is gi!en &ithout delay.

Lnilateral haemorrhage "ausing a lesser degree of systemi" upset and not asso"iated&ith infe"tions has een des"ried. This type of "ase resemles a perinephri" as"ess

or other upper adominal a"ute "ondition.

9onfirming the diagnosis. :t is futile to a&ait the result of a lood "ulture. Cilateral

tenderness $ "m elo& the "ostal margin, "lear urine -oliguria is often present0 and an

asen"e of signs in the lungs help to "all attention to the adrenal glands. :n

meningo""o"al infe"tion the diplo"o""us may e demonstrated y smears otained

from a pun"tured pete"hial spot in the s3in.

Treatment. Antiioti" therapy must e gi!en intensi!ely y the intra!enous route.

Hydro"ortisone /## mg is gi!en intra!enously -i.!.0, or intramus"ularly -i.m.0 if

!enous a""ess is diffi"ult. Lp to ## mg hydro"ortisone may e re;uired in the first

+ hours. No mineralo"orti"oid is needed as the &ea3 intrinsi" salt1retaining a"tion of

hydro"ortisone suffi"es at this dosage. Oral medi"ation may e "ommen"ed after the

first day and then o!er aout days redu"ed to a maintenan"e le!el. O6ygen should

also e administered. ollo&ing su"h treatment, impro!ement often sets in &ithin ?

hours, and a numer of patients has re"o!ered.

9rises of infantile hyper"ortism. ury,

they are usually asso"iated &ith intra1adominal sepsis, pneumonia, "oagulation

defe"ts and "an"er. Thromosis of the adrenal !eins is the "ause of infar"tion of

glands.

9hroni" hypo"orti"ism -Addison5s disease0

This is due to adreno"orti"al insuffi"ien"y "onse;uent upon progressi!e destru"tion

&ith lympho"yti" infiltration of the %ona reti"ularis, the %ona fas"i"ulata, the %ona

glomerulosa and the medulla of the adrenal glands, in that order. :n aout =# per "ent

of "ases the "ondition is elie!ed to e due to an autoimmune disease, sometimes inasso"iation &ith autoimmune thyroiditis -9hapter 0 and perni"ious anaemia.


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Tuer"ulosis, metastati" "ar"inoma and amyloidosis a""ount for the remaining # per

"ent.

9lini"al features

Addison5s disease usually "ommen"es in the third or fourth de"ade. ustifiale to perform se6 determination y a s3in iopsy efore the age of / year.

emale pseudohermaphroditism &ith !irilism is in!arialy asso"iated &ith disease of

the adrenal "orte6, usually ilateral hyperplasia of the "orte6. Hormonal studies ha!esho&n that there is a "ongenital failure of the adrenal glands to synthesise

gl"o"orti"oids. O&ing to this la"3, these infants are liale to a"ute phases of adrenal

insuffi"ien"y during stress or infe"tion, or to suffer from periodi" hypogly"emi"

atta"3s. They need "orti"osteroid repla"ement, not only in the emergen"y, ut as long1

term therapy, therey inhiiting the se"retion of e6"essi!e androgens. :n the asen"e

of su"h treatment, the epiphyses >oin early, the patients are d&arfed, menstruation

does not o""ur and the reasts do not de!elop. These tenden"ies are "orre"ted y

hydro"ortisone gi!en orally, +$ mg or more daily, the dose eing determined y /J1

3etosteroid estimations -


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There is ne!er any dout as to the se6 of the infant at irth and during the !ery early

years of life the "hild is normal. The symptoms "ommen"e at aout the age of $ or =

years.

:n the female. Pui" and a6illary hair appear, ut there is no gross enlargement of the

"litoris. The "hild is short in stature, the legs eing espe"ially stunted, ut she loo3s

mu"h older than she is. Puerty is often pre"o"ious, menstruation, if it o""urs, eings"anty. There is a deepening of the !oi"e at this time.

:n the male. The term 4infant Her"ules5 is des"ripti!e. He is e6tremely short, mus"ular

and hirsute. The genitalia assume adult proportions and spermato%oa are often present

in the seminal fluid.

:n oth se6es, /J13etosteroid "ontent of the urine is in"reased. A !ery high reading

supports the diagnosis of an adreno"orti"al tumour, &hi"h must al&ays e e6"luded.

:n oth males and females, &ith a later onset or the passage of time, the features of

9ushing5s syndrome e"ome superadded.

Treatment. This is identi"al to that of 9ushing5s syndrome.

Postpuertal or adult hyper"orti"ism -9ushing5s syndrome0

Postpuertal or adult hyper"orti"ism -9ushing5s syndrome0 is due to an e6"essi!eendogenous produ"tion of glu"o"orti"oids, mainly hydro"ortisone. :t is an un"ommon

"ondition, often suspe"ted ut seldom "onfirmed. Pituitary1dependent 9ushing5s

syndrome is the "ommonest form of endogenous hyper"orti"ism a""ounting for up to

t&o1thirds of all "ases. An adrenal adenoma a""ounts for +# per "ent and "ar"inoma

-&hi"h may e ilateral0 $per "ent. :n the remainder there is no dis"ernile stru"tural

alteration in the glands and the "ondition is due to an e"topi" sour"e of an A9TH1li3e

sustan"e eing se"reted, y either a enign tumour -e.g. ron"hial "ar"inoid0 or a

malignant tumour of ron"hus, mediastinum or pan"reas. NonA9TH1dependent

primary adreno"orti"al hyperplasia is a rare "ause of 9ushing5s syndrome.

Al"oholism also must e "onsidered.

:n its most typi"al form, 9ushing5s syndrome is e6ogenous and is seen in patients

treated &ith large doses of "ortisone o!er long periods for nonendo"rine diseases,

parti"ularly rheumatoid arthritis, and in patients re"ei!ing transplants.

9lini"al features. The female to male ratio is at least ?(/. The great ma>ority of "ases

-e6"luding those indu"ed y "ortisone therapy0 o""urs in females et&een /$ and ?#

years of age, in &hom it produ"es highly "hara"teristi" features. Although the

patient5s &eight is not ne"essarily in"reased, there is a deposition of fat in "ertain

situations. The fa"e e"omes rui"und, rounded li3e a full moon, and the lips are

pursed. The adomen e"omes protuerant, the ne"3 thi"3, the supra"la!i"ular fossae

oliterated and a roll of fat appears o!er the region of the !ertera prominens -uffalo

hump0. The arms, and espe"ially the legs, are relati!ely thin, the mus"ularde!elopment is poor, and the patient "omplains of in"reasing &ea3ness. As the

disease progresses, so the general "ontour e"omes more and more that of a 4lemon

on mat"h1sti"3s5 -ig. $.)0. 9onse;uent upon the inhiitory effe"t of the

hyper"orti"ism on firous tissue, the s3in e"omes of tissue1paper "onsisten"y and

inelasti". E6"eedingly "hara"teristi" are purple1red striae distentiae, mostly on the

adomen -ig. $.K0,of a te6ture that "an e li3ened to an o!erstret"hed garter.

E""hymoses are fre;uent and ruising o""urs on the slightest trauma. A"ne is

"ommon and there is a lo& resistan"e to s3in infe"tions. Often there is in"reased

gro&th of lanugo hair, ut hirsutism is usually asent. Amenorrhoea is usual or, in the

male, impoten"e. O&ing to a negati!e "al"ium alan"e, the matri6 of one e"omes

thin and se!ere osteoporosis results. Pathologi"al fra"tures, parti"ularly "ompressionfra"ture of a !ertera, are "ommon, and this is sometimes the first reason for the


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patient see3ing ad!i"e. *ild gly"osuria is often present. Hypertension is fre;uent and

e!entually "ongesti!e heart failure super!enes. :n aout =# per "ent of "ases, !arious

psy"hoses o""ur.

9ushing5s syndrome is rare in "hildren8 &hen it o""urs, the patient is nearly al&ays a

female and an adrenal tumour is usually the "ause.

A sugroup, proaly due to an e6"essi!e se"retion of adrenal androgens-adrenogenital syndrome0, "ommen"es et&een the ages of /$ and +$ and is "onfined

to females. One of the first indi"ations of its onset is amenorrhoea or

oligomenorrhoea. There follo&s an e6"essi!e gro&th of hair on the fa"e -ig.

$./#0,a"ne, atrophy of the reasts, alteration in odily "ontour and mus"ular

de!elopment, deepening of the !oi"e and enlargement of the "litoris. e&ish and


14/20

method of "onfirming and lo"alising pituitary1dependent 9ushing5s disease if 9T is

unhelpful.

Treatment.Trans1sphenoidal pituitary adene"tomy in s3illed hands is no& the

treatment of "hoi"e for pituitary lesions. E6ternal pituitary irradiation is less reliale

in terms of long1term remission ut is more su""essful in "hildren. Yttrium1K#

implantation is an alternati!e form of pituitary irradiation. Cilateral totaladrenale"tomy is a reliale pro"edure for patients &ith 9ushing5s disease in &hom

pituitary treatment has failed.

The treatment of an adrenal tumour is surgi"al rese"tion and rese"tion of enign

e"topi" A9TH1se"reting tumour is "urati!e. *any, ho&e!er, are malignant and

&idely disseminated &hen 9ushing5s syndrome e"omes "lini"ally apparent.

Nelson5s syndrome

Hyperpigmentation and pituitary enlargement o""ur in aout +# per "ent of "ases after

ilateral adrenale"tomy and are a!oided y sele"ti!e pituitary mi"rosurgery.

Prognosis. *ost patients are ali!e +# years after su""essful rese"tion of an adrenal

adenoma, ut sur!i!al eyond $ years is rare &ith a "ar"inoma -Welourn0. Pituitary

mi"roadene"tomy in e6pert hands results in "ure in aout )# per "ent of patients !eryrarely, the adrenogenital syndrome appears in youths and men. O&ing to e6"essi!e

produ"tion of oestrogeni" hormones y the adrenal "orte6, gynae"omastia, atrophy of

the testi"les and psy"hi"al signs of effemina"y appear -adrenal feminism0.

Postmenopausal hyper"orti"ism

Postmenopausal hyper"orti"ism is usually "hara"terised y the gro&th of a eard -the

earded &oman of the "ir"us0 and is often a""ompanied y mental aerration. A lesser

degree of hirsutism is almost a natural a""ompaniment of the ageing pro"ess,

parti"ularly in dar31haired females, and it is diffi"ult to dra& the line et&een the

normal and the pathologi"al. Thus it is that operati!e treatment is usually

disappointing.

Primary aldosteronism

Primary aldosteronism -9oon5s syndrome0 is a surgi"ally "orre"tale type of

hypertension found in /'+ per "ent of all hypertensi!e patients. :t is "hara"terised y

autonomous e6"essi!e aldosterone se"retion &hi"h leads to sodium retention and a

fall in serum potassium. The latter "auses the typi"al asso"iated features of the

syndrome, namely episodes of mus"ular &ea3ness asso"iated &ith polyuria and

polydipsia. The plasma sodium is high and the potassium is lo&, ut simple

administration of potassium does not relie!e the "ondition. enin and angiotensin

le!els are depressed. The "ause is either an aldosteronese"reting adrenal adenoma or

ilateral adreno"orti"al hyperplasia -less "ommon0. 9T and adrenal s"anning &ith

radioa"ti!e1laelled "holesterol are the appropriate lo"alisation tests to distinguishet&een them. When these fail, adrenal !enous sampling &ith measurement of

aldosterone to "ortisol ratios is the ne6t step. Lnilateral adrenale"tomy is the

treatment for an aldosterone1produ"ing adenoma and has a high "ure rate, &hereas

surgery has een disappointing in adreno"orti"al hyperplasia and these patients are

generally managed medi"ally.


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enign lesion. Opinion is di!ided aout management ut essentially fun"tioning

lesions are e6"ised &hereas nonfun"tioning lesions are managed a""ording to si%e.

@esions less than ? "m in si%e should e follo&ed ?1monthly for a time y 9T and

e6"ised if they enlarge, &hereas those larger than ? "m should e e6"ised toe6"lude

malignan"y.

Adrenale"tomy for hyper"orti"ism:t is essential that all patients &ho are to e su>e"ted to adrenale"tomy are supported

intra operati!ely and postoperati!ely y adreno"orti"al hormone repla"ement therapy,

irrespe"ti!e of the e6tent of adrenal rese"tion.

9orti"osteroid therapy

9orti"osteroids are started &hen anaesthesia is indu"ed. There is no ad!antage of one

steroid o!er another e6"ept for their different durations of a"tion. Hydro"ortisone is

!ery short a"ting, prednisolone intermediate and de6amethasone long a"ting. Ea"h

may e gi!en intra!enously or intramus"ularly.

During the first + hours after indu"tion of anaesthesia, the patient should re"ei!e no

more than ?## mg hydro"ortisone, =# mg prednisolone or = mg de6amethasone. The

dosage should e hal!ed ea"h day until a maintenan"e dose orally -hydro"ortisone ?#mg, prednisolone $ mg or de6amethasone #.$ mg0 is rea"hed. ludro"ortisone #./ mg

daily -repla"ing aldosterone0 is usually added to the maintenan"e dose of

"orti"osteroid to regulate fluid and salt alan"e.

After total adrenale"tomy the patient should al&ays "arry a "ard stating the dosage of

"orti"osteroid eing re"ei!ed. Any stress -e.g. further operation or infe"tion0 is an

indi"ation to in"rease the dosage.

Operation

When an adrenal tumour has een demonstrated preoperati!ely, e6"ision of that

adrenal gland alone is "arried out.

Posterior approa"h

An ample posterolateral in"ision, su"h as is used for nephre"tomy -9hapter =0, is

used. After superiosteal rese"tion of the /+th ri, the lo&er order of the pleura is

defined and prote"ted. The in"ision is e6tended through the ed of the /+th ri to

re!eal the perinephri" fat, &ithin &hi"h the adrenal gland is identified, as des"ried

elo&.


16/20

against the are surfa"e of the li!er. The fas"ia "o!ering the lateral surfa"e of the

gland is in"ised. A finger "an then e inserted ao!e the upper pole of the gland into

the spa"e et&een the t&o layers of fas"ia en"losing the gland -ig. $.//0. This

pre!ents the gland from e"oming displa"ed up&ards, &hi"h other&ise it is prone to

do. The anterior fas"ial layer is then in"ised trans!ersely and the gland "an e

disse"ted under !ision, as on the left side. After remo!al, ea"h gland should einspe"ted to "he"3 its "ompleteness, and ea"h adrenal ed must e sear"hed for the

presen"e of a""essory adrenal tissue, &hi"h is present in ?+ per "ent of "ases. :f this

important step is omitted, failure of the operation is not unli3ely.

Thora"oadominal approa"h

or remo!al of a large adrenal tumour -/#'/$"m in diameter0 a thora"oadominal

in"ision gi!es the &ide e6posure ne"essary for radi"al rese"tion en lo" &hi"h may

in!ol!e remo!al of the ipsilateral 3idney or spleen and tail of the pan"reas.

@aparos"opi" adrenale"tomy

@aparos"opi" adrenale"tomy is a de!eloping te"hni;ue &hi"h may in sele"ted

patients, parti"ularly patients &ith 9oon5s syndrome, pro!ide an alternati!e operati!e

approa"h using a full lateral de"uitus transperitoneal flan3 approa"h. :t is "laimedthat su"h a te"hni;ue offers a less painful postoperati!e re"o!ery, &ith the in1patient

stay redu"ed from a mean of ) days for open surgery to ?' days. This must e

offset against a douling of the operating time, a possile in"reased in"iden"e of

&ound infe"tion and port site hernia formation.

@eft adrenale"tomy. oining a

suhepati" !ein ao!e the main adrenal !ein. The adrenal arteries, superior, middle

and the main inferior one "oming from the renal artery, are disse"ted on the right side

of the !ena "a!a. The last step is straightfor&ard "oagulation, !essel "lipping and

di!iding as on the left side.Adrenal medulla

Physiology. The medulla of the adrenal glands -"hromaffin tissue0, &hi"h is

de!eloped, together &ith sympatheti" ner!es, from e"toderm, is grey in "olour and

"onne"ted intimately, oth anatomi"ally and fun"tionally, &ith splan"hni" ner!es.

9hromaffin tissue is so "alled e"ause the large polyhedral "ells of &hi"h it is

"omposed "ontain granules that stainyello& &ith "hromi" a"id. These granules are the

internal se"retion of the adrenal medulla itself, for they "an e oser!ed eing

e6truded in toto into radi"les of the adrenal !ein. The se"retion "onsists of the

"ate"holaminest, adrenaline and noradrenaline. :n health, )# per "ent of the output is

adrenaline and +# per "ent is noradrenaline. Ho&e!er, in hyper fun"tioning medullary

tumour -phaeo"hromo"ytoma0 this ratio is "ompletely re!ersed. ear, anger, pain and


17/20

effort gi!e rise to an in"reased output in response to the stimuli re"ei!ed !ia the

splan"hni" ner!es.

An amino a"id peptide adrenomedullin has re"ently een isolated from human

phaeo"hromo"ytoma. :t has a stru"ture similar to "al"itonin gene1related peptide and

amylin. :ntra!enous administration eli"its a strong, long1lasting hypotensi!e effe"t. :t

has een dete"ted in human plasma and !as"ular smooth mus"le "ells &ith spe"ifi"re"eptors. :t de"reases lood pressure y lo&ering total peripheral resistan"e and

in"reasing urine flo& and urinary sodium e6"retion.

A"tions of "ate"holamines. 9ate"holamines e6ert their effe"ts through spe"ifi" "ell1

surfa"e re"eptors( alpha1re"eptors and eta1re"eptors -Tale $./0.These mediate the

a"tions of the endogenously released "ate"holamines, noradrenaline and adrenaline,

and some of the a"tions of dopamine. The re"eptors ha!e ;uite different

pharma"ologi"al properties and an organ may ha!e more than one type. The "omple6

a"tions of "ate"holamines in"lude altering en%yme a"ti!ity, metaoli" path&ays and

the permeaility of "ell memranes to ions.

Pharma"ologi"al inhiitors of alpha stimulation -alpha1lo"3ers0 in"lude the long1

a"ting pheno6yen%amine -Dienyline0 and short1a"ting phentolamine -ogitine0.Ceta1lo"3ers in"lude propranolol -:nderal0 and pra"tolol -Eraldin0.

Tumours of the adrenal medulla

Tumours of the adrenal medulla are "lassified as follo&s(

7neoplasms of the sympatheti" neurons(

' ganglioneuroma,

' neurolastoma -sympatheti"olastoma08

7neoplasm of "hromaffin "ells( phaeo"hromo"ytoma.

Those o""urring at any age

A ganglioneuroma is relati!ely enign. This neoplasm is symptomless, gro&s to a

large si%e and "onstitutes one of the !arieties of retroperitoneal sar"oma5 -9hapter

$=0. Only /$ per "ent in!ol!e the adrenal, the remainder o""urring in any position

along the sympatheti" "hain. :f remo!ed "ompletely at a "omparati!ely early stage, a

"ure may e e6pe"ted.

Those o""urring in infants and "hildren

Neurolastoma

Neurolastoma is a malignant tumour of neural "rest origin arising from sympatheti"

ner!ous tissue from the orit to the pel!is. Three1;uarters arise in the adomen and

half of these from the adrenal gland. :t is the most "ommon solid tumour of infan"y

and "hildhood, and y far the most "ommon in the ne&orn. The in"iden"e isappro6imately / per /# ### li!e irths. Ninety per "ent of "ases of neurolastoma

o""ur under the age of )8 o!er half o""ur in "hildren under + years.

9lini"al features. Three1;uarters of patients present &ith an adominal mass.

*etastati" spread, !ia lymphati"s and loodstream, o""urs at an early stage, and

appro6imately J# per "ent of "ases ha!e metastases at the time of initial diagnosis

-ig. $./+0. Weight loss, failure to thri!e, adominal pain and distension, fe!er and

anaemia may e present. E6"essi!e "ate"holamine produ"tion may "ause

hypertension, flushing, s&eating and general irritaility.


18/20

Diagnosis. O!er )# per "ent of patients e6"rete "ate"holamine metaolites in the

urine. The most "ommon yprodu"ts assayed in the urine are !anillylmandeli" a"id

-2*A0 and homo!anilli" a"id -H2A0, and su"h measurements may e useful in

monitoring the "ourse of the disease.

Plain radiography sho&s fine, stippled "al"ifi"ation in $# per "ent of "ases.

Adominal ultrasound e6amination sho&sthe anatomi"al margins and e6tent of thedisease, and is parti"ularly helpful in e!aluating the results of treatment.

9T demonstrates "al"ium in )# per "ent of "ases and a""urately e!aluates intraspinal

e6tension as &ell as hepati" and renal metastati" disease. *: is a promising

te"hni;ue &hi"h may supersede 9T in many patients. :t &ill also e!aluate one

marro& metastases.

*eta1iodoen%yl1guanidine -*:CG, see elo&0 is metaolised y neurolastoma "ells

and may e used for imaging, espe"ially in small residual tumours not e!ident on

other "on!entional imaging studies.

Cone1see3ing isotope -te"hnerium1KKm0, as &ell as demonstrating one in!ol!ement,

is also "on"entrated y =# per "ent of adrenal lesions.

Treatment. Although surgi"al e6"ision is the mainstay of "ure in lo"alised disease,&idespread disease at presentation often ma3es surgery inappropriate as the primary

form of treatment. *ulti drug "hemotherapy and radiotherapy are instituted in

ad!an"ed disease.


19/20

The importan"e of phaeo"hromo"ytoma as a "omponent of the multiple endo"rine

neoplasia syndromes *EN ::a and *EN :: should e rememered -see earlier and

9hapter 0.

9lini"al features. A typi"al "omplaint is that of fear ' 4: thought : &as going to die5.

The most "ommon symptoms, in order of fre;uen"y, are( heada"he -$$ per "ent0,

palpitation, !omiting, s&earing, dyspnoea, &ea3ness and pallor ' i.e. the symptomsof adrenal o!erdosage. The paro6ysmal atta"3 may !ary from a fe& minutes to some

hours. The lood pressure may e !ery high and hypergly"aemia present. The

symptoms may e mista3en for hyperthyroidism, hypo"al"aemia, an a"ute an6iety

state, paro6ysmal atrial ta"hy"ardia and "ar"inoid syndrome. The main osta"le to the

diagnosis of a phaeo"hromo"ytoma is the failure to thin3 of it as a "ause of the

oser!ed symptoms.

Diagnosti" tests

The asis of the laoratory diagnosis is measurement of ele!ated "ate"holamines and

their metaolites in urine and lood.

7 Lrine studies. 9onfirmation of the diagnosis is usually readily made y

measurement of free "ate"holamines, 2*A and metadrenalines -metanephrines0 in+1hour "olle"tions of 1 urine. Patients &ith phaeo"hrorno"ytoma usually e6"rete free

"ate"holamines in e6"ess of /## ag+ hours, 2*A in e6"ess of J mg+ hours and

metadrenalines in e6"ess of /.? mg+ hours. @aoratories !ary in the relian"e they

pla"e on these !arious estimations8 at the *ayo 9lini", for e6ample, most relian"e is

pla"ed on urinary metadrenalines. alse1positi!e ele!ations of metadrenaline

e6"retion may o""ur in patients ta3ing monoamine o6idase1inhihiting drugs, and in

those &ho ha!e re"ently had angiographi" "ontrast studies.

7Plasma "ate"holamines.


20/20

The alpha1adrenergi" lo"3ing drugpheno6yen%amine in an initial dose of +#'#

mgday is in"reased until hypertension is "ontrolled and mild orthostati" hypotension

indu"ed.

Documents

45.the Parathyroid and Adrenal Glands