Chapter 11: Endocrine Disorders 139
Table 11–6
Oral Diabetes Medications
Class Brand Names
Chemical/
Generic Names Mechanism of Action Adverse Effects
Sulfonylureas Glucotrol,
Glucotrol XL,
Glucotrol XR
Glipizide Causes the pancreas to
secrete more insulin
Hypoglycemia, weight gain
Biguanides Glucophage Metformin Helps cells become more
sensitive to insulin so
the body is able to use
its own insulin better;
prevents liver from
releasing too much
glucose
Hypoglycemia, weight gain;
not recommended for people
with kidney or liver disease
Thiazolidinediones Actos
Avandia
Pioglitazone
Rosiglitazone
Improves cellular
response to insulin and
decreases the release of
glucose from the liver
Hypoglycemia, sometimes liver
irritation, worsening of
congestive heart failure
Meglitinides Prandin Repaglinide Causes pancreas to
produce insulin faster
Hypoglycemia
Amino acid
derivative
(phenylalanine)
Starlix Nateglinide Similar to Prandin;
produces insulin faster
Hypoglycemia
Alpha-glucosidase
inhibitors
Precose
Glyset
Acarbose
miglitol
Slows breakdown of
starchy foods so blood
sugar does not rise as
quickly after a meal
Diarrhea, stomach bloating, gas
Dipeptidyl
peptidase-4
(DPP-4) inhibitors
Januvia Sitagliptin Increases insulin release
from the pancreas and
decreases glucagon
production
Less likely to cause
hypoglycemia because it works
primarily when glucose levels
are high; used with caution in
people with kidney disease
Combination Oral Medicines
Actoplus Met Actos and metformin
Avandamet Avandia and metformin
Glucovance Glyburide and metformin
Metaglip Glipizide and metformin
Avandaryl Avandia and glimeperide
Hyperthyroidism (Thyrotoxicosis)
General Characteristics
Thyroiddiseaseisoneofthemostcommonendocrinedis-
orders,secondonlytoDM.Theprevalenceofhyperthyroid-
ismis1.2percentintheUnitedStates.
9
Hyperthyroidismis
morecommoninwomenthanmen(5:1ratio)andinsmok-
ers.
10
The overall prevalence of hyperthyroidismincreases
to4to5percentinolderwomen.
11
Gravesdisease,aform
ofautoimmunethyrotoxicosis,isseenmostofteninyounger
patients,andtoxicnodulargoiterismorecommoninolder
individuals.
Thethyroidglandconsistsoftwolaterallobesjoinedby
anisthmusandhasanaverageweightof10–20gramsin
adults.Oneofthemainfunctionsofthethyroidistoregu-
latethebody’smetabolism(howthebodyusesandstores
energy). The thyroid is regulated by thyroid-stimulating
hormone(TSH)secretedbythepituitarygland(
Figure 11–2).
When stimulated by TSH, the thyroid increases iodine
uptakeandstimulatesthyroidcellgrowth.Theresultisthe
140 PART II: PRIMARY CARE DISORDERS
releaseofthehormonesthyroxine(T
4
)andthemorepotent
formcalledtriiodothyronine(T
3
).ThemajorityofT
4
and
T
3
areboundbyvariousproteins,butitistheunboundor
freecomponentthatisbiologicallyactive.BothT
4
andT
3
providenegativefeedbacktothepituitarytoinhibitTSH
(Figure 11–2). One of the main functions of these hor-
monesistoregulatethebody’smetabolism.
Thyrotoxicosisisthebroadtermgiventodescribethe
stateofincreasedlevelsofthyroidhormonewithoutspeci-
fyingthesourcecausingtheexcess.Thetermhyperthyroid-
ism specically implies that the cause of the excess is
directlyfromthethyroidgland,althoughmostgeneralcli-
niciansusethetermsinterchangeably.Thyrotoxicosishasa
widespectrumofpresentations,varyinginseverityfroman
asymptomaticsubclinicalhyperthyroidismtoaverysymp-
tomaticanddangerouslife-threatening“thyroidstorm.”
Itisnecessarytoidentifythecorrectcauseofthyrotoxi-
cosis so that appropriate therapy may be initiated. The
multiple etiologies are best differentiated by categories
of whether there is an increase or decrease uptake of
radiotracerduringthyroidscanning(Table 11–7).Ahigh
radioiodineuptakeusuallyindicatesdenovoproduction
ofthyroidhormone.Thethreemainsyndromesassocia-
ted with increased uptake include Graves disease, toxic
multinodular goiter (TMNG), and solitary toxic nodule.
Elevated uptake may also be seen with Hashimoto thy-
roiditisoriodineinsufciency.Alowradioiodineuptake
usuallyindicates eitherinammation anddestruction of
thyroidtissuewithreleaseofpreformedhormoneintothe
circulation or an extrathyroidal source of thyroid hor-
mone. The three main syndromes typied by decreased
uptake are subacute or painless thyroiditis, exogenous
Figure 11–2 The normal hypothalamic pituitary axis.
HYPOTHALAMUS
ANTERIOR PITUITARY
THYROID T4 AND T3
TRH
(Thyrotropin-Releasing Hormone)
TSH
(Thyroid Stimulating Hormone)
Chapter 11: Endocrine Disorders 141
thyroidhormoneintake,andiodineintoxication(includ-
ingcontrastdyesoramiodarone).
Gravesdiseaseisthemostcommonformofthyrotoxi-
cosis.Itaccountsforupto80percentofthecasesinthe
UnitedStatesandoccursinapproximately0.5percentof
thepopulation.
14
Itismostcommoninwomenbetween
theagesof20and40years,butitcanoccuratanyage
inboth genders. Itisan autoimmune disorderresulting
from thyrotropin (TSH)-receptor antibodies (also called
thyroid-stimulatingimmunoglobulin,abbreviated asTSI
orTSHR-Ab),whichstimulatethyroidglandgrowthand
excessivethyroidhormoneproduction.Theclassicsymp-
toms associated with Graves disease include goiter
(an enlarged thyroid gland is usually associated with a
thyroidbruit),ophthalmopathy(onlyfoundin5percent
of patients), and dermopathy (distalextremityorfacial
pufness/myxedema, which is found in approximately
1percentofpatients).Upto10percentofpatientswith
Graves disease may present with ocular manifestations
andeuthyroidstatus.
12
Thepresenceofserumautoanti-
bodies(TSHR-Ab)inadditiontotheocularabnormali-
ties differentiates the disorder from other causes of
hyperthyroidism and diffuse goiter. Possible precipitat-
ingandpredisposingriskfactorsfordevelopingGraves
disease include infection, stress, smoking, genetic sus-
ceptibility,pregnancy,andcertainmedications.
TMNGisthesecondmostcommoncauseandoccurs
in 15 to 20 percent of patients with thyrotoxicosis.
12
It
occursmorecommonly in elderlyindividuals,especially
inpatientswithalong-standinggoiter.Thyroidhormone
excess develops very slowly over time and often isonly
mildlyelevatedatthetimeofdiagnosis.TMNGwilloften
present with cardiovascular symptoms, such as palpita-
tions, tachycardia, and atrial brillation, because of the
olderagepopulationaffected.
Toxicsolitaryadenomaiscausedbyasinglehyperfunc-
tioningfollicularthyroidadenoma.Thesecompriseapp-
roximately3to5percentofpatientswhoarethyrotoxic.
12
Excesssecretionofthyroidhormoneoccursfromabenign
tumorthatisusuallylargerthan2.5cmindiameter,which
suppressesTSH levels. Radioactive iodine uptake is ele-
vatedoverthehyperactivenodule(termedhotnode),and
the remainder ofthe normal thyroid gland may be sup-
pressedbecausetheTSHlevelislow.However,frequently
thereisnotenoughsuppressionoftheremainderof the
thyroid,sothescanwillshowahotnodewithuptakein
theremainderofthegland.
Ofthethyrotoxicconditionstypicallyrelatedtodecrea-
sedradioactiveiodineuptake,subacute/painlessthyroidi-
tisisthemostcommon.Duringtheonset,theinammatory
process destroys the thyroid tissue and releases stored
thyroidhormone,whichresultsinsuppressedTSHaswell
asdecreasednewhormonesynthesis.Thyroiditismaybe
categorized by the absence or presence of pain and thyroid
tenderness. Some forms of thyroiditisarepreceded by a
viral infection and arethought tobe relatedto a subse-
quentautoimmuneprocess.Virusesthathavebeenlinked
to thyroiditis include adenovirus, echovirus, inuenza,
Coxsackievirus,andmumpsvirus.Theincidenceishigh-
estinthesummer,coincidingwiththepeakofenterovirus
season.
12
Provided that the thyroid has not been com-
pletely destroyed by the inammation, the thyroid hor-
mone production usually returns to normal. The entire
cycle from onset to resolution ranges from2–4 months,
butitisoftenvariable.Permanenthypothyroidismisrela-
tivelyrareafterthyroiditis,occurringin5to15percentof
patients.
15
Excessiveexogenousiodineintakecanoccasionallyoccur
fromlarge amounts ofiodine in the form of radiographic
contrastmaterials,increaseddietarysources(vitamins,kelp,
seaweed),ormedicationssuchasamiodarone.Amiodarone,
adrugusedtotreatcardiacdysrhythmias,isauniquesub-
stance that contains 37 percent iodide, or approximately
75mgper200mgtablet.Itcanremainincorporatedinthe
Table 11–7
Causes of Thyrotoxicosis and Hyperthyroidism
Common Forms (85–90%
of cases)
Neck Radioactive
Iodine Uptake
Graves disease (diffuse toxic
goiter)
Increased
Toxic multinodular goiter
(Plummer disease)
Increased
Thyrotoxic phase of subacute
thyroiditis (viral or inammatory)
Decreased
Toxic adenoma Increased
Less Common Forms
Iodide-induced thyrotoxicosis Decreased
Thyrotoxicosis factitia Decreased
Drug induced:
Amiodarone
Lithium
Alpha-interferon
Interleukin-2
Variable
Postpartum thyroiditis Variable
Uncommon Forms
Pituitary tumors producing TSH Increased
Excess human chorionic
gonadotropin/trophoblastic tumors
(molar pregnancy/choriocarcinoma)
Increased
Pituitary resistance to thyroid
hormone
Increased
Metastatic thyroid carcinoma Decreased
Struma ovarii with thyrotoxicosis Decreased
Sources: Data from Nayak B, Hodak S. Hyperthyroidism. Endocrinol Metab
Clin N Am. 2007;36:617–656
12
; Lee SL, Ananthakrishnan S. Hyperthyroid-
ism. http://emedicine.medscape.com/article/121865-overview. Accessed
February 5, 2010.
13

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