Download Hyperthyroidism

Thyroid Benign Disease
JAMAL ALDARAWSHEH MD
CONSULTANT ENDOCRINOLOGIST
PRINCESS BASMA TEACHING HOSPITAL
HYPERTHYROIDISM
HYPERTHYROIDISM
SIGNS AND SYMPTOMS
Skin: Increased Sweating and heat intolerance, onycholysis,
hyperpigmentation, pruritus and thinning of the hair.
Eyes: Stare and lid lag, exophtalmos if graves disease
Cardiac: Palpitations, exertional dyspnea, anginal-like chest pain,
tachycardia, atrial fibrillation, CHF
GI: Weight loss, diarrhea
Neuro-psych: Anxiety, restlessness, irritability, emotional lability,
psychosis, agitation, and depression
Metabolic/Endocrine: Hyperglycemia, low serum total and high-density
lipoprotein (HDL) cholesterol
GRAVES’ DISEASE
Signs and symptoms of hyperthyroidism
Exopthalmos, proptosis, lid lag, orbital edema
Diffuse goiter
TSH receptor antibodies
Increased RAI uptake
MUST KNOW
T4 and T3 are produced in thyroid gland but T3 is the active
component.
T3 can also come form T4.
T4-to-T3 conversion is stopped by starvation, liver disease and
certain drugs (propylthiouracil, propranolol, prednisone)
T4 and T3 are circulating as bound proteins-TBG (thyroid binding
globulin)
If TBG goes up-T4 and T3 would go up. If TBG goes down-T4 and
T3 would go down.
GENERAL RULE
Hyperthyroidism with a high radioiodine uptake indicates
de novo synthesis of hormone.
Hyperthyroidism with a low radioiodine uptake indicates
either inflammation and destruction of thyroid tissue with
release of preformed hormone into the circulation, or an
extrathyroidal source of thyroid hormone.
FACTITIOUS VS. SUBACUTE
THYROIDITIS
FACTITIOUS
HYPERTHYROIDISM
SUBACUTE
THYROIDITIS
THYROID GLAND
Painless gland
Painful gland
SERUM
THYROGLOBULIN
Low/Normal
High
SEDIMENTATION RATE
Normal
High
Thyroid benign disease
1)Hyperthyroidism
Diffuse Toxic Goiter
Toxic Multinodular Goiter
Toxic Adenoma
Thyroid Storm
2)Hypothyroidism
3)Thyroiditis
4)Riedels Thyroiditis
5)Goiter
6)Solitary Thyroid Nodule
Age and Sex
Age
Graves disease
20 to 40
Toxic MNG
> 50 yrs
Toxic Single Adenoma
35 to 50
Sub Acute Thyroiditis
age
Any
Sex M : F ratio
Graves Disease
1: 5 to 1:10
Toxic MNG
1: 2 to 1: 4
Hyperthyroidism
This disease result from an excess of circulating thyroid
hormone.that may arise from a number of
condition(graves disease,drug induced,thyroiditis,thyroid
cancer…)
its very important to distinguish disorders:
1.Cause excess production of hormone
such as graves disease
from
2.An other condition which release stored hormone such
as thyroiditis.
First disorder characterized by increasing in radioactive
iodine uptake.
Diffuse toxic Goiter(Graves disease)
Its an autoimmune disease with a strong
familial predisposition.there is a high
incidence in female especially between 40_60
years.
the exact etiology of this disease is not known but
some condition such as iodine excess,lithium
therapy,bacterial & viral infection…suggested
as triggers.genetic factor especially present of
HLADQA1.0501,HLADR3,HLAB8 also play important
role.
The clinical manifestation of graves disease divided
into 2category:
1.those related to hyperthyroidism & 2.those specific
to Graves disease.
Hyperthyroid symptom include:heat
intolerance,incresed sweating & thirst,weight
loss,palpitation,fatigue,diarrhea,increased incidence
of miscarriages,…
Nearly 50% of patiant have ophthalmopathy & 1 to
2% have dermopathy.eye symptoms include lid
lag(von graefes sign),spasm of upper eyelid revealing
the sclera(dalrymple sign),conjunctival swelling &
congestion(chemosis)…
Diagnostic tests:
the diagnosis of hyper thyroidism is made by a
suppressed TSH with or without an elevated free T4
or T3 level.but if eye sign are present other tests are
not needed.in patient with out eye sign (I 123)uptake
with diffusely enlarged gland can confirm diagnosis.
Other tests including:determining T3 level(in T3
toxicosis), anti TG antibodise,TPO antibodies,TSAB
Treatment: graves disease may be treated by any of
3 treatment modalities:
1.Antithyroid drugs 2.radioactive iodine therapy(RAI)
3.thyroidectomy
1.Antithyroid medications:
generally are administered before RAI ablation or
surgery.
Drugs: Propylthiouracil(PTU) have less side effect
Methimazole
the proper dose of drugs depend on TSH & T4 levels.
2.Radioactive iodine therapy:
This method most often used in:
Older patient with small or moderate sized goiter. *
Patient with relapse after medical or surgical therapy. *
Those in whom 2other method are contraindicated. *
Absolute contraindication: pregnancy
3.Surgical treatment
Patients with coexistent thyroid cancer,those who refuse
RAI therapy or have severe ophtalmopathy or have life
threatening reaction to antithyroid medication should
undergo surgery.
Toxic Multinodular Goiter
Occur in older individuals with nontoxic multinodular
goiter,over several years become autonomous and
cause hyperthyroidism.
Sign & diagnostic studies are similar to Graves
disease.
Treatment surgical + thyroid hormone suppression
therapy(to prevent recurrence)
RAI is recommended in patient with high risk for
surgery.
Toxic Adenoma
In this disease hyperfunction of single nodule cause
hyperthyroidism,especially in young patients.
RAI scanning shows a hot nodule with suppression
the rest of thyroid gland.
These nodules are rarely malignant.
Treatment
Small nodule need medication therapy & RAI
Large nodule surgery
Thyroid storm
Is condition of hyperthyroidism accompained by
fever,agitation,cardiovascular dysfunction that may
result from infection , surgery,or trauma.
Treatment:administration of B_blocker,corticosteroid
& Lugols iodine,oxygen supplemention & control of
hemodynamic.
Anti Thyroid Drugs (ATD)
Imp. considerations
Methimazole
Propylthiouracil
Efficacy
Very potent
Potent
Duration of action
Long acting BID/OD
Short acting QID/TID
In pregnancy
Contraindicated
Safely can be given
Mechanism of action
Iodination, Coupling
Iodination, Coupling
Conversion of T4 to T3
No action
Inhibits conversion
Adverse reactions
Rashes, Neutropenia Rashes, ↑Neutropenia
Dosage
20 to 40 mg/ OD PO
100 to 150mg qid PO
How long to give ATD ?
Reduction of thyroid hormones takes 2-8
weeks
Check TSH and FT4 every 4 to 6 weeks
In Graves, many go into remission after 12-18
months
In such pts ATD may be discontinued and
followed up
40% experience recurrence in 1 yr. Re treat
for 3 yrs.
Treatment is not life long. Graves seldom
Radio Active Iodine (RAI Rx.)
In women who are not pregnant
In cases of Toxic MNG and TSA
Graves disease not remitting with ATD
RAI Rx is the best treatment of hyperthyroidism in
adults
The effect is less rapid than ATD or Thyroidectomy
It is effective, safe, and does not require
hospitalization.
Given orally as a single dose in a capsule or liquid
form.
Very few adverse effects as no other tissue absorbs
RAI
Radio Active Iodine (RAI Rx.)
I123 is used for Nuclear Scintigraphy (Dx.)
I131 is given for RAI Rx. (6 to 8 milliCuries)
Goal is to make the patient hypothyroid
No effects such as Thyroid Ca or other malignancies
Never given for children and pregnant/ lactating women
Not recommended with patients of severe
Ophthalmopathy
Not advisable in chronic smokers
Surgical Treatment
Subtotal Thyroidectomy, Total Thyroidectomy
Hemi Thyroidectomy with contra-lateral subtotal
ATD and RAI Rx are very efficacious and easy – so
Surgical treatment is reserved for MNG with
1. Severe hyperthyroidism in children
2. Pregnant women who can’t tolerate ATD
3. Large goiters with severe Ophthalmopathy
4. Large MNGs with pressure symptoms
5. Who require quick normalization of thyroid function
Preoperative Preparation
ATD to reduce hyper function before surgery
βeta blockers to titrate pulse rate to 80/min
SSKI 1 to 2 drops bid for 14 days
This will reduce thyroid blood flow
And there by reduce per operative bleeding
Recurrent laryngeal nerve damage
Hypo parathyroidism are complications
Summary of Hyperthyroidism
Hyperthyroidism
Graves (TSI Ab
Age
%
Enlarged Pain
RAIU Treatment
20 - 40
60% Diffuse
None
↑↑
ATD – 18 m
Toxic MNG
> 50
20% Lumpy
Pressure
↑
RAI, Surgery
Toxic Single
Adenoma
35 - 50
5%
None
±
RAI, ATD
Yes
↓↓
NSAID, Ster.
eye, dermo, bruit)
Single
S Acute Thyroiditis Any age 15% None
TSH is markedly low, FT4 is elevated
Thyrotoxicosis Factitia
Excessive intake of Thyroxine causing thyrotoxicosis
Patients usually deny – it is willful ingestion
This primarily psychiatric disorder
May lead to wrong diagnosis and wrong treatment
They are clinically thyrotoxic without eye signs of
Graves
High doses of Thyroxine lead to TSH suppression
This causes shrinkage of the thyroid
Stop Thyroxine and give symptom relief drugs
Hypothyroidism Standard Guideline
Diagnosis
Raised TSH and Low FT4 = overt hypothyroidism
Treatment
Start 50-100 mcg levothyroxine
Only 12.5 -25 mcg in the elderly or cardiac patients
Re assess after 8 weeks (exceptions)
Aim of treatment is TSH within reference range; once
normal then annual follow up
Optimising Therapy
Remember to take it - time place
Before meal 1 hour, Morning?
Not with iron, calcium, aluminium (4 hrs)
Decide dosing and testing strategy ,
age , heart dis , AF, post menopause TSH >0.1
Reassess after other diagnoses,
» drug changes, Sertraline, phenytoin,
carbamazepine Coeliac disease
Higher doses needed if athyrotic , less T3 conversion.
Subclinical hypothyroidism
Raised TSH and normal FT4 and
FT3
Adverse Metabolic and lipids
Consider trial of treatment if
symptoms
Pregnancy now or later? Treat as
Hypothyroid
Treatment of Subclinical and
Clinical Hypothyroid in the Pregnant
and Pre-pregnant woman
1999 NEJM
TSH above normal, the mother and
pregnancy are at increased risk. The
foetus is at risk of a lower IQ measured as
-7 points between ages 7-9.
So treat all Subclinical pre-pregnant
women
Hypothyroidism
Deficiency in circulating levels of thyroid hormone
lead to hypothyroidism and cause neurologic
impairment and retardation in neonates(cretinism).
hypothyroidism also may occur in Pendreds
syndrome.(associated with deafness) and turners
syndrome.
In adult symptoms are non specific:weight gain,cold
intolerance,constipation,dry skin,dry hair,sever hair
loss….
Laboratory findings: low level of T3 &T4
In primary hypothyroidism raised TSH level
In second hypothyroidism suppressed TSH level
Treatment :administering T4
Dosage depend on condition of patient.
Hypothyroidism
Anti-Thyroid Antibodies
Markers of Chronic Thyroiditis
Anti- Thyroglobulin Antibodies
Does not Correlate with hypothyroidism
Anti-Thyroid Peroxidase Antibodies
(formerly known as Anti-microsomal
Antibodies)
Correlate with the development of
hypothyroidism
Anti- TSH Receptor Antibodies
TSHRAb
Used in the diagnosis and monitoring of
Graves’
TSI (Thyroid Stimulating Immunoglobulin)
TBII (TSH Binding Inhibitory
Immunoglobulin)
Severity of Primary Hypothyroidism by Thyroid
Levels
TSH rises first and
abruptly
Decline of T4
and T3 slower
and later
Serum T3 Level Should not be Used
to Diagnose Hypothyroidism
R10.
Serum total T3 or
assessment of serum free T3
should not be done to diagnose
hypothyroidism Grade A, BEL 2;
Upgraded because of many
independent lines of evidence and
expert opinion.
When Should Antithyroid Antibodies
Be Measured?
R1.Thyroid peroxidase antibody
(TPOAb) measurement should be
considered when evaluating patients
with subclinical hypothyroidism. Grade
B, BEL 1; Downgraded. If positive,
hypothyroidism rate of 4.3% versus
2.6% per year. Therefore, may or may
not influence the decision to treat .
TSH is Lower Particularly in 1st trimester
Free T4 in pregnancy unreliable
10
weeks gestation
+100
20
30
40
E2
TBG
hCG
+50
TT4
%
Change
0
vs.
Non-pregnant
TSH
FT4
-50
1st. Trimester
2nd. Trimester 3rd. Trimester
Pregnancy Thyroid Testing
Increased pregnancy loss rate in thyroid antibody
negative women with TSH levels between 2.5 and
5.0 in 1st trimester provides strong physiological
evidence to support redefining TSH upper limit of
normal in 1st trimester to 2.5 mIU/liter.
Negro, J Clin Endocrinol Metab. 2010 Sep;95(9)
Pregnancy normal-range TSH
values
R. 14.2 In pregnancy, the upper limit of the
normal range should be based on trimesterspecific ranges for that laboratory. If trimesterspecific reference ranges for TSH are not
available in the laboratory, the following upper
normal reference ranges are recommended:
first trimester, 2.5 mIU /L; second trimester,3.0
mIU/L; third trimester, 3.5 mIU/L. Grade B,
BEL 2.
Role for TPOAb?
R3.
TPOAb measurement
should be considered when
evaluating patients with infertility,
particularly recurrent miscarriage.
Grade A, BEL 2; upgraded because
of favorable risk-benefit potential .
Treatment of TPOAb+ Women?
R20. Treatment with L-thyroxine should be
considered in women of child-bearing age with
normal thyroid hormone levels when they are
pregnant or planning a pregnancy including
assisted reproduction if they have or have had
positive levels of serum TPOAb, particularly
when there is a history of miscarriage or past
history of hypothyroidism Grade B, BEL 2
Thyroid hormone should not be
used to treat obesity
R30.
Thyroid hormone should not be
used to treat obesity in euthyroid
patients. Grade A, BEL 2
Upgraded to A because of potential
harm— inconclusive benefit and
induces subclinical hyperthyroidism
Hypothyroidism and the Heart
Hypertension (Diastolic)
Diastolic Dysfunction
Elevated Cholesterol*
Long Q-T Syndrome
Serum CK Elevation (*Statin Hazard?)
Coagulopathy
Treatment of TSH between 5 and 10?
Depends…
R16. Treatment should be considered
particularly if they have symptoms suggestive
of hypothyroidism, positive TPO antibodies or
evidence of atherosclerotic cardiovascular
disease, heart failure or have associated risk
factors for these diseases.
Grade B, BEL 1; evidence not fully
generalizable to stated recommendation and
there are no prospective, interventional
studies.
Vanderpump MP et al. 1995 Clin Endo 43:55-68 (EL2). Vanderpump MP & Tunbridge WM 2002
Thyroid 12:839-47 (EL4). Hollowell JG et al. 2002 JCEM 87:489-99 (EL1). Huber G et al. 2002
JCEM 87:3221-26 (EL2). McQuade C et al. 2011 Thyroid 21:837-43 (EL3). Ochs N et al. 2008 Ann
Treatment of TSH levels > 10 is recommended
R15. Patients whose serum TSH levels exceed 10
mIU/L are at increased risk for heart failure and
cardiovascular mortality, and should be considered
for treatment with L-thyroxine.
Grade B, BEL 1; not generalizable and meta-analysis
does not include prospective interventional studies.
Hypothyroid patients treated with normalized TSH
are still more likely to feel poorly (Saravan Clinical Endo 2002;
Boeving Thyroid 2011)
Surks et al. 2004 JAMA 291:228-38 (EL4). Rodondi
N et al. 2010 JAMA
304:1365-74 (EL2). Razvi S et al. 2010 JCEM
95:1734-40 (EL3).
Gencer B et a.2012 Circulation Epub before print
(EL1).
Initiating therapy in overt
hypothyroidism
Recommendation 22.7.1: When initiating therapy in
young healthy adults with overt hypothyroidism,
beginning treatment with full replacement doses should
be considered. Grade B, BEL 2
Recommendation 22.7.2: When initiating therapy in
patients older than 50-60 years old with overt
hypothyroidism, without evidence of coronary heart
disease, an L-thyroxine dose of 50 mcg daily should be
considered. Grade D, BEL 4
Initiating treatment in subclinical
hypothyroidism
Recommendation 22.8: In patients with
subclinical hypothyroidism initial Lthyroxine dosing is generally lower than
what is required in the treatment of
overt hypothyroidism.
A daily dose of 25 to 75 mcg should be
considered, depending on degree of TSH
elevation. Further adjustments should be
guided by clinical response and follow up
laboratory determinations including TSH
values. Grade B, BEL 2
Question 3.12 How should hypothyroidism be
treated and monitored?
R23. L-thyroxine should be taken with water
consistently 30 to 60 minutes before
breakfast or at bedtime 4 hours after the last
meal. It should be stored properly per
product insert and not taken with substances
or medications that interfere with its
absorption.
Grade B, BEL 2.
Bolk N et al. 2010 Arch IM 170:1996-2003 (EL2).
Bach-Huynh TG 2009 JCEM 94:3905-12 (EL2.)
Thyroiditis
Classified into acute,subacute,and chronic forms.
Acute(suppurative)thyroiditis:
Thyroid gland is resistant to infection but some times
infectious agents can seed it
*Via the hematogenous
*After penetrating trauma
*Due to immunosuppression……
This disease is more common in children and
characterized by severe neck pain(radiating to jaws or
ear),fever,chill,odynophagia,&dysphonia.
The diagnosis confirm by leukocytosis on blood tests
and FNAB for Grams stain,culture,and cytology.
Treatment:
Antibiotic + drainage of abscesses.
Subacute Thyroiditis
Can occur in the painful or painless forms.exact
etiology is not known but:
Painful: viral infection,genetic(HLAB35)
In this disease cytotoxic T lymphocytes stimulate and
damage thyroid follicular cell.
Its common in women,characterized by sudden or
gradual onset of neck pain.the gland is large,tender
& firm.(T4,T3.ESR high / TSH low
The disorder progresses through 4stage:
Hyperthyroidism , euthyroidism, hypothyroidism,
euthyroidism.
Treatment
Aspirin,NSAID,thyroid hormone
therapy,& some times thyroidectomy
Painless: may be an autoimmune disease and
especially occur in women after delivery.
symptoms and clinical course are similar to painful
form.
Treatment B-blocker, thyroid hormone, and some
times thyroidectomy or RAI ablation
Choronic thyroiditis lymphocytic
Is an autoimmune process initiated by the activation
of CD4 T helper lymphocytes which destruct
thyrocytes. antibodies directed against 3main Ag:
Tg,TPO,TSH-R
Disease is common in women between 3040years.minimally or moderately enlarged firm
granular gland discover in examination.FNAB can be
useful that in pathology we see follicles lined by
Ashanazy cell.
Diagnostic studies:
Elevated TSH and present of thyroid autoantibody
confirm the diagnosis.
Treatment: thyroid hormone,surgery(for suspicion
of malignancy,or cosmetic deformity)
Riedels Thyroiditis
Is rare variant of thyroiditis which characterized by
replacement of all or part of the thyroid parenchyma
by fibrous tissue.it presents as painless,hard(woody)
neck mass.
Symptom include:
Dysphagia ,dyspnea, hoarsness, choking,
hypothyroidism, hypoparathyroidism…
Biopsy is necessary.
Treatment : surgery
Goiter
Familial goiter resulting from dificiencies in
enzymes necessary for thyroid hormone synthesis
hypothyroidism
Endemic goiter resulting from iodine deficiency
and can be treated by iodine.
Clinical feature:most patients are
asymptomatic,although patients often complain of
pressure sensation in the neck.
We can find soft enlarged gland(simple goiter)or
nodules of various size(in multinodular goiter)
Thyroid tests are usually normal.
Treatment:
Patient with small,diffuse goiter do not need
treatment
In large goiter thyroid hormone therapy can be
useful.
Algorithm for Hyperthyroidism
Measure TSH and FT4
 TSH, FT4 N
 TSH,  FT4
Primary (T4)
Thyrotoxicosis
Measure FT3
 TSH,  FT4
N TSH, FT4 N
Pituitary Adenoma
FNAC, N Scan
Features of Grave’s
Yes
Rx. Grave’s
No
 RAIU
Low RAIU
Single Adenoma, MNG
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High
T3 Toxicosis
Normal
Sub-clinical Hyper
F/u in 6-12 wks
Sub Acute Thyroiditis, I2, ↑ Thyroxine
Solitary thyroid nodule
History such as time of onset,change in size of
nodule and associated
symptom(pain,dysphagia,dyspnea…) is very
important.
We should ask from ionizing radiation and familial
history of malignancy.
Nodules that are hard,or fixed to surrounding
structure are most likely to be malignant.
Diagnostic investigations
FNAB has become the most important test.
After FNAB nodules can be categorized into:beningsuspicious-malignant
Ultrasound is inexpensive and noninvasive method
that can be helpful for detecting nonpalpable thyroid
nodule,differentiating solid from cystic
nodule.calcification….
Solitary Thyroid Nodule
Algorithm for Thyroid Nodule
Thyroid Nodule
Low TSH
Normal TSH
TC 99 Nuclear Scan
Hot Nodule
RAI Ablation,
Surgery or
ATD
FNAC or US
guided biopsy
Cold Nodule
4%
Malignant
Surgery
10%
69%
Suspicious or
follicular Ca
Benign
T4
suppression
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Cyst
17%
Non diagnostic –
repeat FNAC
Surgery or
Cytology
management
But in patient with history of previous irradiation of
thyroid gland or familial thyroid cancer,
surgery should be done.