Upload
manish-vinayak
View
1.097
Download
5
Embed Size (px)
Citation preview
1
CHAIRPERSON:DR.ARDAMAN SINGH
SPEAKER:DR.MANISH VINAYAK
APPROACHAPPROACH
Where to look for thyroid? How to examine thyroid? What are the normal steps in thyroid hormogenesis? What is thyrotoxicosis ? What is hyperthyroidism ? What are the various causes ? What test should we order? How to differentiate the causes ? What is the appropriate treatment ?
2
3
Where to look for Thyroid ?Where to look for Thyroid ?
4
Clinical Anatomy of ThyroidClinical Anatomy of Thyroid
How to examine Thyroid?How to examine Thyroid?
There is no consensus regarding which is the best way to examine thyroid.
Examination from front begins with examiner identifying the cricoid cartilage and then identifies the isthmus directly below this. Then left lobe is palpated with right hand, lateral to trachea and medial to sternocleidomastoid muscle. Similarly repeated on the other side.
Examination from back consists of simultaneously using fingers of both hands with neck in relaxed position.
5
6
Clinical Exam of ThyroidClinical Exam of Thyroid
PSEUDOGOITRE: Apparent thyroidal enlargement when no true goiter is present, in thin patient when gland is located higher in neck, overlying the thyroid cartilage.
MODIGLIANI SYNDROME: Denotes illusion of goitre, seen when patient with long,curved necks have exaggerated cervical spine lordosis.
7
WHO Classification of GoitreWHO Classification of Goitre
GRADE 0: No goitre presence is found.GRADE 1: Neck thickening not visible in the
normal position, however palpable.GRADE 2: Neck swelling visible when neck is
in normal position.
8
9
10
Thyroid Regulation
PLASMA T4 + FT4
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
THYROID T4 and T3
PLASMA T3 + FT3
TISSUES FT4 to FT3, rT3
TSH -R
Thyrotoxicosis/HyperthyroidismThyrotoxicosis/Hyperthyroidism
THYROTOXICOSIS refers to clinical syndrome of hypermetabolism and hyperactivity those results from excessive thyroid hormones.
HYPERTHYROIDISM denotes sustained increase in thyroid hormones biosynthesis and secretion by thyroid gland.
11
12
While many patients with thyrotoxicosis have hyperthyroidism, it is not so in others such as- those in whom it is caused by thyroiditis or exogenous thyroid hormone administration.
Causes of thyrotoxicosis??Causes of thyrotoxicosis??
Primary Thyrotoxicosis Secondary
hyperthyoridism without hyperthyroidism hyperthyroidism
13
Primary HyperthyroidismPrimary Hyperthyroidism
Graves disease (m.c cause) Toxic multinodular goitre Toxic adenoma Functioning thyroid metastasis Struma ovarii Activating mutation of TSH receptor Activating mutation of Gsa (McCune-Albright
syndrome) Drugs: iodine excess (Jod-Basedow phenomenon)
14
Thryotoxicosis without Thryotoxicosis without hyperthyroidismhyperthyroidism
Subacute thyroiditisSilent thyroiditisThyrotoxicosis factitiaThyroid destruction: use of amiodarone,
lithium, interferon-alpha & beta, interleukin-2, radiation & infarction of adenoma
15
Secondary hyperthyroidismSecondary hyperthyroidism
TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome Chronic gonadotropin secreting tumors Gestational thyrotoxicosis. Testicular malignancies.
16
Graves DiseaseGraves Disease The most common cause of thyrotoxicosis (50-60%). Organ specific auto-immune disease The most important autoantibody is
– Thyroid Stimulating Immunoglobulin (TSI) or TSA
– TSI acts as proxy to TSH and stimulates T4 and T3
Anti thyro peroxidase (anti-TPO) antibodies Anti thyro globulin (anti-TG) Autoimmune diseases - Pernicious Anemia, T1DM, RA,
Myasthenia Gravis, Vitiligo, Adrenal insufficiency. In long term, spontaneous hypothyroidism can develop in up to
15% of patients.17
Toxic Multinodular Goiter (TMG)Toxic Multinodular Goiter (TMG) TMG is the next most common hyperthyroidism -
20% More common in elderly individuals – long standing
goiter Mild elevation of FT4 and FT3
Progresses slowly over time Clinically multiple firm nodules (called Plummer’s
disease) Scintigraphy shows - hot and normal areas
18
MNG and GravesMNG and Graves
19
Huge Toxic MNG Diffuse Graves Thyroid
Sub Acute Thyroiditis (SAT)Sub Acute Thyroiditis (SAT)
Also called as De-Quervain Thyroiditis.
SAT is the next most common hyperthyroidism – 15%
T4 and T3 are extremely elevated in this condition
Immune destruction of thyroid due to viral infection
Destructive release of preformed thyroid hormone
Thyroid gland is painful and tender on palpation
Nuclear Scintigraphy scan - no RIU in the gland Hyperthyroidism (3-6 weeks) is followed by transient hypothyroid
phase(4-6 months) If the gland is non-tender, called as silent thyroiditis Disease is self limiting with 95% remission rate.
20
Toxic Single Adenoma (TSA)Toxic Single Adenoma (TSA)
TSA is a single hyper functioning follicular thyroid adenoma.
Benign monoclonal tumor that usually is larger than 2.5 cm
It is the cause in 5% of patients who are thyrotoxic
Nuclear Scintigraphy scan shows only a single hot nodule
TSH is suppressed by excess of thyroxines
So the rest of the thyroid gland is suppressed
21
Thyrotoxicosis FactitiaThyrotoxicosis Factitia
Excessive intake of Thyroxine causing thyrotoxicosis Patients usually deny – it is willful ingestion This is a 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, so impalpable thyroid gland Stop Thyroxine and give symptom relief drugs Epidemic of thyrotoxicosis has been caused by consumption of
ground beef contaminated with bovine thyroid gland.
22
Hashimoto thyroiditisHashimoto thyroiditis
It may cause transient hyperthyroidism during the initial destructive phase.
Occurs due to release of stored thyroid hormone.
23
Amiodarone Induced Amiodarone Induced Thyrotoxicosis (AIT)Thyrotoxicosis (AIT)
Drug resembles T4 and contains 37% of iodine by weight.
23% of patients receiving amiodarone can develop AIT.
It can occur 4 months to 3 yrs after initiation of amiodarone and may develop many months after amiodarone has been discontinued.
24
Type 1 AITType 1 AIT
Type 1 AIT is caused by active elaboration of excessive thyroid hormone and may occur by either of two mechanisms:
1. Free iodine may cause toxic MNG in iodine deficient individuals with preexisting autonomous thyroid nodules (Jod-Basedow phenomenon)
2. Free iodine can trigger immunologic attack on thyroid causing Grave`s disease commonly with diffuse thyroid enlargement and anti TPO Ab`s.
25
Type 2 AITType 2 AIT
It is destructive thyroiditis with release of preformed thyroid hormone. Hyperthyroidism can last for 1-3 months and may be followed by hypothyroidism.
26
Clinical FeaturesClinical Features
1. Those that occur with any type of thyrotoxicosis
2. Those that are specific to Graves disease
In the elderly, features of thyrotoxicosis may be
subtle or masked, and patients may present with
fatigue and weight loss, known as APATHETIC
THYROTOXICOSIS. It can be mistaken for
depression in elderly.
27
Common SymptomsCommon Symptoms
1. Nervousness, anxiety
2. Heat intolerance
3. Tremor
4. Hyperactivity
5. Palpitations
6. Weight loss despite increased appetite
7. Oligo-menorrhea, loss of libido
8. Diarrhea, polyuria
9. Fatigue and weakness28
Common SignsCommon Signs
1. Sinus tachycardia or PAC, AF, Thyrotoxic cardiomyopathy, ppt of CHF
2. Systolic hypertension, wide pulse pressure
3. Goitre
4. Warm, moist skin
5. Fine hair & Onycholysis
6. Fine tremor of out stretched hands – format's sign
7. Hyperreflexia, proximal myopathy, chorea
8. Hypokalemic periodic paralysis
9. Gynecomastia29
Common Eye SignsCommon Eye Signs
Dalrymple sign- Upper eyelid retractionVon Graefe sign- lid lag with downward gazeKocher sign- staring appearance
These signs can occur with thyrotoxicosis of any etiology
30
Specific to Graves DiseaseSpecific to Graves Disease
1. Diffuse painless goitre with audible bruit.
2. Ophthalmopathy – Eye manifestations – 20-40% of cases Sense of sand in eyes, periorbital edema, conjunctival edema
(chemosis), proptosis , extraocular muscle dysfunction leading to diplopia
Weakness of upward gaze ( Stellwag sign ) Weakness of convergence ( Moebius sign ) Optic nerve compression leading to pappiledema, field defect
and permanent loss of vision
Eye changes are unilateral in 10% of cases.
Severity of eye disease does not correlate with severity of thyrotoxicosis. some cases are EUTHYROID.
31
REMEMBER, diplopia in Grave disease can be caused by exophthalmos or by coexistent ocular myasthenia gravis, which is usually mild, often with selective eye involvement.
AChR Ab levels are elevated in only 36% of such patients and thymoma is present in 9% only.
32
Thyroid OphthalmopathyThyroid Ophthalmopathy
33
Proptosis Staring appearance
Ophthalmopathy in GravesOphthalmopathy in Graves
34Periorbital edema and chemosis
Graves DermopathyGraves Dermopathy
Deposition of glycosamino glycans in the dermis of the lower leg – non pitting edema, associated with erythema and thickening of the skin, without pain or pruritus - called as pre tibial myxedema
35
Thyroid DermopathyThyroid Dermopathy
36
Pink and skin coloured papules, plaques on the shin
Thyroid AcropachyThyroid Acropachy
Presents with clubbing & swelling of fingers and toes.
It is so strongly associated with thyroid dermopathy that an alternative cause of clubbing sholud be sought in Graves patient without coincident skin and orbital involvement.
37
Thyroid AcropathyThyroid Acropathy
38
Clubbing and Osteoarthropathy
39
40
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
BASIC THYROID EVALUATION
41
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
EUTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
42
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4 PRIMARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
43
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SECONDARYHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
44
LO
W
N
OR
MA
L
HIG
H
FR
EE
T
HY
RO
XIN
E
or
FT
4
SUB-CLINICALHYPERTHYROID
LOW NORMAL HIGH
THYROID STIMULATING HORMONE - TSH
BASIC THYROID EVALUATION
45
THYROID HORMONES
TEST REFERENCE RANGE
TSH Normal Range 0.3 - 4.0 mU/L
Free T4 Normal Range 0.7-2.1 ng/dL
TSH upper limit will soon be revised to 2.5 mU/L
T3/T4 RATIOT3/T4 RATIO
Graves disease and toxic nodular goitre typically present with increased T3 production, with T3/T4 ratio greater than 20.
While thyrotoxicosis caused by thyroiditis, iodine exposure or exogenous levothyroxine intake, T4 is the predominant hormone and T3/T4 ratio is usually less than 20.
46
Thyroid AntibodiesThyroid Antibodies
Anti thyroid peroxidase (TPO)Anti thyroglobulinTSH-R antibodiesTSH-R Ab are helpful in diagnosis & management
of grave`s disease.It also helps in prediction of post-partum grave`s
disease % neonatal thyrotoxicosis.Helps in identification of orbitopathy in absence of
features of thyrotoxicosis.47
Nucleotide Scintigraphy
CAUSE OF THYROTOXICOSIS
Grave`s disease Toxic nodular goitre (uni or
multinodular) Subacute thyroiditis Silent thyroiditis Iodine induced & factitious
thyrotoxicosis Struma ovarii Follicular carcinoma TSH induced thyrotoxicosis
PATTERN OF DISTRIBUTION
Homogenous Restricted to region of
autonomy No uptake No uptake No uptake
Uptake in ovary Uptake in tumour metastasis Homogenous
48
Nucleotide ScintigraphyNucleotide Scintigraphy
49
Algorithm for HyperthyroidismAlgorithm for Hyperthyroidism
Measure TSH and FT4
TSH, FT4
Measure FT3Primary (T4)
Thyrotoxicosis
High
Pituitary Adenoma FNAC, N Scan
Normal
TSH, FT4 N TSH, FT4 N TSH, FT4 N
T3 Toxicosis
Sub-clinical Hyper
Features of Grave’s
Yes
Rx. Grave’s
No
Single Adenoma, MNG
Low RAIU RAIU
Sub Acute Thyroiditis, I2, ↑ Thyroxine
F/u in 6-12 wks
Treatment OptionsTreatment Options
1. Symptom relief medications (β-blockers)
2. Anti Thyroid Drugs – ATD
Methimazole, Carbimazole
Propylthiouracil (PTU)
3. Other agents- iodine, potassium perchlorate, lithium, cholestyramine.
4. Radio Active Iodine treatment – RAI Rx.
5. Thyroidectomy – Subtotal or Total
6. NSAIDs and Corticosteroids – for SAT51
Anti Thyroid Drugs (ATD)Anti Thyroid Drugs (ATD)
Imp. considerationsImp. considerations Methimazole Methimazole PropylthiouracilPropylthiouracil
EfficacyEfficacy Very potentVery potent PotentPotent
Duration of actionDuration of action Long acting BID/ODLong acting BID/OD Short acting QID/TIDShort acting QID/TID
In pregnancyIn pregnancy ContraindicatedContraindicated Safely can be givenSafely can be given
Mechanism of actionMechanism of action Iodination, CouplingIodination, Coupling Iodination, CouplingIodination, Coupling
Conversion of TConversion of T44 to T to T33 No actionNo action Inhibits conversionInhibits conversion
Adverse reactionsAdverse reactions Rashes, NeutropeniaRashes, Neutropenia Rashes, ↑NeutropeniaRashes, ↑Neutropenia
DosageDosage 20 to 40 mg/ OD PO20 to 40 mg/ OD PO 100 to 150mg qid PO100 to 150mg qid PO
Adverse effects of ThionamidesAdverse effects of Thionamides
Abnormal taste, arthralgias, pruritis, urticariaAgranulocytosis- usually occurs in first three
months, related to dose of methimazole (>30mg/day) and not of PTU.
Routine assessment of blood counts has not been useful and is not recommended.
HepatitisVasculitis, SLE like syndrome
53
ββ – Blocking Drugs – Blocking Drugs
Control cardiovascular and hyperadrenergic manifestations.
There is also rapid metabolism of propranolol in thyrotoxicosis hence larger doses are needed.
In addition to β blocking effect, propranolol in doses greater than 160mg/day decreases T3 generation by inhibiting 5-monodeiodinase enzyme.
54
Role of IodineRole of Iodine
Iodine in high concentrations, blocks release of pre-stored hormone and dec iodide transport and oxidation called as WOLF-CHAIKOFF EFFECT.
But this effect is transient and within 1-2 weeks complete escape from inhibition occurs.
So while treating thyrotoxicosis with iodine, addition of thionamides is essential to prevent aggravation of symptoms with loss of Wolf-chaikoff effect.
55
Potassium perchloratePotassium perchlorate
Inhibits iodine uptakeUsed orally in doses of 500mg twice daily.S/E include aplastic anaemia & nephritic
syndrome.Use of this agent is in initial stages for about 1
month with doses not greater than 1gm/day.Particularly useful in amiodarone induced
thyrotoxicosis.
56
LithiumLithium
Inhibits coupling and also decreases thyroid hormone release.
Doses of 300 mg 8 hrly.Lithium toxicity has to be avoided by
monitoring serum levels and maintaining them below 1 mEq/L.
57
CholestyramineCholestyramine
Decreases reabsorption of thyroid hormones from the enterohepatic circulation.
Used orally at rate of 4g four times daily, in combination with methimazole or PTU.
58
How long to give ATD ?How long to give ATD ?
Reduction of thyroid hormones takes 2-8 weeks
Check TSH and FT4 every 4 to 6 weeks
In Graves, once patient is rendered euthyroid options include use of ATD for 12-18 weeks or definitive treatment with RAI or surgery.
After cessation of therapy, close follow up for 3-6 months is required to detect relapse.
40% experience recurrence in 1 yr. in such situation RAI or surgery has to be considered.
MNG and Toxic Adenoma will not get cured by ATD. For them ATD is not the best. Treat with RAI.
59
Radio Active Iodine (RAI Rx.)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
60
Radio Active Iodine (RAI Rx.)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
61
Surgical TreatmentSurgical Treatment
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
6. Suspicious of biopsy proven malignant nodules
7. Co-morbidity requiring surgery like hyperparathyroidism.
62
Management of AITManagement of AIT
Colour flow doppler ultrasound may reveal hypervascularity in type 1 disease and in type 2 reduced blood flow might be apparent.
Drug should be discontinuedType 1 is treated with high doses of ATD with
addition of potassium perchlorate to prevent further uptake of iodine.
Type 2 responds to high dose corticosteroids (prednisolone 20-40 mg/day)
63
Thyrotoxic Crisis/StormThyrotoxic Crisis/Storm
Ppt factors- infection, stress, thyroid surgery, radio iodine therapy, DKA, parturition, vigorous palpation of thyroid
Presents with fever, tachyarrhythmia, CCF psychosis, adrenocortical failure leading to hypotension, coma.
Treat dehydration and hyperpyrexia.Glucorticoids indicated.
64
Excessive thyroid hormones can be treated with iodides, given as potassium iodide 15 mg 6 hrly orally or i.v
Alternatively iodinated X-Ray contrast media can be given to inhibit peripheral conversion of T4 to T3 in dosage of 1gm/day.
Use propranolol 80 mg 6hrly to counteract increased catecholamine activity.
65
THANKS66