Transcript Thyroid Function Tests - Audley Mills Surgery HOME

The Thyroid and Thyroid Function Tests
6th November 2007
Dr Mahmud’s Surgery
Dr Rehman Khan FRCP(Lond)
Basildon University Hospital
Inaugural Basildon Lecture
Wednesday 28th November 6 PM
Pharmaceutical promenade and hot buffet dinner
Prof Parveen Kumar
“Can doctors meet the expectations of the media
and the masses”
In UK 10 million requests per
year at an estimated cost of
£30 million
Menu
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Physiology
 Hypothyroid
 Thyroid and pregnancy
 Hyperthyroid
 Thyroid Nodule
UK Guidelines for the use of
Thyroid Function Tests
The Association for Clinical Biochemistry
British Thyroid Association
British Thyroid Foundation
July 2006
Questions Frequently asked by
General practitioners
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What is the diff between Total T4/T3 and free T4/T3 ?
Why do you attach so much significance to TSH results ?
Why don’t you always give me the same combination of tests ?
How long should it take for me to get the results back ?
How accurate are you results ?
Do Thyroid Hormones have diurnal or seasonal variation ?
Why do I have to wait two months before adjusting dose ?
Should TSH always be normal in patients taking Thyroxine ?
What do results of TSH 5 – 10 mU/l mean ?
How should I interpret a positive antibody test ?
Thyroid Gland

First described by Galen who thought its
function was to lubricate the phyranx
 Derived from the Greek word Thyreos
which means shield
A Thyroid History
1779 The first use of the term hypothyroidism by William Coxe.
1871 Sir William Gull at Guy's hospital described an adult with a condition similar to childhood cretins.
1877 W.M. Ord named the adult disease Myxedema.
1879 Charcot, a Frech physician, called it "cachexie pachydermique"
1882-1883 Reverdin, and Kocher made the connection between the clinical syndrome and absence
of the thyroid gland.
1883 Sir Felix Semon presented the view that cretinism, myxedema, and
surgical removal were all due to a deficiency of the thyroid gland
function.
Prior to 1883, the thyroid was felt to have no function. The doctors felt it could be removed without harm to
the patient!
Emil Kocher, famed Swiss Surgeon, removed the whole thyroid in 24 subjects. The results were unfavorable in 16.
They all developed loss of energy, weakness, swelling of the face, and legs, followed by the swelling of the whole
body! Mental processes slowed dramatically. It was finally noticed that total removal of the thyroid caused a disease
similar to cretinism, a childhood form of hypothyroidism
Physiology
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Thyroid gland produces Thyroxine
 Converted to active form T3 in tissue
 Scattered C cells within thyroid
 Thyroid stimulated by TSH from anterior
Pituitary
 Anterior Pituitary stimulated by TRH from
Hypothalamus
Physiology
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Thyroxine (T4) and Triiodothyronine (T3)
secreted by Thyroid Gland
 80% T4 and 20% T3
 TSH produced from Anterior Pituitary
stimulates Thyroid
 T4 Up, TSH Down
 T4 Down, TSH Up
Hypothyroidism
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Conginital absence of gland
Inherited defeciency of enzymes
Severe Iodine defeciency
Goitrogens; cassava to lithium
Iatrogenic ; surgical or radioiodine therapy
Secondary to hypopituitarism
Thyroid hormone resistance
Thyroiditis
Auto Immune
Hypothyroidism
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Dry skin
Brittle and lustreless hair
Weight gain
Tiredness
Constipation
Muscle aches
Bradycardia
Cold intolarance
Depression
Memory Loss
Heavy periods
Recommended Daily Intake
Adults
150 micrograms/day
Children
90-120 micrograms/day
Pregnant Women
200 micrograms/day
 In North America, the higher values are mainly due to an increased
intake in salt. In Japan, where foods rich in iodine are consumed
regularly, the intake may be as high as over 1000 micrograms/day.
Although iodine consumption is generally lower in Europe, the people in
these countries do not usually develop thyroid disease. However, when
they are exposed to unaccustomed, large amounts of iodine (such as
moving to North America and increasing their iodine intake), they can
develop thyroid disease. This occurs particularly in people who have an
underlying predisposition to developing thyroid disease.
Thyroid Function Tests
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TSH
 Thyroxine (T4)
 Ttriiodothyronine (T3)
 Thyroid Antibodies
Imaging
Thyroid Ultrasound scan
Thyroid Isotope Scan
Guidelines
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The diagnosis of primary hypothyroism
requires the measurement of both TSH and
T4
Thyroid Antibodies
Thyroid Peroxidase(thyroid microsomal)
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100% in Hashimato thyroiditis
 87% with graves disease
Thyroglobulin Antibody
 76% of Graves Disease
Thyroid receptor antibody
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Normally present in 12 –18 % of female population
Thyroid antibody 2
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Thyroid autoimmunity and miscarriage
Mark Prummel and Wilmer Wiersingha
Euro Journal of endocrinology 2004 150 751-55
Meta analysis of 18 studies
Odds ratio 2.73
Confounding factors
Other auto immune conditions
Higher TSH
Higher Age
No clear relationship to actual levels
Selenium level
Levothyroxine treatment in euthyroid pregnant women with
autoimmune thyroid disease: effects on obstetrical
complications
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Negro R, Formoso G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H.Department of
Endocrinology, Azienda Ospedaliera LE/1, P.O. "V. Fazzi", Piazza F. Muratore, 73100 Lecce,
Italy. [email protected]
CONTEXT: Euthyroid women with autoimmune thyroid disease show impairment of thyroid
function during gestation and seem to suffer from a higher rate of obstetrical complications.
OBJECTIVE: We sought to determine whether these women suffer from a higher rate of
obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects.
DESIGN: This was a prospective study. SETTING: The study was conducted in the
Department of Obstetrics and Gynecology. PATIENTS: A total of 984 pregnant women were
studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody
positive (TPOAb(+)). INTERVENTION: TPOAb(+) patients were divided into two groups:
group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869
TPOAb(-) patients (group C) served as a normal population control group. MAIN OUTCOME
MEASURES: Rates of obstetrical complications in treated and untreated groups were
measured. RESULTS: At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH
remained higher in group B compared with groups A and C throughout gestation. Free T(4)
values were lower in group B than groups A and C after 30 wk and after parturition. Groups A
and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than
group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25;
and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of
premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI =
1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7). CONCLUSIONS:
Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid
function, which is associated with an increased risk of miscarriage and premature
deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage
Case 1
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56 years old female
 Tired and weight gain
 Thyroxine(T4) = 8 pmol/l ( 12 – 23 )
 TSH
= 12 mU/l ( 0.4 – 4 )
What is the diagnosis ?
What other tests are required ?
What is the treatment ?
What Precautions are required ?
Answer 1
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Probable primary hypothyroidism
 Thyroid Antibodies
 Thyroxine 50 mcgm 1OD
 Advice re interactions
NO THYROID ULTRA SOUND SCAN
Hypothyroidism
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Common
 Mainly Females
 2 - 8% of UK female population affected
 Usually runs in family
 Other autoimmune conditions
Autoimmune disorders
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Hypothyroidism
 Hyperthyroidism
 Addisons Disease
 Pernicious Anaemia
 Premature Ovarian Failure
 Vitiligo
 Down Syndrome
History and Examination
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Symptoms
Family History
Other autoimmune disorders
Cardiac History
Other drugs
Viral Infections
Neck Pain
Diabetes
Guideline 2.3.2
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Patients with type-1 diabetes should have a
check of thyroid function included in their
annual review. Patients with type-2 diabetes
should have their function checked at
diagnosis but routine annual thyroid
function testing is not recommended
Thyroid Preparations
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Eltroxin (Levothyroxine sodium) Goldshield Pharmaceuticals
Levothyroxine ( non-proprietary )
Tetroxin ( Liothyronine ) T3 Goldshield Pharmaceuticals
Triiodothyronine injections Goldshield Pharmaceuticals
Armour ( Natural Hog extract available in US ) variable strengths
approx,. T4 38 mcgms and T3 9 mcgms
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Hypothyroidism and the Role of Armour Thyroid, Seaweed, Exercise, and More
Cutting-Edge Interview with Joseph Mercola, D.O.
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by Mary Shomon
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Dr. Joseph Mercola is an osteopathic physician, board certified in family medicine, who runs the Optimal
Wellness Center, located outside Chicago in Schaumburg, Illinois. He has been trained in and practices
both conventional and natural medicine, and writes a monthly column for a natural alternative medical
journal (The Townsend Letter for Doctors and Patients) and has been interviewed on national and local
news, including ABC's World News Tonight with Peter Jennings.
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Q. You have said that you feel that it's a "big myth" that that an elevated
TSH (thyroid stimulating hormone) level is always required before a
diagnosis of hypothyroidism can be made. First, can you explain why you
feel this is a big myth? And second, why do you feel that conventional
medicine seems to cling pretty firmly to this myth as the sole means of
diagnosing hypothyroidism?
WE CAN MAKE A DIFFERENCE
Set out at the bottom of the page is Dr Gordon Skinner's rebuttal of the new guidelines for Thyroid Stimulating
Hormone (TSH).
This page is for those who wish to be pro-active regarding undetected hypothyroidism (whether sufferer, carer,
family, or friend) because of the clinical practice that has been carried out, by the medical profession for the last 30
years.
Over this period millions of people have either, died unnecessarily at an early age (due to organ complications
because of hypothyroidism e.g. heart or pancreatic related conditions - diabetes of the latter), or lived many years
with ill health resulting in a poor quality of life. Relationships have been broken into tiny pieces with no hope of
salvation. The potential of millions has been lost over the years.
Why won’t the doctors listen to you?
Do you feel angry?
Do you feel frustated?
Do you feel sad for the lost years?
Do you feel cheated out of years of healthy living?
These feelings of anger, frustration and sadness are injurious to our beings.
But we can convert them into something constructive.
Be pro-active and do something about it.
Remember WE CAN make a difference.
SUFFERERS, FAMILY, CARERS, FRIENDS,
READ THE GUIDANCE NOTES FIRST
THE PETITION FOLLOWS.
THYROID PETITION
We the undersigned [thyroid patients, families/friends] wish to lodge this
petition with the General Medical Council as a formal complaint against the
clinical practice of the majority of the medical profession with regard to the
diagnosis and management of hypothyroidism on four counts: 1. Over reliance on thyroid blood test results and a total lack of reliance on
signs, symptoms, history of the patient and a clinical appraisal.
2. The emotional abuse and blatant disregard by the majority of general
practitioners and endocrinologists over the suffering experienced by
untreated/incorrectly treated thyroid patients and their lack of compassion
over the fate of these patients.
3. Stubbornness by the majority of general practitioners and endocrinologists
to treat patients suffering with hypothyroidism with a level of medication that
returns the patient to optimum health. In addition, the unwillingness to
prescribe alternative thyroid treatment for patients on individual clinical
grounds. For example a combination of T4/T3, T3 alone or a natural thyroid
treatment such as Armour Thyroid.
Thyroxine metabolism
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Mainly absorbed from Jejunum and Ileum
 Some absorption from Duodenum
 Usually 80% absorbed but large variation
 Large variation in clearance rates
Drugs affecting absorbtion
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Iron
 Calcium
 Antacids
Ferrous sulphate reduces thyroxine
efficacy in patients with hypothyroidism
Campbell NR, Hasinoff BB, Stalts H, Rao B
Ann internal Med 1992 Dec 15;117(12);1010-3
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14 Patients on stable thyroxine replacement
 Ferrous Sulphate 300mgm for 12 days
simultaneously
 TSH(mean)rose from 1.6 to 5.4
 9 patients had increase in signs and
symptoms
Other drugs that interfere with
thyroxine absorbtion
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Calcium
Binds with Thyroxine, Milk, Antacids
 Raloxifene
 Caffiene
 Sucralfate
Sucralfate and absorbtion of L Thyroxine
Campbell et al, Annals of Internal medicine 1993
Does Sucralfate impede Thyroxine therapy
Khan F, et al, Annals of Internal Mediciene 1993
Effect of calcium carbonate on the
absorption of levothyroxine.
Singh N, Singh PN, Hershman JM.
Division of Endocrinology and Metabolism, Endocrinology 111D, VA Greater
Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA
90073. [email protected]
CONCLUSIONS: This study of 20 patients receiving long-term
levothyroxine replacement therapy indicates that calcium carbonate
reduces T(4) absorption and increases serum thyrotropin levels.
Levothyroxine adsorbs to calcium carbonate in an acidic environment,
which may reduce its bioavailability. JAMA. 2000;283:2822-2825
Case 2
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48 years old male
 Known IHD and angina
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Thyroxine T4 ; 8
 TSH
; 12
Any special precautions
Case 2 cont
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Low dose recommended
 12.5 – 25 microgram
Diseases of the Thyroid
Wheeler and Lazurus
Case 3
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24 year old female
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Thyroxine ; 8
 TSH
; 12
Further investigations ?
Dose ?
Precautions ?
OCP
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Oestrogen increase Thyroxine metabolism
 Thyroxine levels decrease after
commencing OCP
 Check levels and increase dose
Pregnancy
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Normal gland increase in size by 30%
 Output increased
 Thyroxine requirement increases by 30 –
50%
 Thyroxine required for CNS development
Pregnancy 2
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Maternal Thyroid Deficiency during pregnancy
and subsequent nueropsychological development
of the child
Haddow et al, NEJM 1999 341;549-55
 IQ of offsprings (at ages 7-9) of 62 with TSH
high cf 124 matched control with normal TSH.
 IQ diff 7 points
Pregnancy 3
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Maternal Hypothyroxemia during early
pregnancy and subsequent child
development; a 3 year follow up study
Pop V et al, Clin Endo 2003 59;282-8
63 children at age 2 of mothers who had T4
values below 10th percentile cf 62 children
whose mother had T4 values 50-90th
percentile. Significant difference.
Guidelines
2.4.2
 In pregnancy there may be need to increase the
dose by atleast 50ugm daily to maintain a normal
TSH which should be measured in each trimester
5.2
 The thyroid status of hypothyroid patients should
be checked with TSH + T4 during each trimester
Guidelines 5.2
Ideally the following sequence of TFT shoould be performed
in the hypothyroid women during pregnancy
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Before conception
 At time of diagnosis of pregnancy
 At antenatal booking
 At least once in 2nd and 3rd trimester
 Again after delivery at 2 –4 weeks post partum
 Newly diagnosed hypothyroid will need testing every 4 – 6
weeks until stable
Case 4
55 years old female
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Thyroxine ; 2.4
 TSH
; 150
Further investigations ?
Dose ?
Precautions ?
Initiation of therapy with full dose
Thyroxine in hypothyroid patient is safe
and convenient
Roos A, et al Arch Int Med 2005; 165;1714-20
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50 patients
 Mean age 47 years
 Treated with 1.6 mcgm/kg vs 25mcgm
Case 5
30 years old male
Painful neck and flu like symptoms
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Thyroxine ; 4
 TSH
; 18
Further investigations ?
Dose ?
Thyroiditis
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Silent Thyroiditis. Silent Thyroiditis is the third and least common type of thyroiditis.
It was not recognized until the 1970's although it probably existed and was treated as
Graves' Disease before that. This type of thyroiditis resembles in part Hashimoto's
Thyroiditis and in part De Quervain's Thyroiditis.
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The blood thyroid test are high and the radioactive iodine uptake is low
(like De Quervain's Thyroiditis), but there is no pain and needle biopsy resembles
Hashimoto's Thyroiditis. The majority of patients have been young women following
pregnancy. The disease usually needs no treatment and 80% of patients show complete
recovery and return of the thyroid gland to normal after three months. Symptoms are
similar to Graves' Disease except milder. The thyroid gland is only slightly enlarged and
exophthalmos (development of "bug eyes") does not occur. Treatment is usually bed rest
with beta blockers to control palpitations (drugs to prevent rapid heart rates).
Radioactive iodine, surgery, or antithyroid medication is never needed.
A few patients become permanently hypothyroid and needed to be placed on
thyroid hormone
Case 6
44 years old female
Tired and weight gain
 Thyroxine ; 14 (range 12 – 23 )
 TSH
; 8 ( range 0.4 – 4 )
Strongly positive antibodies
Diagnosis ?
Treatment ?
No Caption Found
McDermott, M. T. et al. J Clin Endocrinol Metab 2001;86:4585-4590
Copyright ©2001 The Endocrine Society
Subclinical Hypothyroidism
Risk of conversion to HYPOthyroidism
over 20 years
 If TSH raised and Antibodies raised ; 50%
 If TSH raised and AB negative
; 33%
 If TSH normal and AB positive
; 25%
2 recent contradictory studies
Subclinical hypothyroidism but not subclinical
hyperthyroidism is asociated with increase in
fatal and non-fatal CVD
Walsh et al Arch Int Med 2005 ; 165; 2467-72
2064 subjects from western Australia
6% subc hypo, 2% subc hyper and 92% normal
CVD 15% vs 8%
Subclinical hypothyroidism is associated with CCF
but not increased CVD
Rodondi et al , Arch Int med 2005; 2460-6
Guidelines recommendations
-If TSH greater than 10 and FT4 low = treat
- If TSH greater than 10 and FT4 normal = treat
- If TSH is above the reference range but < 10 then thyroid
antibodies should be checked,. If antibodies high than TSH should
be checked annually or earlier is symptoms develop. T4 started if
TSH >10. If antibody negative check every 3 years
-There is no evidence to support the benefit of routine early
treatment in non-pregnant patients with a serum TSH above ref
range but<10. Physician may wish to consider the suitability of a
therapeutic trial of thyroxine on an individual patient basis
Case 7
44 years old female
Symptomatic
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Thyroxine ; 12
 TSH
; 4.1
What is normal TSH
J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8.
The evidence for a narrower thyrotropin reference range is compelling.
Wartofsky L, Dickey RA.
Department of Medicine, Washington Hospital Center, 110 Irving Street NW, Washington
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Debate and controversy currently surround the recommendations of a recent
consensus conference that considered issues related to the management of early,
mild, or so-called subclinical hypothyroidism and hyperthyroidism. Intimately
related to the controversy is the definition of the normal reference range for TSH. It
has become clear that previously accepted reference ranges are no longer valid as a
result of both the development of more highly sensitive TSH assays and the
appreciation that reference populations previously considered normal were
contaminated with individuals with various degrees of thyroid dysfunction that
served to increase mean TSH levels for the group. Recent laboratory guidelines
from the National Academy of Clinical Biochemistry indicate that more than 95%
of normal individuals have TSH levels below 2.5 mU/liter. The remainder with
higher values are outliers, most of whom are likely to have underlying Hashimoto
thyroiditis or other causes of elevated TSH. Importantly, data indicating that
African-Americans with very low incidence of Hashimoto thyroiditis have a mean
TSH level of 1.18 mU/liter strongly suggest that this value is the true normal mean
for a normal population. Recognition and establishment of a more precise and true
normal range for TSH have important implications for both screening and treatment
of thyroid disease in general and subclinical thyroid disease in particular
Guidelines
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The measurement of both TSH and Ft4 is required to
optimise thyroxine replacement treatment
The primary target of tyroxine replacement therapy is to
make the patient feel well and to achieve a TSH that is
within the reference range. The corresponding FT4 will be
within or slightly above the reference range
The minimum period to achieve a stable concentration
after a change in dose is two months and TFTs should not
be requested before this period has elapsed
Guidelines continued 3.1.5
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Patients stabilised on long term thyroxine
treatment should have TSH checked
annually
Case 8
44 years old female
Known Hypothyroid on Thyroxine 125 mcgms
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Thyroxine ; 18
 TSH
; 2.2
Still Symptomatic
Dissatisfaction with Thyroxine
treatment
Bristol survey
 Feeling of well being
 Symptoms of hypothyroidism
 397 hypothyroid patients and 551 controls
 48.6% vs 35%
T4 T3
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Effects of Thyroxine as compared with
thyroxine plus triiodothyronine in patients
with hypothyroidism.
Robertas Bunevicius et al, NEJM 340;424-9
Kuanus Medical University , Lithuania
33 patients, two 5 weeks period
Usual dose. 50 mcgms of T4 replaced by 12.5mcgms
of T3
T4 T3 -2
Combined therapy with T4 and T3 in two
ratios compared with T4 monotherapy
Bente c, JCEM 2005 90(5) 2666-74
144 patients
T4 vs T4;T3 (1;10) vs T4;T3 (1;5)
Pt preference ; 29% vs 41% vs 52%
Not explained by neurocognitive function
Slight decrease in weight which was associated with
treatment satisfaction
Other studies on T4/T3
Studies
Bunevicius
1999 (n=33)
Mean
T4 dose
175
Mean T4 levels
Before
After
25.7
23.1
T3 dose
used
12.5 od
Well
being
Better
Significance
0.04 <0.001
Saravanan
2003 (n=697)
127
21.1
13.73
10 od
Better
<0.01*
Bunevicius
2002 (n=20)
115
20.7
12.3
10 od
Same
0.09
Clyde 2002
(n=38)
NA
15.83
10.7
7.5 bd
Same
0.28
Sawka 2003
(n=40)
NA
15.7
10.5
19 as
bd
Same
0.28 – 0.35
Walsh 2003
(n=101)
136
15.3
11.4
10 od
Worse
0.03 - <0.01
Guidelines 3.1.3
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There is no consistent evidence to
recommend the use of combined therapy
with thyroxine and T3 in comparison to
thyroxine alone
TFTs and Lipids
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55 years old lady with elevated lipids
 Total Cholesterol = 5.9
 HDL = 0.8
 LDL = 4.1
 TSH = 15
 T4 = 11
 What next ?
TFT and lipids -2
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55 years old lady with strong family history
of IHD
TC = 6.8
 HDL = 0.8
 T4 = 11
 TSH = 5.8
TFTS and Lipids - 3
TSH-controlled L-thyroxine therapy reduces cholesterol levels and
clinical symptoms in subclinical hypothyroidism: a double blind,
placebo-controlled trial (Basel Thyroid Study).
Meier C, et al
Division of Endocrinology, Department of Central Laboratories, University Hospital Basel, Petersgraben 4, CH4031 Basel, Switzerland. [email protected]
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This study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids
and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven
subclinical hypothyroidism (TSH, 11.7 +/- 0.8 mIU/liter) were randomly assigned to receive Lthyroxine or placebo for 48 wk.
This is double blind study shows that physiological L-thyroxine replacement in patients
with subclinical hypothyroidism has a beneficial effect on low density lipoprotein
cholesterol levels and clinical symptoms of hypothyroidism. An important risk reduction
of cardiovascular mortality of 9-31% can be estimated from the observed improvement
in low density lipoprotein cholesterol.
TFT and Lipids - 5
Clinical review 115: effect of thyroxine therapy on serum lipoproteins in
patients with mild thyroid failure: a quantitative review of the
literature.
Danese MD, et al
Department of Epidemiology, The Johns Hopkins University School of Hygiene and Public Health,
The Johns Hopkins Medical Institutions, Baltimore, Maryland 21205-2223, USA.

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The objective of our study was to estimate the expected change in serum lipoprotein
concentrations after treatment with T4 in patients with mild thyroid failure (i.e.
subclinical hypothyroidism). Our data sources included MEDLINE, between January 1966
and May 1999, and review of references from relevant articles. There were 1,786
published studies identified, 461 abstracts reviewed, 74 articles retrieved, 24 articles
evaluated against predetermined entry criteria, and 13 studies systematically reviewed
and abstracted. All studies reported serum total cholesterol concentration changes
during T4 treatment, 12 reported triglyceride changes, 10 reported high-density
lipoprotein (HDL) cholesterol changes, and 9 reported low-density lipoprotein (LDL)
cholesterol changes. There were 247 patients in 13 studies. The mean decrease in the
serum total cholesterol concentration was -0.20
These results, although based on fewer than 250 patients, suggest that T4 therapy in
individuals with mild thyroid failure lowers mean serum total and LDL cholesterol
concentrations. The reduction in serum total cholesterol may be larger in individuals
with higher pretreatment cholesterol levels and in hypothyroid individuals taking
suboptimal T4 doses. There do not seem to be significant effects of T4 on serum HDL or
triglyceride concentrations
TFT and Lipids - 4
Clin Endocrinol (Oxf). 1993 May;38(5):451-2.
Thyroxine replacement therapy and circulating lipid
concentrations.
Franklyn JA, Daykin J, Betteridge J, Hughes EA, Holder R, Jones SR, Sheppard MC.
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, UK.

OBJECTIVE: Hypothyroidism is a common disorder and while the association of
overt hypothyroidism with hypercholesterolaemia is clear, the effect upon lipids
of the minor abnormalities of thyroid function often found in those receiving T4
replacement therapy is unclear. The aim of the present studies was to define in
those with hypothyroidism the effect upon circulating lipids of subtle changes in
thyroid status, indicated by serum TSH values below or above the normal range.
CONCLUSION: Effects of T4 upon lipid measurements suggest that
patients with subclinical hypothyroidism should receive
replacement therapy. Doses of T4 which suppress TSH to below
normal may have a more significant influence upon lipids than
doses of T4 which restore TSH to the normal range.
Hyperthyroidism
Case 9
38 years old female
Palpitation, tremors, etc

Thyroxine ; 44
 TSH
; < 0.01
Investigations
Treatment
Precautions
Hyperthyroidism
Causes

AutoImmune
 Thyroiditis
 Iatrogenic
 Solitary Nodule
 Toxic multinodular Goitre
Hyperthyroidism
Clinical Features
Palpitations
Heat intolerance
Nervousness
Insomnia
Breathlessness
Increased bowel movements
Light or absent menstrual periods
Fatigue

Tachycardia
Tremors Weight loss
Muscle weakness
Warm moist skin
Hair loss
Staring gaze
History and examination

Symptoms
 Family History
 Exclude Thyroiditis
 Astma ?
 Eye problem
 Thyroid acropachy and PTM
Investigations

TSH
 T4
 T3
 Thyroid antibodies
 ? Thyroid receptor antibody
 ? Thyroid Isotope Scan
Treatment Options

Surgery
 Radio-Iodine
 Medications
Titration Regime
Block and replacement regime
Increased Chance of
Recurrence

Large Goitre
 Male Sex
 Initial T3 levels
Surgery

Curative
Indications







Large Goitre
Cosmetic
Suspected or confirmed malignancy
Pressure symptoms
Thyroid Eye Disease
Drug Intolerance
Recurrence
Surgery
Problems

Hypothyroidism
 Damage to Parathyroid glands
 Damage to recurrent laryngeal nerve
 Thyroid Storm
 Keloid Scars
Partial or Total Thyroidectomy ?
Anti Thyroid Medications
Carbimazole 5 mgm and 20 mgm tablets
Maximum Dose 40 mgm
 Propylthioouracil 50 mgm tablets
Maximum dose 400 mgm

Beta Blockers
Lithium
2 Regimes
Block and replacement
Titration
Titration regimen is as effective and better tolerated
than block-replacement regimen in the therapy of
Graves Hyperthyroidism ; a systemic review
AbrahamP, Avenell A Bevan JS, Aberdeen

19 randomised trial( 2177 patients )
 9 trials compared B-R with TT
 Relapse rates ; 53% vs 58%
 Side effects ; 11% vs 5%
Case 10
38 years old female
Palpitations, tremors, etc.

Thyroxine ; 98
 T3
; 44
 TSH
; <0.01
Further management ?
Radio Iodine treatment

More popular in USA
 Useful in toxic nodule
 Recurrent thyrotoxicosis
 Isolation
 Thyroid eye disease
Radio Iodine Treatment

3 weeks of isolation from children and
women of childbearing age
 Permanent hypothyroidism
Guidelines 4.1.1.

Patients with confirmed hyperthyroidism
should be referred for specialist care in
order to establish the diagnosis and optimal
management plan
Case 11

38 years old female with vague symptoms

Thyroxine ; 20
 TSH
; <0.01
Causes ?
Investigations ?
Treatment ?
Subclinical hyperthyroidism
T3 Toxicosis
Solitary nodule
Early thyrotoxicosis
Multi nodular goitre
Subclinical Hyperthyroidism
Atrial fibrillation
Osteopenia
Guidelines 4.2.2

Patient with subclinical hyperthyroidism that cannot be
explained by non thyroidal illness or drug therapy should
have repeat TFT with a frequency initially determined by
the clinical findings

Persistent sub clinical hyperthyroidism should prompt
specialist referral

Untreated sub clinical hyperthyroidism should be followed
into the long term by testing TFT every 6 –12 months
Subclinical Thyroid Dysfunction: A Joint Statement on
Management from the American Association of Clinical
Endocrinologists, the American Thyroid Association, and The
Endocrine Society
Hossein Gharib, R. Michael Tuttle, H. Jack Baskin, Lisa H. Fish, Peter Singer

Subclinical hyperthyroidism is much less common than subclinical hypothyroidism (10,
23, 24). We found the consensus panel’s recommendations to observe and monitor
patient’s with partial TSH suppression (0.1–0.4 mU/liter), but to treat patients with
complete TSH suppression (<0.1 mU/liter), acceptable and consistent with previous
published guidelines (12, 16). Although we agree with the consensus panel’s
recommendations with regard to subclinical hyperthyroidism, it is important to point out
that the strength of evidence is, in our opinion, as insufficient for making definitive
recommendations for this condition as it is for making recommendations for subclinical
hypothyroidism.

CLINICIAN'S CORNER
Subclinical Thyroid Disease Scientific Review and
Guidelines for Diagnosis and Management
Martin I. Surks, MD; Eduardo Ortiz, MD, MPH; Gilbert H. Daniels,
MD; Clark T. Sawin, MD; Nananda F. Col, MD, MPP, MPH;
Rhoda H. Cobin, MD; Jayne A. Franklyn, MD; Jerome M.
Hershman, MD; Kenneth D. Burman, MD; Margo A. Denke,
MD; Colum Gorman, MD, PhD; Richard S. Cooper, MD; Neil J.
Weissman, MD
JAMA. 2004;291:228-238
Conclusions Data supporting associations of subclinical thyroid disease with
symptoms or adverse clinical outcomes or benefits of treatment are few. The
consequences of subclinical thyroid disease (serum TSH 0.1-0.45 mIU/L or 4.5-10.0
mIU/L) are minimal and we recommend against routine treatment of patients with TSH
levels in these ranges. There is insufficient evidence to support population-based
screening. Aggressive case finding is appropriate in pregnant women, women older
than 60 years, and others at high risk for thyroid dysfunction.
What do I do ?

History
 Thyroid Isotope Scan to exclude Toxic Adenoma (
radio iodine treatment) or Thyroiditis
 Bone density
 Document pulse and/or ECG
 Follow up
Consider treatment if severe osteoporosis or atrial
fibrillation


20 years old man with painful neck
Thyroxine ; 29 mmol
 TSH ; 0.01
 Antibody negative
Thyroid Eye disease

Thyroid Opthalmopathy
 Dysthyroid Eye Disease
 Thyroid Associated Opthalmopathy
Thyroid Eye Disease

Cosmetic
 Exposure
 Optic nerve pressure
 Eye movements
Case 13
34 years old lady presents saying her friend at work
says she has a lump on her neck which is painless
TFTs are normal
Thyroid Nodule

Very common
 30 – 60 years old ; 4.2% ( Palpation)
 19 – 67% by ultrasound
 Autopsy ; 50%

Thyroid Cancer is rare ; 4 / 100,000
 Ocult thyroid cancer in 6 – 24 % autopsy
Thyroid Nodule 2

Thyroid nodule very common
 Thyroid cancer very rare but curable
AIM IS NOT MISS THYROID CANCER
Thyroid nodule Risk factors








Exposure to radiation as child
Family history
Under 20 years
Over 60 years
?male sex
Hourseness
Fixed hard nodule
Similar risk for multinodular and single nodule
Thyoid Nodule
Invesigations

TFTs
 Ultra sound scan
 Thyroglobulin and Calcitonin not
recommended ( US Guidelines)
 Fine needle Aspration(FNA)
Thyroid nodule
Ultrasonography

Hypoechogenecity
 Microcalcification
 Irregular margin
 Absence of halo
 Increased vascularity
Thyroid Nodule
FNA

Sensitivity of 97% with US
 Thy –1 ; Insufficient material
 Thy – 2 ; Indeterminate, follicular cells
 Thy – 3 ; Possibly malignant
 Thy – 4 ; Probably malignant
 Thy – 5 ; Definitely malignant
Thank you
Any Questions ?
T4 T3 - 3