Pakistan Society of Chemical PathologistsDistance Learning Programme in Chemical

Pathology

Lesson No 2Thyroid Functional Disorders

By By

Surg Commodore Aamir IjazSurg Commodore Aamir IjazMCPS, FCPS, FRCP (Edin)MCPS, FCPS, FRCP (Edin)

Professor of Pathology / Consultant Chemical PathologistProfessor of Pathology / Consultant Chemical PathologistBahria University Medical & Dental College / Bahria University Medical & Dental College /

PNS SHIFA KarachiPNS SHIFA Karachi

andand

Dr Lena JafriDr Lena JafriFCPS (Chem Path)FCPS (Chem Path)

Instructor Chemical PathologyInstructor Chemical PathologyDepartment of Pathology and Microbiology; Extension Department of Pathology and Microbiology; Extension

19311931Aga Khan UniversityAga Khan University

19/04/2319/04/23 01:0601:06 11

Q 1. Q 1. A 26 year Pakistani female has lethargy and bradycardia. Screening of thyroid dysfunction should be carried

out by:

d. TSH onlyd. TSH only11

a. T3 and T4 estimation onlyb. TSH and Free T4 c. TSH and T4 d. TSH onlye. TSH, T3 and T4 estimation

19/04/2319/04/23 01:0601:06 22

• The measurement of TSH in a basal The measurement of TSH in a basal blood sample by a sensitive blood sample by a sensitive immunoassay provides the single immunoassay provides the single most sensitive, specific and reliable most sensitive, specific and reliable test of thyroid status in thyroid test of thyroid status in thyroid disorders. disorders.

• Thyroid dysfunctional disorders with Thyroid dysfunctional disorders with normal TSH are very rare.normal TSH are very rare.

• So in many countries ‘TSH only’ So in many countries ‘TSH only’ strategy is adopted for the strategy is adopted for the diagnosis.diagnosis.

TSH Only Strategy for Thyroid TSH Only Strategy for Thyroid ScreeningScreening

19/04/2319/04/23 01:0601:06 33

Reflexive testing for Reflexive testing for Thyroid DysfunctionThyroid Dysfunction

Serum TSH normal — no further testing performed

Serum TSH high — free T4 added to determine the degree of hypothyroidism

Serum TSH low — free T4 and T3 added to determine the degree of hyperthyroidism

19/04/2319/04/23 01:0601:06 44

Some exceptions to TSH only Strategy

Measure serum TSH with Thyroid hormones:

In a young woman with amenorrhea (e.g. Sheehan`s Syndrome).If the patient has convincing symptoms of hyper- or hypothyroidism despite a normal TSH result.In critical ill patients with strong suspicion of a thyroid disorderSome other rare situations

19/04/2319/04/23 01:0601:06 55

Q 2: Q 2: Serum T4 of a patient decreased from 3.0 pg/ml to 1.5 pg/ml. The expected change in

TSH is:

b. b. One hundred fold increase in TSHOne hundred fold increase in TSH22

a. Fifty fold increase in TSHb. One hundred fold increase in TSHc. Ten fold increase in TSHd. Two fold decrease in TSHe. Two fold increase in TSH

19/04/2319/04/23 01:0701:07 66

If T4 halves, TSH increases If T4 halves, TSH increases by 100 fold or even moreby 100 fold or even more

If T4 doubles, TSH If T4 doubles, TSH decreases by 100 fold or decreases by 100 fold or even lesseven less

19/04/2319/04/23 01:0701:07 77

Sensitivity of TSH Sensitivity of TSH (Hormone from Mother (Hormone from Mother

Gland)Gland)

Q Q 3: 3: A 65 year old female has following thyroid profile:

Serum fT3 2.16 pg/ml (1.60-4.20)Serum fT4 1.34 ng/ml (0.70-1.68)Serum TSH 5.62 mIU/L (0.30-4.0)

The most probable diagnosis in this patient is:

a. Normal thyroid profile for the age b. Primary Hypothyroidism c. Secondary Hypothyroidism d. Sick Euthyroid Syndrome e. Sub-Clinical Hypothyroidism

19/04/2319/04/23 01:0701:07 88

e. e. Sub-Clinical Hypothyroidism1

• Subclinical hypothyroidism is defined biochemically as a normal T4 concentration in the presence of an elevated TSH.

• Clinical symptoms may or may not be present

• So it can only be diagnosed on the basis of laboratory test results.

• It is also called ‘Mild Hypothyroid It is also called ‘Mild Hypothyroid Disease’Disease’19/04/2319/04/23 01:0701:07 99

Subclinical Hypothyroidism Subclinical Hypothyroidism (SHO)(SHO)

What is Elevated TSH?What is Elevated TSH?

Upper limit of TSH is important in defining Upper limit of TSH is important in defining SHO.SHO.

Many surveys have recommended upper Many surveys have recommended upper limit to be 2.5 mU/L.limit to be 2.5 mU/L.

But consensus is on 4.0 to 4.5 mU/L.But consensus is on 4.0 to 4.5 mU/L. A higher upper limit is suggested in very A higher upper limit is suggested in very

advance age (e.g.> 80 y) but without any advance age (e.g.> 80 y) but without any agreement.agreement.

So we use 4.0 mIU/L as upper limit.So we use 4.0 mIU/L as upper limit.

19/04/2319/04/23 01:0701:07 1010

Causes of SHOCauses of SHO

Causes of SHO are the same as of Causes of SHO are the same as of Overt Hypothyroidism (High TSH, Overt Hypothyroidism (High TSH, Low T4).Low T4).

SHO is far more common than overt SHO is far more common than overt disease e.g. among all hypothyroid disease e.g. among all hypothyroid 70-80% are SHO.70-80% are SHO.

19/04/2319/04/23 01:0701:07 1111

Treatment of SHOTreatment of SHO

Patients with TSH > 8-10 mU/L should Patients with TSH > 8-10 mU/L should be treated.be treated.

Controversy over treatment in patients Controversy over treatment in patients with TSH 4-8 mU/L (in both children and with TSH 4-8 mU/L (in both children and adults).adults).

In patients with TSH 4-8 mU/L treatment In patients with TSH 4-8 mU/L treatment should be considered in pregnancy and should be considered in pregnancy and in patients with hyperlipidaemia and in patients with hyperlipidaemia and heart disease, etc.heart disease, etc.

19/04/2319/04/23 01:0701:07 1212

Q 4: Q 4: A 68 year old male admitted with pneumonia and sepsis has following thyroid

profile. Serum fT3 0.16 pg/ml (1.60-4.20)Serum TSH 0.22 mIU/L (0.30-4.0)

c. c. Sick Euthyroid Syndrome1

a.Secondary Hyperthyroidism b. Secondary Hypothyroidism c. Sick Euthyroid Syndromed. Sub-Clinical Hyperthyroidism e. Thyroid crisis

19/04/2319/04/23 01:0701:07 1313

Non Thyroidal Illness Non Thyroidal Illness (sick euthyroid syndrome)(sick euthyroid syndrome)

Non Thyroidal Illness (sick Non Thyroidal Illness (sick euthyrodism) is characterized by euthyrodism) is characterized by Normal / low TSH and low T3 and/ or Normal / low TSH and low T3 and/ or T4.T4.

It is a protective response of body in It is a protective response of body in chronic illness to reduce metabolismchronic illness to reduce metabolism

19/04/2319/04/23 01:0701:07 1414

Low T3 is common in critical Low T3 is common in critical illnessillness

19/04/2319/04/23 01:0701:07 1515

19/04/2319/04/23 01:0701:07 1616

Thyroid function in non-Thyroid function in non-thyroidal illnessthyroidal illness

Thyroid function should not be Thyroid function should not be assessed in seriously ill patients assessed in seriously ill patients unless there is a strong suspicion of unless there is a strong suspicion of thyroid dysfunction. thyroid dysfunction.

If you suspect thyroid dysfunction in If you suspect thyroid dysfunction in a critical patient then TSH assay may a critical patient then TSH assay may be accompanied by T4.be accompanied by T4.

19/04/2319/04/23 01:0701:07 1717

Critically ill patients with low serum Critically ill patients with low serum T3 and low T4 T3 and low T4 SHOULD NOT BE SHOULD NOT BE TREATED TREATED with thyroid hormonewith thyroid hormone

19/04/2319/04/23 01:0701:07 1818

Q 5: Q 5: A 22 years female had undergone total thyroidectomy after a diagnosis of thyroid carcinoma. She is on thyroid replacement therapy. Which of the following values constitutes an important part of the treatment goals in this patient:

d. d. Serum TSH < 0.2 mIU/L1,3

a. Serum Free T3 > 3 nmol/Lb. Serum Free T4 > 22 pmol/Lc. Serum TSH 2- 3 mIU/Ld. Serum TSH < 0.2 mIU/Le. Serum Thyroglobulin > 40 mg/L

19/04/2319/04/23 01:0701:07 1919

Thyroid Function TestingThyroid Function Testing in Thyroid Cancer in Thyroid Cancer

TSH has to be kept very much suppressed after TSH has to be kept very much suppressed after surgery for thyroid cancersurgery for thyroid cancer

This is done by giving exogenous thyroid This is done by giving exogenous thyroid hormone. hormone.

British Thyroid Association has recommended British Thyroid Association has recommended TSH level suppressed to <0.10mU/LTSH level suppressed to <0.10mU/L33

The serum FTThe serum FT44 should be elevated should be elevated

So in these patients TSH and FTSo in these patients TSH and FT4 4 do not need to do not need to be within the ‘reference range’; be within the ‘reference range’;

However, clinical features of over treatment However, clinical features of over treatment should be noted. should be noted.

19/04/2319/04/23 01:0701:07 2020

Target TSH value in Patients Target TSH value in Patients with Thyroid Malignancy with Thyroid Malignancy

TSH may provide stimulation TSH may provide stimulation of any remnant thyroid of any remnant thyroid secondariessecondaries

A higher dose of thyroxin is A higher dose of thyroxin is given to the patient to given to the patient to suppress TSH. suppress TSH.

19/04/2319/04/23 01:0701:07 2121

Serum Thyroglobulin (Tg) and Serum Thyroglobulin (Tg) and Thyroglobulin Antibodies (TgAb)Thyroglobulin Antibodies (TgAb)

It is an excellent marker for monitoring It is an excellent marker for monitoring treatment of thyroid cancers but only in patients treatment of thyroid cancers but only in patients with with total thyroidectomy total thyroidectomy oror 131131iodine ablationiodine ablation..

In such patients detectable serum Tg (>2ug/L) is In such patients detectable serum Tg (>2ug/L) is highly suggestive of residual or recurrent highly suggestive of residual or recurrent tumour. So the treatment goal is < 2ug/L (and tumour. So the treatment goal is < 2ug/L (and not in the ref range).not in the ref range).

TgAb is recommended to be measured at the TgAb is recommended to be measured at the same time as Tg to exclude interference of same time as Tg to exclude interference of endogenous TgAb in Tg assaysendogenous TgAb in Tg assays

Tg has no rule in diagnosis of thyroid cancer.Tg has no rule in diagnosis of thyroid cancer.

19/04/2319/04/23 01:0701:07 2222

Monitoring of Monitoring of Hypoparathyroidism in patients Hypoparathyroidism in patients

with Thyroid Cancerwith Thyroid Cancer In patients with total In patients with total thyroidectomy or thyroidectomy or 131131iodine iodine ablation, hypoparathyroidism will ablation, hypoparathyroidism will be presentbe present

So Ca, P and Mg has to be So Ca, P and Mg has to be monitored and kept within monitored and kept within reference range.reference range.

19/04/2319/04/23 01:0701:07 2323

Q 6: Q 6: A 24 years female is pregnant for 10 weeks. She has severe nausea, excessive vomiting, electrolyte disturbances, and weight loss of more than 5% of body weight. She has no goitre or exophthalmos. Her Thyroid profile shows:

Serum Free T3 3.26 ng/ml (1.60-4.20)Serum T4 1.80 pg/ml (0.70-1.68)Serum TSH 0.12 mIU/L (0.30-4.0)

Most probable diagnosis in this patient is:

a. a. Gestational Hyperthyroidism1

19/04/2319/04/23 01:0701:07 2424

a. Gestational Hyperthyroidismb. Grave`s Diseasec. Overt Hyperthyroidism (requiring immediate

treatment)d. Sick Euthyroid Syndromee. Sub-clinical Hyperthyroidism

19/04/2319/04/23 01:0701:07 2525

Effects of Pregnancy on Effects of Pregnancy on Thyroid BiochemistryThyroid Biochemistry

Physiologic Change Thyroid-Related Consequences

↑ Serum thyroxine-binding globulin ↑ Total T4 and T3; ↑ T4 production

↑ Plasma volume ↑ T4 and T3 pool size; ↑ T4

production; ↑ cardiac output

D3 expression in placenta and (?) uterus ↑ T4 production

First trimester ↑ in hCG ↑ Free T4; ↓ basal thyrotropin; ↑ T4

production

↑ Renal I- clearance ↑ Iodine requirements

↑ T4 production; fetal T4 synthesis during

second and third trimesters

 

↑ Oxygen consumption by fetoplacental unit, gravid uterus, and mother

↑ Basal metabolic rate; ↑ cardiac output

19/04/2319/04/23 01:0701:07 2626

Q 7: Q 7: A 34 year female underwent TRH stimulation test which showed a peak of TSH at 30 minutes which comes to baseline by 60 minutes. The patient is most probably having:

a. Hypothalamic Hypothyroidismb. Normal Axisc. Pituitary Hypothyroidismd. Primary Hyperthyroidisme. Primary Hypothyroidism

b.Normal Axis2

19/04/2319/04/23 01:0701:07 2727

19/04/23 01:07 28

Q 8: Q 8: You are a newly appointed Consultant Chemical Pathologist in a Public Sector Hospital. You find that Thyroid profile (TSH, T3 and T4) are carried out in a nearby Government Nuclear Medical Centre on a Radioimmuno- Assay (RIA). The patients get reports after 2-3 weeks and there are problems in clinical correlation, too. Several commercial firms are ready to provide you Hormone Autoanalysers based on Chemiluminescence methodology on Reagent Rental basis. Considering the above mentioned scenario please answer following queries:

19/04/2319/04/23 01:0701:07 2929

a. Give THREE advantages of replacing RIA with this Chemiluminescence –based system.

b. Running test cost is a big issue in Chemiluminescence –based systems. How will you justify this additional expenditure?

c. What thyroid-testing strategy you will formulate to reduce the workload to a rationalized level?

Radioimmunoassay (RIA) Radioimmunoassay (RIA) and and ChemiluminescenceChemiluminescence

RIA (Antigen labeled classical Radioimmunoassay) is a First Generation TSH Assay. It has detection limits of about 1 mU/L. It is not sufficiently sensitive to distinguish between normal serum TSH concentrations and the low serum TSH concentrations present in most patients with hyperthyroidism.

IRMA (Antibody labeled immunometric assay) is a Second Generation TSH assay having detection limit of about 0.1 mU/L. Again these assays are not good enough to evaluate TSH levels in Hyperthyroidism

19/04/2319/04/23 01:0701:07 3030

Radioimmunoassay (RIA) and Radioimmunoassay (RIA) and ChemiluminescenceChemiluminescence (Cont) (Cont)

Chemiluminescence assay (Third generation TSH assay) has detection limit of about 0.01 mU/L. This can, therefore, provide detectable TSH measurement even in mild hyperthyroidism.

In order to reliably detect values of serum TSH in the hyperthyroid range, one needs a Third Generation assay with a functional sensitivity of at least ≤0.05 mU/L.

Chemiluminescence assay can easily differentiate serum TSH values in patients with hyperthyroidism from those in euthyroid patients because of the considerably lower detection limit, even with poor quality control.

19/04/2319/04/23 01:0701:07 3131

Suggested answer of Q.8Suggested answer of Q.81,21,2

a.a. Chemiluminescence has following Chemiluminescence has following advantages over RIA:advantages over RIA:

i.i. Can perform highly sensitive TSH assay Can perform highly sensitive TSH assay to clearly differentiate Hyperthyroidism to clearly differentiate Hyperthyroidism from normalfrom normal

ii.ii. Random access autoanalysis is Random access autoanalysis is available. So no need to wait for batch available. So no need to wait for batch analysis as in RIA.analysis as in RIA.

iii.iii. No hazards of radioactivity and disposal No hazards of radioactivity and disposal is not a problem. is not a problem.

19/04/2319/04/23 01:0701:07 3232

Suggested answer of Q.8 Suggested answer of Q.8 (cont)(cont)

b. Justification of higher running costb. Justification of higher running costi.i. No down payment and good maintenance No down payment and good maintenance

service due to Reagent Rental System. service due to Reagent Rental System.

ii.ii. Better patient satisfaction as they can get Better patient satisfaction as they can get reports within hours instead of weeks.reports within hours instead of weeks.

iii.iii. Decision making by physicians can be Decision making by physicians can be quickened and hospital stays will be quickened and hospital stays will be reduced.reduced.

iv.iv. Better clinical correlation due to highly Better clinical correlation due to highly sensitive assay. sensitive assay.

19/04/2319/04/23 01:0701:07 3333

Suggested answer of Q.8 Suggested answer of Q.8 (cont)(cont)

c. Strategy to rationalize work loadc. Strategy to rationalize work loadi.i. TSH should be done as the first testTSH should be done as the first test

ii.ii. Since 70-80% patients have normal Since 70-80% patients have normal tests, they will not require Ttests, they will not require T33 or T or T44

iii.iii. Patients with higher TSH may undergo Patients with higher TSH may undergo TT4 4 as a reflex testing.as a reflex testing.

iv.iv. TT33 and T and T4 4 may be done in patients with may be done in patients with low TSH.low TSH.

v.v. Clinical colleagues can be persuaded Clinical colleagues can be persuaded by an awareness campaign. by an awareness campaign.

19/04/2319/04/23 01:0701:07 3434

Q 9: Q 9: During mandatory screening on 4th day of life, a neonate had following TSH result:

TSH: 33.2 mIU/mL

a. What is the most probable diagnosis in this baby?b. Write THREE clinical features you will like to see in this patient for confirmation of the diagnosis?c. If no signs or symptoms are found would you still strict to your diagnosis? d. What immediate actions you will like to take to prevent the child from adverse effect of the disease?

19/04/2319/04/23 01:0701:07 3535

Clinical Features of Clinical Features of Congenital Hypothyroidism (CH)Congenital Hypothyroidism (CH)

The vast majority (more than 95 percent) of infants with congenital hypothyroidism have few if any clinical manifestations of hypothyroidism at birth

The signs and symptoms may be so subtle that they can be easily missed.

Clinical Features of CH (Cont)Clinical Features of CH (Cont) Constipation Lethargy Prolonged jaundice Hypotonia Umbilical hernia Large fontanels Slow movement Hoarse cry Feeding problems Macroglossia Dry skin Hypothermia

Cut off limits for TSHCut off limits for TSHNormal < 15 IU/LNormal < 15 IU/LBorderline 15 – 30 IU/LBorderline 15 – 30 IU/LHypothyroidism >30 IU/LHypothyroidism >30 IU/L

Exclusion of Transient CHExclusion of Transient CH

It is important to perform TFT on the It is important to perform TFT on the mother in cases with abnormal resultsmother in cases with abnormal results

History of anti-thyroid medication History of anti-thyroid medication ingestion during the pregnancy should ingestion during the pregnancy should be obtainedbe obtained

Exclude the possibility of placental Exclude the possibility of placental transfer of maternal antibodies that transfer of maternal antibodies that block the action of TSH. block the action of TSH.

19/04/2319/04/23 01:0701:07 3939

Treatment of CHTreatment of CH Ideally treatment should be initiated in an

infant with a clearly positive screening test as soon as confirmatory blood samples have been drawn, pending results.

In cases in which screening tests are borderline, a treatment decision can be made after results of the confirmatory tests return

Treatment should NEVER be delayed beyond 18 days of life.

Treatment of CH (Cont)Treatment of CH (Cont) Immediate diagnosis and treatment of Immediate diagnosis and treatment of

congenital hypothyroidism in the neonatal congenital hypothyroidism in the neonatal period is critical to normal brain period is critical to normal brain development and physical growth development and physical growth

There is an inverse relationship between age at clinical diagnosis and treatment initiation and intelligence quotient (IQ) later in life, so that the longer the condition goes undetected, the lower the IQ

Treatment for CH is lifelongTreatment for CH is lifelong..

Suggested answer of Q.9Suggested answer of Q.911

a.a. MMost probable diagnosis Congenital Hypothyroidism

b. Most Common Clinical featuresThe most common neonatal symptoms

are constipation, lethargy, and prolonged jaundice while the most common physical signs are hypotonia, umbilical hernia, and large fontanels

19/04/2319/04/23 01:0701:07 4242

Suggested answer of Q.9 Suggested answer of Q.9 (Contd)(Contd)

c. Yes. In many babies the change may be so subtle that it may be missed clinically.

d. This baby requires urgent thyroxin replacement. The paediatrician should be informed immediately. Venous serum sample should be drawn for TSH and T4 by chemiluminescence (usually neonatal screening is not done on immunoassays). The paediatrician will start thyroxin after sending the sample. Mother should also undergo Thyroid Function Tests and TgAb to rule out Transient CH.

19/04/2319/04/23 01:0701:07 4343

Q 10:Q 10: A 72 years female has following thyroid profile:Serum fT3 2.26 pg/ml (1.60-4.20)Serum TSH 0.11 mIU/L (0.30-4.0)Your Physician colleague has referred the case to you with following queries:

19/04/2319/04/23 01:0701:07 4444

a. What is the most probable diagnosis in this case?

b. Should anti-thyroid treatment be started in this patient?

c. What are the dangers if this patient is not given anti-thyroid treatment for some time?

Sub-Clinical Hyperthyroidism Sub-Clinical Hyperthyroidism (SHE)(SHE)

19/04/2319/04/23 01:0701:07 4545

Low serum TSH concentrations (<0.5 mU/mL) but normal free T4 and fT3 concentrations, a constellation of biochemical findings defined as subclinical hyperthyroidism.

The term overt hyperthyroidism refers to patients with elevated levels of free T4, T3, or both, and a subnormal TSH concentration.

Both subclinical and overt hyperthyroidism are biochemical definitions since hyperthyroid symptoms are non-specific and may be present in patients with subclinical disease, and absent in those with overt disease, especially the elderly

Types of SHETypes of SHE

19/04/2319/04/23 01:0701:07 4646

 Exogenous SHE: is the term used to describe hyperthyroidism caused by ingestion of excessive amounts of thyroid hormone.

Endogenous SHE: Autonomously functioning thyroid adenomas and multi-nodular goiters are the most common causes of endogenous SHE. Nearly 57% patients with multi-nodular goiters have SHE.

Adverse effects in SHEAdverse effects in SHE

19/04/2319/04/23 01:0701:07 4747

Increased Bone Resorption: i.e. Osteoprosis and susceptibility to fractures

Cardiovascular Effects: e.g. – Atrial Fibrillation– Coronary Artery Disease– Heart Failure etc.

Poor Quality of Life: e.g. Disturbances in sleep and decreases in some physical functions

Dementia

Incidence of Atrial Fibrillation Incidence of Atrial Fibrillation over age 60 based on TSH over age 60 based on TSH

LevelLevel

19/04/2319/04/23 01:0701:07 4848

Patients of SHE with Higher Patients of SHE with Higher RiskRisk

19/04/2319/04/23 01:0701:07 4949

Elderly patients >65 years Patients with risk factors for cardiac

arrhythmias Postmenopausal women with or at

risk for osteoporosis

Consideration for treatment of Consideration for treatment of SHESHE

Patients at high risk for complications In patients at high risk use the following approach:If the serum TSH value is <0.1 mU/L,  treat the patient.If the serum TSH is 0.1 to 0.5 mU/L, treatment if there is:

– underlying cardiovascular disease – the bone density is low. – one or more focal areas of high uptake (ie, evidence of

autonomy. Subclinical hyperthyroidism due to autonomous nodule(s) is more likely to progress to overt hyperthyroidism than is subclinical hyperthyroidism due to Graves' disease).

Measure TSH, free T4, and T3 every six months if the above mentioned features are not present.

19/04/2319/04/23 01:0701:07 5050

Consideration for treatment of SHE Consideration for treatment of SHE (Contd)(Contd)

Patients at low risk for complications In patients at low risk for complications of hyperthyroidism (young individuals, premenopausal women), use the following approach:

– If the serum TSH value is <0.1 mU/mL, treat if the patient has symptoms suggestive of hyperthyroidism and/or if a thyroid radionuclide scan shows one or more focal areas of increased uptake.

– If the TSH is between 0.1 to 0.5 mU/mL, observation alone is appropriate i.e. measure TSH, free T4, and T3 every six months.

19/04/2319/04/23 01:0701:07 5151

Suggested answer of Suggested answer of Q.10Q.101,3,41,3,4

a.a. DiagnosisDiagnosis

Subclinical HyperthyroidismSubclinical Hyperthyroidism

b.b. Since the patient is >65 years treatment Since the patient is >65 years treatment should be considered if following co-should be considered if following co-morbidities are present:morbidities are present:• Presence of heart disease Presence of heart disease • OsteoprosisOsteoprosis• Symptoms of hyperthyroidismSymptoms of hyperthyroidism

Otherwise just monitor by repeating tests after an Otherwise just monitor by repeating tests after an appropriate interval.appropriate interval.

19/04/2319/04/23 01:0701:07 5252

Suggested answer of Q.10 Suggested answer of Q.10 (cont)(cont)

c. If treatment is delayed in spite of c. If treatment is delayed in spite of presence of above mentioned features presence of above mentioned features she may develop cardiac arrhythmias she may develop cardiac arrhythmias or fractures and poor quality of life.or fractures and poor quality of life.

19/04/2319/04/23 01:0701:07 5353

Q 11:Q 11: A 24 year female has menstrual irregularities and has not conceived one year after marriage. Her hormonal profile is as following:• Serum TSH: > 100 mIU/L (0.30-4.0)• FSH: 9 mIU/mL• LH: 34 mIU/mL• Prolactin: 41 ng/ml (7-26)• Testosterone: 3.4 nmol/LConsultant Gynaecologist has referred the patient to you for your opinion regarding:

19/04/2319/04/23 01:0701:07 5454

a. Hormonal Diagnosis of the patient.  b. Most probable cause(s) of increased Prolactin. 

c. Should anti-prolactin treatment given to her alongwithThyroxin?

 

Suggested answer of Q.11Suggested answer of Q.1111

a.a. Hormonal DiagnosisHormonal Diagnosis– Primary Hypothyroidism Primary Hypothyroidism – Hyperprolactinaemia Hyperprolactinaemia – Hormonal Features of PCOS i.e. Increased LH:FSH ratio, Hormonal Features of PCOS i.e. Increased LH:FSH ratio,

Hyperandrogenaemia and HyperprolactinaemiaHyperandrogenaemia and Hyperprolactinaemia

(Plz note that in Secondary and Tertiary Hyperthyroidism TSH is (Plz note that in Secondary and Tertiary Hyperthyroidism TSH is not that high and they are extremely rare conditions) not that high and they are extremely rare conditions)

b.b. Increased prolactin may be secreted due to:Increased prolactin may be secreted due to:– High TRH as a result of Primary Hypothyroidism may cause High TRH as a result of Primary Hypothyroidism may cause

stimulation of pituitary to release prolactin. stimulation of pituitary to release prolactin. – Hyperprolactinaemia is also a known feature of PCOSHyperprolactinaemia is also a known feature of PCOS– Prolactin may be secreted from a microadenoma in pituitary. Prolactin may be secreted from a microadenoma in pituitary.

19/04/2319/04/23 01:0701:07 5555

Suggested answer of Q.11 Suggested answer of Q.11 (cont)(cont)

c. c. Patient should be treated for :Patient should be treated for :– Primary Hypothyroidism i.e. Tab Primary Hypothyroidism i.e. Tab

Thyroxin after Thyroxin after confirmationconfirmation of of diagnosis by repeating TSH with T4.diagnosis by repeating TSH with T4.

– PCOS e.g. Metformin. PCOS e.g. Metformin. – Hyperprolactinaemia with specific Hyperprolactinaemia with specific

medicines if prolactin levels remains medicines if prolactin levels remains high when TSH decreases markedly. high when TSH decreases markedly.

19/04/2319/04/23 01:0701:07 5656

ReferencesReferences1. UpToDate. (online) Cited on 22 Mar 2013. Available at:

https://www.uptodate.com2. Demers LM and Spencer C. The Thyroid:

Pathophysiology and Thyroid Function Testing. In Burtis CA, Ashwoods ER and Bruns DE, (edi) Teitz Textbook oF Clinical Chemistry. 4th ed. W. B. Saunders Company; 2006;pp 2053-2095.

3. UK guidelines for the Use of Thyroid Function - British Thyroid Association (online) Cited on 22 Mar 2013. Available at: www.british-thyroid-association.org/Guidelines/

4.4. Cooper DS. Approach to the Patient with Subclinical Hyperthyroidism. J Clin Endocrinol Metab.2007;92:3–9.

19/04/2319/04/23 01:0701:07 5757

Thank YouThank You

19/04/2319/04/23 01:0701:07 5858