DISORDERS OF ENDOCRINE FUNCTION: THE THYROID GLAND

Question 1

The thyroid gland is responsible for the production of which three hormones?

Answer 1

Thyroxine (T4)
Triiodothyronine (T3)
Calcitonin

Question 2

What is Calcitonin?

Answer 2

Calcitonin is secreted by parafollicular C cells and is involved in calcium homeostasis. Usually use in diagnosis of Medullary Cancer of the Thyroid

Question 3

What are the function of thyroid gland hormone?

Answer 3

Acting through nuclear receptors, these hormones play a critical role in:

regulation of body metabolism
cell differentiation during development
neurologic development
maintain thermogenic and metabolic homeostasis in the adult
numerous other body functions.

Question 4

Clinical conditions that affect CALCITONIN levels are much more common than those affecting THE THYROID HORMONE
T/F

Answer 4

FALSE
Clinical conditions that affect THE THYROID HORMONE levels are much more common than those affecting CALCITONIN

Question 4

What is the parathyroid gland?

Answer 4

Posterior to the thyroid gland are the parathyroid glands that regulate serum calcium levels and the recurrent laryngeal nerves that innervate the vocal cords

These posterior structures become important during thyroid surgery, when care must be exercised to avoid injury that could lead to hypocalcemia or permanent hoarse voice.

Question 5

What is the thyroid gland?

Answer 5

The thyroid gland is positioned in the lower anterior neck and is shaped like a butterfly

It is made up of two lobes that rest on each side of the trachea, with a band of thyroid tissue—called the isthmus—running anterior to the trachea and bridging the lobes

It is normally 12 to 20 g in size, highly vascular, and soft in consistency

Question 6

Discuss the development of the thyroid gland

Answer 6

Fetal thyroid develops from the foregut at the base of the tongue and migrates to its normal location over the thyroid cartilage in the first 4-8 weeks of gestation

The thyroid gland begins to produce measurable amounts of thyroid hormone by the 11th week of gestation

Maternal thyrotropin-releasing hormone (TRH) readily crosses the placenta; maternal thyroid-stimulating hormone (TSH) and T4 do not.
T4 from the fetal thyroid is the major thyroid hormone available to the fetus.

The fetal hypothalamic–pituitary–thyroid axis is a functional unit distinct from that of the mother—active at 18–20 weeks

Thyroid hormone is critical to neurologic development of the fetus

Iodine is an essential component of thyroid hormone

Question 7

What occurs in severe iodine deficiency in pregnant women?

Answer 7

In severe iodine deficiency, neither the mother nor the fetus can produce thyroid hormone and both develop hypothyroidism

The impact is most severe on the fetus because hypothyroidism leads to mental retardation and cretinism

Congenital hypothyroidism occurs in 1 of 4,000 live births.

If the mother has normal thyroid function, the fetus will be protected during development by small amounts of maternal thyroid hormone crossing the placenta.

Immediately postpartum, however, these newborns require initiation of appropriate doses of thyroid hormone or their neurologic development will be significantly impaired.

Question 8

What is the relationship between iodine and thyroid hormone?

What is the recommended daily intake of iodine?

Answer 8

Thyroid hormone is made from trace element Iodine

Iodine is found in seafood, dairy products, iodine-enriched breads, and vitamins

It is also present in amiodarone, a medication used to treat certain heart conditions.

The recommended minimum daily intake of iodine is 150µg

If iodine intake drops below 50µg daily, the thyroid gland is unable to manufacture adequate amounts of thyroid hormone and thyroid hormone deficiency hypothyroidism results

Question 9

What are the Steps in Thyroid Hormone Synthesis?

Answer 9

(1) Iodide (I) trapping by thyroid follicular cells; through the sodium/iodide symporter (NIS).

Uptake is blocked by thiocyanate and perchlorate.
Another transporter, Pendrin is located at apical surface of the cell; it is used to pump iodide into the colloid of the lumen (which contains thyroglobulin).

Deficiency leads to Pendrin Syndrome

(2) Diffusion of iodide to the apex of the cell and transport into the colloid

(3) Oxidation of inorganic iodide to iodine by thyroperoxidase enzyme and incorporation of iodine into tyrosine residues within thyroglobulin molecules in the colloid by the same enzyme; this step is inhibited by carbimazole and propylthyiouracil

(This step is called iodination)

The incorportation forms 2 DIT, 1 MIT and another 1 DIT

(4) The 2 diiodotyrosine (DIT) molecules are coupled to form tetraiodothyronine (thyroxine, T4) or of monoiodotyrosine (MIT) coupled with DIT to form triiodothyronine (T3)

(5) Uptake of thyroglobulin from the colloid into the follicular cell by endocytosis, fusion of the thyroglobulin with a lysosome, and proteolysis and release of T4 and T3

(6) Release of T4 and T3 into the circulation

Question 10

How does the Peripheral conversion of T4 to T3 occur?

Answer 10

Approximately 80% of T4 is metabolized into either T3 (35%) or reverse T3 (r T3) (45%)

T3 is 3–8 times more metabolically active than T4,its the active form of thyroid hormone

T4 is the “pre” hormone (with thyroglobulin being the “prohormone”)
Conversion of T4 to T3 takes place in the peripheral tissues especially the liver and kidneys by de-iodination of T4.

About 80% of T3 is produced by this conversion while the remaining 20% is secreted by the thyroid gland.

The T3 binds more avidly to thyroid receptors than T4 and is the main active form

Preferential conversion to rT3 occurs in starvation and severe illness, presumably in an attempt to limit whole body energy expenditure

Question 11

What are the Factors affecting (increase and decrease) the conversion of T4 to T3?

Answer 11

1) Reduced
systemic illness,
prolonged fasting,
drugs such as β-blockers e.g. Propanolol and amiodarone

2) Increased by drugs that induce hepatic enzyme activity such as phenytoin

Question 12

What are the types of Deiodinase Enzymes?

Answer 12

Type 1 iodothyronine 5-deiodinase
The most abundant form
Found mostly in the liver and kidney and is responsible for the largest contribution to the circulating T3 pool.
Certain drugs (e.g., propylthiouracil, glucocorticoids, and propranolol) can slow the activity of this deiodinase and are used in the treatment of severe hyperthyroidism.

Type 2 iodothyronine 5-deiodinase
Found in the brain and pituitary gland.
Its function is to maintain constant levels of T3 in the central nervous system.
Its activity is decreased when levels of circulating T4 are high and increased when levels are low.

Type 3 iodothyronine 5-deiodinase
Responsible for production rT3 which is metabolically inactive

Question 13

What is the effect of the activity of the deiodination enzymes ?

Answer 13

Activity of the deiodination enzymes gives another level of control on thyroid hormone activity beyond hypothalamic-pituitary control through thyrotropin-releasing hormone (TRH) and TSH

Question 14

When does Increase concentration of Thyroxine binding globulin (TBG) occur?

Changes in the plasma concentration of TBG, alter plasma total T4 and T3 concentration and the concentration of free hormones T/F

Answer 14

Increase concentration of TBG occurs in
Pregnancy or in newborn due to high concentration of estrogen
Estrogen therapy such as contraceptives pills
Tamoxifen
Hepatitis A (Chronic active)
Biliary Cirrhosis
Inherited TBG excess

Changes in the plasma concentration of TBG, alter plasma total T4 and T3 concentration but NOT the concentration of free hormones

Question 15

What proteins are invloved in the protein binding of thyroid hormones?

Answer 15

Thyroxine Binding globulin (TBG)
Low concentration (1-2mg/dl)
High affinity for thyroid hormones (T4>T3)
Binds about 75%

Transthyretin (TTR)
Also known as Thyroxine binding pre-albumin (TBPA)
Binds about 10% (majorly T4)

Albumin
High concentration (3.5g/dl)
Low affinity for thyroid hormones (T3>T4)
Binds about 10-15%

The unbound free hormone is the physiologically active form, and it regulates TSH secretion from the anterior pituitary.

Question 15

What are THYROID UPTAKE SCANS?

Answer 15

The thyroid gland selectively transports radioisotopes of iodine (123I, 125I, 131I) and 99mTc pertechnetate, allowing thyroid imaging and quantitation of radioactive tracer fractional uptake.

Thyroid uptake scans involves the oral ingestion of radioactive iodide, with an active uptake of the iodine to the thyroid (Radioactive Iodide Uptake) with the distribution in the thyroid determined using a gamma camera.
Thyrotoxic patient
Grave’s disease: uniformly increased uptake
Toxic multinodular goitre: patchy uptake

Single active ‘hot’ adenoma, or acute thyroiditis: uniformly poor or absent uptake.

It can also identify ectopic thyroid tissue (eg sublingual thyroid), or outline a ‘cold’,

Question 16

When does Decrease concentration of TBG occur?

Answer 16

Decrease concentration of TBG occurs in
Severe illness
Nephrotic syndrome due to loss low molecular weight protein
Large doses of corticosteroids
Androgen or danazol treatment
Drugs e.g. Phenytoin
Inherited TBG deficiency

Question 16

How is a thyroid function test carried out?

Answer 16

Assessment of thyroid hormone secretion can be made by measuring plasma
TSH
Free T4 or total T4
Free T3 or total T3

First-line screening test for thyroid function is a sensitive plasma TSH assay:
low values indicating hyperthyroidism
high values indicating hypothyroidism

Each test has its advantage and disadvantage

Free thyroid assay are more reliable than total

Question 17

How is the TRH stimulation test carried out?

What can it diagnose?

Answer 17

A TRH stimulation test involves measuring basal TSH, then giving an intravenous dose of TRH and measuring the plasma TSH response at 20 and 60 minutes.
Procedure: 200µg of TRH is injected intravenously over a minute
Blood sample are collected at 20 and 60 minutes after injection to measure TSH
Interpretation
Primary hypothyroidism shows an exaggerated response at 20minutes and a slight fall at 60minutes
Primary hyperthyroidism shows a flat response.
However, since it gives no extra information beyond that provided by basal TSH measurement, this test is reserved for diagnosis of pituitary or hypothalamic disease.
In pituitary disease there is a flat response,
In hypothalamic disease there is a response, albeit delayed, due to chronic understimulation of thyrotrophs i.e. the 60 minutes TSH value is > the 20 minutes.

Question 17

How do you screen for thryroid disease?

Answer 17

• Patients with atrial fibrillation or hyperlipidemia

Periodic (within every 6 months) assessment in patients receiving medications such as amiodarone hydrochloride and lithium carbonate.

Annual check of thyroid function in annual review of diabetic patients

Women with type 1 diabetes in the first trimester of pregnancy and post-delivery (3-fold increase in incidence of postpartum thyroid dysfunction in such patients)

Women with a past history of postpartum thyroiditis

Previous thyroid dysfunction or goiter

History of surgery or radiotherapy affecting the thyroid gland

Vitiligo

Pernicious anemia

Annual check of thyroid function in Down syndrome, Turner syndrome, and primary adrenal insufficiency (Addison’s disease) in light of the high prevalence of hypothyroidism in such patients.

Women with thyroid autoantibodies have 8 × risk of developing hypothyroidism over 20 years compared to antibody-negative controls

Women with thyroid autoantibodies and isolated elevated TSH have 38 × risk of developing hypothyroidism, with 4% annual risk of overt hypothyroidism.

Question 18

The most common presenting clinical features of thyroid disease are the results of what conditions?

Answer 18

The most common presenting clinical features of thyroid disease are the results of
Hypothyroidism, due to deficiency of thyroid hormones

Hyperthyroidism, due to excessive thyroid hormones

Goitre, due to presence of nodules which may be diffuse or solitary.

Question 19

What is Hypothyroidism?

Answer 19

Hypothyroidism results from a variety of abnormalities that cause insufficient secretion of thyroid hormones.

The most common cause is autoimmune thyroid disease (hashimoto thyroiditis).

Myxedema is severe hypothyroidism in which there is accumulation of hydrophilic mucopolysaccharides in the ground substance of the dermis and other tissues leading to thickening of the facial features and doughy induration of the skin.

Subclinical hypothyroidism refers to elevated TSH levels in the presence of normal concentrations of free thyroid hormones.

Question 20

What are primary and secondary Hypothyroidism?

Answer 20

Primary Hypothyroidism:
Iodine deficiency
Autoimmune Thyroiditis or Hashimoto’s thyroiditis
Exogenous goitrogens
Dyshormonogenesis (Inherited deficiency of enzymes involve in synthesis of thyroid hormones)
Surgical treatment of thyrotoxicosis (Iatrogenic)
Radiation injury to the thyroid gland
Infective causes e.g. viral or bacteria

Secondary Hypothyroidism:
Pituitary disease-TSH deficiency
Hypothalamic disease-TRH deficiency.

Question 21

What is Congenital Hypothyroidism?

Answer 21

Hypothyroidism occurs in about 1 in 4000 newborns.
It may be transient if the mother has TSH-R blocking antibodies or has received antithyroid drugs
Permanent hypothyroidism occurs in the majority.
Neonatal hypothyroidism is due to
Thyroid gland dysgenesis in 80 to 85%,
Inborn errors of thyroid hormone synthesis in 10 to 15%
TSH-R antibody-mediated in 5% of affected newborns.
The developmental abnormalities are twice as common in girls.
Mutations that cause congenital hypothyroidism are being increasingly recognized, but the vast majority remain idiopathic
The majority of infants appear normal at birth, and <10% are diagnosed based on clinical features that includes:
Prolonged jaundice
Feeding problems
Hypotonia
Enlarged tongue
Delayed bone maturation
Umbilical hernia
Permanent neurologic damage results if treatment is delayed.
Typical features of adult hypothyroidism may also be present.
Other congenital malformations, especially cardiac, are four times more common in congenital hypothyroidism

Question 22

What is the Diagnosis and Treatment of Congenital Hypothyroidism?

Answer 22

If untreated there is severe neurologic consequences

Neonatal screening programs have been established in developed countries.

They are based on measurement of TSH or T4 levels in heel-prick blood specimens.

When the diagnosis is confirmed, T4 is instituted at a dose of 10 to 15 µg/kg per day and the dosage is adjusted by close monitoring of TSH levels.

T4 requirements are relatively great during the first year of life, and a high circulating T4 level is usually needed to normalize TSH.

Early treatment with T4 results in normal IQ levels, but subtle neurodevelopmental abnormalities may occur in those with the most severe hypothyroidism at diagnosis or when

Question 23

What are the Symptoms and Signs of Hypothyroidism?

Answer 23

Symptoms:

Tiredness,
weakness
Dry skin
Feeling cold
Hair loss
Difficulty concentrating and poor memory
Constipation
Weight gain with poor appetite
Dyspnea
Hoarse voice
Menorrhagia (later oligomenorrhea or amenorrhea)
Paresthesia
Impaired hearing

Signs:
Dry coarse skin;
Cool peripheral extremities
Puffy face, hands, and feet (myxedema)
Diffuse alopecia
Bradycardia
Peripheral edema
Delayed tendon reflex relaxation
Carpal tunnel syndrome
Serous cavity effusions

Question 24

What are the Laboratory investigation of suspected hypothyroidism?

Answer 24

Plasma TSH and fT4 or total T4 should be measured
Slightly elevated plasma TSH with normal fT4:
Suggest compensated hypothyroidism.
Measure circulating thyroid antibodies to rule out autoimmune disorders
Raised TSH with low fT4:
Suggest primary hypothyroidism
Low TSH with low fT4:
Suggest secondary hypothyroidism (Pituitary or Hypothalamic)
Raised TSH with raised/normal fT4 in the presence of hypothyroid symptoms:
Suggest thyroid hormone resistance

Question 24

What is Myxedema Coma?

Answer 24

Occasionally hypothyroid patients may present with hypothermia and stupor or coma, a condition termed ‘myxoedema coma’.
Almost always occurs in the elderly and is usually precipitated by factors that impair respiration, such as:
drugs (especially sedatives, anesthetics, antidepressants),
pneumonia,
congestive heart failure,
myocardial infarction,
gastrointestinal bleeding,
or cerebrovascular accidents.
Sepsis should also be suspected.
Exposure to cold may also be a risk factor.
Hypoventilation, leading to hypoxia and hypercapnia, plays a major role in pathogenesis; hypoglycemia and dilutional hyponatremia also contribute to the development of myxedema coma

Question 25

What are the biochemical changes observed in hypothyroidism?

Answer 25

Apart from the clinical features listed any unexplained biochemical changes should raise the suspicion of hypothyroidism

Hypercholesterolaemia

Elevated creatine kinase

Hyponatraemia due to increase release of antidiuretic hormones

Hyperprolactinaemia

Plasma SHBG reduction

Macrocytic anaemia

Sometimes abnormal LFT and RFT may occur.

Question 26

How is a Biochemical diagnosis of hypothyroidism made?

Answer 26

Biochemical diagnosis is quite straightforward
decreased fT4 with a markedly increased TSH

The disease often begins insidiously; in its early stages, the only abnormality may be an increased TSH, to which the failing gland responds by secreting enough T4 to keep the fT4 within the normal range (usually close to the lower end).

In such cases, high titres of anti-thyroid antibodies provide supportive evidence of auto-immune thyroid disease.

Question 27

What is the Treatment of Hypothyroidism?

Answer 27

Treatment is also simple and cheap
Lifelong administration of sufficient thyroxine to normalise the plasma f T4 and TSH.
Monitoring Treatment
Abnormally high TSH indicates inadequate replacement or erratic compliance,
whereas suppressed TSH suggests excessive replacement.
T3 treatment is used
where rapid onset of action is desired (eg. treatment of myxoedema coma) or
where rapid reversal of overdosage is important (eg. treating hypothyroid patients with ischaemic heart disease).
This is because of the rapid onset of action and shorter half-life of T3 compared to T4.

Question 28

What are the Clinical manifestations of Myxoedema Coma?

Answer 28

Clinical manifestations include:
Reduced level of consciousness,
Seizures,
Features of hypothyroidism
Hypothermia can reach 23°C (74°F).
There may be a history of treated hypothyroidism with poor compliance,
The patient may be previously undiagnosed
This is a medical emergency that carries a high risk of mortality.
Apart from T3 replacement, one needs to restore body temperature and correct electrolyte imbalance (typically hyponatraemia from water retention).

Question 29

What is Hyperthyroidism and clinical features?

Answer 29

Hyperthyroidism causes sustained high plasma concentration of T3 and T4.
There is often generalised increase in the metabolic rate, evidence of clinically by
Heat intolerance
Fine tremor
Tachycardia
Weight loss
Tiredness
Anxiety
Sweating
Diarrhea

Question 30

What is thyrotoxicosis?

Answer 30

The term thyrotoxicosis denotes the clinical, physiological, and biochemical findings that result when the tissues are exposed to excess thyroid hormone.

It can arise in a variety of ways.

It is essential to establish a specific diagnosis as this determines therapy choices and provides important information for the patient regarding prognosis.

The term hyperthyroidism should be used to denote conditions in which hyperfunction of the thyroid leads to thyrotoxicosis.

Question 31

What is Grave’s disease?

Answer 31

Accounts for 60 to 80% of thyrotoxicosis
Prevalence varies among populations, depending mainly on iodine intake (high iodine intake is associated with an increased prevalence of Graves’ disease)
More common in female than male
Rarely begins before adolescence and typically occurs between 20 and 50 years of age, but it also occurs in the elderly
It is an autoimmune disease with a varing degree of circulating antibodies such as anti-TPO, TSI
May be associated with other autoimmune diseases such as type 1diabetes mellitus, adrenal insufficiency, pernicious anaemia

Question 31

What are the types of hyperthyroidism?

Answer 31

Primary hyperthyroidism
Grave’s disease
Toxic multinodular goitre
Toxic Adenoma
Thyroid carcinoma
Metastatic thyroid carcinomas
Activating mutation of the TSH receptor Activating mutation of Gsα (McCune-Albright syndrome)
Administration of iodine to a patient with iodine deficiency (Jod-Basedow syndrome)
TSH secreting tumours e.g. pituitary tumours, trophoblastic tumours
Struma ovarii
Thyrotoxicosis without hyperthyroidism
Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction: amiodarone, radiation, infarction of adenoma
Thyrotoxicosis factitia (self administration of thyroid hormones)

Secondary hyperthyroidism
TSH-secreting pituitary adenoma
Thyroid hormone resistance syndrome: occasional patients may have features of thyrotoxicosis
Chorionic gonadotropin-secreting tumors
Gestational thyrotoxicosis

Question 31

What are the Symptoms and Signs of Hyperthyroidism?

Answer 31

Symptoms

Hyperactivity,
irritability,
dysphoria
Dyspnea
Heat intolerance and sweating
Palpitations
Fatigue and weakness
Weight loss with increased appetite
Diarrhea
Thirst and Polyuria
Pruritus
Oligomenorrhea,
loss of libido

Signs:

Sinus Tachycardia; atrial fibrillation in the elderly
Hyperkinesia and hyperreflexia
Fine Tremor
Palma erthyma, oncolysis
Goiter
Warm, moist skin
Hair loss
Muscle weakness, proximal myopathy
Periodic paralysis
Congestive (high output) heart failure
Chorea
Pschosis
Lid retraction or lag
Gynecomastia

Question 32

Grave’s disease is characterized by what?

Answer 32

Thyroid Ophthalmopathy:
Exophthalmos, due to lymphocytic infiltration and swelling of retro-orbital tissues of the eyes

Thyroid Acropathy:
A form of finger clubbing found in <1% of patients with Graves’ disease. It
is so strongly associated with thyroid dermopathy that an alternative cause of clubbing

Thyroid Dermatopathy:
Pretibial myxedema, localized thickening of the subcutaneous tissue over the shin

Question 33

What are other manifestations of Graves’ disease?

Answer 33

Diffuse goiter

A feeling of grittiness and discomfort in the eye

Retrobulbar pressure or pain, eyelid lag or retraction

Periorbital edema, chemosis, scleral injection

Exophthalmos (proptosis)

Extraocular muscle dysfunction

Exposure keratitis

Optic neuropathy

Question 34

What is Subacute thyroiditis?

Answer 34

Also known as de Quervain’s thyroiditis
A destructive thyroiditis resulting in release of preformed thyroid hormones
There three subtypes:
1) Granulomatous or painful: a viral disease associated HLA-Bw35
2) Lymphocytic or silent and painless: autoimmune
3) Postpartum: autoimmune, occuring in 5-8% of pregnant women
Associated with extremely elevated thyroid hormones
Treatment is supportive

Question 35

What are toxic nodules?

Answer 35

Either single or multiple
Secrete thyroid hormone autonomously
Nodules may be detected by uptake of radioactive iodine or technetium with suppression of uptake in the rest of the thyroid tissue
Found mostly in adult patients, who present usually with artrial fibrillation
Toxic multinodular goitre is also called Plummer’s disease

Question 36

What are some examples of Rare Hyperthyroid states?

Answer 36

Jod-Basedow syndrome: excessive iodide intake

Thyroid carcinoma: primary thyroid cancer that can be papillary, follicular, or anaplastic

Metastatic thyroid carcinoma: metastasis from other organs to the thyroid causing hyper activity of the thyroid gland

Struma ovarii: ectopic thyroid tissue found in dermoid cyst or ovarian carcinoma

HCG secreting trophoblastic tumours: choriocarcinoma or molar pregnancy; HCG activate TSH receptor.

Question 37

What is Subclinical Hyperthyroidism?

Answer 37

May occur with low or suppressed TSH but normal (usually high normal) plasma fT4 and fT3
May progress to full blown hyperthroidism
May be associated with atrial fibrillation

Question 38

What is GOITER AND NODULAR THYROID DISEASE?

Answer 38

Goiter refers to an enlarged thyroid gland.

Biosynthetic defects, iodine deficiency, autoimmune disease, and nodular diseases can each lead to goiter, though by different mechanisms.

Biosynthetic defects and iodine deficiency are associated with reduced efficiency of thyroid hormone synthesis, leading to increased TSH, which stimulates thyroid growth as a compensatory mechanism to overcome the block in hormone synthesis.

Graves’ disease and Hashimoto’s thyroiditis are also associated with goiter.

Nodular disease is characterized by the disordered growth of thyroid cells, often combined with the gradual development of fibrosis.

Because the management of goiter depends on the etiology, the detection of thyroid enlargement on physical examination should prompt further evaluation to identify its cause.

Thyroid function tests should be performed in all patients with goiter to exclude thyrotoxicosis or hypothyroidism

Question 39

What is Euthyroid Hyperthyroxinaemia?

Answer 39

Either the plasma total or fT4 is abnormally raised without clinical evidence of thyroid disease
May be transient or persist, with high, normal or low total or fT3 concentration

Question 39

What is Euthyroid Goitre?

Answer 39

Under the influence of prolonged stimulation by TSH, the number of thyroid cells increases (cellular hyperplasia) and plasma thyroid hormone concentration are maintained at the expense of the development of goitre
Iodide deficiency due to paraaminosalicylic acid, or partial deficiency of the enzymes involve in thyroid hormone synthesis

Question 40

What is Sick Euthyroid Syndrome?

Answer 40

Any acute, severe illness can cause abnormalities of circulating TSH or thyroid hormone levels in the absence of underlying thyroid disease, making these measurements potentially misleading
Any severe illness may be associated with low plasma total or fT4 concentration and may make the interpretation of thyroid function test extremely difficult
Plasma TSH may be low, normal or high
The assessment of TFT is deferred till patient has recovered from illness

Question 41

What is a THYROID STORM?

Answer 41

Also known as thyrotoxic crisis, is an acute, life-threatening complication of hyperthyroidism.
It is an exaggerated presentation of thyrotoxicosis.
It comes with sudden multisystem involvement.
The mortality associated with thyroid storm is estimated to be 8-25% despite modern advancements in its treatment and supportive measures.
It is very important to recognize it early and start aggressive treatment to reduce mortality.

Question 42

What are the precipitating factors of a thyroid storm?

Answer 42

The precipitating factors are:

Abrupt discontinuation of antithyroid medicine
Thyroid surgery
Non-thyroid surgery
Trauma
Acute illness like infections, diabetic ketoacidosis, acute myocardial infarction, cardiovascular accident, cardiac failure, drug reaction
Parturition
Recent use of Iodinated contrast medium
Radioiodine therapy (rare)
Burns
Stroke
Medication side effect e.g. amiodarone, anesthetics, salicylates.

Question 43

What is the Clinical presentation of a thyroid storm?

Answer 43

Clinical presentation includes hyperpyrexia, dehydration, tachycardia, cardiac failure, CNS manifestation and GIT manifestation

Thyroid function tests show high FT4/FT3 and low TSH.

It is not necessary to have a veryhigh level of thyroid hormone to cause thyroid storm.

Other lab abnormalities may include hypercalcemia, hyperglycemia, abnormal LFTs, high or low white blood cell (WBC) count.

It is a medical emergency associated with significant mortality and requires urgent treatment.

Question 44

What is the Laboratory investigation of suspected hyperthyroidism?

Answer 44

Plasma f T4 and f T3 are elevated, with TSH suppressed suggest hyperthyroidism
Plasma f T4 is elevated, with normal TSH suggestive of Euththyroid thyroxinaemia
Plasma f T4 is normal, f T3 is elevated with normal TSH suggestive of T3 toxicosis
Presence of plasma antibodies TSI, anti-TPO suggest Grave’s disease

Question 45

Name Other biochemical features of Hyperthyroidism

Answer 45

Hypercalceamia due to increased bone resorption

Elevated alkaline phosphatase

Hypercalciuria is also common

Hypocholesterolaemia due to increased LDL clearance

Hypokalaemia associated with hyperthyrotoxic periodic paralysis

Plasma SHBG is increased

Plasma creatine kinase may be increased because of thyrotoxic myopathy

Question 46

Discuss THYROID FUNCTION IN PREGNANCY including the factors that alter thyroid function in pregnancy

Answer 46

Four factors alter thyroid function in pregnancy:

1. Transient increase in hCG during the first trimester, which stimulates the TSH-R
2. Estrogen-induced rise in TBG during the first trimester, which is sustained during pregnancy
3. Alterations in the immune system, leading to the onset, exacerbation, or amelioration of an underlying autoimmune thyroid disease
4. Increased urinary iodide excretion, which can cause impaired thyroid hormone production in areas of marginal iodine sufficiency

Women with iodine intake (<50 µg/d) are most at risk of developing a goiter during pregnancy

Iodine supplementation should be considered to prevent maternal and fetal hypothyroidism and the development of neonatal goiter.

hCG-induced changes in thyroid function can result in transient gestational hyperthyroidism and/or hyperemesis gravidarum; characterized by severe nausea and vomiting and risk of volume depletion.

Antithyroid drugs are rarely needed, and parenteral fluid replacement usually suffices until the condition resolves.

Maternal hypothyroidism occurs in 2 to 3% of women of child-bearing age and is associated with increased risk of developmental delay in the offspring.

Thyroid hormone requirements are increased by 25 to 50 µg/d during pregnancy