To be able to relate the anatomy and physiology of thyroid gland with clinical presentation.

To highlight the pattern of distribution and causes of hypothyroidism.

To identify clinical features of hypothyroidism To investigate and interpret results of

possible hypothyroidism To identify treatment modalities for

hypothyroidism.

The thyroid gland- located below the larynx

Anterior to the trachea, recurrent laryngeal nerve

Weighs 15-20g in adults.

The thyroid secretes two major hormones T4 and T3, respectively. Thyroid also secrete calcitonin

Rich arterial supply from the superior thyroid arteries and inferior thyroid arteries

Venous drainage into superior, middle and inferior thyroid veins

Active transport of I- by thyroid (trapping) Oxidation of I- & iodination (organification) Coupling of Iodotyrosines → Iodothyronines Proteolysis of Tg & release of T3, T4 into blood Deiodination of iodotyrosines within thyroid

cell with release of Iodine Intrathyroidal 5’-deiodination of T4 to T3

Regulates basal metabolic rate Inotrophic & chronotropic effects on the

heart Increases bowel motility Increases speed of muscle contraction Decreases cholesterol (LDL) Required for fetal growth particularly neural

Function influenced by

Central axis (TRH)

Pituitary function (TSH)

Co-morbid diseases

Environmental factors (iodine intake)

Hypothyroidism is a clinical syndrome resulting from a deficiency of thyroid hormones, which in turn results in a generalized slowing down of metabolic processes.

Cretinism refers to the syndrome of mental retardation, deafness, short stature, and characteristic facial deformities occurring with untreated congenital hypothyroidism.

Hypothyroidism can be classified on the basis of: Time of onset ~ Congenital ~ Acquired Level of endocrine dysfunction responsible ~ Primary ~ Central- 2° or 3° Severity ~ Overt [clinical] ~ Mild [subclinical]-normal free T4 levels with

slightly high serum TSH concentration.

Common disorder: prevalence ~ 2% in adults, & subclinical ~ 5-17%

Iodine deficiency - most common cause internationally.

Race: higher prevalence in whites than in people of Hispanic descent or African Americans.

Gender: F:M - vary. Generally, more common in females than in males, with reports of prevalence 2-8 times higher in females.

AGE: ↑s with age; most prevalent in elderly populations (2-20% of older age groups).

PRIMARY Congenital Agenesis Ectopic thyroid remnants

Defects of hormone Infiltration synthesis Iodine deficiency Dyshormonogenesis Drugs- Antithyroid drugs

Other drugs e.g. lithium, amiodarone, interferon, expectorants (KI) Excessive iodine intake e.g radiocontrast dyes

Autoimmune thyroid hormone Atrophic thyroiditis Hashimoto's thyroiditis Postpartum thyroiditis

Infective Post-subacute thyroiditis Post Surgery Post irradiation – radioiodine therapy, external neck irradiation Infiltration

SECONDARY: Hypopituitarism from pituitary adenoma,

pituitary ablative surgery, or pituitary destruction TERTIARY: Hypothalamic dysfunction PERIPHERAL RESISTANCE TO THE ACTION OF THYROID

HORMONES

Autoimmune: One of the most frequent cause of acquired hypothyroidism is autoimmune thyroiditis (Hashimoto thyroiditis).The body recognizes the thyroid antigens as foreign, and a chronic immune reaction ensues, resulting in lymphocytic infiltration of the gland and progressive destruction of functional thyroid tissue. Up to 95% of affected individuals have circulating antibodies to thyroid tissue.

Antimicrosomal or antithyroid peroxidase (anti-TPO) antibodies are found more commonly than antithyroglobulin antibodies (95% vs 60%). These antibodies may not be present early in the disease process and usually disappear over time. Usually hypothyroid but may be euthyroid- initial period of hyperthyroidism may be present initially.

Iodine deficiency or excess: Worldwide Iodine deficiency is the most common cause of hypothyroidism.

Excess iodine, as in radiocontrast dyes, amiodarone, health tonics, and seaweed, inhibits iodide organification and thyroid hormone synthesis – Wolff-Chaikoff effect.

Most healthy individuals have a physiologic escape from this effect; however those with abnormal thyroid glands may not. These include patients with autoimmune thyroiditis, surgically treated Graves hyperthyroidism (subtotal thyroidectomy) and prior radioiodine therapy

Localized disease of the thyroid gland that results in ↓d thyroid hormone production is the most common cause of hypothyroidism. Under normal circumstances, the thyroid releases 100-125 nmol of T4 daily and only small amounts of T3. The half-life of T4 is approximately 7-10 days. T4, a prohormone, is converted to T3, the active form of thyroid hormone, in the peripheral tissues by 5’-deiodination.

Early in the disease process, compensatory mechanisms maintain T3 levels. Decreased production of T4 causes an increase in the secretion of TSH by the pituitary gland. TSH stimulates hypertrophy and hyperplasia of the thyroid gland and thyroid T4-5'-deiodinase activity. This, in turn, causes the thyroid to release more T3.

Because all metabolically active cells require thyroid hormone, the effects of hormone deficiency vary. Systemic effects are either due to derangements in metabolic processes or direct effects by myxedematous infiltration, that is accumulation of glucosaminoglycans in the tissues.

The myxedematous changes in the heart result in decreased contractility, cardiac enlargement, pericardial effusion, decreased pulse, and decreased cardiac output. In the GI tract, achlorhydria and decreased intestinal transit with gastric stasis can occur.

Delayed puberty, anovulation, menstrual irregularities, and infertility are common. Decreased thyroid hormone effect can cause increased levels of total cholesterol and low-density lipoprotein (LDL) cholesterol and a possible change in high-density lipoprotein (HDL) cholesterol due to a change in metabolic clearance.

GENERAL Tiredness Somnolence Cold intolerance Hoarseness Goitre Dull facial expression Coarse facial features Periorbital puffiness Macroglossia

CARDIORESPIRATORY Bradycardia Hypertension Angina Cardiac failure Xanthelasma Pericardial/pleural

effusion

NEUROMUSCULAR Aches/pains Muscle stiffness Delayed relaxation of

tendon reflexes Carpal tunnel

syndrome Deafness Depression/psychosis Cerebellar ataxia Myotonia

DERMATOLOGICAL Dry, flaky skin and hair Alopecia Purplish lips and malar

flush Carotenaemia Vitiligo Myxoedema

HAEMATOLOGICAL Macrocytosis Anaemia ~ Iron deficiency (pre- menopausal

women) ~ Normochromic ~ Pernicious

REPRODUCTIVE Menorrhagia Infertility Galactorrhoea Impotence GASTROINTESTINAL Constipation Ileus Ascites

Thyroid Function Test (TFT) 1° hypothyroidism

↑TSH,↓T4 &↓T3 - ↑TSH & ↓FT4 identifies 1° hypothyroidism T3 levels variable: may be normal

20 hypothyroidism ↓TSH ,↓T4 & ↓T3

Subclinical hypothyroidism ↑TSH + Normal T3 & T4

Thyroid autoantibodies (antimicrosomal or anti-TPO antibodies) and

antithyroglobulin (anti-Tg) may be helpful in determining the etiology (e.g Hashimoto’s) in predicting future hypothyroidism

FNAC Thyroid scan CT / MRI

Other laboratory findings Hypercholesterolaemia. Hyponatraemia. Anaemia. Elevations of creatinine phosphokinase &

LDH. Hyperprolactinaemia.

Treatment goals Reversal of clinical progression and Corrections of metabolic derangements as

evidenced by normal blood levels of TSH and free T4.

Rx- Oral thyroxine replacement with Levothyroxine (LT4).

T4 has a t1/2 of ~ 7days. The starting dose will depend upon the

severity of the deficiency and on the age and fitness of the patient, especially cardiac performance.

In the young and fit- 50-100μg/d (starting dose)

In patients with ischaemic heart ~ 25μg/d

Myxedema coma (or critical hypothyroidism) is an uncommon presentation of severe hypothyroidism that is potentially fatal.

Usually in the older age with F>M. It can develop from all causes of hypothyroidism.

Precipitating factors- Infections, especially pneumonia, are perhaps the most common precipitating factor. Cardiac events (myocardial infarction, congestive heart failure), cerebral infarction, trauma, hemorrhage, hypothermia, hypoglycemia, and respiratory depression secondary to anesthetics or sedatives have also been implicated

Clinical findings in myxedema coma are similar to those encountered with hypothyroidism, but they are typically seen in greater magnitude. It is a state of profound decreased metabolic activity. Cardinal features include impaired thermoregulation (hypothermia), hypotension, bradycardia, and mental status depression.

Mental status depression is a common clinical feature and may progress to stupor, obtundation, or frank coma. The hypometabolic state and mental status depression may result in centrally mediated hypoventilation and hypercapnic respiratory failure. There may be ass. adrenal insufficiency.

Most patients with myxedema coma have a prior diagnosis of hypothyroidism, may however be the initial presentation in a few. The diagnosis is suspected clinically and confirmed with TFT. Treatment should not be delayed for laboratory confirmation

TREATMENT – ideally be in the ICU Thyroid hormone replacement should be

given intravenously to ensure rapid restoration of bioactive thyroxine levels and resolution of symptoms.

Intravenous thyroxine is given as a bolus of 300-500 μg, followed by 50-100 μg daily depending on the patient's age, weight, and risk of complications

Alternatively, I.V liothyronine may be given as 10-25μg 12hrly.

I.V Hydrocortisone 100mg 8hrly Hypertonic saline may be required Supportive care should be provided while

thyroid hormone levels are replaced. Ventilatory support, passive rewarming, and correction of underlying electrolyte abnormalities are commonly required

Treat precipitating factor(s).