DISORDERS OF THYROID HORMONE! The disorders of the TH are among the most common of the endocrine disorders. The fall into 2 major categories: HYPER & HYPO thyroidism. A number of specific causes can give rise to the different disorders. Whatever the cause, the consequences of too little or too much TH are largely predictable, given that there is knowledge of the functions of the TH.

Thyroid hormones are NOT essential for life, but they do affect the QUALITY of life…. The main function of thyroid hormones in adults is to provide substrates for oxidative metabolism. Thyroid hormones are thermogenic & calorigenic in nature.

HYPERTHYROIDISM

Excess (increased) thyroid hormone secretion leads to Hyperthyroidism Causes of Hyperthyroidism: Primary Hyperthyroidism: GRAVE’S DISEASE THYROID ADENOMA SUBACUTE THYROIDITIS EXCESSIVE INTAKE OF IODINE EXCESSIVE INTAKE OF EXOGENOUS THYROID HORMONE (THYROTOXICOSIS FACTITIA) 2. Secondary: Secondary to increased TSH secretion (anterior pituitary adenoma) Secondary to increased TRH secretion (hypothalamic tumor)

Diffuse enlargement of the gland GRAVE’S DISEASE (also called toxic goitre or thyrotoxicosis) It is an autoimmune disorder in which abnormal thyroid stimulating immunoglobulins (TSI) attach to the TSH receptors on the thyroid gland. ↓ Diffuse enlargement of the gland Stimulation of thyroid hormone secretion which suppress the TSH secretion from the Ant. Pituitary ↑ levels of TH + Goiter + Exophathalmos

Signs and symptoms of Hyperthyroidism THYROID ADENOMA (also called Nodular toxic disease or Plummer’s disease) It is a localized adenoma or tumor that develops in the thyroid gland & secretes large quantities of thyroid hormone. ↓ ↑ levels of TH Signs and symptoms of Hyperthyroidism Secretory function of the rest of the gland is almost totally inhibited as the thyroid hormone from the adenoma depresses the production of TSH from the anterior pituitary.

CLINICAL FEATURES Increased metabolism Weight loss Increased appetite Involvement of CVS Cardiac failure Tachycardia Atrial fibrillation Raised pulse pressure Murmurs Involvement of Reproductive system Impotence Loss of libido Oligomenorhea or polymenorrhea Eye changes Exophthalmos Lid lag Involvement of respiratory system & GIT Breathlessness Diarrheoa Miscellaneous Fine, silky hair Pretibial myxedema Thick brittle nails Increased metabolism Weight loss Increased appetite Heat intolerance Warm moist skin Sweating Muscle weakness (thyrotoxic myopathy) Involvement of CNS Irritability/ behavior changes Restlessness Anger Insomnia Emotional instability Psychosis Fine Tremors Brisk tendon reflexes ALL THE PATIENTS OF HYPERTHYROIDISM CAN PROGRESS TO THYROID STORM IF LEFT UNTREATED

GRAVE’S DISEASE

EXPHTHALMOS: It is the protrusion of the eyeballs. Usually seen only with Grave’s disease CAUSE: Immunoglobulins are found in the blood that react with muscles of the eye ↓ Edema & swelling of retro-orbital tissue + Degenerative changes in the extra-ocular muscles Stare + Lid Lag Failure of the eye to close completely esp. the upper lid fails to completely close Dryness of the eye, irritation, infections, pain, double vision In severe cases, protrusion of the eyeball stretches and damages the optic nerve leading to BLINDNESS

How will you diagnose HYPERTHYROIDISM?

Diagnosis of HYPERTHYROIDISM ↑ T3 & T4 ↓ TSH ↓ TRH However, both TRH & TSH will be raised if cause is excess hypothalamic or pituitary secretion: ↑ T3 & T4 & ↑ TRH & TSH Anti-thyroid antibodies TSI (Thyroid stimulating Immunoglobulins) Scanning images show thyroid tumor if present

TREATMENT 3 options: Anti-thyroid drugs Surgery Radioiodine

Size of thyroid gland & its blood supply decreased ANTI-THYROID DRUGS All the drugs that cause suppression of Thyroid hormone secretion are called Anti-thyroid drugs. THIOCYANATE: Prevent iodide trapping by competitively binding to sodium-iodide symporter instead of Iodide itself. Percholate & nitrate ions also follow the same M.O.A. It can lead to Goiter!!..........HOW? PROPYLTHIOURACIL: e.g. methimazole, carbimazole M.O.A: 1: partly blocks peroxidase enzyme 2 : partly blocks coupling It also causes Goiter as it does not stop synthesis of TG. IODINE: If Increased Iodide conc. in the blood (more than 100 times) ↓ Most activities of the thyroid gland are decreased as IODIDE itself inhibits the enzymes needed for synthesis of TH Size of thyroid gland & its blood supply decreased So, Iodine usually given 2-3 weeks before surgery, to reduce the size of the gland decreasing the necessary amount of surgery & especially the amount of bleeding!! With thiocyanates, decreased thyroid hormone secretion leads to increased TSH secretion. It stimulates the follicular cells & b/c thiocyanate is not preventing the TG production, synthesis of TG continues without check leading to increase in the size of the gland!

SITES OF ACTION OF ANTI-THYROID DRUGS

HYPOTHYROIDISM

Decreased secretion of Thyroid hormone is called Hypothyroidism. PRIMARY HYPOTHYROIDISM (due to primary failure of the Thyroid gland) Hashimoto’s Thyroiditis Endemic Colloid Goiter Idiopathic Non-toxic Colloid Goiter Tumors Thyroiditis Post-surgery Post- Irradiation 2. SECONDARY HYPOTHYROIDISM Secondary to decreased Hypothalamic secretion Secondary to decreased anterior pituitary secretion or Decreased TSH secretion 3. DUE TO IODINE DEFICIENCY.

CAUSES OF HYPOTHYROIDISM (Primary causes) 1. HASHIMOTO’S THYROIDITIS: It is an autoimmune disorder in which, like the Grave’s disease, there is production of abnormal antithyroid antibodies against the thyroid follicular cells and the TSH receptors. However, unlike the Grave’s disease where these antibodies were stimulatory, in Hashimoto’s disease the antibodies are inhibitory or block the Thyroid function and destroy the Thyroid gland. This process develops very slowly. Classical symptoms of Hypothyroidism are seen. These patients may also develop other autoimmune disorders.

CAUSES OF HYPOTHYROIDISM (Primary causes) 2. ENDEMIC COLLOID GOITER caused by dietary Iodine deficiency in specific areas: -In areas of Insufficient Iodine in the soil, the food does not contain even the minute quantities that are required . -In the absence of iodized table salts, these populations develop very large goiters called Endemic goiters. -M.O.A of production of a Goiter: lack of Iodine ↓ Decreased secretion of T3 & T4 Increased secretion of TSH by the anterior pituitary Stimulates the thyroid cells to secrete large amounts of TG into the follicular colloid Gland grows larger & larger Still no mature hormone, so TSH secretion continues Stimulus by the TSH continues to stimulate the thyroid cells Follicles enlarge tremendously & the gland may increase to 10-20 times normal size

CAUSES OF HYPOTHYROIDISM (Primary causes) 3. IDIOPATHIC NON-TOXIC COLLOID GOITRE: These patients do not have iodine deficiency The thyroid hormone may be normal or (more frequently) depressed. Usually, thyroiditis occurs which is inflammation of some or all of the thyroid follicles. The inflamed area then becomes replaced by the fibrous tissue and all secretory activity is lost: ↓ Decreased thyroid hormone secretion from the inflamed areas Increased TSH secretion from the Anterior Pituitary Enlargement of the non-inflamed parts of the thyroid gland Therefore, nodular growth seen - Also seen in populations eating Goitrogenic foods.e.g. turnips & cabbages

CLINICAL FEATURES DECREASED METABOLISM Weight gain (not burning fuels at a normal rate) Decreased appetite (decreased BMR) Cold intolerance (lack of calorigenic effect) Fatigue (lower energy production) Cold peripheries (lower energy production) Thin, dry skin, brittle nails and thinning hair: All due to effect on the protein metabolism. INVOLVEMENT OF CNS Mental sluggishness Listlessness Lethargy & fatigue Somnolence Psychosis Depression Poor memory Slow reflexes INVOLVEMENT OF CVS: Cardiac failure Bradycardia (due to reduction in rate and strength of cardiac contraction and a lowered cardiac output) REPRODUCTIVE SYSTEM Loss of libido Mennorhagia or oligomenorrhea GIT Constipation MISCELLANEOUS FROG-LIKE HUSKY VOICE Deafness Loss of eyebrows

Protein+ hyaluronic acid+ chondroitin sulphate MYXEDEMA CAUSE: In patients with total lack of thyroid hormones, a condition known as Myxedema develops!! Patients suffer from all the symptoms of Hypothyroidism and show following symptoms too: There is characteristic accumulation of a water-retaining complex which forms the matrix in which other materials are deposited: Protein+ hyaluronic acid+ chondroitin sulphate SITE: interstitial spaces, particularly skin. Because of its osmotic effect, this material causes the water to accumulate in these spaces, giving rise to the typical non –pitting edema seen in hypothyroid patients. Atherosclerosis: leading to peripheral vascular disease, deafness & coronary artery disease & early death. Myxedema coma Myxedema depression

MYXEDEMA COMA A clinical diagnosis at the end of a hypothryoid continuum. The patient is usually a case of undiagnosed Hypothyroidism OR was diagnosed but took no medication. In such a patient the following symptoms are seen: Bradycardia, Hypotension Hypothermia Hypoventilation Stupor, Coma Delayed deep tendon reflexes Dry, puffy skin Precipitating Factors: Severe Illness Infection Cerebrovascular Accident Seizure GI Hemorrhage Surgery Sedative Drugs, Anesthetics

Hypothyroidism Lab studies Decreased T4 and T3 levels. Increased TSH (If the cause is Primary) Presence of antithyroid antibodies (If the cause is Autoimmune) Elevated cholesterol (due to poor secretion of cholesterol into the bile)

1 daily oral tablet of thyroxine leads to complete cure!! TREATMENT There is only one treatment which is TH replacement except when the cause is Iodine Deficiency in which case IODINE should be given.. Thyroxine replacement: 1 daily oral tablet of thyroxine leads to complete cure!! Iodine

CRETINISM It is a condition in which the infant or the child has TH deficiency from birth. CAUSE: extreme hypothyroidism during fetal life, infancy or childhood. TYPES: Congenital cretinism (absence of thyroid gland at birth). Failure of the thyroid gland to produce the hormone due to a genetic defect. e.g: PENDRED Syndrome in which the protein PENDRIN is lacking. Endemic cretinism (iodine lack in the diet)

CRETINISM CHARACTERISTICS: A neonate without a thyroid gland may be of normal appearance & function b/c he was supplied by the mother in utero! A few weeks after birth: Movements become sluggish Physical retardation (skeletal growth more retarded than soft tissue) Mental retardation Obese Stocky Short appearance Large tongue sometimes to the extent that its huge size obstructs swallowing & breathing inducing guttural breathing that sometimes chokes the child. Obese, stocky, large tongue b/c skeletal growth more retarded than the soft tissue growth which then seemed to be growing excessively!!

6 MONTHS OLD BOY with CRETINISM & 4 MONTHS AFTER TREATMENT STARTED

CRETINISM TREATMENT: - Thyroid hormone replacement immediately within a few weeks as later no matter how much treatment given then irreversible, permanent mental retardation!

GOITRE Large size of the thyroid gland OR thyroid gland enlargement is called Goitre. Causes: Physiological: puberty pregnancy Autoimmune disorder: Grave’s disease Thyroiditis Iodine deficiency goitre (endemic) Goitrogens Tumors Multinodular goitre

GOITER CHARACTERISTICS: It can cause dysphagia & difficulty in breathing, indicating oesophageal or tracheal compression! The patients can show all the symptoms of Hypothyroidism Or Hperthyroidism depending on the cause of the goiter!