HYPOTHYROIDISM:
Hypothyroidism is a syndrome resulting from deficiency of thyroid hormones and is
manifested largely by a reversible slowing down of all body functions. In infants and
children, there is striking retardation of growth and development that results in dwarfism and
irreversible mental retardation. The most common cause of hypothyroidism in the USA at
this time is probably Hashimoto’s thyroiditis, an immunologic disorder in genetically
predisposed individuals. In this condition, there is evidence of humoral immunity in the
presence of antithyroid antibodies and lymphocyte sensitization to thyroid antigens. Certain
medications can also cause hypothyroidism.
PATHOPHYSIOLOGY: Under normal circumstances, the thyroid releases 100-125 mcg 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 5’-deiodinase
activity, thereby increasing T3 production.
SIGN AND SYMPTOMS:
Skin and appendages: Pale, cool, puffy skin; dry and brittle hair; brittle nails.
Eyes, face: Drooping of eyelids; periorbital edema; loss of temporal aspects of eyebrows;
puffy, non pitting facies; large tongue.
Cardiovascular system: Increased peripheral vascular resistance; decreased heart rate, stroke
volume, cardiac output, pulse pressure; low output heart failure; ECG: bradycardia,
prolonged PR interval, flat T wave, low voltage; pericardial effusion.
Hematopoietic system: Decreased erythropoiesis; anemia
Reproductive system: Hypermenorrhea; infertility; decreased libido; impotence;
oligospermia; decreased gonadal steroid metabolism
Metabolic system: Decreased basal metabolic rate; slight positive nitrogen balance; delayed
degradation of insulin with increased sensitivity; increased cholesterol and triglycerides;
decreased hormone degradation; decreased requirements for fat- and water-soluble vitamins;
decreased drug metabolism; increased warfarin requirement.
TREATMENT:
Standard treatment for hypothyroidism involves daily use of the synthetic thyroid hormone
levothyroxine. This oral medication restores adequate hormone levels, reversing the signs
and symptoms of hypothyroidism.
1- LEVOTHYROXINE:
MECHANISM OF ACTION:Levothyroxine acts like the endogenous thyroid hormone
thyroxine (T4, a tetra-iodinated tyrosine derivative). In the liver and kidney, T4 is converted
to T3, the active metabolite. In order to increase solubility, the thyroid hormones attach to
thyroid hormone binding proteins, thyroxine-binding globulin, and thyroxine-binding
prealbumin (transthyretin). Transport and binding to thyroid hormone receptors in the
cytoplasm and nucleus then takes place. Thus by acting as a replacement for natural
thyroxine, symptoms of thyroxine deficiency are relieved.
ADVERSE EFFECTS:
● Increased appetite
● Weight loss
● Excessive sweating
● Hypersensitivity
● Headache
● Nervousness
● Anxiety
● Irritability
● Mood swings etc.
2- LIOTHYRONINE:
MECHANISM OF ACTION: The hormones, T4 and T3, are tyrosine-based hormones
produced by the thyroid gland. Iodine is an important component in their synthesis. The
major form of thyroid hormone in the blood is thyroxine (T4). This is converted to the more
active liothyronine form by deiodinases in peripheral tissues. Liothyronine acts on the body
to increase the basal metabolic rate, affect protein synthesis and increase the body's
sensitivity to catecholamines (such as adrenaline). The thyroid hormones are essential to
proper development and differentiation of all cells of the human body. To various extents T4
and T3 regulate protein, fat and carbohydrate metabolism. Their most pronounced effect is on
how human cells use energetic compounds. The thyroid hormone derivatives bind to the
thyroid hormone receptors initially to initiate their downstream effects.
ADVERSE EFFECTS:
● Hair loss
● Headache
● Sweating
● Diarrhea
● Chest pain
● Trouble breathing
● Allergic reactions
● High blood pressure
● Irregular heart beat etc.
HYPERTHYROIDISM:
Hyperthyroidism (thyrotoxicosis) is the clinical syndrome that results when tissues are
exposed to high levels of thyroid hormones.The most common form of hyperthyroidism is
Graves’ disease, or diffuse toxic goiter.
PATHOPHYSIOLOGY: Graves’ disease is considered to be an autoimmune disorder in
which helper T lymphocytes stimulate B lymphocytes to synthesize antibodies to thyroidal
antigens. The antibody (TSH-R Ab [stim]) is directed against the TSH receptor site in the
thyroid cell membrane and has the capacity to stimulate growth and biosynthetic activity of
the thyroid cell. Spontaneous remission occurs but some patients require years of antithyroid
therapy.
SIGN AND SYMPTOMS: Skin and appendages: Warm, moist skin; sweating; heat
intolerance; fine, thin hair; Plummer’s nails; pretibial dermopathy (Graves’ disease).
Cardiovascular system: Decreased peripheral vascular resistance; increased heart rate, stroke
volume, cardiac output, pulse pressure; high output heart failure; increased inotropic and
chronotropic effects; arrhythmias; angina
Respiratory system: Dyspnea; decreased vital capacity.
Central nervous system: Nervousness, hyperkinesia; emotional lability.
Hematopoietic system: Increased erythropoiesis; anemia.
Reproductive system: Menstrual irregularities; decreased fertility; increased gonadal steroid
metabolism.
Metabolic system: Increased basal metabolic rate; negative nitrogen balance; hyperglycemia;
increased free fatty acids; decreased cholesterol and triglycerides; increased hormone
degradation; increased requirements for fat- and water-soluble vitamins; increased drug
metabolism; decreased warfarin requirement.
TREATMENT: The three primary methods for controlling hyperthyroidism are antithyroid
drug therapy, surgical thyroidectomy, and destruction of the gland with radioactive iodine.
ANTITHYROID DRUG THERAPY:
1- PROPYLTHIOURACIL:
MECHANISM OF ACTION: Propylthiouracil binds to thyroid peroxidase and thereby
inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to
iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the
resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines
found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-
iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore
propylthiouracil effectively inhibits the production of new thyroid hormones.
ADVERSE EFFECTS:
● Stomach upset
● Nausea
● Vomiting
● Mild rash or itching
● Headache
● Dizziness
● Spinning sensation
● Joint or muscle pain
● Hair loss etc.
2- METHIMAZOLE:
MECHANISM OF ACTION: Methimazole is a thioamide inhibitor of the enzyme thyroid
peroxidase (TPO), with antithyroid activity. Upon administration, methimazole inhibits the
metabolism of iodide and the iodination of tyrosine residues in the thyroid hormone precursor
thyroglobulin by TPO; this prevents the synthesis of the thyroid hormones triiodothyronine
(T3) and thyroxine (T4).
ADVERSE EFFECTS:
● Muscle/joint/nerve pain
● Drowsiness
● Swelling
● Hepatitis
● Nephritis
● Urticaria
● Headache
● Edeme etc
REFERENCES:
● KATZUNG
● LIPPINCOTT
● https://www.drugbank.ca/drugs/DB00550
