Endocrine disease Prepared by: Siti Norhaiza Binti Hadzir
Introduction • Endocrinology- the study of hormones, which are secreted from specialized glands into the blood to influence the activity of cells at distance sites in the body.
Types of Hormones • Peptides or proteins- hypothalamic factor (thyrotrophin releasing hormones), and pituitary gonadotropin. • Amino acid derivatives- e.g thyroid hormones and adrenaline • Steroid hormones- derivatives from cholesterol (e.g estrogen)
Measurement of Hormones • Radioimmunoassay • Monoclonal antibodies
Endocrine Disease • Described as over or under secretion of hormones • Failure of hormones responsiveness
The Pituitary Gland • The location • Anterior pituitary-hormone secreted • Posterior pituitary-hormone secreted • Hypersecretion-tumours (prolactin secreting adenoma the most common) • Hypopituitarism-is uncommon; the clinical presentation depends on the age, sex or the person.
Growth disorders • Growth in children can be divided into 3 i) rapid growth-1st 2 years –condition in utero and nutrition ii) Steady growth-around 9 years-mainly controlled by GH iii) puberty- sex hormones and GH -Other hormones involve in growth
Growth hormone insufficiency • Is a rare cause of impaired physical growth. • Test of GH insufficiency: - serum GH in response to exercise, nocturnal sample - Stimulant (clonidine) • Treatment: genetically engineered GH for children
Excessive growth • Extremely rapid linear growth (gigantism). The condition is rare often due to pituitary tumor. • Other causes; congenital adrenal hyperplasia, hyperthyroidism, inherited disorders. • ↑GH later in life-Acromegaly due to pituitary adenoma
Diagnosis of Acromegaly • OGTT- a normal person will suppress GH in plasma in response to glucose load. • Acromegaly-not suppress • ↑ IGF 1 • Treatment-surgery, radiotherapy, drugs (octreotide-somastostatin analogue) and bromocriptine
The Thyroid Gland • The location • Thyroid hormone- thyroxine (T4) and tri-iodothyronine (T3). • Most cells capable of taking up T4 and deiodinating to the more biologically active T3. • It is T3 which binds to receptors and triggers the end-organ effects of the thyroid hormones. • T4 can be metabolized to reverse T3 (inactive)
Thyroid Hormone Action • Essential for the normal maturation and metabolism of all the tissues in the body. Thyroid hormones in blood
_ Hypothalamus TRH + _ Anterior pituitary TSH + Thyroid T4 + T3 Regulation of thyroid hormones
Thyroid Function Test • TSH (thyroid stimulating hormone) • Total T4 (bound hormone + free) • Free T4 • TBG level • Free T3 • Total T3 (bound hormone + free) • Titre of auto-antibodies to thyroid tissue antigens
TRH test • Involves intravenous injection of TRH and the measurement of pituitary TSH secreted in response to the stimulation. • Purposes: i) Investigation of pituitary disorders ii) Investigation of hyperthyroidism
TRH Normal response 20 60 Time (minutes) Pituitary responses to TRH TRH Primary hypothyroid TSH TSH Normal response Hyperthyroidism Secondary (pituitary) hypothyroid 20 60 Time (minutes)
Goitre • A goitre is an enlarged thyroid gland. • This may be associated with hypofunction, hyperfunction or indeed normal concentrations of thyroid hormones in blood.
Hypothyroidism • 90% of cases of hypothyroidism occur as a consequence of: - autoimmune destruction of the thyroid gland (Hashimoto’s disease) - radioiodine or surgical treatment of hyperthyroidism
Diagnosis of Hypothyroidism • Hypothyroidism is caused by a deficiency of thyroid hormones. • Primary hypothyroidism – failure of the thyroid organ itself-elevated TSH concentration is diagnostic • Secondary hypothyroidism-failure of pituitary to secrete TSH (less common). • Treatment- thyroxine (tablet) therapy.
Non-thyroidal Illness • In systemic illness the normal regulation of TSH, T4 and T3 secretion and subsequently metabolism of the thyroid hormones, is disturbed. • ↑ T4 are converted to the reverse T3. • Reduction in thyroid hormone activity does not result in an increased serum TSH concentration. • TSH secretion is suppressed→ ↓ T4 and T3. • TBG decrease
Neonatal Hypothyroidism • The failure of the thyroid gland to develop properly during early embryonic growth. • Children develop irreversible mental retardation and characteristic feature of cretinism. • The screening test- ↑ blood TSH concentration.
Hyperthyroidism • Hyperthyroidism can be result from: - Graves’ disease, diffuse toxic goitre - Toxic multinodular goitre - solitary toxic adenoma - thyroiditis - exogenously administered iodine and iodine- containing drugs, e.g amiodarone - excessive T4 and T3 ingestion
Graves’ disease • An autoimmune disease in which antibodies to the TSH receptor on the surface of the thyroid cells appear to mimic the action of the pituitary hormones. • The normal regulatory controls on T4 synthesis and secretion are lacking. • Pituitary secretion of TSH is completely inhibited by the ↑ conc. of thyroid hormones in the blood-eyelid retraction
Diagnosis • Suppressed TSH concentration,↑ T4 and T3- primary hyperthyriodism • Occasionally, biochemical confirmation of suspected hyperthyroidism will prove more difficult e.g in pregnancy.
Treatment • Anti-thyroid drugs (such as carbimazole and propylthiouracil)- younger patient • Radioiodine-therapy with sodium I131is commonly used in older pt. Most will require eventually require replacement thyroxine. • Surgery-thyroidectomy