Endocrine System 2 PDF

Endocrine System II Karen Gil MD, MHSN Thyroid Gland Butterfly shape Located inferior to the larynx Rich blood supply Weight 30 gr. Anatomically – 2 lobes connected by an isthmus Right and left Histology – Thyroid follicules walls compose of Follicular cells – Produce the thyroid hormones T3 - triio...

Endocrine System II Karen Gil MD, MHSN Thyroid Gland Butterfly shape Located inferior to the larynx Rich blood supply Weight 30 gr. Anatomically – 2 lobes connected by an isthmus Right and left Histology – Thyroid follicules walls compose of Follicular cells – Produce the thyroid hormones T3 - triiodothyroinine T4 - thyroxine Parafollicular cells – Involved in the production of Calcitonin Regulate calcium homeostasis THYROID GLAND Lt Isthmus Control of Thyroid Hormone Secretion TRH from the hypothalamus and TSH from the anterior pituitary stimulate synthesis release of thyroid hormones TSH promote release of thyroid hormones by the thyroid gland Thyrotropin (TRH) Stimulates synthesis and secretion of thyroid hormones T3 triiodothyronine T4 tetraiodothyroxine Regulation mechanism – TRH (thyrotropin releasing hormone) produced in hypothalamus – Release is dependent on TSH, T3 and T4 working in a feedback mechanism – Other factors which regulates production and secretion of thyroid hormone glucose levels metabolic rate among others Thyroid hormone After its production and release into peripheral circulation more than 99 % of both are bound to specific carrier T3 (tri-iodothyronin) T4 (Tetraiodothyronin) Thyroid binding globulin (TBG) Actions of Thyroid Hormones Increase basal metabolic rate Regulation of oxygen use on standard or basal conditions (awake, rest, fasting) Stimulate synthesis of enzymes that run the Na+ - K+ pump producing a calorigenic effect (helps maintaining body temperature) At the cellular level it stimulates Protein synthesis Lipolysis Increase Glucose use Helps in growth and development together with hGH Enhance some actions of epinephrine and norepinehrine – Increase heart rate and blood pressure – More forceful heartbeats (signs of hyperthyroidism) Goiter Most common thyroid disease produce enlargement of the gland Reflects impaired production of thyroid hormone most often cause due to iodine deficiency Multinodular goiter is asymptomatic and patient is euthyroid More common on females EPIDEMIC Geographic areas in which with > 10% population is affected (places were water and soil don’t have enough iodine) SPORADIC Ingestion of substances that interfere with hormone synthesis (Lithium, amiodarone) Goiter Clinical features Cosmetic change (neck mass) Dysphagia Cough Hoarseness Swallow difficulties Compression of large vessels Laboratory Normal T4, T3 and TSH * Treatment The goiter, if significant in size, should be removed surgically thyroidectomy, radioactive iodine therapy, and levothyroxine therapy Hyperthyroidism Hypermetabolic State Arrythmias Tachycardia and palpitations Nervousness and diaphoresis (excess sweating) Diarrhea (hypermotility with malabsorption) Heat intolerance Hyperreflexia Weakness and tremors Skin warm, moist and flush Weigh loss despite a good appetite Exophthalmos Upper lid retraction Graves Disease Autoimmune disease Characterized by production of IgG autoantibodies to the TSH receptors Clinical features – – – – – – – Females > males 20-40 y/o Thyrotoxicosis Diffuse goiter Exophthalmos (40%) Pretibial myxedema Periorbital swelling Graves disease Hyperplasic follicules with scalloped colloid Graves disease PATHOGENESIS Autoimmune disease Antibodies against TSH receptors – TSI (thyroid stimulating Ig) – TGI (thyroid growth Ig) – TBII’s (TSH binding inhibitory Ig) Graves Disease Laboratory findings: Decreased serum levels of TSH Increased serum levels of T3 & T4 Increase – TSI (thyroid stimulating Ig) – TGI (thyroid growth Ig) Graves Disease Treatment – Adrenergic hyperfunction treated with betaadrenergic blockers (propanolol, atenolol) – Anti-thyroid medications that block the synthesis of thyroid hormones PTU propylthiouracil Metimazole (block iodine oxidation so inhibits thyroid synthesis) – Radioactive iodine Most common Contraindicated in pregnancy – Surgery Graves Ophthalmopathy Stages – Inflammatory Edema deposition of glycosaminoglycan in the extraocular muscles – – – – – – Orbital swelling Stare Diplopia Periorbital edema Pain (occasionally) Dry eye – Fibrotic Further diplopia and lid retraction Graves Ophthalmopathy Therapeutic measures – Artificial tears and ointment – Sunglasses – Eye patches – Nocturnal taping of the eyes – Prisms – Elevating the head at night Hypothyroidism Cause: destruction of thyroid gland cells – – – – Hashimoto’s Thyroiditis (autoimmune, most common) Surgical ablation Radiation ablation Primary idiopathic hypothyroidism LABORATORY FINDINGS Increased TSH serum levels Decreased serum levels of T3 & T4 Hypothyroidism Secondary Hypothalamus produces insufficient TRH, or the pituitary produces insufficient TSH After pituitary or hypothalamic damage (tumor, ischemia) LABORATORY FINDINGS Decreased TSH serum levels Decreased serum levels of T3 & T4 Elevated TSH (usually 4.5-10.0 mIU/L) with normal free T4 or FTI (free thyroxine index) is considered mild or subclinical hypothyroidism Hypothyroidsm Hypothyroidism Clinical Manifestations: Fatigue and lethargy Sensitivity to cold temperatures Decreased cardiac output (low heartbeat) obese Myxedema (accumulation of proteoglycans and water) – – – – Facial and periorbital edema Peripheral edema of hands and feet Deep voice Macroglossia Constipation Anovulatory cycles Iatrogenic Hypothyroidism Most common cause of hypothyroidism in US Secondary to thyroidectomy or radioactive iodine treatment Treatment: – Thyroid hormone replacement Levothyroxine (Synthroid) 25 – 300 mcg (0.25 – 3.00 mg) Congenital Hypothyroidism (Cretinism) Hypothyroidism during infancy or early childhood CLINICAL FINDINGS: Impaired development of skeletal system (developmental delay) Impaired development of CNS – SEVERE MENTAL RETARDATION Coarse facial features with protruding tongue, jaundice Umbilical hernia Hoarse cry, hypotonia TREATMENT: Levothyroxine (Initial dosages of 10-15 mcg/kg/d) Hashimoto’s Thyroiditis Chronic autoimmune inflammatory process due to formation of specific CD8 cells and auto-antibodies (destruction of the thyroid gland – hypothyroidism) Not well understood initiating process More common in women 10:1 Age 40-65 Auto-antibodies directed against TSH receptor + Increased risk for B cell leukemia Hashimoto’s Thyroiditis CLINCAL FINDINGS Painless enlargement of gland Transient thyrotoxicois followed by hypofunction Calcification Lymphoid follicle SUBACUTE THYROIDITIS (de Quervain’s) Unknown etiology More common in females between 30 – 50 y/o Preceded by a viral illness CLINICAL FINDINGS – – – – – – Neck pain Fever Malaise variable enlargement of gland Transient HYPERTHYROIDISM Usually self limited to 6 – 8 weeks Thyroid Benign Tumors Adenoma – follicular are the most common (derives from follicular epithelium) – Solitary nodule (painless mass) “cold nodule” on thyroid scans – hypofunctional or nonfunctional thyroid tissue (suspect malignancy) “hot nodule” functional cause hyperthyroidism warm nodules suggest normal thyroid function Thyroid scintigraphy Thyroid Adenoma. Malignant tumors Papillary carcinoma (75-85%) Follicular carcinoma (10 - 20%) Medullary carcinoma (5%) Anaplastic carcinoma ( males age 20-50 years-old Associated with ionizing radiation Multifocal lesion Usually produce metastasis to regional lymph nodes in 50% 10-year survival rate up to 85% Papillary Carcinoma Diagnosis depend on nuclear characteristics (“Orphan Annie eye” nuclei) Treatment Resection – Total Thyroidectomy Thyroid replacement therapy after Levothyroxine Follicular Carcinoma Second most common malignancy (15%) females > males 40- 60 y/o Solitary “cold” nodule Hematogenous metastasis – Lungs – Bones – Liver Rx. Surgical resection Medullary Carcinoma 5% malignant tumors Neuroendocrine tumor derived from C cells (parafolicullar cells) – secrets calcitonin Sporadic in 80 % Other 20% associated with MEN (Multiple Endocrine Neoplasia syndromes) 5-year survival rate 50% Anaplastic Carcinoma Presentation – – – – Females > males age >60 Firm, enlarging, bulky mass Dyspnea and dysphagia Very aggressive lesion (high mortality rate) Rapid growth with spread to adjacent structures and distant metastasis Death occur within 1 year due to compromise of local vital structures (trachea and esophagus) Parathyroid glands Anatomically are 4 - 6 mustard colored glands Arranged geographically around the Thyroid gland with which has NO direct relation Parathyroid Glands Histology Principal or chief cells – produce PTH Oxyphilic cells Calcitonin- CT Produced by the parafollicular cells of the thyroid gland Control secretion – High blood calcium levels stimulate secretion – Low blood calcium levels inhibit secretion Actions – Lower blood levels of calcium and phosphates by inhibiting bone resorption by osteoclasts Parathyroid Glands Production- Parathohormone (PTH) Main functions: Regulator of the levels of Ca++, Mg++ and HPO4 2- ions (calcium, magnesium, phosphate) Is an antagonist for Ca++ reabsorption Inhibits phosphate reabsorption from renal filtrate Promote formation of calcitriol (active metabolite of Vitamin D) Parathyroid glands Regulation mechanism Ca++ levels in serum directly controls secretion of PTH and Calcitonin according to a negative feedback loop doesn’t involve the Pituitary gland Low blood calcium levels stimulate secretion PTH High blood calcium levels inhibit secretion of PTH Parathyroid Glands Diseases Primary hyperparathyroidism – Etiology Parathyroid adenoma (80%) Parathyroid hyperplasia (15%) – enlarged glands composed of chief cells Parathyroid carcinoma (rare) – Pathogenesis Excess of production of PTH – hypercalcemia – Clinical features Calcium and PTH elevated Asymptomatic Kidney stones, osteoporosis, neurologic changes Parathyroid Glands Diseases Secondary hyperparathyoridism – Etiology Chronic renal failure Vitamin D deficiency Malabsorption – Pathogenesis Hyperplasia of the parathyroid in response to decrease calcium levels Disease that cause hypocalcemia lead to increase secretion of PTH – Tx. Parathyroidectomy Parathyroid Glands Diseases Hypoparathyroidism Etiology: Surgical removal, idiopathic, DiGeorge syndrome (congenital chromosome anomaly on chromosome 22) Lab findings- hypocalcemia , low PTH Neuromuscular excitability and tetany Hypomagnesemia, hypokalemia and alkalosis (hyperventilation) Rx: vitamin D and calcium