Endocrine System 3 PDF

Endocrine System 3 Karen Gil MD Adrenal Gland or Suprarenal Glands Each gland lie superior to each kidney Flattened pyramidal shape Weight 3.5-5 g. Adrenal Gland Two structurally and functionally distinct regions: Adrenal cortex 80-90% (surround the inner medulla) Adrenal medulla (inner part) Adrena...

Endocrine System 3 Karen Gil MD Adrenal Gland or Suprarenal Glands Each gland lie superior to each kidney Flattened pyramidal shape Weight 3.5-5 g. Adrenal Gland Two structurally and functionally distinct regions: Adrenal cortex 80-90% (surround the inner medulla) Adrenal medulla (inner part) Adrenal Gland Adrenal Medulla Consists of specialized chromaffin cells that secrete epinephrine (adrenaline) norepinephrine (noradrenaline) Impulses from the hypothalamus stimulate sympathetic preganglionic neurons which stimulate the secretion of epinephrine and norepinephrine Epinephrine constitutes 80 % of total secretion and both are responsible for the fight or flight response Adrenal Gland Adrenal Medulla Unlike hormones from the cortex, they are NOT essential for life Effects include: Dilation of airways of the lung Decrease rate of digestion Increase in heart rate and blood pressure Increase blood glucose levels Stimulate cellular metabolism Adrenal Gland Adrenal Cortex Functionally and anatomically divided into 3 sections or zones 1. Zona glomerulosa 2. Zona fasciculata 3. Zona reticularis Adrenal Gland Adrenal Cortex Zona glomerulosa Secretes mineralocorticoids Aldosterone 95% Major function is in the control of water and electrolytes (Na+ and K+) Aldosterone increase absorption of Na+ from the urine to blood and stimulates excretion of K+ into the urine Aldosterone also helps adjust blood pressure and blood volume Regulation Renin, Angiotensin and Aldosterone loop Adrenal Gland / Adrenal Cortex Zona Fasciculata Secrete glucocorticoids Cortisol or Hydrocortisone (most abundant) Corticosterone Cortisone Regulate metabolism and resistance to stress Major effects include: Increase rate of protein catabolism Gluconeogenesis Lipolysis Resistance to stress Increased in blood pressure Anti-inflammatory actions Decrease blood capillary permeability Retard tissue repair - slow wound healing Depress the immune response at high doses Adrenal Gland/ Adrenal Cortex Zona Reticularis Secretes small amounts of androgen The major androgen secreted is DHEA (dihydroepiandorstenedione) Assist in early growth of axillary and pubic hair In females it may contribute to libido DHEA may be converted into estrogen by body tissues which is significant in menopause where estrogen production by ovaries diminishes Adrenocorticotropic Hormone ACTH or Corticotropin Corticotropin releasing hormone (CRH) from the hypothalamus stimulates its secretion No corticotropin inhibiting hormone Corticotroph synthesize ACTH on the adenohypophisis Stress, low blood glucose, physical trauma and interleukin-1 stimulate the release of ACTH Adrenocorticotropic Hormone ACTH or Corticotropin ACTH controls production and secretion of glucocorticoids (produced by adrenal cortex) Glucocorticoids inhibit CRH and ACTH release via negative feedback Adrenal Gland- Adrenal Cortex Glucocorticoids Regulation Low levels of glucocorticoids stimulate the release of CRH CRH stimulates release of ACTH ACTH stimulates glucocorticoids secretion Low glucose levels also can increase the synthesis of glucocorticoids Melanocyte Stimulating Hormone MSH Involved in production of skin pigment by accumulation of melanin granules inside melanocytes High levels of CRH can stimulate MSH release Addison’s Disease Chronic or Primary adrenocortical insufficiency Destruction of adrenal cortex Hyposecretion of Glucocoticoids Mineralocorticoids Androgens This condition is a medical emergency and needs immediate treatment and hormonal (steroid) replacement for maintenance of life Addison’s Disease Etiologies Autoimmune (75 – 90%) In 50% disease restricted to adrenal gland (cortex) Infectious disorders Tuberculosis Fungal infections Bacterial sepsis Metastatic cancer Addison’s Disease Clinical manifestations Gradual onset of weakness Anorexia Skin pigmentation and mucosa Nausea and vomiting and weigh loss Hypoglycemia Decrease levels of Na+ Low blood pressure Dehydration Decrease cardiac output, arrhythmia and potential cardiac arrest Treatment IV hydrocortisone sodium Glucose IV isotonic sodium chloride solution Cushing Syndrome Results from hypersecretion of glucocorticoids: cortisol and cortisone Characterized by “moon face” “buffalo hump” hirsutism pendulous abdomen with stria hyperglycemia osteoporosis weakness hypertension increased susceptibility to infections decreased resistance to stress mood swings Cushing Syndrome Cushing syndrome Etiology 1. Pituitary Cushing syndrome Anterior pituitary tumor (ACTH production) 2. Adrenal Cushing syndrome Adrenal adenoma 3. Paraneoplastic Cushing syndrome ACTH producing tumor (lung cancer Pancoast tumor) 4. Iatrogenic Cushing syndrome Exogenous administration of ACTH or cortisol Most common Cushing Syndrome Treatment: Surgical Resection Pasireotide (Signifor) somatostatin analog that inhibition of ACTH secretion Pheocromocytoma Uncommon benign tumor of the adrenal medulla Produces catecholamines (norepinephrine and epinephrine) Clinical manifestations: Severe headache Tachycardia and palpitations Diaphoresis and anxiety Hypertensive episodes Sweating and tremors Increased risk for myocardial ischemia, heart failure, renal ischemia, cerebrovascular accidents and sudden cardiac death Pheochromocytoma Rule of 10’s 10% occur in children 10% bilateral 10% occur outside the adrenal gland 10% are malignant Diagnosis Elevated urinary vanillylmandelic acid (VMA) and catecholamines* (urine and plasma) Treatment Surgical removal for control of patient’s blood pressure Multiple Endocrine Neoplasia Syndroms (MEN) Autosomal dominant inheritance Characterized by hyperplasia and tumors of endocrine glands MEN Type I (Werner syndrome) 3 P’s tumors on Parathyroid (hyperparathyroidism is most common finding) Pancreas Pituitary Multiple Endocrine Neoplasia Syndroms (MEN) MEN Type IIa (Sipple syndrome) Pheochromocytoma Medullary carcinoma of the thyroid (100 %) MEN Type IIb or III (William syndrome) Pheochromocytoma Medullary carcinoma of the thyroid Mucocutaneous neuromas (skin,eyelids, oral mucosa, GI, respiratory tract) A) Large, erythematous upper eyelid lesion on the lateral canthus of the right eye with a smaller upper eyelid margin lesion medial to the larger lesion. Posterior Pituitary Gland Oxytocin and antidiuretic hormone are synthesized in the hypothalamus and released into capillaries in the posterior pituitary Posterior Pituitary Neurohypophysis Histologically consists Pituicytes axon terminals hypothalamic neurosecretory cells bodies are localized in Supraoptic nuclei Paraventricular nuclei Oxytocin (OT) Primarily produced in Paraventricular Nuclei During and after delivery of a baby it mainly act on the uterus and mammary glands During lactation it stimulates the ejection of milk (let- down effect) in response of mechanical stimulus produced by sucking of the baby In non pregnant women and males its function is not clear but may be related to the feeling of sexual pleasure during intercourse Oxytocin Regulation Neuroendocrine reflex through stretch receptors in uterine cervix and letdown effect by nipple suckling during lactation OT also inhibits secretion of PIH Antidiuretic Hormone (ADH) Hormone produced in the Supra-optic nuclei It is main function is the control of body water This is possible through osmoreceptors in the hypothalamus ADH Osmoreceptors in the hypothalamus activate the synthesis of ADH ADH acts to retain body water on the kidneys and increase blood pressure with constriction of arterioles In the skin sweat glands decrease water loss Pancreas Is a combined endocrine and exocrine gland Pancreatic cells are arranged in groups or acini which perform exocrine functions Scattered in the parenchyma are groups of endocrine cells called pancreatic islets of Langerhan’s Pancreas The endocrine portion if composed of 4 different cells Alpha: produce glucagon Beta: produce insulin Delta: produce somatostatin F cells: produce pancreatic polypeptide Pancreas Delta cells Produce Somatostatin Inhibits both, glucagon and insulin release slows absorption of nutrients from GI F cells Produce Pancreatic polypeptide Inhibits contraction of gallbladder and secretion of digestive enzymes Glucagon Alpha cells Principal physiologic effect: Increase blood glucose levels conversion of glycogen into glucose in the liver (glycogenolysis) formation of glucose from lactic acid and amino acids (gluconeogenesis) This in turn will determine the secretion of Glucagon and insulin via a negative feedback Hyperglycemia inhibits glucagon Hypoglycemia inhibits insulin Insulin Beta cells Functions: Accelerates facilitated diffusion of glucose into the cells Speed conversion of glucose into glycogen (glycogenesis) Increase amino acid intake by increasing protein synthesis Slows glycogenolysis and gluconeogenesis Speeds lipogenesis (triglyceride breakdown) Diabetes Mellitus Chronic systemic disease Characterized by insulin deficiency or peripheral resistance Resulting in hyperglycemia Insulin-dependant diabetes mellitus (IDDM) Type 1 Lack of insulin due to autoimmune destruction of Beta cells Non-insulin-dependant diabetes mellitus (NIDDM) Type 2 Reduced insulin secretion Diabetes Mellitus Risk factors: A family history of DM Hispanic, Native American, African American, Asian American, or Pacific Islander descent Obesity Hypertension Dyslipidemia (high triglycerides or low HDL) Women with a history of gestational diabetes, birth of a child greater than 9 pounds Prior abnormal fasting glucose or glucose tolerance test Known vascular disease Polycystic ovarian syndrome (which results in insulin resistance) Age greater than 45 y/o Pre-diabetes State of abnormal glucose regulation with about 2 risk factors for developing diabetes and modestly increased risk for developing cardiovascular disease Normal Glucose levels (75-99 mg/dl) Diagnosis: Fasting: 100 to 125 mg/dL 2-hr OGTT: 140 to 199 mg/dL Type 2 DM Consists of an array of dysfunctions characterized by Hyperglycemia resulting from the combination of resistance to insulin action inadequate insulin secretion excessive or inappropriate glucagon secretion Type 2 DM Many patients with type 2 diabetes are asymptomatic Clinical manifestations include the following: Polyuria, polydipsia, polyphagia, and weight loss Blurred vision Lower-extremity paresthesias Yeast infections Type 2 DM Normal levels of glucose are defined as follows: Fasting: