DISORDERS OF ENDOCRINE SYSTEM Dr. Ibtesam G. Auda M.Sc. , Ph.D

*Feedback mechanisms *Down-regulation Responsiveness of target cell to hormone depends on: 1- Plasma concentrations *Feedback mechanisms - hypo- and hyper-secretion of hormone (ex: thyroid) 2- Number of receptors *Down-regulation - desensitization – prolonged exposure of high levels of hormone -example: Grave’s disease (autoimmune – thyroid) *Up-regulation -

Disorders of the Endocrine System Addison's disease Caused by hyposecretion of the hormones produced by the cortex of the adrenal gland Cretinism Condition resulting from a congenital deficiency of thyroid secretion or hypothyroidism Cushing’s syndrome Disorder that causes hyperactivity of the adrenal glands, which is triggered by the oversecretion of the pituitary hormone ACTH Diabetes insipidus From an acquired or inherited decrease in the antidiuretic hormone secreted by the pituitary Diabetes mellitus A disorder of carbohydrate, fat, and protein metabolism resulting from insufficient insulin production by the pancreas

Dwarfism Gigantism Graves’ disease Hyperparathyroidism Hypoglycemia Results from hyposecretion of the growth hormone of the pituitary gland, which has been caused by a tumor, infection, genetic factors, or trauma Gigantism An excessive growth of the long bones caused by hypersecretion of the somatotropic hormone Graves’ disease Caused by hyperthyroidism or thyrotoxicosis Hyperparathyroidism Causes hypercalcemia, an increased calcium blood level Hypoglycemia Results from increased insulin production by the pancreas Hypoparathyroidism A decreased secretion of parathyroid hormone that causes tetany Hypothyroidism Also called Hashimoto's disease, results from an insufficient production of thyroxine

I. Alterations of the hypothalamic - pituitary system Deficiency of hypothalamic hormones Variety of manifestations can be seen: - In adult women: menses cease- absence of GnRH In adult men: spermatogenesis is impaired-absence of GnRH ACTH response to low serum cortisol levels is decreased due to absence of CRH Hypothalamic hypothyreoidism - absence of TRH Low levels growth hormone - absence of GH regulatory hormones

Pituitary Disorders Hypersecretion of growth hormones acromegaly thickening of the bones and soft tissues problems in childhood or adolescence gigantism if oversecretion dwarfism if hyposecretion

Alterations of thyroid function Hyperthyroidism is a condition in which thyroid hormones (TH) exert greater-than-normal response Causes: - Graves disease - exogenous hyperthyroidism (iatrogenic, iodine induced) - thyroiditis - toxic nodular goiter - thyroid cancer metabolic effect of increased circulating levels of thyroid hormones   metabolic rate with heat intolerance and increased tissue sensitivity to stimulation by sympathetic division of the autonomic nervous system;

The major manifestations of hyperthyroidism enlarged thyroid gland - oligomenorrhea or amenorrhe due to hypothalamic or pituitary disturbances - impotence and decreased libido in men weight loss and associated increase in appetite due to increased catabolism - nausea, vomiting, anorexia, abdominal pain - excessive sweating, flushing, and warm skin - heat loss - hair faint, soft, and straight, temporary hair loss - nails that grow away nail beds

Hypothyroidism Hypothyroidism - deficient production of TH by the thyroid gland and/or action to the tissue A. Primary hypothyroidism is caused by 1. congenital defects or loss of thyroid tissue 2. defective hormone synthesis - due to: autoimmune thyroiditis, endemic iodine deficiency, antithyroid drugs B. Secondary hypothyroidism is caused by: 1. insufficient stimulation of the normal gland 2. peripheral resistance to TH

The major manifestations of hypothyroidism The individual develops a low basal metabolic rate, cold intolerance, slightly lowered basal body temperature A decrease in TH   production of TSH  goiter confusion, syncope, slowed thinking, memory loss, hearing loss, slow movements cerebellar ataxia -  androgen secretion in men  estriol formation in women due to altered metabolism of estrogens and androgens - anovulation, decreased libido spontaneous abortion  hart rate, enlarged heart  peripheral vascular resistance  cool skin dyspnoea - due to pleural effusions constipation, weight gain

Insulin from Beta cells reduce blood sugar Glucagon from Alpha cells increase blood sugar

Diabetes mellitus Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both. Diabetes mellitus may present with characteristic symptoms such as thirst, polyuria, blurring of vision, and weight loss. In its most severe forms, ketoacidosis or a non–ketotic hyperosmolar state may develop and lead to stupor, coma and, in absence of effective treatment, death.

The long–term effects of diabetes mellitus include progressive development of the specific complications of retinopathy with potential blindness, nephropathy that may lead to renal failure, and/or neuropathy with risk of foot ulcers, amputation, Charcot joints, and features of autonomic dysfunction, including sexual dysfunction. People with diabetes are at increased risk of cardiovascular, peripheral vascular and cerebrovascular disease.

Types of Diabetes 1-Type 1 Diabetes Mellitus Was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. Type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin that regulates blood glucose. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Type 1 diabetes may account for 5% to 10% of all diagnosed cases of diabetes. Risk factors for type 1 diabetes may include autoimmune, genetic, and environmental factors.

2-Type 2 diabetes Was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. Type 2 diabetes may account for about 90% to 95% of all diagnosed cases of diabetes. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce insulin. Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. Type 2 diabetes is increasingly being diagnosed in children and adolescents.

3- Gestational diabetes A form of glucose intolerance that is diagnosed in some women during pregnancy. Gestational diabetes occurs more frequently among African Americans, Hispanic/Latino Americans, and American Indians. It is also more common among obese women and women with a family history of diabetes. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant. After pregnancy, 5% to 10% of women with gestational diabetes are found to have type 2 diabetes. Women who have had gestational diabetes have a 20% to 50% chance of developing diabetes in the next 5-10 years.

Adrenal Disorders Cushing syndrome is excess cortical secretion causes hyperglycemia, hypertension, weakness, edema muscle and bone loss occurs with protein catabolism buffalo hump & moon face = fat deposition between shoulders or in face Adrenogenital syndrome (AGS) adrenal androgen hypersecretion accompanies Cushing syndrome causes enlargement of external sexual organs in children & early onset of puberty

Addison’s Disease Cause: Severe or total deficiency of adrenal cortical hormones – primarily cortisol and aldosterone. Due to destruction of adrenal cortex (autoimmune). • Symptoms: Fatigue, weakness in muscles, loss of appetite, weight loss. Blood pressure is low → lightheadedness. Irritability and depression.