Endocrine+and+Metabolic+System+disorder.2023.pdf

Endocrine and Metabolic System disorder KYCO Ayesha Ghayur Learning Objectives • Compare and contrast the pathophysiology of type 1 and type 2 diabetes mellitus regarding the pathogenesis, typical age of onset, and the role of insulin • Understand the pathophysiology of diabetes insipidus and its...

Endocrine and Metabolic System disorder KYCO Ayesha Ghayur Learning Objectives • Compare and contrast the pathophysiology of type 1 and type 2 diabetes mellitus regarding the pathogenesis, typical age of onset, and the role of insulin • Understand the pathophysiology of diabetes insipidus and its clinical manifestation • Define hypothyroidism and hyperthyroidism and list the common causes of these • Discuss the role of parathyroid hormone and list the consequences of hyperparathyroidism and hypoparathyroidism • Define Addison’s disease and its clinical consequences • Describe Cushing syndrome • Be able to describe the pathogenesis of pheochromocytoma and its presentation Diabetes Mellitus The Pituitary Gland Thyroid Disorders Parathyroid Hormone Adrenals • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla The Islet of Langerhans 70-80% glucAgon BIn SaD (suppresses insulin, glucagon, GI, endocrine, exocrine, pancreatic, and pituitary secretions) Metabolic Actions Of Insulin Classification of Diabetes Mellitus Type 1: • ∼ 5% of all patients with diabetes • Childhood onset; but can occur at any age; peaks at age 4–6 years and 10–14 years • Highest prevalence in non-Hispanic whites Type 2: • The estimated prevalence in the US is 9.3%. • 1.4 million new cases of diabetes are diagnosed each year in the US • Adult onset: typically > 40 years • Highest prevalence in Hispanics, Native Americans, Asian Americans, African Americans Normal blood glucose: 70 to 120 mg/dL Clinicians should aim to achieve an HbA1c level between 7% and 8% in diabetics Copyrights apply Type 1 Diabetes • Autoimmune disease • Genetic susceptibility & environmental trigger →autoimmune destruction of beta cells by the T cells • Destruction of beta cells  production of autoantibodies (Anti-glutamic acid decarboxylase antibody) targeting beta-cells progressive destruction of beta cells • Destruction of 80–90% of β cells  absolute insulin deficiency  hyperglycemia and DM • Polyuria, Polydipsia, polyphagia Type 1 Diabetes • Association with other autoimmune conditions • Hashimoto thyroiditis • Celiac disease Because of the high prevalence of thyroiditis and its potential clinical impact, all children with T1DM should be screened regularly for thyroid disease celiac disease J Clin Invest. 2021;131(8):e142242 https://doi.org/10.1172/JCI142242 Type 2 DM (1) Decreased ability of peripheral tissues to respond to insulin (insulin resistance) (2) Beta cell dysfunction  inadequate insulin secretion 3) Decrease in the number of insulin receptors Strong genetic association (up to 90% concordance in monozygotic twins) Polyuria, Polydipsia, polyphagia Insulin Resistance What is the primary pathological mechanism underlying type 1 diabetes? A. Insulin resistance B. Autoimmune destruction of pancreatic beta cells C. Excessive insulin production D. Genetic mutations in insulin receptors Pathology of Type 1 DM Pathology of Type 2 DM Autoimmune “insulitis” Amyloid deposition in the islets  beta cell apoptosis Breakdown in self-tolerance T lymphocytes infiltration in the islets Antibodies against beta cells and insulin Insulin resistance and failure of compensation by beta cells Beta cell depletion islet atrophy Mild beta cell depletion Autoimmune insulitis. Arrows points to inflammation Amyloid accumulation in islet of Langerhans (congo-red stain) Type 1 Diabetes Type 2 Diabetes Definition Autoimmune Insulitis Insulin resistance  less sugar being removed from the blood Etiology Genetic, environmental and autoimmune factors, idiopathic Genetic, obesity (central adipose), physical inactivity HLA association HLA DR3 and DR4 None Commonly Afflicted Groups Children/teens Adults, elderly, certain ethnic groups Common physical attributes found Mostly Normal or Thin Mostly Overweight or Obese Insulin Too little or no insulin Insulin resistance Percentage of occurrence 5% -10% 90% - 95%-of total cases Affected age group Between 5 - 25 Usually >40 Treatment Insulin Injections, dietary plan, regular check up of blood sugar levels, daily exercise Diet, exercise, weight loss, and in many cases medication to release insulin from the pancreas. Insulin Injections may also be used Onset Rapid (weeks) Slow (years) Which of the following statements accurately describes a key difference between type 1 and type 2 diabetes mellitus in terms of their underlying pathology? A. Both type 1 and type 2 diabetes are characterized by insulin resistance. B. In type 1 diabetes, there is an autoimmune destruction of pancreatic beta cells, leading to absolute insulin deficiency, while in type 2 diabetes, pancreatic beta cells function normally initially C. Obesity is a common feature in individuals with type 1 diabetes, but not in those with type 2 diabetes. D. Type 2 diabetes typically presents at a younger age compared to type 1 diabetes.usually Case • Bella is a 56-year-old female with type 2 DM. Her previous family doctor has told Bella that she has to see her eye doctor once a year. She lives in a remote area and has to travel a long distance for that. She says she can see fine and asks you if she can stop seeing the eye doctor every year. • What would you recommend to her and why? • Discuss the pathophysiology of two primary types of retinopathy in diabetics Diabetic Retinopathy (DR) • The most common cause of visual impairment and blindness in patients aged 25–74 years in the US • In the United States, it is estimated that at least 4.2 million adults have DR, and 655,000 have vision-threatening DR • Manifestations: • Retinopathy • Cataract formation • Glaucoma • Frequent eye exams: • T1DM: Start 5 years after diagnosis (do yearly or more frequently if needed) • T2DM: Start at the time of diagnosis (do yearly or more frequently if needed) Pathogenesis Of Diabetic Retinopathy (DR) • Pericyte loss outpouching of weakened capillaries  Micro aneurysms • Weakened blood vessels rupture dot/ blot hemorrhages • Damaged and leaky blood vessels  leakage of plasma proteins  Hard exudates • ↓Blood supply  areas of infarction  cotton wool spots (iSchemia Soft exudates) • Retinal ischemia  upregulates VEGF  irregular and easily friable neovascularization • New vessels  bleed, and fibrosis  retinal traction Diabetic Retinopathy Non proliferative DR Proliferative DR Earliest clinical manifestation (background retinopathy), reversible Rapid progression to blindness Microaneurysms (red dots) Retinal ischemia  neovascularization of the retinal vessels due to hypoxia-induced overexpression of VEGF in the retina Occluded, dilated, tortuous vessels Fragile vessels  vitreous hemorrhage Intraretinal hemorrhage Subsequent fibrosis and tractional retinal detachment Soft exudates (iSchemia, cotton wool spots/infarcts) Hard exudates (plasma proteins and lipid deposits) Macular edema Retinal thickening and edema involving the macula. It can occur during nonproliferative or proliferative retinopathy What does A refers to What does B refers to Soft iSchemia Copyrights apply B A 55-year-old male presents to the ophthalmology clinic with a complaint of blurry vision in both eyes. He has a history of type 2 diabetes mellitus for the past 10 years, which has been managed with oral hypoglycemic agents. On examination, his visual acuity is 20/40 in the right eye and 20/30 in the left eye. What is the most likely finding in this patient's fundus examination related to diabetic changes? A. B. C. D. Black spots on retina Swollen optic disc Retinal hemorrhages Drusen Which of the following is the earliest manifestation of diabetic retinopathy? A. B. C. D. Proliferative diabetic retinopathy Macular edema Nonproliferative diabetic retinopathy Vitreous hemorrhage What role does Vascular Endothelial Growth Factor (VEGF) play in the context of eye vascularization and eye diseases? A. VEGF inhibits abnormal blood vessel growth in the eye. B. VEGF promotes the growth of blood vessels in the eye. C. VEGF has no impact on eye vascularization. D. VEGF is only associated with non-vascular eye diseases Diabetes Mellitus The Pituitary Gland Thyroid Disorders Parathyroid Hormone Adrenals • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla The Pituitary Gland The Pituitary Gland • Disruption of the hypothalamic-pituitary axis: • Primary (disorders of the Peripheral endocrine gland) • Secondary (pituitary dysfunctions), and • Tertiary (hypothalamic disorders) Anti-Diuretic Hormone (ADH) Anti-Diuretic Hormone (ADH) • ADH= Anti Diuretic Hormone • ADH= Always Digging Holes (to reabsorb water) Posterior Pituitary • Dehydration releases ADH  kidney  reabsorption of water ADH ADH ADH Deficiency  Diabetes Insipidus • Causes of ↓ ADH: • Including head trauma • Tumors • Surgical procedures • ↓ ADH  inability of the kidney to resorb water from the urine  excess diuresis  Diabetes Insipidus • Clinical manifestations: • Large volumes of dilute urine • ↑ Serum sodium • ↑ Thirst Which of the following statements best characterizes Diabetes Insipidus (DI)? A. DI is a form of diabetes caused by a deficiency of insulin. B. DI is a metabolic disorder resulting from excessive sugar intake. C. DI is a condition characterized by excessive thirst and frequent urination due to inadequate ADH production or response. D. DI is a type of diabetes caused by an autoimmune reaction against pancreatic beta cells. The Hypothalamic Pituitary axis • The hypothalamus regulates the secretion of hormones from the anterior pituitary gland by releasing stimulatory hormones F: FSH • Corticotropin-releasing hormone, CRH L: LH A: ACTH • Growth hormone-releasing hormone, GHRH T: TSH • Gonadotropin-releasing hormone, GnRH P: Prolactin G: GH • Thyrotropin-releasing hormone (TRH) • Inhibitory factors (growth hormone inhibitory hormone, GIH or somatostatin; prolactin inhibitory factor, PIF or dopamine) • These, in turn modulate the release of six hormones from the anterior pituitary Anterior Pituitary Disease 1. Hyperpituitarism causes • Usually adenoma 2. Hypopituitarism causes • Ischemic injury, • Surgery, radiation • Inflammatory reactions 3. Local mass effects • Non-functional pituitary adenomas  compress neighboring parenchyma  hypopituitarism • Compress decussating fibers in the optic chiasm  Visual field defects • Expanding intracranial mass,  elevated intracranial pressure  including headache, nausea, and vomiting Associated Syndrome Pituitary Cell Type Hormone Lactotroph Prolactin • Galactorrhea and amenorrhea (in Somatotroph GH • • Most common hyperfunctioning pituitary adenoma Second most common females) • Gigantism (children, before the epiphyses, closes) • Acromegaly (adults, after the epiphyses close) • DM Note the coarse facial features and moderate prognathism (Reproduced with permission from Richard P. Usatine, MD.) Key Features • • • Prolactinoma Diagnosed earlier in females due to amenorrhea Prolactin inhibits FSH and LH  hypogonadism, infertility, and decreased libido • • Manifestations may be subtle  late presentation GH excess  stimulates the hepatic secretion of insulin-like growth factor 1 (IGF1)  induce overgrowth of bones and muscle GH  peripheral insulin resistance  DM Increased risk for gastrointestinal cancers (colon cancer) • • Separation of the teeth in acromegaly Normal Growth Hormone Function Growth Hormone • GH excess before the epiphyses closes  gigantism • This condition is characterized by a generalized increase in body size, with disproportionately long arms and legs • GH excess after the epiphyses closes  acromegaly • Growth is most conspicuous in soft tissues, skin, viscera, and the bones of the face, hands, and feet. • Enlargement of the jaw results in its protrusion (prognathism ) • Broadening of the lower face and separation of the teeth. • The hands and feet are enlarged, and the fingers are broad and sausage-like. • Develop slowly over decades • GH excess insulin resistance  diabetes mellitus A 45-year-old patient presents to the endocrinology clinic with a complaint of gradual changes in appearance and facial features over the past few years. On examination, you notice coarse facial features, enlarged hands and feet, as well as skin thickening. The patient also mentions experiencing headaches and joint pain recently. Laboratory tests reveal elevated levels of insulin-like growth factor 1 (IGF-1). What is the most likely diagnosis for this patient. A. B. C. D. Cushing's syndrome Hyperthyroidism Acromegaly Addison's disease Which hormone is primarily responsible for the characteristic clinical features seen in acromegaly? A. B. C. D. Thyroid-stimulating hormone (TSH) Prolactin Growth hormone (GH) Adrenocorticotropic hormone (ACTH) Diabetes Mellitus The Pituitary Gland Thyroid Disorders Parathyroid Hormone Adrenals • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla Thyroid Disorders Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) Graves’ disease (Hyperthyroidism) Age Age 45- 65 years Females > males Age 20 and 40 years Females > males Causes Autoimmune destruction of the thyroid gland Autoimmune stimulation of the thyroid gland Goiter Painless goiter Positive TPO (thyroid peroxidase antibody) autoantibodies Painless goiter Thyroid-stimulating immunoglobulin (TSI) autoantibodies Thyroid Status First Hyperthyroid later predominantly hypothyroid Hyperthyroid Pathologic findings Dense lymphocytic infiltrate The thyroid gland is enlarged with diffuse hypertrophy & hyperplasia Labs ↑ TSH ↓ T4 and T3 ↓ TSH ↑ T4 and T3 Symptoms • • • • • • • • • • • • • • Eye Findings Fatigue, Constipation Increased sensitivity to cold Pale, dry skin A puffy face Unexplained weight gain Excessive or prolonged menstrual bleeding Depression Fast and irregular heartbeat frequent bowel movements or diarrhea Heat intolerance Nervousness or irritability Trembling hands Trouble sleeping Weight loss Exophthalmos (40% of patients)  abnormal protrusion of the eyeball. Sympathetic overactivity  characteristic wide, staring gaze and lid lag Goiter = Large thyroid gland. Doesn’t tell us about its function. It can be hypothyroid or hyperthyroid Graves Disease Autoantibody TSI Thyroid-stimulating immunoglobulin (TSI) Binds to the TSH receptor and mimics the action of TSH Increased release of thyroid hormones Relatively specific for Graves disease Graves Disease Graves' dermopathy a skin condition characterized by red, swollen skin Proptosis or Exophthalmos Also Called Thyroid Eye Disease: a buildup of GAGs (glycosaminoglycans) in the muscles and tissues behind the eyes Diabetes Mellitus The Pituitary Gland Thyroid Disorders Parathyroid Hormone Adrenals • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla Functions Of PTH- RIB PTH= Phosphate Trashing Hormone PTH  RIB  ↑Calcium, ↓Phosphate https://consultqd.clevelandclinic.org/phosphorusbinders-the-new-and-the-old/ Hyperparathyroidism • Primary hyperparathyroidism: An autonomous, spontaneous overproduction of PTH • Adenoma—85% to 95% • Primary hyperplasia (diffuse or nodular)—5% to 10% • Parathyroid carcinoma—1% • Secondary & tertiary hyperparathyroidism • Secondary or reactive phenomena: • Chronic renal insufficiency Primary hyperparathyroidism • https://www.parathyroid.com/parathyroid-disease.htm • Primary hyperparathyroidism: An autonomous, spontaneous overproduction of PTH • Adenoma—85% to 95% • Primary HPTH  ↑ Calcium • Usually asymptomatic & the most common cause of hypercalcemia overall • Renal issues: Stones and kidney failure • Heart: Arrythmias • Nervous system: Fatigue • Increased osteoclast activity  bone resorption, and osteopenia • Treatment: surgical removal Hypercalcemia Memory tool Signs and Symptoms Causes Painful Bones Painful bones, fractures, Renal Stones Kidney Stones  renal failure Abdominal Groans GI symptoms: Nausea, Vomiting, Constipation, Indigestion Psychiatric Moans Effects on nervous system: lethargy, fatigue, memory loss, psychosis, depression Polyuria. Throne refers to the toilet you sit on as a throne! Sitting on Throne Calcific Band Keratopathy • Corneal degeneration • Composed of fine dust-like calcium deposits in the: • Sub-epithelium • Bowman's layer and • Anterior stroma Band-shaped, horizontal, gray-white, opacity in the interpalpebral fissure with involvement of the visual axis. A moderately dense nuclear sclerotic cataract is present Hypoparathyroidism • Less common than hyperparathyroidism The major causes : 1. Surgical ablation 2. Congenital absence 3. Autoimmune hypoparathyroidism Clinical Manifestations of Hypoparathyroidism • Decreased plasma Ca++ and increased plasma PO4 • Acute Hypocalcemia  increased neuromuscular irritability • Chvostek sign—tapping of facial nerve (tap the Cheek)  contraction of facial muscles • Trousseau sign—occlusion of brachial artery with BP cuff (cuff the Triceps) carpal spasm • Cardiac arrhythmias Hypoparathyroidism and the Eye • Cataract • Blurry vision A 35-year-old patient presents to the clinic with constipation, kidney stones, hyporesponsive reflexes and skeletal muscle weakness. You diagnose him with hypercalcemia. Which of the following could have caused the hypercalcemia? A. B. C. D. Hyperparathyroidism Hypoparathyroidism Hypothyroidism Hyperthyroidism Diabetes Mellitus The Pituitary Gland Thyroid Disorders Parathyroid Hormone Adrenals • Type 1 Diabetes • Type 2 Diabetes • Type 1 vs Type 2DM • • • • The Hypothalamic Pituitary axis Anti-Diuretic Hormone (ADH) and Diabetes Insipidus Prolactinoma Growth Hormone • Hypothyroidism vs Hyperthyroidism • Chronic Lymphocytic (Hashimoto) Thyroiditis (Hypothyroidism) • Graves disease (Hyperthyroidism) • The function of Parathyroid Hormone (PTH) • Hyperparathyroidism • Hypoparathyroidism • Cushing Syndrome • Adrenal Insufficiency • Adrenal Medulla Adrenals-Cushing Syndrome Cushing syndrome has a cushion of steroids Zones Hormones Produced Controlled by Hyper Functioning Hyperaldosteronism Cushing syndrome Virilizing syndromes (Masculinization) Pheochromocytoma GFR & Salt, Sugar, Sex, Cushing Syndrome Adrenal Cortex Adenoma Adrenocortical adenoma: solitary & well circumscribed Early manifestations of Cushing syndrome • Hypertension • Increased peripheral vascular sensitivity to adrenergic agonists • Weight gain • Characteristic redistribution of adipose tissue  truncal obesity, “moon facies,” and accumulation of fat in the posterior neck and back (“buffalo hump”) called dorsocervical fat pad x • Skin thinning and easy bruising Consequence of excess corticosteroid • ↑Blood sugar  secondary diabetes • Loss of proteins like collagen  thin and fragile skin, easily bruised • ↑ Bone loss  ↑ fracture risk • ↑ Androgen  acne and ↑ hair growth in females • Immune suppression • Mood swings, depression A 55-year-old female presents to the clinic with central obesity, loss of muscle mass, and hypertension. Which of the following could also be a symptom? A. B. C. D. Increase bone loss Calves hypertrophy Palpitations Proptosis Adrenal Insufficiency Adrenocortical Insufficiency Zones Hormones Produced Controlled by Hyper Functioning Hyperaldosteronism Cushing syndrome Virilizing syndromes (Masculinization) Pheochromocytoma GFR & Salt, Sugar, Sex, Adrenal Insufficiency AI • Primary AI: Primary adrenal disease also called Addison's disease • Secondary AI: ACTH deficiency • Tertiary AI: CRH deficiency Symptoms of Addison's disease Cortisol Deficiency: • Extreme fatigue • Weight loss and decreased appetite • Low blood sugar (hypoglycemia) Aldosterone deficiency: • Salt craving • Low blood pressure, even fainting • Nausea, diarrhea or vomiting (gastrointestinal symptoms) Androgen deficiency: • Body hair loss or sexual dysfunction in women ACTH Excess: • Darkening of your skin (hyperpigmentation) Autoimmune most important cause Adrenal Insufficiency- Treatment • Cortisol is replaced with a corticosteroid, most often hydrocortisone • To replace aldosterone fludrocortisone is given which helps balance the amount of sodium and fluids in your body A 47-year-old man presents with slowly progressive fatigue, weakness, and skin hyperpigmentation. Serologic studies show low levels of cortisol and aldosterone. What is the most common cause of this A. Abdominal trauma B. Autoimmune adrenal destruction C. Disseminated tuberculosis infection D. Tumor of the pancreas E. Pituitary damage Adrenal Medulla Zones Hormones Produced Controlled by Hyper Functioning Hyperaldosteronism Cushing syndrome Virilizing syndromes Pheochromocytoma GFR & Salt, Sugar, Sex, Adrenal Medulla • Has Chromaffin (neural crest cells) • Pheochromocytomas are neoplasms of chromaffin cells • Pheochromocytoma  secrete catecholamines (epinephrine& norepinephrine) Pheochromocytoma • Surgically correctable form of hypertension (paroxysmal episodes) • 10% are extra-adrenal • 10% are malignant • 10% in children (usual age group 40-60) • 25% are due to hereditary (germline mutations): • RET gene Clinical Features • Episodic hypertension Sudden release of catecholamines  HTN • Diaphoresis • Heart palpitations, tachycardia • Pallor, anxiety • Abdominal pain and nausea • Weight loss due to increased basal metabolism 5 important problems (5 P’s) of Pheochromocytoma: • Increased blood Pressure, • head Pain (headache), • Perspiration, • Palpitations, and • Pallor • Papilledema Pheochromocytoma Treatment: Surgical removal The tumor is enclosed in a capsule and demonstrates areas of hemorrhage What cells are responsible for secreting catecholamines? A. B. C. D. Chromaffin Langerhans Alpha cells Parietal cells A patient is diagnosed with pheochromocytoma. you know that the patient will present with hypertension, sweating, and palpations due to excessive catecholamine production from the? A. B. C. D. Adrenal Cortex Adrenal Zona Fasciculata Adrenal Medulla Adrenal Glomerulosa Questions