Week 12 & 13 Endocrine Disorders Notes PDF

Week 12 & 13 Endocrine Disorders - Doris Pierce Intro- Causes of endocrine dysfunction Primary - Originate in the glands responsible for producing the hormone Secondary - Caused by defective levels of stimulating hormones from pituitary gland but normal endocrine gland function Tertiary cause...

Week 12 & 13 Endocrine Disorders - Doris Pierce Intro- Causes of endocrine dysfunction Primary - Originate in the glands responsible for producing the hormone Secondary - Caused by defective levels of stimulating hormones from pituitary gland but normal endocrine gland function Tertiary cause - result from hypothalamic dysfunction, affecting pituitary function All forms of endocrine disturbance can impact oral health and the management of dental patients safety Pituitary disorders Growth hormone deficiency In children - short stature and immature facial features - Impacts linear bone growth before epiphyseal fusion - delayed puberty/sexual development but normal intelligence - impacts Mandibular and maxillary growth - malocclusion associated with smaller dental arches - retarded tooth root - delays in tooth eruption In adults - primarily affects metabolism - destruction of bone cells (fractures and osteoporosis) Growth hormone excess Pituitary gigantism - nearly always caused by an adenoma (tumor of the pituitary gland) secretes GH - Abnormal Large height and weight but normal body proportions - Abnormally large hands and feet - facial features can include … enlarged forehead and jaw, pronounced underbite, spreading of teeth, enlarged tongue, nose, and lips - Hyperglycaemia and overactive Beta cells in pancreas - type 2 diabetes - death in early childhood Acromegaly - person doesn’t grow taller but bones become thicker and more deformed (more likely in hands, feet, and membranous bones) - lower jaw protrusion, hunchback - enlarged soft tissue organs including tongue, liver, heart, and kidneys - Increased risk of bronchitis, diabetes, and heart failure Characteristic craniofacial changes in acromegaly - Mandibular prognathism and thickening - increased thickness and height of alveolar process - spacing and flaring of anterior teeth with associated malocclusion, enlargement of tongue - Spiky exostosis-like growths in the alveolar bone as an early sign of acromegaly - Dentists are well placed to detect the insidious onset of these craniofacial changes Antidiuretic hormone deficiency - ADH stimulates water reabsorption in kidneys in response to increased plasma osmolarity - ADH deficiency causes diabetes insipidus (excessive water loss) - xerostomia is the leading oral issue Thyroid disorders Hyperthyroidism Causes - Graves’ disease = autoimmune disorder associated with thyroid-stimulating antibodies - overactive thyroid nodules or thyroiditis - Too much iodine - Non-cancerous tumor of the pituitary Common signs and symptoms - excessive sweating and increased temperature in skin - Tachycardia or irregular heart rate - tiredness, muscle weakness but difficulty sleeping - twitching, anxiety, nervousness - Exophthalmos (protruding eyes with lid retraction) - Increased sensitivity to catecholamines Hyperthyroidism (acquired) - caused by sugary drugs such as lithium, excessive or lack of iodine - Hashimoto thyroiditis most common causes… autoimmune disease where an autoimmune reaction may completely destroy the thyroid gland (more common in women) - Impact related to hypometabolism (fatigue, weight gain despite loss of appetite, cold intolerance…etc, affects almost all organ systems)  - severely advances form = myxoedema (puffy appearance) can lead to myxedema crisis Hypothyroidism (congenital) - also known as cretinism - partial or complete loss of thyroid gland function in infants - common cause is shortage of iodine in mothers diet (15-20% genetic causes) - if untreated, can lead to impaired neurological function, stunted growth, and physical deformities - thickening of lips and macroglossia due to increased accumulation of subcutaneous mucopolysaccharides - In older children and adults; slowing metabolic processes and myxoedema down, can range from mild to life threatening Parathyroid glands Hyperparathyroidism - Usually caused by a tumor or hyperplasia of the gland - key sign is bone lesions associated with excessive osteoclast activity - Malocclusion due to drifting with define spacing of teeth may be one of the first signs - higher risk of bone fracture Hypoparathyroidism - Mainly affects nerve and muscle activity - enamel hypoplasia, delayed tooth eruption, and may be multiple unerupted teeth - more prone to dental caries Adrenal disorders Addison disease - Primary adrenal cortical insufficiency, caused by autoimmune disorder, infection(TB), trauma, cancer or hemorrhage Glucocorticoid deficiency - poor stress tolerance, hypoglycaemia, lethargy, weakness, nausea, vomiting Mineralocorticoid deficiency - dehydration, low blood pressure, fatigue  - High ACTH levels in primary adrenal insufficiency = skin hyperpigmentation (darker) Addison disease (treatment) - relies on hormone replacement, but long term corticosteroid therapy (>14 days) can suppress adrenal function (secondary adrenal insufficiency) - limited ability of adrenal cortex to deal with stress - predisposing factor of acute adrenal insufficiency (addisonian/adrenal crisis) - stress reduction protocol, effective anesthesia and postoperative analgesia are very important in these situations - supplemental doses of corticosteroids can be used to help the body cope with stress Cushing syndrome - Disorder resulting from long term excess cortisol ACTH dependent hypercortisolism from - hypersecretion of ACTH by the pituitary gland due to pituitary adenoma (Cushing disease) - secretion of ACTH by a non pituitary tumor, such as small cell lung carcinoma or a carcinoid tumor (ectopic ACTH syndrome) ACTH independent hypercortisolism from - Therapeutic administration of exogenous corticosteroids for treatment of inflammatory diseases (most common) - Adrenocortical adenomas or carcinomas Cushing syndrome signs are the exaggerated actions of cortisol - Altered fat metabolism and abnormal fat distribution - rounding the puffiness of the face (moon face) - protein breakdown and muscle wasting - thin and easily bruising skin - Osteoporosis due to calcium resorption - Deranged glucose metabolism - hyperglycemia and increased insulin requirement (may lead to diabetes) - Immune suppression - Increased gastric acid secretion (gastric ulceration) - Emotional and sleep disturbance (depression-like) Dental concerns - immune suppression and increased risk of infection, as well as alveolar bone loss and impaired wound healing - Comorbidities such as obesity, osteoporosis, and diabetes may influence periodontal attachment apparatus Diabetes Mellitus  - Metabolic condition from imbalance between the body need for glucose and the availability/effectiveness of insulin - Lack of secretion or reduced activity of insulin - compromised transport of glucose into fat and muscle cells — > blood sugar levels remain high - Increased fat and protein breakdown to compensate and provide an energy source for these cells - Discovery of insulin in 1922 transformed from being a fatal disease into a manageable condition Type 1 diabetes - type 1 diabetes prone to ketoacidosis - free fatty acids converted to ketone in the liver - insulin normally inhibits lipolysis and release of free fatty acids from adipocytes - Without insulin, ketone conversion happens in an uncontrolled manner, leading to ketoacidosis - Need insulin replacement to stop fat and protein catabolism and prevent ketoacidosis Type 2 diabetes - Heterogeneous condition primarily considered a lifestyle disease (not associated with autoantibodies) - disorder of both insulin levels (beta cell dysfunction) and insulin function (insulin resistance) —> hyperglycaemia and wide-ranging complications - Glucosuria - Polyuria due to osmotic pull of glucose in urine and/or diuretic effect of certain medications - Inflammatory process in dysfunctional visceral adipose tissue - systemic inflammation and insulin resistance - upregulated insulin production in beta cells to overcome diminished insulin action - Over time, increasing beta cell dysfunction and exhaustion - some develop absolute insulin deficiency and require insulin therapy Other specific types of diabetes - Formerly known as secondary diabetes and describes diabetes associated with other conditions and syndromes may occur with - pancreatic disease - endocrine disorders, such as GH excess - environmental agents, including viruses and chemical toxins - various drugs, including diuretics and antiretroviral therapy - Polycystic ovarian syndrome - pregnancy (gestational diabetes) Diabetes diagnosis and treatment Diagnostic tests - Blood tests based on fasting or casual plasma glucose levels or a glucose challenge test - Capillary blood tests valuable for near patient testing in diabetic patients (normal is 4- 6mmol/L) - Glycated hemoglobin test (HbA1c) - how much glucose is bounded to red blood cells - indirect measure of average blood sugar level over past 2 to 3 months - lifespan of RBC around 120 days - assesses long term glycemic control Lifestyle management - desired outcome for both type 1 and 2 diabetes - normalise blood glucose levels Type 1 - food intake and used as a basis for adjusting insulin replacement therapy - Good routine required for balance between insulin administration, carbohydrate intake, and glucose levels Type 2 - Diabetics need to target glucose, lipid, and blood pressure goals, as well as weight loss if required Drug management - Incretins - gastrointestinal peptides with blood glucose-lowering effects - reduced levels in diabetics - Glucagon-like peptide-1 (GLP-1) and glucose dependant insulinotropic polypeptide (GIP) - Stimulate insulin secretion, slow gastric emptying, and reducing appetite and energy intake Osteoporosis and PCOS Osteoporosis - Oestrogens normally promote apoptosis (death) of osteoclasts - Decrease in bone mass with diminishing hormone levels, particularly after menopause - Bone resorption by osteoclasts outpaces bone deposition by osteoblasts - Demineralisation can begin at 30 in females, 60 in males other contributing factors - poor diet - lack of exercise - smoking - diabetes - osteoporosis medication, including bisphosphonates and RANK ligand inhibitors decrease osteoclast activity/bone resorption - Problem of medication-related osteonecrosis of the jaw (MRONJ) associated with the use of these medications - Osteonecrosis; non-healing exposed bone in the maxillofacial region, which may occur following oral surgery - MRONJ pathophysiology not completely elucidated - tooth extraction a “common” factor but teeth commonly had existing periodontal or periodical disease - Greater risk with IV antiresorptive medications as opposed to oral and with chronic use Exposed necrotic bone in the left anterior maxilla Polycystic ovarian syndrome (PCOS) - PCOS is most common endocrine disorder among women of reproductive age (26% in western societies) - substantial negative effects on metabolic, psychological, and cardiovascular health - Irregular or absent menstrual periods, infertility, and symptoms like acne, excess hair growth, and/or unintended weight gain - associated with other comorbidities (insulin resistance, obesity, cardiovascular disease, and periodontal disease) - mechanisms include altered secretion of GnRH, defect in androgen synthesis, and development of insulin resistance. Presence of many small, fluid filled sacs or cysts inside ovaries in case of PCOS Endocrine disorders wrap up lecture Thyroid disorders - Oral manifestations Hypothyroidism in dental practice considerations for dental practice - Generally, tolerate dental treatment well - poor cardiovascular health may be primary consideration - Delayed wound healing due to decreased fibroblast activity (susceptibility to infections) - sedatives (benzodiazepines) and opioids to be used with caution (increased sensitivity to their actions) Hyperthyroidism in dental practice - patients more prone to caries and periodontal disease, as well as other oral problems, such as burning mouth syndrome - Patients very sensitive to adrenaline-containing products - hypertensive crisis - increased levels of anxiety - stressful dental procedures can elicit life-threatening thyrotoxic crisis (caused by high thyroid hormone levels) - Particularly for invasive dental therapy, best to liaise with physician to see how well controlled condition is Parathyroid glands - oral manifestation Pregnancy - oral health - Pregnancy gingivitis most common - mainly due to estrogen and progesterone enhancing the inflammatory response - possible painless tumor - like growths - pregnancy granulomas (epulis gravidarum) - normally regress following parturition increased risk of caries mainly due to - snacking - reduced oral hygiene (gag reflex, fatigue) - morning sickness - hormone induced xerostomia Avoidance of dental visits mostly due to concern about the babies health Pregnancy considerations - routine dental care is safe and benefits both mother and child - weeks 14-20 most comfortable times for visits - drug use is always a concern, excessive can also be a concern during the first trimester - Good safety records for lignocaine and mepivacaine - few antibiotics (amoxicillin) and antifungal (nystatin) may be used - Paracetomol is preferred analgesic - best to avoid NSAIDs during 1st and 3rd trimesters - sedation should be avoided - if required nitrous oxide may be used with medical consultation Menopause - declining levels of estrogen and progesterone impact oral health - use of hormone replacement therapy is controversial  - good oral hygiene practice essential Polycystic ovarian syndrome - Dental concerns - low grade chronic systemic inflammation - possible link to periodontal disease - gingivitis difficult to treat due to underlying inflammation - Altered sex hormones may impair epithelial barrier to bacterial injury or compromise collagen maintenance and repair - decline of oestrogen with aging - risk of bone loss density - Suspect POCS if patient struggle with receding gums, difficulty chewing and tooth loss despite good oral hygiene - Good oral hygiene important in managing symptoms of PCOS - Prevention includes special care of teeth and gums - brushing, flossing, antiseptic mouthwash, and bi-annual dentist visits Diabetes in the dental practice Oral signs of diabetes - xerostomia due to polyuria and dehydration - increased rate and severity in periodontal disease in type 1 and 2 diabetes - increased incidence of root caries - due to increased root exposure from periodontitis combined with xerostomia - Xerostomia + high salivary glucose + impaired immune function are more prone to oral infections and mucosal disorders (lichen planus, burning mouth syndrome) - vascular and immune dysfunctions - poor wound healing  - Good oral health management essential and may improve diabetic control AGEs and periodontal disease in diabetes - Advanced glycation end products (AGE); proteins or lipids that become glycated after exposure to sugars - pro inflammatory mediators and link diabetes to periodontal disease (excessive formation in diabetes) - AGEs bind to receptors and accumulate in periodontal tissue that leads to accumulation of inflammatory mediators - cascade of cytokine upregulation, further increasing levels of pro-inflammatory cytokines - inflammation - mediated activation of osteoclasts and destruction or oral tissues - Uncontrolled diabetes strongly correlated to increased alveolar bone loss - Main element responsible for the development. Of micro and macrovascular complications in DM Pharmacokinetics - Dr.Miller Pharmacokinetics intro Pharmacology - the study of the effects of drugs on the function of living systems Components of pharmacology - Pharmacokinetics Pharmacodynamics - drug has to interact with target - Has to reach target - Therapeutic concentration Phases of drug action - Liberation - Absorption - Distribution - Metabolism - Excretion - Acronym - LADME Absorption - drugs have to enter circulation - Barriers (epithelial lining, and endothelial lining of blood vessels) - Cell membrane of target cells - Mostly passive diffusion between cells (concentration gradients) Absorption Affected by - formulation - Administration route - Surface area - Blood flow - Facilitated transport/receptors - Solubility - pKa and environment pH Routes of administration Oral or rectal - most common Intravenous - 100% absorption Percutaneous - skin Intramuscular - muscle Intrathecal - CSF Inhalation - lungs Other ways include - Ocular - Buccal - Sublingual - Transdermal Drugs - small molecules - Chemical structures (weak acids, bases, ionised and non-ionised) - Proportions depend on pH and pKa (Ionised = A-,H+ = hydrophilic) (non-ionised AH,= Lipophilic) pKa - acid dissociation constant - Allows prediction of behavior of drug at a specific pH (PH of drug and pH of environment) - PH at which half of the drug is ionized - Drugs have to be non ionized to cross membranes Absorption in the GI tract Oesophagus - pH of 7 Stomach - pH of 1-2.5 (5 when fed) Proximal small intestine- pH of (6.15-7) Descending colon - pH of 5.2-7 Distal small intestine - pH of 6.8-7.8 Ascending colon - pH of 5.2-6.7 Blood flow - more blood flow = more adsorption Absorption of oral drugs - molecules absorbed in GI tract enter hepatic portal vein - Hepatic first pass Hepatic first pass Bioavailability - Percentage of administered dose that is available therapeutically - 100% for iv, less for other routes of administration Hepatic extraction ratio Amount removed by liver cells (80%) - >0.8 = lower bioavalibility -