Endocrine and metabolic disorders RCW Wong
Endocrine and metabolic disorders • Endocrine glands regulate homeostasis by secretion of hormones which affect many organ systems • Metabolism - process body uses to get or make energy from food. • Metabolic disorders occur when abnormal chemical reactions disrupt this process. • too much or too little of some substances • occurs when some organs, e.g. liver or pancreas, become diseased or do not function normally.
Endocrine glands • Hypothalamus • Pituitary • Pineal • Thyroid • Parathyroid • Thymus • Pancreas • Adrenal • Sex organs Mainly regulated in negative feedback loop
Endocrine disorders • Pituitary tumours –gigantism, acromegaly, diabetes insipidus • Diabetes mellitus • Adrenal insufficiency • Thyroid disorders- hypo or hyperthyroid • Parathyroid-hypo or hyper • Tumours- multiple endocrine neoplasia, phaeochromocytoma
Inherited disorders of metabolism • Acid lipase disease • Barth syndrome • Central pontine myelinosis • Phenylketonuria • Lesch-Nyhan disease • G6PD deficiency • Pompe disease • Mitochondrial myopathies • Muscular dystrophy • Lipid storage disease • Mucolipidosis • Mucopolysaccharidosis • Porphyria • Hereditary fructose intolerance • Type I glycogen storage disease • Hypercholesterolemia • Diabetes mellitus type I
Acquired disorders of metabolism • Diabetes mellitus Type II • Hypercholesterolemia • Metabolic syndrome /Syndrome X
Important disorders • Diabetes mellitus • Adrenocorticalhypofunction • Thyroid disorders • G6PD
Diabetes mellitus • Diabetes mellitus (DM) is a heterogenous disorder of metabolism due to absolute or relative deficiency of insulin • It affects 9% of the population aged 18-69 years in Singapore causing multi-organ damage and dysfunction • Associated with 9.3% of all deaths National Health Survey 1998, Epidemiology and Disease Control, Department of Ministry of Health, Singapore.
Classification of diabetes • Type 1 (primary diabetes-insulin dependant diabetes mellitus)-due to severe insulin deficiency caused by destruction of the pancreatic beta cells • Type 2 (primary diabetes -non-insulin dependent diabetes mellitus)-due to varying degrees of insulin resistance and insulin deficiency
Classification of diabetes • Gestational diabetes-diabetes that is first recognized or occurs during pregnancy • Miscellanous group- includes diabetes caused by chronic pancreatitis, drugs like steroids, hemochromatosis, acromegaly
Signs and Symptomsof diabetes mellitus Type I mainly juvenile and occasionally non-obese individuals/elderly when hyperglycaemia first appears • Polyuria • Polydipsia • Rapid weight loss associated with hyperglycaemia • Postural hypotension • Muscle weakness • Ketoacidosis • Ketonuria
Signs and Symptomsof diabetes mellitus Type II (mainly over 40 and obese) • Polyuria • Polydipsia • Non-ketotic form of diabetes • Candidalvaginitis in women • Chronic skin infections • Generalized pruritus • Associated with hypertension, hyperlipidemia and atherosclerosis
Known risk factors • positive family history • Hypertension • Overweight • previous gestational diabetes • impaired glucose tolerance • plasma HDL-cholesterol less than 0.9mmol/L and plasma trigylceride above 2.8 mmol/L
Diagnosis • Based on clinical history • symptoms and • lab analysis
Lab analysis Urinanalysis: • Glucosuria- certain drugs like salicylates, ascorbic acids can give false negative results. A normal renal threshold and a reliable bladder is essential for interpretation. • Ketonuria Capillary blood glucose measurements by bedside (Hypocount) in a hospital setting requires rigorous quality control programs and certification of personnel to avoid errors
Lab analysis • Fasting plasma glucose- Repeated fasting plasma glucose over 7 mmol/L and /or random plasma glucose over 11 mmol/L in an asymptomatic individual is enough for diagnosis. In symptomatic persons, only one of the above values is required. • Glucose tolerance test: gold standard for diagnosis of diabetes but not always necessary
Lab analysis • Glycosylatedhaemoglobin (HbA1c): HbA1c is abnormally high in diabetics with chronic hyperglycaemia. The normal value should be 4-6% of total haemoglobin. This reflects the state of gycaemia in the preceeding 8-12 weeks • Attempts to use this for diagnosis of diabetes are controversial as the sensitivity in detecting diabetes with this test is only 85% i.e. diabetes cannot be excluded by a normal value. However, elevated levels are quite specific (91%) in identifying diabetes
Therapy for type 1 diabetes consists of dietary management and insulin. • Therapy for type 2 diabetes consists of dietary management and possibly oral hypoglycemic agents or insulin
Management of diabetic pts • The clinician should assess the disease severity, including the presence of chronic complications of DM e.g. IHD, renal disorders, neuropathy. • The degree of control, the types of medication (dosage, duration) and past history of acute infections and hospital admissions should be noted.
Minor surgery/outpatients • Routine dental treatment or minor oral surgery (under local anaesthesia [LA]) can be carried out in well-controlled diabetics • Schedule such patients first thing in the morning after breakfast and after their routine anti-diabetic medication
Minor surgery/outpatients • Keep appointments short; watch out for signs of hypoglycaemia (in the dental setting, a collapse of a known diabetic is usually due to hypoglycaemia since ketoacidosis takes some time to develop). • Onset of hypoglycaemia requires termination of the procedure and administration of a sweetened drink. • If unconscious, give 1mg glucagon IM followed by a glucose drink. Alternatively, if an IV line can be secured, give 50ml of 50% dextrose intravenously
Minor surgery/outpatients • Diabetic ketoacidosis (DKA) occurs in patients with type 1 disease because of stress or worsening glucose control, which produces hyperglycemia that causes osmotic diuresis, leading to severe dehydration and hyponatremia
Minor surgery/outpatients • Post-operative antibiotics may be considered after surgical procedures, if infection is a concern • If patients are unable to take their normal diet post-operatively, their insulin or oral hypoglycaemic medication may need to be reduced. Patients must be told to monitor their blood glucose at home, as is usually done.
GA/ major surgery • For diabetics/pts with hyperglycaemia/suspected diabetes undergoing major oral surgery procedures (under GA), consultation with the anaesthetist and physician/endocrinologist is essential. • A regime needs to be worked out to ensure good blood glucose control preoperatively, perioperatively and postoperatively. (Glucose/Insulin Sliding scale) • Start hypocount measurements 6 hourly and target insulin therapy on a sliding scale.
Introduction • Medulla secretes epinephrine and norepinephrine into adrenal veins when stimulated • Cortex secretes steroids regulating metabolism, vascular tone, cardiac contractility, TBW/Na/K balance, androgenic function
Adrenal Physiology • Cyclic secretion controlled by time of day, HPA axis, renin-angiotensin system, serum potassium levels • Stress increases basal glucocorticoid and mineralcorticoid levels 5-10 fold • Occurs within minutes
Adrenal Failure • Basal failure results in adrenal insufficiency • Leads to insidious wasting disease • Stress failure results in adrenal crisis • Life-threatening • Absence of glucocorticoids is most critical
Corticosteroids • Three classes (by effect): • Glucocorticoids • Mineralcorticoids • Androgenic steroids
Glucocorticoids • Regulate fat, glucose, protein metabolism • Catecholamine and b-adrenergic receptor synthesis • Maintain vascular tone and cardiac contractility • Control endothelial integrity/vascular permeability
Glucocorticoids • Cortisol • Controlled by HPA axis • Hypothalamus CRH and arginine vasopressin in circadian rhythm (max 2-4am) • Anterior Pituitary ACTH • Adrenal cortex cortisol • Peak @ 8am; declines throughout day
Glucocorticoids • Cortisol • 25mg produced daily (non-stressed) • 5-10% free and physiologically active • Remainder bound to cortisol-binding globulin • Becomes uncoupled in times of stress • Negatively feeds back to control hypothalamus • Role in adrenal insufficiency
Adrenal Insufficiency • Primary = failure of adrenal glands • Secondary = failure of HPA axis • Usually due to chronic exogenous glucocorticoid administration • pituitary failure • Tertiary = Hypothalamic dysfunction
Primary Adrenal Insufficiency • Loss of all three types of adrenal steroids • 90% of glands must be destroyed to manifest clinically • High functional reserve • Adrenoleukodystrophy = X-linked inherited d/o of very-long-chain fatty acid metabolism • Progressive neurological symptoms from demyelination
Primary Adrenal Insufficiency • Addison disease = autoimmuneThrombosis/hemorrhage • Sepsis, DIC, antiphospholipid syndrome • Infiltrative diseases • Bilateral cancer metastasis • Amyloidosis, hemosiderosis (rare)
Primary Adrenal Insufficiency • TB = m.c. infectious cause worldwide • HIV = m.c. infectious cause in US • 50% have degree of destruction • Only 5% have clinical symptoms of A.I. • CMV infection, ketoconazole use, macrophage-released cytokines are risk factors
Secondary Adrenal Insufficiency • HPA axis failure • deficiency of glucocorticoids and adrenal androgens • mineralcorticoids are unaffected • #1 cause=chronic exogenous glucocorticoid • suppresses diurnal CRH/AV release • both time- and dose-related • reversible • recovery may take up to a year
Secondary Adrenal Insufficiency • Less common causes • Postpartum necrosis (Sheehan syndrome) • Adenoma hemorrhage(s) • Pituitary destruction from head trauma • typically have associated focal neurological changes, visual deficits, diabetes insipidus or panhypopituitarism
Secondary Adrenal Insufficiency MYTHBUSTERS! • Short course (2-3 weeks) is unlikely to suppress the HPA axis • Daily doses of prednisone 5mg or less are unlikely to cause secondary insufficiency
Management • adrenocortical crisis and collapse if the patient is subjected to trauma, stress (pain/ anxiety induced), and general anaesthesia • The associated medical condition which required the patient to be placed on systemic corticosteroids can complicate dental care as well. This includes asthma, autoimmune disorders and recipients of organ transplant
Management • Patients on systemic corticosteroids or those who have had steroids within the previous year may need supplemental steroid for “stressful” clinical procedures (extensive dental procedures, oral surgery). • Steroid supplementation is not normally required for routine dental procedures.
Management • Stress reducing protocols should be implemented which involve achieving good pain control intraoperatively and postoperatively • Blood pressure should be monitored during procedure and post-operatively (half-hourly for two hours post-operatively)
Management Corticosteroid supplementation may be considered in : • patients currently on systemic corticosteroids • patients who were on systemic corticosteroids in the past 2 weeks to one month or who have been on it for more than one month in the past year where the amount of corticosteroids taken above is/was more than the equivalent of 7.5mg prednisolone daily
Corticosteroid cover regime * oral dose to be taken within 2hrs of surgery
Adrenal Crisis CLINICAL PRESENTATION • Life-threatening emergency • May be primary or secondary • HYPOTENSION • Typically resistant to catecholamine and IV fluid resuscitation
THYROID DISORDERS HYPERTHYROIDISM HYPOTHYROIDISM
THYROID HORMONES • Metabolism in all body organs • Stimulate the heart • heart rate • stroke volume • cardiac output • blood flow
HYPERTHYROIDISM INCREASED THYROID HORMONES: • Hypermetabolism • sympathetic nervous system activity • Effects protein, lipid and carbohydrate metabolism