diabetes mellitus
TRANSCRIPT
Endocrine Endocrine System (2)System (2)Ema A. Dragoescu, M.D.Ema A. Dragoescu, M.D.
June 11, 2009June 11, 2009
Adrenal GlandAdrenal Gland
CortexCortex Zona glomerulosa Zona glomerulosa
aldosteronealdosterone Zona fasciculata Zona fasciculata
cortisolcortisol Zona reticularis Zona reticularis sex sex
hormoneshormones Medulla Medulla
cathecolamines cathecolamines (epinephrine)(epinephrine)
Adrenocortical Adrenocortical HyperfunctionHyperfunction
Hormones Hormones produced by produced by adrenal cortex:adrenal cortex: CortisolCortisol
AldosteroneAldosterone
Sex hormones Sex hormones (androgens)(androgens)
Syndromes:Syndromes:
Cushing SyndromeCushing Syndrome
Hyperaldosteronism Hyperaldosteronism (Conn syndrome)(Conn syndrome)
Adrenogenital (or Adrenogenital (or virilizing) virilizing) syndromessyndromes
Cushing SyndromeCushing Syndrome
EndogenousEndogenous
2.2. Pituitary hypersecretion of ACTHPituitary hypersecretion of ACTH
3.3. Adrenal hypersecretion of cortisol (adenoma, Adrenal hypersecretion of cortisol (adenoma, carcinoma, nodular hyperplasia)carcinoma, nodular hyperplasia)
4.4. Ectopic ACTH (small cell lung cancer)Ectopic ACTH (small cell lung cancer)
ExogenousExogenous
4. Adm. of exogenous glucocorticoids4. Adm. of exogenous glucocorticoids
Cushing SyndromeCushing Syndrome
Adrenal cortical adenoma. Single, bright yellow nodule. Morphology is identical to that of a nonfunctional adenoma or adenoma from Conn syndrome. The yellow color is due to increased lipid content of the adrenal cortical cells.
Adrenal cortical hyperplasia. The cortex is diffusely thickened and yellow.
Adrenal cortical adenomaAdrenal cortical adenoma
FunctionalFunctional Cortisol: Cushing Cortisol: Cushing
syndromesyndrome Aldosterone: Conn’s Aldosterone: Conn’s
syndrome (primary syndrome (primary hyperaldosteronism)hyperaldosteronism)
NonfunctionalNonfunctional
Cushing Syndrome – Cushing Syndrome – Clinical FeaturesClinical Features
HypertensionHypertension Weight gain:Weight gain:
Truncal obesityTruncal obesity ““moon” facemoon” face ““buffalo hump”buffalo hump”
Decreased muscle massDecreased muscle mass HyperglycemiaHyperglycemia Catabolic effect on proteins with loss of collagen: cutaneous Catabolic effect on proteins with loss of collagen: cutaneous
striae, easy brusing, osteoporosisstriae, easy brusing, osteoporosis Hirsutism, amenorrheaHirsutism, amenorrhea Increased risk of infections (because of decreased immune Increased risk of infections (because of decreased immune
response)response)
Cushing syndrome. Round face, red cheeks, hirsutism.
Cushing syndrome. Truncal obesity and abdominal striae.
Oral candidasis in a patient taking inhaler steroids for asthma
Dental Management of the Dental Management of the Patient Taking Patient Taking CorticosteroidsCorticosteroids
Routine procedures (excluding surgery)Routine procedures (excluding surgery)
a. Good local anesthesia & postoperative a. Good local anesthesia & postoperative
pain control if necessarypain control if necessary
b. Monitor blood pressure during b. Monitor blood pressure during procedureprocedure
Dental extractions or surgeryDental extractions or surgery
a. Corticosteroid dose generally will need a. Corticosteroid dose generally will need to be increased, consult patient’s MD prior to be increased, consult patient’s MD prior to the procedureto the procedure
HyperaldosteronismHyperaldosteronism
Na retention and K excretion Na retention and K excretion HTN, HTN, hypokalemiahypokalemia
Primary (Conn syndrome)Primary (Conn syndrome) Adrenal cortical adenoma Adrenal cortical adenoma Suppression of RAA: plasma renin = lowSuppression of RAA: plasma renin = low
SecondarySecondary Due to decreased renal perfusion (renal artery Due to decreased renal perfusion (renal artery
stenosis, arteriolar nephrosclerosis, CHF)stenosis, arteriolar nephrosclerosis, CHF) Activation of RAA: plasma renin = highActivation of RAA: plasma renin = high
Adrenocortical Adrenocortical insufficiencyinsufficiency
AcuteAcute Massive adrenal hemorrhage (DIC, Massive adrenal hemorrhage (DIC,
sepsis = Waterhouse-Friderichsen sdr.)sepsis = Waterhouse-Friderichsen sdr.) Sudden withdrawal of long-term Sudden withdrawal of long-term
corticosteroid therapycorticosteroid therapy Stress in patients with chronic Stress in patients with chronic
adrenocortical insufficiencyadrenocortical insufficiency Chronic (Addison disease)Chronic (Addison disease)
Autoimmune, infections (TB, fungal), Autoimmune, infections (TB, fungal), AIDS, metastatic cancersAIDS, metastatic cancers
Addison diseaseAddison disease
Progressive weaknessProgressive weakness GI symptoms: anorexia, vomiting, GI symptoms: anorexia, vomiting,
weight lossweight loss HyperpigmentationHyperpigmentation Low aldosterone: hyponatremia, Low aldosterone: hyponatremia,
hypotensionhypotension Low cortisol: hypoglycemiaLow cortisol: hypoglycemia Death if untreatedDeath if untreated
Addison disease. Heavy pigmentation of the skin and blothcy pigmentation of the tongue. Oral pigmentation in Addison disease is most common in areas subject to masticatory trauma (cheeks), but can involve any part of the oral mucosa. Oral pigmentation can be the initial presentation of adrenal insufficiency.
PheochromocytomaPheochromocytoma Tumor of adrenal Tumor of adrenal
medulla in adultsmedulla in adults Paroxysmal episodes of Paroxysmal episodes of
hypertensionhypertension Urinary excretion of of Urinary excretion of of
free cathecolamines and free cathecolamines and their metabolites (VMA)their metabolites (VMA)
10% tumor (familial, 10% tumor (familial, children, malignant, children, malignant, extra-adrenal, bilateral)extra-adrenal, bilateral)
Familial syndromes with Familial syndromes with pheochromocytomapheochromocytoma
MEN IIa, IIbMEN IIa, IIb Von Hippel-Lindau (renal cell carcinoma, Von Hippel-Lindau (renal cell carcinoma,
cerebellar hemangioblastoma)cerebellar hemangioblastoma) NF1 (neurofibromas, café-au-lait spots, NF1 (neurofibromas, café-au-lait spots,
schwannoma, meningioma, glioma)schwannoma, meningioma, glioma) Sturge-Weber (cavernous hemangioma of Sturge-Weber (cavernous hemangioma of
55thth nerve distribution) nerve distribution)
Sturge-Weber syndrome. Hemangiomatous malformation of the face over the maxillary branch of trigeminal nerve. Hemangiomas may also occur in the oral mucosa.
Diabetes MellitusDiabetes Mellitus
= hyperglycemia, with secondary = hyperglycemia, with secondary damage to:damage to: Kidneys Kidneys ESRD ESRD Eyes Eyes blindness blindness Nerves Nerves peripheral sensory and peripheral sensory and
autonomous neuropathyautonomous neuropathy Blood vessels Blood vessels extremities amputation extremities amputation
7% of US population7% of US population
Blood glucoseBlood glucose Normal: 70-110 mg/dLNormal: 70-110 mg/dL Diabetes (one of the 3):Diabetes (one of the 3):
random: ≥ 200 mg/dLrandom: ≥ 200 mg/dL 110-200 mg/dL has 110-200 mg/dL has impaired glucose impaired glucose
tolerancetolerance Fasting glucose ≥126 mg/dLFasting glucose ≥126 mg/dL
110-126 mg/dL has 110-126 mg/dL has impaired glucose impaired glucose tolerancetolerance
OGTT ≥ 200 mg/dLOGTT ≥ 200 mg/dL 140-200 mg/dL has 140-200 mg/dL has impaired glucose impaired glucose
tolerancetolerance
Diabetes MellitusDiabetes Mellitus
Type 1: Type 1: absoluteabsolute deficiency of deficiency of insulin secretioninsulin secretion Autoimmune destruction of Autoimmune destruction of ββ cells cells Starts in childhoodStarts in childhood Depend on exogenous insulin for Depend on exogenous insulin for
survivalsurvival Type 2: Type 2: relativerelative deficiency of insulin deficiency of insulin
Peripheral resistance to insulinPeripheral resistance to insulin Inadequate Inadequate ββ cells function cells function
Effects of insulinEffects of insulin
anabolic effectanabolic effect increased synthesis increased synthesis
and decreased and decreased degradation of:degradation of: GlycogenGlycogen LipidLipid ProteinProtein
Acute complications of Acute complications of diabetesdiabetes
Diabetic ketoacidosisDiabetic ketoacidosis Marked hyperglycemia (>500 mg/dL)Marked hyperglycemia (>500 mg/dL) DehydrationDehydration Metabolic ketoacidosis (nausea, Metabolic ketoacidosis (nausea,
vomiting, respiratory difficulties)vomiting, respiratory difficulties) Hyperosmolar nonketotic comaHyperosmolar nonketotic coma Hypoglycemia!Hypoglycemia!
Long-term complications of Long-term complications of diabetesdiabetes
After 15-20 years; responsible for After 15-20 years; responsible for morbidity and mortalitymorbidity and mortality
Vascular: accelerated atherosclerosis with Vascular: accelerated atherosclerosis with MI, PVD, renal atherosclerosisMI, PVD, renal atherosclerosis
Ocular: retinopathy, cataract, glaucomaOcular: retinopathy, cataract, glaucoma Kidney: glomerular, vascular, Kidney: glomerular, vascular,
pyelonephritispyelonephritis NeuropathyNeuropathy Increased sensibility to infectiousIncreased sensibility to infectious Poor wound healingPoor wound healing
Diabetic nephropathy. Nodular glomerulosclerosis (Kimmelstiel-Wilson lesion). Eventually this will lead to ischemia scarring of the glomerulus.
Diabetic nephropathy. Renal arteriolosclerosis.
Oral Complications of Oral Complications of DiabetesDiabetes
Lowered resistance to infections with Lowered resistance to infections with increased fungal infections increased fungal infections (Candidiasis)(Candidiasis)
Xerostomia (Dry mouth)Xerostomia (Dry mouth) Poor or delayed wound healingPoor or delayed wound healing Increased incidence of periodontal Increased incidence of periodontal
disease with periodontal abscessesdisease with periodontal abscesses
Multiple Endocrine Multiple Endocrine Neoplasia SyndromesNeoplasia Syndromes
Autosomal dominant inheritedAutosomal dominant inherited Hyperplasia/adenoma/carcinoma of Hyperplasia/adenoma/carcinoma of
multiple endocrine organsmultiple endocrine organs Younger age than sporadic tumorsYounger age than sporadic tumors Multifocal in a given endocrine organMultifocal in a given endocrine organ More aggressive, recur more More aggressive, recur more
frequently that sporadic tumorsfrequently that sporadic tumors
Multiple Endocrine Multiple Endocrine Neoplasia Type 1 (MEN-1)Neoplasia Type 1 (MEN-1)
Due to inactivation of MEN1 gene on Due to inactivation of MEN1 gene on 11q1311q13
Involves (“3P”):Involves (“3P”): Parathyroid: parathyroid hyperplasia Parathyroid: parathyroid hyperplasia
primary hyperparathyroidism primary hyperparathyroidism Pancreas: functional endocrine tumors Pancreas: functional endocrine tumors
(leading cause of death in MEN-1)(leading cause of death in MEN-1) Insulinoma Insulinoma hypoglicemia hypoglicemia Gastrinoma Gastrinoma Zollinger-Ellison syndrome Zollinger-Ellison syndrome
Pituitary: prolactinomaPituitary: prolactinoma
Multiple Endocrine Multiple Endocrine Neoplasia Type 2 (MEN-2)Neoplasia Type 2 (MEN-2)
2 distinct group of disorders2 distinct group of disorders Mutations of Mutations of RETRET protooncogene protooncogene
(10q11.2)(10q11.2) MEN-2AMEN-2A
Medullary thyroid carcinomaMedullary thyroid carcinoma Develops in ALL casesDevelops in ALL cases In the first 2 decades, multifocalIn the first 2 decades, multifocal
PheochromocytomaPheochromocytoma Parathyroid hyperplasia Parathyroid hyperplasia primary primary
hyperparathyroidismhyperparathyroidism
Multiple Endocrine Multiple Endocrine Neoplasia Type 2 (MEN-2)Neoplasia Type 2 (MEN-2)
MEN-2BMEN-2B Medullary thyroid carcinomaMedullary thyroid carcinoma PheochromocytomaPheochromocytoma Do NOT develop parathyroid hyperplasiaDo NOT develop parathyroid hyperplasia Develop extraendocrine manifestationsDevelop extraendocrine manifestations
Ganglioneuromas on mucosal surfaces (lips, tongue, Ganglioneuromas on mucosal surfaces (lips, tongue, GI tract)GI tract)
Marfanoid habitusMarfanoid habitus
Family members with germ-line RET Family members with germ-line RET mutations: prophylactic thyroidectomymutations: prophylactic thyroidectomy
Medullary Thyroid Carcinoma