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

1.1. Pituitary hypersecretion of ACTHPituitary hypersecretion of ACTH

2.2. Adrenal hypersecretion of cortisol Adrenal hypersecretion of cortisol (adenoma, carcinoma, nodular (adenoma, carcinoma, nodular hyperplasia)hyperplasia)

3.3. 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 Adrenal cortical adenomaadenoma

FunctionalFunctional Cortisol: Cushing Cortisol: Cushing

syndromesyndrome Aldosterone: Aldosterone:

Conn’s syndrome Conn’s syndrome (primary (primary hyperaldosteronismhyperaldosteronism))

NonfunctionalNonfunctional

Cushing Syndrome – Clinical Cushing Syndrome – Clinical FeaturesFeatures

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: Catabolic effect on proteins with loss of collagen:

cutaneous striae, easy brusing, osteoporosiscutaneous striae, easy brusing, osteoporosis Hirsutism, amenorrheaHirsutism, amenorrhea Increased risk of infections (because of Increased risk of infections (because of

decreased immune response)decreased immune 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