PathologyPathologyNURS3518NURS3518

Endocrine System: Endocrine System: Review and Alterations IReview and Alterations I

Nancy Downing, PhD, RN, SANE-ANancy Downing, PhD, RN, SANE-AUI College of NursingUI College of Nursing

ObjectivesObjectives

Describe effects of altered pituitary functionDescribe effects of altered pituitary function Compare altered negative feedback system in Compare altered negative feedback system in

primary et secondary hyperthyroidismprimary et secondary hyperthyroidism Distinguish b. Graves disease et thyroid stormDistinguish b. Graves disease et thyroid storm Compare mechanisms of 1Compare mechanisms of 1◦◦ et 2 et 2 ◦◦ hypothyroidism hypothyroidism Relate how hyperparathyroidism affects CaRelate how hyperparathyroidism affects Ca++++

levels et consequence of these Calevels et consequence of these Ca++++ alterations alterations Understand pathophysiology of DI et SIADHUnderstand pathophysiology of DI et SIADH Recognize s/s of Cushing disease/syndromeRecognize s/s of Cushing disease/syndrome Compare alterations of adrenal hypo and hyper Compare alterations of adrenal hypo and hyper

function function

Endocrine SystemEndocrine System

Endocrine System ReviewEndocrine System Review

Hormones: chemical messengers secreted Hormones: chemical messengers secreted from endocrine glandsfrom endocrine glands

Integrated with nervous systemIntegrated with nervous system Functions of hormones:Functions of hormones:

Growth et developmentGrowth et development Regulation of reproductive systemRegulation of reproductive system HomeostasisHomeostasis AdaptationAdaptation

Endocrine MechanismsEndocrine Mechanisms

Secreted in rhythms or patternsSecreted in rhythms or patterns e.g. diurnal cortisol levelse.g. diurnal cortisol levels

Operate in feedback systemsOperate in feedback systems e.g. HPA Axise.g. HPA Axis

Hormone ReceptorsHormone Receptors

Hormones secreted into circulationHormones secreted into circulation Only affect cells with appropriate receptorsOnly affect cells with appropriate receptors Receptors bind to hormone, release signal Receptors bind to hormone, release signal

Hormone Alteration MechanismsHormone Alteration MechanismsInappropriate amounts of hormone Inappropriate target cell response

Inadequate hormone synthesis•Decreased hormone precursors•Failure to convert to active hormone

Alteration in cell surface receptor•↓ number of receptors•Hormones can’t bind properly•Hormones bind but don’t function•Antibodies against receptors

Failure of feedback systems•Failure to recognize positive feedback— ↓ synthesis•Failure to recognize negative feedback— ↑ synthesis

Intracellular disorder•Defective intracellular signalling•Inadequate 2nd messenger synthesis•Altered enzymes or proteins in path•Altered protein synthesis

Inactive hormones•Non functional hormones•Hormones prematurely degraded•Antibodies against hormones

Dysfunctional delivery system•Inadequate blood supply•Inadequate carrier proteins•Ectopic sources w/out feedback

PITUITARY ALTERATIONSPITUITARY ALTERATIONS

Pituitary GlandPituitary Gland

Hypopituitarism Hypopituitarism

Absence/deficiency of pituitary hormonesAbsence/deficiency of pituitary hormones Failure of hormonal functionFailure of hormonal function May involve 1 or more types of hormoneMay involve 1 or more types of hormone

Causes of HypopituitarismCauses of Hypopituitarism

InfarctInfarct Postpartum, shock, sickle cell disease, Postpartum, shock, sickle cell disease,

pregnancy w/DMpregnancy w/DM Genetic abnormalitiesGenetic abnormalities Head trauma, internal head bleedHead trauma, internal head bleed Pituitary tumors (mechanical compression)Pituitary tumors (mechanical compression) InfectionsInfections Upstream problem with hypothalamusUpstream problem with hypothalamus

HypopituitarismHypopituitarism GH GH

s/s vary if child vs. adults/s vary if child vs. adult TSH TSH

Hypothyroidism Hypothyroidism ACTHACTH

Cortisol insufficiencyCortisol insufficiency• ↓↓glycogen, ↓gluconeogenesis, ↓body hair, ↓libidoglycogen, ↓gluconeogenesis, ↓body hair, ↓libido• s/s: N/V, anorexia, fatigue, weaknesss/s: N/V, anorexia, fatigue, weakness

FSH et LH FSH et LH Amenorrhea, atrophic vagina, uterus, breastsAmenorrhea, atrophic vagina, uterus, breasts

GH Deficiency in ChildrenGH Deficiency in Children

Dwarfism, hypoglycemia Dwarfism, hypoglycemia May be geneticMay be genetic

GHRHGHRH gene mutation (AR) gene mutation (AR) Loss of Loss of GHGH gene gene Altered GH receptorAltered GH receptor Altered IGF-1 synthesis Altered IGF-1 synthesis Altered IGF-1 receptor Altered IGF-1 receptor Pituitary or hypothalamus Pituitary or hypothalamus

tumors/lesionstumors/lesions

GH Deficiency in AdultsGH Deficiency in Adults

Vague s/s: fatigue, loss of Vague s/s: fatigue, loss of motivation, ↓ wellbeing, ↓ motivation, ↓ wellbeing, ↓ lean mass, ↑ body fat, lean mass, ↑ body fat, osteoporosis, dry skin, osteoporosis, dry skin, depression, social depression, social withdrawal, ↓ motivationwithdrawal, ↓ motivation

Usually r/t structural or Usually r/t structural or functional abnormalities of functional abnormalities of pituitarypituitary

HyperpituitarismHyperpituitarism Primary adenomaPrimary adenoma

Benign, slow-growing tumorBenign, slow-growing tumor May compress surrounding tissueMay compress surrounding tissue

Visual px, sinus px, hypothalamus alterationsVisual px, sinus px, hypothalamus alterations Oversecretion of specific hormonesOversecretion of specific hormones

Esp. GH et. prolactinEsp. GH et. prolactin Undersecretion of other pituitary hormonesUndersecretion of other pituitary hormones

↓ ↓ tthyroid et adrenal function due to lack of hyroid et adrenal function due to lack of TSH et ACTH; TSH et ACTH; ↓ ↓ FSH et LHFSH et LH

GigantismGigantism

GH et IGF-1 oversecretion in childrenGH et IGF-1 oversecretion in children Excessive long bone growthExcessive long bone growth Occurs throughout the ages in all culturesOccurs throughout the ages in all cultures

AcromegalyAcromegaly Connective tissue proliferationConnective tissue proliferation Most common cause: pituitary tumorMost common cause: pituitary tumor

Enlargement of bones in face, hands, et feetEnlargement of bones in face, hands, et feet Growth of tongue, sebaceous glands, skin, hairGrowth of tongue, sebaceous glands, skin, hair

Hyperglycemia, ↑metabolic rate, insulin Hyperglycemia, ↑metabolic rate, insulin resistance, cardiac hypertrophy, HTN, resistance, cardiac hypertrophy, HTN, atherosclerosis, arthritisatherosclerosis, arthritis

Later stages: nerve damageLater stages: nerve damage

ADH ALTERATIONSADH ALTERATIONS

Diabetes InsipidusDiabetes Insipidus

Decreased ADHDecreased ADH Insufficient production or activityInsufficient production or activity

→ → inability to concentrate urineinability to concentrate urine NeurogenicNeurogenic

Insufficient ADH productionInsufficient ADH production• Tumors or lesionsTumors or lesions

NephrogenicNephrogenic Kidneys don’t respond to ADH stimulationKidneys don’t respond to ADH stimulation

• Genetic or acquiredGenetic or acquired

DI: s/sDI: s/s

Polydipsia (excessive thirst et drinking)Polydipsia (excessive thirst et drinking) Cold fluids preferred Cold fluids preferred

Polyuria, nocturiaPolyuria, nocturia Up to 8-10L/dayUp to 8-10L/day

Low urine osmolality (<200mOsml/kg)Low urine osmolality (<200mOsml/kg) High serum osmolality (≥300mOsml.kg)High serum osmolality (≥300mOsml.kg) NaNa++ ≥145mEq/L ≥145mEq/L

SIADHSIADH Increased ADHIncreased ADH Syndrome of inappropriate ADHSyndrome of inappropriate ADH Causes: Anything that ↑ADHCauses: Anything that ↑ADH

Pituitary tumorPituitary tumor Transient fluid shiftsTransient fluid shifts

• Pulmonary DO, CNS DO, surgery Pulmonary DO, CNS DO, surgery RxRx

• Antidepressants, narcotics, antipsychotics, Antidepressants, narcotics, antipsychotics, anesthetics, chemo, NSAIDsanesthetics, chemo, NSAIDs

SIADH PathophysiologySIADH Pathophysiology

ADH released from post. ADH released from post. pituitary or tumorpituitary or tumor

↑ ↑ renal Hrenal H22O retentionO retention

↑ ↑ ECF volumeECF volume Low serum et urine Low serum et urine

osmolalityosmolality Dilutional hyponatremiaDilutional hyponatremia

SIADH: s/sSIADH: s/s

Hypervolemia w/out edemaHypervolemia w/out edema Primary issue is hyponatremiaPrimary issue is hyponatremia

NaNa++ 130mEq/L 130mEq/L• Thirst, impaired taste, anorexia, dyspnea on Thirst, impaired taste, anorexia, dyspnea on

exertion, fatigue, dulled sensoriumexertion, fatigue, dulled sensorium NaNa++ 120mEq/L 120mEq/L

• GI cramps, vomitingGI cramps, vomiting NaNa++ <115mEq/L <115mEq/L

• Confusion, lethargy, muscle twitching, convulsionsConfusion, lethargy, muscle twitching, convulsions

THYROID ALTERATIONSTHYROID ALTERATIONS

Thyroid FunctionThyroid Function

Controls rates of metabolic processesControls rates of metabolic processes Thyroid hormone (TH) regulated via Thyroid hormone (TH) regulated via

feedback loopsfeedback loops

Hyperthyroidism: PrimaryHyperthyroidism: Primary

Thyrotoxicosis: excess THThyrotoxicosis: excess TH Hyperthyroidism: excess Hyperthyroidism: excess

secretion from thyroid glandsecretion from thyroid gland Affects 0.7-2.1% of people in USAffects 0.7-2.1% of people in US

Causes: Graves disease, Causes: Graves disease, hyperfunctioning nodules, hyperfunctioning nodules, thyroiditis, thyroid Rx, tumorthyroiditis, thyroid Rx, tumor

Hyperthyroidism: SecondaryHyperthyroidism: Secondary

Pituitary tumorPituitary tumor Excess TSH secretionExcess TSH secretion Pituitary gland can’t Pituitary gland can’t

respond to negative respond to negative feedback from excess THfeedback from excess TH

Hyperthyroidism: s/sHyperthyroidism: s/s

Goiter: enlarged thyroid glandGoiter: enlarged thyroid gland ↑ ↑ metabolic ratemetabolic rate

Weight loss, ↑ appetiteWeight loss, ↑ appetite Heat intoleranceHeat intolerance

↑ ↑ SNS stimulationSNS stimulation SweatingSweating ↑ ↑ cardiac outputcardiac output Dyspnea Dyspnea Restlessness, distractibility, insomniaRestlessness, distractibility, insomnia

Hyperthyroidism: CausesHyperthyroidism: Causes

Graves DiseaseGraves Disease

Stimulation of thyroid glandStimulation of thyroid gland Accounts for 50-80% of hyperthyroidismAccounts for 50-80% of hyperthyroidism More common in womenMore common in women

Hypersensitivity reaction (Type II)Hypersensitivity reaction (Type II) Autoantibodies against TSH receptorsAutoantibodies against TSH receptors

• Thyroid-stimulating immunoglobulins (TSI)Thyroid-stimulating immunoglobulins (TSI)• → → hyperplasia et goiterhyperplasia et goiter

• → ↑ → ↑ TH (esp TTH (esp T33))

Graves Disease: s/sGraves Disease: s/s

Goiter Goiter Enlarged thyroid glandEnlarged thyroid gland

Protruding eyesProtruding eyes Ophthalmopathy Ophthalmopathy

Skin changes Skin changes Dermopathy of legsDermopathy of legs

• SwellingSwelling• Induration Induration • ErythemaErythema

Thyroid StormThyroid Storm

Acute, can be fatal within 48 hrs w/out txAcute, can be fatal within 48 hrs w/out tx Most common cause: Most common cause:

undiagnosed/undertreated undiagnosed/undertreated hyperthyroidism et ↑ stresshyperthyroidism et ↑ stress Burns, trauma, infection, surgery, emotional Burns, trauma, infection, surgery, emotional

distress, OB complications, dialysis, CV or distress, OB complications, dialysis, CV or pulmonary disorderspulmonary disorders

s/s: hyperthermia, tachycardia, s/s: hyperthermia, tachycardia, dysrhythmias, heart failure, N/V/D, dysrhythmias, heart failure, N/V/D, agitation, deliriumagitation, delirium

HypothyroidismHypothyroidism More common than hyperthyroidismMore common than hyperthyroidism Affects 0.1-2% in USAffects 0.1-2% in US Deficient production of THDeficient production of TH Can be congenital—cretinism Can be congenital—cretinism

HypothyroidismHypothyroidism

Hypothyroidism: s/sHypothyroidism: s/s

Low basal metabolic rateLow basal metabolic rate Weight gain, lethargy, Weight gain, lethargy,

tiredness, cold intolerance,tiredness, cold intolerance, anemia, ↓cardiac output, anemia, ↓cardiac output,

enlarged heart, bradycardia, enlarged heart, bradycardia, dyspnea, ↓renal blood flow et dyspnea, ↓renal blood flow et glomerular filtration rate, glomerular filtration rate, constipation, edema, muscle constipation, edema, muscle ache, dry et flaky skinache, dry et flaky skin

MyxedemaMyxedema s/s severe or chronic hypothyroidisms/s severe or chronic hypothyroidism Systemic ↑ protein et mucopolysaccharides Systemic ↑ protein et mucopolysaccharides

(MPS) between connective fibers(MPS) between connective fibers MPS bind water → non-pitting, boggy edemaMPS bind water → non-pitting, boggy edema

Eyes, hands, feet, tissue around claviclesEyes, hands, feet, tissue around clavicles Tongue enlargement → speech changesTongue enlargement → speech changes Can → ↑ ICP et comaCan → ↑ ICP et coma

Hyperthyroidism vs. Hyperthyroidism vs. HypothyroidismHypothyroidism

PARATHYROID ALTERATIONSPARATHYROID ALTERATIONS

Parathyroid FunctionParathyroid Function

Secrete PTHSecrete PTH Regulates CaRegulates Ca++++ et phosphorus levels et phosphorus levels

Hyperparathyroidism Hyperparathyroidism ↑ ↑ secretion of PTHsecretion of PTH Primary—cause unknownPrimary—cause unknown

↑ ↑ secretion in 1+ glandssecretion in 1+ glands Adenomas or hyperplasiaAdenomas or hyperplasia Failure of negative feedbackFailure of negative feedback

• No ↓ PTH secretion with ↑ CaNo ↓ PTH secretion with ↑ Ca++++

Secondary—r/t ↓CaSecondary—r/t ↓Ca++++ ↑ ↑ PTH secretion r/t chronic diseasePTH secretion r/t chronic disease Renal failure or intestinal malabsorptionRenal failure or intestinal malabsorption

• ↓↓CaCa++++ stimulates ↑PTH secretion stimulates ↑PTH secretion

Hyperparathyroidism: s/sHyperparathyroidism: s/s

Primary: ↑ CaPrimary: ↑ Ca++++ et et ↓ ↓ phosphorusphosphorus Kidney stonesKidney stones Insulin resistanceInsulin resistance

Secondary: Secondary: ↓ ↓ CaCa++++ et ↑ et ↑ phosphorusphosphorus Can → cardiac problemsCan → cardiac problems

Hyperparathyroidism: s/sHyperparathyroidism: s/s

Both include ↑bone resorption Both include ↑bone resorption 11o o : : ↑ PTH → bone resorption↑ PTH → bone resorption 22oo : ↓ Ca++ : ↓ Ca++ → ↑ PTH → bone resorption→ ↑ PTH → bone resorption

Bones break down to release CaBones break down to release Ca++++

Fractures, kyphosis, compression fracturesFractures, kyphosis, compression fractures

ADRENAL ALTERATIONSADRENAL ALTERATIONS

s/s Depend on Area of s/s Depend on Area of AlterationAlteration

Adrenal CortexAdrenal Cortex GC—mainly cortisol GC—mainly cortisol MC—mainly aldosterone MC—mainly aldosterone Androgens et estrogens—secondary sourceAndrogens et estrogens—secondary source

Adrenal MedullaAdrenal Medulla Catecholamines Catecholamines

Cushing Disease/SyndromeCushing Disease/Syndrome Cushing disease: ACTH Cushing disease: ACTH

oversecretion by pituitaryoversecretion by pituitary Cushing syndrome: ↑ cortisol Cushing syndrome: ↑ cortisol

r/t any causer/t any cause Endogenous diseaseEndogenous disease

ACTH-secreting tumorsACTH-secreting tumors Adrenal tumor, hyperplasiaAdrenal tumor, hyperplasia

Medication-induced syndromeMedication-induced syndrome Glucocorticoids (e.g prednisone)Glucocorticoids (e.g prednisone)

Cushing Syndrome: s/sCushing Syndrome: s/s

Weight gainWeight gain Adiposity of face, neck, trunkAdiposity of face, neck, trunk

Glucose intoleranceGlucose intolerance Cortisol-induced insulin resistanceCortisol-induced insulin resistance ↑ ↑ gluconeogenesis/glycogen storagegluconeogenesis/glycogen storage

Immune suppressionImmune suppression Poor wound healingPoor wound healing

““moon face”moon face”

Cushing Syndrome: s/sCushing Syndrome: s/s

Catabolic effects of cortisolCatabolic effects of cortisol Muscle wastingMuscle wasting Loss of collagen—purple striae Loss of collagen—purple striae ↑ ↑ bone resorption, bone resorption, ↓ ↓ bone formationbone formation

↑ ↑ melanocyte stimulating hormonesmelanocyte stimulating hormones Hyperpigmentation Hyperpigmentation Hair, mucous membranes, skin Hair, mucous membranes, skin

Cushing Syndrome: s/sCushing Syndrome: s/s

↑ ↑ catecholamine sensitivitycatecholamine sensitivity Vasoconstriction et HTNVasoconstriction et HTN

Neurological changesNeurological changes Irritability, depression, Irritability, depression,

psychosispsychosis Females: ↑ facial hair, Females: ↑ facial hair,

acne, oligomenorrheaacne, oligomenorrhea

Cortex HyperfunctionCortex Hyperfunction

Mostly r/t adrenal tumorsMostly r/t adrenal tumors Hyperaldosteronism Hyperaldosteronism

Na+ et HNa+ et H220 retention0 retention K+ lossK+ loss Insulin resistance Insulin resistance

Secondary sex hormonesSecondary sex hormones Feminization in malesFeminization in males Hirsutism in femalesHirsutism in females

Cortex HypofunctionCortex Hypofunction

Primary: Addison diseasePrimary: Addison disease Relatively rare Relatively rare Autoimmune, infection, adrenal destructionAutoimmune, infection, adrenal destruction

s/s: weakness, fatigue, hyperpigmentation, s/s: weakness, fatigue, hyperpigmentation, anorexia, nausea, vomiting, diarrha, anorexia, nausea, vomiting, diarrha, hypotension w/ risk of shock, loss of body hypotension w/ risk of shock, loss of body hair in women, mood et motivation hair in women, mood et motivation disturbancesdisturbances

Medulla AlterationsMedulla Alterations

HypofunctionHypofunction No noticeable effectsNo noticeable effects NE secretion sufficientNE secretion sufficient

HyperfunctionHyperfunction Oversecretion of NEOversecretion of NE

• HTN, diaphoresis, tachycardia, palpitations, severe HTN, diaphoresis, tachycardia, palpitations, severe HA, hypermetabolism, glucose intolerance, heat HA, hypermetabolism, glucose intolerance, heat intolerance, weight loss, constipationintolerance, weight loss, constipation