Alterations of Hormonal Regulation Chapter 21 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc

Alterations of Hormonal RegulationAlterations of Hormonal Regulation

Chapter 21Chapter 21

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

Elevated or Depressed Elevated or Depressed Hormone LevelsHormone Levels

Failure of feedback systemsFailure of feedback systems Dysfunction of an endocrine glandDysfunction of an endocrine gland

Excessive/inadequate hormone productionExcessive/inadequate hormone production Altered hormone inactivation/degradationAltered hormone inactivation/degradation Ectopic hormone releaseEctopic hormone release

NonendocrineNonendocrine Autonomous production, no feedback mechanismsAutonomous production, no feedback mechanisms


Target Cell FailureTarget Cell Failure Receptor-associated disordersReceptor-associated disorders

Decrease in number of receptorsDecrease in number of receptors Impaired receptor functionImpaired receptor function Presence of antibodies against specific receptorsPresence of antibodies against specific receptors Antibodies that mimic hormone actionAntibodies that mimic hormone action Unusual expression of receptor functionUnusual expression of receptor function


Intracellular DisordersIntracellular Disorders

Inadequate synthesis of a second messengerInadequate synthesis of a second messenger Cyclic adenosine monophosphate (cAMP)Cyclic adenosine monophosphate (cAMP)

Failure of the target cell to produce anticipated Failure of the target cell to produce anticipated hormonal responsehormonal response Faulty response to hormone-receptor bindingFaulty response to hormone-receptor binding

• Failure to generate required second messenger Failure to generate required second messenger

• Abnormal response to the second messengerAbnormal response to the second messenger


Alterations of the Alterations of the Hypothalamic-Pituitary SystemHypothalamic-Pituitary System


Diseases of the Posterior Diseases of the Posterior PituitaryPituitary

Syndrome of inappropriate antidiuretic hormone Syndrome of inappropriate antidiuretic hormone (SIADH) secretion(SIADH) secretion Ectopic secretion of ADH most common cause; also Ectopic secretion of ADH most common cause; also

common after surgerycommon after surgery For diagnosis, normal adrenal and thyroid function For diagnosis, normal adrenal and thyroid function

must existmust exist Clinical manifestations Clinical manifestations

• Related to enhanced renal water retentionRelated to enhanced renal water retention• HyponatremiaHyponatremia• HypoosmolarityHypoosmolarity


Diseases of the Posterior Diseases of the Posterior PituitaryPituitary

Diabetes insipidusDiabetes insipidus Insufficiency of ADHInsufficiency of ADH Polyuria and polydipsiaPolyuria and polydipsia Partial/total inability to concentrate the urinePartial/total inability to concentrate the urine NeurogenicNeurogenic

• Insufficient amounts of ADHInsufficient amounts of ADH

NephrogenicNephrogenic• Inadequate response to ADHInadequate response to ADH


Diseases of the Anterior PituitaryDiseases of the Anterior Pituitary Pituitary is vascular and therefore vulnerable Pituitary is vascular and therefore vulnerable

to ischemia and infarctionto ischemia and infarction HypopituitarismHypopituitarism

Pituitary infarctionPituitary infarction• Sheehan syndromeSheehan syndrome

• Hemorrhage Hemorrhage

• ShockShock

Others: head trauma, infections, and tumorsOthers: head trauma, infections, and tumors


Diseases of the Anterior PituitaryDiseases of the Anterior Pituitary HypopituitarismHypopituitarism

Panhypopituitarism (all hormones absent)Panhypopituitarism (all hormones absent)• ACTH deficiencyACTH deficiency

• TSH deficiencyTSH deficiency

• FSH and LH deficiencyFSH and LH deficiency

• GH deficiencyGH deficiency Glucose intoleranceGlucose intolerance


Diseases of the Anterior PituitaryDiseases of the Anterior Pituitary HyperpituitarismHyperpituitarism

Commonly due to a benign, slow-growing pituitary Commonly due to a benign, slow-growing pituitary adenomaadenoma

ManifestationsManifestations• Headache and fatigueHeadache and fatigue

• Visual changesVisual changes

• Hyposecretion of neighboring anterior pituitary hormonesHyposecretion of neighboring anterior pituitary hormones


Diseases of the Anterior PituitaryDiseases of the Anterior Pituitary Hypersecretion of growth hormone (GH)Hypersecretion of growth hormone (GH)

AcromegalyAcromegaly• Hypersecretion of GH during adulthoodHypersecretion of GH during adulthood

• Slowly progressiveSlowly progressive Mortality: cardiac hypertrophy, hypertension, Mortality: cardiac hypertrophy, hypertension,

atherosclerosis, type 2 diabetes mellitus lead to coronary atherosclerosis, type 2 diabetes mellitus lead to coronary artery diseaseartery disease

Malignancies common Malignancies common

GiantismGiantism• GH hypersecretion in children and adolescentsGH hypersecretion in children and adolescents


Clinical Manifestations of Clinical Manifestations of AcromegalyAcromegaly

Connective tissue proliferationConnective tissue proliferation Enlarged tongue, interstitial edema, increase in the Enlarged tongue, interstitial edema, increase in the

size and function of sebaceous and sweat glands, size and function of sebaceous and sweat glands, coarse skin and body haircoarse skin and body hair

Bony proliferation Bony proliferation Large joint arthropathy Large joint arthropathy Periosteal vertebral growth Periosteal vertebral growth

• KyphosisKyphosis Enlargement of facial bones and hands and feet Enlargement of facial bones and hands and feet

• Protrusion of the lower jaw and forehead Protrusion of the lower jaw and forehead • Need for increasingly larger sizes of shoes, hats, rings, and Need for increasingly larger sizes of shoes, hats, rings, and

gloves gloves


Hypersecretion of GHHypersecretion of GH


Diseases of the Anterior PituitaryDiseases of the Anterior Pituitary

Hypersecretion of prolactinHypersecretion of prolactin Caused by prolactinomasCaused by prolactinomas

• Most common hormonally active pituitary tumorMost common hormonally active pituitary tumor

• In females, increased levels of prolactin cause amenorrhea, In females, increased levels of prolactin cause amenorrhea, galactorrhea, hirsutism, and osteopeniagalactorrhea, hirsutism, and osteopenia

• In males, increased levels of prolactin cause hypogonadism, In males, increased levels of prolactin cause hypogonadism, erectile dysfunction, impaired libido, oligospermia, and erectile dysfunction, impaired libido, oligospermia, and diminished ejaculate volumediminished ejaculate volume


Alterations of Thyroid FunctionAlterations of Thyroid Function PrimaryPrimary

Dysfunction or disease of thyroid glandDysfunction or disease of thyroid gland• TH productionTH production

SecondarySecondary Alteration of pituitary TSH productionAlteration of pituitary TSH production


Alteration in Thyroid FunctionAlteration in Thyroid Function

PrimaryPrimary Hyperthyroidism, hypothyroidismHyperthyroidism, hypothyroidism ThyrotoxicosisThyrotoxicosis Graves' diseaseGraves' disease

• Pretibial myxedemaPretibial myxedema Hyperthyroidism resulting from nodular thyroid Hyperthyroidism resulting from nodular thyroid

diseasedisease• GoiterGoiter

Thyrotoxic crisisThyrotoxic crisis


Thyrotoxicosis (Graves' Disease)Thyrotoxicosis (Graves' Disease)


Alterations of Thyroid FunctionAlterations of Thyroid Function HypothyroidismHypothyroidism

Primary hypothyroidismPrimary hypothyroidism• Subacute thyroiditisSubacute thyroiditis• Autoimmune thyroiditis (Hashimoto disease)Autoimmune thyroiditis (Hashimoto disease)• Painless thyroiditisPainless thyroiditis• Postpartum thyroiditisPostpartum thyroiditis• Myxedema comaMyxedema coma

Congenital hypothyroidismCongenital hypothyroidism Thyroid carcinomaThyroid carcinoma


HypothyroidismHypothyroidism


Alterations of Parathyroid Alterations of Parathyroid FunctionFunction

HyperparathyroidismHyperparathyroidism Primary hyperparathyroidismPrimary hyperparathyroidism

• Excess secretion of PTH from one or more parathyroid Excess secretion of PTH from one or more parathyroid glandsglands

• 85% caused by parathyroid adenomas85% caused by parathyroid adenomas

Secondary hyperparathyroidismSecondary hyperparathyroidism• Increase in PTH secondary to a chronic diseaseIncrease in PTH secondary to a chronic disease

Renal failureRenal failure Dietary deficiency of vitamin D, calciumDietary deficiency of vitamin D, calcium



HyperparathyroidismHyperparathyroidism HypercalciuriaHypercalciuria Alkaline urineAlkaline urine HyperphosphaturiaHyperphosphaturia

• Predisposes to the formation of calcium stones Predisposes to the formation of calcium stones



HypoparathyroidismHypoparathyroidism Abnormally low PTH levelsAbnormally low PTH levels

• Depressed serum calcium level Depressed serum calcium level

• Increased serum phosphate levelIncreased serum phosphate level

Usually caused by parathyroid damage in thyroid Usually caused by parathyroid damage in thyroid surgerysurgery



Hypoparathyroidism clinical signsHypoparathyroidism clinical signs Hypocalcemia Hypocalcemia

• Lowering of the threshold for nerve and muscle Lowering of the threshold for nerve and muscle excitation excitation

• Muscle spasms; hyperreflexia; tonic-clonic convulsions; Muscle spasms; hyperreflexia; tonic-clonic convulsions; laryngeal spasms; death from asphyxiation laryngeal spasms; death from asphyxiation

Phosphate retentionPhosphate retention


Diabetes MellitusDiabetes Mellitus Type 1Type 1 Type 2Type 2 Gestational diabetesGestational diabetes Glucose intoleranceGlucose intolerance

Fasting, 2 hour post glucose load, AFasting, 2 hour post glucose load, A11CC

Other typesOther types


Type 1 Diabetes MellitusType 1 Diabetes Mellitus Demonstrates pancreatic atrophy and loss of Demonstrates pancreatic atrophy and loss of

beta cellsbeta cells Macrophages, T and B lymphocytes, and Macrophages, T and B lymphocytes, and

natural killer cells are presentnatural killer cells are present Two typesTwo types

Immune Immune NonimmuneNonimmune


Type 1 Diabetes MellitusType 1 Diabetes Mellitus

Genetic susceptibilityGenetic susceptibility Environmental factorsEnvironmental factors Immunologically mediated destruction of beta Immunologically mediated destruction of beta

cellscells


Type 1 Diabetes MellitusType 1 Diabetes Mellitus

Clinical manifestationsClinical manifestations HyperglycemiaHyperglycemia

• 80% to 90% of the function of the insulin-secreting beta cells 80% to 90% of the function of the insulin-secreting beta cells in the islet of Langerhans is lost in the islet of Langerhans is lost

Polydipsia, polyuria, polyphagia, weight loss, and Polydipsia, polyuria, polyphagia, weight loss, and fatiguefatigue


Dysfunction of the PancreasDysfunction of the Pancreas Type 2 diabetes mellitusType 2 diabetes mellitus

Affects adults and childrenAffects adults and children Genetic environmental interactionGenetic environmental interaction Metabolic syndromeMetabolic syndrome TreatmentTreatment

• Exercise, treatment of obesity, medicationExercise, treatment of obesity, medication Clinical manifestationsClinical manifestations

• Recurrent infections, vision problems, neuropathyRecurrent infections, vision problems, neuropathy


Diabetes MellitusDiabetes Mellitus Maturity onset diabetes of youth (MODY)Maturity onset diabetes of youth (MODY) Gestational diabetesGestational diabetes


Acute Complications of Acute Complications of Diabetes MellitusDiabetes Mellitus

HypoglycemiaHypoglycemia Diabetic ketoacidosisDiabetic ketoacidosis

Usually associated with Type 1Usually associated with Type 1 Illness, trauma, surgery, emotionsIllness, trauma, surgery, emotions Total body (not serum) potassium deficiencyTotal body (not serum) potassium deficiency Cerebral edema, especially in childrenCerebral edema, especially in children



Hyperosmolar hyperglycemic nonketotic Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS)syndrome (HHNKS) Usually associated with Type 2Usually associated with Type 2 Higher glucoseHigher glucose Less ketosisLess ketosis Severe dehydration and potassium deficitSevere dehydration and potassium deficit



Somogyi effectSomogyi effect Usually associated with Type 1Usually associated with Type 1 Hypoglycemia with rebound hyperglycemiaHypoglycemia with rebound hyperglycemia Not as common as once thoughtNot as common as once thought

Dawn phenomenonDawn phenomenon Early morning glucose elevation without nocturnal Early morning glucose elevation without nocturnal

hypoglycemiahypoglycemia Related to nocturnal growth hormone elevationRelated to nocturnal growth hormone elevation


Chronic Complications ofChronic Complications ofDiabetes MellitusDiabetes Mellitus

Hyperglycemia and nonenzymatic glycosylationHyperglycemia and nonenzymatic glycosylation Hyperglycemia and the polyol pathwayHyperglycemia and the polyol pathway

Sorbitol and fructose increase intracellular osmotic Sorbitol and fructose increase intracellular osmotic pressure (attracts water, leading to cell injury)pressure (attracts water, leading to cell injury)

Evident in the eye lens, nerves, RBCsEvident in the eye lens, nerves, RBCs Protein kinase CProtein kinase C

• Enzyme inappropriately activated by hyperglycemiaEnzyme inappropriately activated by hyperglycemia

Microvascular diseaseMicrovascular disease RetinopathyRetinopathy Diabetic nephropathyDiabetic nephropathy


Diabetic NephropathyDiabetic Nephropathy


Complications of Diabetes MellitusComplications of Diabetes Mellitus Macrovascular diseaseMacrovascular disease

Coronary artery diseaseCoronary artery disease• Most common cause of death in persons with type 2Most common cause of death in persons with type 2

• Prevalence increases with duration of diseasePrevalence increases with duration of disease

StrokeStroke Peripheral arterial diseasePeripheral arterial disease

Diabetic neuropathiesDiabetic neuropathies InfectionInfection


Diabetic NeuropathyDiabetic Neuropathy


Alterations of Adrenal FunctionAlterations of Adrenal Function Disorders of the adrenal cortexDisorders of the adrenal cortex

Cushing diseaseCushing disease• Excessive anterior pituitary secretion of ACTHExcessive anterior pituitary secretion of ACTH

Cushing syndromeCushing syndrome• Excessive level of cortisol, regardless of causeExcessive level of cortisol, regardless of cause


Cushing DiseaseCushing Disease



HyperaldosteronismHyperaldosteronism• Primary hyperaldosteronism (Conn disease)Primary hyperaldosteronism (Conn disease)

• Secondary hyperaldosteronismSecondary hyperaldosteronism


Primary HyperaldosteronismPrimary Hyperaldosteronism



Adrenocortical hypofunctionAdrenocortical hypofunction• Primary adrenal insufficiency (Addison disease)Primary adrenal insufficiency (Addison disease)

Idiopathic Addison diseaseIdiopathic Addison disease

• Secondary hypocortisolismSecondary hypocortisolism



Hypersecretion of adrenal androgens and Hypersecretion of adrenal androgens and estrogensestrogens• FeminizationFeminization

• VirilizationVirilization


VirilizationVirilization


Alterations of Adrenal FunctionAlterations of Adrenal Function Disorders of the adrenal medullaDisorders of the adrenal medulla

Adrenal medulla hyperfunctionAdrenal medulla hyperfunction• Caused by tumors derived from the chromaffin cells of Caused by tumors derived from the chromaffin cells of

the adrenal medullathe adrenal medulla PheochromocytomasPheochromocytomas

• Secrete catecholamines on a continuous or episodic Secrete catecholamines on a continuous or episodic basisbasis


PheochromocytomaPheochromocytoma

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Alterations of Hormonal Regulation Chapter 21 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc