Chapter 18

DysfunctionInitially described

Excessive – hypersecretionInsufficient - hyposecretion

TodayAbnormal receptor functionAltered intracellular responseCirculating inhibitors* water-soluble hormones (not steroids –

lipid-soluble)

Alterations of the Hypothalamic – Pituitary System

“interruption of the pituitary stalk”

Destructive lesionsRupture after head injury Surgical transactionStem tumor

Loss of Hypothalamic Hormones

Diseases of the Posterior Pituitary

Syndrome of inappropriate anti-diuretic hormone secretion (SIADH)Hypersecretion of ADHEctopically produced (small cell carcinoma)Brain injury or infection (pulmonary

disease)Psychiatric/drugs

Water intoxication ( ↓Na+, hypo-osmolality)

Diseases of the Posterior Pituitary

Diabetes insipidusInsufficiency of ADHPolyuria and polydipsiaPartial or total inability to concentrate urineNeurogenic

Insufficient amounts of ADH

Nephrogenic Inadequate response to ADH

Psychogenic

Diseases of the Anterior Pituitary

Hypopituitarism – “spectrum”

Pituitary infarctionSheehan syndrome ( pituitary necrosis)

HemorrhageShock Other: head trauma, infections and tumors

Diseases of the Anterior Pituitary

Hypopituitarism Panhypopituitarism

ACTH deficiencyTSH deficiencyFSH & LH deficiencyGH deficiency

Dwarfism

Diseases of the Anterior Pituitary

Hyperpituitarism Commonly caused by a benign slow- growing pituitary adenoma

ManifestationHeadache and fatigueVisual changesHyposecretion of neighboring anterior pituitary hormones

Diseases of the Anterior Pituitary

Hypersecretion of growth hormone (GH)Acromegaly

Hypersecretion of GH during adulthood

Gigantism Hypersecretion of GH in children and

adolescents

Diseases of the Anterior PituitaryHypersecretion of growth hormone (GH)

Gigantism

Barry Bonds HGH & Steroids

Diseases of the Anterior PituitaryHypersecretion of prolactin

(most common)

Caused by prolactinomaIn females – amenorrhea, galactorrhea, hirsutism and osteopenia

In males – hypogonodism, erectile dysfunction, impaired libido, oligospermia and ↓ ejaculate volume

Alterations of Thyroid Function

HyperthyroidismThyrotoxicosisGraves diseaseHyperthyroidism resulting from nodular thyroid diseaseGoiter

Thyrotoxic crisis

Common Causes ofHyperthyroidism

Alterations of Thyroid FunctionHypothyroidism (most common)

PrimarySubacute thyroiditisAutoimmune thyroiditis (Hashimoto disease)

Painless thyroiditisPostpartum thyroiditisMyxedema coma

CongenitalThyroid carcinoma

Thyrotoxicosis: Graves Disease

Mechanism for Primary & Secondary Hypothyroidism

MyxedemaOrbital Edema, Facial Puffiness,

Dry Skin

HypothyroidismCongenital Hypothyroidism

“cretin”

Alterations of Parathyroid Function

Hyperparathyroidism Primary

Excess secretion of PTH from one or more parathyroid gland

Secondary↑ PTH 2° to a chronic disease

Alterations of Parathyroid Function

Hypopararthyroidism Abnormally low PTH levelsUsually caused by parathyroid damage in

thyroid surgery

Dysfunction of the Endocrine Pancreas

Diabetes Mellitus (Table 18-4)“group of disorders characterized by glucose intolerance”

DiagnosisRandom glucose > 200 mg/dlFBS > 126 mg/dl (8° fast)2 hour plasma glucose > 200 mg/dl

(75 gram OGTT)

Pre-diabetesIGT – impaired glucose tolerance - ↓ insulinIFG – impaired fasting glucose - ↑ hepatic glucose output

Glycosylated hemoglobin – HbA1cGoals

Maintain euglycemia, avoid hypoglycemiaPrevent severe cardiovascular and neurologic

complications

International Diabetes Foundation366 million people worldwide have this

disease

4.6 million death per year due to diabetes

465 billion dollars per year

Association for the Study of Diabetes Annual Meeting, Lisbon Portugal, Sept. 2011

Dysfunction of the Endocrine Pancreas

Diabetes Mellitus Type 1

Pancreatic atrophy and specific loss of beta cells

Macrophages, T and B – lymphocytes, and natural killer (NK) cells are present

Two typesImmuneNon-immune

Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus Genetic susceptibility – HLA-DR3 & DR 4

Environmental Factors DrugsNutritional intakeViruses

Mumps, coxsackie, rubella, cytomegalovirus

Immunologically mediated destruction of beta cellsBeta cell autoantibodiesAntibodies to insulin

Manifestations Hyperglycemia, polydipsia, polyuria,

polyphagia, weight loss, and fatigue – Table 18.5

Type 2 Diabetes Mellitus Non-insulin dependent

More common (90%)Risk factors: obesity, family history, ethnic

minority, puberty, female and metabolic syndrome

CauseUnknown

Genetic susceptibility Environmental factors

Cellular resistance to insulinObesity↓Beta cell response to plasma glucoseAbnormal glucagon secretion

Type 2 Diabetes Mellitus Pathophysiology

CombinationExcess nutrients (glucose/fat) → beta cell apoptosis

ObesityInflammatory cytokinesObesity related (intra-abdominal fat) cytokines (adipokines) and ↑ FFA release

Major factors: insulin resistance and beta cell death

Gestational Diabetes“glucose intolerance appears during

pregnancy”Risk factors

Family historyHigh-risk ethnic groupAdvanced maternal age (> 25 years old)Prior historyPCO syndromeBMI > 25 kg/m2

Past obstetrical complications - GD

Acute Complications of Diabetes Mellitus (Table 18-7)

Hypoglycemia (45 to 50 mg/dl)90% Type 1Insulin shock or reaction

Diabetic ketoacidosisSerious↓Insulin → ↑ counter regulatory hormones

Catecholamines, cortisol, glucagon, growth hormone

Peaks in adolescence

DKA & HHNKS

Acute Complications of Diabetes Mellitus

Hyperosmolar Hyperglycemic Nonketotic SyndromeType 2 – elderlyElevated serum glucose (500 mg/dl)Severe dehydration (↑↑ serum osmotic

pressure) → low blood volume ↓ BPKetosis – less common → insulin to # lipolysis

and protein catabolism

Somogyi effect – counter regulatory hormoneRebound hyperglycemia

Dawn phenomenon – GHEarly AM rise blood glucose

Chronic Complications of Diabetes Mellitus (Table 18-8)

Hyperglycemia and non-enzymatic glycosylation

Hyperglycemia and the polyol pathwayProtein kinase C

Microvascular diseaseRetinopathyDiabetic nephropathy

Chronic Complications of Diabetes Mellitus

Macrovascular disease (Type 2)Coronary artery diseaseStrokePeripheral artery disease

Diabetic neuropathiesInfection

Diabetes Mellitus & Atherosclerosis

Alterations of Adrenal Function

Disorders of the adrenal cortex

Cushing diseaseExcessive anterior pituitary secretion of ACTH

Cushing syndromeExcessive level of cortisol regardless of cause

Cushing Disease

Alterations of Adrenal Function Disorders of the adrenal cortex

HyperaldosteronismPrimary – Conn diseaseSecondary

Alterations of Adrenal Function Disorders of the adrenal cortex

Adrenocortical hypofunctionPrimary (Addison disease)Idiopathic Addison disease Secondary hypocortisolism

Alterations of Adrenal Function Disorders of the adrenal cortex

Hypersecretion of adrenal androgens and estrogensFeminizationVirilization

Virilization

Alterations of Adrenal Function

Disorders of the adrenal medulla

HyperfunctionChromaffin cell tumorPheochromocytoma

Secretions of catecholamines on a continuous or episodic basis (norepinephrine)