chapter 18. dysfunction initially described excessive – hypersecretion insufficient -...
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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)
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