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Alterations of Hormonal Regulation. Chapter 18. Dysfunction Initially described Excessive – hypersecretion Insufficient - hyposecretion Today Abnormal receptor function Altered intracellular response Circulating inhibitors * water-soluble hormones (not steroids – lipid-soluble).

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slide2

Dysfunction

  • Initially described
    • Excessive – hypersecretion
    • Insufficient - hyposecretion
  • Today
    • Abnormal receptor function
    • Altered intracellular response
    • Circulating inhibitors

* water-soluble hormones (not steroids – lipid-soluble)

slide4

Alterations of the Hypothalamic – Pituitary System

“interruption of the pituitary stalk”

  • Destructive lesions
  • Rupture after head injury
  • Surgical transaction
  • Stem tumor
slide6

Diseases of the Posterior Pituitary

  • Syndrome of inappropriate anti-diuretic hormone secretion (SIADH)
    • Hypersecretion of ADH
    • Ectopically produced (small cell carcinoma)
    • Brain injury or infection (pulmonary disease)
    • Psychiatric/drugs
  • Water intoxication ( ↓Na+, hypo-osmolality)
slide7

Diseases of the Posterior Pituitary

  • Diabetes insipidus
    • Insufficiency of ADH
    • Polyuria and polydipsia
    • Partial or total inability to concentrate urine
    • Neurogenic
      • Insufficient amounts of ADH
    • Nephrogenic
      • Inadequate response to ADH
    • Psychogenic
slide8

Diseases of the Anterior Pituitary

  • Hypopituitarism – “spectrum”
    • Pituitary infarction
      • Sheehan syndrome ( pituitary necrosis)
      • Hemorrhage
      • Shock
    • Other: head trauma, infections and tumors
slide9

Diseases of the Anterior Pituitary

  • Hypopituitarism
    • Panhypopituitarism
      • ACTH deficiency
      • TSH deficiency
      • FSH & LH deficiency
      • GH deficiency
slide11

Diseases of the Anterior Pituitary

  • Hyperpituitarism
    • Commonly caused by a benign slow- growing pituitary adenoma
    • Manifestation
      • Headache and fatigue
      • Visual changes
      • Hyposecretion of neighboring anterior pituitary hormones
slide12

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 pituitary
Diseases of the Anterior Pituitary
  • Hypersecretion of growth hormone (GH)
slide15

Diseases of the Anterior Pituitary

  • Hypersecretion of prolactin (most common)
    • Caused by prolactinoma
      • In females – amenorrhea, galactorrhea, hirsutism and osteopenia
      • In males – hypogonodism, erectile dysfunction, impaired libido, oligospermia and ↓ ejaculate volume
slide16

Alterations of Thyroid Function

  • Hyperthyroidism
    • Thyrotoxicosis
    • Graves disease
    • Hyperthyroidism resulting from nodular thyroid disease
      • Goiter
    • Thyrotoxic crisis
slide19

Alterations of Thyroid Function

  • Hyporthyroidism (most common)
    • Primary
      • Subacute thyroiditis
      • Autoimmune thyroiditis (Hashimoto disease)
      • Painless thyroiditis
      • Postpartum thyroiditis
      • Myxedema coma
    • Congenital
    • Thyroid carcinoma
slide22

Alterations of Parathyroid Function

  • Hyperparathyroidism
    • Primary
      • Excess secretion of PTH from one or more parathyroid gland
    • Secondary
      • ↑ PTH 2° to a chronic disease
slide23

Alterations of Parathyroid Function

  • Hypopararthyroidism
    • Abnormally low PTH levels
    • Usually caused by parathyroid damage in thyroid surgery
slide24

Dysfunction of the Endocrine Pancreas

Diabetes Mellitus

“group of disorders characterized by glucose intolerance”

  • Diagnosis
    • Random glucose > 200 mg/dl
    • FBS > 126 mg/dl (8° fast)
    • 2 hour plasma glucose > 200 mg/dl

(75 gram OGTT)

  • Pre-diabetes
    • IGT – impaired glucose tolerance - ↓ insulin
    • IFG – impaired fasting glucose - ↑ hepatic glucose output
  • Glycosylated hemoglobin – HbA1c
  • Goals
    • Maintain euglycemia, avoid hypoglycemia
    • Prevent severe cardiovascular and neurologic complications
slide25

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 types
      • Immune
      • Non-immune
slide26

Type 1 Diabetes Mellitus

  • Genetic susceptibility – HLA-DR3 & DR 4
  • Environmental Factors
    • Drugs
    • Nutritional intake
    • Viruses
      • Mumps, coxsackie, rubella, cytomegalovirus
  • Immunologically mediated destruction of beta cells
    • Beta cell autoantibodies
    • Antibodies to insulin
  • Manifestations
    • Hyperglycemia, polydipsia, polyuria, polyphagia, weight loss, and fatigue – Table 18.5
slide27

Type 2 Diabetes Mellitus

  • Non-insulin dependent
    • More common (90%)
    • Risk factors: obesity, family history, ethnic minority, puberty, female and metabolic syndrome
  • Cause
    • Unknown
      • Genetic susceptibility
      • Environmental factors
  • Cellular resistance to insulin
    • Obesity
    • ↓Beta cell response to plasma glucose
    • Abnormal glucagon secretion
slide28

Type 2 Diabetes Mellitus

  • Pathophysiology
    • Combination
      • Excess nutrients (glucose/fat) → beta cell apoptosis
      • Obesity
      • Inflammatory cytokines
      • Obesity related (intra-abdominal fat) cytokines (adipokines) and ↑ FFA release
    • Major factors: insulin resistance and beta cell death

Table 18-6 Manifestations

slide29

Gestational Diabetes

“glucose intolerance appears during pregnancy”

  • Risk factors
    • Family history
    • High-risk ethnic group
    • Advanced maternal age (> 25 years old)
    • Prior history
    • PCO syndrome
    • BMI > 25 kg/m2
    • Past obstetrical complications - GD
slide30

Acute Complications of Diabetes Mellitus

  • Hypoglycemia (45 to 50 mg/dl)
    • 90% Type 1
    • Insulin shock or reaction
  • Diabetic ketoacidosis
    • Serious
    • ↓Insulin → ↑ counter regulatory hormones
      • Catecholamines, cortisol, glucagon, growth hormone
    • Peaks in adolescence
slide32

Acute Complications of Diabetes Mellitus

  • Hyperosmolar Hyperglycemic NonketoticSyndrome
    • Type 2 – elderly
    • Elevated serum glucose (500 mg/dl)
    • Severe dehydration (↑↑ serum osmotic pressure) → low blood volume ↓ BP
    • Ketosis – less common → insulin to # lipolysis and protein catabolism
  • Somogyi effect – counter regulatory hormone
    • Rebound hyperglycemia
  • Dawn phenomenon – GH
    • Early AM rise blood glucose
slide33

Chronic Complications of Diabetes Mellitus

  • Hyperglycemia and non-enzymatic glycosylation
  • Hyperglycemia and the polyol pathway
    • Protein kinase C
  • Microvascular disease
    • Retinopathy
    • Diabetic nephropathy
slide34

Chronic Complications of Diabetes Mellitus

  • Macrovascular disease (Type 2)
    • Coronary artery disease
    • Stroke
    • Peripheral artery disease
  • Diabetic neuropathies
  • Infection
slide35

Alterations of Adrenal Function

  • Disorders of the adrenal cortex
    • Cushing disease
      • Excessive anterior pituitary secretion of ACTH
    • Cushing syndrome
      • Excessive level of cortisol regardless of cause
slide38

Alterations of Adrenal Function

  • Disorders of the adrenal cortex
    • Hyperaldosteronism
      • Primary – Conn disease
      • Secondary
slide39

Alterations of Adrenal Function

  • Disorders of the adrenal cortex
    • Adrenocortical hypofunction
      • Primary (Addison disease)
        • Idiopathic Addison disease
      • Secondary hypocortisolism
slide40

Alterations of Adrenal Function

  • Disorders of the adrenal cortex
    • Hypersecretion of adrenal androgens and estrogens
      • Feminization
      • Virilization
slide42

Alterations of Adrenal Function

  • Disorders of the adrenal medulla
    • Hyperfunction
      • Chromaffin cell tumor
      • Pheochromocytoma
    • Secretions of catecholamines on a continuous or episodic basis (norepinephrine)