Pharmacy CLI 307: Endocrine Disorders

Pathophysiology of Endocrine Disorders

Introduction to Endocrine System

• The endocrine system is one of the two major systems for coordination and control of organ function.
• It consists of endocrine glands that secrete chemical messengers called hormones.
• Hormones are defined as chemical signals secreted into the bloodstream that act on distant tissues, usually in a regulatory fashion.
• The primary functions of hormones include:
  • Control of reproduction
  • General growth and development of the body
  • Regulation of electrolyte composition of bodily fluids
  • Control of energy metabolism

Classification of Hormones

• Hormones can be classified into three main groups:
  • Amino acid derivatives (e.g. epinephrine, norepinephrine, thyroxine)
  • Steroids (e.g. cortisol, estrogen, progesterone, testosterone, vitamin D)
  • Proteins/Polypeptides (e.g. insulin, glucagon, GH, PTH, TSH, LH, FSH, β-hCG, TRH, vasopressin)

Endocrine Glands

• The major endocrine glands that function primarily to secrete hormones include:
  • Pituitary gland
    • Produces hormones such as ADH, oxytocin, ACTH, GH, TSH, LH, FSH, prolactin
  • Thyroid gland
    • Produces hormones such as thyroxine, triiodothyronine, and calcitonin
  • Parathyroid gland
    • Produces parathyroid hormone
  • Adrenal gland
    • Produces hormones such as cortisol, aldosterone, epinephrine, and sex steroids
  • Pancreas
    • Produces hormones such as insulin, glucagon
  • Ovaries and testicles
    • Produce hormones such as androgens, estrogens, and progesterone
  • Pineal gland
    • Produces melatonin
• Other endocrine glands and tissues include:
  • Heart (produces atrial natriuretic peptide)
  • Kidney (produces erythropoietin)
  • Liver (produces somatomedin)
  • Skin (produces vitamin D3)
  • Gastrointestinal tract (produces gastrin, CCK, and VIP)
  • Adipose tissue (produces leptin)
  • Hypothalamus (produces CRH, TRH, GnRH, dopamine)

Action of Hormones

• Hormones elicit their effects by binding to receptors, which can be:
  • Cell-surface membrane receptors (e.g. amino acid derivatives, peptide hormones)
  • Intracellular nuclear receptors (e.g. steroids, thyroid hormones, vitamin D)
• Hormones can regulate intracellular metabolic processes through:
  • Second messengers (e.g. c-AMP, c-GMP, phospholipase C-Ca2+, tyrosine kinase)

Pituitary Gland

• The pituitary gland is divided into two parts:
  • Anterior pituitary (adenohypophysis)
  • Posterior pituitary (neurohypophysis)
• Hormones produced by the pituitary gland include:
  • GH, TSH, LH, FSH, prolactin, ACTH

Pathophysiology of Endocrine Diseases

• Endocrine diseases can be divided into three major types:
  • Hormone excess (hypersecretion)
  • Hormone deficiency (hyposecretion)
  • Hormone resistance
• Endocrine disorders can be caused by:
  • Genetic defects
  • Tumors
  • Infection
  • Infiltrative processes
  • Vascular disorders
  • Trauma
  • Immune-mediated injury
  • Metabolic abnormalities
  • Drugs

Hormones of the Anterior Pituitary Gland

• Growth Hormone (GH)
  • Functions: stimulates cell growth and expansion, antagonizes insulin
  • Deficiency: short stature in children
  • Excess: gigantism, acromegaly
• Thyroid-Stimulating Hormone (TSH)
  • Functions: stimulates thyroid gland to secrete T3 and T4
  • Deficiency: hypothyroidism
  • Excess: hyperthyroidism
• Adrenocorticotropic Hormone (ACTH)
  • Functions: stimulates adrenal cortex to secrete glucocorticoids and sex steroids
  • Deficiency: hypocortisolism
  • Excess: Cushing's syndrome
• Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)
  • Functions: stimulate development of ovarian follicle and oestrogen production
  • Deficiency: amenorrhoea, sterility, loss of sexual potency
  • Excess: sexual precocity
• Prolactin
  • Functions: stimulates development of breast tissue, lactation
  • Deficiency: failure of lactation
  • Excess: galactorrhoea, hypogonadism

Hormones of the Posterior Pituitary Gland

• Vasopressin (ADH)
  • Functions: stimulates reabsorption of water in kidneys, vasoconstriction
  • Deficiency: diabetes insipidus
  • Excess: SIADH (syndrome of inappropriate ADH)
• Oxytocin
  • Functions: stimulates uterine contraction, milk ejection
  • Deficiency: failure of milk ejection
  • Excess: none known

Adrenal Gland

• Adrenal Cortex
  • Produces glucocorticoids, mineralocorticoids, and sex steroids
  • Functions: regulate carbohydrate, protein, and fat metabolism, electrolyte balance
  • Disorders: Cushing's syndrome, Addison's disease, Conn's syndrome
• Adrenal Medulla
  • Produces epinephrine and norepinephrine
  • Functions: stimulates "fight or flight" response
  • Disorders: pheochromocytoma

Pancreas

• Produces insulin, glucagon, and somatostatin
• Functions: regulate blood glucose levels
• Disorders: diabetes mellitus, insulinoma

Thyroid Gland

• Produces thyroxine (T4), triiodothyronine (T3), and calcitonin
• Functions: regulate basal metabolic rate, cardiac contractility, and growth
• Disorders: hyperthyroidism, hypothyroidism, thyroiditis