Endocrinology

• Hormones

  • Hypothalamus
  • Pituitary gland
  • Adrenal gland
  • Thyroid gland
  • Parathyroid gland
  • Pancreas
  • Ovaries and Testes
  • Placenta
• Endocrine System

  • also termed as neuroendocrine system
  • made of a network of ductless glands that releases chemical signals (hormones) into interstitial connective tissue (blood) and carried to a target tissue
  • controlled by feedback mechanism
  • consist of parenchymal cells
• Hormones


  Function: maintenance of the homeostasis of chemical composition of ECF and ICF and control metabolism, growth, fertility, and response to stress

  Regulation:

  1. Positive Feedback Mechanism - elevation of activity of system and production rate
  2. Negative Feedback Mechanism - decrease of activity of system and production rate
• Circadian rhythm 


  a change in level of hormone every 24 hours

  Example: Cortisol, GH, aldosterone, prolactin, TSH, testosterone, LH and FSH
• Infradian rhythm


  rhythms that are longer than circadian rhythm

  Example: menstrual cycle; FSH and LH are on monthly cycle
• Ectopic hormones


  hormones that were produced from a nonendocrine source

  Example: some benign and malignant tumors manufacture hormones similar to the hormone produced by the endocrine gland
• Classification of Hormones

  1. Steroid hormones - precursor: cholesterol, examples: estrogen, progesterone, testosterone, cortisone, Vit D, aldosterone
  2. Protein hormones - composed of amino acids and are usually produced by the partial hydrolysis of proteins, examples: pituitary gland hormones, parathormone, placental and pancreatic hormone
  3. Amine hormones - derived from tyrosine, example: T3 and T4 (secreted by thyroid glands, and sympathomimetic hormones (secreted by adrenal medulla)
• Deficiency

  • Congenital
  • Acquired

  Excess

  • Endogenous overproduction
  • Exogenous overmedication

  Resistance

  • Receptor-mediated
  • Post-receptor-mediated
  • Target tissue

  Primary problem - target gland: hypothyroidism

  Secondary problem - pituitary

  Tertiary problem - hypothalamus
• Hypothalamus


  *infundibulum - hypothalamus and pituitary gland

  • Corticotropin-Releasing Hormone (CRH) - stimulates secretion of ACTH
  • Gonadotropin-Releasing Hormone(GnRH) - stimulates secretion of FSH and LH
  • Growth Hormone-Releasing Hormone (GHRH) - stimulates secretion of GH
  • Thyrotropin-Releasing Hormone (TRH) - stimulates secretion of TSH and prolactin
  • Dopamine - inhibits prolactin release
  • Somatostatin - inhibits secretion of TSH and GH
• Pituitary Gland

  • "spit mucus"; "master gland"
  • Transponder - translates neural input into hormonal product
  • Hypophysis - undergrowth: pointing out its unique position under hypothalamus
  • Part of pituitary gland:
  • Anterior pituitary (adenohypophysis)
  • Intermediate lobe (pars intermedialis)
  • Posterior pituitary (neurohypophysis)
• Anterior Pituitary Hormones

  • Follicle-Stimulating Hormone
  • Luteinizing Hormone
  • Adrenocorticotropic Hormone
  • Thyroid-Stimulating Hormone
  • Prolactin
  • Growth Hormone (Somatotropin)
• Follicle-Stimulating Hormone

  • Function: stimulate growth of ovarian follicles and increases the plasma estrogen level
  • Regulation: under the control of gonadotropin-releasing hormone
  • Clinical significance: Women - high FSH ; Men - FSH stimulates to produce sperm
  • Assessment: Home test, first-morning-voided urine specimen, monitor during perimenopausal years and detect the beginning of menopause
• Luteinizing Hormone

  • Function: stimulates the production of progesterone at ovulation
  • Regulation: under the control of GnRH
  • Women - LH stimulates ruptured follicle after ovulation; Men - LH stimulates production of androgens
  • Assessment: measured to see hypogonadism, secondary failure: FSH and LH are low, primary failure: FSH and LH levels in serum and urine are high
• Adrenocorticotropic Hormone

  • Function: stimulates cortisol synthesis; regulator of adrenal androgen synthesis
  • Secretion: diurnal variation, highest levels in morning (6-9 am), lowest levels in early evening (6-11 pm), can also be found at 11-3 am
  • Stimuli: CRH, cortisol levels
  • Clinical significance: Addison's disease, ectopic tumors, after protein-rich meals
  • Assessment: ACTH Stimulation Test with Metyrapone - screening test decreasing ACTH; ACTH Suppression Test with Dexamethasone - screening test increased ACTH
• Thyroid-Stimulating Hormone

  • aka thyrotropin
  • Function: hormone responsible for synthesis of T3 and T4, promotion of thyroid gland growth and uptake of iodine by thyroid gland
  • Nocturnal levels approximately twice daytime levels
  • Blood levels may contribute to the evaluation of infertility
• Prolactin

  • Function: initiation and maintenance of lactation
  • affects the immune system
  • conjugates with estrogen and progesterone to promote breast development
  • peaks at 4 and 8 am, and 8 and 10 pm
  • Physiologic stimuli: (increased) exercise, sleep, stress, pain, coitus
  • Pharmacologic: (increased) >200 ng/mL
  • Clinical significance: Increased - hypogonadism; Decreased - panhypopituitarism, prolactinoma, Sheehan's syndrome (post-partum pituitary hemorrhage), Simmon's syndrome (low prolactin)
• Growth Hormone (Somatotropin)

  • Function: stimulate growth of bone; antagonistic effect to insulin, stimulates gluconeogenesis, promotes protein synthesis
  • Stimuli: GHRH; ghrelin, deep sleep
  • Inhibitory: Somatostatin (SS)
  • Secretion: pulses, average interpulse interval of 2 to 3 hours
  • Stimulates GH secretion: Sleep, exercise, a-agonist (norepinephrine), B-blockers (propranolol), fasting, levodopa
  • Inhibits GH secretion: glucose loading, B-agonists(epiephrine), a-blockers (phentolamine)
• Growth Hormone

  • Clinical Significance

  Increased Levels: pituitary gigantism (children), acromegaly (adult), low protein diet, hypoglycemia

  Decreased Levels: pituitary dwarfism (children), hypothyroidism (adult), hyperglycemia

  • Assessment:

  Children: GH measured to evaluate lack of growth

  Adults: GH measured as one assessment of pituitary function

  • Test for Deficiency

  Physical Tolerance Test (screening) - if GH fails to increase confirmation must be made

  Insulin Tolerance Test (once considered gold standard) - 24 hour or nighttime

  Arginine Stimulation Test - 2nd confirmatory test
• Test for Acromegaly


  IGF-1 or Somatomedin C (screening)

  Glucose Suppression Test or OGTT (confirmatory)

  -performed after an overnight fast

  -patient is given 100-gram oral glucose load GH is measured at time zero and at 60 and 120 minutes after glucose ingestion

  • normal: 1 ng/mL

  if GH fails to decline, it is diagnostic of acromegaly
• Posterior Pituitary Hormones

  • Antidiuretic Hormone (vasopressin)
  • Oxytocin
  • synthesized in hypothalamus
• Antidiuretic Hormone (vasopressin)

  • controls water homeostasis and enhancing water resorption
  • raises blood pressure
  • stimulates ACTH secretion
  • renal free water clearance, lowering plasma osmolality
  • Clinical Significance: Increased - SIADH (syndrome of inappropriate ADH secretion), ectopic tumor; Decreased - polyuria, diabetes insipidus (neurogenic DI and nephrogenic DI) and polydipsia
• Neurogenic DI

  • true DI
  • hypothalamic DI
  • cranial DI
  • central DI
• Nephrogenic DI

  • kidneys
• Oxytocin

  • Stimuli: uterine contraction during childbirth (Ferguson reflex)
  • tactile receptors which causes ejection of breastmilk
  • pitocin - synthetic oxytocin
• Pineal Gland

  • midbrain
  • controlled by nerve stimuli
  • Melatonin - sleep pattern, decreases the pigmentation of skin
  • Serotonin - happy hormone
• Adrenal Gland

  • Adrenal cortex - from mesenchymal cells that differentiate 3 distinct zones
  • Adrenal medulla - arises from neural crest during 2nd month of fetal development
  • Pyramid-like shape in retroperitoneal space
• Adrenal Cortex

  • Zona Glomerulosa (G-Zone)- 10% synthesize aldosteron for sodium retention
  • Zona Fasciculata (F-Zone)-75% synthesize glucocorticoids
  • Zona Reticularis Cells (15%) sulfate DHEA to DHEA-S main adrenal androgen
• Steroidogenesis

  • Precursor: cholesterol
  • Cytochrome P450
• Zona Glomerulosa

  • Aldosterone - electrolyte regulation, control of RAAS, negative feedback mechanism in juxtaglomerular apparatus
  • Clinical Significance: hypoaldosteronism - 21-hydroxylase deficiency ; hyperaldosteronism
• Hyperaldosteronism in Zona Glomerulosa

  • 1' hyperaldosteronism - Conn's syndrome
  • 2' hyperaldosteronism - excessive production of renin
  • Liddle's syndrome - pseudohyperaldosteronism
  • Bartter's syndrome - bumetanide-sensitive
  • Gitelman's syndrome - thiazide-sensitive
• Cortisol in Zona Fasciculata

  Function: stimulates gluconeogenesis

  Stimuli: ACTH

  Secretion: diurnal, associated with sleep-wake cycle

  Excreted in urine as 17-hydroxycorticosteroid
• Hypocortisolism

  • 1' hypocortisolism: Addison's disease
  • 2' hypocortisolism: hypothalamic-pituitary with loss of ACTH
  • Assessment: ACTH stimulation test - Cosyntropin or Metyrapone Test
• Hypercortisolism

  • Cushing's syndrome - 1' hypercortisolism, weight gain but thin limbs, "buffalo hump", decreased WBC
  • Cushing's disease - 2' hypercortisolism; increased ACTH
  • Small cell lung lung CA
  • Adrenal cortex cancer
  • Assessment: 24 h urine free cortisol test (screening)
  • low dose dexamethasone (confirmatory)
• Congenital Adrenal Hyperplasia

  -autosomal recessive

  -caused by 21-hydroxylase, 11 B-hydroxylase, 3 B-hydroxysteroid dehydrogenase-isomerase

  • Hirsutism - male pattern of hair growth in women
  • Virilization - like hirsutism but also frontal bleeding
  • Defeminization - decreased breast size and amenorrhea
• Weak androgens or adrenal androgens in Zona Reticularis

  • Functions: precursors for production of more potent androgens and estrogens
  • Precursors: pregnenolone and 17-OHP
  • androstenedione and DHEA
  • CS: pseudohermaphroditism
  • Assessment: free testosterone and DHEA-S
  • Principle: DHEA
• Adrenal Medulla

  • composed of chromaffin cells and secrete catecholamine
• Adrenal Medulla

  • composed of chromaffin cells and secrete catecholamine
  • L tyrosine
  • Metabolism: norepi and epi (monoamine oxidase)
  • Stimulants: acetylcholine
• Catecholamines - Metanephrines - Aromatic Acid
• Dopamine - 3-Methoxy-tyramine - HVA

  Noradrenaline - Normetaphrine - VMA

  Adrenaline - Metanephrine - VMA
• Adrenal Medulla

  • Norepinephrine
  • Epinephrine
  • Dopamine