Endocrinology 1

• common abbreviations in endocrinology

  
• Major endocrine glands:

  • Pituitary, thyroid, Parathyroid and adrenal
  • Hypothalamus is neuroendocrine origin
  • Some have endocrine and exocrine functions (Pancreas, gonads and placenta)
• what are the three major classes of molecules that function as hormones?


  • polypeptides - water soluble
  • amines - water soluble
  • steroids - lipid soluble
• outline the signalling pathways that peptides/amines vs steroid homornes use to cause change in the target cell

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• the hypothalamic pituitary relationship - alot of the signalling that controls homeostasis in the body is determined by this mechanism

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• the regulation of hormone secretion is regulated by the implementation of positive and negative feedback 


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• the hypothalamus/central endocrine gland sits under the thalamus and is connected to the pituitary gland by the infundibulum. The pituitary gland is made of two lobes, what are they and what is their embryological root? 


  1. anterior pituitary gland (Adenohypophysis) – protrusion of ectoderm from roof of mouth (Rathke’s pouch)
  2. posterior pituitary gland (Neurohypophysis) - from the neuroectoderm
• how does the hypothalamus act on the posterior piuitary to respond to changes in homeostasis?


  1. Hormone synthesis and Transport via Axons: hormones synthesized in cell bodies of neurons in hypothalamus and transported along axons through the infundibulum to posterior pituitary gland.
  2. Storage and Release: stored in nerve terminals until needed, stimulated by nerve impulses from hypothalamus or physiological cues, released into bloodstream.
  3. Control by Hypothalamus: oxytocin and vasopressin under control of hypothalamus response to stimuli
• what is the difference between the anterior and posterior pituitary in terms of storing and synthesising


  Anterior pituitary synthesize and stores hormones

  Posterior pituitary doesn't synthesize hormones but only stores and release them
• how does the hypothalamus act on the anterior piuitary

  1. Hormone Synthesis: The hypothalamus produces and releases hypothalamic-releasing hormones or hypothalamic-inhibiting hormones.
  2. Hypothalamic-Pituitary Portal System: hypothalamic hormones transported to anterior pituitary gland network of blood vessels called hypothalamic-pituitary portal system, allows direct communication.
  3. Stimulation or Inhibition: hypothalamic-releasing hormones stimulate release of pituitary hormones, while hypothalamic-inhibiting hormones suppress others AKA trophic hormones
  4. Regulated by Feedback Loops:
• outline how the Hypothalamo-hypophyseal Relationship causes the hypothalmus to promote the release of pituitary hormones

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• the anterior lobe has 5 different types of cells, what are they and what do they secrete?

  1. somatotrophs - Growth hormone (GH)
  2. thyrotrophs - TSH
  3. Corticotrophs - ACTH
  4. Gonadotrophs - FSH and LH
  5. Lactrotrophs - LH
• what does the Posterior Lobe hormones secrete?


  üThe posterior lobe of the pituitary secretes ADH and oxytocin. Both ADH and oxytocin are neuropeptides synthesized in cell bodies of hypothalamic neurons and secreted from nerve terminals in the posterior pituitary.
• what can cause hypersecretory disorders in the endocrine system


  1.Hormone secreting tumors (Adenoma or Carcinoma)

  2.Hyperplasia

  3.Autoimmune stimulation

  4.Ectopically produced peptide hormone
• what can cause hyposecretory disorders in the endocrine system


  1.Autoimmune disease

  2.Tumors

  3. Infection

  4.Hemorrhage
• which hypothalmic hormones control the release of pituitary hormones?

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• how is growth hormone/somatotrophin released?

  hypothalamus releases GHRH -> stimulates somatorophs in the anterior ituitary to release GH

  inhibited by GHIH

  GH secretion in is a pulsatile manner due to the pulasatile release of GHRH and GHIH -> due to negative feedback by the bloodstream
• what are the two major actions of GH/Somatotropin and what are the two ways this is acheived?


  • promotes the growth of skeletal and soft tissues
  • metabolic on carbs, lipid, proteins

  two ways:

  1. indirect - through the action of insulin-like growth factor 1 (IGF-1)
  2. Direct - through the action of the RG receptors in target tissue

  
• name three ways that growth hormone deficiencies can affect individuals


  1. pituitary dwarfism
  2. Laron dwarfism
  3. GH deficiency in adults
• explain what happens in pituitary dwarfism, how does this affect GH and IGF-1


  the pituitary gland does not release GH

  causes -> reduced growth rate and short stature

  brain development and intellectualism good

  GH and IGF-1 are both decreased
• Explain what happens in Lawson's Dwarfism, how does this change plasma GH and IGF levels?


  • defective GH receptors
  • decreased IGF but increased GH in the blood
  • a type fo GH insensitivity syndrome
• what happens if someone acquires a GH deficiency as an adult


  the fusion of the epiphyseal plates has happened so no change to height

  • but lack of GH causes -> increased body fat, decreased muscle mass, increased fatigue and decreased physical fitness
• which 2 conditions are associted with excess GH in adults vs children

  • adults - acrogmegaly
  • children - gigantisim
• what happens in gigantisms

  • Gigantism is the pituitary disorder characterized by excess growth of the body
  • Excess GH secretion before the fusion of the epiphyseal plates of the long bones
  • Rapid increase in height and weight
  • Other features are: Large hands and feet, coarsening of the facial features with frontal bossing and prognathism (projection of the jaw), headaches, and excessive sweating.
  • May be because of a tumor in the anterior pituitary that hyper-secretes GH

  
• what happens in acromegaly

  • Excess GH secretion after the fusion of the  epiphyseal plates (in adults).
  • Excessive skeletal, soft tissue and internal organ growths.
  • Acral bony overgrowth results in frontal  bossing, increased hand and foot size,  mandibular enlargement with prognathism  (projection of the jaw), and frontal bossing.
  • Other features: Headaches, ↑BP, excessive  sweating and ↑blood glucose.
  • Treatment-Somatostatin analogues (Lanreotide/Octreotide / Pasireotide)
• what is proglactin and its function in men and women?

  • peptide hormone secreted by lactotrophs
  • inhibited by hypothalamic Dopamine/ PIH in males and females
  • Serum level very low in both men and women.
  • PRL level increases only during pregnancy and breast feeding in women.
  • Actions of Prolactin on target tissue 1) breast development 2) milk production (lactogenesis), but not ejection of milk
  • PRL suppresses sexual drive in both sex.
  • In the ovary, PRL causes anovulation.

  
• explain how prolactinomas affect men, women, both and the tx

  most common type of pituitary tumours - 40% of all

  In Male:

  • Loss of libido

   • Low sperm count

  • Erectile dysfunction

  • Low testosterone

  • Gynecomastia

  In Female:

  • Loss of menstruation

   • Anovulation

  • Loss of sexual drive

  • Galactorrhea

  both - visual defects, headcaches, infertility, secondary hypothyroididm

  tx - dopamine agonists, surgical + radiological
• what are the two post pituitary hormones and what are they synthesised from?


  • vasopressin and ADH
  • both are synthesised from a large peptide prohormone called neurophysin
• oxytocin:

  • where is it synthesised
  • where does it act
  • which feedback loop

  • paraventricular nucleus
  • targets

  Action of oxytocin

  Myoepithelial cells of the mammary gland---- Milk ejection

  Smooth muscles of the uterus (Myometrium)---- Expulsion of fetus and placenta 

  • positive feedback mechanism
• where is ADH produced and where does it act?

  • supraoptic neucleus
  • ADH increases the water permeability of principal cells in the late distal tubule and collecting duct.
  • ADH also acts via V1 receptors in the vascular smooth muscles to cause contractions
• which factors increase ADH/AVP release?

  Increased body fluid osmolality

  Decrease blood volume

  Decrease blood pressure

  Angiotensin II

  Pain/Stress

  • Nausea and Vomiting
• which factors inhibit the release of ADH/AVP


  • Decreased body fluid osmolality
  • Increased blood volume
  • Increased blood pressure
  • Atrial natriuretic peptide
  • Ethanol
  • Diuretic
• decreased ADH action can cause diabetes insipidus, there are two types of DI, what are they?

  • neurogenic DI
  • nephrogenic DI
• what do the gonadotropic cells in the anterior pituitary secrete and what are their functions?


  LH - gametes production (egg/sperm)

  FSH - stimulate production of gonadal hormones (progesterone, oestrogen and testosterone), in females - mature follicles of the egg and ovulation
• why is the production of sex hormones important and how are they affected by the HPA

  • sex hormones are vital for bone metabolism
  • GnRH secretion is pulsatile
  • HPA affected by environmental factors such as stress, exercise, weight loss
  • Deregulation of HPA leads to menopause in female
  • HPA activity in males decreases over time
• what is hypopituitarism and panhypopituitarism?


  •Hypopituitarism means deficiency of one or more hormones of the  pituitary

  •Panhypopituitarism means a condition of inadequate or absent  production of ALL ANTERIOR PITUITARY HORMONES
• what can cause hypopituitarism and panhypopituitarism?


  •congenital or acquired pituitary gland deficit

  •impaired functioning of hypothalamus to secrete hypophysiotropic hormones

  •Most common causes are  compression (tumor), Gene mutation, tumors, blockage in blood flow(ischemia),iatrogenic or chronic inflammation

  • Clinical features:

  Depend on what hormone/s are deficient (LH,FSH and GH lost before TSH and ACTH hormone)
• signs and symptoms, Ix and Tx and of Diabetes insipidus

  Sign and Symptoms

  • polyuria, nocturia and polydipsia in adults
  • large volumes of dilute urine
  • Marked dehydration
  • Anorexia and epigastric fullness
  • Hypernatremia 
  • Fatigue

  Investigation and treatment

        -Serum osmolality

        -Serum electrolyte level

        -Urine osmolarity

        -Water deprivation test followed by  Vasopressin  test

  vTreatment

   In central DI, the synthetic AVP analogue desmopressin (DDAVP)

  Nephrogenic DI is treated with an adequate fluid intake; salt restriction
• increased ADH/ Syndrome of inappropriate ADH secretion (SIADH)


  Causes

  • Small cell lung cancer
  • Severe brain trauma
  • Sepsis or infection of brain (Meningitis)

  Sign and Symptoms

  Plasma ADH high

  Physiologic ADH regulation is not working

  Highly concentrated (hypertonic) urine with low volume

  Hyponatremia and osmolality

  These patients have normal BP or high blood pressure

  Treatment

  Stop fluid and treatment of underlying cause

  
• Diabetes insipidus is when there are low levels of ADH


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