Week 2

• Anatomy of hypothalamus

  • Lies at base of brain in midline
  • Hypo (under) thalamus (chamber)

  Anatomical landmarks

  • Forms floor and lateral wall of 3rd ventricle
  • within optic chiasm antero-inferiorly
  • Situated inferiorly to pituitary gland
• Functions of the hypothalamus

  • Coordinating centre of the endocrine system
  • Behavioural responses
  • Appetite and satiety
  • Thirst
  • Thermoregulation
  • Circadian rhythm/sleep-wake cycle
• Hypothalamic-Pituitary Axis

  • Control centre of the endocrine system

  Input signals

  • via cortical inputs for the autonomic nervous system, environment and peripheral endocrine system

  Output signals

  • Peptide hormones to pituitary
  • Pituitary controls multiple endocrine glands
• Primary vs secondary vs tertiary problem

  
  

  Primary dysfunction

  • Problem with the end organ for example: thyroidectomy, hypothyroidism and primary hypothyroidism

  Secondary dysfunction

  • Pituitary problem, for example: pituitary macroadenoma and Secondary hypothyroidism.

  Tertiary dysfunction

  • Problem with hypothalamus, for example: Hypothalamic tumour
• Anatomy of hypothalamus

  • Derived from ventral diencephalon
  • Comprised of neurons and supporting cells
  • Neuron cell bodies form nuclei, the Supra-optic nucleus that secretes arginine vasopressin (AVP).
  • While the paraventricular nucleus secretes oxytocin and AVP
  • Median eminence connected to pituitary gland via pituitary stalk (infundibulum)
• The hypothalamic-pituitary axis

  
  

  Posterior pituitary

  • Direct extension of hypothalamus
  • Secretes 2 hormones (AVP and oxytocin) made in hypothalamus

  Anterior pituitary

  • Embryologically distinct structure
  • Hypothalamic hormones released into hypophyseal portal system
• Hypothalamic Hormones

  • Small peptide hormones with no known binding proteins that rapidly degrade
  • Secreted into hypothalamic-pituitary portal system
  • Bathes in anterior pituitary before secretion in a pulsatile manner
• Hypothalamic dysfunction

  • Local mass effect with loss of hypothalamic hormones
  • Hypopituitarism (ant and post)
  • Loss of thirst and satiety
  • Impaired thermoregulation and memory
• Pituitary gland (Hypophysis)

  • Midline Endocrine gland
  • Attached to brain by pituitary stalk (infundibulum)
  • Sits in sella turcica (Turkish saddle) of sphenoid bone
• Anatomical planes

  
  

  Sagittal plane

  • Divides body into left and right halves
  • View from the side along the sagittal suture

  Coronal plane

  • Divides body into front and back sections
  • View from the front

  Transverse (axial) plane

  • Divides body into superior and inferior parts
• Pituitary gland – Anatomy, which divides into anterior and posterior pituitary lobes

  • Anterior pituitary has Glandular tissue, so makes and secretes 6 hormones
  • Posterior pituitary has neural tissue and secretes 2 hormones.

  Boundaries

  • Inferior to Sphenoid bone and air sinus

  Cavernous sinus

  • Lateral and temporal lobes
  • Superior to optic chiasm & diaphragma sella

  Cavernous sinus contents

  • Internal carotid artery
  • CN III, IV, VI and CN V1/V2
• Posterior pituitary (neurohypophysis)

  • Direct extension of hypothalamus
  • Has Supraoptic nucleus and paraventricular nucleus synthesise oxytocin and AVP
  • The hormones travel down neurons to posterior pituitary, where they are released
• Pituitary gland – Blood supply

  • Hypothalamus communicates with anterior pituitary via hypothalamic hormones released into hypophyseal portal system.
  • Inferior petrosal artery directly supplies posterior pituitary lobe.
  • Pituitary veins drain into cavernous sinus, then inferior petrosal sinus and finally internal jugular vein.
• Anterior Pituitary (Adenohypophysis) - Histology containing 5 secretory cell types

  • Somatotrophs (50%): secrete growth hormone (GH)
  • Lactotrophs (20%): secrete prolactin (PRL)
  • Corticotrophs (20%): secrete adrenocorticotropic hormone (ACTH)
  • Gonadotrophs (5%): secrete lutenising hormone and follicle stimulating hormone (LH & FSH)
  • Thyrotrophs (5%): secrete thyroid stimulating hormone (TSH)
• The hypothalamus is the region in the ventral brain above the pituitary gland and below the third ventricle, which coordinates the endocrine system.

  It receives signals from various regions of the brain and releases hormones that act on the pituitary gland to direct the functions of various organs.

  The hypothalamus affects the functions of the pituitary gland, thyroid gland, adrenal glands, kidneys, musculoskeletal system, and reproductive organs.
• Afferent pathways to the hypothalamic nuclei arise from the brainstem, thalamus, basal ganglia, cerebral cortex, and olfactory areas.
• The hypothalamic-neurohypophysial tract connects the para-ventricular and supraoptic nuclei of the hypothalamus to the nerve terminals in the median eminence, towards the anterior pituitary gland, and the posterior pituitary gland.
• The para-ventricular nucleus releases mostly oxytocin and some ADH, while the supraoptic nucleus releases mostly ADH and some oxytocin directly into the bloodstream.
• The pituitary gland is comprised of the adenohypophysis (anterior pituitary) and the neurohypophysis (posterior pituitary).
• The hypothalamus releases hormones such as thyrotropin-releasing hormone (TRH), gonadotropin-releasing hormone (GnRH), growth hormone-releasing hormone (GHRH), corticotropin-releasing hormone (CRH), somatostatin, and dopamine into the blood, which travel to the anterior pituitary.
• Vasopressin (ADH) and oxytocin are hormones made in the hypothalamus itself and travel to the posterior pituitary.
• Impairment or damage to any of the hypothalamic nuclei can cause deficits in their respective functions, leading to various abnormalities.
• Disorders of the hypothalamic-pituitary axis can manifest in various clinical syndromes, such as acromegaly and pituitary gigantism.
• Pituitary gigantism occurs in adolescents and children with excess growth hormone before the fusion of their epiphyseal growth plates.
• Acromegaly occurs in adults with excess growth hormone after the fusion of their epiphyseal growth plates.
• Excess growth hormone can originate from excess hypothalamic growth hormone-releasing hormone, excess growth hormone production by pituitary somatotroph cells, or rarely from an ectopic source.
• Excess growth hormone leads to excess secretion of insulin-like growth factor, which mediates growth-promoting effects in various cells and regulates cellular DNA synthesis.
• Pituitary gigantism presents with rapid abnormal increase in height and weight gain in adolescents and children.
• Acromegaly presents with soft tissue overgrowth, skin thickening, enlarged hands and feet, and other characteristic features in adults.
• Central diabetes insipidus is a condition caused by a decrease in anti-diuretic hormone production, most commonly due to idiopathic destruction of ADH-secreting hypothalamic nuclei.

  Central diabetes insipidus presents with polyuria, polydipsia, and nocturia, and can lead to hypernatremia if thirst is impaired.
• Syndrome of inappropriate anti-diuretic hormone (SIADH) occurs due to inappropriately high serum ADH concentration, commonly caused by central nervous system disorders, malignancies, and certain medications.

  SIADH presents with hyponatremia and associated symptoms.
• Functional Hypothalamic Amenorrhea is characterized by secondary amenorrhea due to low body weight disorders, excessive exercise, inadequate caloric intake, and emotional stress. Symptoms include low bone density, anovulatory infertility, breast and vaginal atrophy, dyspareunia, sexual dysfunction, and mood disorders.
• Hyperprolactinemia is caused by an excess of prolactin secretion due to decreased dopamine release from the hypothalamus. Symptoms vary depending on gender, with pre-menopausal women experiencing infertility, headaches, oligomenorrhea, and galactorrhea, post-menopausal women rarely presenting symptoms, and men having hypogonadotropic hypogonadism resulting in decreased libido, impotence, infertility, gynecomastia, and rarely galactorrhea.
• Treatment of hypothalamic dysfunction depends on the underlying cause and may involve medications, hormone replacement therapy, and supportive care.
• The hypothalamus is a small region within the brain that controls various bodily functions and serves as a link between the nervous and endocrine systems.
• Factors that indirectly influence hypothalamic function include the light-dark cycle, temperature, signals from other members of the same species, and various sensory stimuli.
• The pituitary gland consists of two parts: the anterior pituitary and the posterior pituitary.
• The anterior pituitary produces hormones that stimulate target glands or directly affect target organs, including adrenocorticotropic hormone (ACTH), gonadotropins, thyroid-stimulating hormone (TSH), growth hormone (GH), and prolactin.
• Hormones such as GH and thyroid hormone can modify blood sugar levels and insulin release
• Prolactin

  • Excess in females leads to galactorrhoea, oligo/amenorrhoea and low libido
  • Excess in males leads to low libido and erectile dysfunction
  • Due to breast-feeding/nipple stimulation, pregnancy, pituitary lactotroph adenoma, the stalk effect stress (venepuncture/fit)
  • Medications include antipsychotics and metoclopramide
  • Deficiency in females leads to Inability to lactate