Role of the pituitary

Question 1

Describe the anatomy of the pituitary

Answer 1

The Pituitary Gland
- Small outgrowth of the forebrain
- Two functional parts
- Adenohypophysis (anterior pituitary)
- Rathke’s pouch – ectoderm above mouth
- Neurohypophysis (posterior pituitary)
- Hypothalamus (outgrowth of )
- Anterior and posterior parts Move together during development

Relational anatomy:
- superior: lateral ventricle and optic chaasm
- lateral: internal carotid
- inferior: sphenoid sinus

Key takeaway : anterior and posterior pituitary can be differentiated on MRI.

Question 2

Describe the inputs to the hypothalamus

Answer 2

• Autonomic function
• Higher centres
• Endocrine feedback
• Environmental cues e.g. temperature
  **All of the above inputs into the hypothalamus, which then signals the pituitary, which then signals the endocrine glands.

The hypothalamus can be considered the interface between the brain and the hormonal system.
Associated with autonomic function.

Question 3

Describe vasculature and innervation of pituitary

Answer 3

• Hypothalamus
  
  • Hypothalamic neurons release hormones directly into capillary plexus
• Anterior Pituitary
  
  • Blood supply from median eminence of hypothalamus – portal system
  • Hormones from hypothalamus to pituitary
  • Sympathetic/parasympathetic –note that these are not present in posterior pituitary
• Posterior Pituitary
  
  • Supraoptic and paraventricular nuclei in hypothalamus
  • axons and axon terminals in posterior pituitary

Question 4

Describe the release of hormones from the anterior and posterior pituitary

Answer 4

• hypothalamic neurons releasing hormones
• axon terminals in portal vessel
• transport releasing hormones into anterior pituitary
• pituitary hormones produced, released into capillary plexus of anterior pituitary
• axons travelling down pituitary stalk
• released into capillary plexus of posterior pituitary

Question 5

Describe the regulation of secretion from hypothalamus and pituitary

Answer 5

• Higher Centres
• Hypothalamus
  
  • Releasing Hormone
• Pituitary
  
  • Pituitary Hormone
  • • Short Feedback Loop (eg. LH, ACTH, GH, from pituitary) to hypothalamus
• Target Gland
  
  • Hormone
    
    • Long Feedback Loop (eg. Thyroxine, Cortisol, from endocrine glands)

Question 6

Describe the posterior pituitary hormones

Answer 6

• Vasopressin/Antidiuretic Hormone (ADH)
  
  • Produced by supraoptic nucleus
  • Conserves water - concentrates urine
  • Water reabsorption by collecting tubule
  • Deficiency: diabetes insipidus
    
    • Extreme thirst and polyuria
    • ↑ plasma sodium and osmolality
  • Excess: inappropriate ADH “water intoxication”, hyponatremia
• Oxytocin
  
  • Milk let-down
  • no pathological derangement recorded in the literature

Question 7

Describe the anterior pituitary hormones and their broad function, hormones produced and inhibiting factors

Answer 7

• Thyroid Stimulating Hormone (TSH)
  
  • Stimulates:
    
    • Thyroxine synthesis
    • Thyroid growth
  • Regulation:
    
    • TRH: stimulates release
    • Inhibited by thyroid hormones (T3, T4) – feedback inhibition
      
      • eg due to insult, low T4 leads to high TSH
      • TSH is a sensitive means of diagnosing underactive thyroid
      • vice versa can occur eg high T4 low TSH
  • Acts via cAMP
• Corticotrophin (ACTH)
  
  • Released as prohormone: pro-opio-melanocortin
    
    • endogenous opiate
  • Maintenance of adrenal cortical function
    
    • Cortisol
    • Other adrenocortical hormones (eg androgens)
    • Pigmentation in excess (Addison’s disease, due to POMC)
  • Control of ACTH secretion:
    
    • CRH
    • Cortisol (feedback inhibition)
      
      • similar to thyroxine, high cortisol low CRH, high CRH low cortisol
• Luteinising Hormone (LH)
  
  • Males:
    
    • Leydig/interstitial cells – testosterone
    • Inhibited by testosterone
  • Females:
    
    • Interstitial cells – estrogen, androgens, progestins ^[double check]
    • Inhibited by estrogen
• Follicle Stimulating Hormone (FSH)
  
  • Regulation of gametogenesis
  • Males:
    
    • Sertoli cells – development of spermatozoa
    • Inhibited by inhibin
  • Females:
    
    • Granulosa cell of ovarian follicle
• Works synergistically with LH

Question 8

Describe prolactin

Answer 8

• Secreted by lactotrophs of anterior pituitary
• Lactation: only known function
• Inhibits reproductive hormone secretion
• Release inhibited by dopamine (“prolactin inhibitory factor”)
  
  • no stimulating factor
• In animals, it plays a role in osmoregulation and growth
• Stalk transection leads to an increase in prolactin levels

Question 9

Describe growth hormone

Answer 9

• Promotes growth in the skeleton, muscles, and viscera
• Its effects are mediated by somatomedins, particularly IGF-1 (Insulin-like Growth Factor-1)
• Growth hormone is released at night during growth
• It has a variety of metabolic effects:
  
  • Anabolic, leading to a positive nitrogen balance
  • Anti-insulin effects
• Growth hormone secretion is stimulated by GHRH (Growth Hormone-Releasing Hormone), stress, and exercise
• It is inhibited by somatostatin, which is secreted in the gastrointestinal system and the central nervous system
  
  • Somatostatin acts as a regulatory hormone, primarily functioning in a paracrine manner

Question 10

Describe the pituitary releasing hormones

Answer 10

• These are small peptides
• They are active at relatively high concentrations
• Rapidly degraded
• Present in low concentrations in peripheral circulation
• Special circulation mechanisms allow for high concentrations to reach their target tissues, and create ‘short-acting+’
• Some examples include:
  
  • CRH (Corticotrophin Releasing Hormone)
  • TRH (Thyrotrophin Releasing Hormone)
  • GHRH (Growth Hormone-Releasing Hormone)
  • Somatostatin (which inhibits GH)
  • Vasopressin (which stimulates ACTH secretion)
  • GnRH (Gonadotrophin-Releasing Hormone, responsible for LH and FSH secretion)
    
    • pulsatile secretion- LSH and FSH secretion depends on magnitude and frequency of pulses
    • if secretion is continuous, FSH and LH levels drop ^[manipulated e.g. in anticancer treatments - prostate]
  • Dopamine (inhibits Prolactin)
    
    • important neurotransmitter – basal ganglia (movement disorders)
    • inhibited by drugs e.g. anti-psychotics and end-stage renal failure
    • agonists used to treat hyperprolactinaemia

Question 11

Describe pituitary disorders: hyperfunction

Answer 11

• Hyperfunction of the pituitary gland is usually caused by a tumour
  
  • drugs can shrink size
• Prolactin is the commonest
• The most common hyperfunction involves Prolactin, leading to symptoms such as galactorrhea (abnormal lactation in females), amenorrhea (lack of periods), and infertility
• Other hyperfunctional conditions include:
  
  • ADH (Antidiuretic Hormone) excess, leading to the syndrome of inappropriate ADH secretion (SIADH) from nonpituitary causes (leads to hyponatraemia, water intoxication, brain oedema)
  • Acromegaly, which results from excess Growth Hormone
  • Cushing’s syndrome, often accompanied by ACTH excess, which may also have an adrenal or ectopic source –> cortisol
  • Disorders related to TSH, LH, FSH, and oxytocin are exceedingly rare

Question 12

Describe pituitary dysfunction: hypofunction

Answer 12

• Hypofunction of any pituitary hormone (except Prolactin and oxytocin) doesn’t result in recognized clinical syndromes
• Hypofunction can range from mild (e.g., Growth Hormone) to lethal (e.g., ACTH)
• Causes of hypofunction can include tumors, trauma, infection, developmental issues
• In some cases, multiple hormones can be affected, leading to panhypopituitarism

Question 13

Describe mass effects

Answer 13

• Pituitary tumors can lead to mass effects, as they enlarge upwards
• Common mass effect symptoms include:
  
  • Absent headache
  • Impingement on the optic chiasm, resulting in bitemporal hemianopia
  • Cranial nerve effects
  • Hydrocephalus
  • Hypopituitarism
  • Mild hyperprolactinemia due to stalk compression or disruption
  • Diabetes insipidus (when the tumor is suprasellar)- hypothalamus and pituitary damage, poor ADH, thirst and urination

Question 14

Describe acromegaly

Answer 14

• Acromegaly is characterized by growth hormone excess in adults
• In children, this condition is known as gigantism
• Acromegaly is often not recognized for 10-20 years in adults because linear bone growth is no longer possible after the fusion of epiphyses
• Clinical features of acromegaly include:
  
  • Increased ring, shoe, glove, and hat sizes
  • Enlargement of the nose, lips, soft tissues of the face, tongue, and jaw (prognathism), leading to facial coarsening
  • A deep cavernous voice
  • Fleshy, enlarged hands and feet
  • Increased metabolic rate, resulting in sweating and warm skin
  • Skin tags and joint problems ^[hypertrophy of skin]

Question 15

Describe the metabolic and visceral features of acromegaly

Answer 15

• Acromegaly is associated with several metabolic and visceral features, including:
  
  • Hypertension
  • Glucose intolerance
  • Cardiac enlargement and heart failure
  • Enlargement of the liver, spleen, kidneys, thyroid, and adrenal glands
• Mortality is increased in acromegaly patients, with a 72% higher risk compared to the general population, and a reduction in survival within 10 years ^[damage can persist even with treatment]
  
  • this is reduced by surgery
• Surgery, such as trans-sphenoidal or transfrontal procedures, is the primary treatment option for acromegaly
• Somatostatin agonists may also be indicated
• Radiotherapy: may take several years for effect
• Dopamine agonists - bromocriptine and cabergoline (although not very effective)