Hypothalamus Pituitary inter relations

• Hypothalamus
  • Hypothalamic peptides stimulate secretion of anterior pituitary hormones
  • Dopamine inhibits prolactin secretion
  • Under neural regulation by variety of neurotransmitters
  • Regulated by closed -loop feedback system
  • TRH, GnRF, CRF, GRF are releasing hormones
• Anterior pituitary 
  • Adenohypophysis
  • Derived from Rathke's pouch
  • Somatomammotropins
    • Growth hormone
    • Prolactin / lactogenic
    • Chorionic somatomamotropin
  • Corticotrophin (ACTH)
    • Stimulate secretion of glucocorticoid by adrenal cortex
  • Pituitary glycoprotein hormones
    • Thyroid stimulating hormone (TSH)
    • Follicle stimulating hormone (FSH)
      • Regulate ovulation and secretion of steroid by ovary
    • Leuteinizing hormone (LH)
      • Regulate ovulation and secretion of steroid by ovary
• Posterior pituitary 
  • Neurohypophysis
  • Anatomical extension of hypothalamus
  • Derived from diencephalon
  • Located in sella tursica
  • In the base of brain
• Tests of anterior pituitary function
  • ACTH
    • ACTH / undetectable in normal basal state
    • Deficiency: Stimulation by induced hypoglycemia / of hypothalamus
      • CRF not available for clinical use
      • Hypothalamic problem
        • Positive CRF test
        • Negative response to hypoglycemia
      • Pituitary problem
        • Negative CRF test
        • Negative response to hypoglycemia
    • ACTH excess
      • Suppression with dexamethasone
  • TSH
    • Deficiency: TRH stimulation: TSH levels increase up to 15
      • Pituitary problem: Flat response
      • Hypothalamic problem: Normal response
    • Excess
      • Flat response to TRH
  • Gonadotropins
    • Deficiency
    • GnRH stimulation
    • Clomiphere stimulation
      • Hypothalamic dysfunction
        • Normal response to GnRH stimulation
        • Response to Clomiphere stimulation
      • Pituitary dysfunction
    • Excess
  • Prolactin
  • Growth hormone
    • Measurable
    • Deficiency: stimulation by hypoglycemia, L-dopa, GRF
    • Excess: Glucose loading

Anterior pituitary hypofunction

• Hypothalamic defect
• Pituitary gland defect
• Common Etiology
  • Tumors
  • Granulomas
  • Vascular necrosis
  • Surgery
  • Radiation
  • Compression by a space occupying lesion
• Clinical features
  • Growth hormone
    • Short stature
    • Delayed puberty
  • ACTH
    • Symptoms of adrenal cortical deficiency
  • TSH
    • Symptoms of hypothyroidism
  • Gonadotropin
    • Amenorrhea
    • Diminished libido
    • Loss of pubic and axillary hair
    • Atrophy of breast and Testis
• Diagnosis
  • Differentiate from polyglandular deficiency states 
  • Deficiency of major target organ products
  • Absence of compensatory increases of tropic hormones of pituitary
  • Establish abnormality in the hypothalamic-pituitary-axis
  • Use of stimulation studies
  • Use of hypothalamic releasing factors to distinguish between Hypothalamic and pituitary dysfunction
• Treatment
  • Replacement of specific hormones
    • Caution in thyroid replacement. Concomitant or preceding replacement of glucocorticoids
  • Treat etiology

Anterior pituitary hyperfunction

• Usually benign slow growing tumors
  • Neurological symptoms (Headache)
  • Visual defects (bitemporal hemianopsia)
  • Pituitary insufficiency
  • Excessive secretion of any of the anterior pituitary hormones
    • Prolactin / Galactorrhea
    • Growth hormone / Acromegaly, Gigantism (in young)
    • ACTH / Cushing's syndrome
  • Diagnosis
    • Clinical picture
    • Excess of the hormone
    • Inability to suppress by physiological maneuvers
    • MRI and high resolution CT for evaluation of tumor
  • Treatment options
    • Correct deficiencies
    • Surgery
    • Radiation
    • Bromocriptine

Disorders of posterior pituitary

• Oxytocin / Release of breast milk, promote uterine contraction in labor

• Anitdiuretic hormone (ADH) / Regulates water metabolism
  • Response to serum osmolality, hypovolemia and hypotension
  • Normal serum osmolality 285
  • Acts on distal nephron to induce an increased water permeability
  • Excess: Water intoxication. Syndrome of inappropriate ADH secretion
  • Deficiency: Diabetes insipidus
    • Central vs Nephrogenic 
    • Central : due to hypothalamic rather than pituitary problem
    • AVP is stored in pituitary but synthesized in the hypothalamus
    • Polyuria (>3 L/day) and polydypsia
    • Dilute urine (sp gr <1010 or osmolality <300)
    • Need to distinguish from psychogenic polydypsia
    • Water deprivation test followed by pitressin 
  • Treatment
    • Chlorpropamide
    • ADH replacement by nasal insufflations