Pituitary Gland

The pituitary gland is divided into the anterior lobe & posterior lobe. All hormones of the anterior lobe are under the control of hypothalamus, so hypothalamus will increase or decrease the level of anterior pituitary hormones. If there is a loss of connection / lesion between the pituitary and hypothalamus , then the level of all anterior pituitary hormones will decrease and only the prolactin level will increase. Growth hormone Inhibiting hormone and prolactin are under inhibitory control (GHIH and PIH, respectively). Prolactin is under only inhibitory control because there is no releasing hormone for prolactin.

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1. Growth Hormone Inhibiting Hormones (GHIH) / Somatostatin

Somatostatin uses

S - Secretory diarrhea

O - Oesophageal varices

M - Malignancy [islet cell tumors]

A - Acromegaly

• Somatostatin: Short acting therefore not effective
• Octreotide: Long acting somatostatin derivative, therefore it is preferred
• Any drug ending with “-tide” is peptide
• Any endogenous substance ending with “-in” are peptides

Eg:

• Somatostatin
• Vasopressin
• Oxytocin
  • Peptides can't be given orally
  • Octreotide → Given by S/C route

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2. Prolactin-Inhibiting Hormone (PIH) or Dopamine [DA]

Hypothalamus

↓

Secrete PIH

↓

Stimulate dopamine receptors in anterior pituitary

↓

↓ Serum prolactin

• DA acts through D2 receptors
• Dopamine Agonists (Drugs stimulating Dopamine Receptors act like PIH i.e. drugs decreasing prolactin)
• Eg. Bromocriptine, Cabergoline (Long acting)

Uses of Dopamine Agonists

• Dopamine: Diabetes mellitus type 2 (Bromocriptine is approved for this because it decreases insulin resistance)
• Agonists: Acromegaly (by decreasing GH)
• Suppress: Suppression of lactation
• Plasma: Parkinsonism (Bromocriptine can be used)
• Prolactin: Hyperprolactinemia
• Dopamine Agonists Suppress Plasma Prolactin

Acromegaly

Drugs given are:

1. Decrease GH release - Octreotide and Cabergoline
2. GH receptor antagonist - Pegvisomant

Pegvisomant

• Somatotropin antagonist (not somatostatin antagonist)
• Polyethylene glycol added to make it long acting
• Visual problems is its main S/E
• Pegvisomant and Octreotide are injectable drugs
• Cabergoline and Bromocriptine are oral drugs.
• Cabergoline is longer acting than Bromocriptine
• Suppression of lactation
  • Prolactin is a milk secreting hormone
  • Decreasing the level of prolactin can suppress lactation. Cabergoline can be used.

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3. Gonadotropin Releasing Hormone (GnRH)

Indications of GnRH

i. In pulsatile manner

1. Anovulatory infertility
2. Hypogonadotropic hypogonadism
3. Delayed Puberty

ii. In continuous Fashion

1. Cancers
   • Prostate cancer
   • Breast cancer
2. Endometriosis
3. Precocious Puberty
   • GnRH Agonists include:
     • Leuprolide
     • Nafarelin (nasal route)
     • Goserelin
     • Busurelin
     • Histarelin
   • Not effective orally (Mostly given by subcutaneous route)
   • Flare-up reaction: When these are given in a continuous manner, during the initial 2-3 days there is aggravation of disease. This is called a flare-up reaction. To prevent this, we give GnRH antagonists.

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GnRH Antagonists:

• Cetrorelix
• Ganirelix
• Abarelix
• Degarelix
  • No flare-up reaction
  • But they do not↑sex hormones (used only to↓sex hormones)
  • Not effective orally
• Elagolix
  • Recently approved oral GnRH antagonist
  • No other GnRH agonist or antagonist is effective orally
  • Approved for pain due to endometriosis

Posterior Pituitary

Secretes 2 main hormones: Oxytocin, Vasopressin / Antidiuretic hormone (ADH)

Oxytocin functions 

• Main function: contracts the uterus
  • DOC for augmentation of labor
  • DOC for postpartum hemorrhage
• Other function: ejection of milk
• DOC for breast engorgement

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Vasopressin (Antidiuretic hormone) Acts On:

• V1 receptors: V1 receptor are present in blood vessels and cause vasoconstriction
• V2 receptors: V2 receptors are present in the Kidney and cause decrease in urine. V2 receptors are also present in endothelium of blood vessels where vWF and Factor VIII are released

Vasopressin Receptor Antagonists:

• They cause Vasodilation (via V1 ) and increase in urine (via V2 ) 
• Vasopressin Antagonists are '-vaptans'
• These include:
  • Conivaptan: Given via intravenous route
  • Tolvaptan: Given via oral route
• Uses of vaptans:
  • Congestive heart failure (due to property of diuresis and Vasodilation)
  • SIADH

SIADH (Syndrome of Inappropriate ADH Secretion)

• Function of ADH is to retain only water
• Excessive ADH causes increased water retention leading to Hyponatremia
• Stepwise management in cases of SIADH
  • Fluid restriction
  • 3% NaCl (Hypertonic saline)
  • If symptoms persist, then drugs are given. DOCvaptans (Conivaptan / Tolvaptan)
  • Demeclocycline (inhibits the release of ADH from posterior pituitary)

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