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Hypothalamic
&
Pituitary Hormones
Kaukab Azim, MBBS, PhD
Uses of Hypothalamic & Pituitary Hormones
• Short stature due to hypopituitarism (Pituitary dwarfism)
• Acromegaly and gigantism
• Carcinoid syndrome, VIPoma, and ruptured esophageal
varices
• Hyperprolactinemia
• Induction of labor
• Diabetes insipidus
• SIADH
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Concepts in Endocrinology
• Primary, secondary and tertiary endocrine disorders
• Feedback regulation
• Endocrine disorders:
– Deficiency, or
– Excess
• Mechanisms of action
• Uses of hormones /analogs:
– Diagnostic use
– Therapeutic use
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Growth hormone releasing hormone
(GHRH)
• GHRH analog: Sermorelin
• Used rarely as a diagnostic test for GH responsiveness
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Growth Hormone
• Secretion of GH is stimulated
by GHRH and inhibited by GIH
(somatostatin)
• GH preparations for
therapeutic use:
– Somatropin: Recombinant
human GH
IGF-1 as
Peripheral
effector
– Somatrem: Recombinant
human GH
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Growth hormone (Somatotropin)
• Most of the actions of GH are
mediated by IGF-1 ( insulinlike growth factor 1)
“somatomedins” - the
peptides produced in the
liver and cartilage.
• The somatomedins stimulate
skeletal growth, amino acid
transport, protein synthesis,
nucleic acid synthesis and
cell proliferation.
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Therapeutic uses of GH
• Short stature due to
Congenital/acquired GH
deficiency (Pituitary Dwarfism)
• GH deficiency in adults
• Turner’s syndrome
• AIDS related muscle wasting
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GH preparations: Adverse effects
In children
• Increased Intracranial
tension
• Headache
• Papilledema
• Scoliosis
• Diabetes mellitus
In adults
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•
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•
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Peripheral edema
Arthritis
Arthralgia
Myalgia
Carpal tunnel syndrome
Diabetes mellitus
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Growth hormone inhibiting hormone
(Somatostatin)
Somatostatin analogs:
• Octreotide – S/C, daily
• Sandostatin-LAR - (Slow release preparation of
octreotide) once every 4 weeks
• Administration of somatostatin analogs result in
decrease in GH and IGF-1 levels
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Somatostatin analogs: Therapeutic uses
• Acromegaly
• To prevent gigantism
• Carcinoid syndrome
• VIPoma, gastrinoma
• Ruptured esophageal
varices
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Somatostatin analogs:
Adverse drug reactions
• GIT problems:
– Abdominal cramps, diarrhea, malabsorption,
steatorrhea
– Gall stones
– Vitamin B12 deficiency
• Cardiovascular problems:
– Sinus bradycardia, conduction disturbances
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GH antagonist
Pegvisomant
• Decreases IGF-1; GH remains high
• Effective in those who do not/stop responding
to octreotide
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Molecular and Cellular Basis of GH Action
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Prolactin
Secretion of prolactin is under
the control of DOPAMINE
(prolactin inhibiting hormone)
secreted by hypothalamus
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Hyperprolactinemia
• Prolactin secreting pituitary adenoma
• Drug induced hyperprolactinemia
– Antipsychotics
– Metochlopramide
Drugs to manage hyperprolactinemia:
• Bromocriptine
• Cabergoline (ka-BER-goe-leen)
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Oxytocin
Actions meditated through
IP3/DAG
↑ Ca+2
Therapeutic uses
• To induce and augment labor after cervix has
ripened
• To control post-partum hemorrhage
• To improve milk ejection – nasal oxytocin
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Oxytocin : Adverse reactions
• Cardiac arrhythmia, CNS stimulation, excessive
uterine contractions, and hyponatremia.
Contraindications:
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Fetal distress
Abnormal fetal presentation
Prematurity
CPD (cephalo-pelvic disproportion)
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Vasopressin
(arginine-vasopressin)
Vasopressin has:
– Antidiuretic activity
– Vasopressor activity (Vasoconstriction)
• Decreased secretion/response to ADH causes
Diabetes insipidus
• Excessive secretion of ADH causes: SIADH
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Vasopressin receptors
1. V1 receptors:
– On vascular smooth muscles
– Pressor effect: meditated through IP3/DAG
↑Ca+2
2. V2 receptors
– Renal: On distal and collecting duct cells of nephron
• Antidiuretic effect: mediated through ↑cAMP
– Extrarenal:
• Release of coagulation factors VIIIc and Von
willebrand factor
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Therapeutic uses of vasopressin/analogs
• Vasopressin (Pitressin)
 Therapeutic uses
• Advanced Cardiac life support
• Bleeding esophageal varices
• Desmopressin
 Long-acting synthetic analog of vasopressin
 Antidiuretic : vasopressor activity = 3000:1
 Therapeutic uses:
• Neurogenic diabetes insipidus
• Von Willebrand disease and hemophillia
• Enuresis
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SIADH
• Due to excessive secretion of ADH
Drug induced SIADH:
– Carbamazepine, vinca alkaloids, Chlorpropamide
Drugs to manage SIADH
– Demeclocycline
– Conivaptan (vasopressin antagonist)
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Questions…
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