1. Hypothalamic & Pituitary Hormones
Kaukab Azim, MBBS, PhD

2. 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

3. 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

4. Growth hormone releasing hormone (GHRH)
GHRH analog: Sermorelin
Used rarely as a diagnostic test for GH responsiveness

5. IGF-1 as Peripheral effector
Growth Hormone
Secretion of GH is stimulated by GHRH and inhibited by GIH (somatostatin)
GH preparations for therapeutic use:
Somatropin: Recombinant human GH
Somatrem:
Recombinant human GH
IGF-1 as Peripheral effector

6. Molecular and Cellular Basis of GH Action

7. Growth hormone (Somatotropin)
Most of the actions of GH are mediated by IGF-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.
Gluconeogenesis

8. 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

9. GH preparations: Adverse effects
In children
Increased Intracranial tension
Headache
Papilledema
Scoliosis
Diabetes mellitus
In adults
Peripheral edema
Arthritis
Arthralgia
Myalgia
Carpal tunnel syndrome
Diabetes mellitus

10. 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

11. Somatostatin analogs: Therapeutic uses
Acromegaly
To prevent gigantism
Carcinoid syndrome
VIPoma, gastrinoma
Ruptured esophageal
varices

12. Somatostatin analogs: Adverse drug reactions
GIT problems: abdominal cramps, diarrhea, malabsorption, steatorrhea
Gall stones
Vitamin B12 deficiency
Cardiovascular problems: Sinus bradycardia, conduction disturbances

13. GH antagonist Pegvisomant Decreases IGF-1; GH remains high
Also effective in those who do not/stop responding to octreotide

14. Prolactin
Secretion of prolactin is under the control of dopamine (prolactin inhibiting hormone) secreted by hypothalamus

16. Prolactin

17. Hyperprolactinemia Prolactin secreting pituitary adenoma
Drug induced hyperprolactinemia
Antipsychotics
Metochlopramide
Drugs to manage hyperprolactinemia:
Bromocriptine
Cabergoline (ka-BER-goe-leen)

18. 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

19. Oxytocin : Adverse reactions
Cardiac arrhythmia, CNS stimulation, excessive uterine contractions, and hyponatremia.
Contraindications:
Fetal distress
Abnormal fetal presentation
Prematurity
CPD (cephalo-pelvic disproportion)

20. Vasopressin (arginine-vasopressin)
Vasopressin has:
Antidiuretic activity
Vasopressor activity (Vasoconstriction)
Decreased secretion/response to ADH causes Diabetes insipidus
Excessive secretion of ADH causes: SIADH

21. Vasopressin receptors
V1 receptors:
On vascular smooth muscles
Pressor effect: meditated through IP3/DAG ↑Ca+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

22. 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

23. SIADH Due to excessive secretion of ADH Drug induced SIADH:
Carbamazepine, vinca alkaloids, Chlorpropamide
Drugs to manage SIADH
Demeclocycline
Conivaptan (vasopressin antagonist)

24. Questions…