Kaukab Azim, MBBS, PhD

Hypothalamic &

Pituitary Hormones

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

2

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

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

5

IGF-1 as Peripheral

effector

6

Growth hormone (Somatotropin)• Most of the actions of GH are

mediated by IGF-1 ( insulin-like 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.

Gluconeogenesis

7

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

8

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

9

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

10

Somatostatin analogs: Therapeutic uses

• Acromegaly• To prevent gigantism• Carcinoid syndrome• VIPoma, gastrinoma• Ruptured esophageal

varices

11

Somatostatin analogs: Adverse drug reactions

• GIT problems: –Abdominal cramps, diarrhea, malabsorption,

steatorrhea–Gall stones –Vitamin B12 deficiency

• Cardiovascular problems: – Sinus bradycardia, conduction disturbances

12

GH antagonist

Pegvisomant

• Decreases IGF-1; GH remains high• Effective in those who do not/stop responding

to octreotide

Molecular and Cellular Basis of GH Action

13

14

Prolactin

Secretion of prolactin is under the control of DOPAMINE (prolactin inhibiting hormone) secreted by hypothalamus

16

Hyperprolactinemia

• Prolactin secreting pituitary adenoma• Drug induced hyperprolactinemia– Antipsychotics– Metochlopramide

Drugs to manage hyperprolactinemia:

• Bromocriptine• Cabergoline (ka-BER-goe-leen)

17

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

18

Oxytocin : Adverse reactions

• Cardiac arrhythmia, CNS stimulation, excessive uterine contractions, and hyponatremia.

Contraindications:

• Fetal distress• Abnormal fetal presentation• Prematurity• CPD (cephalo-pelvic disproportion)

19

Vasopressin (arginine-vasopressin)

Vasopressin has:

–Antidiuretic activity–Vasopressor activity (Vasoconstriction)

• Decreased secretion/response to ADH causes Diabetes insipidus

• Excessive secretion of ADH causes: SIADH

20

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

21

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

22

SIADH

• Due to excessive secretion of ADH

Drug induced SIADH:

– Carbamazepine, vinca alkaloids, Chlorpropamide

Drugs to manage SIADH

–Demeclocycline– Conivaptan (vasopressin antagonist)

23

Questions…