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

➲ SIADH2

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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: SermorelinUsed 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

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IGF-1 as Peripheral

effector

Molecular and Cellular Basis of GH Action

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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

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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➲ 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➲ Also effective in those who do not/stop

responding to octreotide

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Prolactin

Secretion of prolactin is under the control of dopamine (prolactin inhibiting

hormone) secreted by hypothalamus

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Prolactin

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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:

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…