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Kaukab Azim, MBBS, PhD

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

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Kaukab Azim, MBBS, PhD

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  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. 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. 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. Growth hormone (Somatotropin) Gluconeogenesis

  8. Short stature due to Congenital/acquired GH deficiency (Pituitary Dwarfism) GH deficiency in adults Turner’s syndrome AIDS related muscle wasting Therapeutic uses of GH

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

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

  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

  15. Prolactin

  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 • 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 factorsVIIIc 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…

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