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

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

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

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

Molecular and Cellular Basis of GH Action

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

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

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

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

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

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

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

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

Prolactin

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

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

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

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

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

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

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

Questions…