HYPOTHALAMIC, PITUITARY AND THYROID PHARMACOLOGY DR FATAI OLUYADI USMLEINCLINED.COM 1

HYPOTHALAMO-PITUITARY HORMONES AND PHARMACOLOGICAL APPLICATION Here we take a look at the normal Hypothalamic and Pituitary hormones and their several pharmacological applications USMLEINCLINED.COM 2

HYPOTHALAMIC HORMONES CORTISOL RELEASING HORMONE (CRH) – Controls the adrenocortical axis by stimulating anterior release of ACTH DOPAMINE – Inhibits the release of Prolactin from the anterior pituitary GROWTH HORMONE RELEASING HORMONE (GHRH)- Controls the growth hormone axis by stimulating anterior pituitary release of Growth Hormone GONADOTROPIN RELEASING HORMONE (GnRH)- controls the sex steroid pathways by stimulating the anterior pituitary release of LH and FSH THYROID RELEASING HORMONE (TRH) – Controls the thyroid hormone axis by stimulating the anterior pituitary release of Thyroid Stimulating Hormone SOMATOSTATIN – Suppresses Anterior Pituitary release of Growth Hormone and Thyroid stimulatory hormone USMLEINCLINED.COM 3

HYPOTHALAMIC HORMONE PHARMACOLOGY The following are Hypothalamic Hormones with pharmacological applications DOPAMINE – Dopamine agonists such as Bromocriptine can be used in the treatment of galactorrhea by reducing prolactin release from the anterior pituitary. Dopamine antagonists (e.g Antipsychotics (Chlorpromazine)) can cause galactorrhea due to hyperprolactinemia. GHRH- Tesamorelin, a GHRH analog is used to treat HIV-associated lipodystrophy GnRH- Analogs of GnRH (e.g Leuprolide) are used to treat Infertility, prostate cancer uterine fibroids and precocious puberty depending on the pattern of administration. Pulsatile GnRH used in the treatment of infertility. Continuous/Tonic is used in the treatment of Prostate cancer, uterine fibroids and precocious puberty. Please note that GnRh has agonist effects when used in the pulsatile pattern and antagonist effects when used in the Continuous/Tonic pattern. Somatostatin – Analogs (e.g Octreotide) used to treat Acromegaly, Carcinoid syndrome, Gastrinoma, Glucagonoma, acute esophageal variceal bleeding. USMLEINCLINED.COM 4

ACROMEGALY USMLEINCLINED.COM 5

PRACTICE Q A 32-year-old woman with a history of schizophrenia presents to the physician with amenorrhea and a milky discharge from both nipples. A pregnancy test is negative. Laboratory results show an increased level of prolactin, decreased gonadotropin levels, and normal thyroid function tests. Which of the following medications is the most likely cause of this patient’s symptoms and laboratory findings? (A) Amantadine (B) Bromocriptine (C) Cabergoline (D) Chlorpromazine (E) Clozapine USMLEINCLINED.COM 6

HYPOTHALAMIC AGENTS RECAP Dopamine agonists – Bromocriptine, pramipexole, ropinirole GHRH analog – Tesamorelin GnRH analog – Leuprolide Somtostatin analog - Octreotide USMLEINCLINED.COM 7

PITUITARY HORMONES ANTERIOR PITUITARY HORMONES: PROLACTIN GROWTH HORMONE ADRENOCORTICOTROPIN HORMONE THYROID STIMULATING HORMONE LEUTINIZING HORMONE FOLLICLE STIMULATING HORMONE USMLEINCLINED.COM 8

PITUITARY HORMONES POSTERIOR PITUITARY HORMONES: ANTIDIURETIC HORMONE (VASOPRESSIN) OXYTOCIN USMLEINCLINED.COM 9

PHARMACOLOGICAL APPLICATIONS OF ANTERIOR PITUITARY HORMONES Amongst the anterior pituitary hormones, an established pharmacological use is seen with Growth Hormone in the treatment of Growth Hormone deficiency (pituitary dwarfism) and Turner syndrome. Pegvisomant is a Growth Hormone receptor antagonist used in the treatment of Acromegaly refractive to other modes of treatment. Cosyntropin is an analog of ACTH used in the diagnosis of Adrenal Insufficiency to differentiate between the primary and secondary adrenal insufficiency. USMLEINCLINED.COM 10

PHARMACOLOGICAL APPLICATIONS OF THE POSTERIOR PITUITARY HORMONES Desmopressin is a synthetic replacement for Antidiuretic Hormone (Vasopressin) and is used in the treatment of Central Diabetes Insipidus and Von willebrand factor deficiency (Desmopressin causes the release of von-willebrand factor stored in the endothelium. ADH antagonists e.g Conivaptan, Tolvaptan are used in the treatment of Syndrome of Inappropriate ADH (SIADH). They block the action of ADH on the V2 receptors in the Kidneys Demeclocycline is an antibioitic with V2 antagonist properties. Used sometimes to treat SIADH Oxytocin is used to stimulate labor via the induction of uterine contraction. It can also be used in the control of uterine haemorrhage by inducing uterine contraction which clamps the haemorrhaging arteries. USMLEINCLINED.COM 11

THYROID HORMONE SYNTHESIS USMLEINCLINED.COM 12

THROID HORMONE FUNCTIONS Increase the number of B1 receptors in the heart causing increases in Cardiac Output, Heart rate. Increase basal metabolic rate via increase in the Na/K ATPase activity leading to an increase in Oxygen consumption, Respiratory rate and Body Temperature These factors lead to the changes seen in cases of hyperthyroidism which include Palpitations, Weight Loss, Heat Intolerance. USMLEINCLINED.COM 13

CAUSES OF HYPERTHYROIDISM Graves disease Thyroid adenoma Toxic Multinodular goiter Thyroiditis Iodine Excess Amiodarone TSH-secreting tumor (rare) USMLEINCLINED.COM 14

GRAVES DISEASE USMLEINCLINED.COM 15

SYMPTOMS OF HYPERTHYROIDISM Palpitations, Tacchycardia, Chest pain Heat Intolerance, Sweating Weight Loss Increase apetite Hyperactivity Diarrhea Increased reflexes, Tremor Warm, moist skin. Fine Hair USMLEINCLINED.COM 16

ANTITHYROID DRUGS Propylthiouracil – Blocks the thyroid peroxidase enzyme, inhibiting the oxidation of iodide and the organification of iodine. Ultimately leads to the inhibition of thyroid synthesis. Propythiouracil also prevents the peripheral conversion of T4 to T3 by blocking the enzyme 5’ deiodinase. Methimazole – has same mechanism of action as propylthiouracil except it doesn’t block the 5’ deiodinase enzyme. Both medications are used in the treatment of hyperthyroidism. USMLEINCLINED.COM 17

ADVERSE EFFECTS OF ANTITHYROID MEDICATIONS Aplastic anemia Agranulocytosis (rare) Skin rash Hepatotoxicity (Propylthiouracil) Aplasia Cutis congenita (Methimazole) USMLEINCLINED.COM 18

APLASIA CUTIS USMLEINCLINED.COM 19

THYROID STORM Thyroid storm is an acute, life threatening hypermetabolic state induced by excessive release of thyroid hormones and catecholamines in individuals with Hyperthyroidism. It is usually stress induced. Presents with: Agitation, delirium, fever, diarrhea, coma and taccharrhythmia which is usually the cause of death. Treatment: Propanolol which blocks the cardiac effects of thyroid hormones and also blocks the peripheral conversion of T4 to T3 by blocking the 5’ Deiodinase. Propylthiouracil which blocks the thyroid peroxidase enzyme as well as the 5’ deiodinase USMLEINCLINED.COM 20

CAUSES OF HYPOTHYROIDISM Autoimmune Thyroiditis (e.g Hashimoto Thyroiditis) Thyroid gland ablation ( by radioiodine treatment or surgery) Iodine Deficiency Drug Toxicity (Lithium, Amiodarone) Pituitary Dysfunction (Decreased TSH) Hypothalamic dysfunction (very rare) USMLEINCLINED.COM 21

SYMPTOMS OF HYPOTHYROIDISM Cold Intolerance Weight Gain Decrease appetite Constipation Bradycardia Hypoactivity Hyporeflexia Lethargy, fatigue, weakness Dry cool skin, coarse brittle hair USMLEINCLINED.COM 22

THYROID REPLACEMENT THERAPY Levothyroxine – Replacement for T4 Triiodothyronine – Replacement for T3 These medications work like endogenous thyroid hormones and are used as Thyroid Hormone replacements in the treatment of Hypothyroidism and Myxedema. Toxicity is expected to mimic cases of hyperthyroidism and will present with Tacchycardia, Tremors, Sweating, Arrhythmias. USMLEINCLINED.COM 23