* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download hormones of the pituitary and thyroid
Bovine somatotropin wikipedia , lookup
Hormonal contraception wikipedia , lookup
History of catecholamine research wikipedia , lookup
Mammary gland wikipedia , lookup
Polycystic ovary syndrome wikipedia , lookup
Neuroendocrine tumor wikipedia , lookup
Endocrine disruptor wikipedia , lookup
Xenoestrogen wikipedia , lookup
Triclocarban wikipedia , lookup
Hormone replacement therapy (menopause) wikipedia , lookup
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency wikipedia , lookup
Breast development wikipedia , lookup
Menstrual cycle wikipedia , lookup
Vasopressin wikipedia , lookup
Hormone replacement therapy (male-to-female) wikipedia , lookup
Bioidentical hormone replacement therapy wikipedia , lookup
Hyperandrogenism wikipedia , lookup
Adrenal gland wikipedia , lookup
Graves' disease wikipedia , lookup
PITUITARY & THYROID HORMONES 1 2 Neuroendocrine system is mainly controlled by pituitary and hypothalamus, which coordinates many of the body functions by transmitting the messages to the individual cells and tissues. 3 1 Thyrotropin-realising hormone – is to control the release of TSH from the adenohypophysis. 2 Gonadotropin-releasing hormone – to control gonadotropin secretion 3 Corticotropin releasing hormone – to control ACTH secretion 4 Growth hormone releasing hormone -major role is to control GH release 4 ANTERIOR Pituitary Gland Six hormones TSH- Thyroid stimulating hormone ACTH-Adreno corticotrophin hormone LH - Luteinizing hormone FSH- follicle stimulating hormone PROLACTIN GH- growth hormone 5 POSTERIOR PITUITARY HORMONES – Oxytocin, vasopressin. Hormones secreted by the hypothalamus and pituitary are all peptides Hormones of the anterior and posterior pituitary are administered either IM, SC or intranasally but not orally 6 Growth hormone(somatotropin, somatrem) Released by the ant. Pituitary following stimulation by GHRH of the hypothalamus GH is released in a pulsatile manner, with the highest levels occurring during sleep It is inhibited by the hormone somatostatin It mediates it action directly at its target tissues, as well as others through somatomedins (IGF-I, IGF-II) 7 pharmacokinetics Plasma half life: 20-25 minutes Clearance: hepatic Administration: Mostly I.M 8 THERAPEUTIC USES Somatotropin is used to treat growth deficiency in children (pituitary dwarfism), osteoporosis Somatotropin and somatrem should not be used in individuals with closed epiphysis or an enlarging intracranial mass. 9 Somatostatin -Growth hormoneinhibiting hormone It suppresses GH and TSH release half-life-- 1-3 minutes Has limited clinical use Ocreotide the synthetic analog of somatostatin has a longer half-life than the natural compound. 10 Therapeutic uses of Ocreotide Treatment of acromegaly Treatment of secretory diarrhea associated with tumors producing vasoactive intestinal peptide Treatment of acute esophageal variceal bleeding Carcinoid syndrome Side effects: flatulence, nausea, steatorrhea and gall stone formation 11 12 pegvisomant Treatment of acromegaly that is refractory to other modes of surgical, radiologic or pharmacologic intervention 13 Adrenocorticotropic hormone(corticotropin) CRH is responsible for the synthesis and release of ACTH causing the synthesis of adrenocorticosteroids and adrenal androgens CRH is used to diagnostically differentiate between cushing’s disease and ectopic ACTH – producing cells ACTH is released from the pituitary in pulses with the highest being around 6am , and lowest in the evening Synthetic form of ACTH--cosyntropin Adrenocorticotropin, ACTH SYNTHETIC - COSYNTROPIN Clinical Use: To differentiate between primary(↑ACTH) and secondary adrenal insufficiency(↓ACTH) following cosyntropin: In primary adrenal insufficiency: no change in cortisol levels (i.e., still reduced) In secondary adrenal insufficiency: ↑cortisol levels Therefore cosyntropin is used for diagnosis of adrenal insufficiency as well as treatment of infantile spasm 15 Gonadotropin releasing hormones (GnRH) Also called Gonadorelins Pulsatile secretion is important for the release of gonadotropins (FSH, LH) from the pituitary. Continuous administration inhibits gonadotropin release. 16 Synthetic forms of gonadorelins Leuprolide Nafarelin Buserelin Goserelin Histrelin 17 ROUTE : I V, I M , S C , NASAL Pulsatile IV administration FSH & LH secretion stimulation Continuous GnRH administration Inhibition of Gonadotropin release 18 Therapeutic Applications: GnRH Stimulation: pulsatile admin. To treat Infertility and hypogonadism in males and females Inhibition: Continuous admin. Prostate cancer, Uterine fibroids, Endometriosis Precocious puberty 19 adverse effects: GnRH Dermatitis, hypersensitivity and headache. In women: hot flushes, sweating, diminished libido, depression and ovarian cyst In men: bone pain, edema, gynecomastia and diminished libido Contraindicated in pregnancy and breastfeeding. 20 Gonadotropins hMG - - Menotropins FSH -- Urofollitropin hCG – LH agonist LH 21 Therapeutic uses of gonadotropins Infertility in men and women 22 Toxicity: Gonadotropins Hyperstimulation syndrome Ovarian Hyper Stimulation syndrome (OHSS) hMG -induced ovarian enlargement Hemoperitoneum (secondary to ruptured ovarian cyst) Arterial thromboembolism Multiple births In men: gynecomastia 23 24 prolactin Similar in structure to GH Secreted by the ant. Pituitary whose secretion is inhibited by dopamine and stimulated by TRH FUNCTION: to stimulate and maintain lactation Decreases sexual drive and reproductive function 25 Prolactin Abnormal prolactin levels: Deficiency: hypoProlactinemia--Manifestations: lactation failure Excess: hyperProlactinemia Galactorrhea Hypogonadism Amenorrhea 26 Bromocriptine and cabergoline Dopamine Agonists Actions Dopamine-like action Used to treat hyperprolactinemic states as well as microadenomas and macroprolactinomas 27 Side effects GI side effects: constipation, dyspepsia, symptoms of reflux esophagitis peptic ulceration with bleeding Psychiatric problems CVS: Common: postural/orthostatic hypotension Arrhythmias 28 Posterior pituitary hormones Release of these hormones are not regulated by the releasing hormones of the hypothalamus Are instead synthesized in the hypothalamus and stored in the post. Pituitary till when needed in response to signals such as High urine osmolality or parturition. 29 Posterior Pituitary Hormone Oxytocin : Uses : stimulate uterine contraction to induce labor Milk ejection SE: HTN crisis, Uterine rupture Fetal death CI: premature delivery, Abnormal fetal presentation, fetal distress 30 Vasopressin Actions : has both antidiuretic and well as vasopressor effects V 1 recep – found in the liver and vascular smooth muscle (vasoconstriction) V 2 recep – renal system, water reabsop. SE: Water intoxication, hyponatremia, headache, tremor. Care : CAD, asthma, epilepsy. Uses: Diabetes insipidus Nocturnal enuresis To control bleeding due to esophageal varices and colonic diverticular 31 desmopressin Synthetic form of vasopressin Has minimal to no activity on V1 receptor resulting in minimal to no pressor effect It is now preferred for diabetes insipidus and nocturnal enuresis Treatment of Von-Willibrand Disease Longer acting than vasopressin Administered intranasally 32 Thyroid hormones Secreted by the thyroid gland Facilitates normal growth and maturation in tissues that needs it for their normal function Secretes Two major thyroid hormones: T3 and T₄ but can also secrete calcitonin Not essential for life, but under and over secretion could result in disease state 33 34 Symptoms of hypothyroidism Bradycardia Poor resistance to cold Mental and physical slowing In children can result in dwarfism and mental retardation Menstrual irregularities Weigh gain despite decreased intake Diagnosed by an ↑TSH & ↓T3, T4 35 Symptoms of hyperthyroidism Tachycardia Arrhythmias Body wasting despite adequate intake Nervousness Tremors Intolerance to heat Exolphthalmus Diagnosed by a ↓TSH & ↑ T3, T4 36 pharmacokinetics T3 & T4 given orally IV-myxedema T3 – the most active form Food, calcium preparations and aluminum antacids can decrease absorption of T4 but not T3 Are metabolized via through microsomal P450 system. Therefore inducers of P450 accelerates the metabolism of thyroid hormones. 37 Treatment of hypothyroidism LEVOTHYROXINE, LIOTHYRONINE Given once daily Toxicity manifests as: symptoms of hyperthyroidism. 38 Treatment of hyperthyroidism (thyrotoxicosis) Goal : Removing part or all of the thyroid gland Inhibiting synthesis of hormones Blocking release of hormones from the follicles 39 surgery Removal of part or all of the thyroid: done surgically or by destruction of the gland by radioactive iodine 40 Antithyroid Drugs Thioamides Iodides Radioactive iodine Anion inhibitor 41 Thioamides pharmacokinetics Propylthiouracil Methimazole Carbimazole Both Crosses placenta but PTU is safer in pregnancy 42 Inhibition of thyroid hormone synthesis: using thioamides such as propylthiouracil (PTU)and methimazole PTU & methimazole inhibits the oxidation(peroxidase), iodination and coupling (condensation)step of tyrosine synthesis PTU & propanolol can also block deiodinase in the conversion of T4 to T 3 43 SIDE EFFECTS OF THIOAMIDES Agranulocytosis: ↓neutrophil count(<500) Rash edema 44 Iodide Used for treatment hyperthyroidism MOA: blocks the iodination of tyrosine as well as the release of the hormones into the blood Used prior to surgery to decrease the vascularity of the gland Not useful for long term therapy because thyroid gland ceases to respond after a few weeks SE: sore mouth and throat, rashes, metallic taste in mouth 45 Anion Inhibitors Competitive inhibition: Perchlorate Pertechnetate Thiocyanate Inhibits iodide uptake by thyroid 46 Thyroid storm A rare but severe complication of untreated hyperthyroidism in which the thyroid gland secretes excess thyroid hormones resulting widespread sympathetic symptoms Treatment: β-blockers such as propanolol Calcium channel blockers, diltiazem in pts suffering from severe heart failure and asthma 47