Transcript hormones of the pituitary and thyroid

PITUITARY &
THYROID
HORMONES
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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.
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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
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ANTERIOR Pituitary Gland
Six hormones
TSH- Thyroid stimulating hormone
ACTH-Adreno corticotrophin hormone
LH - Luteinizing hormone
FSH- follicle stimulating hormone
PROLACTIN
GH- growth hormone
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 POSTERIOR
PITUITARY
HORMONES – Oxytocin, vasopressin.
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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
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Growth hormone(somatotropin,
somatrem)
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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)
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pharmacokinetics
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Plasma half life: 20-25 minutes
Clearance: hepatic
Administration: Mostly I.M
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THERAPEUTIC USES
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Somatotropin is used to treat growth deficiency
in children (pituitary dwarfism), osteoporosis
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Somatotropin and somatrem should not be
used in individuals with closed epiphysis or
an enlarging intracranial mass.
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Somatostatin -Growth hormoneinhibiting hormone
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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.
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Therapeutic uses of Ocreotide

Treatment of acromegaly
Treatment of secretory diarrhea associated
with tumors producing vasoactive intestinal
peptide
Treatment of acute esophageal variceal
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bleeding
Carcinoid syndrome
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Side effects: flatulence, nausea, steatorrhea and
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gall stone formation
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pegvisomant
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Treatment of acromegaly that is refractory to
other modes of surgical, radiologic or
pharmacologic intervention
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Adrenocorticotropic
hormone(corticotropin)
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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
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Gonadotropin releasing
hormones (GnRH)
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Also called Gonadorelins
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Pulsatile secretion is important for the release of
gonadotropins (FSH, LH) from the pituitary.
Continuous administration inhibits
gonadotropin release.
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Synthetic forms of gonadorelins
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Leuprolide
Nafarelin
Buserelin
Goserelin
Histrelin
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ROUTE : I V, I M , S C , NASAL
Pulsatile IV administration
FSH & LH secretion stimulation
Continuous GnRH administration
Inhibition of Gonadotropin release
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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
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adverse effects: GnRH
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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.
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Gonadotropins
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hMG - - Menotropins
FSH -- Urofollitropin
hCG – LH agonist
LH
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Therapeutic uses of
gonadotropins
 Infertility
in men and women
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Toxicity: Gonadotropins
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Hyperstimulation syndrome
Ovarian Hyper Stimulation syndrome (OHSS)
hMG -induced ovarian enlargement
Hemoperitoneum (secondary to ruptured ovarian cyst)
Arterial thromboembolism
Multiple births
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In men: gynecomastia
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prolactin
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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
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Prolactin
Abnormal prolactin levels:
 Deficiency: hypoProlactinemia--Manifestations:
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lactation failure
Excess: hyperProlactinemia
 Galactorrhea
 Hypogonadism
 Amenorrhea
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Bromocriptine and cabergoline Dopamine Agonists
Actions
 Dopamine-like action
 Used to treat hyperprolactinemic states
 as well as microadenomas and
macroprolactinomas
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Side effects
GI side effects:
 constipation, dyspepsia, symptoms of reflux
esophagitis
 peptic ulceration with bleeding
 Psychiatric problems
CVS:
 Common: postural/orthostatic hypotension
 Arrhythmias
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Posterior pituitary hormones
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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.
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Posterior Pituitary Hormone
Oxytocin :
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Uses : stimulate uterine contraction to induce labor
Milk ejection
SE: HTN crisis,
 Uterine rupture
 Fetal death
CI: premature delivery,
 Abnormal fetal presentation, fetal distress
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Vasopressin
Actions : has both antidiuretic and well as vasopressor effects
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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
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desmopressin
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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
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Thyroid hormones
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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
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Symptoms of hypothyroidism
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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
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Symptoms of hyperthyroidism
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Tachycardia
Arrhythmias
Body wasting despite adequate intake
Nervousness
Tremors
Intolerance to heat
Exolphthalmus
Diagnosed by a ↓TSH & ↑ T3, T4
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pharmacokinetics
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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.
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Treatment of hypothyroidism
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LEVOTHYROXINE, LIOTHYRONINE
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Given once daily
Toxicity manifests as: symptoms of
hyperthyroidism.
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Treatment of hyperthyroidism
(thyrotoxicosis)
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Goal :
Removing part or all of the thyroid gland
Inhibiting synthesis of hormones
Blocking release of hormones from the follicles
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surgery
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Removal of part or all of the thyroid: done
surgically or by destruction of the gland by
radioactive iodine
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Antithyroid Drugs
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Thioamides
Iodides
Radioactive iodine
Anion inhibitor
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Thioamides
pharmacokinetics
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Propylthiouracil
Methimazole
Carbimazole
Both Crosses placenta but PTU is safer in
pregnancy
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Inhibition of thyroid hormone synthesis:
using thioamides such as propylthiouracil
(PTU)and methimazole
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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
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SIDE EFFECTS OF
THIOAMIDES
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Agranulocytosis: ↓neutrophil count(<500)
Rash
edema
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Iodide
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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
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Anion Inhibitors
 Competitive inhibition:
Perchlorate
 Pertechnetate
 Thiocyanate
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Inhibits iodide uptake by thyroid
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Thyroid storm
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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
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