ENDOCRINE SYSTEM - GLANDS

• Pituitary

• Thyroid

• Parathyroid

• Adrenals

• Gonads
• Islet of Langerhans
PITUITARY HORMONES

• Thyroid Stimulating Hormone (TSH)

• Adrenocorticotropic Hormone (ACTH)

• Follicle Stimulating Hormone (FSH)

• Lutenizing Hormone (LH)

• Growth Hormone (GH)

THYROID HORMONES

• Thyroxine (T4)

• Tri-iodothyronine (T3)
ADRENAL AND GONADAL HORMONES

• Estrogen

• Progestron
• Testosterone
• Cortisol

• Aldosterone
PANCREAS-ISLET OF LANGERHANCE

• Insulin – beta cells

• Glucagon – α2 cells

• Somatostatin – Delta cells

HYPOTHALAMIC HORMONES
• Growth hormone releasing hormone (GHRH)

• Growth hormone inhibiting hormone (Somatostatin)

• Thyrotropin-releasing hormone (TRH)

• Corticotropin-releasing hormone (CRH)

• Gonadotropin-releasing hormone (GnRH)

• Prolactin-inhibiting hormone (Dopamine)

POSTERIOR PITUITARY HORMONES

• Oxytocin

• Vasopressin (ADH)

• Desmopressin
OXYTOCIN
• Myometrial contraction
• Myoepithelial cells surrounding
mammary alveoli
• Induce labor
• Uterine inertia
• Incomplete abortion
VASOPRESSIN
• Vascular smooth muscle contraction
– v1 receptor
• Water resorption in the collecting
tubules – v2 receptor
• Pituitary diabetes insipidus

• Nocturnal enuresis
THYROID HORMONES-BASIC AND CLINICAL
PHARMACOLOGY

• Genesis and Fate

• Mechanism and Biological Actions

• Clinical Features and Treatment of

Hypo and Hyperthyroidism
THYROID HORMONES

• Thyroxine (T4)

• Tri-iodothyronine (T3)

• Calcitonin
THYROID HORMONES - BIOSYNTHESIS

• Active Transport Iodide

• Thyroglobulin Synthesis

• Iodination of Tyrosyl Residues

(organification)

• Coupling of Iodotyrosines → T3 & T4

Thyroid Hormones and Antihyperthyroid Drugs
TRH

Somatic Negative T3 Pituitary

cells TSH
and T4
Feedback
Tf Follicular
cell Follicular
Blood lumen
TGB
+ - +
-
TBPA
TBA Phagocytosis and DIT
T3 Pinocytosis MIT
Hydrolysis T3
T4 Release TG
Tf
TG T4
Liver I2
TG
Lysosymes
MIT
DIT I-
Iodine I-
Intake Trapping
Plasma I -

Gut

Principle features of the biosynthesis and metabolism of thyroid hormone(s)

THYROID HORMONE - PLASMA PROTEINS

• T4 binding Globulin (75%)

• Prealbumin (Transthyretin)

• Albumin
 INACTIVATION

Deamination
Decarboxylation
Conjugation
(glucuronide or
Sulfate)

Thyroxine

Deiodination
ACTIVATION INACTIVATION

3,3’,5’-Triiodothyronine
3,5,3’-Triiodothyronine (reverse T3)
(T3)
 T3
T4 R T3
T3 F F R F PP
T4

PB
T3 T3
Pre-mRNA
Cytoplasm Nucleus

Response
mRNA
Protein
ACTIONS OF THYROID HORMONES
1. Normal growth and development of nervous,
skeletal and reproductive systems

2. Control of metabolism of fat, carbohydrate,

protein and vitamine
3. Elevation of basal metabolic rate with
concomittent increase in O2 consumption and
heat production
4. Modulation of the actions of parathyroid
hormone and calcitonin
 Cold Trauma Stress

Hypothalamus

Somatostatin TRH
- +

Anterior pituitary
-
Thyrotrophin
I-

+ +
Thioureylenes -
Thyroid
Iodide -
131
I - T4
T3
HYPOTHYROIDISM

• Primary – Thyroid Defect

• Secondary – Pituitary disease

• Target Tissues – Thyroid Hormone

Resistance
PRIMARY HYPOTHYROIDISM - CAUSES
• Chronic Lymphocytic Thyroiditis
(Hashimoto’s Disease)
• Idiopathic Hypothyroidism
• Radioactive Iodine Ingestion

• Iodine Deficiency or Excess

• Defect in Thyroid Hormogenesis
• Creatinism
• Antithyroid drugs
HYPOTHYROIDISM- CLINICAL FEATURES
• Bradycardia
• Poor Resistance to Cold
• Mental and Physical Slowing
• Skin Abnormalities (Dryness, Hair Loss,
Thinning)
• Puffiness (Hand, Face, Feet)
• Drooping of Eyelids and Periorbital
Edema
HYPOTHYROIDISM - TREATMENT
• Levothyroxin (T4) {Levothroid,
synthroid,
Levoxyl}
• Tri-iodothyronin (T3) {Cytomel,
Triostat}

• Liotrix (T3 & T4) {Thyrolar}

• Thyroid Extract
THYROID HORMONES – SIDE EFFECTS

• Tachycardia and Arrhythmias

• Insomnia

• Heat Intolerance

• Weight loss and Headache

MYXDEMA COMA – CLINICAL FEATURES

• Confusion and psychoses

• Hypoventilation

• Hypoglycemia and Hyponatremia

• Hypothermia
HYPERTHYROIDISM - CAUSES
• Diffuse Toxic Goiter (Grave’s Disease)

• Toxic Multi-nodular Goitar

• Thyroiditis

• Thyroid Hormone Ingestion

• TSH Secreting Adenoma

HYPERTHYROIDISM – CLINICAL FEATURES

• Tachycardia – Cardiac Arrhythmias

• Body Wasting

• Tremor and Nervousness, Insomnia

• Excess Heat Production

• Occular Abnormalities (Exophthalmos,

Eyelid Retraction)
HYPERTHYROIDISM - TREATMENT

• Antithyroid Drugs (Propylthiouracil

Methimazol)
• Radioactive Iodine

• β-Adrenoceptor Antagonists (Propranolol)

• Iodide Salt
THYROID STORM – CLINICAL SYMPTOMS

• Hypermetabolism

• Excessive Adrenergic Activity

• Flushing and Sweating

THYROID STORM - TREATMENT
• Propranolol, 1-2 mg, IV or 40-80 mg, PO
• Diltiazem, 5-10 mg/hr, IV, 90-120 mg, PO

• Sodium ipodate

• Potassium iodate
• Methimazol or propylthiouracil

• Hydrocortisone, 50 mg every six hours

CALCITONIN – CLINICAL EFFICACY
• Maintain bone density

• BMD

• Bone loss
• Osteoclast activity

• Analgesic effect
CALCITONIN – PHARMACOKINETICS
• Subcutaneous (Calcimer, Miacalcin):
100-200 U/ml

• Intranasal (Miacalcin): 200 IU/puff

• T ½ ( < 1 hr)

• Duration (few weeks)

PTH - FUNCTION

• Plasma Ca++ concentration

• Plasma PO4- concentration

• Bone formation (low concentration)

PTH – PHYSIOLOGICAL ACTIONS

• Intestinal Ca++ absorption

• Renal Ca++ reabsorption

• Bone Ca++ mobilization

• Renal phosphate excretion

PTH – CLINICAL EFFICACY

• Bone mass

• BMD

• Vertebral and peripheral fractures

• Osteocalcin (55%)

• Cross linked n-telopeptide (20%)

PTH – MECHANISM OF ACTION

• Recruitment of preosteoblasts

• Lifespan of mature osteoblasts

• Osteoblast apoptosis

• Osteocyte number and density

• cAMP/protein kinase A