hormones

Thyroid hormone Dr.maha talal

Thyroid stimulating hormone(thyrotropin)
*TSH is glycoprotein *secreted in pulsatile rhythm being highest during sleep at night. TSH secretion is controlled by thyrotropine releasing hormone (TRH)which is inhibited by TH negative feed back *TSH stimulate thyroid to synthesize:

Thyroid hormone

TH secretion controlled by :1-TSH 2- iodine concentration in the blood 3- the hypothalamic – pituitary – thyroid axis .

Action of TH

Thyroid gland secrete : -T3 ( triiodothyronine) -T4 ( thyroxin) TH diffuse across the cell membrane and bind to intracellular receptors in target tissues, T 4 converted to T3 which has more affinity to receptors than T4 and more potent than T4..
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Thyroid hormone

TH action lead to synthesis of proteins which are important in producing actions which are : 1- normal development and metabolism 2- growth by direct action and by potentiation of GH. 3- normal response to parathyroid hormone and calcitonin. 4- it is important for nerve and skeletal tissues.

5- TH are regulator of metabolism in most tissues: -increase basal metabolic rate -increase respiratory rate -stimulate the heart -increase energy utilization

Synthesis of thyroid hormones

MIT +DIT T3 DIT+DIT T4 The ratio of T4:T3 is 4:1 Thyroid H are then released by proteolysis Of thyroglobulin.


Thyroid hormone

THYROID DISORDERS

Hypothyroidism Decrease thyroid hormone secretion Thyroid deficiency during development is called cretinism and in adults is called myxoedema.

THYROID DISORDERS

Sign and symptoms of hypothyroidism: - lethargy ,fatigue - loss of energy (ambition) - slow motor activity - decrease appetite , increase weight - dry , cold , coarse skin ,hair loss - cold intolerance -hypotension -increase capillary fragility - exaggerated response to sedative and narcotic analgesics.

hypothyroidism

cretinism
Thyroid deficiency during development delay growth mental retardation puffy face open mouth protruding tongue

myxoedema

Thyroid deficiency in adults Swollen face myxoedematous skin Mental dullness Sexual atrophy Anemia Bradycardia

hypothyroidism

Treatment (replacement therapy) preparation of T4 levothyroxine sodium preparation of T3 liothyronine sodium Mixture of T3 , T4 liotrix These drugs are well absorbed orally specially on empty stomach in the morning.

THYROID DISORDERS

Hyperthyroidism there is excess of TH secretion (grave's disease) diffuse toxic goiter , which is an autoimmune disease.


THYROID DISORDERS
Hyperthyroidism sign and symptoms: Increase metabolic rate Increase HR Increase sensitivity to catecholamine Increase appetite, decrease weight Increase body temperature Sensitivity to heat Nervousness , tremor Exophthalmous

hyperthyroidism

Hyperthyroidism 
Treatment:1- surgical2-pharmacological A- radioactive iodine : I131 isotope have tЅ of 8 days and emit γ radiation and β particles , it will be given orally and concentrated in thyroid gland , β particles destroy the gland , improvement occurs within days to weeks .

Radioactive iodine

Advantages: 1- selective for thyroid gland 2- low cost 3- no death from treatment

Hyperthyroidism

2-pharmacological B- thiourylenes : act by inhibition of thyroid peroxidase and decrease Iodine oxidation so less TH will be synthesized. e.g. Propylthiouracil methimazole

B- thiourylenes :

Goiter
Enlargement of thyroid gland due to : 1- iodide deficiency (endemic goiter) 2- hypothyroidism 3- ingestion of goitrogens in large quantities for long duration e.g. cabbage

GIOTER

C-Iodide
Iodide is the oldest remedy for thyroid disorders. Iodine/ iodides are required for thyroid hormone synthesis. high concentrations of iodide limit its own transport. In addition, high concentrations of iodide inhibit synthesis of iodotyrosines and iodothyronines (organification) and inhibit thyroid hormone release.

Iodideside effects

-hypersensitivity -iodism(toxicity) unpleasant taste. Burning mouth and throat. Soreness of teeth and gingiva. Increase salivation. Gastric irritation and diarrhea. Inflammation of larynx, tonsils , and lung. Enlargement of salivary glands.

Implication in dentistry

1- the dentist may be in position to detect sign and symptoms of subclinical thyroid disease and refers patient to medical evaluation. 2- subclinical hypothyroidism showed as delayed eruption of teeth , malocclusion and skeletal retardation , tongue enlargement.

Implication in dentistry

3- in case of myxoedema , stressful situation such as surgery , trauma , infection may precipitate myxedematous coma (50% mortality rate)

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Implication in dentistry

4- in case of hyperthyroidism: *patient become sensitive to epinephrine *oral complications : A - osteoporosis of alveolar bone B-more frequent dental caries and periodontal disease. C-in children: teeth , jaws develop more rapidly ,early loss of deciduous teeth and early eruption of permanent teeth D- changes in gingiva E- ill fitting dentures.

Adrenal corticosteroids

The adrenal gland consists of 2 parts: 1-the medullary portion which secrete epinephrine and norepinephrine on sympathetic stimulation. 2-the adrenal cortex which produces 2 types of steroids: A- androgens B- corticosteroids

Regulation: HPA axis

Corticosteroids divided into:
1-glucocorticoids 2- miniralocorticoids(aldosterone)

Glucocorticoids

Those are secreted by the middle zone (zona faciculata) of adrenal cortex , they bind to specific intracellular cytoplasmic receptors in target tissues which are widely distributed through out the body. The receptor-hormone complex go into nucleus and attaches to gene promoter and turn the genes on or off to produce effects.

Glucocorticoids

The principal human glucocorticoid is called cortisol which is normally produced in diurnal with peak early in the morning followed by a decline.

Glucocorticoids effects:

1-promote metabolism : *increase gluconeogenesis through increase amino acid up take by liver and kidney. *stimulate protein catabolism and lipolysis *provide the building blocks for glucose and lead to increase in plasma glucose level (anti-insulin effects)

Glucocorticoids effects:

2-increse resistance to stress: *it provide the body with energy required to combat stress e.g. trauma, fright ,infection , bleeding *it increase blood pressure by vasoconstriction.

Glucocorticoids effects:

3- Alter blood cell level in plasma: *it will decrease eosinophils, basophiles, monocytes, and lymphocytes . This lead to ?

Glucocorticoids effects:

4-the anti-inflammatory action and immune suppression and this is due to:lowering lymphocytes and macrophageslowering antibody productiondecrease production of prostaglandins and leukotrienes which are responsible for the inflammatory action. –reduce histamine that is released from basophiles and mast cells.

Glucocorticoids effects:

5-affect other hormones : *like increase in growth hormone production and increase in TSH. 6-lipid metabolism: *inhibit fatty acid synthesis *induce mobilization of Fat by lipolytic hormones *long term use lead to fat redistribution and store fat in central location of the body (centripetal obesity).

miniralocorticoids

*help to control body's water volume and concentration of electrolytes. *Aldosterone act on kidney and cause: - Na, bicarbonate and water reabsorption -decrease reabsorption of K which is lost in urine. -increase Na reabsorption from GIT mucosa , sweat , saliva ALL THESE LEAD TO INCREASE IN BLOOD VOLUME AND BLOOD PRESSURE

THERAPUTIC USES OF ADRENAL CORTICOSTEROIDS

1-replacement therapy for primary adrenocortical insufficiency e.g. Addison's disease which is caused by adrenal cortex dysfunction 2- replacement therapy for secondary or tertiary adrenocortical insufficiency caused by defect in hypothalamus or pituitary gland.



THERAPUTIC USES OF ADRENAL CORTICOSTEROIDS
3- diagnosis of Cushing syndrome which is caused by hypersecretion of glucocortecoids 4- relief of inflammatory symptoms:it reduce the manifestation of inflammations including the redness , swelling , heat and tenderness.

5-treatment of allergy:glucocorticoide are beneficial in Rx of bronchial asthma, allergic rhinitis and drug allergic reaction. 6-accellaration of lung maturation in premature infant

CORTICOSTEROIDS

Therapeutic uses in dentistry

1-oral ulcerations

Ulcerations due to denture, trauma, recurrent aphthous , stomatitis desequmative gingivitis, ect. Treated by topical and/or systemic glucocorticoids It will relief symptomes and shorten the clinical course of the disease Topical application is of greatest benefits (direct contact with lesion)

oral ulcerations

2-pulpal hypersensitivity
Pulp of tooth become inflammed by operative trauma, invasion by bacteria ect.

3-Tmj disorders

Tmj pain due to trauma, bruxism, rheumatoid arthritis Need conservative treatment and careful diagnosis

4-postoperative sequels

Reduce postoperative complications mainly: edema trismus

5-anaphylaxis and allergic reactions

It is used with epinephrine to control anaphylactic shock The immunosuppressant and anti inflammatory effects of glucocorticoids used to treat manifestation of allergy: urticaria , contact dermatitis , allergic rhinitis

CORTICOSTEROIDSpharmacokinetics

can be given orally , I.V , I.M ,topical and inhalation Very good absorption through GIT 90%of the absorbed glucocorticoid are bound to plasma proteins. Metabolized by liver Excreted by kidney

CORTICOSTEROIDSpharmacokinetics

Duration of action: short (8-12 hr) e.g. cortisone intermediate(18-36hr) e.g. prednisolone long(36-72hr) e.g. betamethazone , dexamethazone

CORTICOSTEROIDS

General notes *all corticosteroids can be given orally *cortisone , triamcinolon , desoxycorticosterone are given IM *dexamethasone , hydrocortisone , methylprednisolone and prednisolone are given IV , IM. *Beclomethasone , fluticasone ,triamcinolone can be given as an aerosol * Beclomethasone, hydrocortisone, dexamethasone and triamcinolone are applied topically.

CORTICOSTEROIDSadverse effects

1-osteoporosis:common , caused by suppression of intestinal calcium absorption 2-cushing like syndrome: caused by hypersecretion of glucocorticoids and characterized by redistribution of body fat , puffy face , increase body hair growth, acne , insomnia , increase appetite .

Easy bruising

Fragile skin

Skin thinning

Skin thinning

acne

Stretch mark

CORTICOSTEROIDSadverse effects

3-hyperglycemia which lead to diabetes mellitus 4-increase susceptibility to infection (why?) 5- edema and hypokalemia 6-CNS effects: euphoria, insomnia, nervousness, psychosis 7-increase intraocular pressure



CORTICOSTEROIDSadverse effects
8-peptic ulcer: due to decrease synthesis of PGI2 and PGE2 which are protective for gastric mucosa. 9-imbalance between protein synthesis and degradation which lead to nitrogen loss. 10-suppression of growth 11-myopathy:muscle wasting and weakness.

CORTICOSTEROIDSadverse effects

12-vascular effects: hypertension and increase atherosclerotic disease risk13-atrophy of skin and mucosa14- metabolic effects : obesity and hyperlipidemia15-poor wound healing may occurs during long –term use. (why?)16-suppression of pituitary-adrenal function

For dental patients:

Adrenal insufficiency *normal person respond to stress , infection , surgery with increase in ACTH and cortisol production *patients with suppressed adrenal function is unable to increase cortisol production *30 mg of hydrocortisone / 4 wk 80 mg of hydrocortisone / 2 wk Both can cause adrenal suppression (prlong use) *during dental procedure dose of glucocorticoids should be double or triple

Adrenal crisis( acute insufficiency)

Hypotension Severe weakness Progressive mental confusion Nausea and vomiting Abdominal, lower back or leg pain Hyperthermia Hypoglycemia Hyperkalemia Loss of consciousness Coma death

Management of adrenal crisis

Place the patient in a supine position with leg elevated 200 mg hydrocortisone IV repeated as necessary Oxygen if necessary Transportation to a medical facility as soon as possible.

Addison's disease

Caused by adrenal dysfunction and diagnosed by the lack of patients response to corticotropins. Treatment by hydrocortisone.

Pigmentation of gum (Addison's disease)

Pigmentation of buccal mucosa (Addison's disease)

Pigmentation of buccal mucosa (Addison's disease)

Insulin oral hypoglycemic And glucagons


Pancreases both an endocrine gland that produce insulin, glucagons and somatostatin and exocrine gland that produce digestive enzymes.

Diabetes mellitus

is group of syndromes characterized by elevation of blood glucose caused by deficiency of insulin.

Types of Diabetes mellitus

A-type I (insulin dependant , juvenile)*common around time of puberty*absolute insulin deficiency*autoimmune-mediated β cell necrosis and destruction *pancreas fail to respond to glucose *polydipsea , polyurea, polyphagia and weight loss


*treatment: -by insulin -to control hyperglycemia , avoid ketoacidosis, maintain level of HbA1c ( glycosylated hemoglobin) (a form of hemoglobin used primarily to identify the average plasma glucose concentration over prolonged periods of time.)

In the normal 120-day life span of the red blood cell, glucose molecules join hemoglobin, forming glycated hemoglobin. In individuals with poorly controlled diabetes, increases in the quantities of these glycated hemoglobins are noted.


Ketoacidosis is a type of metabolic acidosis which is caused by high concentrations of ketone bodies, formed by the deamination of amino acids, and the breakdown of fatty acids. This is most common in untreated type 1 diabetes mellitus, when the liver breaks down fat and proteins Ketoacidosis can be smelled on a person's breath. It is often described as smelling like fruit or paint thinner

Types of Diabetes mellitus

B-Type II diabetes mellitus*influenced by genetic factors, aging, obesity*Lack of sensitivity of target organs to insulin*treatment (why we treat diabetes?) -type II diabetes treated with oral hypoglycemic agents . -with progression of the disease β cell function decline and insulin therapy is required.

Insulin

Hormone consist of 2 peptide chains that are connected by disulfide bondsIt is synthesized as a precursor (pro-insulin) that undergoes proteolysis to from insulin that is secreted by β cells of pancreasSecretion of insulin is regulated by: *blood glucose level *certain amino acid *other hormones( e.g. cortisones) *autonomic mediators(epinephrine,Ach….ect)

Insulin

Sources of insulin
Human insulin replaced by beef or pork insulin for therapeutic uses Human insulin is produced by recombinant DNA technology by modification of A.A sequences of human insulin, insulin with different properties is produced.

recombinant DNA technology

Insulin
Insulin given SC injection (not given orally , why?) For emergency can given IV,IM Aerosol preparation (spray) is available.

Insulin given SC injection

SQ insulin differ from physiological secretion in 2 ways:
SQ absorbed slowly SQ diffuse to peripheral not to portal circulation

Insulin adverse effects

1-hypoglycemia due to over dose (tachycardia, confusion, vertigo, hypersensitivity). 2-lipodystrophy:which is local atrophy of sc fatty tissues at the site of injection. 3-allergy.

Insulin preparations

I-rapid onset and ultrashort acting : *regular insulin: short acting, soluble, given sc, IV in emergency, safely used in pregnancy. *lispro, aspart and glulisine: ultrashort acting, more rapid absorption and action, shorter duration of activity

Insulin preparations

II-intermediate acting a-lente insulin *slower onset of action *longer duration *not suitable for IV route b-isophane NPH insulin suspension (Neutral Protamine Hagedorn) *delayed absorption , intermediate action *given sc only



Insulin preparations
III-Prolonged acting a-ultralente insulin (extended zinc insulin) *have larger particles , slow dissolve slow onset of action, long duration b-insulin glargine * it precipitate at site of injection, extended action, slow onset , given sc

Oral hypoglycemic agentsinsulin secretagogues

A- sulfonylureasMechanism of action: promote insulin release from βcells of pancreas and this is by:1-block potassium channels2-reduction of serum level of glucagons3-increase binding of insulin to receptors

Oral hypoglycemic agentsinsulin secretagogues

Kinetics: given orally, metabolized by liver, excreted by liver and kidney

Oral hypoglycemic agentsinsulin secretagogues

Adverse effects: Weight gain, hyperinsulinemia, hypoglycemia. Contraindicated in hepatic and renal diseases, pregnancy

e.g. of insulin secretagogues Tolbutamide Glyburide Glipizide

B-meglitinide analogs

Oral hypoglycemic agentsinsulin sensitizers

These agents lower blood sugar by improving target cell response to insulin without increase pancreatic insulin secretion.

Oral hypoglycemic agentsinsulin sensitizers

A-Biguanides: -Metformin is only available biguanide -it requir insulin for it is action -it will increase glucose uptake and decrease insulin resistance -it will not increase insulin secretion.

Oral hypoglycemic agentsinsulin sensitizers

Mechanism of action: *reduce hepatic glucose out put *slow intestinal absorption of sugars *reduce hyperlipidemia

Pharmacokinetics:

*well absorbed orally *not bound to serum proteins *not metabolized *highest concentration are in saliva and intestinal wall *excretion via urine

SIDE EFFECTS

Biguanides: * cause GIT disturbance * interfere with vit B12 absorption *contraindicated in: renal / hepatic diseases cardiac and respiratory insufficiency history of alcohol abuse sever infection pregnancy

Oral hypoglycemic agentsinsulin sensitizers

B- thiazolidinediones or glitazones e.g. pioglitazone rosiglitazones


Oral hypoglycemic agentsalpha –glucosidase inhibitors Acarbose and miglitol Mechanism Of action: Taken at the beginning of meals to delay the digestion of Carbohydrates and reduce glucose absorption , Also they inhibit alpha- glucosidase in the intestine which an enzyme responsible for hydrolysis of oligosaccharides to glucose .



Oral hypoglycemic agentsalpha –glucosidase inhibitors Kinetics: poor absorption metabolized by intestinal bacteria excreted in urine It cause GIT disturbances , and contraindicated in colonic ulceration and intestinal obstruction. (glucose not sucrose should be given to patients treated by alpha-glucosidase inhibitor in case of hypoglycemia, why?)

glucagons

Synthesized in the α cell of pancreasGlucagon increase blood glucose concentration by: 1-decresae glycogen synthesis 2- stimulate breakdown of stored glycogen. 3- increase gluconeogenesis in the liver.

glucagons

Not affect skeletal muscle glycogenKinetics: rapidly degraded in plasma, liver and kidney, t1/2 is 3-6 minTherapeutic uses: I-emergency treatment of sever hypoglycemia II-reverse the cardiac effects of toxic amounts of β-adrenergic receptor blocker.Adverse effects: nausea and vomiting

Implications for dentistry

Implications for dentistry
Dentist expect to have an increasing number of diabetic patients, diabetes mellitus is chronic complex not curable disease Complications: -neuropathy -microangiopathy(is a disease process affecting small blood vessels in the body ) -macrovascular disease( is a disease of any large (macro) blood vessels in the body) -numbness, tingling, deep burning pain -oral paresthesia and burning mouth

Implications for dentistry

Complications: -more susceptibility to infection, impaired ability to deal with infection and delayed wound healing -Infection , stress, surgical procedures disturb control of diabetes -diabetics complain of xerostomia , increase incidence of caries, candidiasis , gingivitis , periodontal disease and periapical abscesses -progressive periodontal disease and multiple periodontal abscesses -type II diabetics have impaired taste detection



Implications for dentistry
Complications: -hypoglycemia *mild (hunger, weakness,tachycardia,pallor, sweating) *modrate(incoherance,uncooerativeness, lack of judgment, poor orientation) *sever (unconsciousness)

Effects of cortisol and insulin on blood glucose level

What The diabetic need In Dental clinics?