«confirm» on methodical meeting of endocrinology department a chief of endocrinology department, prof. Vlasenko M. V. “ 31 ” august 2012 y methodological recomмendations icon

«confirm» on methodical meeting of endocrinology department a chief of endocrinology department, prof. Vlasenko M. V. “ 31 ” august 2012 y methodological recomмendations




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MINISTRY OF HEALTH PROTECTION OF UKRAINE

Vynnitsa national medical university named after M.I.Pyrogov





«CONFIRM»

on methodical meeting of endocrinology department

A chief of endocrinology department, prof. Vlasenko M.V.


_________________

“_31_”_august___ 2012 y



METHODOLOGICAL RECOMМENDATIONS

for independent work of students

by preparation for practical classes



Scientific discipline

Internal medicine

Мodule № 1

^ Basis of Internal medicine

substantial module №1

Diagnostic, treatment and prophylactic basis of main endocrinology diseases”


Topic

Topic №12: Treatment of diffuse toxic goiter. Thyrostatics. Surgical treatment. Postoperative conplication. Tyrotoxic crisis: clinics, diagnostics, treatment. Clinucal features of diffuse toxic goiter in teenagers, pregnant women and eldery patients.

Course

4

Faculty

Medical № 1



Vynnitsa – 2012


^ METHODOLOGICAL RECOMМENDATIONS

for the students of 4-th course of medical faculty for preparation to the practical classes from endocrinology


1.Тopic №12: Treatment of diffuse toxic goiter. Thyrostatics, surgical treatment. Postoperative conplication. Tyrotoxic crisis: clinics, diagnostics, treatment. Clinucal features of diffuse toxic goiter in teenagers, pregnant weman and eldery patients.


2. Relevance of topic: Hyperthyroidism is the condition resulting from the effect of excessive amounts of thyroid hormones on body tissues. Thyrotoxicosis is a main syndrome. Sometimes the term hyperthyroidism can be used in a narrower sense to denote this state when the thyroid gland is producing too much thyroid hormones in contrast with excessive ingestion of thyroid hormone medication. At one time or another, approximately 0,5 % of the population suffers from hyperthyroidism. Graves disease is the most common cause of hyperthyroidism and is fairly common in the population. It is responsible for over 80 % of hyperthyroid cases. It occurs most often in young women, but it may occur in men and at any age.


^ 3. Aim of lesson:

- to defne treatment tactic, appoint adequate pathogenetic and symptom­atic therapy.

- to know the features of course of toxic goiter in children and elderly and pregnant women;

- to be able to diagnose and treat basic complications of thyrotoxicosis.

- to carry out the clinical care of patients with a diffuse toxic goiter.

- to estimate the working capacity of patient.

- to formulate deontologycal principles of work with patients with a dif­fuse toxic goiter.

- to acquire skills of establishment of psychological contact and creation of atmosphere of trust between a doctor and patient with a diffuse toxic goiter and his family.

- to form sense of responsibility for a timeliness and plenitude of inspec­tions of patient with a diffuse toxic goiter, and also for being informed of patient about possible methods of treatment and its side effects.


4. References

4.1. Main literature

  1. Endocrinology. Textbook/Study Guide for the Practical Classes. Ed. By Petro M. Bodnar: - Vinnytsya: Nova Knyha Publishers, 2008.-496 p.

  2. Basіc & Clіnіcal Endocrіnology. Seventh edіtіon. Edіted by Francіs S. Greenspan, Davіd G. Gardner. – Mc Grew – Hіll Companіes, USA, 2004. – 976p.

  3. Harrison‘s Endocrinology. Edited J.Larry Jameson. Mc Grew – Hill, USA,2006. – 563p.

  4. Endocrinology. 6th edition by Mac Hadley, Jon E. Levine Benjamin Cummings.2006. – 608p.

  5. Oxford Handbook of Endocrinology and Diabetes. Edited by Helen E. Turner, John A. H. Wass. Oxford, University press,2006. – 1005p.

4.2. Additional literature

  1. Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC Graw-Hill Book, 1985. - P. 232-236. Pediatric Endocrinology. 5th edition. – 2006. – 536p.

  2. Thyroid Disordes (Aclevelend Clinic Guide) by Mario Skugor, Jesse Bryant Wilder Clevelend Press,2006. – 224p.


Basic Level.

  1. Localization of thyroid gland.

  2. Normal sizes and weight of thyroid gland.

  3. Biological effects of thyroid hormones’ action.

  4. Regulation of thyroid gland function.


Students’ Independent Study Program.

You should prepare for the practical class using the existing text books and lectures. Special attention should be paid to the following:

1. Particularities of hyperthyroidism in young, adult and pregnant patients.

  1. The main methods of treatment patients with diffuse toxic goiter.

  2. Antithyroid preparations: mechanism of action, side effects.

  3. Classifcation of thyreostatic preparations.

  4. Indications for surgical treatment and radioiodine treatment

  5. Usage of β-blockers, glucocorticoids, thyroid hormones.

  6. Surgical treatment.

  7. Iodine therapy.

  8. Treatment of endocrine ophthalmopathy.

  9. Thyroid storm: diagnostic criteria, treatment.


Short content of theme

Treatment of diffuse toxic goiter

  1. 1. Antithyroid drugs.

2. Drugs to ameliorate thiroid hormone effects .

  1. 131 I- therapy

  2. Surgery.




  1. 1. Antithyroid drugs

Propylthiouracil (PTU) and methimazole (MML) are effective inhibitors of thyroid hormone biosynthesis. PTU also inhibits extrathyroidal conversation of T4 to T3.

The usual starting dosage is 100 to 150 mg orally g 8h and for MML 10 to 15 mg when the patient becomes eythyroid the dosage is decreased to the lowest effective amount, usually 100 to 150 mg PPU in 2 or 3 divided doses or 10 to 15 mg MML daily. In general control can be achieved within 6 wk to 3 month. More rapid control can be achieved by increasing the dose of PPU to 400 to 600 mg /day , the risk of increasing the incidence of side effects, maintenance doses can be continued for one year or many years depending on the clinical circumstances.

Carbinazole (merkazolile ) is rapidly converts in vivo to MML. The usual starting dosage is 10 to 15 mg orally q 8h, maintenance dosage is 10 to 15 mg/ daily. The incidence of agranulocytosis appears to be higher for carbimazole than for eighter PPU or MML.

Adverse effects include:

  • allergic reactions;

  • nausea;

  • loss of weight;

  • fever;

  • arthritis, hepatitis;

  • anemia, thrombocytopenia;

  • agranulocytosis (in < 1% of patients).

If the patient allergic to one agent, it is acceptable to go to other, but there is a chance of cross sensitivity. In case of agranulocytosis, it is unacceptable to go to another agent, and more definitive therapy should be invoked, such as radioiodine or surgery.


Basic thyrostatics and their property



Chemical name




Dose (mg)




Indirect action




Name of preparation

Initial dose

Main­taining dose

2,5–10 12,5–50

Mechanism of action




1-Meth-yl-2-Mer-capto-imidasol

Merkazolil, thyrosol, thyamasol, methymasol, methysol, favistan

30–40




Inhibition of thyroid hor­mones synthesis as a result of block of iodinat-ion and conjuga­tion

Limfadenopathy, polyneuropathy, exantema, leuko-and thrombocyt-openia (in 2–6 % cases), goiter-оgenic effect, hypothyroidism (temporary)

4-Metyl-2-thyura-cil

Metil-thyouracil, propicyl, thyreostat

200–400




Inhibition of thy-roxin to tri iodo-thyronine trans­formation in tis­sues, reduces the synthesis of T3, T4 (depresses activity of per-oxydases, forma­tion of io dine-thyronins from iodinethyrosins)

Those

Dependence of thyrostatics initial dose on thyrotoxicosis severity



Severity

Dose (mg/day)




Tirozol

Propilthyouracil

Mild

20

200

Moderate

30–40

300–400

Severe

50–60

400–600


2. Some manifestations of hyperthyroidism are ameliorated by adrenergic antagonists - β – adrenergic blocking drugs.

Propranolol has had the greatest use phenomena that can be improved: tachycardia, tremor, mental symptoms, heat intolerance and sweating (occasional), diarrhea (occasional), proximal myopathy (occasional).

  1. Radioactive sodium iodine (131I)

It can be used in patients > 40 yr of age, because 131I might cause thyroidal or other neoplasm or gonadal damage.

There are only two important untoward effects of 131I therapy: persistent hyperthyroidism and hypothyroidism.

  1. Surgery is used: - in patient <21 yr. who should not receive radioiodine;

  • in persons who can not tolerate other agents because of hypersensitivity or other problems;

  • in patient with very large goiters (100 to 400 gm) (normal thyroid weights 20gm);

  • in some patients with toxic adenoma and multinodular goiter;

  • hyperthyroidism during pregnancy;

  • recurrent hyperthyroidism after course of antithyroid treatment.

Precautions:

- patient must be euthyroid before operation.

Results of the surgery:

  • normalization of thyroid gland function;

  • postoperative recurrences (2-9 %);

  • hypothyroidism (in about 3 % of patient the first years and in about 2 % with each succeeding year);

  • vocal cord paralysis;

  • hypoparathyroidism.

Iodine is used in preparing the patient for surgery. Surgical procedures are more difficult in patients who previously have undergone thyroidectomy or radioiodine therapy.


Advantages and disadvantages of basic methods of treatment of diffuse toxic goiter

(A.Weetman, 2003)

Thyrostatics Radio-active I131 Operative treatment



Effciency like a treatment of the frst line

40 – 50 %

>80 – 95 %

>95 %

Achieving of euthyroidism

2 – 4 weeks

4 – 8 weeks

Preparation by thyrostatics is needed

Hypothyroidism

15 % in 15 years

Depending on a dose (10 – 20 % in the frst year, in future 5 % in a year)

Hesitates, but approximately so much as after 131I

Adverse effects

5 % – moderate;

<1 % – heavy

<1 %

For pregnant

Method of dose titration

Contra-indicated

Possibly in the second trimester

At a large goiter

High risk of relapse

It is necessary introduction of large activity

Rapid effect

In children

Treatment of the frst choice

Treatment of the third choice

Treatment of the second choice


Treatment of endocrine ophthalmopathy include:

  • steroid therapy: prednisolone 20 – 40 mg daily;

  • electrophoresis with glucocorticoids or KI;

  • aloe, FIBS;

  • dehydration therapy;

  • cavinton, piracetam;

  • lateral tarsorrhaphy: when there is corneal ulcer due to inability to close the lids;

  • extra – ocular muscle surgery: to correct persistent diplopia.


Thyroid storm.


Thyroid storm is a life- threatening emergency requiring prompt and specific treatment.

In is characterized by abrupt onset of more severe symptoms of thyrotoxicosis, with some exacerbated symptoms and signs atypical of uncomplicated Graves disease:

  • fever;

  • marked weakness and muscle wasting;

  • extreme restlessness with wide emotional swings;

  • confusion;

  • psychosis or even coma;

  • hepatomegaly with mild jaundice;

  • the patient may present with cardiovascular collapse or shock.

Thyroid storm results from:- untreated or inadequately treated thyrotoxicosis

It may be precipitated by:

  • infection;

  • trauma

  • surgery;

  • embolism;

  • diabetic acidosis;

  • fright;

  • toxemia of pregnancy;

  • labor;

  • discontinuance of antithyroid medication;

  • radiation thyroiditis.

Treatment of thyroid storm

Iodine-30 drops Lugol’s solution/day orally in 30g 4 divided doses; or 1 to 2 gr. sodium iodide slowly by i/v drip.

Propylthiouracil (merkazolil) - 900 to 1200 mg/day orally or by gastric tube.

Propranolol - 160mg/day orally in 4 divided doses; or 1mg slowly i/v g 4h under careful monitoring; a rate of administration should not exceed 1mg/min; a repeat 1mg dose may be given after 2 min i/v glucose solutions .

Correction of dehydration and electrolyte imbalance cooling blanket for hypertermia.

Digitalis if necessary.

Treatment of underlying disease such as infection.

Corticosteroids-100 to 300mg hydrocortisone/day i/v.

Iodine in pharmacological doses inhibits the release of T3 to T4 within hours and inhibits the organification of iodine, a transitory effect lasting from a few days to a week (”escape phenomenon”.)

Indications it is used for

  • the emergency management of thyroid storm;

  • thyrotoxic patients undergoing emergency surgery;

  • preoperative preparation of thyrotoxic patients selected for subtotal thyroidectomy /since it also decreases the vascularity of the thyroid gland.

It is not used for routine treatment of hyperthyroidism. The usual dosage is 2 to 3 drops of satured potassium iodide solution orally tid or dig 1300 to 600 mg/day; or 0,5gr sodium iodide in 0,9% sodium chloride solution given i/v slowly g 12h.

Complication of iodine therapy include:

  • inflammation of the salivary glands;

  • conjunctivitis;

  • skin rashes;

  • a transient hyperthyroidism (iod-BASEDOW phenomenon) (it can be observed in patients with nontoxic goiters after administration of iodine-contrast agents).

Antithyroid drugs

Doses of PPU of 450-600 mg/day or greater 800 to 1200mg/day are generally reserved for the patient with thyroid storm, because such doses block the peripheral conversation of T4 to T3.

β-adrenergic blocking drugs. Propranolol rapidly decreases heart rate, usually within 2 to 3 h when given orally and within minutes when given i/v.


Tests and Assignments for Self-assessment.

Multiple Choice.

Choose the correct answer/statement:

  1. The normal weight (gr.) of the thyroid gland is:

  1. 7 – 10;

  2. 1 – 3;

  3. 20 – 30;

  4. 45 – 55;

  5. 50 – 60.

  1. A patient of 28 years old has diffuse toxic goiter. Takes mer-kasolilum in the dose of 50 mg per day. In 3 weeks after the beginning of treatment the temperature rose to 38,1 °C, pain appeared in a throat, painful ulcers in a mouth. Blood examination: erythrocytes of 3,1×1012/l; hemo­globin of 94 g/l; color index 1,0; leucocytes of 1,0×109/l, ESR - 28 mm/h. What can be the most credible reason of worsening of patient state?

    1. Beginning of agranulocytosis

    2. Development of paratonsilar abscess

    3. Acute respiratory infection

    4. Development of thyrotoxic crisis

    5. An allergic reaction on merkasolil

Answer: 1 – B. 2 – A.


Real-life situations to be solved:


Patient F, 38 years old, complaints on general weakness, increased sweating, palpitation. Physical examination shows: skin is moist, hot; trembling of the fingers, thyroid gland is enlarged, positive eye’s symptoms, pulse rate 116/minute, systolic murmur on the region of the heart and thyroid. Put previous diagnosis and make the plan of the examination.

Answer: Hyperthyroidism, moderate stage of thyrotoxicosis. Ultrasonic examination of the thyroid gland, the levels of TSH, T3,T4.


Students Practical Activities.


Work 1 : Students’ group is divided into 2 sub-groups, that work near the patients’ bed: ask the patients on organs and systems, take anamnesis of the disease , anamnesis of life, make objective exam. With the teacher’s presence. In the class-room they discuss the patients, learn data of laboratory and instrumental exam. of these patients.

1.To group the symptoms into the syndromes.

2.To find out the leading syndrome and make differential diagnosis.

3.To formulate the diagnosis.

4.To make a plan of treatment.


Methodological recommendation prepared assistant, c.m.s. Chernobrova O.I.

It is discussed and confirm on endocrinology department meeting

" 31 " august 2012 y. Protocol № 1.

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