CC BY
7
graves disease
Zhamaldinov K.U.1, Ismailova M.A.1, Makataeva D.T.1, Smolinov I.G.1, Sharipbai K.Zh.1, Sharipova Z.M.1, Shokebaev A.A.2, Orynbasar N.T.2
1 "S.D. Asfendiyarov Kazakh National Medical University" NC JSC, Almaty, Kazakhstan
2 "A.N. Syzganov National Scientific Center for Surgery" JSC, Almaty, Kazakhstan
Abstract
Hyperthyroidism (Graves' disease (GD)), is a relatively rare disease in adults and children. Treatment options for adults and children are antithyroid drugs (ATD), radioactive iodine (RAI), or thyroidectomy, but the risks as well as benefits of each are different.
https://doi.org/10.35805/BSK2022IV047 Zhamaldinov K. orcid.org/0000-0002-8686-4656 Ismailova M.
orcid.org/0000-0001-8249-7441 Makataeva D.
orcid.org/0000-0002-6168-9644 Smolinov I.
orcid.org/0000-0002-0450-8691 Sharipbai K.
orcid.org/0000-0002-2686-2886
Sharipova Z.
orcid.org/0000-0002-2487-3741
Shokebaev A.A.
orcid.org/0000-0003-2395-3843 Orynbasar N.T.
orcid.org/0000-0001-5369-8682
Грейвс ауруы
Жамалдинов К.У.1, Исмаилова М.А.1, Макатаева Д.Т.1, Смолинов И.Г.1, Шарипбай К.Ж.1, Шарипова З.М.1, Шокебаев А.А.2, Орынбасар Н.Т.2
1 Хирургияльщ аурулар кафедрасы, «С. Д. Асфендияров атындагы ^аза^ ¥лттьщ медицина университет» Ке А^, Алматы ^аза^стан
2 «А.Н. Сызганов атындагы ¥лттьщ гылыми хирургия орталыгы» А^, Алматы Казахстан
Ацдатпа
Гипертиреоз (Грейвс ауруы (ГА)), ересектер мен балаларда салыстырмалы mYpde сирек кездесетн ауру. Ересектер мен балалардагы емдеу нус;алары антитиреоидты препараттар (АТП), радиоакmивmi йод (RAI) немесе тириоидэктомия болып табылады, б'ра; эр эд'кт'щ ;ауiп-;атерi мен пайдасы эртYрлi.
Болезнь Грейвса
Жамалдинов К.У.1, Исмаилова М.А.1, Макатаева Д.Т.1, Смолинов И.Г.1, Шарипбай К.Ж.1, Шарипова З.М.1, Шокебаев А.А.2, Орынбасар Н.Т.2
1 Кафедра Хирургических болезней, АО «Национальный медицинский университет имени С.Д. Асфендиярова», г.Алматы, Казахстан
2 АО «Национальный научный центр хирургии им. А.Н. Сызганова», г. Алматы, Казахстан
Аннотация
Гипертиреоз (болезнь Грейвса (БД)), является относительно редким заболеванием у взрослых и детей. Варианты лечения у взрослых и детей - антитиреоидные препараты (АТП), радиоактивный йод (RAI) или тириоидэктомия, но риски, а также преимущества каждого способа различны.
Corresponding author. Orynbasar N.T. - Surgeon of Department of gastrointestinal tract and endocrine surgery of "A.N. Syzganov National Scientific Center for Surgery" JSC, Almaty Kazakhstan E-mail: nur_ibn@mail.ru Conflict of interest The authors declare that they have no conflicts of interest
Keywords:
hyperthyroidism, diffuse toxic goiter, Graves'disease, radioactive iodine, thyroidectomy Хат алысатын автор. Хат алысатын автор. Орынбасар Н.Т. - Ас^азанчшек жолдары жэне эндокринд/к хирургия ôeniMiHiH хирург дэр:гер1, «А.Н. Сызганов атындагы ¥лтты% гылыми хирургия орталыгы» АК,Алматы Казахстан E-mail: nur_ibn@mail.ru
Мудделер к,ак,тыгысы
Авторлар MYдделер %а%тыгысыныц жо^тыгын мэлiмдейдi Туйш сездер:
гипертиреоз, диффузды токсикалы% зоб, Грейвс ауруы, радиоактивтi йод, тиреоидэктомия.
Автор для корреспонденции: Орынбасар Н.Т. - Хирург отделения желудочно-кишечного тракта и эндокринной хирургии, АО «Национальный научный центр хирургии им. А.Н. Сызганова» г. Алматы, Казахстан E-mail: nur_ibn@mail.ru Конфликт интересов Авторы заявляют об отсутствии конфликта интересов
Ключевые слова:
гипертиреоз, диффузный токсический зоб, Болезнь Грейвса, радиоактивный йод, тиреоидэктомия
Introduction
Graves' disease is an autoimmune disease resulting in generalized hyperfunction of the thyroid gland, i.e., hyperthyroidism.
It is named after Robert Graves, the Irish doctor who described this form of hyperthyroidism about 150 years ago. It occurs 7-8 times more often in women than in men [1].
Etiology
It is generally recognized that Graves' disease has a pronounced hereditary component, implementing a significant role of genetic factors.
Human leukocyte antigen (HLA), CD40, CTLA-4, PTPN22, Tg and TSHR are the main genes contributing to hypertheriosis. Impaired immune response (autoaggression) proteintyrosine phosphatase, non-re-
ceptor type 22 (PTPN22). PTPN22 is a strong inhibitor of T-cell activation [2].
In Graves' disease these antibodies (called thyrotropin receptor antibodies (trab) or thyroid stimulating immunoglobulins (TSI) act in the opposite way [3].
Antibodies in Graves' disease bind to receptors on the surface of thyroid cells and stimulate these cells to overproduce and release thyroid hormones [4].
The term "primary hyperthyroidism" is sometimes used to refer to hyperthyroidism that develops as a result of thyroid disease. Secondary hyperthyroidism develops due to pathological processes occurring outside the thyroid gland, such as a TSH-secreting pituitary tumor. The 3 most common causes of thyrotoxicosis are also associated with thyroid hyperfunction:
• Diffuse thyroid hyperplasia associated with Graves' disease (85% of observations);
• hyperfunctional multinodular goiter;
• hyperfunctional thyroid adenoma.
Epidemiology
Iodine deficiency is the most common cause of goiter worldwide, affecting approximately 2.2 billion people. The prevalence and incidence of goiter depend on the degree of iodine deficiency. With mild iodine deficiency, the incidence of goiter is between 5% and 20%. With moderate deficiency, the prevalence increases to 20-30%, and with severe iodine deficiency, the incidence rises to over 30% [5].
Graves' disease is the most common cause of hyperthyroidism, accounting for 60% to 80% of hyperthy-roidism cases. The prevalence in the general population is 1% to 1.5%. The incidence is 20 to 30 cases per year per 100,000 population [6].
Classification Grade Characteristics
Table 1. According to the degree of enlargement of the thyroid gland (WHO) [7] 0 >No palpable or visible goitre.
1 A goitre that is palpable but not visible when the neck is in the normal position (i.e. the thyroid gland is not visibly enlarged). Nodules in a thyroid that is otherwise not enlarged fall into this category.
2 A swelling in the neck that is clearly visible when the neck is in a normal position and is consistent with an enlarged thyroid gland when the neck is palpated.
Table 2.
According to the severity of clinical manifestations and hormonal disturbances [8]
Subclinical (mildflow) The clinical picture is absent or mild. TSH content is decreased, T4 and T3 levels are within the reference values.
Manifest (medium flow) An elaborate clinical picture. The TSH content is significantly decreased, and the concentrations of T4 and T3 are elevated.
Complicated (severe flow) Thyrotoxicosis and its complications: Atrial fibrillation, heart failure, relative adrenal insufficiency, dystrophic changes in the parenchymatous organs, psychosis, severe weight loss. TSH levels are significantly decreased, with elevated concentrations of T4 and T3 [8].
Diagnosis
Diagnosis begins with complaints and a general examination of the patient. Laboratory data are the main diagnostic measures for diagnosis. Namely -general blood test and biochemistry, determination of the content of TSH, T3, T4, pituitary hormones, antibody titer to the TSH receptor, "classical" antibodies to
the thyroid gland titer. An ultrasound or MRI scan of the thyroid gland is also important [8].
Serology
Measurement of serum TSH has the highest sensitivity and specificity of any single blood test used in evaluating suspected hyperthyroidism and should be used as an initial screening test (Fig.1) [9].
Figure 1.
Serology of Graves disease [9]
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BECTHMK XMPyPrMM KA3AXCTAHA №73 • 2022
As in other autoimmune thyroid diseases, high levels of classical antithyroid antibodies - at-TPO and at-(at
least 70-80% of cases) can be determined in HD [10]. Tactics patients management (Fig.2) [9].
Figure 2.
Algorithm for the management of a patient with Graves' hyperthyroidism [9]
Differential diagnosis
Disease Distinguishing features
Thyroid-producing pituitary adenoma «-» TSH reaction to thyrolyberine
Thyroid cancer metastases Surgical treatment in anamnesis
Iatrogenic thyrotoxicosis History of taking lithium, interferon, and drugs containing large amounts of iodine
Multinodular toxic goiter Heterogeneity of scintigraphicpattern [11].
Treatment
Methods of treatment:
- Conservative therapy
- RAI therapy
- Surgical treatment
Conservative therapy
Conducted with antithyroid therapy (ATT). The mechanisms of the drugs are as follows:
Intrathyroid inhibition:
- Iodine oxidation.
- Iodothyrosine compound.
- Thyroglobulin biosynthesis
- Follicular cell growth
Extrathyroid inhibition of T4/T3 conversion (PTU) [9].
The main ATT drugs are thionamides such as pro-pylthiouracil (PTU), carbimazole (CBZ), and the active metabolite of CBZ, methimazole (MMI)
The usual daily maintenance doses of ATP in the titration regimen are 2.5-10 mg MMI and 50-100 mg PTU. In addition, daily doses of 30 mg MMI may be given in combination with the addition of levothyroxine (L-T4) (blocking and replacement mode) to avoid medication-induced hypothyroidism [12].
Advantages:
- Early treatment of the disease
- Availability
Disadvantages:
- Frequent relapses
- Duration of treatment
- Adverse complications (liver cirrhosis, toxic hepatitis, unresponsiveness to ATP) [13].
Both groups had recurrence of hyperthyroidism after discontinuation of methimazole, according to the results of the study. Secondary key findings were both clinical and subclinical hypo- and hyperthyroidism during methimazole treatment [14].
RAI radioactive iodine therapy
One of the treatments for Graves' disease is radioactive iodine therapy. The mechanism of action is that radioactive iodine (RAI) exerts its effect when it is absorbed by follicular thyroid cells, emitting beta-rays that further cause permanent local damage to thyroid tissue.
RAI treatment can predispose patients to irreversible hypothyroidism because it causes permanent destruction of thyroid tissue. Patients may require lifelong thyroxine therapy [15].
Radioiodine (RAI) therapy is contraindicated in the following cases:
- Pregnancy
- Breast-feeding
- Cancer without iodine absorption
- Graves' ophthalmopathy (moderate to severe)
- Severe thyrotoxicosis
- Vomiting
- Diarrhea [16].
Radioiodotherapy worsens the course of ophthal-mopathy. This is because radiation, by affecting thyro-cytes, leads to a massive release of antigens shared
with the retrobulbar tissue, which in turn stimulates the formation of antibodies that induce the appearance or activation of EOP [17]. Early complications
- Teratogenicity
- Bone marrow suppression
- Radiation-induced thyroiditis
- Transient thyrotoxicosis Late complications
- Bone marrow depression
- Pulmonary fibrosis
- Leukemia
- Hypothyroidism [16].
Radioiodine therapy is an effective treatment for Graves' disease. A high dose of radioiodine provides a high remission rate. The use of radioiodine as a therapeutic agent is simple, safe, effective and cost-effective [18].
Surgical treatment
Thyroidectomy is the most commonly chosen treatment. In recent American and European surveys, surgery is the first-line treatment. However, thyroidectomy is an effective treatment when the thyroid gland is enlarged, when primary hyperparathyroidism or suspected malignant nodules are present, or when the patient wishes to avoid exposure to ATD (Anti Thyroid Drugs) or RAI (radioactive iodine).
Indications Contraindications
Large goitre Thyreostatic allergy Ineffectiveness of conservative therapy Chronic diseases in the acute stage Contraindication of RAI [19].
The advantages of thyroidectomy include no radio- Advantages and disadvantages of total thyroidec-active iodine risk, rapid control of hyperthyroidism and tomy for Graves' hyperthyroidism: no detrimental effects on ophthalmopathy.
Advantages Disadvantages
No recurrent hyperthyroidism No radiation risk Rapid control of hyperthyroidism No evidence of harmful effects on the course of Graves' ophthalmopathy Risk of postoperative hypoparathyroidism Risk of recurrent laryngeal nerve palsy Persistent hypothyroidism Risks related to anaesthesia or surgery Hospitalisation Postoperative scarring
To minimize the risk of complications, surgery must be performed by a qualified surgeon. To minimize the risk of intra- or postoperative exacerbation of thyrotox-icosis, hyperthyroidism must be adequately controlled with ATD treatment before surgery. The use of saturated potassium iodide solution (SSKI) is useful in the immediate preoperative period (10 days) to reduce thyroid vascularisation and intraoperative blood loss (9).
Complications:
1. Post-operative bleeding (up to 6%)
2. Defeat of the recurrent laryngeal nerve and dys-phonia (10%)
3. Hypoparathyroidism (20%) (20).
Despite all the variety of drug treatments for patients with hypertheriosis, it has lost its "predominant role" in the choice of treatment. As studies show, 50%
References
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Predictors of relapse
Potential predictors of recurrence: marked thyroid enlargement, young age, high levels of TSH-R-Ab, and the presence of thyrotoxicosis complications [22]. Conclusion
After reviewing all treatment methods, comparing the advantages and disadvantages of each, we have concluded that surgical treatment is currently the "leading" treatment for Graves' Disease. Thanks to advances in surgery, surgical thyroid removal has been made safer by the development of new surgical, haemostatic and other techniques such as intraoperative monitoring of the recurrent laryngeal nerve. Thereby lowering the rate of complications in patients.
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