HYPO- AND HYPERTHYROIDISM. Esztella Mikolás MD Semmelweis University 2nd Department of Medicine

Size: px

Start display at page:

Download "HYPO- AND HYPERTHYROIDISM. Esztella Mikolás MD Semmelweis University 2nd Department of Medicine"

Bryce Oliver
5 years ago
Views:

1 HYPO- AND HYPERTHYROIDISM Esztella Mikolás MD Semmelweis University 2nd Department of Medicine

2 Anatomy

3 Histology

4 Thyroxin synthesis and excretion Häggström, Mikael (2014). "Medical gallery of Mikael Häggström 2014". WikiJournal of Medicine 1 (2). DOI: /wj m/ ISSN Production is regulated by TSH (thyroid-stimulating hormone) level and iodine supply

5 Regulation of thyroid hormone secretion Hypothalamic-pituitary-thyroid axis From the collection of Dr Sheikh-Ali

6 Physiological effects thyroid hormone receptors (nuclear): TR-alpha 1: widely expressed (heart, skeletal muscles, bone) TR-alpha 2: antagonistic TR-beta 1: brain, liver, kidney TR-beta 2: pituitary gland, hypothalamus increase basal metabolic rate and thermogenesis stimulate water- and electrolyte transport accelerate the substrate-turnover, the amino acid and lipid metabolism potentiate the effect of catecholamine compounds regulate growth and neurological development

7 TSH - thyroid stimulating hormone normal range: mu/l depends on age, iodine supply, BMI, pregnancy, ethnicity, test method, etc.

8 T3 and T4 Biologically active portion: FT4 (free T4) ~0,015% FT3 (free T3)~0,33% normal range: FT4: pmol/l FT3: pmol/l T3 is 2-10-fold more potent Binding proteins: thyroxine binding protein, transthyretin, albumin

9 Conversion Deiodinase 1: expressed mainly in liver and kidney, with lesser expression in the thyroid Produces small amount of circulating T 3 (approx. 24%) Preserves iodide by removing iodine from inactive metabolites of T 3 and T 4 in the liver and kidney Deiodinase 2: central nervous system, pituitary gland, thyroid, heart, brown adipose tissue, and skeletal muscle T4=>T3 conversion (approx 60%) Deiodinase 3: brain and skin T4=>T2 T4=>rT3 Pol et al, DOI: /s

10 HYPOTHYROIDISM

11 Definition and frequency subclinical hypothyroidism: elevated TSH, normal FT4 prevalence: 4-10% manifest hypothyroidism: elevated TSH, low FT4 prevalence: 0,2-1% secondary hypothyroidism: elevated/normal/low TSH, low/normal FT4

12 Clinical symptoms general: fatigue, headache, cold intolerance, weight gain, anemia cardiac: pericardial fluid, heart contractility and pulse rate decrease, but hypertension (peripheral resistance increases) metabolic: dyslipidemia, hyponatremia GI tract: constipation, dysphagia skin: pale, cold, atrophic, myxedema, hair loss, weak, fragile nails neurological: ataxia, dementia, cognitive dysfunction, hypo-areflexia respiratory system: hypoventilation, sleep apnea reproductive system: amenorrhea, decrease of sex drive, infertility, hyperprolactinemia musculoskeletal: elevation of creatin-kinase, myopathy, myalgia, rhabdomyolysis

13 Etiology primary hypothyroidism (99%): autoimmune thyroiditis iatrogenic (radioiodine treatment, surgery, amiodarone) congenital iodine insufficiency malignancy transient (Wolff-Chaikoff effect, thyroiditis, thyreostatic treatment, Li-carbonate, IFalpha, IL-2) secondary hypothyroidism: pituitary tertiary hypothyroidism: hypothalamic origin thyroid hormone resistance

14 /d/df/hypothyroidism.jpg

15 Diagnostic protocol aspecific symptoms (elderly!) history: previous irradiation, thyreostatic treatment, amiodarone, surgery TSH, if out of normal range FT4 thyroid specific antibodies neck ultrasonography

17 Treatment I. Main goals (ATA 2014): to provide resolution of the patients' symptoms and hypothyroid signs, including biological and physiologic markers of hypothyroidism to achieve normalization of serum thyrotropin with improvement in thyroid hormone concentrations to avoid overtreatment (iatrogenic thyrotoxicosis), especially in the elderly.

18 When to treat: manifest hypothyroidism subclinical hypothyroidism: Treatment II. TSH>10 mu/l goiter ischemic heart disease pregnancy atpo positivity older than 70, TSH>8 mu/l + any of above symptomatic disease

19 Treatment III. levothyroxine (L-T4): µg/kg ( µg) T 1/2 : 7-8 days => orally once daily absorbed only at low ph value => 30 min before meal start with lower dose, especially in elderly and/or in case of cardiac disease (25-50 µg) first TSH control after 4 weeks TSH control 6 weeks after every dose adjustments if stable - yearly

20 Pregnancy placental deiodinase => ~45% higher L-T4 dose needed trimester specific target values: 1st: mu/l 2nd: mu/l 3rd: mu/l subclinical cases have to be treated closer TSH control screening in case of atpo or atg positivity, autoimmune history, goiter, any relevant symptoms present, positive family history, radioiodine therapy, surgery, miscarriage routine screening?

21 Elderly I. Age-Specific Distribution of Serum Thyrotropin and Antithyroid Antibodies in the U.S. Population: Implications for the Prevalence of Subclinical Hypothyroidism Martin I. Surks, and Joseph G. Hollowell J Clin Endocrinol Metab DOI:

22 Elderly II. sensitivity of feedback mechanism decrease with age alteration of biological activity of TSH decrease of thyroidal sensitivity to TSH apathetic hyperthyroidism

23 Thyroiditis acute infective thyroiditis radiation-induced thyroiditis palpation-induced thyroiditis subacute de Quervain thyroiditis painless thyroiditis drug induced (amiodarone, alpha-interferon, IL-2) chronic Hashimoto-thyroiditis infective thyroiditis (immunodeficiency)

24 De Quervain thyroiditis (subacute granulomatosis thyroiditis) etiology: viral infection (?) female:male=5:1 clinical signs: myalgia, fatigue, thyroid is painful, swollen laboratory markers: high sedimentation rate, elevated CRP, elevated TG level, moderate leucocytosis low 24 hour radioiodine uptake hyper-, eu-, hypothyroidism, euthyroidism therapy: NSAID, corticosteroids, propranolol recovery in 3-6 months short term relapse ~20%, long term relapse ~4%

25 Hashimoto thyroiditis organ-specific autoimmune disease => 90% follicular destruction => chronic hypothyroidism female: male=10:1 prevalence: 2-7% (female) histology: infiltration of lymphocytes, Hürtle-Askanazy cells, follicular destruction, fibrosis (FGF-23) atpo and atg positivity >95% laboratory markers: sedimentation, CRP mildly elevated radioiodine uptake: salt and pepper pattern clinical signs: mild thyroid enlargement, sensitivity, transitional hyperthyroidism, permanent hypothyroidism, rare endocrine orbitopathy therapy: levothyroxine substitution ( µg) TSH target: 2.5 mu/l prednisolon in acute phase if necessary

26 Normal Hashimoto-thyroiditis De-Quervain-thyroiditis

27 Congenital hypothyroidism hypothyroidism is present at birth incidence: primary form: 1: secondary form: 1: more frequent in girls and twins in Hungary screened since 1984 only 1/3 of the world is screened!

28 Orphanet Journal of Rare Diseases20105:17

29 HYPERTHYROIDISM

30 Definition subclinical hyperthyroidism: low TSH (0.1 mu/l>), normal FT4 manifest hyperthyroidism: low TSH (0.1 mu/l>), high FT4 prevalence: ~0.75% secondary hyperthyroidism: elevated/normal TSH, elevated FT4

31 Clinical symptoms general: weakness, fatigue, high body temperature, hot intolerance, weight loss with good appetite, resting tremor skin: warm, wet skin, intense sweating cardiac: tachycardia, systolic blood pressure elevation, lower diastolic pressure, positive inotropic effect metabolic: high metabolic rate GI tract: diarrhea neurological: tremor, hyperactivity respiratory system: hyperventilation reproductive system: irregular period, amenorrhea, sex hormone binding protein musculoskeletal: muscle weakness

32 Etiology Thyroid hormone overproduction TSH-receptor stimulation Graves-Basedow-disease mola hydatiosa choriocarcinoma TSH overproduction TSH-producing pituitary adenoma thyroid hormone resistance Thyroid autonomy toxic adenoma toxic multinodular struma Unregulated hormone excretion subacute Hashimoto silent (painless) thyroiditis postpartum iodine induced Extra thyroidal hormone production DTC struma ovarii Factitious hyperthyroidism

33 Diagnosis I. Anamnesis and physical examination Laboratory markers: low TSH, elevated FT4 and FT3 levels TSH can remain low for months after treatment FT4 and FT3 indicate severity better grey zone TSH µu/l => repeat test 1-3 months later

34 Diagnosis II. Radiology: ultrasonography (hypervascularisation, nodules) 99m Tc gamma scan low uptake => thyroiditis high uptake => Graves-Basedow disease focal high uptake => toxic adenoma

35 Graves-Basedow disease incidence: 5-10/ year-old female patients TSH-receptor stimulating IgG antibody (TSHR-Ab) in half of all cases genetic predisposition: HLA-A1, -B8, DR3 physical signs: thyroid can be enlarged, look for signs of EOP or pretibial myxedema

36 Graves-Basedow disease -> Thyroid inferno pattern (increased vascularity and arteriovenous shunting)

37 Gamma scan

38 Treatment I. Thyreostatic treatment thionamides thiamazol (methimazol) mg/die => dose reduction continue for at least one year in euthyreotic state TSH in every 6-8 weeks propylthiouracil (PTU) mg/die => dose reduction carbimazol Side effects agranulocytosis 1:1000 => radioiodine or surgery ANCA positive vasculitis fulminant hepatitis (PTU)

39 Treatment II. Radioiodine (RI) treatment 131 I-isotope orally dose: 70 Gy expected to be effective in 2-6 months in case of severe, active EOP RI is contraindicated! preventive corticosteroid for 6-12 weeks in risk groups (smokers, EOP in history, year-old females) Subtotal thyroidectomy - indications Basedow-Graves disease + cold thyroid nodule RI not possible size reduction needed

40 Endocrine orbitopathy I. inflammation of the orbital tissue and ocular muscles 10-30% present in Basedow-Graves disease TSH-R is expressed on orbital fibroblasts => lymphocyte and macrophage activation => increase of glycosaminoglycan and sulphated mucopolysaccharide formation edema, thickening of orbital muscles, exophthalmos smoking increases risk by 70%! diagnosis: MRI T1 - muscle thickening ATA classification clinical activity score

41 Endocrine orbitopathy II. treatment indications: loss of sight, subluxation of eyeball, change in color sight, cornea blurriness, progressive exophthalmos, papillary edema, permanently visible cornea treatment: euthyreosis avoidance of smoking immunosuppression corticosteroid (per os or iv) pentoxyphyllin selenium retrobulbar irradiation (contraindicated in diabetes mellitus) surgical decompression antalgic treatment

Toxic adenoma (TA) hot nodules on gamma camera malignancy is extremely rare compensated TA: normal thyroid tissue function decreases decompensated TA:

43 Toxic adenoma (TA) hot nodules on gamma camera malignancy is extremely rare compensated TA: normal thyroid tissue function decreases decompensated TA: normal thyroid tissue is completely suppressed subclinical cases have to be treated therapy: RI 300 Gy radio ablation laser ablation surgery

44 Toxic multinodular goiter mainly in older age can be contrast- or drug induced therapy: RI 150 Gy (contraindication: significant trachea compr.) surgery Kamal A.S. Al-Shoumer, Hossein Gharib entokey.com

45 THYROID EMERGENCIES

46 Thyreotoxicosis (thyroid storm) potentially life threatening condition provoking factors: RI treatment, surgery, trauma, myocardial infarction, iodine exposition symptoms: fever, sweat, flush, tachycardy, cardiac failure, vomiting, diarrhea, loss of conciousness, coma FT3 and FT4 is increased but not extreme Treatment thyreostatic treatment (thiamazole 80 mg per day/ PTU 250 mg/6 hours) iodine compounds (Lugol iodine or potassium iodine) glucocorticoids beta-blockers sedatives

47 Myxedema coma multi organ failure more common in elderly symptoms: severe myxedema, hypotension, bradycardia, low body temperature, hypoventillation (CO2-retention), SIADH, convulsion, coma treatment: iv 500 µg levothyroxine (or µg T3 every 12 hours) 100 µg levothyroxine per day 5-10 mg/hour hydrocortisone hyperosmolar fluids only

48 THANK YOU FOR YOUR ATTENTION!

Diseases of thyroid & parathyroid glands (1 of 2)

Diseases of thyroid & parathyroid glands (1 of 2) Thyroid diseases Thyrotoxicosis Hypothyroidism Thyroiditis Graves disease Goiters Neoplasms Chronic Lymphocytic (Hashimoto) Thyroiditis Subacute Granulomatous