1. Hypothyroidism. Iodine deficiency disorders.
Department of Internal Medicine N2
as.-prof. Svystun I. I.

2. Anatomy of thyroid gland
The thyroid is a firm vascular organ lying in the neck, caudal to cricoid cartilage.
It is composed of two nearly equal lobes connected by a thin isthmus and weights approximately 20 – 30 g.
Rests of thyroid tissue are occasionally presents in sublingual or retrosternal areas.
Thyroid secrets: T3, T4, calcitonin.
Hyoid Bone
Cricothyroid Ligament
Thyroid Cartilage
Cricoid Cartilage
Thyroid Gland
Pyramidal Lobe
Right Lobe
Isthmus
Left Lobe
Trachea

3. A follicle is structural and functional unit of the thyroid gland
The follicle contains colloid (which consists of thyroglobuline, a glycoprotein, containing T3 and T4 within its matrix)
Epithelial cells
Parafollicle cells (C-cells) (synthesized calcitonine)
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4. The thyroid hormones, thyroxine (T4) and triiodothyronine (T3)
are secreted under the stimulatory influence of pituitary thyrotropin (thyroid-stimulating hormone or TSH). TSH secretion is primary regulated by a dual mechanism:
thyrotropin-releasing hormone (TRH);
thyroid hormone.
Thyroid hormone exits in circulation in both free and bound formas. The thyroid gland is the sole source of T4 and only 20% of T3 is secreted in the thyroid. Approximately 80% of T3 in blood is derived from peripheral tissue (mainly hepatic or renal) deiodinatoin of T4 to T3.
Hypothalamus
TRH stimulation
inhibition
Pituitary
Free hormone Bound hormone T4 T3
Liver
Thyroid
Binding
proteins
TSH stimulation
Thyroid

5. Thyroid hormone synthesis
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6. Major deiodinative and non-deiodinative pathways of thyroid hormones metabolism.

7. Physiologic effects of thyroid hormones
Increasing of protein metabolism in virtually every body tissue
Increasing of O2 consumption by increasing the activity of Na+ H+ ATPase (Na pump), primarily in tissues responsible for basal O2 consumption (i.e., liver, kidney, heart and skeletal muscle).)
Stimulation of erythropoesis
Positive chrono- inotropic effects on myocardium
Achievement of formation of nervous system and skeleton in perinatal period

8. Goitre
is an enlargement of the thyroid gland.

9. GOITRE
HYPERTHYROIDISM
HYPOTHYROIDISM
EUTHYROIDISM

11. Degrees of thyroid gland enlargement (WHO, 1994)
0 –goiter is absent
1- we can palpate but can’t see
2 – thyroid gland can be palpated and seen

12. Hypothyroidism (myxedema)
is the characteristic reaction to thyroid hormone deficiency.
The spectrum of hormone ranges from a few non – specific symptoms to overt hormone, to myxedema coma.

13. Historical perspective
The first full clinical description of the hypothyroidism and mixedema was made in 1874 by Gull (by the cretinoid state supervening in adult life in women)
Term “myxedeme” first used by Ord in 1978

14. Epidemiology
- Hypothyroidism occurs in 3 to 6 % for the adult population, but is symptomatic only in a minor of them.
Usually develops after the age of 30
It occurs 8 to 10 times more often in women than in men

15. Classification I. Congenital 1. Primary (thyroid gland disturbances).
II. Acquired
1. Laboratory (subclinical) hypothyroidism
2. Clinical hypothyroidism
1. Primary (thyroid gland disturbances).
2. Secondary (due to pituitary disease).
3.Tertiary (due to hypothalamic disease).
4.Peripheral.

16. Etiology of primary hypothyroidism
Congenital
Maldevelopment –hypoplasia or aplasia
Inborn deficiencies of biosynthesis or action of thyroid hormone
Atypical localization of thyroid gland
Severe iodine deficiency
Acquired
iodine deficiency
autoimmune processes (Hashimoto’s thyroiditis): MAE 1 & 2
surgical subtotal removal or total thyroidectomy
irradiation therapy (organs of the neck)
I131 therapy
during or after therapy with propylthyouracil, methimazole, iodides for hyperthyroidism
infiltrative diseases (tuberculosis, actynomycosis)
trauma
medications such as amiodarone, interferon alpha, thalidomide

17. Etiology of secondary and tertiary hypothyroidism
Congenital
- Congenital pituitary or hypothalamus disorders (anatomical or physiological)
Acquired
Tumors or metastasis
hemorrhagic necrosis (Sheehan’s syndrome)
Inflammatory disorders (infection, infiltrative process)
Trauma
surgical and radiation treatment for pituitary or hypothalamic disease
Chemical and pharmacological intoxications (reserpin, bromocriptine).

18. Etiology of peripheral hypothyroidism
peripheral tissue resistance to thyroid hormones
decreasing of T4 peripheral transformation into T3 (in liver or in kidneys)
production of antibodies to thyroid hormones

19. Skin and hair Skin is dry, thick and silk, is often cool and pale.
Nonpitting edema of the hands, feet and periorbital regions (myxedema). Pitting edema also may be present.
The faces are puffy and features are coarse.
the loss of the lateral aspect of the eyebrow, sometimes termed Queen Anne's sign

20. Skin and hair Skin may be orange due to accumulation of carotene.
Hair may become course and brittle, hair growth slows and hair loss may occur. Lateral eyebrows thin out and body hair is scanty.
Hypothyroidism does not cause obesity, but modest weight gain from fluid retention and fat deposition often occurs

21. Patients complain on fatigue, loss of energy, lethargy, forgetfulness, reduced memory.
Their level of physical activity decreases, and they may speak and move slowly. Mental activity declines and there is inattentiveness, decreased intellectual function, and sometimes may be depression.
Neurological symptoms include also hearing loss, parasthesias, objective neuropathy, particularly the carpal tunnel syndrome, ataxia.
Tendon reflex shows slowed or hung-up relaxation.
Nervous system

22. Cardiovascular system
Complains on: dyspnea, pain in the region of the heart
Objective examination:
Increased peripheral resistance
Hypertension
Bradycardia
LV hypertrophy with decreased contractility, reduced cardiac output
Pericardial effusion
Congestive heart failure
The ECG may show low voltage and/or non-specific ST segment and T wave changes.
Hypercholesterolemia
Cardiovascular system

23. Gastrointestinal system
Gastrointestinal motility is decreased loading to constipation and abdominal distension, pseudoobstruction of intestines, paralytic ileus.
Abdominal distension may be caused by ascities as well. Ascitic fluid, like other serous effusions in myxedema, has high protein content.
Achlorhydria occurs, often associated with pernicious anemia.

24. Renal system Respiratory system
Reduced excretion of a water load may be associated with hyponatriemia
Renal blood flow and glomerular filtration rate are reduced, but serum creatinine is normal
May be mild proteinuria and infections of urinary tract
Respiratory system
Dyspnea of effort is common.
This complaint may be caused by enlargement of the tongue and larynx, causing upper airway obstruction, or by respiratory muscle weakness, interstitial edema of the lungs, and for plural effusions which have high protein content
Hoarseness from vocal curt enlargement often occurs

25. Musculoskeletal system
Muscle and joint aches, pains and stiffness are common
Objective myopathy and joint swelling or effusions are less often present
The relaxation phase of the tendon reflexes is prolonged
Serum creatine phosphokinase and alanine aminotransferase activities are often increased, probably as much to slowed enzyme degradation as to increased release from muscle

26. Blood disorders Anemia, usually normocytic,
caused by decreased red blood
cell production, may occur.
It is probably from decreased need of peripheral oxygen delivery rather than hematopoetic defect
Megaloblastic anemia suggests coexistent pernicious anemia
Most patients have no evidence iron, folic acid or cyancobalamin deficiency

27. Endocrine system Thyroid gland: nonpalpable or enlargement.
Adrenal glands: hypofunction
Pituitary system: secretion of growth
hormone is deficient because thyroid hormone
is necessary for synthesis of growth
hormone. Growth and development of
children are retarded. Epiphyses remain open.
Gonadal glands: menorrhagia (from
anovulatory cycles), secondary amenorrhea,
infertility and galactorrhea; decreased potention in men

28. Metabolic system Hypothermia is common
Hyperlipidemia with increase of serum cholesterol and trigliceride occurs because of reduced lipoprotein lipase activity

29. Clinical features
Hypothyroidism can be presented in many different ways and can mimic other disorders
Because many manifestations of hypothyroidism
are non-specific,
the diagnosis is particularly likely to be overlooked
in patients with other chronic illnesses and elderly
and can lead to significant morbidity and even mortality

30. Subclinical (laboratory) hypothyroidism
It is a state in which we can’t find clinical features of hypothyroidism and euthyroidism is reached by compensatory increasing of TSH secretion and that’s why synthesis and secretion of such level of thyroid hormone that will be enough for organism.
It is an asymptomatic state in which serum T4 and free T4 are normal, but serum TSH is elevated. This designation is only applicable when thyroid function has been stable for weeks or more, the hypothalamic-pituitary-thyroid axis is normal, and there is no recent or ongoing severe illness.

32. Diagnosing and Managing Thyroid Disease in the Nursing Home. JAMDA
Diagnosing and Managing Thyroid Disease in the Nursing Home . JAMDA. Volume 9, Issue 1 , Pages 9-17, January 2008

33. Screening recommendations
Recommendations of Six Organizations Regarding Screening of Asymptomatic Adults for Thyroid Dysfunction
Organization
Screening recommendations
American Thyroid Association
Women and men >35 years of age should be screened every 5 years.
American Association of Clinical Endocrinologists
Older patients, especially women, should be screened.
American Academy of Family Physicians
Patients ≥60 years of age should be screened.
American College of Physicians
Women ≥50 years of age with an incidental finding suggestive
of symptomatic thyroid disease should be evaluated.
U.S. Preventive Services Task Force
Insufficient evidence for or against screening
Royal College of Physicians of London
Screening of the healthy adult population unjustified

34. Treatment of hypothyroidism
No specific diets are required for hypothyroidism.
Regimen is not restricted
the cause
Therapy of
replacement therapy
Pathogenetic
hormones
Thyroid
Symptomatic
of complications
Treatment

35. Replacement therapy Synthetic preparations Combined: Thyrocomb
T4 (l-thyroxine)
T3 (liothyronine sodium)
Combined:
Thyrocomb
Thyrotom
Thyroidin
Novothyral
Side effects
Allergic reactions
Angina pectoris
Cardiac arrhythmia

37. Congenital hypothyroidism
Children are born with increased weight
Subcutaneous edema
Hypotermia
Prolonged jaundice
Physical (dwarfism) and mental retardation (cretinism)

38. Peculiarities of treatment
< 3 month – 25 mcg/day
3 -12 month – 37,5 mcg/day
1 – 5 years – 75 mcg/day
5 – 7 years – 75 – 100 mcg/day
> 7 years – 100 mcg/day

39. Precipitating factors include
Myxedema coma - is a life-threatening complication of hypothyroidism
Precipitating factors include
exposure to cold
infection
Trauma
Surgery
Myocardial infarction
Bleeding
Stress situation
Drugs that suppress the CNS

40. Clinical signs of myxedema coma
Slow development (weakness, somnolence, coma)
extreme hypothermia (temperatures 24 to 32)
Areflexia
Seizures
Bradycardia, hypotension
Polyserositis
CO2 retention, and respiratory depression caused by decreased cerebral blood flow, nonreversible brain changes
Rapid diagnosis (based on clinical judgment, history, and physical examination) is imperative because early death is likely.

41. Treatment of myxedema coma
large doses of T4 ( mcg i/v bolus 3 – 4 times a day) or T3 if available (40 – 100 mcg i/v bolus 3 times a day), because TBG must be saturated before any free hormone is available for response.
The maintenance dose for T4 is 50 mkg/day i/v and for T mcg/day i/v until the hormone can be given orally.

42. Treatment of myxedema coma
Corticosteroid therapy (hydrocortisone 200 – 400 – 600 mg/day i/v).
The patient should not be rewarmed rapidly because of the threat of cardiac arrhythmia.
Hypoxemia is common, so PaO2 should be measured at the outset of treatment. If alveolar ventilation is compromised, immediate mechanical ventilatory assistance is required.

43. Thyroiditis
The various types of thyroiditis encompass a heterogeneous group of inflammatory disorders of diverse etiologies and clinical features.
With all forms of thyroiditis, destruction of the normal architecture of the thyroid follicular occurs, yet each disorder has distinctive histologic characteristics.

44. Classification Acute thyroiditis. Subacute thyroiditis:
subacute granulamatous thyroiditis;
subacute lymphocytous thyroiditis.
Chronic thyroiditis:
Hashimoto thyroiditis;
Ridel struma.
Specific thyroiditis.
Thyroiditis caused by mechanical or physical factors.

45. Acute thyroiditis is an acute bacterial inflammation
Clinical signs: fever, chills and other signs of abscess formation.
Anterior neck swelling and pain radiating to the ear or mandible.
The physical examination suggests the presence of an abscess, with erythema of the skin, marked tenderness to palpation, and at times fluctuance.
Laboratory:
Leucocytosis with a left shift,
increased ESR.
Thyroid hormone concentrations in blood are normal, although hyperthyroxinemia has been reported
Etiology: a bacterial pathogen:
St. aureus,
Str. hemolyticus,
Str. pneumonie,
anaerobic organisms,
E. coli,
coccidiodomycosis.
Infection occurs either
secondary to hematogenous or lymphatic spread,
or direct introduction of an infective agent by trauma.

46. Treatment Patient should be treated at surgical department.
Parental antibiotics should be administered according to the specific pathogen identified.
If fluctuance is present, incision and drainage might be required.
Bacterial thyroiditis must be treated early and aggressively, since abscess formation can occasionally dissect downward into the mediastinum. Recurrences of the disorder are very rare.
(Duration of the treatment must be nearly 1,5-2 month).

47. Subacute thyroiditis – an acute inflammatory disease of the thyroid probably caused by a virus with destruction of thyrocytes
subacute granulamatous thyroiditis;
subacute lymphocytous thyroiditis

48. Subacute thyroiditis Clinical signs
unilateral anterior neck pain, often associated with unilateral radiation of pain to the ear or mandible.
Pain is often proceeded by a few weeks prodrome of myalgias, low-grade fever, malaise and sore throat.
Dysphagia
Symptoms of hyperthyroidism
Physical examination: an exquisitely tender, very hard, nodular enlargement, which is most often unilateral.
Tenderness is often so extreme that palpation is limited.
Tachycardia, a widened pulse pressure, warm skin and diaphoresis are also observed when hyperthyroidism is present.
Etiology
Coxsackie virus
Adenovirus
Mumps
Echovirus
Influenza
Epstein-Barr viruses
A genetic predisposition is likely because of the association of HLA-BW 35 histocompatibility antigens.

49. Subacute thyroiditis Laboratory findings Treatment
Early in the disease we can find an increase in T4, a decrease in RAI uptake (often 0), leucocytosis and a high ESR.
After a several weeks, the T4, is decreased and the RAI uptake remains low.
Full recovery is the rule; rarely, patients may become hypothyroid.
Treatment
- An acute phase lasts from 4-8 weeks, during which treatment is symptomatic (aspirin 600 mg q 3-4 h, prednisolone mg orally tid; after 1 week prednisolone can be tapered by 5 mg every 2-3 days; thus glucocorticoids are usually not required for longer than several weeks.
Symptomatic therapy due to the phase (hyperthyroid – anrithyroid drugs, beta-blockers, hypothyroid – thyroid hormone replacement (levothyroxine mkg/day).
Following the hypothyroid phase recovery occurs, and the normal histologic features and secretory capacity of the thyroid are restored.

50. Ultrasound of the right lobe of the thyroid demonstrates an ill-defined irregular region of heterogeneous hypoechogenicity without elevation of flow on Colour Doppler examination. 

51. Chronic thyroiditis. Hashimoto thyroiditis (chronic lymphocytic thyroiditis) HT
HT is an organ - specific autoimmune
disorder, a chronic inflammation of
the thyroid with lymphocytic infiltration
of the gland generally though to be
caused by autoimmune factors.
It is more prevalent (8:1) in woman than men and is most frequent between the ages of 30 and 50 .
A family history of thyroid disorders is common, and incidence is increased in patients with chromosomal disorders, including Turners, Down and Klinefelters syndromes.
Histologic studies reveal extensive infiltration of lymphocytes in the thyroid.

52. Clinical features
HT is characterized by a wide spectrum of clinical features, ranging from no symptoms and the presence of small goiter to frank myxedema.
sensation of tightness in the area of the anterior neck
mild dysphagia.
Physical examination usually discloses a symmetrically enlarged, very firm goiter, a smooth or knobby consistency. Occasionally patients present with a single thyroid nodule.
A small group of patients have a form of HT termed primary idiopathic hypothyroidism, goiter is usually absent in this group (atrophic form of HT).
Yet a small subset of patients(probably 2-4%) present with hyperthyroidism and have so-called hashitoxicosis (hypertrophy from of HT).

53. Laboratory findings
early in the disease - high titers of antithyroid (antimicrosomal) antibodies. Late in the disease, the patient develops hypothyroidism with a decreased in T4,T3 and antibodies in this stage are usually no longer detectable;
the thyroid scan typically shows a irregular pattern of iodine uptake;
fine-needle biopsy of
the nodule or enlarging area
should be done to rule out
a coexistent neoplasm.

55. Ultrasound of thyroid gland
Ultrasound reveals - hypoechoic thyroid gland with coarse or "micronodular" echotexture of the gland - color doppler imaging reveals augmentation of the vascularity of the gland

56. Treatment
treatment of HT requires lifelong replacement with thyroid hormone to correct and prevent hypothyroidism. The average oral replacement dose with L-thyroxine is 100 to 150 mkg/day;
glucocorticoids have been reported to be effective in HT when true is a rapidly enlarging goiter associating with pressure symptoms;
symptomatic therapy

57. National iodine status in 2013

58. The resulting low level of thyroid hormones in the blood (hypothyroidism) is the principal factor responsible for damage to the developing brain and other harmful effects known collectively as “iodine deficiency disorders” . The adoption of this term emphasizes that the problem extends far beyond simply goitre and cretinism.

60. Recommended iodine intake
UNICEF, ICCIDD, and WHO recommend that the daily intake of iodine should be as follows:
• 90 μg for preschool children (0 to 59 months);
• 120 μg for schoolchildren (6 to 12 years);
• 150 μg for adolescents (above 12 years) and adults;
• 250 μg for pregnant and lactating women.

61. Diagnostic procedures

62. Diagnostic procedures

63. Diagnostic procedures

64. Blood constituents TSH
Thyroglobulin (The thyroid hyperplasia and goitre characteristic of iodine deficiency increases serum Tg levels, and in this setting serum Tg reflects iodine nutrition over a period of months or years)
thyroxin (T4) and triiodothyronine (T3), is usually not recommended for monitoring iodine nutrition (the serum T4 is typically lower and the serum T3 higher than in normal populations)

65. Treatment Iodine Replacement (In an adult, 150 mcg/day)
Universal salt iodization (USI)
Iodine supplementation
Levothyroxine
Surgery (standard of care for large goiter associated with obstructive symptoms such as dough, stridor, and dysphagia is thyroidectomy, if the goiter extends into the anterior mediastinum)

66. THYROID NODULES Benign nodular goiter Chronic lymphocytic thyroiditis
Simple or hemorrhagic cysts
Follicular adenomas
Subacute thyroiditis
Papillary carcinoma
Follicular carcinoma
Hürthle cell carcinoma
Poorly differentiated carcinoma
Medullary carcinoma
Anaplastic carcinoma
Primary thyroid lymphoma
Sarcoma, teratoma, and miscellaneous tumors
Metastatic tumors

67. Indications for US of thyroid gland:
Patients at risk for thyroid malignancy
Patients with palpable thyroid nodules or MNGs
Patients with lymphadenopathy suggestive of a malignant lesion

68. Indications for FNA
Of diameter larger than 1.0 cm that is solid and hypoechoic on US
Of any size with US findings suggestive of extracapsular growth or metastatic cervical lymph nodes
Of any size with patient history of neck irradiation in childhood or adolescence; PTC, MTC, or MEN 2 in first-degree relatives;
Of any size with patient history of previous thyroid surgery for cancer;
Of any size with patient history of increased calcitonin levels in the absence of interfering factors;
Of diameter smaller than 10 mm along with US findings associated with malignancy ;
the coexistence of 2 or more risk of thyroid cancer
Nodules that are hot on scintigraphy should be excluded from FNA biopsy

69. Suspicion of malignancy

70. Suspicion of malignancy

71. FNA Results and Recommendations
Benign
Observation
Nondiagnostic
Repeat ultrasonography-guided FNA
Papillary thyroid cancer
Surgery with preoperative ultrasonography
Suspicious for papillary thyroid cancer
Indeterminate
Hürthle cell neoplasm: Surgery

72. Bethesda System Category Risk of Malignancy Recommended Therapy
Nondiagnostic or unsatisfactory
1%-4%
Ultrasonography-guided FNA
Benign
0%-3%
Observation
Atypia or follicular lesion of undetermined significance
5%-15%
Repeat FNA
Follicular neoplasm or suspicious for follicular neoplasm
15%-30%
Thyroid lobectomy
Suspicious for malignancy
60%-75%
Near total thyroidectomy or lobectomy
Malignant
97%-99%
Near total thyroidectomy
An alternative method of reporting thyroid cytopathology is the Bethesda System. In The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), it is recommended that every report begin with 1 of 6 diagnostic categories. Clinicians can use the diagnostic category and the implied risk of malignancy to guide treatment planning.