Hypothyroidism. Iodine deficiency disorders.

Department of Internal Medicine N2

as.-prof. Svystun I. I.

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

Trachea

Thyroid GlandPyramidal Lobe

Right LobeIsthmus

Left Lobe

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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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

TSH stimulation

Thyroid

T4

T3Liver

ThyroidBindingproteins

Free hormone Bound hormone

Thyroid hormone synthesis

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Major deiodinative and non-deiodinative pathways of thyroid hormones metabolism.

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Physiologic effects of thyroid hormones

1. Increasing of protein metabolism in virtually every body tissue

2. 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).)

3. Stimulation of erythropoesis

4. Positive chrono- inotropic effects on myocardium

5. Achievement of formation of nervous system and skeleton in perinatal period

Goitre• is an enlargement of the thyroid gland.

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

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.

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

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

Classification

I. CongenitalII. 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.

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

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).

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

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

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

Nervous system

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.

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

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.

Renal 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

-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

Respiratory system

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

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

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

Metabolic system

- Hypothermia is common

- Hyperlipidemia with increase of serum cholesterol and trigliceride occurs because of reduced lipoprotein lipase activity

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

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.

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

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

Treatment of hypothyroidism

Replacement therapy

• Synthetic preparations – T4 (l-thyroxine)– T3 (liothyronine sodium)

• Combined:- Thyrocomb- Thyrotom- Thyroidin- Novothyral

Side effects- Allergic reactions- Angina pectoris- Cardiac arrhythmia

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

(cretinism)

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

Precipitating factors include• exposure to cold• infection• Trauma• Surgery• Myocardial infarction• Bleeding • Stress situation• Drugs that suppress the CNS

Myxedema coma - is a life-threatening complication of hypothyroidism

- 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.

Clinical signs of myxedema coma

Treatment of myxedema coma- large doses of T4 (200-500

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 T3 10 -20 mcg/day i/v until the hormone can be given orally.

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.

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.

1. Acute thyroiditis.2. Subacute thyroiditis:• subacute granulamatous thyroiditis;• subacute lymphocytous thyroiditis.3. Chronic thyroiditis:• Hashimoto thyroiditis;• Ridel struma.4. Specific thyroiditis. 5. Thyroiditis caused by mechanical or

physical factors.

Classification

Acute thyroiditis is an acute bacterial inflammation

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.

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

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).

Subacute thyroiditis –an acute inflammatory disease of the

thyroid probably caused by a virus with destruction of thyrocytes

• subacute granulamatous thyroiditis;

• subacute lymphocytous thyroiditis

Subacute thyroiditisEtiology- Coxsackie virus- Adenovirus- Mumps- Echovirus- Influenza- Epstein-Barr virusesA genetic

predisposition is likely because of the association of HLA-BW 35 histocompatibility antigens.

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.

Subacute thyroiditis• Laboratory findings- 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 10-20 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 100-150 mkg/day).

• Following the hypothyroid phase recovery occurs, and the normal histologic features and secretory capacity of the thyroid are restored.

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. 

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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.

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).

Laboratory findings

1. 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;

2. the thyroid scan typically shows a irregular pattern of iodine uptake;

3. fine-needle biopsy of the nodule or enlarging areashould be done to rule out a coexistent neoplasm.

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

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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

National iodine status in 2013

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• 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.

Recommended iodine intakeUNICEF, 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.

Diagnostic procedures

Diagnostic procedures

Diagnostic procedures

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)

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)

THYROID NODULESBenign 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

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

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

Suspicion of malignancy

Suspicion of malignancy

FNA Results and Recommendations

FNA Result Recommendation

Benign Observation

Nondiagnostic Repeat ultrasonography-guided FNA

Papillary thyroid cancer Surgery with preoperative ultrasonography

Suspicious for papillary thyroid cancer

Surgery with preoperative ultrasonography

Indeterminate Hürthle cell neoplasm: Surgery

Bethesda SystemCategory 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.