Thyroid Disorders

Hasan AYDIN, MD

Yeditepe University Medical Faculty

Department of Endocrinology and Metabolism

Thyroid Regulation

PLASMA T4 + FT4

HYPOTHALAMUS - TRH

ANT. PITUITARY - TSH

THYROID T4 and T3

PLASMA T3 + FT3

TISSUES FT4 to FT3

TSH -R

Thyroid Hormones

THEY ARE NOT ESSENTIAL FOR LIFE, BUT ARE EXTREMELY HELPFUL

THYROID GLAND DISORDERS

THYROID HORMONE EFFECTS:

Affects every single cell in the body

Modulates:

Oxygen consumption

Growth rate

Maturation and cell differentiation

Turnover of Vitamins, Hormones, Proteins, Fat, CHO

Thyroid Gland Disorders

Overproduction of thyroid hormones

Underproduction of thyroid hormones

Thyroid nodules

Thyroiditis

Thyroid neoplasms

Hyperthyroidism

Thyroid Gland Disorders

TSH High usually means Hypothyroidism

Rare causes: TSH-secreting pituitary tumor Thyroid hormone resistance Assay artifact

TSH low usually indicates Thyrotoxicosis

Other causes First trimester of pregnancy After treatment of hyperthyroidism Some medications (Steroids-dopamine)

Thyroid Gland Disorders

THYROTOXICOSIS: is defined as the state of thyroid hormone excesss

HYPERTHYROIDISM:

is the result of excessive thyroid gland function

Abnormalities of Thyroid Hormones

Thyrotoxicosis PrimarySecondaryWithout HyperthyroidismExogenous or factitious

HypothyroidismPrimarySecondaryPeripheral

Causes of Thyrotoxicosis

Primary HyperthyroidismGrave´s diseaseToxic Multinodular GoiterToxic adenomaFunctioning thyroid carcinoma metastasesActivating mutation of TSH receptorStruma ovaryDrugs: Iodine excess

Causes of Thyrotoxicosis

Thyrotoxicosis without hyperthyroidism Subacute thyroiditis Silent thyroiditis Other causes of thyroid destruction:

Amiodarone, radiation, infarction of an adenoma Exogenous/Factitia

Secondary Hyperthyroidism TSH-secreting pituitary adenoma Thyroid hormone resistance syndrome Chorionic Gonadotropin-secreting tumor Gestational thyrotoxicosis

Thyrotoxicosis

Symptoms: Hyperactivity Irritability Dysphoria Heat intolerance &

sweating Palpitations Fatigue & weakness Weight loss with increased

appetite Diarrhea Polyuria Sexual dysfunction

Signs: Tachycardia Atrial fibrillation Tremor Goiter Warm, moist skin Muscle weakness,

myopathy Lid retraction or lag Gynecomastia Exophtalmus Pretibial myxedema

Manifestations of Thyrotoxicosis

Differential Diagnosis

Panic attacks

Psychosis

Mania

Pheochromocytoma

Hypoglycemia

Occult malignancy

Treatment

Reducing thyroid hormone synthesis: Antithyroid drugs (Methimazole, Propylthyouracil) Radioiodine (131I) Subtotal thyroidectomy

Reducing Thyroid hormone effects: Propranolol Glucocorticoids Benzodiazepines

Reducing peripheral conversion of T4 to T3 Propylthyouracil Glucocorticoids Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

Treatment: Special Considerations

Thyrotoxic crisis or Thyroid storm: It´s a life-threatening exacerbation of thyrotoxicosis,

acompanied by fever, delirium, seizures, coma, vomiting, diarrhea, jaundice.

Mortality rate reachs 30% even with treatment It´s usually precipitated by acute illness, such as:

Stroke, infection,trauma, diabetic ketoacidosis, surgery, radioiodine treatment

Propylthyouracil IV or Nasogastric tube Radioiodine (131I) Propranolol Glucocorticoids Benzodiazepines Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)

HYPOTHYROIDISM

Definition

A deficiency of thyroid hormones, which in turn results in a

generalized slowing down of metabolic processes.

In infants and children => marked slowing of growth and

development, with serious permanent consequences including

mental retardation.

In adulthood => a generalized slowing down of the organism,

with the clinical picture of myxedema.

Causes of Hypothyroidism

Primary

Congenital

Acquired

Transient

Secondary

Pituitary

Hypothalamic

Hypothyroidism

Symptoms: Tiredness Weakness Dry skin Sexual dysfunction Hair loss Difficulty concentrating

Signs: Bradycardia Dry coarse skin Puffy face, hands and

feet Diffuse alopecia Peripheral edema Delayed tendon reflex

relaxation Carpal tunel syndrome Serous cavity effusions.

Hypothyroidism

Special Considerations

Myxedema coma Reduced level of consciousness, seizures Hypotension/shock Hypothermia Hyponatremia

Usually in elderly hypothyroid pts.

Usually precipitated by intercurrent illnesses that impairs ventilation

It´s an Emergency with a high mortality rate

Treatment: Lyotironine(T3) or T4, Hydrocortisone, external warming, IV fluids

Many Causes, One Treatment

Goal : Normalize TSH level regardless of cause of hypothyroidism

Treatment : Once daily dosing with Levothyroxine sodium (1.6

µg/kg/day)

Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage

change

Treatment: Special Considerations

Elderly patients

Coronary Artery Disease

Poor adrenal gland reserve

Childrens

Pregnancy

Emergency surgery (Non thyroid related)

Goiter and Thyroid Cancer

Goiter is a diffuse or nodular enlargement of the thyroid gland resulting from excessive replication of benign thyroid epithelial cells.

Definitions

A thyroid nodule is a discrete lesion within the thyroid gland that is palpably and/or ultrasonog- raphically distinct from the surrounding thyroid parenchyma

Etiology of Nontoxic Goiter

Iodine deficiency

Goitrogen in the diet

Hashimoto's thyroiditis

Subacute thyroiditis

Inherited defect in thyroidal enzymes necessary for

T 4 and T 3 biosynthesis

Generalized resistance to thyroid hormone (rare)

Neoplasm, benign or malignant

Multinodular Goiter Clinical Issues

Hyperthyroidism

Suspicion of malignancy

Compressive/obstructive symptoms

Cosmetic concerns

MULTINODULAR GOITERPresentation

Asymptomatic

Neck mass discovered by patient or physician

Abnormal CXR

Symptomatic

Pressure symptoms

Hoarseness

Thyrotoxicosis

NODULAR GOITERSuspicious Nodule or Goiter

High suspicion Family history of medullary thyroid carcinoma Rapid tumor growth A nodule that is very firm or hard Fixation of the nodule to the adjacent structures Paralysis of the vocal cord Regional lymphadenopathy Distant metastasis

Moderate suspicion Age of either<20 or >70 years Male sex History of head and neck irradiation A nodule >4 cm in diameter or partially cystic Symptoms of compression, including dysphagia, dysphonia,

hoarseness, dyspnea, and cough

Ultrasonographic Cancer Risk Factors for a Thyroid Nodule hypoechogenicity, microcalcifications, irregular margins, increased nodular flow visualized by Doppler, the evidence of invasion or regional lymphadenopathy

Ultrasound

Multinodular Goiter : Evaluation

TSH

FT4, T3

Radionuclide Scan / RAIU

US

CT Scan (without contrast)

FNA biopsy

Multinodular Goiter Fine Needle Aspiration Evaluation

Biopsy all accessible nodule(s)

Biopsy suspicious nodule(s) cold on scan;

firm by palpation; growing in size

Results less reliable in large goiters

Most common diagnosis is “colloid nodule”

Fine Needle Aspiration Evaluation

FNA results Malignant- pt needs to have surgical management

Benign- observation with interval ultrasounds and clinical examinations

Indeterminate- radioisotope scan- perform suppression scan and if cold proceed to surgical management- if hot nodule consider observation

Non diagnostic- repeat FNA or U/S guided FNA

Thyroid Cancers

Thyroid adenoma is a benign neoplastic growth contained within a capsule.

Benign Neoplasms of the Thyroid

Embrional adenoma

Fetal adenoma

Microfollicular adenoma

Macrofollicular adenoma

Papillary cystadenoma

Hurtle cell adenoma

Thyroid Cancer

Papillary (mixed papillary and follicular)75%

Follicular carcinoma 16%

Medullary carcinoma 5%

Undifferentiated carcinomas 3%

Miscellaneous (lymphoma, fibrosarcoma, 1% squamous cell carcinoma, malignant hemangioendothelioma, teratomas, and metastatic carcinomas)

Papillary Carcinoma

very slowly grow and remain confined to the thyroid gland and local lymph nodes for many years.

In older patients, more aggressive and invade locally into muscles and trachea.

in later stages, they can spread to the lung.

Death is usually due to local disease, with invasion of deep tissues in the neck less commonly, death may be due to extensive pulmonary metastases..

Follicular Carcinoma

is characterized by the presence of small follicles, colloid formation is poor.

capsular or vascular invasion.

more aggressive and local invasion of lymph nodes or by blood vessel invasion with distant metastases to bone or lung.

often retain the ability to concentrate radioactive iodine, to form thyroglobulin, and, rarely, to synthesize T3 and T4.

Follicular Carcinoma

rare ''functioning thyroid cancer'' is almost always a

follicular carcinoma.

more likely to respond to radioactive iodine therapy.

In untreated patients, death is due to local extension or

to distant bloodstream metastasis with extensive

involvement of bone, lungs, and viscera.

Medullary Carcinoma

a disease of the C cells (parafollicular cells) derived

calcitonin, histamin, prostaglandins, serotonin, other peptides

more aggressive , but not undifferentiated thyroid cancer.

locally into lymph nodes and into surrounding muscle and trachea.

lymphatics and blood vessels and metastasize to lungs and viscera.

Calcitonin and CEA clinically useful markers for diagnosis and follow-up.

Medullary Carcinoma

About 80% are sporadic

the remainder are familial. four familial patterns:

without associated endocrine disease (FMTC);

MEN 2a medullary carcinoma, pheochromocytoma, and

hyperparathyroidism;

MEN 2B, medullary carcinoma, pheochromocytoma,

and multiple mucosal neuromas;

MEN 3 : with cutaneous lichen amyloidosis, a pruritic

skin lesion located on the upper back.

Undifferentiated (Anaplastic) Carcinoma

small cell, giant cell, and spindle cell carcinomas.

usually occur in older patients with a long history of goiter in whom the gland suddenly -over weeks or months- begins to enlarge and produce pressure symptoms, dysphagia, or vocal cord paralysis.

Death from massive local extension usually occurs within 6-36 months These tumors are very resistant to therapy .

Lymphoma

only type of rapidly growing thyroid cancer that is responsive to therapy

as part of a generalized lymphoma or may be primary in the thyroid gland.

occasionally with long-standing Hashimoto's thyroiditis

characterized by lymphocyte invasion of thyroid follicles and blood vessel walls, which helps to differentiate thyroid lymphoma from chronic thyroiditis.

If there is no systemic involvement, the tumor may respond dramatically to radiation therapy

Cancer metastatic to the thyroid

Cancers of the breast and kidney, bronchogenic carcinoma, and malignant melanoma.

The primary site of involvement is usually obvious,

Occasionally , the diagnosis is made by needle biopsy or open biopsy of a rapidly enlarging cold thyroid nodule.

The prognosis is that of the primary tumor,

Management of Thyroid Cancer

Papillary and Follicular Carcinoma: Low-risk group under age 45 with primary lesions under 1 cm

and no evidence of intra- or extraglandular spread.

For these patients, lobectomy is adequate therapy

All other patients high-risk, and for these total thyroidectomy and-if there is evidence of lymphatic spread -a modified neck dissection are indicated.

Prophylactic neck dissection is not necessary.

For the high-risk group, postoperative radioiodine ablation

Management of Thyroid Cancer

Follow-up at intervals of 6-12 months should include careful examination of the neck for recurrent masses.

If a lump is noted, needle biopsy is indicated to confirm or rule out cancer.

Serum TSH should be checked

Serum Tg should be < 1 ng/ml .

Thyroiditis

Definition

Infectious or autoimmune inflammatory

diseases of thyroid gland

• Hashimoto thyroiditis

• Subacute granulomatous thyroiditis

• Infectious thyroiditis

• Radiation & Trauma induced thyroiditis

• Subacute Lymphocytic thyroiditis

• Postpartum thyroiditis

• Drug induced thyroiditis

• Riedel’s thyroiditis

Classification

HASHIMOTO’s THYROIDITISChronic Lymphocytic Thyroiditis

•Is the most prevalent form of thyroid autoimmune disease

(3-4 % of popul.) and most common cause of hypothyroidism

•Is characterized by gradual thyroid failure, goitre or both

•Is more common in middle age

•Clusters in families

•May be associated with other autoimmune

disorders

Dr. Hakaru Hashimoto

Subacute Granulomatous (de Quervain’s) Thyroiditis

•Most frequent cause of thyroid pain and tenderness

•Postviral inflammatory process(Coxsackievirus, mumps, measles, adenovirus, other)

•Strongly associated with HLA-B35, most common in

40-50 years old women

•Transient thyroiditis (thyrotoxic for 2-6 wks)

Clinical Presentation

•Hoarseness,dysphagia

•Fever, palpitation, nervousness,

lassitude

•Tender, enlarged, firm and often

nodular

•Previous viral infection (in 1-3 weeks)

•Pain over thyroid,upper neck, jaw, throat,ears

Treatment of DeQuervain’s Thyroiditis

A nonsteroidal antiinflammatory drug Aspirin: 2.4-3.6 g in divided doses

Naproxen: 1.0-1.5 g in divided doses

Prednisone : 30-40 mg qd

A beta blocker Propranolol : 40-120 mg

Atenolol : 25-50 mg

Infectious Thyroiditis

Acute (with abscess formation) Gram-positive or negative organisms (via blood

or a fistula from the piriform sinus adjacent to the larynx)

Chronic Mycobacterial Fungal Pneumocystis

Infectious Thyroiditis

Acute Usually unilateral neck pain and tenderness Fever, chills, a unilateral neck mass (fluctuant) USG, FNAB, drainage and antibiotics

Chronic Bilateral, less prominent neck pain Some patients have hypothyroidism FNAB

Radiation and Trauma-Induced Thyroiditis

Radiation Thyroiditis

Radioiodine treatment of Graves disease

Develops 5-10 days later and is mild

Trauma-induced Thyroiditis

Palpation, thyroid biopsy, surgery, car seat belt

Subacute Lymphocytic Thyroiditis(Painless, Silent, Lymphocytic)

A variant form of Hashimoto’s thyroiditis Associated with HLA-DR3 Postulated initiating factors :

Excess iodine intake Various cytokines

Treatment of Subacute Lymphocytic Thyroiditis

Most patients need no treatment

Symptomatic treatment during the hyperthyroid

phase : propranolol or atenolol

T4 ( 50-100 µg daily) given for 8-12 wks,

discontinued and reevaluated 4-6 wks later

Postpartum Thyroiditis

•Occurs in 3-16% of pregnancies (25 % in T1DM)

•Is seen within 1 year after parturition

•Is likely to recur after subsequent pregnancies

•Thyrotoxicosis is mild and transient

•Antithyroid antibodies are elevated

•RAIU is low

•Slightly increased ESR

Presentation of Postpartum Thyroiditis

Transient hyperthyroidism (2-8 wks) followed by hypothyroidism (2-8 wks) and then recovery 20-30 %

Transient hyperthyroidism alone 20-40 %

Transient hypothyroidism alone 40-50 %

Drug-Induced Thyroiditis

Interferon-alpha thyroiditis

Interleukin-2 thyroiditis

Amiodarone

Riedel’s Thyroditis

Is a fibrotic process associated with a mononuclear cell inflammation that extends beyond the thyroid into soft tissue

Can involve the parathyroids, the recurrent laryngeal nerve, trachea, mediastinum, ant. chest wall

Fibrosclerosis may involve the retroperitoneal space, mediastinum, retroorbital space, the biliary tract

Treatment of Riedel’s Thyroiditis

Thyroxine

Surgery

Glucocorticoids

Tamoxifen

Methylprednisone pulse therapy + azathioprine or

penicillamine