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Guidelines

Guidelines for the Diagnosis of Graves' Disease

Guidelines for the Diagnosis of Hypothyroidism

Guidelines for the Diagnosis of Painless Thyroiditis

Guidelines for the Diagnosis of Chronic Thyroiditis

Guidelines for the Diagnosis of Subacute Thyroiditis

Guidelines for the Diagnosis of Graves' Disease
Findings
a)
Clinical findings
1.Signs of thyrotoxicosis such as tachycardia, weight loss, finger tremor, and sweating.
2.Diffuse enlargement of the thyroid gland
3.Exophthalmos and/or specific ophthalmopathy
b)
Laboratory findings
1.Elevation in serum free thyroxine (FT4) and/or free triiodothyronine (FT3) level
2.Suppression of serum thyroid stimulating hormone (TSH) : less than 0.1μU/ml.
3.Positive for anti-TSH receptor antibody(TRAb or TBII) or thyroid stimulating antibody (TSAb)
4.Elevated radioactive iodine (or 99mTcO4-) uptake to the thyroid gland.
Criteria
1)
A patient shall be said to have Graves' disease if he/she has satisfied at least one of the clinical findings and all 4 laboratory findings.
2)
A patient shall be said probably to have Graves' disease if he/she has satisfied at least one of the clinical findings and 3 laboratory findings 1 through 3.
3)
A patient is suspected of having Graves' disease if he/she has satisfied at least one of the clinical findings and laboratory findings 1 and 2. Elevation in serum FT4 has usually been present for at least 3 months.
【Notes】
1.
Decrease of serum cholesterol and increase of serum alkaline phosphatase are often observed.
2.
There are rare cases with free triiodothyronine (FT3) elevation alone and normal FT4.
3.
A patient shall be said to have "euthyroid Graves' disease" or "euthyroid ophthalmopathy", if he/she has ophthalmopathy and is positive for TRAb or TSAb, but shows normal FT4 and TSH.
4.
In an elderly patient, clinical symptoms and signs including an enlargement of the thyroid gland, may not be clear.
5.
In children, decreased scholastic ability, accelerated growth, restlessness and other symptoms are observed.
6.
FT3 / FT4 ratio is helpful to exclude painless thyroiditis.
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Guidelines for the Diagnosis of Hypothyroidism

【Primary hypothyroidism】

Findings
a)
Clinical findings
Any one of the symptoms and/or signs indicating hypothyroidism, which include loss of ambition, fatigue, periorbital puffiness, cold intolerance, weight gain, slow movements, drowsiness, memory impairment, constipation, and hoarseness.
b)
Laboratory findings
Decrease in serum free thyroxine (FT4) and increase in serum thyroid stimulating hormone (TSH)
Criteria
1)
A patient shall be said to have primary hypothyroidism if he/she has satisfied the criteria a) and b)
【Notes】
1.
When a patient has autoimmune thyroiditis (Hashimoto disease), anti-thyroid microsomal (or thyroid peroxidase (TPO)) antibody and/or anti-thyroglobulin antibody may be positive.
2.
Occasionally, blocking antibody to TSH receptor causes primary hypothyroidism.
3.
Increase of serum cholesterol and increase of serum creatine phosphokinase are often observed.
4.
Hypothyroidism shall be transient when it is postpartum onset or due to excessive iodine intake.
5.
In children, growth retardation and/or thyroid enlargement are observed.

【Central hypothyroidism】

Findings
a)
Clinical findings
Any one of the symptoms and/or signs indicating hypothyroidism, which include loss of ambition, fatigue, periorbital puffiness, cold intolerance, weight gain, slow movements, drowsiness, memory impairment, constipation, and hoarseness.
b)
Laboratory findings
Normal or low level of serum thyroid stimulating hormone (TSH) in the presence of decreased serum free thyroxine (FT4).
Criteria
1)
A patient shall be said to have central hypothyroidism if he/she has satisfied the criteria a) and b).

Exclusionary conditions
A patient may not be said to have central hypothyroidism if he/she is:
 ・in a convalescent phase from thyrotoxicosis,
 ・in extremely poor physical condition,
 ・medicated a drug which decreases TSH secretion.

【Notes】
1.
In some cases with hypothalamic central hypothyroidism, serum TSH level is rather increased as high as ~10μU/ml.
2.
In the diagnosis of central hypothyroidism, consultation to an endocrine specialist is recommended since provocative tests for pituitary hormone secretion are essential.
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Guidelines for the Diagnosis of Painless Thyroiditis
Findings
a)
Clinical findings
1.Thyrotoxicosis without pain of the thyroid gland
2.Spontaneous improvement of thyrotoxicosis (usually within 3 months)
b)
Laboratory findings
1.Elevation of serum free thyroxine (FT4)
2.Suppression of serum thyroid stimulating hormone (TSH) : less than 0.1μU/ml.
3.Negative for anti-TSH receptor antibody.
4.Decreased radioactive iodine (or 99mTcO4-) uptake to the thyroid gland
Criteria
1)
A patient shall be said to have painless thyroiditis if he/she has satisfied all 6 criteria
2)
A patient shall be said probably to have painless thyroiditis if he/she has satisfied both clinical criteria a)-1 and a)-2, and three laboratory criteria b)-1 through 3.

Exclusionary conditions
A patient may not be said to have painless thyroiditis if he/she is taking excessive thyroid hormone.

【Notes】
1.
Painless thyroiditis occurs during a course of Hashimoto thyroiditis or Graves' disease in remission.
2.
Painless thyroiditis often occurs in postpartum women in several months after parturition.
3.
Thyrotoxicosis is usually mild.
4.
A patient with painless thyroiditis may be found by transient hypothyroidism, if thyrotoxicosis in the early phase was not noticed.
5.
There are rare cases with positive anti-TSH receptor antibody.
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Guidelines for the Diagnosis of Chronic Thyroiditis
(Hashimoto’s Disease)
Findings
a)
Clinical findings
Diffuse swelling of the thyroid gland without any other cause (such as Graves' disease).
b)
Laboratory findings
1.Positive for anti-thyroid microsomal antibody or anti-thyroid peroxidase (TPO) antibody.
2.Positive for anti-thyroglobulin antibody.
3.Lymphocytic infiltration in the thyroid gland confirmed with cytological examination.
Criteria
1)
A patient shall be said to have chronic thyroiditis if he/she has satisfied clinical criterion and any one laboratory criterion.
【Notes】
1.
A patient shall be suspected to have chronic thyroiditis, if he/she has primary hypothyroidism without any other cause to induce hypothyroidism.
2.
A patient shall be suspected to have chronic thyroiditis, if he/she has anti-thyroid microsomal antibody and/or anti-thyroglobulin antibody without thyroid dysfunction nor goiter formation.
3.
If a patient with thyroid neoplasm has anti-thyroid antibody by chance, he or she should be considered to have chronic thyroiditis.
4.
A patient is possible to have chronic thyroiditis if hypoechoic and/or inhomogeneous pattern was observed in thyroid ultrasonography.
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Guidelines for the Diagnosis of Subacute Thyroiditis
(Acute Phase)
Findings
a)
Clinical findings
Swelling with pain and tenderness in the thyroid gland.
b)
Laboratory findings
1.Elevation of C-reactive protein and/or erythrocyte sedimentation rate.
2.Elevation of serum free thyroxine (FT4) and suppression of serum thyroid stimulating hormone (TSH) : less than 0.1μU/ml
3.Hypoechoic lesion at a painful portion of the thyroid gland confirmed by ultrasonography.
Criteria
1)
A patient shall be said to have subacute thyroiditis if he/she has satisfied all 4 criteria.
2)
A patient shall be said probably to have subacute thyroiditis if he/she has satisfied clinical criterion a), and 2 laboratory criteria b)-1 and b)-2.

Exclusionary conditions
A patient may not be said to have subacute thyroiditis if he/she is experiencing:
 ・acute exacerbation of chronic thyroiditis,
 ・bleeding into a thyroid cyst,
 ・acute suppurative thyroiditis,
 ・thyroid anaplastic carcinoma.

【Notes】
1.
Patients often have preceding episodes of upper respiratory inflammation and high fever.
2.
Pain and tenderness often moves gradually (creeps) to the opposite lobe of the thyroid gland.
3.
Anti-thyroid autoantibodies are usually negative, but may rarely become weak-positive transiently during the course.
4.
Polynuclear giant cells are observed in cytological or histological examinations, but neither tumor cells nor any findings characteristic of chronic thyroiditis are noted.
5.
Radioactive iodine (or 99mTcO4-) uptake to the thyroid gland is decreased in the acute phase.
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