Updated: 5/7/2019

Hashimoto Thyroiditis

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Snapshot
  • A 38-year-old woman presents to her primary care physician with complaints of increased fatigue. On further review, she also reports that she has been experiencing a 15-pound weight gain, cold intolerance, and constipation over the past few months. On physical exam, she is bradycardic, has a puffy face with periorbital edema, has thinning hair, exhibits delayed relaxation of deep tendon reflexes, and is without a goiter.
Introduction
  • Clinical definition
    • primary hypothyroidism due to the autoimmune destruction of the thyroid gland
  • Epidemiology
    • most common cause of primary hypothyroidism
    • predominantly female (10-15 x higher)
    • 30-50 years of age
  • Risk factors
    • family history
    • autoimmune disease
  • Pathogenesis
    • anti-thyroid antibodies destroy thyroid cells leading to insufficient production of thyroid hormone
      • anti-thyroid peroxidase 
      • anti-thyroglobulin
    • damaged thyroid cells can initially leak stored thyroid hormone into circulation leading to transient hyperthyroidism before the onset of hypothyroidism
  • Associated conditions
    • pernicious anemia
    • celiac disease
    • type 1 diabetes
  • Prognosis
    • excellent with treatment
    • myxedema coma has a high mortality rate
Presentation
  • Symptoms 
    • weakness and fatigue
    • cold intolerance
    • constipation and ileus
    • weight gain
    • depression, slow mentation, and inability to concentrate
    • heavy menstruation
    • galactorrhea  
      • thyrotropin-releasing hormone can stimulate prolactin secretion
    • hoarseness
    • myopathy
  • Physical exam
    • dry and cold skin
    • puffy face with periorbital edema
    • non-pitting edema (myxedema due to glycosaminoglycan in the interstitium)
    • thinning hair and nails
    • bradycardia
    • delayed relaxation of the deep tendon reflexes
    • thyroid gland can be atrophic, normal, or enlarged
  • Special presentation
    • subclinical 
      • elevated thyroid stimulating hormone (TSH) but normal thyroid hormones
      • does not require treatment unless auto-antibody positive or symptomatic
Studies
  • Diagnostic testing
    • diagnostic approach
      • screen and confirm with lab tests
    • studies
      • TSH and free T4
        • primary screening
        • TSH is the most sensitive measure
        • lab results may be confounded by high doses of biotin supplementation
      • autoantibody
        • diagnose Hashimoto versus other etiologies of hypothyroidism
        • anti-thyroid peroxidase (90% of cases)
        • anti-thyroglobulin (50% of cases)
        • 10-15% are antibody negative
    • imaging
      • not routinely indicated
    • biopsy
      • fine needle aspiration for any dominant nodule or fast-growing goiter
      • histopathology is the gold standard for diagnosis but invasive
        • diffuse lymphocytic and plasma cell infiltration is characteristic of Hashimoto thyroiditis 
  • Diagnostic criteria
    • ↑ TSH and ↓ free T4
      • in early disease, TSH and free T4 may be normal
    • positive antithyroid autoantibodies
Differential
  • Euthyroid sick syndrome
    • distinguishing factors
      • ↓ thyroid hormone but also ↓TSH
      • secondary to nonthyroidal systemic illness
  • Thyroid lymphoma
    • distinguishing factors
      • rapidly enlarging goiter
      • lymphoma on histopathology
  • Panhypopituitarism
    • distinguishing factor
      • loss of pituitary hormones in addition to ↓ T4 including ↓ cortisol, ↓ sex steroids, ↓ growth hormone, and ↓ antidiuretic hormone
  • Major depressive disorder
    • distinguishing factor
      • lack of cold intolerance, integumentary changes, myxedema, and goiter
Treatment
  • Management approach 
    • thyroid hormone replacement to achieve a euthyroid state within 2-4 weeks
    • monitor clinically and with TSH
    • monitor for other associated complications 
      • mild anemia
      • ↑ total cholesterol, low-density lipoprotein, and triglycerides
      • ↓ high-density lipoprotein
      • hyponatremia
  • First-line
    • lifelong levothyroxine replacement
      • requires adjustment during pregnancy 
      • adverse effects include overreplacement leading to osteoporosis and arrhythmias
  • Second line
    • surgery
      • indicated for obstructive symptoms (dysphagia, stridor, and hoarseness), malignancy, and cosmesis 
Complications
  • Thyroid lymphoma or other thyroid malignancy 
  • Iatrogenic overreplacement
  • Myxedema coma
 

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Questions (9)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.EC.4753) A 26-year-old Caucasian female presents to her primary care physician in January with several months of worsening fatigue and weight gain. She reports a gradual onset of daytime fatigue as well as difficulty sleeping, and she has been drinking several cups of coffee a day to stay awake at work. She notes that her new job involves long hours such that she often does not see daylight. She also feels that despite her appetite being unchanged, she has gained 12 pounds, mostly in her abdomen and hips. On review of systems, she also reports new onset constipation and noticed one episode of painless bright red blood per rectum on wiping. In addition, she has missed her menses in the last three months, which is unusual for her. She is sexually active and uses inconsistent contraception. She has a family history of type I diabetes in her sister and vitiligo in her mother. At this visit, the patient’s temperature is 98.5°F (36.9°C), blood pressure is 124/77 mmHg, pulse is 70/min, and respirations are 14/min. On exam, the patient appears tired but comfortable and conversant. The patient's eyebrows appear as those in Figure A, and the skin on her hands and face is noted to be dry. She has a capillary refill of 2 seconds, and there is no palpable thyroid nodularity or enlargement. The remainder of her exam is unremarkable. Which of the following laboratory abnormalities is most likely present in this patient? Review Topic

QID: 108822
FIGURES:
1

Low serum iron

0%

(0/18)

2

Elevated thyroid stimulating hormone (TSH)

67%

(12/18)

3

Low vitamin D

6%

(1/18)

4

Elevated human chorionic gonadotropin (hCG)

17%

(3/18)

5

No specific lab abnormalities

6%

(1/18)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 2

(M2.EC.4868) A 57-year-old woman presents to her primary care physician for weakness. The patient states that she barely feels able to lift a bag of groceries from her car into her house anymore. The patient has a past medical history of a suicide attempt, constipation, anxiety, asthma, and atopic dermatitis. Her current medications include fluoxetine, lisinopril, albuterol, diphenhydramine, sodium docusate, and a multivitamin. She was recently started on atorvastatin for dyslipidemia. Her temperature is 97°F (36.1°C), blood pressure is 90/65 mmHg, pulse is 70/min, respirations are 11/min, and oxygen saturation is 98% on room air. On physical exam, you note a fatigued appearing woman with thinning hair. Cardiopulmonary exam is within normal limits. She demonstrates 3/5 strength in her upper and lower extremities with 1+ sluggish reflexes. Sensation is symmetrical and present in the upper and lower extremities. Pain/tenderness upon palpation of the patient's extremities is noted. Laboratory values are ordered as seen below:

Hemoglobin: 12 g/dL
Hematocrit: 36%
Leukocyte count: 5,500/mm^3 with normal differential
Platelet count: 190,000/mm^3

Serum:
Na+: 139 mEq/L
Cl-: 101 mEq/L
K+: 4.4 mEq/L
HCO3-: 24 mEq/L
BUN: 20 mg/dL
Glucose: 90 mg/dL
Creatinine: 1.1 mg/dL
Ca2+: 10.1 mg/dL
AST: 12 U/L
ALT: 10 U/L

Which of the following is the best next step in management? Review Topic

QID: 109578
1

Discontinue atorvastatin

21%

(8/39)

2

Coenzyme Q10

3%

(1/39)

3

TSH level

74%

(29/39)

4

Aldolase level

3%

(1/39)

5

Muscle biopsy

0%

(0/39)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M2.EC.4755) A 57-year-old female presents to her primary care physician with a chief complaint of feeling tired all the time. She states her symptoms began several months ago, around the time that her husband committed suicide. Since then she has had thoughts of joining her husband. She complains of feeling excessively weak and states that she no longer has enough energy to go to the gym which she attributes to her 15 pound weight gain over the last month. The patient's medical history includes joint pain, a skin rash that recently resolved, obstructive sleep apnea, and metabolic syndrome. The patient takes ibuprofen and omeprazole as needed but otherwise cannot remember any other medications that she takes. On physical exam you note an overweight woman who has an overall depressed affect. The patient's cardiac exam reveals a normal rate and rhythm. The pulmonary exam reveals bilateral clear lung fields with good air movement. The patient's skin is very dry and tight appearing and her hair is coarse. Overall the patient appears somewhat unkempt.

Laboratory work is performed and reveals the following:

Hemoglobin: 13.0 g/dL
Hematocrit: 37%
Leukocyte count: 4,500 cells/mm^3 with normal differential
Platelets: 250,000/mm^3

Serum:
Na+: 140 mEq/L
K+: 4.4 mEq/L
Cl-: 102 mEq/L
BUN: 15 mg/dL
Glucose: 122 mg/dL
Creatinine: 1.0 mg/dL
Thyroid-stimulating hormone: 5.3 µU/mL
Ca2+: 10.2 mg/dL
AST: 11 U/L
ALT: 13 U/L

Which of the following laboratory findings is most likely to be abnormal in this patient? Review Topic

QID: 108705
1

Anti-DNA topoisomerase antibodies

6%

(1/16)

2

Anti-nuclear antibodies

0%

(0/16)

3

Anti-histidyl-tRNA synthetase antibodies

0%

(0/16)

4

Anti-thyroid peroxidase antibodies

94%

(15/16)

5

5-hydroxyindoleacetic acid in CSF

0%

(0/16)

M2

Select Answer to see Preferred Response

PREFERRED RESPONSE 4
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