Diagnosis

Hypothyroidism

Etiology

Cause [1mf][ucp][rft]

1. Primary: Most common

   • Iodine deficiency: most common cause world wide

   • Chronic autoimmune thyroiditis: Hashimoto thyroiditis

   • Iatrogenic:

     • Surgery (for hyperthyroidism, goitre or thyroid cancer)

     • Neck irradiation (neck neoplasms, breast cancer, or Hodgkin disease)

   • Genetic (including variations causing congenital hypothyroidism)

   • Drug-induced: Radioactive iodine, Iodinated contrast, Amiodarone, Interferon alfa, Thalidomide, Lithium, Valproate, Stavudine, Tyrosine kinase inhibitors, Bexarotene, Perchlorate, Interleukin (IL)-2, Ethionamide, Rifampin, Phenytoin, Carbamazepine, Phenobarbital, Aminoglutethimide, Sulfisoxazole, p -Aminosalicylic acid, Monoclonal antibodies, Immune inhibitors (Ipilimumab, pembrolizumab, nivolumab)

   • Transient thyroiditis: post-partum (92 per 100,000 pregnancies), viral infection (De Quervain syndrome)

   • Thyroid infiltration: infectious, malignant (primary thyroid or metastatic) and other autoimmune conditions, such as sarcoidosis

2. Secondary (central): rare

   • Hypothalamic failure and/or dysfunction

   • Sheehan syndrome

   • Pituitary adenoma and/or apoplexy

   • Tumors impinging on the hypothalamus

   • Lymphocytic hypophysitis

   • Brain or pituitary irradiation

   • Congenital nongoitrous hypothyroidism type 4

   • TRH resistance/deficiency

   • Resistance to TSH or thyrotropin releasing hormone

   • Drug-induced (dopamine, somatostatins, prednisone, opioids)

3. Extra-thyroidal:

   • Consumptive hypothyroidism

   • Tissue-specific secondary to genetic mutations (THRα, THRβ and MCT8)

Pathophysiology [rft]

1. The hypothalamus --> thyrotropin-releasing hormone (TRH)

2. The pituitary gland --> thyroid-stimulating hormone (TSH)

3. Thyroid gland produce:

   • T4 100 to 125 nmol daily --> converted to T3 peripherally

   • Smaller quantities of triiodothyronine (T3)

4. Negative feedback on TRH and TSH is exerted primarily by T3 and T4

5. Primary hypothyroidism: high TSH and low thyroxine levels

6. Secondary hypothyroidism: low TSH and low thyroxine levels

Complications [rft]

• Myxedema crisis: encephalopathy, hypothermia, seizures, hyponatremia, hypoglycemia, arrhythmias, cardiogenic shock, respiratory failure, and fluid retention

Epidemiology

Incidence per 100.000 [kdk][noe][u8b][igq]

Approach

• Blood test: TSH, FT4, FT3, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin antibodies (anti-Tg), TSAb

• Ultrasonography of the neck and thyroid

• Fine-Needle Aspiration Biopsy

• FDG-PET [ucp]

• ECG

Treatment

1. Levothyroxine 1.6 µg/kg/day titrated to optimal TSH levels (0.4–4.0 mIU/L) [ucp]

   • Pregnant women will require doses about 25% higher

   • Reduced (1/4th or half) dose in:

     • Elderly patients

     • Atrial fibrillation

     • Ischemic heart disease

   • If higher dose than expected --> consider gastritis or celiac disease

   • Malabsorption: [rft]

     • IV thyroid hormone 50% to 75% of the oral dose

     • Liquid and gel capsule formulations

2. Hypothyroidism in pregnancy:

   • Preeclampsia

   • Anemia

   • Postpartum hemorrhage

   • Cardiac ventricular dysfunction

   • Increased risk of spontaneous abortion

   • Low birth weight

   • Impaired cognitive development in offspring

   • ADHD, autism, fetal mortality

3. Myxedema coma:

   • LT4 4 µg/kg body weight (~200-250 µg) as an IV bolus

   • 24 hours later, give 100 µg IV

   • Subsequently, give 50 µg/day IV, along with stress doses of IV glucocorticoids

Differential diagnoses

Acute thyroiditis, Adrenal insufficiency, Anemia, Anxiety, Cardiac tamponade, Constipation, Depression, Dysmenorrhea, Eosinophilia, Eosinophilia-myalgia syndrome, Fibromyalgia, Gastrointestinal obstruction, Hashimotos thyroiditis, Hypopituitarism, Hypothermia, Lymphoma, Menopause, Mononucleosis, Obesity, Obstructive sleep apnea, Pituitary adenoma, Postpartum thyroiditis, Riedels fibrosing thyroiditis, Subacute thyroiditis, Syndrome of inappropriate antidiuretic hormone secretion, Thyroid lymphoma, Toxic nodular goiter