Thyroid d/o

Thyroid gland produces two related hormones, thyroxine (T4) and triiodothyronine (T3).

• • Graves dz: anti-TG abs and anti-TPO abs both are +ve. TSH low

  • Hashimotos: TSH high, anti-TG ab titers >1:400

  • TSH levels usually remain in ref range or are low in 2° hypothyroidism due to pituitary or hypothalamic causes.

  • Hyperthyroidism: low TSH, high T4, T3; or T4 normal, T3 high (T3 thyrotoxicosis)

  • ** Normal TSH level precludes 1° hypothyroidism and hyperthyroidism.

  • TSH mildly elev upto 20 mcU/mL in some euthyroid Pts with other illness and in mild subclinical hypothyroidism

  • TSH may be suppressed to <0.1 mcU/mL in severe non-thyroidal illness or in subclinical hyperthyroidism.

  • Effects of drugs on thyroid function tests:

  • Decrease TSH: high-dose glucocorticoids, dopamine,

  • TSH elev (hypothy): lithium, amiodarone, radioiodine contrast

  • Increase T4: amiodarone, radioiodine, heparin, LMWH, tamoxifen.

  • T4 decreased: furosemide, androgens, ASA

Patterns of thyroid function tests during assessment of thyroid function

Serum TSH/Serum Free T4/Serum T3  Assessment  

Normal hypothalamic-pituitary function  

• • Normal/Normal/ Normal/ = Euthyroid 

  • Normal/Normal or high/Normal or high/ = Euthyroid hyperthyroxinemia 

  • Normal/Normal or low/Normal or low/ = Euthyroid hypothyroxinemia 

  • Normal/Low/Normal or high/ = Euthyroid: triiodothyronine therapy 

  • Normal/Low normal or low/Normal or high/ = Euthyroid: thyroid extract therapy 

  • High/Low/Normal or low = Primary hypothyroidism 

  • High/Normal/Normal/ = Subclinical hypothyroidism 

  • Low/High or normal/High = Hyperthyroidism 

  • Low/Normal/Normal/ = Subclinical hyperthyroidism 

Abnormal hypothalamic-pituitary function  

• • Normal or high/High/High/ = TSH-mediated hyperthyroidism 

  • Normal or low/Low or low-normal/Low or normal/ = Central hypothyroidism 

Central hypothyroidism is caused by a deficiency in thyrotropin production, which leads to decline in free T4 production. The thyrotropin level is frequently in the normal range in the setting of central hypothyroidism, and therefore this deficiency can be missed if free T4 levels are not concurrently measured

Subclinical hypothyroidism is biochemically defined as an elevated serum thyrotropin level in combination with a serum free T4 level that is within the population reference range. Although many patients with subclinical hypothyroidism are asymptomatic, such patients tend to report symptoms of overt hypothyroidism more often than age-matched controls; these symptoms are usually milder than those in patients with overt hypothyroidism and tend to increase in both number and severity with higher thyrotropin levels.  

The risk of progression of subclinical hypothyroidism to overt hypothyroidism is approximately 2 to 6% per year; the risk is higher among women than among men and among persons with higher thyrotropin levels, those with higher levels of antibodies to thyroid peroxidase, and those with low-normal free T4 levels. Among persons who have a single elevated thyrotropin measurement of less than 7 mIU per liter, the thyrotropin level normalizes in up to 46% within 2 years.

Concern exists regarding the long-term adverse effects of subclinical hypothyroidism, particularly with respect to the risk of cardiovascular disease. Subclinical hypothyroidism, particularly among persons with thyrotropin levels of more than 7 mIU per liter, has been associated with increased risks of congestive heart failure and fatal stroke in meta-analyses based on individual participant data. It is unclear whether ameliorating cardiovascular risk factors with the use of levothyroxine treatment will decrease the risk of cardiovascular events.

Because multiple factors, such as subacute thyroiditis, recovery from a nonthyroidal illness, and medication (e.g., amiodarone and lithium), can cause transient abnormalities in the serum thyrotropin level, a transient increase in the thyrotropin level should be ruled out before a diagnosis of subclinical hypothyroidism is made. At least one repeat measurement of thyrotropin and free T4 is indicated, together with a test for antibodies to thyroid peroxidase, after a 2-to-3-month interval. Although a hypoechoic or inhomogeneous pattern on ultrasound examination of the thyroid may provide additional evidence of thyroid autoimmunity, ultrasonography is not recommended routinely for the evaluation of subclinical hypothyroidism.

Treatment:  In general, data suggest that levothyroxine treatment is unlikely to reduce symptoms in persons with modest elevations in thyrotropin levels and with minimal symptoms at baseline, but such treatment may have benefit in symptomatic patients, particularly in those who have a serum thyrotropin level above 10 to 12 mIU per liter. Treatment is generally recommended for persons 70 years of age or younger who have thyrotropin levels of 10 mIU per liter or higher, although long-term benefits have not been shown and the risks of such treatment are unknown. For persons older than 70 years of age or for persons who have a thyrotropin level of less than 10 mIU per liter, treatment decisions should be guided by individual patient factors, including the extent of thyrotropin elevation and whether the patient has symptoms of hypothyroidism, antibodies to thyroid peroxidase, goiter, or evidence of atherosclerotic cardiovascular disease, heart failure, or associated risk factors. If treatment is started because of symptoms of hypothyroidism, the treatment should be discontinued if no alleviation of the symptoms is observed after 3 to 6 months or if adverse effects occur. If no treatment is started, the thyrotropin level should be monitored every 6 to 12 months, and treatment should be initiated if the level increases to 10 mIU per liter or more in persons younger than 70 years of age or if other indications for treatment become apparent. Cutoff values for the levels of thyrotropin and free T4 for the diagnosis and treatment of subclinical hypothyroidism in pregnant women differ from those in nonpregnant women.

Myxedema coma:

• • Common in elderly, NH patients presenting with altered mental status, bradycardia, UTI.

  • Severe hypothyroidism alone rarely causes coma or shock. Some non-thyroidal illness, like UTI or pneumonia lower thyroid hormone levels.

  • Profound hypothyroidism may produce a confusional state, coma, or dementia. Pts may have flat affect, psychomotor retardation, agitation, or psychosis. 

  • Neurological exam may reveal, dysarthria, deafness, or ataxia, but the most characteristic abnormality is delayed relaxation of tendon reflexes. Untreated the condition can progress to seizure and coma.

• Lab: low T3, T4 levels. TSH levels are high. Sr. Chol ▲. Hypoglycemia, hyponatremia. ABG may reveal respiratory acidosis. 

  • CSF protein is typically elevated, OP is slightly elevated.

  • Tx: 

    • Hypoventilation and hypotension is treated intensively, along with the concomitant disease. 

    • TSH and T4 levels should be obtained prior to starting thyroid hormone therapy in the severely ill.

    • T4, 50 - 100 mcg IV q6 - 8h for 24 hours, followed by 75 - 100 mcg IV daily until PO intake is possible.

    • Vital signs should be carefully monitored to detect early signs of exacerbation of heart disease.

    • Hydrocortisone, 50 mg IV q8h, is usually recommended during rapid replacement of thyroid hormone for the possible coexistent adrenal insufficiency.

Thyroid ophthalmopathy (also referred to as thyroid eye disease or Graves ophthalmopathy) is an autoimmune disease that causes progressive edematous changes of the orbital musculature resulting in restriction of eye movements. 

• The inferior rectus muscles are most commonly involved, followed by medial and superior rectus muscles

• Diplopia is most commonly vertical as the lateral rectus muscles are less likely to be involved. 

• Because of progressive enlargement of the extraocular muscles, proptosis and periorbital edema, which tends to be more pronounced on awakening and improves during the course of the day, are associated features.

• Most important, progressive muscle enlargement may cause compression of the optic nerve at the orbital apex; for this reason, formal visual field studies are required to monitor for insidious visual field constriction. 

• Diagnosis can be confirmed by imaging (CT or MRI) of the orbits documenting characteristic edema and hypertrophy of the extraocular muscles

• Laboratory studies for thyroid dysfunction may or may not be abnormal, but measurement of thyroid-stimulating hormone (TSH) receptor antibodies can correlate with disease severity and help monitor for response to treatment.

• In the absence of severe symptoms or impending visual decline, most patients can be managed conservatively with a focus on treating underlying thyroid dysfunction (if present), mitigating corneal exposure related to proptosis, and discontinuation of smoking. Moderate disease can be treated with immunomodulation (typically oral prednisone); severe disease may require surgery for orbital decompression. 

• More recently, an insulin-like growth factor I receptor (IGF-IR) inhibitor (teprotumumab) has been shown to improve proptosis and produce rapid symptomatic improvement as compared to placebo.

Approach to Thyroid nodule

Thyroid nodules are found in about 5% of the adults.  Has high prevalence.

Goal for evaluation is to identify malignant lesions. 

Nodules are more common in iodine deficient areas, in women, and with aging.  Most nodules are palpable, >1 cm in diameter.  Most patients with thyroid nodules have normal thyroid function tests.  Nonetheless, TSH level should be measured.  This may be suppressed by one or more autonomously functioning nodules.  If the TSH is suppressed, a radionuclide scan is done to determine if the identified nodule is “hot,” as lesions with increased uptake are almost never malignant and FNA is unnecessary. 

An ultrasound-guided FNA Bx should be the first step in the evaluation of a thyroid nodule.  The technique is good for the detection of PTC.  Distinction of benign and malignant follicular lesions is often not possible using cytology alone.  Characteristic features of malignancy mandate surgery.  The diagnosis of follicular neoplasm also warrants surgery, as benign and malignant lesions cannot be distinguished by cytopathology or frozen section.  

Management of benign lesions may require TSH suppression or monitor nodule size by ultrasound.  Repeat FNA is indicated if a nodule enlarges.  A second biopsy should be b performed within 2 to 5 years to confirm the benign status of the nodule.

Ultrasound characteristic suggestive of malignancy include microcalcifications, increased vascularity, and hypoechogenicity within the nodule.

Thyrotoxicosis – Storm

• 1. Admit ICU

  2. Monitor VS, cardiac monitoring

  3. Electrolyte q2hr

  4. NPO

  5. Heplock

  6. O2 via nc to keep SpO2 >92%

  7. Bed rest

Labs/Dxtic:

Total T4 – stat. TSH, FT4, total T3, CMP, Mg, Phos, CBC with diff, Beta-HCG in females. CPK, LFTs, UA, Urine C & S

CXR (PA and Lat)

ECG

US thyroid

Thyroid scan

SDS, UDS, BAL, troponin, 

Nuclear thyroid scintitgraphy (cannot perform nuclear scan after saturated sol of KI (SSKI)

Consult: Endocrinology

Avoid: ASA (displaces T4 from TBG, thus raising T4 level); BB in asthma, anticoagulation activity may be increased by PTU

Management of thyroid storm:

https://www.mdcalc.com/burch-wartofsky-point-scale-bwps-thyrotoxicosis

• 1. Adjust PTU and methimazole in pregnancy (decrease dose)

  2. PTU, 300 – 600 mg PO/NG bolus, then 150 – 300 mg PO/NG q6h. Preferred in elderly, pregnant and lactating females, and in cardiac disease) OR

  3. Methimazole (Tapazole), 80 – 100 mg PO/PR/NG bolus, then 30 mg q8hr

  4. SSKI, 5 gtt PO q6 – 8 hr x 24 – 72 hrs, OR

  5. Sodium iodide, 250 mg IV q6hr, OR

  6. Lugol’s solution, 10 gtt added to IVF q8h

  7. Propranolol, 80 – 120 mg PO q4 – 6h or 1 mg/min for 2 – 10 mins (blocks T4 and T3), OR

  8. Esomolol, 5 gm in 500 mL D5W, loading dose of 500 mcg/kg x 1 min, then 50 – 200 mcg/kg/min

  9. Dexamethasone, 2 mg IV q6 – 8h, or hydrocortisone, 100 mg IV q6 – 8h

  10. Tylenol, 325 – 650 mg PO q6h PRN for fever

  11. CHF and atrial fibrillation: Manage with digoxin

  12. Iodine and surgery reserved until patient is euthyroid

  13. Administer PTU and methimazole 1 hour prior to giving iodide to prevent oxidation of iodide to iodine. 

  14. DVT/GI proplylaxis

Levothyoxine needs to be given at 6 AM on an empty stomch with no other medications and no food. She can take this medication with water only