Hypothyroidism

N. Buttar MD

Hypothyroidism

1.8% of total population. Second only to DM as most common endocrine disorder. Incidence increases with age. More common in females. 2-3% of older women.

Etiology
PRIMARY HYPOTHYROIDISM Hoshimotos thyroiditis-most common Idiopathic hypothyroidism-probably old Hoshimotos Irradiation of thyroid Surgical removal Late stage invasive fibrous thyroiditis Iodine deficiency Drug therapy (Lithium, Interferon) Infiltrative Diseases: Sarcoidosis, Amyloidosis Scleroderma, Hemochromatosis

SECONDARY HYPOTHYROIDISM 5% of cases. Pituitary or hypothalmic neoplasm. Congenital hypopituitarism. Pituitary necrosis (Sheehans syndrome)

Signs and Symptoms

Non-specific. May be confused with other conditions especially in postpartum depression and elderly. Maintain high index of suspicion. In older patients, hypothyroidism may be confused with Alzheimers and depression. Patient may end up getting treated for depression.

Common signs and symptoms S/S Weakness Skin changes Slow speech Eyelid edema Cold sensation Decreased sweating Cold skin Thick tongue Facial edema Coarse hair Skin pallor Forgetfulness Constipation

% pts affected 99 97 91 90 89 89 83 82 79 76 67 66 61

Diagnosis
In Primary Hypothyroidism TSH is high. Free thyroid hormone are depressed. In Secondary Hypothyroidism Both TSH and free thyroid hormones are low.

Anti bodies in hypothyroidism

Anti bodies: Anti thyroid peroxidase [ anti microsomal] antibodies Anti thyroglobulin antibodies. Anti bodies against T3 and T4 in auto immune hypothyroid disease. In primary hypothyroidism; - up to 12 % pt do have anti gastric parietal cell antibodies. - these pts. Can develop pernicious anemia.

Generally

Once diagnosis of primary hypothyroidism is made, additional imaging or serologic testing is unnecessary if gland is normal on exam. In secondary hypothyroidism, further testing with pituitary provocative testing and imaging to rule out microadenoma. In general, evidence of decreased levels of more than one pituitary hormone is indicative of a panhypopituitary problem.

Lab Values

TSH level
High

Free T4 level
Low

Free T3 level
Low Normal

Likely Diagnosis

Primary Hypothyroidism Subclinical hypothyroidism with high risk for future development of overt hypothyroidism Subclinical hypothyroidism with low risk for future development of overt hypothyroidism Congenital absence of T4-T3 converting enzyme; amiodarone Cordarone) effect on T4-T3 conversion Peripheral thyroid hormone resistance Pituitary thyroid deficiency or recent withdrawal of thyroxine after excessive replacement therapy

High (>10 U/mL Normal [{10mU/L]} High (6-1uU/mL Normal {6-10mU/L]) High

Normal

High

Low

High Low

High Low

High Low

Thyroid Hormone Replacement

Levothyroxine can cause increases in resting heart rate and blood pressure So replacement should start at low doses in older and patients at risk for cardiovascular compromise

Hormones
In past Thyroid preparations were prepared from dessicated samples of ground cow or pig thyroids. Standards based on iodine contents rather than T3 or T4 content. Actual content of thyroid hormone varies considerably from manufacturer to manufacturer and even within product.

Generic or Brand Name

Study of four products, two brands and two generic preparations showed bioequivalent. Patients switched from one product to another showed insignificance variations in thyroid function Only Synthroid produces more rapid and higher rise in T3 level after administration. However, not statistically significant.

Preparations Available

15 mg(1/4 gr) ,30 mg(1/2 gr) 60 mg(1 gr),90 mg(1.5 gr) 120 mg(2 gr),180 mg(3gr) 300 mg(5 gr) 50-100 mcg of Levothyroxine =60 mg of Armour Thyroid Synthroid (T4) Levothroid (T4) Levoxyl (T4) Levothyroxine Sodium 25,50,75,88,100,112 125,137,150,175,200 300 mcg.

Armour thyroid

Preparations Available

Unithroid (T4)

25, 50, 75, 88,100,112 125,150,175, 200, 300 mcg.

50 mcg tabs. of Synthyroid, Levoxyl,and Unithroid is dye free.

Cytomel(T3) ( Liothyronine Na)

5,25, 50 micrograms

Preparations Available
Thyrolar: Tabs in Grain 1 2 3

Content(mcg)

T3 3.1 6.25 12.5 25 37.5

T4 12.5 25 50 100 150

Preparations Available

Injectables -Levothyroxine Sodium -Synthroid Available in 200 mcg and 500 mcg per 10 mL vials T3 as compare to T4 - 4 times more potent. - Short duration of activity. - Rapid onset of action.

Initiating Treatment

Most healthy adults-1.7 ugm/kg/day Elderly, falls down to 1.0 ugm/kg/day Levothyroixine needed 0.1-0.15 mg/day For full replacement children may need up to 4 ugm /kg/day

Treatment

Younger patients can be started at target dose usually 0.075 mg/day Start low and go slow in elderly and high risk patients, usually 0.025 mg/day Increase in increments of 0.025 mg q four weeks until TSH returns to normal.

What if?
What if the patient still has impaired mood and memory and cold intolerance in spite of stable thyroid function?

In one study: In study of 33 middle aged patients with stable hypothyroid, on levothyroixine, adding 12.5 mcg/ day of triiodothyronine and decrease of 50 mcg/ day of levothyroxine helped impaired symptoms. Long term effects not known.

Monitoring thyroid function

Most patients can be followed by serial TSH measurements. Changes in TSH levels lag behind serum thyroid levels. So TSH should not be checked sooner than four weeks after adjusting of doses. Full effect of replacement on TSH may not become apparent until eight weeks. Patients with pituitary insufficiency, T3 and T4 can be followed. Goal is to keep thyroid hormone level in middle to upper range of normal.

Frequency

TSH or Free T4 monitored yearly. No data supports the practice. Usually once stable dosage is established, it remains stable until 60-70 years. In elderly serum albumin levels may decrease, so dosage may have to be decreased by 20%. Less frequent monitoring in young patients and annually in elderly.

Treatment of Hypothyroidism
Need for replacement
Patients >50 or high risk of Cardiac Disease YES Start Levrothyroxine at 0.025 mg/day NO Start at 0.075 mg/day

-Monitor TSH- Primary hyperthyroidism or

Free T4-Secondary hypothyroidism, every 6-8 Weeks and adjust doses Does patient still have lethargy or memory loss

Yes Consider adding Triiodothyronine 12.5 mcg/day and decrease Levothyroxine by 20%

No
Continue therapy and annual measurement of TSH or a free T4

Sub clinical Hypothyroidism

High TSH with normal Free T4 Commonest cause is chronic autoimmune thyroiditis (Hoshimotos disease) Associated with increased titer of antithyroid antibodies: - Anti thyroglobulin autobodies - Antimicrosomal (Antiperoxidase) antibodies Suspected with thyroid enlargement but may be associated with atrophy

Prognosis

May stay sub clinical May progress to clinical, 5% per year with positive antibodies In elderly risk is 20%/ year

Normal T4, High TSH, Two readings, six weeks apart

TSH >10 mU/L

Check Thyroid antibodies

TSH between 5-10 mU/L

Antibodies or symptoms present Negative Consider therapy Therapy Symptoms positive

Antibodies negative or no symptoms

Positive

No symptoms

Observe, test every six months

Therapy

A patient with bipolar disorder is being treated with lithium. Of the following, which one is the most likely side effect of his therapy?
A) B)

C)
D)

Hypoparathyriodism Hypoaldosteronism Hypothyroidism Diabetes inspidus

Answer: C Lithium is used as a mood stabilizer in bipolar disease and can be used as monotherapy, especially when the depression is mild. A well-recognized side effect of lithium of hypothyroidism. It is recommended that TSH be monitored in patients treated with lithium. Hyperparathyroidism, but not hypoparathyroidism, has been reported, but it is not as common as hypothyroidism. Nephrogenic diabetes insipidus has been reported only rarely. Hypoaldosteronism is not a side effect of lithium therapy.

Which of the following is a cause of thyrotoxicosis characterized by decreased radioactive iodine uptake?
A) B)

C)
D)

Graves disease Subacute thyroiditis Toxic multinodular goiter Solitary toxic thyroid nodule

Answer: B Thyrotoxicosis with high 24-hour radioactive iodine uptake (RAIU) is caused by Graves disease, toxic multinodular goiter, a solitary hot nodule, a TSH-secreting pituitary tumor, molar pregnancy, and choriocarcinoma. Thyrotoxicosis with a low 24hour RAIU may be the result of subacute thyroiditis, sporadic silent thyroiditis, postpartum lymphocytic thyroiditis, radiation-induced thyroiditis, iodine induced thyroiditis, thyrotoxicosis factitia, metastatic follicular thyroid cancer, and struma ovarii.

Which one of the following is associated with galactorrhea?

A) B)

C)
D) E)

Hypothyroidism Breast cancer Fibrocystic breast disease Adrenal insufficiency Graves disease

Answer: A Galactorrhea, or inappropriate lactation, is a relatively common problem with multiple causes. Systemic disease is one cause, the most common being hypothyroidism. Low levels of thyroid hormone result in increased levels of thyrotopinreleasing hormone, which increases prolactin secretion. Galactorrhea and symptoms of hypothyroidism abate with thyroid hormone replacement therapy. This condition is not associated with breast cancer or fibrocystic disease of the breast. Cushings disease, rather than adrenal insufficiency, is associated with galactorrhea.

Your 57-year-old white male patient has been seen in the ICU for the past ten days recovering from an exploratory laparotomy performed for a perforated duodenal ulcer. Postoperatively he developed acute renal failure and sepsis. When the patient became hypothermic three days ago, the resident on duty ordered a thyroid function panel and obtained the following results: T4 RIA.4 ug/dL (N5-12) T3 RIA..60 ng/dL (N70-90) TSH...2.0 uU/mL (N 0.5-5.0)

The patient has no previous history of thyroid disease. His gland is normal in size. His condition today is critical but stable. The most appropriate treatment at this time is to:
A) B) C) D)

Continue present management Order a TRH stimulation test Begin parenteral thyroixine immediately Begin parenteral thyroixine and hydrocortisone immediately

Answer: A This patient in all probability has the euthyroid-sick syndrome, also known as nonthyroid illness syndrome (NTI)-the association of severe nonthyroid illness with biochemical parameters indicative of thyroid hypo function. Low T3 with normal T4 and low T3 with low T4 are the most common variants of this syndrome. TSH is usually normal but may be high or low. A TSH level >20 uU/mL would be inconsistent with NTI and indicates hypothyroidism. Replacement of T4 does not influence the outcome.

A 68-year-old African-American female with primary hypothyroidism is taking L-thyroxine (Synthroid) 125 ug/day. Her thyroid-stimulating hormone (TSH) level is 0.2 uU/mL (N0.5-5.0). She has no symptoms of either

hypothyroidism or hyperthyroidism. Which one of the following is true regarding her management?
A) B) C) D) E)

The L-thyroxine dosage should not be changed The L-thyroxine dosage should be increased The L-thyroxine dosage should be decreased The L-thyroixine should be discontinued A free thyroxine index (FTI) is needed to determine her thyroid hormone status more accurately

Answer: C Because of the precise relationship between circulating thyroid hormone and pituitary TSH secretion, measurement of serum TSH is essential in the management of patients receiving L-thyroxine therapy. Immunoassays can reliably distinguish between normal and suppressed concentrations of TSH. In a patient receiving L-thyroxine, a low TSH level usually indicates over replacement. If this occurs, the dosage should be reduced slightly and the TSH level repeated in 2-3 months time. There is no need to discontinue therapy in this situation, and repeating the TSH level in two weeks would not be helpful. A free thyroxine index would also be unnecessary, since it is not as sensitive as a TSH level for detecting mild states of excess thyroid hormone.

In a patient with symptoms of thyrotoxicosis and elevated free thyroxine (T4), the presence of thyroid TSH receptor site antibodies (TRAbs) would indicate which one of the following?
A) B) C) D) E)

Toxic multinoduler goiter Graves disease Hashimotos (lymphadenoid) thyroiditis Toxic adenoma Subacute (giant cell) thyroiditis

Answer: B When there is a question about the etiology of goiter and thyrotoxicosis, the presence of thyroid TSH receptor immunoglobulins would indicate the presence of Graves disease, which is considered an autoimmune disease. The prevalence of specific forms of TSH receptor site antibodies can distinguish Graves disease from Hashimotos disease. Both are autoimmune diseases, but in Graves disease there is a predominance of TSH receptor antibodies. TSH receptor-blocking antibodies are seen in Hashimotos disease. These immunoglobulins tend to disappear during therapy.

Chronic therapy with which one of the following commonly used drugs is most likely to increase the risk for osteoporosis?
A) B)

C)
D)

Antihypertensives Oral hypoglycemics NSAIDs Thyroid hormone

Answer: D Thyroid hormone stimulates osteoclasts, and recent research shows decreased bone density in patients receiving standard replacement doses of thyroid hormone. This appears to occur even in patients who have never had thyrotoxicosis, a known cause of secondary osteoporosis. In patients taking thyroid hormone replacement for bona fide hypothyroidism, it is important, therefore, to use no more than the minimum dosage necessary to make the patient euthyroid. Also, it is wise to discontinue any thyroid replacement that is not really necessary. The other drugs listed are not associated with increased osteoporosis risk.

A 32-year-old think, white G2 P1 comes to your office for her initial prenatal visit at 20 weeks gestation. On examination, you note slight exopthalmos, a heart rate of 110 beats/min., and a tender, palpable thyroid. She admits she has gained no weight during the pregnancy, but says she is always hungry. Her serum TSH level is 0.01uU/L (N 0.5-5.0) and her free T4 level is 22.5 pmol/L (N7.7-15.6). The most appropriate initial management of this patient would be:
A)

B)
C) D)

Close observation, with repeat thyroid levels every two weeks throughout the pregnancy Propylthiouracil Iodine therapy Surgical referral for subtotal thyroidectomy

Answer: B Prompt Dx and Tx of hyperthyroidism during pregnancy is extremely important to prevent maternal and fetal morbidity and mortality. Anti thyroid therapy with propylthiouracil is the therapy of choice in pregnant women. Iodine freely crosses the placental barrier and is contraindicated in pregnancy, since it may cause fetal goiter and hypothyroidism. Surgery may be performed during pregnancy, but should be reserved for severe cases unresponsive to antithyroid therapy. It carries a significant risk of spontaneous abortion and premature delivery.

A 52-year-old white male is being considered for pharmacologic treatment of hyperlipidemia because of an LDL cholesterol level of 180 mg/dL. Before beginning medication for his hyperlipidemia, he should be screened for:
A) B) C) D) E)

Hyperthyroidism Hypothyroidism Addisons disease Cushings disease Pernicious anemia

Answer: B According to the Summary of the National Cholesterol Education Program Adult Treatment Panel III Report of 2001, any person with elevated LDL cholesterol or any other form of hyperlipidemia should undergo clinical or laboratory assessment to rule out secondary dyslipidemia before initiation of lipidlowering therapy. Causes of secondary dyslipidemia include diabetes mellitus, hypothyroidism, obstructive liver disease, chronic renal failure, and some medications.

A 56-year-old female presents for routine visit. An otherwise normal adult physical exam reveals a 2 cm rightsided thyroid nodule. Her TSH levels are normal. She has no history of neck irradiation, and there is no family history of thyroid cancer. You Recommend:
A) B)

C) D) E)

A fine-needle aspiration biopsy Suppression of the nodule with levothyroxine (Synthroid) Removal of the nodule A serum calcitonin level A radioactive iodine uptake test and thyroid scan

Answer: A In the absence of risk factors for cancer, a patient with a normal TSH level who is found to have a thyroid nodule on physical examination should have a fine-needle aspiration biopsy. Independent of morphology, fine-needle aspiration provides the most direct and specific information about a thyroid nodule.