• Understand the difference between overt and subclinical hypothyroidism.
• Know the different treatment options for subclinical hypothyroidism.
• Identify medications that exacerbate thyroid dysfunction.
• Recognize symptoms of pediatric hypothyroidism.

Thomas G. Kincer , MD
Clinical Professor, Program Director

Irina Licea , MD
Resident Physician

German Alvarez , MD
Resident Physician

Thomas Rose , MD
Resident Physician

Montgomery Family Medicine Residency Program
Montgomery, AL

The University of Alabama School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The University of Alabama School of Medicine designates this educational activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The boards of nursing in many states, including Alabama, recognize Category 1 continuing medical education courses as acceptable activities for the renewal of license to practice nursing.

Overt hypothyroidism, defined as an elevated TSH and low free T4, is present in about 0.3% of the population. Whereas, subclinical hypothyroidism, defined as an elevated TSH with normal free T4 and T3, is present in about 4.3% of the population.[1] Hypothyroidism is more common in women and with advancing age. Common signs and symptoms include fatigue, weight gain, cold intolerance, hair loss, depression and constipation. However, most of these symptoms are common to many illnesses and to the aging process, thereby making it difficult to diagnose hypothyroidism by symptoms alone. One must, therefore, have a low threshold for ordering a TSH level if any of these symptoms are present.

The most common cause of hypothyroidism worldwide is iodine deficiency. In the United States, where iodine deficiency is rare, gland failure due to autoimmune disease (Hashimoto’s Thyroiditis) is the most common cause. In Hashimoto’s thyroiditis, the body recognizes the thyroid antigens as foreign and a chronic destructive process ensues. Up to 95% of these individuals will have antithyroid antibodies. Of those individuals with antithyroid antibodies, 95% will have antithyroid peroxidase antibodies and 80% will have antithyroglobulin antibodies.[2] Less common causes of hypothyroidism include drugs such as amiodarone and lithium, radioactive iodine ablation for Grave’s Disease, central hypothyroidism from hypothalamic or pituitary failure, or transient causes such as viral or postpartum thyroiditis.

Diagnosis is dependent upon laboratory findings. Physiologically, if T4 and T3 levels fall, the hypothalamic-pituitary axis increases the production of TSH to stimulate the thyroid to increase production of T4. Normal TSH levels usually range from 0.1-6 mU/L and free T4 levels range from 0.8 to 2.8 ng/dL. In primary hypothyroidism due to gland failure, the TSH will be elevated and in secondary hypothyroidism from hypothalamic-pituitary failure, the TSH will be low. For this reason, with any abnormal TSH it is recommended to obtain a free T4. The following combinations are to be interpreted as:

• High TSH and low free T4 = overt primary hypothyroidism
• High TSH and normal free T4 = subclinical hypothyroidism
• Low TSH and low free T4 = hypothalamic-pituitary failure

Treatment of overt hypothyroidism with replacement hormone is recommended. This is usually accomplished with levothyroxine. Starting dosage is based on age and weight. Elderly patients should be started at 25-50 micrograms daily and younger patients typically are started at 75-125 micrograms daily. Follow up TSH levels should be done no sooner than four weeks after starting or after each dosage adjustment. Treatment of subclinical hypothyroidism should be considered on a case-by-case basis. In general, if the TSH is between 6-10 mU/L, observation alone is usually adequate. In this case it is recommended to repeat the TSH and free T4 every 6-12 months. Most sources recommend starting levothyroxine if the TSH is greater than 10 and antithyroid antibiodies are positive or symptoms of hypothyroidism are present in spite of a normal free T4.[3] For hypothalamic-pituitary failure it is recommended to search for the underlying cause such as a pituitary mass and begin treatment with levothyroxine. General screening for hypothyroidism is not recommended except in the newborn.

J.S. is a 57-year-old white female whose husband died suddenly of a myocardial infarction two years earlier. Her grieving became prolonged and she experienced high levels of anxiety, worsening sleep disturbances, an inability to concentrate and a constantly depressed mood. The patient consulted her primary care physician for her symptoms six months after onset. She was diagnosed with depression and started on citolapram once daily. However, over the following 16 months her symptoms waxed and waned and several antidepressant regimens were tried without satisfactory response. She was referred to a psychiatrist who is currently prescribing venlafaxine, trazodone, and lithium carbonate. Because of continued symptoms her psychiatrist obtained serum thyroid studies. The results were TSH of 21.2 mU/L (0.1-6 mU/L) and free T4 of 0.9 ng/dL (0.8-2.8 ng/dL).