Woman With Nonspecific Fatigue: Depression? Thyroid Dysfunction? Cancer Recurrence?

A 34-year-old woman presents with the sole complaint of fatigue that has come on gradually over the past 6 months. She works as a schoolteacher and says there has been no change in the demands of the job. She is sleeping well and is happy in her marriage. She and other family members had a viral syndrome 4 months earlier, but none of them are feeling this fatigue. She denies fever, chills, nausea, or vomiting. She has gained approximately 5 lb recently, which she attributes to her lack of energy to exercise.

The patient had nodular sclerosing Hodgkin disease 4 years ago. The disease was limited to the chest and was treated with radiation and chemotherapy. Her oncologist told her at a visit 8 months ago that there was no evidence of disease. 

The patient shows no signs of acute distress but she appears slightly pale. Her blood pressure is 125/90 mm Hg; heart rate, 65 beats/min; and temperature, 36°C (97.4°F). There is no evidence of lymphadenopathy. Examination of the heart, lungs, and HEENT reveals no abnormal findings. There is trace edema in the lower extremities. The WBC count is 4500/µL (normal range, 4500 to 11,000/µL); hemoglobin level, 11.2 g/dL, with a mean corpuscular volume of 84 fL (normal range, 80 to 100 fL); and normal differential and platelet count. Electrolyte balance and kidney and liver function are normal.

What diagnostic clues do the history, physical, and laboratory results offer, and which of the following would be your next step?

A.   Refer her back to her oncologist
B.  Obtain a TSH level
C.  Start antidepressant therapy 
D.  Diagnose fibromyalgia and chronic fatigue and begin treatment with NSAIDs 
E.  Refer her for a bone marrow biopsy

Answers and Discussion on Next Page…

Clues in the history: The chief complaint is fatigue, which is common and nonspecific. Weight gain would be a bit unusual as a manifestation of recurrent Hodgkin disease. Depression is associated with weight loss or gain.

Physical clues: The physical examination is pertinent for what is-and what is not-found. 

The patient has no lymphadenopathy or organomegaly, and her lungs are clear. With recurrent disease one might expect to find lymph nodes or an enlarged spleen or liver. Disease in the lungs might present with rales.

The positive findings are mild and subtle and might easily be overlooked. Her pulse pressure is slightly low as is her pulse and temperature. She also has trace edema for no discernible reason.

Laboratory clues: Tests show a mild anemia with normal platelet count and a WBC count at the lower limits of normal.

Putting these facts together let’s reconsider the options: 

A. Refer her back to the oncologist. There is nothing to suggest recurrent disease and no symptoms (fevers or pruritus) that are consistent with recurrent disease. If the patient had bone marrow involvement, one would expect other manifestations of the disease and all cell lines to be depressed. However, her platelet count and WBC count are normal.

B.Obtain a TSH level. This is the correct answer. (Please see discussion below.) The TSH level returns at 16.5 µIU/mL.

C. Start antidepressants. Depression should be diagnosed only after a reasonable evaluation of other causes. There is no information in the patient’s history to suggest depression and there are other physical findings that suggest another disorder.

D. Tell her she has fibromyalgia and chronic fatigue syndrome and start therapy with NSAIDs. Like depression, chronic fatigue syndrome should be a diagnosis of exclusion. Fibromyalgia should have been accompanied by physical symptoms, such as painful muscular trigger points, which were not elicited.

E.Refer patient for a bone marrow biopsy. The patient has a mild anemia with a normal platelet count and WBC count. The yield of a bone marrow in this setting would be very low. As discussed, the suspicion of marrow involvement with recurrent Hodgkin disease is very low. While it is true that patients treated for lymphomas with chemotherapy are at increased risk for leukemias, presentation with isolated mild anemia would be exceedingly rare.

The Diagnosis: HYPOTHYROIDISM

Hypothyroidism eventually develops in a significant number of patients, such as this one, who receive radiation therapy to their chest. The disorder is secondary to the effects of the radiation on the thyroid gland. Our patient has fatigue and weight gain, which are typical for hypothyroidism. She also has other subtle findings: narrow pulse pressure (related to an increase in diastolic pressure, often seen with hypothyroidism); low heart rate; low body temperature; trace edema; and a mild normochromic, normocytic anemia. These findings were all subtle and may have been overlooked, resulting in a delayed diagnosis and a reduced quality of life for the patient.

Measurement of the TSH level is a simple, inexpensive test that will quickly confirm suspicion of hypothyroidism. As a bonus, the treatment is also easy and inexpensive, and if managed correctly, has virtually no adverse effects.

Teaching Points
• Patients with mild hypothyroidism may have very subtle complaints and physical findings.
• Patients treated for a malignancy are at risk for adverse effects of their treatment many years later.
• Patients who have had a life-threatening disease may also develop common benign disorders.

References:

Sources
DeGroot LJ, Jameson JL. Editors. Endocrinology 5th Edition Vol 2. Elsevier, Philadelphia, PA 2006:2084.
Illes A, Biro E, Milteny, Z et al. Hypothyroidism and thyroiditis after therapy for Hodgkin's disease. Acta Haematol. 2003;109:11-17.
Skla C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000;85:3227-3232.