Primary Organ System Dysfunction to Consider
Based on this patient's constellation of symptoms—fatigue, heavier periods, cold intolerance, weight gain despite maintained exercise and nutrition, plus dry/coarse skin—following upper thoracic radiation for Hodgkin lymphoma, radiation-induced hypothyroidism is the most likely diagnosis and should be evaluated immediately with thyroid function testing (TSH and free T4). 1, 2
Endocrine System: Radiation-Induced Hypothyroidism (Primary Consideration)
Why This is Most Likely
Radiation-induced hypothyroidism (RIHT) occurs in approximately 50% of long-term survivors who received neck or upper mediastinal irradiation, with the thyroid gland receiving mean doses >10 Gy during treatment for Hodgkin lymphoma 1, 2
The clinical presentation is classic: fatigue, cold intolerance, weight gain, menorrhagia (heavier periods), dry/coarse skin, and these symptoms typically manifest 5-10 years post-radiation but can occur earlier 2, 3
Her upper thoracic radiation for Hodgkin lymphoma directly exposed the thyroid gland, and guidelines specifically recommend thyroid function evaluation (TSH) after irradiation of the neck at 1,2, and at least 5 years post-treatment 1
Dose-Volume Relationships
Mean thyroid dose >28 Gy, V40 >49%, and thyroid volume <2.12 cm³ spared from 40 Gy are significant risk factors for developing RIHT 4
Primary hypothyroidism affects 20-30% of patients following curative radiotherapy to the neck region, with approximately half occurring within the first 5 years, though the incidence can reach 50% in Hodgkin lymphoma survivors 2, 3
Immediate Action Required
Order TSH and free T4 immediately—this is a highly treatable cause of her symptoms and should not be missed 2
If confirmed, initiate levothyroxine replacement therapy to restore euthyroid state and resolve symptoms 5
Secondary Organ Systems Requiring Evaluation
Hematologic System: Anemia
Heavy menstrual bleeding (menorrhagia) combined with fatigue mandates evaluation for iron deficiency anemia 2
Order complete blood count with differential, iron studies (ferritin, TIBC, serum iron) to assess for anemia as a contributing factor to fatigue 2
Menorrhagia itself can be a manifestation of hypothyroidism, so thyroid replacement may improve menstrual bleeding 5
Cardiovascular System: Radiation-Induced Cardiac Disease
Upper thoracic/mediastinal radiation for Hodgkin lymphoma carries a 2-7 fold increased risk of coronary artery disease and other cardiac complications 1
Cardiac toxicity typically manifests 10-20 years post-treatment but can present earlier, particularly in younger patients 1
Her symptoms of fatigue and exercise intolerance despite maintained fitness could indicate subclinical cardiac dysfunction (restrictive cardiomyopathy, valvular disease, or coronary disease) 1, 2
Evaluate with: baseline ECG, consider echocardiogram to assess for valvular disease, diastolic dysfunction, or reduced ejection fraction 1
Note that hypothyroidism itself can cause or worsen cardiac symptoms, so thyroid replacement may improve cardiac function if present 5
Malignancy Surveillance: Recurrence or Secondary Cancer
Disease recurrence or secondary malignancies must be considered in any cancer survivor with new constitutional symptoms (fatigue, weight changes) 2
Hodgkin lymphoma survivors have increased risk of secondary malignancies including breast cancer, thyroid cancer, and treatment-related leukemias 1
Her recent 6-month scan showing cancer-free status is reassuring, but ongoing surveillance remains important 6
Additional Contributing Factors to Assess
Metabolic and Nutritional Status
Comprehensive metabolic panel to evaluate electrolytes, renal function, hepatic function, and glucose 2
Vitamin deficiencies (B12, folate, vitamin D) can contribute to fatigue and should be assessed, particularly given her halal diet which may have specific nutritional patterns 2
Gonadal Function
Estrogen levels should be monitored, particularly in younger patients who received intensive chemotherapy, as premature ovarian insufficiency can occur 1
However, at age 48 with regular (albeit heavier) periods, she appears to have intact ovarian function, making this less likely than hypothyroidism 1
Sleep Disorders
Screen for sleep apnea and other sleep disturbances by asking about snoring, witnessed apneas, and sleep quality 1, 2
Hypothyroidism itself can contribute to or worsen sleep apnea, so thyroid replacement may improve sleep if present 5
Psychological Factors
Screen for depression and anxiety, which commonly co-occur with cancer survivorship and can manifest as fatigue and weight changes 2
However, the presence of objective physical findings (dry/coarse skin, menorrhagia, cold intolerance) strongly suggests an organic etiology rather than purely psychological 2
Critical Pitfalls to Avoid
Do not attribute all symptoms to "cancer-related fatigue" without thorough evaluation of treatable medical conditions—hypothyroidism is frequently overlooked despite being extremely common after thoracic radiation 2
Do not delay thyroid function testing—this is the single most likely diagnosis given her symptom constellation and radiation history 1, 2
Do not forget that multiple conditions can coexist—she may have both hypothyroidism AND anemia from menorrhagia, both contributing to fatigue 2
Do not overlook cardiovascular evaluation—while hypothyroidism is most likely, cardiac disease from radiation is a serious late effect that requires surveillance 1
Recommended Diagnostic Algorithm
Immediate laboratory evaluation: TSH, free T4, CBC with differential, iron studies, comprehensive metabolic panel 1, 2
If TSH elevated: Confirm primary hypothyroidism and initiate levothyroxine replacement 1, 5
If anemia present: Treat iron deficiency; menorrhagia may improve with thyroid replacement if hypothyroid 2, 5
Cardiovascular screening: ECG now; consider echocardiogram given radiation history and symptoms 1
Ongoing surveillance: Continue routine cancer surveillance per guidelines; annual thyroid function monitoring lifelong 1