Abstract
Abstract
Background: TFT patterns correlate directly with clinical symptoms in most patients with thyroid disease. However, some patients have TFTs which are at odds to clinical findings, posing a diagnostic challenge. Such cases warrant careful evaluation with a structured, rational approach to avoid misdiagnosis and mistreatment.
Clinical Case: A 48-year-old female liver transplant recipient with HIV presented with an asymptomatic multinodular goiter, low TSH and low/normal fT4. Her medications were nadolol, Bactrim, ursodiol, azithromycin, tacrolimus, efavirenz, emtricitabine, tenofovir and zolpidem. Thyroid US showed 3 dominant nodules with benign pathology on FNA. Uptake scan showed diffuse increased uptake consistent with Grave’s disease. She tried MMI for one year, then opted for RAI ablation and was started on LT4 with titration of dose. fT4 remained low/normal regardless of receiving LT4, MMI or no therapy over the following eight years. TSH was appropriately suppressed from 1.42 to 0.160 (0.45 - 4.500 mIU/L) when LT4 weekly dose was increased from 175 mcg to 350 mcg. On lower dose LT4 (150 mcg to 250 mcg weekly) her fT4 stayed low, 0.50 - 0.74 (0.82 - 1.777mg/dL) with normal TSH of 0.73 - 1.42. She remained clinically euthyroid throughout. Serial yearly thyroid US showed no significant change. Pituitary hormonal work-up (IGF-1, FSH, LH, ACTH, estradiol and cortisol) was appropriate for age. fT4 by direct dialysis assay was low with normal TSH. tT4, T3 uptake, rT3, TBG and TPO Ab were normal. HAMA antibodies were negative. LT4 was stopped and she remains clinically euthyroid with low fT4 0.56 and normal TSH 1.73.
Conclusion: The pattern of low fT4 with normal TSH is uncommon. Potential causes that were systematically evaluated include non-thyroidal illness, central hypothyroidism and assay interference. Normal pituitary function and appropriate TSH suppression while on LT4 ruled out central hypothyroidism. Her overall profile suggested fT4 assay interference. Commonly known interference factors were ruled out; biotin, HAMA Ab, pregnancy, renal failure, TBG excess, familial dysalbuminemic hyperthyroxiemia and trans-thyretin-associated hyperthyroxidemia. Direct dialysis is the gold standard fT4 assay but does not detect agents displacing T4 from TBG. It is less commonly recognized that low fT4 with normal TSH has been described amongst clinically euthyroid persons with HIV, at a prevalence of 1.3%–6.8%. Low fT4 is associated with didanosine, stavudine, and ritonavir, but not her anti-virals. The significance of low fT4 in patients with HIV is unclear, because they do not have a higher rate of hypothyroid symptoms. In the absence of clinical hypothyroidism, such as in this patient, LT4 treatment is not recommended. This case uniquely spans eight years and therefore offers valuable insight into the appropriate work-up, management and long-term natural history of low fT4 in persons with HIV.