Resistance to Thyroid Hormone (RTH) is a rare inherited condition usually caused by mutations of the thyroid hormone receptor beta (THRB), thyroid hormone cell membrane transporters, or thyroid hormone metabolism which can present as asymptomatic, hypothyroidism, or hyperthyroidism. The objective is to report a probable case of RTH presenting with hypothyroidism and to demonstrate the resilience in the diagnosis of endocrine disorders in resource-poor settings. A 23-year old University undergraduate presented with clinical features of hypothyroidism but elevated thyroid hormones and thyroid stimulating hormone (TSH): free T4=38 [normal range 10-24] pmol/L, free T3=11 [normal range 3-8] pmol/L, TSH=3.8 [normal range 0.5-5.0] mU/L; and normal brain MRI. A working diagnosis of RTH was made. Though there was no facility to test for THRB gene mutation, the positive family history of a similar pattern of thyroid function tests, made for a probable diagnosis of RTH, and she was empirically placed on a gradually increased dose of levothyroxine from 50 µg till resolution of symptoms was achieved and maintained 6 months later at 600 µg daily. At 10 months follow-up, the patient felt well with the resolution  of symptoms and improved academic performance despite elevated thyroid hormones and unsuppressed TSH. The diagnosis of RTH requires a high index of suspicion, to enable early diagnosis, and prevent unnecessary invasive treatments. The treatment target should be the resolution of symptoms and signs and not normalization of thyroid hormone levels. This report also underscores the resilience that can be adopted in diagnosing and treating endocrine cases in resource-poor settings.