Resistance to thyroid hormone (RTH) is a syndrome of reduced responsiveness of target
tissues to thyroid hormone (TH). Patients with RTH are identified by persistent elevation
of circulating free TH levels with non-suppressed serum TSH. The underlying genetic
defect is usually, but not always, a mutation in the TRβ gene. The frequency of de
novo mutations is estimated to 21%. The inheritance is autosomal dominant. The clinical
presentation varies significantly among different patients. However, goiter and the
absence of neuropsychological symptoms and metabolic sequences of TH excess belong
to the common features of the syndrome.
A 20 year old Caucasian female was admitted to the emergency department with palpitations.
Her initial ECG showed supraventricular tachycardia. After administration of 5 mg
metoprolol iv a sinus rhythm with heart rate of 85 bpm was documented. Initial laboratory
findings revealed secondary hyperthyroidism. Additional blood tests revealed hyperlipidemia.
The pituitary MRI discovered a lesion of 4 mm in the adenohypophysis. Symptoms and
signs of hypopituitarism or overproduction of pituitary hormones were absent. TRH
stimulation test led to adequate TSH response. Moreover, SHBG and α-GSU/TSH molar
ratio were within normal values, ruling out a TSH-producing adenoma. Genetic analysis
of TRβ gene identified a novel mutation in the 1st mutational cluster in the T3-binding domain of TRβ gene (c.1355C>G (p.Pro452Arg)). Unlike certain polymorphisms of deiodinases, this mutation was not identified
in the genetic analysis of the family members, demonstrating a sporadic, de novo mutation
of TRβ gene. Therapy with TRIAC (initial dosis 0.35 mg/day, gradually increasing to
1.4 mg/day) led to normalization of TSH and cholesterol levels with simultaneous decrease
in the fT4 levels. Furthermore, it could be documented a fall of the initially increased
TTSI after administration of TRIAC.
In patients with TRβ gene mutations and pituitary incidentalomas the differential
diagnosis of the secondary hyperthyroidism might be challenging.
