Endocrine Abstracts

Background: Isolated secondary hypothyroidism is rare. In the majority of cases the causes are genetic (gene mutations) or structural (mass effect or infiltration). Structural causes are usually associated with simultaneous deficiencies of other adenohypophyseal hormones. We present an identical twin with isolated secondary hypothyroidism.

Case report: 1st Twin – 26-year-old obese lady, of Afro-carribean origin, presented with tiredness, weight gain, cold intolerance and menorrhagia. Clinical examination was unremarkable. Her TSH was 0.01(0.3–6)mU/l, total T4 48(50–150)nmol/l, T3 1.0(1–2.5)nmol/l and freeT4 7.7(10–24)pmol/l. Thyroid auto-antibodies were normal. Dynamic pituitary function tests showed adequate cortisol and growth hormone response to hypoglycaemia and normal LH/FSH response to GnRH stimulation. TRH test showed blunted TSH response. MRI scan showed enlarged but homogenous and uniformly enhancing pituitary. No infiltrative cause was found. Her total T4 normalized on 200 micrograms of thyroxine.

2nd Twin – 26-year-old twin sister of the above patient, presented with progressive tiredness, headaches and weight gain. Clinical examination was normal. Her TSH was 1.2 mU/l, totalT4 51 nmol/l, freeT4 7.6 pmol/l and T3 1.1 nmol/l. Thyroid auto-antibodies were normal. Dynamic pituitary function tests showed adequate cortisol, growth hormone and LH/FSH response but blunted TSH response to TRH stimulation. MRI scan showed hyperplasia of the pituitary gland. No infiltrative cause was found. On 200 micrograms of thyroxine her total T4 normalized.

Genetic analysis in both showed no mutations in the exon2 and exon3 Beta subunit of the TSH gene.

Discussion: Isolated TSH deficiency has been reported due to 5 different mutations in the coding region of the Beta subunit of the TSH. To our knowledge, these are the first reported cases of isolated secondary hypothyroidism in identical twins without abnormalities in TSH. The possible mechanism may be a genetic defect in the TRH receptor and the search for any new mutations continues.