Endocrine Abstracts

In the 27 families with FNAH the onset of hyperthyroidism varies from 18 months to 60 years. Also the manifestation of goiters is variable in these families.

A 74 year old women first presented at the age of 69 years in 9/2006 with tachyarrythmia and hypertension. After the initial treatment of her hypertension and oral anticoagulation for her intermittant atrialfibrilation 3/2007 a thyroid workup revealed a suppressed TSH of 0.029 (normal< 0.4 mU/l) and normal fT3 and fT4. TPO, TSH-receptor and thyreoglobulin antibodies were negative. Thyroid ultrasound reveiled a thyroid volume of 102 ml with several nodules with diameters of up to 2.6 cm right and up to 1.8 cm left. Szintigraphy showed a homogeneous Tc uptake of 1.95%. She was treated with 1 GBq I 131 in 6/2007 which normalised her thyroid function untill 12/2007 (TSH 3.05 mU/L). Her brother and sister do not suffer from thyroid diseases. Her 45 year old daughter and her 16, 12 and 11 year old grandsons do not have symptoms of hyperthyroidism and display normal TSH, fT3 und fT4.

Because of the diffuse Tc uptake and the negative TPO, TSH-receptor and thyreoglobulin antibodies her TSH receptor gene was analysed in DNA extracted from EDTA blood.in spite of her negative family history for hyperthyroidism. Sequencing revealed a N 670 S TSH receptor germline mutation. This TSH receptor germline mutation’s constitutive activity could previously only be demonstrated in HEK but not in COS cells (Mueller et al. 2009).

This case illustrates the necessity to analyse patients with hyperthyroidism accompanied by diffuse Tc uptake and negative TPO, TSH-receptor and thyreoglobulin antibodies (so called antibody negative Graves’ disease) for TSH receptor germline mutations. Moreover, it illustrates that TSH receptor germline mutations may first lead to long standing nodular goitrogenesis before the late manifestation of subclinical hyperthyroidism.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector