Endocrine Abstracts

Background: In the majority of cases, the results of TFTs are straightforward. In significant subgroup of patients, the interpretation of TFTs is more challenging, either because. The results appear discordant with the clinical picture (e.g. normal TSH in a patient with suspected thyrotoxicosis), Or measurements appear to contradict each other (e.g. raised TH concentrations, but with non-suppressed TSH).

Case presentation: 29 year old Caucasian female complains of Tiredness, insomnia. amenorrhoea and goitre. Initially diagnosed at T3 Thyrotoxicosis (2009) and treated with Carbimazole. Clinically she was euthyroid with palpable smooth thyroid. TFT showed f T4 19.4, Free T3 7 TSH 15.24.

TPO Abs <30.

Her TFTs (Table 1)

US Thyroid: Thyroid gland upper limit of normal in size. Isthmus appears slightly enlarged. Significantly increased Doppler flow noted.

MRI Pituitary: Bulky pituitary gland but no significant abnormal.

External Assay: TFTs (referred) but no evidence for assay interference.

Delfia TFT: TSH: 30.8 mU/L (0.40–4.0) fT4: 13.7 pmol/L (9–20) fT3: 7.0 pmol/L (3.0–7.5). Total T4: 139.0 nmol/L (69–141) TBG: 23.8 ug/mL (14–31)

Centaur TFT: TSH: 23.33 mU/L (0.35–5.5) fT4: 14.6 pmol/L (10–19.8) fT3: 6.0 pmol/L (3.5–6.5).

Normal a subunits: Genetics showed Mutation in TH receptor b gene (THRb). Patient was treated with Cabergoline, 0.5 mg weekly. Continued on Carbimazole 15 mg. patient’s follow up: periods returned, weight stabilised and symptoms resolved.

Discussion: Causes of elevated total T4 with non-suppressed thyroid stimulating hormone:

• Raised serum binding proteins

• Familial dysalbuminaemic hyperthyroxinaemia

• Anti-iodothyronine/anti-TSH antibodies

• Non-thyroidal illness (including acute psychiatric disorders)

• Neonatal period

• Iatrogenic: thyroxine replacement therapy, drugs (for example, amiodarone, heparin)

• TSH secreting pituitary tumour

• Resistance to thyroid hormone

Amongst the various discordant TFT patterns one of the most challenging distinctions to make is between Resistance to thyroid hormone due to a loss-of-function mutation in the human THRB gene (TRb RTH) And a TSH-secreting pituitary adenoma (TSHoma/thyrotropinoma).

Types of THR:: • Generalised (GRTH)- variable presentations.

• Selective pituitary resistance (PRTH)- thyrotoxicosis.

– 85% of RTH are caused by mutations of TRB gene.

THRB gene sequencing confirms the diagnosis in 85% of cases.

Treatment: • Usually no treatment is required.

• In PRTH:

1) Chronic suppression of TSH with T4, tri-iodothyroacetic acid, octreotide or Dopamine agonist.

2) Thyroid ablation with radioiodine or surgery.