Endocrine Abstracts

We present a case of a 52-year-old man with a past medical history of primary hypothyroidism on treatment, presenting with elevated TSH levels, suggesting inadequate thyroxine (T₄) replacement. The patient was managed with 200 μg of T₄ for 14 years with no compliance issues. TSH levels failed to normalise despite increasing the dose of T₄. In addition to elevated TSH levels the patient noted progressive leg swelling and associated shortness of breath over the preceding 12 months. Examination revealed bilateral pitting oedema up to the abdomen and elevated blood pressure (175/103 mmHg). Initial blood results demonstrated a low albumin of 21 g/l, down from a previous 44 g/l with urinalysis confirming marked proteinuria (+3) in addition to blood (+2). Subsequently, nephrotic syndrome was investigated as a probable cause. Twenty-four hour urinary protein was raised at 12.42 g (normal <0.15 g). A kidney biopsy was performed which demonstrated membranous glomerulonephritis. The nephrotic syndrome was symptomatically managed on frusemide 40 mg b.d. and ramipril 10 mg o.m. The proteinuria improved with reduction of peripheral oedema and stabilization of TSH levels. There are numerous causes of elevated TSH levels in a primary hypothyroidism patient on T₄. One of the less commoner causes is nephrotic syndrome, characterized by oedema, hypoalbuminaemia and proteinuria. Increased glomerular permeability results in loss of thyroxine-binding globulin (TBG) and free T₃/T₄. As a result, the pituitary–hypothalamic axis responded by increasing TSH production to compensate for reduced serum T₃/T₄. This elevation of TSH is not responsive to increasing doses of exogenous T₄ due to urinary loss of TBG. Management is of the underlying nephrotic syndrome. It is important to recognise that many hormones are protein based, as are their carrier molecules calling for a closer analysis of symptoms on presentation of elevated TSH.