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Multiple hormone resistance in a patient with follicular thyroid carcinoma and papillary microcarcinoma

Pseudohypoparathyroidism and related hormone resistance disorders have very heterogeneous clinical course and might be recognized only in the adulthood, particularly with the development of hypocalcemia. We present a 41 years old male patient who underwent a neurological investigation because of progressive muscle weakness and elevated creatinine kinase. Very low serum calcium (1.46 mmol/l) with hyperphosphatemia, low magnesium and high normal PTH were measured. The patient also had slightly higher LH and high FSH with low normal free testosterone, 46 XY karyotype and testes of normal volume. Lumbar bone mineral density was increased. TSH was just over the reference range and thyroxine was normal. On the neck ultrasound 3 cm large suspicious nodule was found in the left thyroid lobe. FNA suggested follicular tumour and left thyroid lobectomy discovered follicular carcinoma with capsular invasion and papillary microcarcinoma. The patient was reoperated for right thyroid lobectomy and radioiodine ablation therapy was further performed. Postoperative PTH was low due to incidental parathyroidectomy. Malignant thyroid disease indicated the need for TSH suppression, but his TSH was persistently elevated despite increasing L-T4 dose up to 250 μg. Free T4 levels also rose and patient had thyrotoxic symptoms. High SHBG reflected tissue thyrotoxicosis. The combination of L-T4 and L-T3 therapy finally succeeded to decrease TSH to the middle of the normal reference range and SHBG was used as an additional marker for its optimization. We presumed that this patient has multiple hormone resistance associated with deficient G-protein α subunit signalling, involving at least PTH and gonadotropins. Low magnesium levels might have contributed to the breakdown of PTH and calcium balance that triggered hypocalcemia. Gonadotropin resistance did not interfere with male phenotype development and some physical features might appear as mild Albright’s hereditary osteodystrophy. TSH resistance might also be found in such patients, but TSH is expected to fall promptly with L-T4 therapy. However, our patient showed inadequate responsiveness to L-T4 therapy suggesting a probable defect in thyroid hormone transport or deiodination. This was partially circumvented with L-T3 treatment, but uncertainties remain whether unsuppressed TSH might have negative impact on the risk for thyroid carcinoma recurrence. In this case we were faced with unexpected challenges of replacement therapy that could not be directly related with the primary disorder. Further genetic evaluation might contribute to our clinical assessment or even point to the common pathogenesis of this patient’s clinical presentation.

pseudohypoparathyroidism ; hormone resistance

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