Endocrine Abstracts

Case description: A 26-year-old female visited an endocrinologist for the first time in 2014 with complaint of neck swelling. Lab results revealed increased blood level of TSH, initially the diagnosis of hypothyroidism was set and levothyroxine therapy was initiated with consequent addition of thiamazole due to increasing levels of free T4 and TSH. In 2015 the diagnosis of TSH-secreting adenoma was made on the basis of MRI findings (pituitary microadenoma 3.1 mm in size) and laboratory results (TSH 7.8 IU/l, free T4 26.9 pmol/l, free T3 6.6 pmol/l). The patient first visited Moscow Endocrinology Research Centre in 2017. In further clinical observation we revealed new clinical data: patient reported face and hand enlargement for the last two years. Family history: father had enlarged facial features, died at the age of 34 from obstructive sleep apnoea, grandfather also had enlarged facial features. Laboratory tests revealed the data consistent with mixed TSH/GH-secreting pituitary adenoma: free T4 29.6 pmol/l, free T3 10.4 pmol/l, TSH 6.3 mIU/l, IGF-1 327.1 ng/ml (less than 280.0), beta-crosslaps 0.71, SSBG 200.0 nmol/l (less 110.0). Short-acting octreotide treatment resulted in normalization TSH and IGF-1. Thyroid ultrasound revealed single 5 mm nodule, increased thyroid volume - 20,5 ml. DEXA revealed no BMD loss. Lab investigations revealed no evidence on hyperparathyroidism: PTH and calcium levels were within the reference range. Due to the young age of the patient we chose a transnasal transsphenoid pituitary surgery as the first-line treatment. Postoperative histological investigation: pituitary adenoma. In the postoperative period levels of free T4 and T3 normalized, but the level of TSH remained slightly elevated - 3.7 mIU/l. One month after surgery, laboratory data revealed recurrence of hyperthyroidism, somatostatin analogue treatment was initiated.

Genetic investigation: Due to the evidence of familial case, a NGS was performed using the gene panel (MEN1, CDKN1B, PRKAR1A, GNAS, AIP, SDHA, SDHB, SDHC, SDHD, PRKCA, CDKN2C, CDKN2A, POU1F1, PTTG2), which revealed following changes: SDHA: NM_004168: exon8:c.G1002A:p.A334A, rs144252500, MAF 0.002; DICER1:NM_177438:exon2:c.A20G:p.Q7R, rs117358479, MAF 0.0035, more likely to be non-pathogenic.

Conclusion: GH/TSH secreting pituitary adenoma is very rare and could be associated with hereditary cause.