Background: Prolonged severe hypothyroidism due to Hashimoto’s thyroiditis (HT) is a rare cause of pituitary hyperplasia (PH) in children. Loss of thyroxine negative feedback causes a TRH-dependent hyperplasia of pituitary thyrotroph cells resulting in adenohypophysis enlargement. A transdifferentiation of pituitary somatotroph cells into thyrotroph cells could explain growth failure in those patients. We report a case series of patients with growth impairment diagnosed with PH due to severe acquired hypothyroidism in which evaluation of anterior pituitary function at diagnosis was performed.
Cases: Ten Caucasian patients (6 females – 4 males) were evaluated in 4 Centre of Peadiatric Endocrinology because of growth arrest (in 70% of patients) or growth impairment. Median age, height and BMI at diagnosis of HT were 11 years (IQR 8 – 14.8), - 2.0 SDS (-3.58 – 0.78) and 1.12 SDS (0 – 3.1), respectively. Difference between the median values of height and target height was 1.5 SDS. Median bone age retardation was 2.5 years (0 – 5.1). No goiter was documented. Brain MRI, performed to exclude intracranial expansive lesions, documented adenohypophysis enlargement in all of children. Median pituitary volume was 650 mm3 (504 - 1965). Hypothyroidism due to HT was confirmed in the entire cohort by biochemical evaluation (median and IQR: TSH 981 mIU/l, 236.6 – 1648; FT4 3.1 pmol/l, 0.5 - 6.2; antibodies to thyroid peroxidase 809 IU/ml, 88.8 – 4480; antibodies to thyroglobulin 352 IU/ml, 15.5 - 2040) and ultrasound evaluation [reduced (40%) or normal (60%) thyroid volume associated with diffusely hypoechogenic, coarse and heterogeneous parenchymal echotexture]. Levothyroxine treatment (2 mg/kg/day, 1.5 - 3.5) was started. Other basal hormonal evaluation demonstrated hyperprolactinemia (60%) and low concentrations of cortisol (40%). IGF-1 was lower than - 2 SDS in 50% of patients; those two patients underwent stimulation test growth hormone was subnormal. Furthermore, 70% of them had high total and LDL-cholesterol levels and 50% showed high triglycerides and transaminases levels.
Conclusions: Since thyroid hormones promote GH biosynthesis, in severe primary hypothyroidism GH deficiency could be expected proportional to the hypothyroidism degree. However, in some hypothyroid patients IGF-1 concentration may be within normal range even though they have growth arrest. This is the largest pediatric cohort with PH due to severe HT in which growth arrest was the most evident presenting sign. Atrophic HT phenotype might be correlated with this specific clinical presentation. Prospective studies are needed to evaluate pituitary enlargement and thyroid volume in patients with extremely high TSH without goiter.
22 Sep 2021 - 26 Sep 2021