Mutations of PROP1 are the most frequent genetic defect in non-syndromic combined pituitary hormone insufficiency and are characterized by growth hormone (GH), prolactin, TSH, and gonadotropin deficiency.
A 3-year-and-3-month-old girl was referred with growth retardation and abnormal thyroid function tests. She was born full-term weighing 3200 g and had no significant medical or family history. Body weight was 10.9 kg (-2.54 SDS), height 80.4 cm (-3.38 SDS), and head circumference was 48.3 cm (-0.57 SDS). Systemic examination was normal and her pubertal development was consistent with Tanner stage 1.
The laboratory workup showed TSH 1.99 μIU/mL (0.4-5.0 μIU/mL), fT3 2.66 pg/mL (1.57-4.71 pg/mL), fT4 0.62 ng/dL (0.8-1.9 ng/dL), and cortisol 6.42 μg/dL (5-25 μg/dL). Celiac antibodies were negative. Pituitary MRI was reported to be normal. L-thyroxine therapy was started with the diagnosis of central hypothyroidism. While euthyroid, the stimulation tests showed insufficient GH response and normal cortisol response thus GH therapy was initiated. At the age of 12 years and 6 months (bone age 12 years), serum prolactin, follicle-stimulating hormone, and luteinizing hormone (LH) levels were found to be 2.15 ng/mL (3.8-26.7 ng/mL), 0.31 mIU/L, and 0.27 mIU/L. Results of LHRH test was consistent with hypogonadotropic hypogonadism (peak LH 0.4 mIU/L) and estrogen therapy was started. Low-dose adrenocorticotropic hormone test was performed because of low basal cortisol. Cortisol response was insufficient and hydrocortisone treatment was added with the diagnosis of central adrenal insufficiency. Repeated MRI showed a pituitary length of 4 mm. PROP1 analysis revealed a previously reported, homozygous c.301_302delAG (p.Leu102Cysfs*8) mutation.
Mutations of the PROP1 primarily affects thyrotroph, lactotroph, gonadotroph, and somatotroph cells. Adrenocorticotropic hormone deficiency is variable. Genetic analysis is important for identification of etiology.