O-03 DELAYED PUBERTY AND GIANT PROLACTINOMA IN A 14-YEAR-OLD GIRL WITH A HISTORY OF ANOREXIA NERVOSA
Authors: Kallio Markus , Martola Juha , Latvala Terho , Karppinen Atte , Kivipelto Leena , Tynninen Olli , Schildt Jukka , Salonen Pia , Holopainen Elina , Miettinen Päivi J , Matikainen Niina , Jäntti Camilla Schalin 
Published: January 2025

Introduction

Giant prolactinomas are rare, especially in children and adolescents and often resistant to the recommended first-line cabergoline monotherapy. In addition, possible second line guideline treatment recommendations (surgery, radiotherapy, temozolomide) are not suitable.

Clinical Case

A 14-year-old girl (51kg/155,7cm/BMI 18.4 kg/m2, bone age 14.37) was referred to pediatric endocrinologist because of primary amenorrhea and delayed puberty. Two years earlier, she underwent a brief episode of anorectic behavior (rapid weight loss of 15.4 kg) but recovered before the age of 14.

Results Clinical examination was normal, excluding Tanner stage M2P3. No galactorrhea was evident. Laboratory work-up revealed hyperprolactinemia (S-PRL 26 817 mU/l (86-324)). Estradiol and gonadotropins were consistent with the pubertal stage (S-Estdiol 0.02 nmol/l; S-FSH 3.2 U/l, S-LH &lt;1.0 U/l). Thyroid function and cortisol secretion (P-Corsol 411 nmol/l, P-ACTH 21 ng/l) were normal, but S-TPOAb elevated at 350 kU/l (&lt;34 kU/l). Genetic testing for AIP, MEN1, GNAS1, MAX, SDHA, SDHC, SDHD, SDHAF2, PRKAR1a mutations was negative. Abdominal ultrasound revealed a small uterus. Brain MRI showed a giant prolactinoma, (21x30x40 mm; Fig. 1A) which extended to the dorsum sellae, infiltrated the left cavernous sinus, filled the suprasellar cistern compressed the optic chiasm. Neuro-ophthalmological examination; visual acuity, fields was normal.

Prolactin level was repeatedly high (30 210 mU/l; 78% (23 672 mU/l) biologically active. The patient was put on cabergoline (0,5mg/week) and the dose was doubled one month later as the prolactin remained high (14 509 mU/l). Tumor size was unchanged on 4 months follow-up MRI. The case was discussed at the multidisciplinary pituitary tumor board. Neither surgery nor radiotherapy were recommended and temozolomide was unsuitable. Cabergoline was increased to 1,5mg/week.

At 5 months, the patient had primary hypothyroidism (P-TSH 5,00 mU/l, free-T4 11; S-PRL 4509 mU/l) and was put on L-T4 (50µg/day). 11C-methionine PET/MRI demonstrated significant uptake throughout the tumor tissue. Tumor size had decreased slightly. Cabergoline was increased to 3mg/week; 11 months after initiation of the treatment, S-PRL had decreased to 4800mU/l. Though no clinical signs of puberty were evident, estradiol and gonadotropin levels had risen (S-Estdiol 0.21 nmol/l, LH 18 IU/l, FSH 7.4 IU/l). Cabergoline was increased to 3.5mg/week. After 13 months of treatment, S-PRL was 3523, S-Estdiol 0.08, FSH 5.9, LH 7.7, TSH 0.08, free-T4 17. Cabergoline was increased to 4mg/week. Next examination, including MRI and laboratory tests, is scheduled 2 months later.

Conclusion

Treatment of adolescents with giant prolactinoma is challenging. There is an unmet need for second line tailored treatments, such as combined D2 and SST2&5 receptor agonist therapy (cabergoline+pasireotide), which, for this case, is the planned second line experimental treatment.Figure 1: