AUTHOR=Jensterle Mojca , Janež Andrej , Vipotnik Vesnaver Tina , Debeljak Maruša , Breznik Nika , Trebušak Podkrajšek Katarina , Herman Rok , Fliers Eric , Battelino Tadej , Avbelj Stefanija Magdalena TITLE=Case Report: Multiple prolactinomas in a young man with Kallmann syndrome and familial hypocalciuric hypercalcemia JOURNAL=Frontiers in Endocrinology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1248231 DOI=10.3389/fendo.2023.1248231 ISSN=1664-2392 ABSTRACT=Introduction

The occurrence of prolactinomas in sex hormone treated patients with central hypogonadism is extremely rare.

Case presentation

We present a Caucasian male patient who was diagnosed with Kallmann syndrome (KS) at age 15 years. Testosterone treatment was started. At age 26 the patient presented with mild headache. MRI revealed two separate pituitary adenomas along with the absence of the olfactory bulbs. Given the presence of marked hyperprolactinemia (17x upper limit of the reference range) the diagnosis prolactinoma was made and treatment with cabergoline was started which resulted in a complete biochemical response and in marked reduction of both adenomas in size. Hypogonadism persisted and testosterone replacement therapy was continued. Genetic testing of genes associated with pituitary tumors, Kallmann syndrome and idiopathic hypogonadotropic hypogonadism was negative. Mild concomitant hypercalcemia in accordance with familial hypocalciuric hypercalcemia (FHH) prompted mutation analysis of the calcium receptor (CASR) gene which yielded a pathogenic inactivating variant.

Discussion/conclusion

The presence of two separate prolactinomas in a patient with KS has not yet been reported in the literature. The effect of sex hormone treatment of KS patients on the possible development of prolactinoma is unknown at present. The occurance of multiple prolactinomas in our patient suggests increased susceptibility. Although CaSR is expressed in GnRH neurons in mouse brain and CaSR deficient mice have a reduced hypothalamic GnRH neuronal population, the relevance of the CASR gene variant in our patient for the KS phenotype is unclear at present.