Case Report: Multiple prolactinomas in a young man with Kallmann syndrome and familial hypocalciuric hypercalcemia

Front Endocrinol (Lausanne). 2023 Oct 30:14:1248231. doi: 10.3389/fendo.2023.1248231. eCollection 2023.

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.

Keywords: Kallmann syndrome; familial hypocalciuric hypercalcemia; hypogonadism; prolactinoma; sex hormones.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Gonadal Steroid Hormones
  • Gonadotropin-Releasing Hormone
  • Humans
  • Hypercalcemia* / diagnosis
  • Hyperparathyroidism*
  • Hypogonadism* / diagnosis
  • Kallmann Syndrome* / complications
  • Kallmann Syndrome* / diagnosis
  • Kallmann Syndrome* / drug therapy
  • Male
  • Mice
  • Pituitary Neoplasms* / complications
  • Pituitary Neoplasms* / diagnosis
  • Pituitary Neoplasms* / drug therapy
  • Prolactinoma* / complications
  • Prolactinoma* / diagnosis
  • Prolactinoma* / drug therapy
  • Testosterone

Substances

  • Gonadotropin-Releasing Hormone
  • Testosterone
  • Gonadal Steroid Hormones

Supplementary concepts

  • Hypocalciuric hypercalcemia, familial, type 1

Grants and funding

The research work was partly funded by the Slovenian research agency project P3-0298. The planning and conduction of the study, the interpretation of data, and the writing of the present manuscript are completely independent of the funder.