Elsevier

World Neurosurgery

Volume 97, January 2017, Pages 595-602
World Neurosurgery

Original Article
Long-Term Follow-Up of Primary Medical Versus Surgical Treatment of Prolactinomas in Men: Effects on Hyperprolactinemia, Hypogonadism, and Bone Health

https://doi.org/10.1016/j.wneu.2016.10.059Get rights and content

Objective

In men with prolactinomas, impaired bone density is the principle consequence of hyperprolactinemia-induced hypogonadism. Although dopamine agonists (DAs) are the first-line approach in prolactinomas, surgery can be considered in selected cases. In this study, we aimed to investigate the long-term control of hyperprolactinemia, hypogonadism, and bone health comparing primary medical and surgical therapy in men who had not had prior DA treatment.

Methods

This is a retrospective case-note study of 44 consecutive men with prolactinomas and no prior DAs managed in a single tertiary referral center. Clinical, biochemical, and radiologic response to the first-line approach were analyzed in the 2 cohorts.

Results

Mean age at diagnosis was 47 years (range, 22–78 years). The prevalence of hypogonadism was 86%, and 27% of patients had pathologic bone density at baseline. The primary therapeutic strategy was surgery for 34% and DAs for 66% of patients. Median long-term follow-up was 63 months (range, 17–238 months). Long-term control of hyperprolactinemia required DAs in 53% of patients with primary surgical therapy, versus 90% of patients with primary medical therapy (P = 0.02). Hypogonadism was controlled in 73% of patients. The prevalence of patients with pathologic bone density was 37% at last follow-up, with no differences between the 2 therapeutic cohorts (P = 0.48).

Conclusions

Despite control of hyperprolactinemia and hypogonadism in most patients independent of the primary treatment modality, the prevalence of impaired bone health status remains high, and osteodensitometry should be recommended.

Introduction

Prolactinoma is the most common hormone-secreting pituitary tumor; however, diagnosis in men is far less frequent than in women.1 Late diagnosis and, therefore, macroprolactinomas are more common in men probably because of the more subtle symptoms in comparison with women. Prevailing symptoms are usually related to hypogonadism, including decreased libido, azoospermia, and sometimes erectile dysfunction.2 Osteopenia or osteoporosis is considered to be the principle consequence of prolonged hyperprolactin-induced hypogonadism in men.3, 4 Gonadal steroid deprivation increases bone resorption leading to impaired bone mineral density.5 Data on the long-term control of hyperprolactinemia, hypogonadism, and bone health in men with prolactinomas treated either primarily surgically or primarily medically are limited because medical therapy with dopamine agonists (DAs) is considered the first-line approach in micro- and macroprolactinoma.6 In this study, we investigated the long-term control of hyperprolactinemia, hypogonadism, and bone health after either treatment.

Section snippets

Materials and Methods

We retrospectively evaluated the medical records of 44 consecutive men managed with primary medical therapy or surgical therapy at our institution between 1997 and 2010. Patients who met the inclusion criteria had not been treated with DAs prior to study entry and had documented long-term follow-up data (more than 12 months). All patients fulfilled the diagnostic criteria of a prolactin (PRL)-secreting pituitary adenoma (i.e., PRL levels >200 μg/L for macroprolactinomas and >30μg/L for

Patient Characteristics at Baseline

Patient allocation to the surgical or medical cohort did not show a significant selection bias for age, chief complaints, affected pituitary axes, bone health status, BMI, or median follow-up time. The number of microprolactinomas, macroprolactinomas, and tumors infiltrating the cavernous sinus was not significantly different between the medical and surgical cohorts (Table 1).

At baseline, serum PRL levels in patients with a macroadenoma were significantly higher than patients with a

Discussion

The main findings of this study can be summarized as follows. (1) After a mean follow-up of more than 7 years, PRL levels were within normal range in 86% of all patients, with persistent need for DAs in 53% of the patients with a primarily surgical approach and 90% of patients with a primarily medical approach. (2) The rate of hypogonadism significantly decreased in all patients; however, long-term testosterone substitution was required in 25% of them. (3) A pathologic bone health status

Conclusions

These data indicate that despite control of hyperprolactinemia and hypogonadism in most men independent of the primary treatment strategy, the prevalence of an impaired bone mineral density remains high, and as a result, osteodensitometry can be recommended.

Acknowledgments

The authors thank Edward R. Laws Jr., MD, FACS, Director, Pituitary and Neuroendocrine Center, Brigham & Women's Hospital, Boston, Massachusetts, USA, for his insightful suggestions, and Dr. Kush Kapur, Clinical Research Center, Boston Children's Hospital, Boston, Massachusetts, USA, for statistical advice.

References (38)

  • E.R. Laws et al.

    A benchmark for preservation of normal pituitary function after endoscopic transsphenoidal surgery for pituitary macroadenomas

    World Neurosurg

    (2016)
  • G. Raverot et al.

    Management of endocrine disease: clinicopathological classification and molecular markers of pituitary tumours for personalized therapeutic strategies

    Eur J Endocrinol

    (2014)
  • A. Ciccarelli et al.

    PRL secreting adenomas in male patients

    Pituitary

    (2005)
  • A. Colao et al.

    Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization

    Clin Endocrinol (Oxf)

    (2000)
  • G. Mazziotti et al.

    Vertebral fractures in males with prolactinoma

    Endocrine

    (2011)
  • M.R. Smith et al.

    Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer

    N Engl J Med

    (2001)
  • P. Iglesias et al.

    Prolactinomas in men: a multicentre and retrospective analysis of treatment outcome

    Clin Endocrinol (Oxf)

    (2012)
  • F.F. Casanueva et al.

    Guidelines of the Pituitary Society for the diagnosis and management of prolactinomas

    Clin Endocrinol (Oxf)

    (2006)
  • L. Andereggen et al.

    10-year follow-up study comparing primary medical vs. surgical therapy in women with prolactinomas

    Endocrine

    (2016)
  • A.M. Landolt et al.

    Perivascular fibrosis in prolactinomas: is it increased by bromocriptine?

    J Clin Endocrinol Metab

    (1984)
  • M. Menucci et al.

    Effect of dopaminergic drug treatment on surgical findings in prolactinomas

    Pituitary

    (2011)
  • W. Saeger et al.

    Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry

    Eur J Endocrinol

    (2007)
  • L. Andereggen et al.

    Selective inferior petrosal sinus sampling without venous outflow diversion in the detection of a pituitary adenoma in Cushing's syndrome

    Neuroradiology

    (2012)
  • J.P. Cottier et al.

    Cavernous sinus invasion by pituitary adenoma: MR imaging

    Radiology

    (2000)
  • M. Babey et al.

    Pituitary surgery for small prolactinomas as an alternative to treatment with dopamine agonists

    Pituitary

    (2011)
  • J.A. Wass

    When to discontinue treatment of prolactinoma?

    Nat Clin Pract Endocrinol Metab

    (2006)
  • A. Colao et al.

    Withdrawal of long-term cabergoline therapy for tumoral and nontumoral hyperprolactinemia

    N Engl J Med

    (2003)
  • X. Qu et al.

    Surgical outcomes and prognostic factors of transsphenoidal surgery for prolactinoma in men: a single-center experience with 87 consecutive cases

    Eur J Endocrinol

    (2011)
  • J. Kreutzer et al.

    Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients

    Eur J Endocrinol

    (2008)
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    Conflict of interest statement: This study is supported by the Swiss National Science Foundation (PBBEB-146099 and PBBEB-155299 to L. Andereggen).

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