Growth hormone and prolactin-staining tumors causing acromegaly: a retrospective review of clinical presentations and surgical outcomes

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OBJECTIVE

Acromegaly results in disfiguring growth and numerous medical complications. This disease is typically caused by growth hormone (GH)–secreting pituitary adenomas, which are treated first by resection, followed by radiation and/or medical therapy if needed. A subset of acromegalics have dual-staining pituitary adenomas (DSPAs), which stain for GH and prolactin. Presentations and treatment outcomes for acromegalics with DSPAs are not well understood.

METHODS

The authors retrospectively reviewed the records of more than 5 years of pituitary adenomas resected at their institution. Data were collected on variables related to clinical presentation, tumor pathology, radiological size, and disease recurrence. The Fisher’s exact test, ANOVA, Student t-test, chi-square test, and Cox proportional hazards and multiple logistic regression were used to measure statistical significance.

RESULTS

Of 593 patients with pituitary adenoma, 91 presented with acromegaly. Of these 91 patients, 69 (76%) had tumors that stained for GH only (single-staining somatotrophic adenomas [SSAs]), while 22 (24%) had tumors that stained for GH and prolactin (DSPAs). Patients with DSPAs were more likely to present with decreased libido (p = 0.012), signs of acromegalic growth (p = 0.0001), hyperhidrosis (p = 0.0001), and headaches (p = 0.043) than patients with SSAs. DSPAs presented with significantly higher serum prolactin (60.7 vs 10.0 µg/L, p = 0.0002) and insulin-like growth factor-1 (IGF-1) (803.6 vs 480.0 ng/ml, p = 0.0001), and were more likely to have IGF-1 levels > 650 ng/ml (n = 13 [81.3%] vs n = 6 [21.4%], p = 0.0001) than patients with SSAs despite similar sizes (1.8 vs 1.7 cm, p = 0.5). Patients with DSPAs under 35 years of age were more likely to have a recurrence (n = 4 [50.0%] vs n = 3 [11.1%], p = 0.01) than patients with SSAs under the age of 35. DSPA patients were less likely to achieve remission with surgery than SSA patients (n = 2 [20%] vs n = 19 [68%], p = 0.01). Univariate analysis identified single-staining tumors (p = 0.02), gross-total resection (p = 0.02), and tumor diameter (p = 0.05) as predictors of surgical remission. Multiple logistic regression demonstrated that SSAs (p = 0.04) were independently associated with surgical remission of acromegaly. Kaplan-Meier analysis revealed that DSPAs had more time until disease remission (p = 0.033).

CONCLUSIONS

Acromegalics with tumors that stain for prolactin and GH, which represented almost a quarter of acromegalics in this cohort, had more aggressive clinical presentations and postoperative outcomes than SSAs. Prolactin staining provides useful information for acromegalics undergoing pituitary surgery.

ABBREVIATIONS ACTH = adrenocorticotropic hormone; DSPA = dual-staining pituitary adenoma; GH = growth hormone; IGF-1 = insulin-like growth factor-1; OR = odds ratio; SSA = single-staining somatotrophic adenoma.

Article Information

Correspondence Manish K. Aghi: California Center for Pituitary Disorders, University of California, San Francisco, CA. aghim@neurosurg.ucsf.edu.

INCLUDE WHEN CITING Published online September 14, 2018; DOI: 10.3171/2018.4.JNS18230.

J.R. and A.J. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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Figures

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    Representative immunostaining of a DSPA. Shown is an example of a DSPA that exhibited robust immunostaining for human GH (A) and prolactin (B). Bar = 80 μm. Figure is available in color online only.

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    Kaplan-Meier analysis of disease remission by prolactin immunohistochemistry. Time (in months) until patients achieve biochemical disease remission with single-staining tumors (solid line) compared to dual-staining tumors (dashed line; p = 0.033).

References

  • 1

    Abu Dabrh AMMohammed KAsi NFarah WHWang ZFarah MH: Surgical interventions and medical treatments in treatment-naïve patients with acromegaly: systematic review and meta-analysis. J Clin Endocrinol Metab 99:400340142014

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2

    Al-Brahim NYYAsa SL: My approach to pathology of the pituitary gland. J Clin Pathol 59:124512532006

  • 3

    Arafah BMNasrallah MP: Pituitary tumors: pathophysiology, clinical manifestations and management. Endocr Relat Cancer 8:2873052001

  • 4

    Chanson PSalenave SKamenicky P: Acromegaly. Handb Clin Neurol 124:1972192014

  • 5

    Cheng JSSalinas RMolinaro AChang EFKunwar SBlevins L: A predictive algorithm for evaluating elevated serum prolactin in patients with a sellar mass. J Clin Neurosci 22:1551602015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Giustina AChanson PKleinberg DBronstein MDClemmons DRKlibanski A: Expert consensus document: A consensus on the medical treatment of acromegaly. Nat Rev Endocrinol 10:2432482014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Halmi NS: Occurrence of both growth hormone- and prolactin-immunoreactive material in the cells of human somatotropic pituitary adenomas containing mammotropic elements. Virchows Arch A Pathol Anat Histopathol 398:19311982

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Huan CCui GRen Z: The characteristics of acromegalic patients with hyperprolactinemia and the differences with hyperprolactinemia patients. Pak J Pharm Sci 28 (2 Suppl):7137182015

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Jiang XZhang X: The molecular pathogenesis of pituitary adenomas: an update. Endocrinol Metab (Seoul) 28:2452542013

  • 10

    Katznelson LLaws ER JrMelmed SMolitch MEMurad MHUtz A: Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 99:393339512014

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Lloyd RVCano MChandler WFBarkan ALHorvath EKovacs K: Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization. Am J Pathol 134:6056131989

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Manuylova ECalvi LMHastings CVates GEJohnson MDCave WT Jr: Late presentation of acromegaly in medically controlled prolactinoma patients. Endocrinol Diabetes Metab Case Rep 2016:16-00692016

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Mao ZGHe DSZhou JYao BXiao WWChen CH: Differential expression of microRNAs in GH-secreting pituitary adenomas. Diagn Pathol 5:792010

  • 14

    Muhammad Avan der Lely AJNeggers SJCMM: Review of current and emerging treatment options in acromegaly. Neth J Med 73:3623672015

  • 15

    Rahman MJusué-Torres IAlkabbani ASalvatori RRodríguez FJQuinones-Hinojosa A: Synchronous GH- and prolactin-secreting pituitary adenomas. Endocrinol Diabetes Metab Case Rep 2014:1400522014

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Robert FPelletier GSerri OHardy J: Mixed growth hormone and prolactin-secreting human pituitary adenomas: a pathologic, immunocytochemical, ultrastructural, and immunoelectron microscopic study. Hum Pathol 19:132713341988

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Rowland NCAghi MK: Radiation treatment strategies for acromegaly. Neurosurg Focus 29(4):E122010

  • 18

    Wang MMou CJiang MHan LFan SHuan C: The characteristics of acromegalic patients with hyperprolactinemia and the differences in patients with merely GH-secreting adenomas: clinical analysis of 279 cases. Eur J Endocrinol 166:7978022012

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

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