Elsevier

World Neurosurgery

Volume 114, June 2018, Pages e158-e164
World Neurosurgery

Original Article
Plurihormonal ACTH-GH Pituitary Adenoma: Case Report and Systematic Literature Review

https://doi.org/10.1016/j.wneu.2018.02.120Get rights and content

Highlights

  • Plurihormonal adenomas represent 10%–15% of all functioning pituitary adenomas.

  • Functioning ACTH-GH pituitary adenomas constitute an extremely rare entity, with only 20 previously reported cases.

  • Most patients present with clinically manifested acromegaly and subclinical Cushing's disease.

  • We report a case of rare ACTH-GH pituitary adenoma, with clinical signs of both acromegaly and Cushing's disease, along with the results of our systematic review of the literature.

Background

Plurihormonal adenomas (PHAs) represent 10%–15% of all functioning pituitary adenomas. The most frequent hormonal associations are with prolactin and growth hormone (GH). Here we describe a rare case of functional adrenocorticotropic hormone (ACTH) and GH microadenoma and report our findings from a systematic literature review of PHA.

Methods

We searched PubMed using the terms “plurihormonal pituitary adenoma,” “ACTH GH pituitary adenoma,” and “acromegaly AND Cushing's disease”. In the 17 articles that were selected for literature review, only 20% (4/20) of patients presented with clinical signs of both diseases. Histologically, 19 were pituitary adenomas composed of two distinct cell populations, while only in 1 case was there evidence of a single cell producing both ACTH and GH. In the case reported here, a 60-year-old woman was incidentally diagnosed with a pituitary microadenoma. Endocrine assessment documented increased levels of insulin-like growth factor 1 and GH; ACTH and cortisol values were within normal ranges. Echocardiography documented ventricular hypertrophy. Because of clinical and biochemical evidence of acromegaly, surgery was recommended. Postoperatively, hormonal replacement therapy was started because of adrenal insufficiency. Her antihypertensive therapy was discontinued due to evidence of normal blood pressure values. Histological examination revealed an ACTH-GH PHA with 2 distinct populations of secreting cells. At 3-year follow-up, the patient showed stable clinical remission and was no longer receiving hormonal replacement therapy.

Conclusions

This is an additional case to the 20 previously reported cases of ACTH-GH PHA. Awareness of this relatively rare entity is clinically relevant. The cytogenesis of ACTH-GH PHA remains a matter of debate, and several hypotheses have been postulated.

Introduction

Pituitary adenomas are usually benign, monoclonal tumors arising from adenohypophyseal cells.1, 2 They represent approximately 15% of all intracranial tumors.2 Functioning pituitary adenomas, the most frequent type, produce clinical syndromes due to pituitary hormonal oversecretion and/or a mass effect.1 The large majority of functioning pituitary adenomas exhibits single hormone production, but the introduction of immunocytochemical analysis has revealed the existence of pituitary lesions with multiple hormonal expression.3 Histologically, plurihormonal pituitary adenomas (PHAs) represent 10%–15% of all pituitary tumors4 (up to 1% of pituitary lesions in unselected autopsy series), but only a small number clinically secrete multiple hormones.5, 6 The most frequent associations are with prolactin (PRL) and growth hormone (GH), and other molecular combinations are rare.5, 7

Here we report a case of a patient with a functioning adrenocorticotropic hormone (ACTH)-GH pituitary adenoma, along with the results of a systematic literature review of PHA.

Section snippets

Systematic Literature Review

The literature review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and PRISMA checklist (Figure 1). We searched PubMed from May 1972 to October 2017 for published articles with the search terms “(plurihormonal OR ACTH and GH) adenoma” and pertinent variations; a language restriction to English papers was applied.

Case Presentation

A 60-year-old female was referred to our pituitary clinic (Spedali Civili, Brescia, Italy) with a diagnosis of a

Systematic Literature Review

On the initial PubMed search, a total of 1234 articles were retrieved, including 692 with “ACTH GH pituitary adenoma,” 396 with “acromegaly AND Cushing's disease,” and 146 with “plurihormonal pituitary adenoma.” After removal of duplicates, 662 articles remained. Of the 35 full-text articles that were selected, 1 was excluded for language constraints (Chinese) (Figure 1).

After full-text evaluation, 17 studies, with a total of 20 patients (13 females and 7 males; mean age, 48 years; range, 5–78

Discussion

PHAs are rare tumors that exhibit cellular immunoreactivity for more than 1 pituitary hormone. Some studies have suggested a prevalence as high as 31%–36% in surgically removed tumors.22 Histologically, PHAs are subclassified as monomorphous (i.e., different hormones expressed from a single morphological cell type) or plurimorphous (i.e., different hormones are expressed by morphologically divergent cells).7

Our PubMed systematic review of the 662 initially screened articles identified only 20

Conclusions

ACTH-GH PHAs are rare entities. Our systematic literature review documented only 20 cases reported to date. Of these, only 4 (20%) presented with clinical signs of both acromegaly and Cushing's disease. We report an additional case in which signs of both conditions were subtle but present.

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    Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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