Diagnosis and Treatment > Signs and Symptoms
Search for other papers by Melissa H Lee in
Google Scholar
PubMed
Search for other papers by Penelope McKelvie in
Google Scholar
PubMed
Search for other papers by Balasubramanian Krishnamurthy in
Google Scholar
PubMed
Search for other papers by Yi Yuen Wang in
Google Scholar
PubMed
Search for other papers by Carmela Caputo in
Google Scholar
PubMed
Summary
Most cases of acromegaly are due to growth hormone (GH)-secreting pituitary adenomas arising from somatotroph cells. Mixed pituitary adenoma and gangliocytoma tumours are rare and typically associated with hormonal hypersecretion, most commonly GH excess. Differentiating these mixed tumours from conventional pituitary adenomas can be difficult pre-operatively, and careful histological analysis after surgical resection is key to differentiating the two entities. There is little literature addressing the possible mechanisms for the development of mixed pituitary adenoma–gangliocytomas; however, several hypotheses have been proposed. It still remains unclear if these mixed tumours differ from a clinical perspective to pituitary adenomas; however, the additional neural component of the gangliocytoma does not appear to modify the aggressiveness or risk of recurrence after surgical resection. We report a unique case of acromegaly secondary to a mixed GH-secreting pituitary adenoma, co-existing with an intrasellar gangliocytoma.
Learning points:
-
Acromegaly due to a mixed GH-secreting pituitary adenoma and intrasellar gangliocytoma is rare.
-
These mixed tumours cannot be distinguished easily from ordinary pituitary adenomas on the basis of clinical, endocrine or neuroradiologic findings, and histological analysis is required for a definitive diagnosis.
-
Surgical resection is usually sufficient to provide cure, without the need for adjuvant therapy.
-
These mixed tumours appear to have a good prognosis although the natural history is not well defined.
-
The pathogenesis of these mixed tumours remains debatable, and ongoing research is required.
Search for other papers by Ekaterina Manuylova in
Google Scholar
PubMed
Search for other papers by Laura M Calvi in
Google Scholar
PubMed
Search for other papers by Catherine Hastings in
Google Scholar
PubMed
Search for other papers by G Edward Vates in
Google Scholar
PubMed
Search for other papers by Mahlon D Johnson in
Google Scholar
PubMed
Search for other papers by William T Cave Jr in
Google Scholar
PubMed
Search for other papers by Ismat Shafiq in
Google Scholar
PubMed
Summary
Co-secretion of growth hormone (GH) and prolactin (PRL) from a single pituitary adenoma is common. In fact, up to 25% of patients with acromegaly may have PRL co-secretion. The prevalence of acromegaly among patients with a newly diagnosed prolactinoma is unknown. Given the possibility of mixed GH and PRL co-secretion, the current recommendation is to obtain an insulin-like growth factor-1 (IGF-1) in patients with prolactinoma at the initial diagnosis. Long-term follow-up of IGF-1 is not routinely done. Here, we report two cases of well-controlled prolactinoma on dopamine agonists with the development of acromegaly 10–20 years after the initial diagnoses. In both patients, a mixed PRL/GH-cosecreting adenoma was confirmed on the pathology examination after transsphenoidal surgery (TSS). Therefore, periodic routine measurements of IGF-1 should be considered regardless of the duration and biochemical control of prolactinoma.
Learning points:
-
Acromegaly can develop in patients with well-controlled prolactinoma on dopamine agonists.
-
The interval between prolactinoma and acromegaly diagnoses can be several decades.
-
Periodic screening of patients with prolactinoma for growth hormone excess should be considered and can lead to an early diagnosis of acromegaly before the development of complications.
Search for other papers by Taiba Zornitzki in
Google Scholar
PubMed
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Search for other papers by Hadara Rubinfeld in
Google Scholar
PubMed
Search for other papers by Lyudmila Lysyy in
Google Scholar
PubMed
Search for other papers by Tal Schiller in
Google Scholar
PubMed
Search for other papers by Véronique Raverot in
Google Scholar
PubMed
Sackler School of Medicine, Tel-Aviv University, Tel Aviv, 69978, Israel
Search for other papers by Ilan Shimon in
Google Scholar
PubMed
Search for other papers by Hilla Knobler in
Google Scholar
PubMed
Summary
Acromegaly due to ectopic GHRH secretion from a neuroendocrine tumor (NET) is rare and comprises <1% of all acromegaly cases. Herein we present a 57-year-old woman with clinical and biochemical features of acromegaly and a 6 cm pancreatic NET (pNET), secreting GHRH and calcitonin. Following surgical resection of the pancreatic tumor, IGF1, GH and calcitonin normalized, and the clinical features of acromegaly improved. In vitro studies confirmed that the tumor secreted large amounts of both GHRH and calcitonin, and incubation of pNET culture-derived conditioned media stimulated GH release from a cultured human pituitary adenoma. This is a unique case of pNET secreting both GHRH and calcitonin. The ability of the pNET-derived medium to stimulate in vitro GH release from a human pituitary-cell culture, combined with the clinical and hormonal remission following tumor resection, confirmed the ectopic source of acromegaly in this patient.
Learning points
-
Signs, symptoms and initial work-up of acromegaly due to ectopic GHRH secretion are similar to pituitary-dependent acromegaly. However, if no identifiable pituitary lesion is found, somatostatin receptor scan and further imaging (CT, MRI) should be performed.
-
Detection of GHRH in the blood and in the tumor-derived medium supports the diagnosis of ectopic GHRH secretion.
-
Functional bioactivity of pNET-secreted GHRH can be proved in vitro by releasing GH from human pituitary cells.
