Clinical Overview > Hormone > Gastrin

You are looking at 1 - 4 of 4 items

Aisha A Tepede Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Aisha A Tepede in
Google Scholar
PubMed
Close
,
James Welch Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by James Welch in
Google Scholar
PubMed
Close
,
Maya Lee Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Maya Lee in
Google Scholar
PubMed
Close
,
Adel Mandl Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Adel Mandl in
Google Scholar
PubMed
Close
,
Sunita K Agarwal Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Sunita K Agarwal in
Google Scholar
PubMed
Close
,
Naris Nilubol National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Naris Nilubol in
Google Scholar
PubMed
Close
,
Dhaval Patel National Cancer Institute (NCI), National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Dhaval Patel in
Google Scholar
PubMed
Close
,
Craig Cochran Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Craig Cochran in
Google Scholar
PubMed
Close
,
William F Simonds Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by William F Simonds in
Google Scholar
PubMed
Close
,
Lee S Weinstein Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Lee S Weinstein in
Google Scholar
PubMed
Close
,
Abhishek Jha Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Abhishek Jha in
Google Scholar
PubMed
Close
,
Corina Millo Clinical Center PET Department (CC PET), National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Corina Millo in
Google Scholar
PubMed
Close
,
Karel Pacak Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD), National Institutes of Health, Bethesda, Maryland, USA

Search for other papers by Karel Pacak in
Google Scholar
PubMed
Close
, and
Jenny E Blau Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)

Search for other papers by Jenny E Blau in
Google Scholar
PubMed
Close

Summary

Pheochromocytoma (PHEO) in multiple endocrine neoplasia type 1 (MEN1) is extremely rare. The incidence is reported as less than 2%. We report a case of a 76-year-old male with familial MEN1 who was found to have unilateral PHEO. Although the patient was normotensive and asymptomatic, routine screening imaging with CT demonstrated bilateral adrenal masses. The left adrenal mass grew from 2.5 to 3.9 cm over 4 years with attenuation values of 9 Hounsfield units (HU) pre-contrast and 15 HU post-contrast washout. Laboratory evaluation demonstrated an adrenergic biochemical phenotype. Both 18F-fluorodeoxyglucose (18F-FDG) PET/CT and 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy demonstrated bilateral adrenal uptake. In contrast, 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT demonstrated unilateral left adrenal uptake (28.7 standardized uptake value (SUV)) and physiologic right adrenal uptake. The patient underwent an uneventful left adrenalectomy with pathology consistent for PHEO. Post-operatively, he had biochemical normalization. A review of the literature suggests that adrenal tumors >2 cm may be at higher risk for pheochromocytoma in patients with MEN1. Despite a lack of symptoms related to catecholamine excess, enlarging adrenal nodules should be biochemically screened for PHEO. 18F-FDOPA PET/CT may be beneficial for localization in these patients.

Learning points:

  • 18F-FDOPA PET/CT is a beneficial imaging modality for identifying pheochromocytoma in MEN1 patients.

  • Adrenal adenomas should undergo routine biochemical workup for PHEO in MEN1 and can have serious peri-operative complications if not recognized, given that MEN1 patients undergo frequent surgical interventions.

  • MEN1 is implicated in the tumorigenesis of PHEO in this patient.

Open access
Bernardo Marques Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Bernardo Marques in
Google Scholar
PubMed
Close
,
Raquel G Martins Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Raquel G Martins in
Google Scholar
PubMed
Close
,
Guilherme Tralhão Surgery Department, Centro Hospitalar e Universitário de Coimbra, EPE, Coimbra, Portugal

Search for other papers by Guilherme Tralhão in
Google Scholar
PubMed
Close
,
Joana Couto Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Joana Couto in
Google Scholar
PubMed
Close
,
Sandra Saraiva Gastroenterology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Sandra Saraiva in
Google Scholar
PubMed
Close
,
Henrique Ferrão Surgery Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Henrique Ferrão in
Google Scholar
PubMed
Close
,
João Ribeiro Oncology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by João Ribeiro in
Google Scholar
PubMed
Close
,
Jacinta Santos Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Jacinta Santos in
Google Scholar
PubMed
Close
,
Teresa Martins Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Teresa Martins in
Google Scholar
PubMed
Close
,
Ana Teresa Cadime Gastroenterology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Ana Teresa Cadime in
Google Scholar
PubMed
Close
, and
Fernando Rodrigues Endocrinology Department, Instituto Português de Oncologia de Coimbra Franscisco Gentil, EPE, Coimbra, Portugal

Search for other papers by Fernando Rodrigues in
Google Scholar
PubMed
Close

Summary

Gastric neuroendocrine neoplasms (GNENs) are classified into three types according to their aetiology. We present a clinical case of a female patient of 66 years and a well-differentiated (grade 2), type 3 GNEN with late liver metastasis (LM). The patient underwent surgical excision of a gastric lesion at 50 years of age, without any type of follow-up. Sixteen years later, she was found to have a neuroendocrine tumour (NET) metastatic to the liver. The histological review of the gastric lesion previously removed confirmed that it was a NET measuring 8 mm, pT1NxMx (Ki67 = 4%). 68Ga-DOTANOC PET/CT reported two LM and a possible pancreatic tumour/gastric adenopathy. Biopsies of the lesion were repeatedly inconclusive. She had a high chromogranin A, normal gastrin levels and negative anti-parietal cell and intrinsic factor antibodies, which is suggestive of type 3 GNEN. She underwent total gastrectomy and liver segmentectomies (segment IV and VII) with proven metastasis in two perigastric lymph nodes and both with hepatic lesions (Ki67 = 5%), yet no evidence of local recurrence. A 68Ga-DOTANOC PET/CT was performed 3 months after surgery, showing no tumour lesions and normalisation of CgA. Two years after surgery, the patient had no evidence of disease. This case illustrates a rare situation, being a type 3, well-differentiated (grade 2) GNEN, with late LM. Despite this, it was possible to perform surgery with curative intent, which is crucial in these cases, as systemic therapies have limited efficacy. We emphasise the need for extended follow-up in these patients.

Learning points:

  • GNENs have a very heterogeneous biological behaviour.

  • Clinical distinction between the three types of GNEN is essential to plan the correct management strategy.

  • LMs are rare and more common in type 3 and grade 3 GNEN.

  • Adequate follow-up is crucial for detection of disease recurrence.

  • Curative intent surgery is the optimal therapy for patients with limited and resectable LM, especially in well-differentiated tumours (grade 1 and 2).

Open access
Shinsuke Uraki The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Close
,
Hiroyuki Ariyasu The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Close
,
Asako Doi The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Asako Doi in
Google Scholar
PubMed
Close
,
Hiroto Furuta The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroto Furuta in
Google Scholar
PubMed
Close
,
Masahiro Nishi The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Masahiro Nishi in
Google Scholar
PubMed
Close
,
Takeshi Usui Department of Medical Genetics, Shizuoka General Hospital, Shizuoka City, Japan

Search for other papers by Takeshi Usui in
Google Scholar
PubMed
Close
,
Hiroki Yamaue The 2nd Department of Surgery, Wakayama Medical University, Wakayama, Japan

Search for other papers by Hiroki Yamaue in
Google Scholar
PubMed
Close
, and
Takashi Akamizu The 1st Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan

Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Close

Summary

A 54-year-old man had gastrinoma, parathyroid hyperplasia and pituitary tumor. His family history indicated that he might have multiple endocrine neoplasia type 1 (MEN1). MEN1 gene analysis revealed a heterozygous germline mutation (Gly156Arg). Therefore, we diagnosed him with MEN1. Endocrinological tests revealed that his serum prolactin (PRL) and plasma adrenocorticotropic hormone (ACTH) levels were elevated to 1699 ng/mL and 125 pg/mL respectively. Immunohistochemical analysis of the resected pancreatic tumors revealed that the tumors did not express ACTH. Overnight 0.5 and 8 mg dexamethasone suppression tests indicated that his pituitary tumor was a PRL-ACTH-producing plurihormonal tumor. Before transsphenoidal surgery, cabergoline was initiated. Despite no decrease in the volume of the pituitary tumor, PRL and ACTH levels decreased to 37.8 ng/mL and 57.6 pg/mL respectively. Owing to the emergence of metastatic gastrinoma in the liver, octreotide was initiated. After that, PRL and ACTH levels further decreased to 5.1 ng/mL and 19.7 pg/mL respectively. He died from liver dysfunction, and an autopsy of the pituitary tumor was performed. In the autopsy study, histopathological and immunohistochemical (IHC) analysis showed that the tumor was single adenoma and the cells were positive for ACTH, growth hormone (GH), luteinizing hormone (LH) and PRL. RT-PCR analysis showed that the tumor expressed mRNA encoding all anterior pituitary hormones, pituitary transcription factor excluding estrogen receptor (ER) β, somatostatin receptor (SSTR) 2, SSTR5 and dopamine receptor D (D2R). PRL-ACTH-producing tumor is a very rare type of pituitary tumor, and treatment with cabergoline and octreotide may be useful for controlling hormone levels secreted from a plurihormonal pituitary adenoma, as seen in this case of MEN1.

Learning points:

  • Although plurihormonal pituitary adenomas were reported to be more frequent in patients with MEN1 than in those without, the combination of PRL and ACTH is rare.

  • RT-PCR analysis showed that the pituitary tumor expressed various pituitary transcription factors and IHC analysis revealed that the tumor was positive for PRL, ACTH, GH and LH.

  • Generally, the effectiveness of dopamine agonist and somatostatin analog in corticotroph adenomas is low; however, if the plurihormonal pituitary adenoma producing ACTH expresses SSTR2, SSTR5 and D2R, medical therapy for the pituitary adenoma may be effective.

Open access
Sally K Abell Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

Search for other papers by Sally K Abell in
Google Scholar
PubMed
Close
,
Jessie Teng Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

Search for other papers by Jessie Teng in
Google Scholar
PubMed
Close
,
Anthony Dowling Department of Oncology, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

Search for other papers by Anthony Dowling in
Google Scholar
PubMed
Close
,
Michael S Hofman Department of Medicine, University of Melbourne, Parkville, Melbourne, Victoria, Australia
Molecular Imaging, Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Melbourne, Victoria, Australia

Search for other papers by Michael S Hofman in
Google Scholar
PubMed
Close
,
Richard J MacIsaac Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia
Department of Medicine, University of Melbourne, Parkville, Melbourne, Victoria, Australia

Search for other papers by Richard J MacIsaac in
Google Scholar
PubMed
Close
, and
Nirupa Sachithanandan Department of Endocrinology and Diabetes, St Vincent's Hospital, PO Box 2900, Fitzroy, Melbourne, 3065 Victoria, Australia

Search for other papers by Nirupa Sachithanandan in
Google Scholar
PubMed
Close

Summary

This paper details the case of a 77-year-old male with refractory hypoglycaemia due to inoperable metastatic pancreatic neuroendocrine tumour (pNET) co-secreting insulin and gastrin. Multiple medical therapies were trialled with limited success, and we describe the complications experienced by our patient. Somatostatin analogues can ameliorate hypoglycaemia and may have tumour-stabilising effects; however, in our case resulted in paradoxical worsening of hypoglycaemia. This rendered our patient hospital dependent for glycaemic support including continuous dextrose infusion. Although this is a reported adverse effect with initiation of therapy, we describe successful initiation of short-acting octreotide as an inpatient followed by commencement of long-acting octreotide. Hypoglycaemic collapse occurred only after dose titration of long-acting octreotide. We outline the pitfalls of somatostatin analogue therapy and the mechanisms that may contribute to worsening hypoglycaemia. This rare side effect cannot be reliably predicted, necessitating close supervision and glucose monitoring during therapy. Our patient achieved disease stabilisation and gradual resolution of hypoglycaemia with peptide receptor radionuclide therapy (PRRT), an emerging therapeutic option for metastatic neuroendocrine tumours with high efficacy and low toxicity. We present a brief but comprehensive discussion of currently available and novel therapies for insulin secreting pNETs.

Learning points

  • Hypoglycaemia due to malignant insulin secreting pNET is frequently severe and may be life-threatening despite supportive therapies.

  • Octreotide can ameliorate hypoglycaemia, and may have anti-proliferative and tumour-stabilising effects in malignant pNETs that are surgically unresectable.

  • Paradoxical worsening of hypoglycaemia may occur with octreotide initiation and dose titration, necessitating close supervision and glucose monitoring.

  • PRRT is emerging as a therapeutic option with high efficacy and low toxicity.

Open access