Asian Cardiovasc Thorac Ann 2002;10:273-274
© 2002 Asia Publishing EXchange Pte Ltd
Acromegaly: a Rare Manifestation of Bronchial Carcinoid
Anil Bhansali, DM,
Rana S Singh, MCh1,
Sujit Bhattacharya, DM,
Rajgopal Muralidharan, DM,
Radharaman J Dash, DM,
Ashru K Banerjee, MD2
Department of Endocrinology
1 Department of Cardiovascular and Thoracic Surgery
2 Department of Histopathology Postgraduate Institute of Medical Education and Research Chandigarh, Punjab, India
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For reprint information contact: Rana S Singh, MCh Tel: 91 172 74 7585 Fax: 91 172 74 4401 email: medinst{at}pgi.chd.nic.in Department of Cardiovascular and Thoracic Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, Punjab 160012, India.
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ABSTRACT
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Bronchial carcinoids usually present with pulmonary symptoms. Neurohumoral manifestations in the form of acromegaly and Cushing’s syndrome are rarely encountered. We report a case of bronchial carcinoid with features of acromegaly due to ectopic production of growth hormone-releasing hormone. Surgical resection of the lung lesion resulted in regression of acromegalic features, normalization of growth hormone secretory dynamics, and remarkable diminution of pituitary size seen on magnetic resonance imaging.
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INTRODUCTION
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Bronchial carcinoids commonly present with pulmonary symptoms, while their manifestation as acromegaly is rare.1 Acromegaly associated with carcinoid tumors is usually caused by ectopic growth hormone-releasing hormone (GHRH) and rarely by growth hormone (GH) secreting tumors. However, the most common tumors secreting GHRH are bronchial and pancreatic islet cell carcinoids.1,2
We report a patient who presented with pulmonary symptoms and was incidentally found to have acromegaly with diffuse pituitary enlargement.
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CASE REPORT
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A 38-year-old woman (Figure 1A
) presented with low-grade fever and pleuritic chest pain for 3 days. Her chest radiograph and computed tomographic scan revealed a right hilar mass (Figures 1B and 1C). Transbronchial lung biopsy of the mass suggested a carcinoid tumor. Because of the coarsening of her facial features and acral enlargement over the last few months, she was investigated for acromegaly. Her menstrual cycles were regular, and she had her last child 8 years ago.
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Figure 1. (A) Clinical profile. (B) Radiograph (posteroanterior view) and (C) contrast-enhanced computed tomographic scan of the chest showing a right hilar mass. (D) Chest radiograph (posteroanterior view) after resection of the mass.
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On examination, her body mass index was 25 kgám-2 and blood pressure was 120/70 mm Hg. Besides coarse facial features and enlarged hands and feet, she had increased sweating. She did not have a goiter or skin tags. Systemic examination was normal, including the fundi. Her hemogram and routine blood biochemistry were normal. Hormonal profile revealed an elevated level of basal serum GH (35 ngámL-1; normal, 1 to 2 ngámL-1), which was nonsuppressible to a 75-g oral glucose load (30 ngámL-1; normal, < 2 ngámL-1), and a raised prolactin level (1,600 mIUáL-1; normal, 100 to 600 mIUáL-1). T3 at 1.4 ngámL-1, T4 at 75 ngámL-1, cortisol at 8 a.m. of 600 nmoláL-1, and urinary hydroxyindoleacetic acid at 24 µmol/day were within normal limits. Magnetic resonance imaging of the sella showed diffuse enlargement of the pituitary with a height of 11 mm and a convex superior border (Figures 2A and 2B). In view of the bronchial mass and diffuse pituitary enlargement with acromegaly, a diagnosis of ectopic acromegaly secondary to GHRH-secreting bronchial carcinoid was made.
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Figure 2. Coronal and sagittal cuts of T1-weighted magnetic resonance images of the pituitary showing (A, B) diffuse pituitary enlargement and (C, D) decrease in pituitary size 4 months postoperatively.
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The patient subsequently underwent right upper lobectomy to resect the lung lesion. Operative findings disclosed a well-circumscribed mass measuring 3 x 3 cm embedded in the right upper lobe. No hilar lymphadenopathy was noticed. Histopathology confirmed the mass to be a bronchial carcinoid, and immunostaining was positive for neurone-specific enolase, chromogranin, and synaptophysin, providing evidence that the tumor consisted of cells with endocrine differentiation. Conclusive immunoreactivity for GHRH was noted. A few scattered tumor cells were immunoreactive for somatostatin, while immunoreactivity was negative for GH, prolactin, adrenocorticotropin, and 
subunits of glycoprotein hormones including thyrotropin, luteinizing hormone, and follicle-stimulating hormone.
The patient experienced reduced sweating and regression of acral enlargement and coarse facial features following surgery. The postoperative chest radiograph did not reveal any residual mass (Figure 1D
). Four months postoperatively, her basal serum GH level was 1.9 ngámL-1 and was suppressed to 0.4 ngámL-1 after glucose load. Magnetic resonance imaging of the sella at this time showed a regression of pituitary height to 7 mm (Figures 2C and 2D).
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DISCUSSION
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Our patient presented with pulmonary symptoms but was incidentally found to have clinical features of acromegaly, abnormal GH secretory dynamics, a bronchial lesion with positive immunostaining for GHRH but not for GH, and diffuse pituitary enlargement on imaging suggestive of its hyperplasia. Ectopic GHRH secretion from the bronchial carcinoid was responsible for somatotroph hyperplasia, leading to GH hypersecretion and development of acromegalic features. Resection of the bronchial lesion resulted in regression of acromegalic features, normalization of GH secretory dynamics, and reduction of pituitary size seen on imaging.
Acromegaly is generally caused by autonomous secretion of GH from a pituitary tumor resulting from clonal expansion of somatotrophs.3 However, extrapituitary GHRH secretion causing acromegaly is reported in 1% to 2% of patients in a large series of acromegaly, with bronchial carcinoids being the most common cause (70%) followed by pancreatic islet cell carcinoids.1,2 In 90% of cases, the tumor originates in the subsegmental or greater bronchus, as in our case, while in 10% the tumor is peripherally located or of the tumorlet type.4 The tumors are generally small, measuring 2 to 4 cm in diameter.
In 1958, a bronchial carcinoid causing acromegaly and enlargement of the sella was first reported.5 Acromegaly regressed after removal of the tumor. Since then, approximately 50 cases have been reported in the literature to date.6 However, the cause-and-effect relationship between carcinoids and acromegaly was proven only in 1979 by demonstrating the GH-releasing activity of bronchial carcinoid extracts from rat anterior pituitary cells in GHRH bioassay.7
The clinical presentation of ectopic acromegaly is indistinguishable from that of a GH-secreting pituitary adenoma.1 In 2% of patients with bronchial carcinoids, there are manifestations of serotonin hypersecretion.4 Similarly, many GHRH-secreting carcinoids do not produce overt acromegaly because of relatively low levels of GHRH and its short half-life.4 Our patient did not have manifestations of serotonin hypersecretion and was asymptomatic for her acromegalic features.
The dynamics of GH hypersecretion in acromegaly due to pituitary somatotropinoma and ectopic GHRH secretion are similar. These include high basal GH levels, nonsuppressibility of GH to glucose load, abnormal GH response to thyrotropin-releasing hormone (TRH), and high basal as well as TRH-stimulated levels of prolactin.1 High basal prolactin is due to the stimulatory effect of GHRH on lactotrophs, as seen in our patient. However, increased levels of plasma GHRH (100- to 300-fold) is diagnostic of ectopic GHRH secretion or, in rare instances, of GHRH-producing hypothalamic gangliocytomas, while the level is low or undetectable in pituitary acromegaly.2 Demonstration of GHRH immunostaining in tumor tissue provides direct evidence of its secretion, as has been shown in our patient.
Patients with acromegaly, regardless of underlying etiology, exhibit the same sequelae of prolonged exposure to elevated GH and its target hormone, insulin-like growth factor I.6 Early diagnosis and effective therapy are crucial to improve the quality of life and life expectancy. Treatment strategies include resection of the carcinoid tumor, which usually results in complete clinical and biochemical recovery.5 It also usually results in the diminution of pituitary hyperplasia, as was demonstrated in our case. Residual, recurrent, or inoperable lesions have been successfully treated with octreotide, in doses varying from 200 to 500 µg 3 times a day.8 Recently, the long-acting somatostatin analog lanreotide (30 mg weekly) has been used to treat metastatic GHRH carcinoids with clinical and biochemical remission, offering a well-tolerated and convenient medical therapy for controlling hormonal hypersecretion induced by excessive GHRH.6
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Acknowledgments
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The authors gratefully acknowledge the help of Kalman Kovacs, Professor of Pathology, Department of Laboratory Medicine and Pathobiology, St. Michael’s Hospital, Toronto, Ontario, Canada, for the immunohistochemical work of this case.
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REFERENCES
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- Sano T, Asa SL, Kovacs K. Growth hormone-releasing hormone-producing tumors: clinical, biochemical, and morphological manifestations. Endocr Rev
1988;9: 357–73.[Abstract/Free Full Text]
- Thorner MO, Frohman LA, Leong DA, Thominet J, Downs T, Hellmann P, et al. Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients. J Clin Endocrinol Metab
1984;59:846–9.[Abstract/Free Full Text]
- Herman V, Fagin J, Gonsky R, Kovacs K, Melmed S. Clonal origin of pituitary adenomas. J Clin Endocrinol Metab
1990;71:1427–33.[Abstract/Free Full Text]
- Huber RM, Schopohl J, Losa M, Wolfram G, Thetter O, Permanetter W, et al. Growth-hormone releasing hormone in a bronchial carcinoid. Cancer
1991;67:2538–42.[Medline]
- Atmann HW, Schutz W. Uber ein knochenhaltiges Bronchuskarzinoid. Beitr Pathol Anat
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- Drange MR, Melmed S. Long-acting lanreotide induces clinical and biochemical remission of acromegaly caused by disseminated growth hormone-releasing hormone-secreting carcinoid. J Clin Endocrinol Metab
1998; 83:3104–9.[Abstract/Free Full Text]
- Saeed uz Zafar M, Mellinger RC, Fine G, Szabo M, Frohman LA. Acromegaly associated with a bronchial carcinoid tumor: evidence for ectopic production of growth hormone-releasing activity. J Clin Endocrinol Metab
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- Melmed S, Ziel FH, Braunstein GD, Downs T, Frohman LA. Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor. J Clin Endocrinol Metab
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ABSTRACT
INTRODUCTION
