Neuroendocrine tumors secreting growth hormone-releasing hormone: Pathophysiological and clinical aspects

Hypothalamic GHRH is secreted into the portal system, binds to specific surface receptors of the somatotroph cell and elicits intracellular signals that modulate pituitary GH synthesis and/or secretion. Moreover, GHRH is synthesized and expressed in multiple extrapituitary tissues. Excessive peripheral production of GHRH by a tumor source would therefore be expected to cause somatotroph cell hyperstimulation, increased GH secretion and eventually pituitary acromegaly. Immunoreactive GHRH is present in several tumors, including carcinoid tumors, pancreatic cell tumors, small cell lung cancers, endometrial tumors, adrenal adenomas, and pheochromocytomas which have been reported to secrete GHRH. Acromegaly in these patients, however, is uncommon. The distinction of pituitary vs. extrapituitary acromegaly is extremely important in planning effective management. Regardless of the cause, GH and IGF-1 are invariably elevated and GH levels fail to suppress (<1 μg/l) after an oral glucose load in all forms of acromegaly. Dynamic pituitary tests are not helpful in distinguishing acromegalic patients with pituitary tumors from those harbouring extrapituitary tumors. Plasma GHRH levels are usually elevated in patients with peripheral GHRH-secreting tumors, and are normal or low in patients with pituitary acromegaly. Unique and unexpected clinical features in an acromegalic patient, including respiratory wheezing or dyspnea, facial flushing, peptic ulcers, or renal stones sometimes are helpful in alerting the physician to diagnosing non pituitary endocrine tumors. If no facility to measure plasma GHRH is available, and in the absence of MRI evidence of pituitary adenoma, a CT scan of the thorax and abdominal ultrasound could be performed to exclude with good approximation the possibility of an ectopic GHRH syndrome. Surgical resection of the tumor secreting ectopic GHRH should be the logical approach to a patient with ectopic GHRH syndrome. Standard chemotherapy directed at GHRH-producing carcinoid tumors is generally unsuccessful in controlling the activated GH axis. Somatostatin analogs provide an effective option for medical management of carcinoid patients, especially those with recurrent disease. In fact, long-acting somatostatin analogs may be able to control not only the ectopic hormonal secretion syndrome, but also, in some instances, tumor growth. Therefore, although cytotoxic chemotherapy, pituitary surgery, or irradiation still remain available therapeutic options, long-acting somatostatin analogs are now preferred as a second-line therapy in patients with carcinoid tumors and ectopic GHRH-syndrome.     

Acromegaly due to ectopic growth hormone (GH)-releasing hormone (GHRH) production: dynamic studies of GH and ectopic GHRH secretion

Dynamic studies of GH and GH-releasing hormone (GHRH) secretion were performed in a man with a GHRH-producing carcinoid tumor and acromegaly. Insulin hypoglycemia stimulated and metoclopramide inhibited both GH and GHRH acutely. Bromocriptine suppressed GH both acutely and chronically without altering circulating GHRH levels and also blunted the GH response to exogenous GHRH. TRH acutely stimulated GH, but not GHRH, secretion, and iv bolus doses of synthetic GHRH-(1-40) stimulated GH release acutely. Somatostatin infusion decreased both GH and GHRH concentrations and blunted the GH responses to TRH and GHRH-(1-40). We conclude that prolonged exposure of the pituitary gland to high concentrations of GHRH is associated with chronic GH hypersecretion and may be accompanied by a preserved acute GH response to exogenous GHRH; a paradoxical response of GH to TRH may be mediated at the pituitary level, consequent to prolonged pituitary exposure to GHRH; bromocriptine suppression of GH in acromegaly is due to a direct pituitary effect of the drug; and somatostatin inhibits both ectopic GHRH secretion as well as GH responsiveness to GHRH in vivo. Since GH secretory responses in patients with somatotroph adenomas are similar to those in this patient, augmented GHRH secretion may play a role in development of the "classic" form of acromegaly.     

Medical management of acromegaly due to ectopic production of growth hormone-releasing hormone by a carcinoid tumor

A 59-yr-old woman with a disseminated carcinoid tumor was evaluated for acromegaly. She had previously undergone a hypophysectomy for acromegaly and an enlarged pituitary, with a reduction in her serum GH levels from 100 to 4 micrograms/L. Recurrence of acromegalic symptoms 2 yr later was accompanied by elevated serum GH (16 micrograms/L) and insulin-like growth factor I (IGF-I; 528 micrograms/L) and plasma GHRH levels (12 micrograms/L; normal, less than 30 ng/L). Computed tomographic scan did not reveal pituitary enlargement. Metastatic carcinoid tissue in bone removed at biopsy contained GHRH (100 pg/mg tissue). High performance liquid chromatography of plasma GHRH revealed predominantly GHRH-(3-40)-OH, a biologically inactive GHRH metabolite, along with mature GHRH forms, while carcinoid tissue contained both GHRH-(1-40)-OH and GHRH-(1-44)-NH2. Treatment with pergolide initially resulted in reduction in serum GH and IGF-I levels and amelioration of symptoms of acromegaly. However, after 14 months of pergolide therapy, serum GH levels increased despite administration of up to 1000 micrograms pergolide/day. Plasma GHRH levels remained elevated throughout the treatment period. Subsequent treatment with SMS 201-995, a long-acting somatostatin analog, for over 1 yr resulted in sustained reductions of ectopic GHRH secretion, GH hypersecretion, and IGF-I levels. Plasma GHRH levels correlated with simultaneously measured serum GH levels in response to acute SMS 201-995 administration. SMS 201-995 was an effective medical treatment for acromegaly caused by ectopic GHRH production in this patient.     

Hirsutismus und Struma multinodosa bei einer 40-jährigen Uhrmacherin

This article presents the case of a female patient with acromegaly caused by ectopic production of growth hormone-releasing hormone (GHRH) secretion. In the presence of typical clinical features of acromegaly but a lack of evidence for a pituitary adenoma the results of somatostatin receptor scintigraphy were indicative of a typical carcinoid of the lungs as the cause of the ectopic secretion of GHRH and the stimulation of pituitary gland growth hormone secretion resulting in acromegaly. Finally, the patient underwent curative surgical treatment.     

Acromegaly due to ectopic secretion of GHRH by bronchial carcinoid in a patient with empty sella

GH hyperproduction due to ectopic secretion of GHRH is a rare cause of acromegaly. Since 1959, approximately 50 cases of ectopic GHRH production from extrapituitary tumors have been described. Here we report the clinical and biochemical features of a 47-yr-old Caucasian woman with ectopic GHRH syndrome sustained by a bronchial carcinoid. The criteria for the diagnosis of acromegaly due to ectopic GHRH secretion were satisfied in our patient (i.e. confirmation of active GH hypersecretion, unequivocal demonstration of GHRH production and secretion from an extrapituitary tumor and cure of acromegaly after neoplasm removal). The tumor was an atypical carcinoid and there was a familial history of lung and colorectal cancer. Acromegaly was slightly active (mean GH value: 7.4 ng/ml, IGF-I: 436 ng/ml) and after tumor removal there was a progressive decline of GH levels, consistent with remission of pituitary somatotroph hyperplasia. Pituitary radiology showed an empty sella demonstrating for the first time its association with ectopic GHRH syndrome.     

Inhibitory effects of GHRH antagonists on human GH-secreting adenoma tissue

Experimental data indicate that antagonists of growth hormone-releasing hormone (GHRH) could be used clinically in disorders characterized by excessive GHRH/growth hormone (GH) secretion, but direct evidence for the effectiveness of GHRH antagonists on human pituitary tissue is still lacking. In this study, we investigated the inhibitory effect of our GHRH antagonists MZ-4-71 and JV-1-36 and the somatostatin (SST) analog RC-160 on superfused pituitary cells obtained from a human GH-secreting adenoma. Using Western blot analysis and immunohistochemistry, we demonstrated profuse expression of the GHRH receptor and its major splice variant SV1 and an increase in the expression of Gsa protein in the adenoma tissue. Exposure of the tumor cells to exogenous pulses of GHRH induced definite GH responses, causing a 3- to 5-fold elevation of the basal GH level. The antagonists MZ-4-71 and JV-1-36 did not alter basal GH secretion, indicating that the adenoma cells did not secrete GHRH in an autocrine manner. However, both antagonists prevented the stimulatory effect of exogenous GHRH. Similarly to the GHRH antagonists, neither SST-14 nor the SST analog RC-160 had an effect on the basal GH secretion of the tumor cells, but both peptides inhibited the stimulatory effect of exogenous GHRH, with RC-160 being more potent than SST. Our study provides direct evidence for the effectiveness of potent GHRH antagonists such as MZ-4-71 and JV-1-36 on human pituitary GH-secreting adenoma tissue and strongly suggests that these drugs could be used for therapy of GHRH-associated forms of acromegaly, particularly for those patients in whom surgery fails or is not an option.     

Acromegaly with no pituitary adenoma and no evidence of ectopic source

More than 99% of patients with acromegaly harbor a growth hormone (GH) secreting pituitary adenoma. As the time from onset of signs/symptoms to diagnosis of acromegaly is long (symptom onset to diagnosis is often 4-10 years), pituitary adenomas that cause GH excess are often large and are nearly always visible on conventional magnetic resonance imaging (MRI). However, in rare circumstances, acromegalic patients without an ectopic source will not have imaging evidence of a pituitary adenoma. Management of these patients poses special challenge, and once ectopic source of GH/growth-hormone-releasing hormone (GHRH) is ruled out, an exploration of pituitary might be useful. We herein report a case of acromegaly with imaging evidence of sellar floor osteoma, but no pituitary adenoma, and negative work up for an ectopic source of GH/GHRH tumor, and on surgical exploration pituitary adenoma could be identified and removed and confirmed on histopathologic examination.     

Octreotide suppresses both growth hormone (GH) and GH-releasing hormone (GHRH) in acromegaly due to ectopic GHRH secretion

Two patients with acromegaly secondary to ectopic GHRH secretion by metastatic carcinoid tumors were studied before and during therapy with the somatostatin analog octreotide (SMS 201-995). GH and GHRH secretory patterns were assessed during intermittent sc administration, continuous sc infusion (CSI), and continuous iv infusion of octreotide. Octreotide reduced serum GH and plasma GHRH levels in the two patients, although there was differential sensitivity of GH and GHRH. Intermittent sc therapy transiently lowered serum GH in both patients. A higher iv dose was required to reduce plasma GHRH by 50% than to reduce serum GH by 50% (2.0 vs. 0.05 micrograms/kg.h, respectively; patient 1). A similar pattern was found during CSI octreotide administration in the same patient. Chronic therapy with intermittent sc and CSI octreotide was assessed by serial 24-h profiles of GH and GHRH secretion in patient 2. Mean hourly serum GH levels decreased from a pretreatment level of 31.5 +/- 3.5 (+/- SE) to 9.5 +/- 1.5 micrograms/L during CSI therapy (1000 micrograms/day or 0.40 micrograms/kg.h). In contrast, plasma GHRH levels were less effectively suppressed. The mean serum GH levels and the variation in hourly GH values were reduced to a greater extent with CSI than with intermittent sc therapy. Serum insulin-like growth factor I also declined from 5.9 x 10(3) to 2.5 x 10(3) U/L during chronic CSI therapy (patient 2). CSI therapy with octreotide can be more effective than intermittent sc therapy in controlling GH excess in the rare syndrome of ectopic GHRH secretion, although serum GH may not decline to normal.     

Studies on the response of growth hormone (GH) secretion to GH-releasing hormone, thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin in acromegaly

The plasma GH response to GH-releasing hormone (GHRH), TRH, or GnRH administration was examined in 25 acromegalic patients. Plasma GH levels increased in 21 patients after GHRH, in 19 after TRH, and in 4 after GnRH. The four GHRH nonresponders had had acromegaly longer than had the GHRH responders. No specific combination of GH responsiveness to these 3 releasing hormones was found among the patients. Infusion of 1 mg GHRH for 150 min gradually increased plasma GH levels, with some fluctuations, from the beginning to the end of infusion in normal subjects and in 7 patients who were GHRH responders, but a bolus injection of 100 micrograms GHRH at the end of the infusion did not further elevate plasma GH levels. These results suggest that desensitization to GHRH occurred in the normal subjects and acromegalic patients. However, in 5 acromegalic patients who responded to both GHRH and TRH, a bolus injection of 500 micrograms TRH given at the end of the 150-min infusion of 1 mg GHRH evoked a further plasma GH rise. In 5 normal subjects and 2 patients who were responders to GHRH but not TRH, a bolus injection of 500 micrograms TRH did not cause plasma GH elevation at the end of 150-min infusion of 1 mg GHRH. These results imply that TRH and GnRH stimulate GH secretion from the adenoma cells in vivo through receptors different from those for GHRH. In vitro studies using cultured pituitary adenoma cells from 2 patients revealed that the responses of GH secretion to GHRH were similar to those in vivo. These data, therefore, suggest that the responsiveness of GH secretion to stimuli is determined by the specificity of the receptors on adenoma cells. The action of somatostatin-28 was more potent than that of somatostatin-14 in the suppression of GH secretion from adenoma cells.     

Ectopic acromegaly.

Ectopic acromegaly is a rare syndrome (less than 1% of acromegalic patients) caused by ectopic growth hormone-releasing hormone (GHRH) or growth hormone (GH)-producing tumors. Its recognition is clinically important because acromegaly may be a symptom of an aggressive tumor, and different therapeutic approaches are required. Most cases are caused by either extra- or intracranial GHRH-producing tumors, whereas in rare instances the underlying disease is an ectopic GH-secreting tumor. The routine evaluation of circulating GHRH in all acromegalic patients may allow its early recognition, because plasma levels greater than 0.3 ng/mL are virtually diagnostic of a GHRH-producing tumor (frequently a bronchial or pancreatic carcinoid), whereas suppressed levels may suggest an ectopic GH-producing tumor. In addition to classic imaging techniques, whole body scintiscan with labeled octreotide may help in the localization of ectopic tumors. Surgical removal of the ectopic tumor is the therapy of choice, but it is not always feasible because patients often present with widespread metastases. Patients with GHRH-induced acromegaly benefit from the administration of the long-acting somatostatin analog, octreotide, which reduces GH, IGF-I, and GHRH, and may shrink the ectopic tumor, its metastases, and the secondary pituitary enlargement.     

Acromegaly with negative pituitary MRI and no evidence of ectopic source: the role of transphenoidal pituitary exploration?

Growth hormone (GH) producing adenomas of the pituitary gland are usually macroadenomas (>10 mm in size). Often these adenomas are locally invasive by the time of diagnosis. Acromegaly secondary to a very small pituitary microadenoma not visualized on pituitary magnetic resonance (MR) imaging is rare. We report a patient with acromegaly and an unremarkable pituitary MR imaging who had negative work up for ectopic growth hormone-releasing hormone (GHRH) or GH secreting tumors. Transsphenoidal pituitary exploration revealed a pituitary adenoma located on the left side of the sella against the medial wall of the cavernous sinus extending posteriorly along the floor of the sella all the way to the right side. The acromegaly was treated with resection of the pituitary adenoma and normalization of serum insulin-like growth factor 1 (IGF-1) and GH levels. In a patient with acromegaly and unremarkable pituitary MR imaging, with no evidence of ectopic GH and GHRH production, transsphenoidal pituitary exploration is a reasonable approach and may result in clinical improvement and biochemical cure in the hand of experienced surgeon. This approach may avoid long term medical treatment with its associated cost.     

Acromegaly due to a growth hormone-releasing hormone-secreting bronchial carcinoid tumor: further information on the abnormal responsiveness of the somatotroph cells and their recovery after successful treatment

We studied GH secretion in a patient with acromegaly and a bronchial carcinoid tumor before and again after surgical removal of this tumor. Before removal of the carcinoid tumor, plasma GH increased slightly after glucose loading (OGTT) and markedly after TRH (650%) and insulin (440%) treatment. Plasma GH did not change after GH-releasing hormone (GHRH), LHRH, or L-dopa administration. Somatostatin (SRIH) infusion lowered plasma GH. No change in plasma immunoreactive GHRH (IR-GHRH) occurred after TRH, glucose, insulin, or SRIH administration. Two weeks after removal of the carcinoid tumor, TRH induced GH secretion (250%) when the IR-GHRH level was undetectable and somatomedin-C was within normal limits. Fifteen weeks after surgery, the patient had normal GH secretion. In conclusion: no pattern of GH secretion is diagnostic of acromegaly due to ectopic GHRH secretion, but the lack of GH response to exogenous GHRH and a large response during hypoglycemia may be features of this condition. When acromegaly and abnormal GH responsiveness are induced by a GHRH-secreting tumor, the increases in plasma GH after TRH, glucose, and insulin administration are not mediated by GHRH. After removal of the GHRH-secreting tumor, persistent paradoxical GH response to TRH does not require abnormally high IR-GHRH levels and does not preclude complete recovery.     

Hypersecretion of growth hormone and prolactin in McCune-Albright syndrome

Acromegaly and hyperprolactinemia have been reported in association with the McCune-Albright syndrome, but the pathophysiology of the GH and PRL hypersecretion that occurs in patients with this disorder has not been defined. We studied GH and PRL secretory dynamics in three patients with McCune-Albright syndrome and hypersecretion of these hormones. Each patient had excessive linear growth, glucose-non-suppressible plasma GH concentration, and GH responsiveness to TRH and GHRH. In response to exogenous GHRH, plasma GH concentrations rose approximately 2-fold in all three patients. Plasma GHRH levels were 20-40 ng/L (normal, less than 30). Study of the spontaneous GH secretory pattern in two patients indicated nocturnal augmentation of GH release. Bromocriptine therapy failed to reduce plasma GH in all patients; in one patient treatment with octreotide, a long-acting somatostatin analog, partially suppressed plasma GH and insulin-like growth factor I levels. These results suggest that hypersecretion of GH in the McCune-Albright syndrome is not due to ectopic GHRH production or autonomous somatotroph function. The results are similar to those described in classic acromegaly due to GH-secreting pituitary tumors. However, the lack of radiographic pituitary enlargement, the variable pituitary pathology reported in similar patients, and frequent concordance of GH and PRL excess suggest that the pathogenesis of this disorder may differ fundamentally from other forms of acromegaly or gigantism. The pathophysiology may reflect abnormal hypothalamic regulation and/or an embryological defect in pituitary cellular differentiation and function.     

Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture

In an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.     

Atypical McCune-Albright syndrome associated with growth hormone-prolactin pituitary adenoma: natural history, long-term follow-up, and SMS 201-995--bromocriptine combined treatment results.

A 35-yr-old woman is described as having atypical McCune-Albright syndrome, associated with acromegaly and hyperprolactinemia due to pituitary adenoma. The patient did not present sexual precocity, but primary amenorrhea. After transphenoidal adenomectomy, the GH plasma levels returned to normal, whereas the PRL values decreased; bromocriptine therapy normalized PRL levels and induced ovulatory menses. After 4 uneventful yr the patient developed relapse of active acromegaly that did not recover after a second neurosurgical exploration. Bromocriptine treatment maintained normal PRL levels but did not significantly reduce GH ones; the association with long-acting somatostatin analog SMS 201-995 by continuous sc pump infusion induced definitive control of GH and somatomedin-C secretion. These results suggest an additive inhibitory effect on GH secretion exerted by the two drugs.     

Ghrelin secretion in humans is sexually dimorphic,suppressed by somatostatin,and not affected by the ambient growth hormone levels

We studied plasma ghrelin and GH concentrations over a 24-h period in young healthy men and women and in patients with acromegaly. Healthy subjects were restudied after administration of GH-lowering agents, octreotide or GHRH antagonist. Ghrelin concentrations in women studied during the late follicular stage of the cycle were about 3-fold higher than in men. Suppression of GH secretion by GHRH antagonist did not alter ghrelin concentration profiles. In the presence of high GH levels (acromegaly), ghrelin levels were similar to those found in healthy men. Administration of somatostatin analog octreotide suppressed both GH and ghrelin concentration profiles. We conclude that: 1) ghrelin secretion is sexually dimorphic in humans, with women in the late follicular stage having higher levels than men; 2) ghrelin secretion is suppressed by somatostatin; and 3) GH has no influence over ghrelin secretion.     

Ectopic secretion of GHRH by a pancreatic neuroendocrine tumor associated with an empty sella

Acromegaly is usually the result of a pituitary growth hormone cell-adenoma or is more rarely due to ectopic secretion of growth hormone releasing hormone (GHRH).We report the case of a 60-year-old woman with acromegaly due to a GH-RH-secreting pancreatic tumor. Laboratory evaluation confirmed the diagnosis of acromegaly. Magnetic resonance imaging revealed a partial empty sella with no signs of adenoma. Ultrasound sonography performed for abdominal pains showed a calcified large heterogeneous infrahepatic mass. Computed tomography scan discovered a heterogeneous pancreatic head mass with a diameter of 10 cm. Measurement of fasting plasma GHRH was performed showing a high concentration of 604 ng/L (normal 10–60). We therefore concluded that the acromegaly was caused by ectopic overproduction of GHRH likely due to the pancreatic tumor. The patient underwent a cephalic duodenopancreatectomy. Histology revealed a well-circumscribed tumor with organoid architecture. Immunohistochemistry demonstrated diffuse positivity for chromogranin A, neuronal specific enolase and synaptophysin and negative immunoreactivity for prolactin, GH and serotonin. These features were concordant with a well-differentiated neuroendocrine tumor of the pancreas. Surgical resection of this pancreatic tumor was followed by significant amelioration of acromegalic signs and normalization of GHRH and GH levels.     

Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery.

A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.     

Acromegaly and bronchial carcinoid tumor. Apropos of a case]

Acromegaly due to ectopic secretion of growth hormone-releasing hormone (GHRH) is rare. A 29-year-old woman with acromegaly secondary to ectopic GHRH secretion by a bronchial carcinoid tumor is presented. Normalization of GHRH levels, reversal of pituitary hyperplasia and regression of acromegaly followed resection of the bronchial tumor. The authors stressed the interest of GHRH dosage in patients with acromegaly and pituitary hyperplasia.