In 1996, the German Registry of Pituitary Tumors was founded by the Pituitary Section of the German Society of Endocrinology as a reference center for collection and consultant pathohistological studies of pituitary tumors. The experiences of the first 10 years of this registry based on 4122 cases will herein be reported. The data supplement former collections of the years 1970-1995 with 3480 surgically removed tumors or lesions of the pituitary region. The cases were studied using histology, immunostainings and in some cases also molecular pathology or electron microscopy. The adenomas were classified according to the current World Health Organization classification in the version of 2004. From 1996 on 3489 adenomas (84.6%), 5 pituitary carcinomas (0.12%), 133 craniopharyngiomas (3.2%), 39 meningiomas (0.94%), 25 metastases (0.6%), 22 chordomas (0.5%), 115 cystic non-neoplastic lesions (2.8%), and 46 inflammatory lesions (1.1%, 248 other lesions or normal tissue (6.0%)) were collected by us. The adenomas (100%) were classified into densely granulated GH cell adenomas (9.2%), sparsely granulated GH cell adenomas (6.3%), sparsely granulated prolactin (PRL) cell adenomas (8.9%), densely granulated PRL cell adenomas (0.3%), mixed GH/PRL cell adenomas (5.2%), mammosomatotropic adenomas (1.1%), acidophilic stem cell adenomas (0.2%), densely granulated ACTH cell adenomas (7.2%), sparsely granulated ACTH cell adenomas (7.9%), Crooke cell adenomas (0.03%), TSH cell adenomas (1.5%), FSH/LH cell adenomas (24.8%), null cell adenomas (19.3%), null cell adenoma, oncocytic variant (5.8%), and plurihormonal adenomas (1.3%).

Gastrointestinal side-effects of prolonged therapy (greater than 2 yr) with the long-acting somatostatin analog octreotide were studied in 10 acromegalic patients. After 2 yr of therapy, 6 of 10 patients had newly developed gallstones, complicated by cholangitis and jaundice in 1. Serum vitamin B-12 concentrations declined in all 10 patients [from 380 +/- 32 to 172 +/- 21 pmol/L (mean +/- SE); P = 0.023] and became abnormally low in 4. Gastric biopsy specimens, obtained during gastroscopy (9 patients), showed moderate to severe active gastritis, with damage to the superficial and deeper layers of the mucosa in 9 of 9 and focal atrophy in 7 of 9 patients. Campylobacter pylori was found in the antral mucosa in 8 of 9 patients. Although information is lacking on similar studies in untreated acromegalic patients, we suggest that patients receiving chronic octreotide therapy be closely monitored for these and possible other side-effects related to gastrointestinal actions of octreotide.

The factors that determine the hormone and volume responses of pituitary adenomas to the somatostatin analog octreotide are poorly understood. We, therefore, studied the correlation between 111indium-pentetreotide somatostatin receptor scintigraphy (SRS) and the clinical and immunohistochemical classification of pituitary adenomas, on the one hand, and hormone and volume responses, on the other hand. Ten patients with GH-secreting (6 females and 4 males; age, 31-67 yr) and 14 patients with clinically nonfunctioning (NF) macroadenomas (5 females and 9 males; age, 22-79 yr) were preoperatively treated with 300 micrograms/day octreotide, which was increased to 600 and 1500 micrograms/day at weekly intervals and then continued for at least 3 months until surgery. SRS was performed before therapy. A sellar magnetic resonance imaging scan was performed before therapy; 1, 2, and 3 weeks and 3 months after start of therapy; and after surgery. Acromegalics also had an 8-h GH profile, insulin-like growth factor-I determination, and a 100-g oral glucose load at these time points. An attempt was made to identify NF adenomas as gonadotroph adenomas using their LH, FSH, and alpha-subunit responses to TRH. In acromegalic patients, octreotide suppressed mean GH (8-h profile) and insulin-like growth factor-I concentrations from 34.9 +/- 9.7 to 8.1 +/- 3.6 micrograms/L and from 2122 +/- 1025 to 701 +/- 208 micrograms/L, respectively, after 3 months. Significant (26-85% decline) tumor shrinkage occurred in 5 of 10 patients, mainly within the first week. Tumor shrinkage and GH suppression were not correlated. Four of 7 patients had increased pituitary 111indium-pentetreotide uptake, but this did not predict GH suppression or tumor shrinkage. Of the NF adenomas, 2 responded with shrinkage (57% and 96% decline). Four of 12 adenomas had increased 111indium-pentetreotide uptake, but this did not correlate with tumor shrinkage (2 adenomas; 1 gonadotroph and 1 null cell adenoma), immunohistochemistry, or clinical classification. We conclude that preoperative octreotide therapy suppresses GH in most patients and reduces tumor volume in up to 50% of acromegalic patients. It also induces shrinkage in some NF adenomas, although less frequently. SRS does not predict shrinkage of either tumor type. Shrinkage does not correlate with clinical classification or immunohistological characteristics. Further studies are needed to identify the factors that determine the hormone and volume responses of pituitary adenomas to octreotide therapy.

Twelve acromegalic patients in whom standard therapy was unsuccessful were evaluated with 24-h serum GH profiles (hourly sampling) and oral glucose tests (oGTT) while being treated with octreotide, a long-acting somatostatin analog. During a dose-response study (300, 600, and 1500 micrograms/day sc, for 4 weeks), serum GH decreased significantly after 300 micrograms/day in 8 of 12 patients [from 14.5 +/- 6.2 (+/- SE) to 4.9 +/- 1.9 micrograms/L]. Higher doses further reduced serum GH concentrations in 3 (600 micrograms/day) and 1 (1500 micrograms/day) patients, respectively. Four patients did not respond to any dose. Serum GH concentrations declined normally (GH nadir, less than 2 micrograms/L) after glucose ingestion in 4 of the 10 nondiabetic acromegalic patients. In 4 patients, including 2 of the initial nonresponders, serum GH further declined during long term treatment (12 and 18 months). In the latter 2 patients, serum insulin-like growth factor I (IGF-I) concentrations had decreased during the dose-response study despite the absence of measurable GH suppression. Eight patients attained normal serum IGF-I concentrations during treatment. Serum IGF-I and GH correlated significantly before, but not during, treatment. Retrospective comparison suggested that in 5 of 6 patients, serum GH was more effectively suppressed by octreotide than by bromocriptine. The 24-h serum octreotide concentration varied greatly among the patients. Although the 24-h serum octreotide and GH concentrations did not correlate with one another, the serum octreotide and IGF-I concentrations when the patients were receiving 300 micrograms/day tended to be negatively correlated (r = -0.496; P = 0.118). The 24-h serum insulin values decreased and those of glucose increased during treatment; after oral glucose, serum insulin was lower and glucose was higher. However, after 12 months of treatment, the 8-h serum insulin profile and peak serum insulin after oral glucose administration had returned to pretreatment values, while serum glucose remained abnormal. We conclude that 1) octreotide lowers serum GH in many, but not all, acromegalic patients resistant to other forms of treatment; 2) doses in excess of 300 micrograms/day should be tested in those patients in whom lower doses are ineffective; 3) serum IGF-I measurement may be a better indicator of treatment success than GH measurement; 4) octreotide concentrations do not correlate with GH suppression; and 5) deterioration of carbohydrate tolerance does occur but tends to improve during chronic treatment.

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.