Thyroid-stimulating hormone pituitary adenomas

OBJECT: Thyroid-stimulating hormone (TSH)-secreting pituitary adenomas are rare, representing < 2% of all pituitary adenomas. METHODS: The authors conducted a retrospective analysis of patients with TSH-secreting or clinically silent TSH-immunostaining pituitary tumors among all pituitary adenomas followed at their institution between 1987 and 2003. Patient records, including clinical, imaging, and pathological and surgical characteristics were reviewed. Twenty-one patients (6 women and 15 men; mean age 46 years, range 26-73 years) were identified. Of these, 10 patients had a history of clinical hyperthyroidism, of whom 7 had undergone ablative thyroid procedures (thyroid surgery/(131)I ablation) prior to the diagnosis of pituitary adenoma. Ten patients had elevated TSH preoperatively. Seven patients presented with headache, and 8 presented with visual field defects. All patients underwent imaging, of which 19 were available for imaging review. Sixteen patients had macroadenomas. RESULTS: Of the 21 patients, 18 underwent transsphenoidal surgery at the authors' institution, 2 patients underwent transsphenoidal surgery at another facility, and 1 was treated medically. Patients with TSH-secreting tumors were defined as in remission after surgery if they had no residual adenoma on imaging and had biochemical evidence of hypo-or euthyroidism. Patients with TSH-immunostaining tumors were considered in remission if they had no residual tumor. Of these 18 patients, 9 (50%) were in remission following surgery. Seven patients had residual tumor; 2 of these patients underwent further transsphenoidal resection, 1 underwent a craniotomy, and 4 underwent postoperative radiation therapy (2 conventional radiation therapy, 1 Gamma Knife surgery, and 1 had both types of radiation treatment). Two patients had persistently elevated TSH levels despite the lack of evidence of residual tumor. On pathological analysis and immunostaining of the surgical specimen, 17 patients had samples that stained positively for TSH, 8 for alpha-subunit, 10 for growth hormone, 7 for prolactin, 2 for adrenocorticotrophic hormone, and 1 for follicle-stimulating hormone/luteinizing hormone. Eleven patients (61%) ultimately required thyroid hormone replacement therapy, and 5 (24%) required additional pituitary hormone replacement. Of these, 2 patients required treatment for new anterior pituitary dysfunction as a complication of surgery, and 2 patients with preoperative partial anterior pituitary dysfunction developed complete panhypopituitarism. One patient had transient diabetes insipidus. The remainder had no change in pituitary function from their preoperative state. CONCLUSIONS: Thyroid-stimulating hormone-secreting pituitary lesions are often delayed in diagnosis, are frequently macroadenomas and plurihormonal in terms of their pathological characteristics, have a heterogeneous clinical picture, and are difficult to treat. An experienced team approach will optimize results in the management of these uncommon lesions.     

Multiple pituitary adenomas in Cushing's disease

OBJECT: Clinically evident multiple pituitary adenomas rarely occur. The authors assess the incidence and clinical relevance of multiple adenomas in Cushing's disease. METHODS: A prospective clinical database of 660 pituitary surgeries was analyzed to assess the incidence of multiple pituitary adenomas in Cushing's disease. Relevant radiographic scans, medical records, and histopathological reports were reviewed. Thirteen patients with at least two separate histopathologically confirmed pituitary adenomas were identified. Prolactinomas (nine patients) were the most common incidental tumors. Other incidental tumors included secretors of growth hormone ([GH], one patient) and GH and prolactin (two patients), and a null-cell tumor (one patient). In two patients, early repeated surgery was performed because the initial operation failed to correct hypercortisolism, in one instance because the tumor excised at the initial surgery was a prolactinoma, not an adrenocorticotropic hormone-secreting tumor. One patient had three distinct tumors. CONCLUSIONS: Multiple pituitary adenomas are rare, but may complicate management of patients with pituitary disease.     

Familial acromegaly with pituitary adenoma. Report of three affected siblings

The authors report the cases of three brothers with pituitary adenomas who had classical findings of acromegaly and gigantism. Two had irreducibly elevated growth hormone (GH) values and underwent transsphenoidal microsurgical extirpation of their tumors. The third acromegalic brother had a normal GH value and evidence of panhypopituitarism; he had a small intrasellar tumor and a partially empty sella. The pattern of inheritance was probably autosomal recessive. A review of literature indicated that familial incidence of isolated acromegaly with pituitary adenomas is rare.     

Ectopic pituitary adenomas with normal anterior pituitary glands

Two patients with ectopic pituitary adenomas and biopsy-proven normal anterior pituitaries are described. Both tumors were located in the sphenoid sinus. One tumor produced prolactin, and the other one was a plurihormonal adenoma that produced predominantly adrenocorticotropin and to a lesser extent thyroid stimulating hormone and alpha subunit. The patient with the plurihormonal tumor, who had Cushing's disease, was cured by surgery while the patient with the prolactinoma was treated by surgery and medical therapy. A review of these two cases and an additional nine cases from the literature of ectopic pituitary adenomas in patients with normal intrasellar anterior pituitaries indicate that these uncommon tumors are capable of secretory function and may be the only cause of excessive pituitary hormone production.     

Pituitary tumors and hyperplasia in multiple endocrine neoplasia type 1 syndrome (MEN1): a case-control study in a series of 77 patients versus 2509 non-MEN1 patients

Patients affected by the multiple endocrine neoplasia type I syndrome (MEN1) display a high incidence of pituitary adenomas, though it is still unknown whether these pituitary tumors have specific pathologic features that would distinguish them from sporadic pituitary adenomas. Pituitary tissue specimens of 77 MEN1 patients from the GTE (Groupe d'étude des Tumeurs Endocrines) register were compared with unselected 2509 non-MEN1 sporadic pituitary tumors and also to a control subgroup of 296 cases, where 1 MEN1 tumor was matched with 4 sporadic tumors of the same hormonal immunoprofile. Sex, age, size, and invasiveness of tumors, and menin gene mutations were documented. Histologic analysis took into account 33 items, including immunocytochemical data, the proliferative marker Ki-67, and an examination of the juxtatumoral pituitary. MEN1 tumors were significantly larger and more often invasive by histology. MEN1 patients with large pituitary tumors (grade IV) were younger than non-MEN1 patients. MEN1 tumors had no other characteristic histologic features and no predominance of any one hormone producing subtype. However, plurihormonal adenomas versus monohormonal and nonimmunoreactive adenomas were more frequent in MEN1 tumors (39%) than in the control non-MEN1 group (P = 0.001). Especially, the growth hormone and prolactin plurihormonality with unusual association with follicle-stimulating hormone, luteinizing hormone, or adrenocorticotropic hormone was more frequent in MEN1 tumors. In addition, multiple adenomas were significantly more frequent (4% vs. 0.1%; P < 0.0001), especially prolactin-adrenocorticotropic hormone. Somatotroph hyperplasia, with or without a microadenoma was found in only 3 MEN1 patients, with growth hormone-releasing hormone hypersecretion by a pancreatic tumor in 2 of them. All types of mutation were observed, including frameshifts, nonsenses, missenses, and 1 case of germline MEN1 encompassing large deletion, strongly suggesting the absence of any phenotype-genotype correlation.     

Pathology of invasive pituitary tumors with special reference to functional classification

Pituitary adenomas may remain intrasellar or infiltrate dura and bone. Invasive adenomas are not considered to be malignant; in biological behavior they are between non-infiltrative adenomas and pituitary carcinomas. The latter are defined as tumors with subarachnoid, brain, or systemic metastasis. Invasion may be defined radiologically, operatively, or histologically. On the basis of operatively assessed tumor size and gross invasion of dura and bone as well as immunocytochemical and ultrastructural analysis of 365 pituitary adenomas, the following data were obtained. There were 23 growth hormone (GH)-cell adenomas: 14% microadenomas and 86% macroadenomas; their overall frequency of invasion was 50%. There were 24 prolactin (PRL)-cell adenomas: 33% microadenomas and 67% macroadenomas, with an overall frequency of invasion of 52%. Mixed GH-cell and PRL-cell adenomas were found in 35 cases; 26% were microadenomas and 74% were macroadenomas, and the overall frequency of invasion was 31%. Sixty patients had adrenocorticotropic hormone (ACTH)-cell adenomas (Cushing's disease): 87% microadenomas and 13% macroadenomas; the overall frequency of invasion was 25% (in 8% of microadenomas and 62% of macroadenomas). Twenty patients had ACTH-cell adenomas (Nelson's syndrome): 30% microadenomas and 70% macroadenomas; the overall frequency of invasion in these cases was 50% (in 17% of microadenomas and 64% of macroadenomas). Silent ACTH-cell adenomas, 100% macroadenomas, were found in 11 patients, with an 82% frequency of invasion. There were 32 follicle-stimulating and luteinizing hormone adenomas, all macroadenomas, with a frequency of invasion of 21%. Four patients had thyroid-stimulating hormone adenomas, all macroadenomas, with a 75% frequency of invasion. Null-cell adenomas were found in 93 cases: 2% microadenomas and 98% macroadenomas, with a frequency of invasion of 42%. There were 63 plurihormonal adenomas (GH, PRL, glycoprotein): 25% microadenomas and 75% macroadenomas, with a 50% overall frequency of invasion. Based on this study, and on their usual frequency of occurrence, the estimated rate of gross invasion by pituitary adenomas of all types is approximately 35%. It is concluded that immunocytochemical and ultrastructural characteristics of pituitary adenomas reflect the tendency of these tumors to infiltrate and hence may be of prognostic significance.     

Combined acromegaly and subclinical Cushing disease related to high-molecular-weight adrenocorticotropic hormone

A 36-year-old man with a 1-year history of diabetes mellitus was referred to the authors' hospital for further endocrinological evaluation of acromegaly. On physical examination, typical acromegalic features but no typical cushingoid features were observed. The clinical diagnosis of growth hormone (GH)-producing pituitary adenoma was confirmed by MR imaging findings, nonsuppression of serum GH levels during a 75-g oral glucose tolerance test (trough GH 6.33 ng/ml), and elevated serum insulin-like growth factor-I levels (1361.3 ng/ml). Moreover, autonomic adrenocorticotropic hormone (ACTH) secretion was suspected, based on inadequate suppression of ACTH or cortisol levels by an 0.5-mg overnight dexamethasone suppression test. Analysis of the patient's plasma by using the gel filtration method revealed the presence of a high-molecular-weight (HMW) form of ACTH known to exhibit low biological activity. Transsphenoidal adenomectomy was performed for the pituitary tumor. Immunohistochemical investigation of the resected specimen showed strong and diffuse immunoreactivity to GH and focal immunoreactivity to ACTH. Although there have been a few cases of pituitary adenoma that produced GH and ACTH concomitantly, this is the first report of the detection of HMW ACTH in patients with GH- and ACTH-producing adenomas. Furthermore, the previous cases also did not exhibit typical cushingoid features. It is suggested that the secretion of ACTH in patients with concurrent GH- and ACTH-secreting adenomas might consist of the HMW form and that the HMW ACTH is consequently associated with a subclinical Cushing state.     

Pituitary adenomas that produce adrenocorticotropic hormone and alpha-subunit: clinicopathological, immunohistochemical, ultrastructural, and immunoelectron microscopic studies in nine cases.

Eight surgical and one autopsy specimen of pituitary adenomas (six cases of Cushing's disease, two of Nelson's syndrome, and one of hypopituitarism) were studied by histochemical, immunohistocytological, and ultrastructural methods. Eight tumors showed the characteristic histochemical profile of corticotroph adenoma--amphophilic to basophilic, and periodic acid-Schiff-positive to some extent. In all tumors, immunohistochemical studies revealed adrenocorticotropic hormone (ACTH) and alpha-subunit in the cytoplasm of some adenoma cells. By electron microscopy, seven tumors were found to be monomorphous; six were typical corticotroph adenomas and one was a subtype II silent corticotroph adenoma. One unique lesion was bimorphous--i.e., composed of corticotrophs as well as cells resembling glycoprotein cells. Immunoelectron microscopy by the double-labeling immunogold technique, performed on one corticotroph adenoma, demonstrated the presence of ACTH and alpha-subunit not only within the same adenoma cells but also within the same secretory granules. The cytogenesis of ACTH alpha-subunit tumors, a rare form of plurihormonal adenoma, remains to be elucidated. The duration of disease associated with these tumors exceeded the duration in patients with ordinary corticotroph adenomas. Given the low frequency with which increases in serum alpha-subunit are detectable in patients with such tumors--13% in this series--hormone production is not recognized at preoperative evaluation.     

Direct intraoperative micromethod for hormone measurements of pituitary tissue in Cushing's disease

BACKGROUNDDuring transsphenoidal surgery (TSS) for Cushing’s disease, the surgeon depends on experience to find minute adenomas. Cytological slide preparations or frozen sections, even when successful, are not specific concerning the hormone activity. In an attempt to improve accurate localization of minute ACTH adenomas, we evaluated a new intraoperative method of ACTH measurements in adenoma and anterior lobe microsamples. As most ACTH adenomas are monohormonal, the possible benefit of a GH measurement was investigated.METHODSWe included pituitary tissue of 32 patients, 22 with Cushing’s disease and 10 endocrine inactive pituitary adenomas as control. All patients underwent TSS by one surgeon. Preoperative data, intraoperative and perioperative hormone measurements of homogenized, weighed pituitary tissue samples, and histological findings are presented.RESULTSIn ACTH adenomas, the median ACTH content was found to be 1,688 ng/mg, minimum 345 ng/mg. The median GH was measured at 36 ng/mg. Anterior lobe tissue contained median 80 ng ACTH/mg, maximum 279 ng/mg. Median GH was 2,200 ng/mg. In hormonally inactive adenomas ACTH was less than 0.1 ng/mg, median GH was 5.5 ng/mg. There was no overlap of ACTH content in the tissues investigated. Therefore, by adopting 300 ng ACTH/mg as a cutoff level, a clear discrimination is given. Additional GH measurements are not necessary.CONCLUSIONThis new intraoperative method permits a clear differentiation between adenoma and pituitary tissue. In addition to intraoperative cytology and histology, this method can serve as a specific proof that the ACTH adenoma has been identified during surgery. This may be valuable in difficult cases with unclear intraoperative findings, especially after previously negative exploration.     

Neurosurgical implications of Carney complex

OBJECT: The authors present their neurosurgical experience with Carney complex. Carney complex, characterized by spotty skin pigmentation, cardiac myxomas, primary pigmented nodular adrenocortical disease, pituitary tumors, and nerve sheath tumors (NSTs), is a recently described, rare, autosomal-dominant familial syndrome that is relatively unknown to neurosurgeons. Neurosurgery is required to treat pituitary adenomas and a rare NST, the psammomatous melanotic schwannoma (PMS), in patients with Carney complex. Cushing's syndrome, a common component of the complex, is caused by primary pigmented nodular adrenocortical disease and is not secondary to an adrenocorticotropic hormone-secreting pituitary adenoma. METHODS: The authors reviewed 14 cases of Carney complex, five from the literature and nine from their own experience. Of the 14 pituitary adenomas recognized in association with Carney complex, 12 developed growth hormone (GH) hypersecretion (producing gigantism in two patients and acromegaly in 10), and results of immunohistochemical studies in one of the other two were positive for GH. The association of PMSs with Carney complex was established in 1990. Of the reported tumors, 28% were associated with spinal nerve sheaths. The spinal tumors occurred in adults (mean age 32 years, range 18-49 years) who presented with pain and radiculopathy. These NSTs may be malignant (10%) and, as with the cardiac myxomas, are associated with significant rates of morbidity and mortality. CONCLUSIONS: Because of the surgical comorbidity associated with cardiac myxoma and/or Cushing's syndrome, recognition of Carney complex has important implications for perisurgical patient management and family screening. Study of the genetics of Carney complex and of the biological abnormalities associated with the tumors may provide insight into the general pathobiological abnormalities associated with the tumors may provide insight into the general pathobiological features of pituitary adenomas and NSTs.     

Clinically silent hypersecretion of growth hormone in patients with pituitary tumors

Hypersecretion of growth hormone (GH) was found in three women aged 25 to 35 years old, with somatotroph adenomas without clinical stigmata of acromegaly. The patients had previously been diagnosed as having nonfunctioning pituitary macroadenomas, with extrasellar extension. Concentrations of GH were elevated preoperatively in all subjects and could not be suppressed during oral glucose tolerance testing. Somatomedin-C concentrations were elevated in two patients. Immunocytochemical studies of surgically obtained tumor tissue demonstrated sparse positive staining for GH in all subjects. Gel-chromatographic analysis of serum and tumor tissue samples demonstrated that the immunoactive GH was authentic GH. On pathological examination, the tumor was cellular in all cases, consisting of partly acidophilic and partly chromophobic cells. Electron microscopic analysis of one tumor showed a cell composition not previously described. These studies further characterize GH hypersecretion in a subset of patients with clinically nonfunctioning pituitary macroadenomas.     

The pathogenesis of acromegaly. Clinical and immunocytochemical analysis in 75 patients

A series of 75 patients with acromegaly and immunocytochemically characterized pituitary adenomas has been analyzed. Tumors secreting growth hormone (GH) only were found in 21% of cases. The remainder had tumors immunoreactive for more than one pituitary hormone: GH and prolactin in 31%; GH, prolactin, and glycoprotein in 40%; and GH and glycoprotein in 8%. Microadenomas were surgically treated in 17 patients with a success rate of 82%. Overall, normalization of basal GH secretion (to less than or equal to 5 ng/ml) was achieved in 54% of cases. The implications of these findings for the pathogenesis and neurosurgical management of acromegaly are discussed.     

43例垂体瘤术后成人生长激素水平调查

[摘要]目的了解垂体瘤患者在接受治疗后生长激素的储备功能及生长激素缺乏与多种垂体激素缺乏之间的关系。方法以2008年5月至2013年7月间,以在河北省沧州市中心医院接受治疗的43位垂体瘤患者作为调查对象,进行胰岛素低血糖兴奋试验（11Tr）,分析生长激素（GH）、促性腺激素（Gn）、促甲状腺激素（TSH）、精氨酸加压素（AVP）和促肾上腺皮质激素（ACTH）的分泌功能。结果共入组43例垂体瘤患者,男性29例,女性14例,中位年龄为48岁。其中仅5例Irrr实验兴奋后GH分泌正常,余38例均患严重的生长激素缺乏症,且表现出一种或一种以上的垂体激素缺乏症状。结论垂体瘤术后,生长激素缺乏症的发生率很高;患有一种或一种以上垂体激素缺乏的患者都会伴有生长激素缺乏症。     

Growth hormone and the kidney: the use of recombinant human growth hormone (rhGH) in growth-retarded children with chronic renal insufficiency.

Hypothalamic production of growth hormone releasing hormone stimulates the anterior pituitary gland to release growth hormone (GH). The clinical manifestations of GH on tissues are either direct or are mediated by insulin-like growth factors (IGF). Both the somatic effects of GH and the renal manifestations of an increase in glomerular filtration rate and renal plasma flow are mediated by IGF. The increase in glomerular filtration rate/renal plasma flow that occurs with either exogenous or endogenous GH is not apparent in patients with chronic renal failure (CRF); therefore, it is unlikely that recombinant human growth hormone (rhGH) treatment of patients with CRF will result in glomerular hyperfiltration. Longitudinal studies are required to determine if the glomerulosclerosis and renal functional impairment occurring in GH and growth hormone releasing hormone transgenic mice occurs after rhGH treatment of growth-retarded uremic rats with GH resulted in an improvement in growth velocity. This led to preliminary studies in growth-retarded children with CRF by using rhGH. The acceleration of growth velocity was dramatic despite the fact that GH levels are elevated in uremia. The elevated IGF carrier proteins in uremic children may contribute to the growth retardation. Treatment with rhGH may be efficacious by stimulating a net increase in the free (unbound) IGF levels. Hyposecretion of GH may contribute to the failure to achieve optimal growth after successful renal transplantation. Treatment with rhGH may be efficacious in improving the growth velocity of renal allograft recipients.     

In vitro secretion of follicle-stimulating hormone by pituitary chromophobe adenomas

Of 20 female and 14 male patients with chromophobe adenomas, 4 male patients, aged 38 to 47 years, and one female patient, aged 54, showed above normal basal plasma levels of follicle-stimulating hormone (FSH). An in vitro tissue culture study that was performed using chromophobe cells obtained from 3 of the 4 male patients and the 1 female patient showed moderate FSH secretion into the culture media. The secretion of FSH by pituitary chromophobe adenomas might be more frequent than hitherto suspected.     

Pituitary adenoma composed of two compartments each secreting prolactin or growth hormone

We report a case of pituitary adenoma with two compartments, i.e. a part within the sella turcica and a part infiltrating the sphenoid bone beneath the sella, producing growth hormone (GH) and prolactin. The patient had the amenorrhea-galactorrhea syndrome, but not acromegalic symptoms. Although the two compartments were united through a small dural perforation, immunohistochemical studies demonstrated that GH and prolactin were separately secreted from the intrasellar and extrasellar components, respectively. Somatotropic adenomas frequently produce prolactin, but it is unusual for these hormones to be secreted from distinctly different parts of the same lesion.     

The natural course of growth hormone-secreting pituitary adenomas after surgery alone--clinical significance of the growth hormone response to thyrotropin-releasing hormone and luteinizing hormone-releasing hormone.

The clinical significance of abnormal growth hormone (GH) secretion in response to thyrotropin-releasing hormone (TRH) and luteinizing hormone-releasing hormone (LHRH) was studied in 52 patients with acromegaly due to GH secreting pituitary adenomas treated by trans-sphenoidal microsurgery. The mean period of postoperative follow-up was 4.1 years. In 27 of the 36 patients who had abnormal GH responses to TRH or LHRH before surgery, basal GH levels normalized and abnormal GH responses disappeared immediately after surgery. Among the remaining nine patients, four had normal basal GH levels with abnormal GH responses and five showed persistently abnormal basal GH levels as well as abnormal GH responses. Recurrence requiring retreatment was not observed during follow-up in any of the 31 patients with normal postoperative basal GH levels, regardless of the GH response to TRH or LHRH. All five patients with abnormal basal GH and abnormal GH responses required additional treatment. Among the patients who underwent long-term postoperative TRH and LHRH testing, abnormal GH responses reappeared in three of 19 whose abnormal responses had disappeared immediately after surgery. The abnormal response disappeared spontaneously in two of three patients who had abnormal responses immediately after surgery. In four patients with both abnormal GH responses and abnormal basal GH levels immediately after surgery, abnormal GH responses persisted throughout the follow-up period. In addition, the abnormal GH responses appeared in two of 14 patients who had been nonresponsive before surgery. These results indicate that the postoperative GH response to TRH or to LHRH was not significantly related to the outcome.(ABSTRACT TRUNCATED AT 250 WORDS)     

Radiosurgery of growth hormone-producing pituitary adenomas: factors associated with biochemical remission

OBJECT: The authors reviewed outcomes after stereotactic radiosurgery for patients with acromegaly and analyzed factors associated with biochemical remission. METHODS: Retrospective analysis was performed for 46 consecutive cases of growth hormone (GH)-producing pituitary adenomas treated by radiosurgery between 1991 and 2004. Biochemical remission was defined as a fasting GH less than 2 ng/ml and a normal age- and sex-adjusted insulin-like growth factor-I (IGF-I) level while patients were not receiving any pituitary suppressive medications. The median follow up after radiosurgery was 63 months (range 22-168 months). Twenty-three patients (50%) had biochemical remission documented at a median of 36 months (range 6-63 months) after one radiosurgical procedure. The actuarial rates of biochemical remission at 2 and 5 years after radiosurgery were 11 and 60%, respectively. Multivariate analysis showed that IGF-I levels less than 2.25 times the upper limit of normal (hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.2-6.9, p = 0.02) and the absence of pituitary suppressive medications at the time of radiosurgery (HR 4.2, 95% CI 1.4-13.2, p = 0.01) correlated with biochemical remission. The incidence of new anterior pituitary deficits was 10% at 2 years and 33% at 5 years. CONCLUSIONS: Discontinuation of pituitary suppressive medications at least 1 month before radiosurgery significantly improved endocrine outcomes for patients with acromegaly. Patients with GH-producing pituitary adenomas should not undergo further radiation therapy or surgery for at least 5 years after radiosurgery because GH and IGF-I levels continue to normalize over that interval.     

Detection of mRNA of prolactin and ACTH in clinically nonfunctioning pituitary adenomas

Clinically nonfunctioning pituitary adenomas have been thought to synthesize some pituitary hormones as shown by studies involving cell culture, immunocytochemistry, or measurement of hormone levels in tumor homogenates. Nevertheless, they are not associated with hypersecretion of pituitary hormones. To further clarify hormone synthesis in such pituitary adenomas, the presence of messenger ribonucleic acid (mRNA) of prolactin (PRL) growth hormone, and adrenocorticotropic hormone (ACTH) in the cytoplasm of 16 nonfunctioning adenomas was determined by means of a hybridization technique, and compared to the immunocytochemical findings. In three adenomas (19%) PRL mRNA was detected and in one case (6%) ACTH mRNA was detected. The hybridization technique appears to be more sensitive than immunohistochemistry for detection of specific mRNA's in assigning the hormone synthesis potential to clinically nonfunctioning tumors. The results suggest that PRL and ACTH are synthesized in some cases of clinically nonfunctioning pituitary adenomas and that hybridization techniques are useful to investigate hormone synthesis in pituitary adenomas. The ability to demonstrate PRL mRNA in tumor tissues allowed differentiation between hyperprolactinemia caused by synthesis of PRL in the tumor and that due to hypersecretion from the adjacent normal pituitary.     

Plasma and pituitary content of growth hormone luteinizing hormone, and prolactin in uremic rats. Effects of chronic infusion of insulin

The influence of chronic renal failure on pituitary content and on serum concentrations of growth hormone (GH), prolactin (PRL), and luteinizing hormone (LH) was studied in chronically uremic rats by comparison with control rats fed ad libitum and diet-restricted rats pair-fed with uremic rats. A decrease of pituitary GH content was found in uremic and diet-restricted rats, in association with a normal circulating GH level. A decrease of pituitary PRL and LH content with respectively high and normal serum values was observed in uremic but not in diet-restricted rats. These data strongly suggest that GH disturbances are related to malnutrition, whereas PRL and LH abnormalities are related to the uremic state per se. As hypoinsulinemia was observed in uremic rats, and as insulin is largely implicated in growth, we have investigated the effects of chronic infusion of insulin, using miniosmotic pumps, on pituitary hormone content. In spite of normalization of circulating insulin levels in uremic rats treated with insulin, pituitary GH, LH, and PRL contents were unaffected. Thus, insulin deficiency did not appear to be responsible for the diminished pituitary reserve of these hormones.