Robert Maurice Salassa.
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Adrenal Cortex Diseases↗
Biomedical subjects
R V Randall
Publications and source records attributed to R V Randall.
The pituitary gland in hyperthyroidism.
The pituitary glands of 33 patients (24 women and 9 men, 18 to 78 years old) who died in thyrotoxicosis (18 with Graves' disease and 15 with toxic multinodular goiter [Plummer's disease]) were examined by histologic and immunocytologic methods. Thirteen patients (39%) died in "thyroid storm." The avidin-biotin-peroxidase complex immunostaining method was used to demonstrate the spectrum of pituitary hormones, including growth hormone, prolactin, adrenocorticotropic hormone, thyrotropin, follicle-stimulating hormone, luteinizing hormone, and alpha-subunit. The most striking finding was a pronounced decrease or loss of immunoreactivity to thyrotropin in all thyrotoxic cases, a consistent change that allowed ready distinction of thyrotoxic from euthyroid pituitary glands. When immunoreactive thyrotrophs were identified, they were sparse and small and demonstrated only faint thyrotropin reactivity. No morphologic differences were noted between the pituitary glands of patients with Graves' disease or Plummer's disease or between sexes. Loss of thyrotropin immunoreactivity was found to be reversible in that thyrotropic cells in the pituitary glands of 16 additional concurrently studied patients, who had thyrotoxicosis but were treated and subsequently had normal thyroid function or hypothyroidism, appeared normal or even hyperplastic. Other types of adenohypophysial cells in both the thyrotoxic and the successfully treated groups exhibited no abnormalities. Pituitary adenomas were incidental findings in 6 of the 33 patients (18%). Their immunotypic spectrum included three prolactin-immunoreactive tumors, two growth hormone-containing adenomas (one of which was plurihormonal), and one tumor with follicle-stimulating hormone and luteinizing hormone; no thyrotropin-containing adenomas were noted. No examples of pituitary hyperplasia were encountered in pituitary glands of thyrotoxic patients, and no hypophysitis or fibrosis was noted.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenoma↗
The pituitary gland in pregnancy: a clinicopathologic and immunohistochemical study of 69 cases.
A histologic and immunocytochemical study of 69 autopsy-obtained pituitaries from women who died during pregnancy, after abortion, or in the postpartum period revealed an accumulation of large chromophobic to slightly acidophilic and periodic acid-Schiff-negative pregnancy cells that were immunoreactive for prolactin but not for other pituitary hormones. This increase in the number of prolactin cells was confirmed by cell counts. Thus, pregnancy cells are capable of prolactin production. The finding of mitotic figures in such cells supports the view that they arise by multiplication from preexisting prolactin cells. With use of "mirror section" techniques, no mammosomatotrophs (cells immunoreactive for growth hormone and prolactin) were identified. Hyperplasia of prolactin cells was evident at 1 month of pregnancy and gradually disappeared within several months after delivery or abortion; the process of involution seemed to be retarded in the one lactating patient investigated. In some pituitaries, the accumulation of prolactin cells was so extensive that the hyperplastic foci resembled microadenomas. Another striking change in the pituitaries of pregnant women was appreciable reduction of immunostaining of gonadotropic cells, a process that was reversible as soon as 1 month after delivery. Among the 69 pituitaries studied, 8 noninvasive microadenomas (12%) were encountered (7 contained prolactin only and 1 was plurihormonal). Prolactin-producing adenomas were no more numerous or larger than were similar tumors encountered in nonpregnant women or normal men; thus, pregnancy neither initiates formation of pituitary adenomas nor accelerates their growth. In the pituitaries that harbored prolactin-producing adenomas, massive pregnancy cell hyperplasia was evident outside the tumor; thus, prolactin production by adenoma cells did not seem to suppress the proliferation of prolactin-containing pregnancy cells.
Adenoma↗
Effects of estrogen on the human pituitary: a clinicopathologic study.
Pituitary glands obtained at autopsy of 67 men treated with diethylstilbestrol were examined for diffuse and nodular lactotrophic hyperplasia as well as prolactin cell tumorlets or adenomas. A control group consisted of 42 untreated patients with prostatic carcinoma and 209 other elderly men. Diffuse and nodular lactotrophic hyperplasia and the percentage of prolactin cells were greater in treated patients, but these differences were not statistically significant. The higher frequency of prolactin cell adenomas among treated patients (19%) than among control subjects (11%) also lacked statistical significance. An apparent low frequency of occurrence of adenoma in control patients with prostatic carcinoma remains unexplained. No correlation was noted between tumor number, size, morphologic features, or immunoreactivity and such factors as dose of estrogen therapy, associated diseases, ultimate cause of death, or patient age. A correlation was noted, however, between duration of estrogen therapy and the total number of pituitary adenomas, including those composed of prolactin cells. Relative proportions of other types of adenoma were similar within the study and control groups. We conclude that estrogen medication cannot be considered a major risk factor in the cause of prolactin-producing adenomas in older men.
Adenoma↗
Combined thyrotroph and lactotroph cell hyperplasia simulating prolactin-secreting pituitary adenoma in long-standing primary hypothyroidism.
Primary hypothyroidism accompanies more than 50% of clinically significant pituitary thyrotroph adenomas. Hypothyroidism may also produce pituitary enlargement secondary to thyrotroph hyperplasia and present with a sellar mass and hyperprolactinemia. Three hypothyroid patients who presented with presumed prolactin-producing adenomas are reported. Although laboratory and radiologic abnormalities of pituitary enlargement may resolve after corrective thyroid therapy, our patients showed no such response and underwent operation. Histologic examination revealed no adenomas, but thyrotroph and lactotroph hyperplasia were present. Thyrotroph hyperplasia probably results from lack of negative feedback of thyroid hormone upon the anterior pituitary. Whether this is due to hypothalamic release of thyrotropin-releasing hormone (TRH) or another mechanism is unclear. Lactotroph hyperplasia may result from excess TRH, which stimulates lactotrophs with resultant hyperprolactinemia, or from reduced hypothalamic dopamine, thereby facilitating prolactin secretion. This study suggest that (a) hyperprolactinemia in hypothyroidism is not necessarily due to the "stalk section effect" secondary to pituitary enlargement, and (b) patients with primary hypothyroidism and sellar mass should initially be managed medically so that potentially reversible pituitary hyperplasia is not mistaken for adenoma.
Adenoma↗
Anorexia nervosa: an immunohistochemical study of the pituitary gland.
The morphologic features of the anterior pituitary gland were studied by immunohistologic methods in 12 patients who had died of complications of anorexia nervosa, 4 patients who had died while on a "crash diet", 13 patients who had died of organic disease associated with inanition, and 5 age- and sex-matched control subjects who had been involved in sudden fatal accidents. All known pituitary hormones were found to be present. Abnormalities noted in both the patients with anorexia and those with organic inanition included relative hypogranulation of adrenocorticotropic and, to a lesser extent, growth hormone cells. These changes are of unknown importance but are likely the result of starvation in that they were not observed in patients on a "crash diet" or in control patients. We conclude that no specific or etiologic abnormalities are present in the pituitary glands of subjects with anorexia nervosa and that the altered secretion of adenohypophyseal hormones often noted in patients with this disorder cannot be attributed to a primary pituitary disorder.
Adolescent↗
The pituitary gland in the Laurence-Moon syndrome.
The apparent hypogonadism in patients with the Laurence-Moon syndrome has been variably attributed to unresponsiveness of target organs to gonadal hormones, primary end-organ failure, hypothalamic dysfunction, or pituitary failure. We report the first immunocytologic study of the pituitary gland in this rare disorder. No morphologic abnormalities were noted. The numbers and immunoreactivities of adenohypophyseal cell types were normal. No microscopic abnormalities were evident in the hypothalamus and target organs. The results of our study are consistent with recent biochemical data that suggest that pituitary function is normal in patients with this syndrome.
Adolescent↗
Pituitary adenomas of the multiple endocrine neoplasia type I syndrome.
In a series of 1,500 pituitary adenomas surgically resected at Mayo Clinic, 41 (2.7%) occurred in the setting of multiple endocrine neoplasia, type I (MEN-I). Of the 40 patients (18 males, 22 females), 21 (52%) presented with clinical evidence of a pituitary neoplasm, 13 with hyperparathyroidism, and two with functional islet cell tumor. Of the 41 tumors, 11 (27%) were microadenomas, and 30 (73%) were macroadenomas. Immunocytochemical studies demonstrated the following reactivities: GH (4), GH/PRL (6), GH/PRL/glycoprotein (7), GH/ACTH/glycoprotein (1), PRL (16), PRL/TSH (1), ACTH (3), and null cell adenoma (3). We conclude that, in comparison with pituitary adenomas occurring in the general population, those occurring in association with MEN-I are (1) more often endocrinologically functional, (2) more frequently GH- or PRL-producing, and (3) clinicopathologically similar in terms of the subjects age and sex as well as of tumor size and invasiveness.
Adenoma↗
Pathology of excessive production of growth hormone.
Since its clinical description in the last century, much progress has been made in our understanding of acromegaly. From an initial description of pituitary enlargement as just another manifestation of generalized visceromegaly, the pituitary abnormality has come to be recognized, in most instances, as the underlying aetiological factor. Gigantism and acromegaly are manifestations of disordered pituitary physiology, but the lesion responsible may be hypothalamic, adenohypophyseal or ectopic in location. The best known pathological hypothalamic basis for acromegaly is represented by a neuronal malformation or 'gangliocytoma'. It usually takes the form of an intrasellar gangliocytoma or, more rarely, a hypothalamic hamartoma. The neuronal elaboration of GHRH may play a role in the development of a growth hormone adenoma; the pituitary process may pass through an intermediate stage of somatotropic hyperplasia. When acromegaly has its basis in a pituitary abnormality, the lesion is almost exclusively an adenoma; the non-tumorous adenohypophysis shows no evidence of coexistent hyperplasia. Surprisingly, such tumours are more often engaged in the formation of multiple hormones rather than GH alone. They frequently produce not only GH and prolactin, the products characteristics of cells of the acidophil line, but also glycoprotein hormones, usually TSH. The spectrum of adenomas also varies in its degree of differentiation from a histogenetically primitive lesion, the acidophil stem cell adenoma, to well-differentiated tumours of varying cellular composition and hormone content. Each adenoma type has its clinicopathological, histochemical, immunocytological and ultrastructural characteristics. The isolation and characterization of GHRH has permitted the identification of neuroendocrine tumours, most of foregut origin, elaborating this releasing hormone. Such functional tumours induce hyperplasia of pituitary somatotrophs and may, on occasion, result in the formation of growth hormone adenomas. Resection of these GHRH-producing neoplasms results in reversal of endocrinological and sellar abnormalities. Future efforts should be directed toward the elucidation of the aetiology of pituitary adenomas, specifically whether they represent a proliferative process having its origin in endocrinological imbalance, presumably a hypothalamic abnormality, or whether it has a 'de novo' origin in the 'usual process of neoplastic transformation'.
Acromegaly↗
The treatment of acromegaly.
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Acromegaly↗
Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas.
Little has been written about the long-term results of transsphenoidal treatment for clinically nonfunctioning pituitary adenomas. The records of 100 patients who had undergone a transsphenoidal procedure for excision of such tumors were reviewed. Immunocytology for pituitary hormones was performed in all cases. The group consisted predominantly of null-cell adenomas, although a small number of prolactinomas and gonadotropic tumors were found. The mean diameter of the tumors at the time of detection was slightly more than 2 cm. In most cases, the presenting symptoms were due to the mass effect of the tumor (that is, visual symptoms in 72 patients, hypopituitarism in 61, headache in 36, and cranial nerve disturbance other than visual loss in 10). Radiation therapy was recommended for patients in whom subtotal removal of the adenoma was expected. Six patients developed symptomatic tumor recurrence, and 10 patients demonstrated radiographic recurrence during the 48 to 100 months (mean 73.4 months) of follow-up observation. Only three of 10 deaths during the follow-up period were due to pituitary disease or treatment.
Adenoma↗
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.
Adenoma↗
Plurihormonal pituitary adenomas.
Plurihormonal adenomas of the pituitary, ie, tumors that engage in the production of unusual combinations of hormones, represent approximately 10% to 15% of all adenomas. Such tumors comprise in excess of 50% of adenomas in the setting of acromegaly and occur with somewhat greater frequency in childhood and adolescence than in adulthood. Eight percent are associated with multiple endocrine neoplasia, type I. The most common variant of plurihormonal adenoma produces growth hormone, prolactin, and one or more glycoprotein hormones, the most common being TSH. Clinical effects most often reflect the presence of growth hormone, and to a lesser extent, prolactin cells; expression of glycoprotein hormone production is rare. The tumors are more often macroadenomas (80%) than microadenomas (20%) and demonstrate gross invasion in 50% of cases. Plurihormonal adenomas may be ultrastructurally monomorphous, bimorphous, or trimorphous; thus, one morphologic cell type may elaborate several hormones.
Adenoma↗
Prolactin cell carcinoma of the pituitary. Clinicopathologic, immunohistochemical, and ultrastructural study of a case with cranial and extracranial metastases.
A patient with a primary adenohypophyseal neoplasm who had a long course marked by multiple surgical resections, radiation therapy, and high-dose dopamine agonist therapy developed local invasion as well as cranial and extracranial osseous metastatic lesions. The serum prolactin levels were greatly elevated, and immunohistochemical studies demonstrated prolactin in the cytoplasm of primary and metastatic tumor cells. Ultrastructural features of lactotrophic differentiation, including misplaced granule exocytosis, were observed. This is the third reported case of prolactin cell carcinoma that metastasized despite high-dose dopamine agonist therapy. Analysis of the patient's serum prolactin showed no abnormality in the chromatographic profile of biologic activity.
Biological Assay↗
Pituitary adenomas associated with hyperprolactinemia: a clinical and immunohistochemical study of 97 patients operated on transsphenoidally.
Immunohistochemical studies were performed on the tumors of 97 of 100 patients who had undergone an operation for a presumed prolactin-secreting pituitary adenoma; no tissue was available for study in the other 3 patients. Appropriate immunohistochemical studies were done to identify the presence of growth hormone, prolactin, adrenocorticotropic hormone, luteinizing hormone, follicle-stimulating hormone, and thyroid-stimulating hormone within the adenoma cells. The presence of a prolactin-producing pituitary adenoma was confirmed in 91 patients, 3 of whom had an adenoma that consisted of cells that contained prolactin and growth hormone. One other patient, not counted among the 91 with prolactinoma, had lactotrope and thyrotrope hyperplasia. Among the five patients whose adenoma did not contain prolactin cells, four had a null cell adenoma and one had a tumor consisting of follicle-stimulating hormone and luteinizing hormone immunoreactive cells. On the basis of preoperative serum prolactin values in these patients, we concluded that moderately increased values (30 to 200 ng/ml) of serum prolactin are not a reliable guide for determining whether a prolactin-producing pituitary adenoma is present, whereas levels exceeding 200 ng/ml are usually associated with a prolactin-secreting tumor.
Adenoma↗
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.
Acromegaly↗
Metastasis to pituitary adenoma.
Neoplasm to neoplasm metastasis is a medical curiosity. We report two cases of adenocarcinoma metastatic to pituitary adenoma. In both, abrupt progression of symptoms referable to the sellar region was noted and followed by the death of the patient.
Adenoma↗
Pituitary gland in hypothyroidism. Histologic and immunocytologic study.
Primary hypothyroidism is associated with hypertrophy and hyperplasia of thyrotropic cells. In addition, pituitary adenomas that produce thyroid-stimulating hormone occur in both hypothyroidism and hyperthyroidism. The relationship between thyrotropic hyperplasia and adenoma formation is, however, unsettled. We summarize the results of a histologic and immunocytologic study of the pituitary glands of 64 patients with long-standing primary hypothyroidism in an effort to characterize the changes in thyrotropic cells as related to the duration and severity of disease, to therapy, and to the development of thyrotropic adenomas. Diffuse and nodular thyrotropic cell hyperplasia was noted in 69% and 25% of glands, respectively. A crude correlation was observed between the degree of thyrotropic cell hyperplasia and the relative lack of thyroid hormone replacement therapy. In 12% of glands, tumorlet formation was observed, perhaps representing an intermediate stage between nodular hyperplasia and the development of microadenoma. Twelve adenomas were noted, five of which contained thyroid-stimulating hormone immuno-reactive cells. Although thyroid hormone deficiency seemed to selectively affect thyrotropic cells, lactotropic hyperplasia was observed in 20% of patients; the mechanism accounting for prolactin cell hyperplasia remains obscure.
Adenoma↗