A rare case of a thyrotropin-secreting pituitary tumor which responded to methimazole

A 52-year-old Japanese male complained of palpitations and excessive sweating. He showed evidence of hyperthyroidism, but without suppression of the serum thyroid-stimulating hormone (TSH). On admission, the serum level of the alpha-subunit of TSH was elevated, but tests for thyroid autoantibodies were negative. The TSH response to thyrotropin-releasing hormone (TRH) was blunted. Imaging studies revealed a pituitary tumor 2 cm in diameter. Administration of methimazole lowered the serum levels of thyroid hormones, and elevated the serum level of TSH. These findings led to the diagnosis of a thyrotropin-secreting pituitary tumor. Immunohistochemical analysis and electron microscopic findings verified the diagnosis.     

Long-term preoperative management of thyrotropin-secreting pituitary adenoma with octreotide

Thyrotropin (TSH)-secreting pituitary adenomas are the less frequent form of presentation of pituitary tumors. Selective transsphenoidal surgical resection of the tumor is the treatment of choice. Given that native somatostatin inhibits TSH secretion, treatment with somatostatin analogues has been recently employed in patients with unresectable tumors or after surgery. We report on the case of a 58 year-old man with a TSH-secreting pituitary adenoma who was treated with octreotide for long-term before neurosurgery. The patient was referred to us because of a pituitary mass on CT scanning. Hormonal evaluation resulted in hyperthyroidism with high serum TSH concentrations. Serum alpha subunit concentration was elevated and TSH response to exogenous TRH stimulation was absent. Magnetic resonance imaging of the hypothalamic-pituitary area confirmed the presence of a pituitary mass (2.0 by 1.8 by 1.7 cm). Acutely administered subcutaneous octreotide (100 microg) was followed by a reduction of the serum TSH concentrations. Therefore, the patient received octreotide, 100 microg three times daily for 12 months. At first month after beginning therapy serum TSH, free thyroxine, total triiodothyronine, and alpha subunit concentrations were normalized and persisted into the normal range for the next 11 months. On the other hand, a shrinkage of the tumor mass (1.6 by 1.7 by 1.4 cm) was noted after 6 months of octreotide therapy, however, its volume did not modify in the following next months. Then, the tumor was removed by transsphenoidal surgery and the diagnosis was confirmed by immunohistochemical staining. This case demonstrates that long-term treatment with octreotide gave rise to a normalization of the thyroid function and a reduction of the tumor volume before surgery. This clinical observation suggests that octreotide therapy might be useful in preparation for pituitary surgery in patients with TSH-secreting pituitary adenomas.     

Recurrent goiter, hyperthyroidism, galactorrhea and amenorrhea due to a thyrotropin and prolactin-producing pituitary tumor

A 22-year-old woman with recurrent goiter, hyperthyroidism, galactorrhea, and amenorrhea due to a pituitary tumor is described. She had been treated surgically twice for recurrent goiter with tracheal compression. Despite clinical signs of hyperthyroidism and slightly elevated plasma thyroid hormone levels (T4: 11 mug/dl; T3: 189 ng/dl), without thyroid hormone replacement therapy the basal TSH level was elevated up to 23 muU/ml and could not be suppressed by exogenous thyroid hormones: even when the serum thyroid hormone levels were raised into the thyrotoxic range (T4: 16.2 mug/dl T3: 392 ng/dl), the basal TSH fluctuated between 12 and 29 muU/ml. The basal PRL level was elevated up to 6000 muU/ml. The administration of TRH (200 mug iv) led only to small increments of TSH and PRL levels. Bromocriptin (5 mg p.o.) or l-dopa (0.5 g p.o.) suppressed TSH and PRL values significantly. After transsphenoidal hypophysectomy, TSH and PRL were below normal and the patient development panhypopituitarism. The adenoma showed two cell types which could be identified as lactotrophs and thyrotrophs by electronmicroscopy and immunofluorescence. From these data we conclude that the patient had a pituitary tumor with an overproduction of thyrotropin and prolactin.     

Recent management of pituitary adenomas

Eight 2-day-old SPF chickens were each inoculated orally with a single dose of 5 x 10(5) oocysts of Cryptosporidium baileyi, and immunoglobulin G (IgG) antibody responses were chronologically measured by indirect immunofluorescent antibody (IFA) assay. Anti-C. baileyi IgG antibody levels remained high (1:106.67 to 1:512.00) for at least 4 months with 330 days of a detectable period. Ten days after the negative conversion, each chicken was re-challenged with 1 x 10(7) oocysts of the same species. Subsequent infection in 340-day-old individuals caused sudden elevated IgG antibody levels and the titer peaked on day 28 postchallenge inoculation (PCI), at 1:1.024 with a 65 days of detection period. Chickens in primary infection showed oocyst shedding profiles, but did not exhibit any oocyst shedding before or after experimental reinfection.     

A thyrotropin-secreting pituitary adenoma as a cause of thyrotoxic periodic paralysis

We describe a patient with thyrotoxic periodic paralysis (TPP) caused by a thyrotropin-secreting pituitary adenoma. The diagnosis TPP was based on the combination of episodes of reversible hypokalaemic paralysis, hyperthyroidism and electrophysiological findings. A thyrotropin-secreting pituitary adenoma was diagnosed on the basis of endocrinological function tests and MRI of the pituitary gland. Before transsphenoidal resection of the adenoma, treatment with octreotide restored euthyroidism both clinically and biochemically. Immunocytochemistry of the pituitary adenoma was positive for TSH exclusively. Incubation with octreotide or quinagolide induced decreased TSH and alpha-subunit production by the cultured adenoma cells, in agreement with the pre-operative in vivo data. This paper is the first to describe in vivo and in vitro characteristics of a thyrotropin-secreting pituitary adenoma in a patient presenting with periodic paralysis.     

Normal final height and apparent cure after pituitary irradiation for Cushing''s disease in childhood: long-term follow-up of anterior pituitary function

1. We evaluated the effects of ethanol on (Na + K)-ATPase activity and cAMP response to vasopressin in native and cultured rat papillary collecting duct (PCD) cells. 2. A significant increase in (Na + K)-ATPase and Mg(2+)-ATPase activities was found in PCD cells either isolated from chronic ethanol-fed rats or cultured in the presence of ethanol. 3. Acute treatment with ethanol resulted in a biphasic effect on the activity of (Na + K)-ATPase, which was enhanced below 1% ethanol and inhibited at higher concentrations. 4. Chronic ethanol treatment did not change the cAMP response of PCD cells to vasopressin. Acutely, in turn, this response was enhanced by ethanol per se. 5. It is suggested that the antinatriuretic effect of ethanol could be at least in part mediated by a (Na + K)-ATPase enhancement in PCD cells. Acutely, ethanol could normalize water balance by its peripheral effects on distal nephron.     

Human mixed somatotrophic and lactotrophic pituitary adenomas

Six patients with acromegaly at examination were found to have pituitary adenomas composed of cells that secreted GH and PRL. This was demonstrated by the elevated serum hormone concentrations, by immunoperoxidase staining of 5 specimens, and by electron microscopic examination of 4. Ultrastructural characteristics, described in detail, suggest that these adenomas were mixed adenomas consisting of 2 well-defined, distinct cell types, each secreting one hormone. By immunoperoxidase staining some cells were found to contain immunoreactive growth hormone, other cells immunoreactive prolactin. No cells were detected exhibiting immunostaining for both growth hormone and prolactin. Eelctron microscopy, consistent with the results of immunostaining, revealed the presence of two distinct cell types, distinguishable from each other by their characteristic fine structural features. No intermediate forms were noted. Thus there was no evidence to suggest that one cell type might transform to the other. Present findings seem to indicate that mixed adenomas secreting growth hormone as well as prolactin and consisting of somatotrophs as well as lactotrophs do occur in the human pituitary gland. Although all the results obtained so far suggest that these tumors are composed of two distinct cell types and thus can be interpreted as representing real mixed adenomas, further work is required to establish whether or not they derive from one common progenitor.     

MRI of the pituitary adenomas with reference to the hormonal activity

Many studies in Magnetic Resonance Imaging (MRI) of pituitary adenomas are already performed. However, few reports exist about MRI findings of pituitary adenomas with reference to the hormonal activity, therefore, we evaluated this problem on the viewpoint of the signal intensity in MRI and pathological features. Fifteen patients with growth hormone producing adenoma (GH-group), 6 patients with prolactin producing adenoma (PRL-group), 15 patients with endocrinologically non-functioning adenoma (Null-group) and 9 cases with normal pituitary gland (normal control group) were examined. Signal intensity values in adenoma (or anterior lobe in normal control group) and in pons as standard value were measured in each cases, then their rates were calculated as signal intensity ratio (SIR). In 24 cases (14 in GH-group, 3 in PRL-group, 7 in Null-group), cellular density were examined with surgically resected specimens. In the T1-weighted images (T1 WIs), PRL-group and Null-group presented more hypointense tendency than normal control group. In the T2-weighted images (T2 WIs), only Null-group presented more hyperintense tendency than other groups. But significant correlation was not observed between SIR and cellular density.     

Null cell adenomas and oncocytomas of the pituitary gland

This review highlights the most interesting features of null cell adenomas and oncocytomas of the pituitary gland. Recently, application of sensitive methods have documented a very low amount of active hormone production in these clinically nonfunctioning tumours. However, further studies are needed to clarify the histogenesis of null cell adenomas and oncocytomas.     

In vivo responsiveness of morphological variants of growth hormone-producing pituitary adenomas to octreotide

The somatostatin analog, octreotide, is an inhibitor of growth hormone (GH) secretion that has been used to treat patients with GH-producing pituitary tumors. In this study we investigated the in vivo responsiveness to treatment with this analog in patients harboring different morphological types of GH-producing pituitary adenomas. Both GH and insulin-like growth factor I (IGF-I) plasma levels in 30 patients treated with octreotide (300 micrograms/day) for 4 months preoperatively were compared with those from 30 patients who did not receive treatment preoperatively. Tissue samples were studied using ultrastructural and immunohistochemical techniques. Amongst patients harboring densely granulated (DG) adenomas, mean GH levels were reduced to 32 +/- 9% by octreotide, to 30 +/- 7% by surgery and to 26 +/- 9% of baseline by both interventions. Surgery was equally as effective in lowering GH levels in patients with sparsely granulated (SG) adenomas as it was in those with DG adenomas; in patients with SG adenomas, GH levels were reduced by surgery alone to 37 +/- 16% and to 24 +/- 15% when performed following octreotide pretreatment. In contrast, treatment with octreotide alone in patients harbouring SG adenomas reduced GH levels to only 70 +/- 13% of baseline (p < 0.02 compared to surgery alone, or surgery and octreotide). We conclude that the GH inhibitory effects of octreotide are significantly better in patients harboring DG somatotroph adenomas compared with those harboring SG adenomas.     

Transferrin and transferrin receptor in human hypophysis and pituitary adenomas

The activity of three human immunodeficiency virus (HIV) protease inhibitors was investigated in human primary monocytes/macrophages (M/M) chronically infected by HIV-1. Saquinavir, KNI-272, and ritonavir inhibited the replication of HIV-1 in vitro, with EC50s of approximately 0.5-3.3 microM. However, only partial inhibition was achievable, even at the highest concentrations tested. Also, the activity of these drugs in chronically infected M/M was approximately 7- to 26-fold lower than in acutely infected M/M and approximately 2- to 10-fold lower than in chronically infected H9 lymphocytes. When protease inhibitors were removed from cultures of chronically infected M/M, production of virus rapidly returned to the levels found in untreated M/M. Therefore, relatively high concentrations of protease inhibitors are required to suppress HIV-1 production in chronically infected macrophages, and such cells may be a vulnerable point for the escape of virus in patients taking these drugs.     

Transnasal stereotactic surgery of pituitary adenomas concomitant with acromegaly

Since 1960 we have performed stereotactic transsphenoidal cryohypophysectomy in 70 patients with pituitary adenomas, 42 women and 28 men, aged 11-59 years. The dominant clinical syndrome was acromegaly in 50 patients, galactorrhea in 9, amenorrhea in 5, adiposogenital dystrophy in 4 and gigantism with mild endocrine symptomatology in 2 patients. In 67 patients the histological structure of the tumor was established by biopsy (50 patients with eosinophil adenoma, 10 with mixed-type adenoma, 4 with chromophobe adenoma and 3 with basophil adenoma). Somatotropic hormone, human growth hormone, prolactin, ACTH and 17-ketosteroid levels indicated active/inactive adenomas. In 42 cases the adenoma was only intrasellar, which was confirmed by contrast X-ray investigations, CT scanning, angiography and ophthalmological investigation. Transnasal stereotactic cryohypophysectomy was performed in all 70 cases using a stereotactic apparatus especially designed for operations on the pituitary. All patients (except 2) tolerated the operation well. No complications occurred. Vision deteriorated after operation in 1 patient. Thrombosis of the left middle cerebral artery developed in another patient. All the other patients noted improvement directly after operation - rapid diminution of signs of acromegaly and rapid restoration of normal values in hormonal tests. Six patients with continuing growth of the tumor underwent a second operation 1.5-6 years after the first operation. We conclude from our own clinical experience and information from the literature that transnasal stereotactic cryodestruction is highly effective and relatively safe in the management of pituitary adenoma.     

Neuro-ophthalmological alternations in patients with pituitary adenomas and intrasellar arachnoidocele

INTRODUCTION, MATERIAL AND METHODS: We studied 103 patients with hypophyseal tumors aged between 15 and 74, with a marked predominance of females. Results. Of these, 49 patients were diagnosed as having macroadenomas (47.5%), 27 with microadenomas (26.2%), 25 with arachnoidoceles (24.3%) and two with craniopharyngiomas (1.9%). Of the total there were 78.9% functioning tumors of which the commonest was prolactinoma. CONCLUSIONS: Kinetic and static perimetry complement each other as diagnostic methods to obtain information about damage to the visual pathway caused by these tumors.     

Cushing's syndrome due to bilateral adrenocortical adenomas with different pathological features

A 48-year-old woman with Cushing's syndrome due to bilateral adrenocortical adenomas is reported. The patient presented with a typical Cushingoid appearance. The serum cortisol level was elevated with loss of the diurnal rhythm and the plasma adrenocorticotropic hormone (ACTH) level was undetectable. Dynamic testing showed no suppression of urinary 17-OHCS by high-dose dexamethasone and no stimulation by metyrapone. An abdominal computed tomography (CT) scan showed bilateral adrenal tumors. Bilateral adrenalectomy was performed. The right adrenal gland contained a tumor that was encapsulated and consisted mainly of compact cells. The surrounding cortex was atrophic. The left adrenal gland contained an encapsulated tumor composed predominantly of clear cells. There were numerous small adrenocortical nodules in the surrounding cortex. Immunohistochemical analysis of steroidogenic enzymes (P450scc, 3beta-HSD, P450c21, P450c17 and P450c11) was performed. Immunoreactivity of all the enzymes was intense in the compact cells of the right adrenocortical adenoma, while the adjacent non-neoplastic cortex was negative for the enzymes. In the left adrenal tumor, the immunoreactivity of 3beta-HSD was intense, while that of P450c17 was weak. In the adrenocortical nodules, 3beta-HSD activity was sporadically observed. G protein genes encoding Gs alpha and Gi2 were examined for activating mutations at codons 201 and 227 (Gs alpha) and codons 179 and 205 (Gi2 alpha) in the bilateral adrenal tumors, but no mutations were found. The bilateral adenomas of this patient showed marked differences in microscopic and immunohistochemical studies, suggesting that the capacity of steroidogenesis differs between the right and left tumors.     

Intact leptin receptor is selectively expressed in human fetal pituitary and pituitary adenomas and signals human fetal pituitary growth hormone secretion

Leptin, a circulating hormone secreted by adipocytes, communicates peripheral nutritional status to hypothalamic centers affecting satiety, energy expenditure, and body weight. The intact leptin receptor (OB-R), a single membrane-spanning peptide containing an approximately 300-amino acid intracellular domain, is highly expressed in the hypothalamus, whereas shorter OB-R isoforms with truncated cytoplasmic regions resulting from alternative splicing have also been identified. We studied expression of OB-R isoforms in human fetal pituitaries, adult anterior pituitaries, and human pituitary adenomas. Using RT-PCR, messenger ribonucleic acid expression of the OB-R intact isoform was detected in fetal anterior pituitary tissues, but not in adult anterior pituitary glands, whereas both fetal and adult tissues expressed the short forms. Messenger ribonucleic acid of both intact and short OB-R isoforms were expressed in 4 of 5 GH-secreting, all 9 PRL-secreting, and 26 of 29 nonfunctioning pituitary adenomas. Recombinant human leptin (3-6 nmol/L) specifically stimulated GH secretion from primary human fetal pituitary cultures by 40-90% (P < 0.05) without altering fetal ACTH, PRL, or gonadotropin secretion. Thus, the intact OB-R is selectively expressed in human fetal and adult pituitary tumor tissues, but not in normal adult pituitary. Leptin specifically stimulates GH release from normal fetal somatotrophs, substantiating the functionality of its intact receptor in the fetal pituitary. Thus, pituitary adenomas appear to revert to a fetal phenotype of leptin receptor expression.     

Manifestation of primary hyperthyroidism after pituitary adenomectomy: a case report

We report a 47-year-old Japanese man who presented with visual disturbance due to a pituitary tumor with suprasellar extension. The patient had mild secondary hypothyroidism preoperatively, and was started on administration of levothyroxine sodium immediately before transsphenoidal surgery. After the operation, levothyroxine sodium was continued for several months. Pathological examination of the surgical specimen, together with endocrinological investigation revealed that the suprasellar tumor was a FSH-producing pituitary adenoma. Since 3 months after the operation, he has developed muscle weakness and finger tremor. He was found to be thyrotoxicosis, and levothyroxine sodium was discontinued. Seven weeks after levothyroxine sodium was discontinued, thyrotoxicosis continued, with a positive thyrotropin binding inhibitory immunoglobulin (TBII) and a high diffuse 123I-uptake by the thyroid. He was started on thiamazole 30 mg/day. Although his thyroid dysfunction improved within 2 months, hyperthyroidism worsened repeatedly on attempts to discontinue thiamazole, and he required continuous treatment at 2.5 mg/day. Patients with occult autoimmune thyroiditis rarely progress to thyrotoxicosis after operations on other endocrine organs such as the adrenal or parathyroid gland. In patients with pituitary adenoma, thyroid function and thyroid-associated autoantibodies should be investigated pre- and post-operatively.