Type 1 diabetes associated with asymptomatic acromegaly successfully treated with surgery after pregnancy: a case report.
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We report a rare case of type 1 diabetes in a woman associated with acromegaly who was treated with surgery after pregnancy. An 18-year-old woman came to our hospital in April, 1998, complaining of thirst, polydipsia, polyuria, appetite loss, body weight loss of 8 kg in a month, and amenorrhea beginning 2 months earlier. Based on laboratory data, she was diagnosed as having type 1 diabetes mellitus. Although we suspected her of having acromegaly because of high growth hormone (GH) levels (6.9 or 8.5 ng/ml), blood levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) were within normal range and the circadian rhythm of her blood GH levels was normally maintained. Her blood GH level was elevated to 12.6 ng/ml 15 minutes after a TRH administration. Blood GH levels were suppressed from 49 ng/ml to 1.5 ng/ml 4 hours after an oral administration of 2.5 mg of bromocriptine. A magnetic resonance images (MRIs) showed pituitary swelling, but no nodules were found in the pituitary. Therefore, we diagnosed her as having acromegaly and observed her without surgery, while prescribing diet therapy and intensive insulin therapy for diabetes. We started a treatment of oral administration of 7.5 mg of bromocriptine per day for the acromegaly from April 28, 2000, because her elevated GH was suspected of causing her diabetes to be poorly controlled. During a pregnancy from October, 2000 to September, 2001, diabetic control was improved with increased administration of insulin under a constant dose of bromocriptine. She delivered a normal full-term infant. After the bromocriptine therapy was stopped as she hoped to breastfeed, blood levels of GH and IGF-1 became elevated and her diabetic control deteriorated. As her pituitary tumor observed in pituitary MRIs became larger during the course, a transsphenoidal surgery was performed on March 8, 2002. After the surgery, blood levels of GH and IGF-1 lowered and diabetic control improved again. We concluded as follows: to rule out acromegaly in patients with poorly controlled diabetes, 1) measurements of serum GH and IGF-1 should be performed, and 2) pituitary MRIs should be performed if blood levels of GH or IGF-1 are high. (+info)
Dopamine receptor subtype 2 and somatostatin receptor subtype 5 expression influences somatostatin analogs effects on human somatotroph pituitary adenomas in vitro.
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Dopamine (DA) and somatostatin (SRIF) receptor agonists inhibit growth hormone (GH) secretion by pituitary adenomas. We investigated DA subtype 2 receptor (DR2) and SRIF receptor (sst) subtypes 2 and 5 expression in 25 GH-secreting pituitary adenomas and tested in primary culture the effects on GH and prolactin (PRL) secretion of sst agonists selectively interacting with sst2 (BIM-23120), sst5 (BIM-23206), and sst2 and sst5 (BIM-23244). All adenomas expressed sst2; eight adenomas expressed both sst5 and DR2, eight sst5 but not DR2, and eight DR2 but not sst5. One tissue lacked expression of DR2 and sst5. GH secretion was inhibited by BIM-23120 in all samples, while it was reduced by BIM-23206 only in adenomas not expressing DR2. BIM-23120's inhibitory effects correlated with sst2 and DR2 expression, whereas DR2 expression correlated inversely with BIM-23206 inhibitory effects on GH secretion. In seven mixed GH-/PRL-secreting pituitary adenomas, PRL secretion was inhibited in sst5-expressing tumors by BIM-23206, but not by BIM-23120. BIM-23244 reduced PRL secretion only in adenomas expressing sst2, sst5 and DR2. sst5 and DR2 expression correlated directly with BIM23206 inhibitory effects on PRL secretion. Our results suggest that adenomas expressing DR2 are less likely to respond to clinically available SRIF analogs in terms of GH secretion inhibition. Therefore, drugs interacting also with DR2 might better control secretion of pituitary adenomas. (+info)
Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease.
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Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome that is characterised by the occurrence of tumours in the parathyroid glands, the endocrine pancreas, the pituitary gland and the adrenal glands and by neuroendocrine carcinoid tumours, often at a young age. The penetrance of MEN1 among gene carriers is reported to be high; 82-99% at age 50. We present a patient with a history of parathyroid adenomas also showing signs of acromegaly. He turned out to be a carrier of a MEN1 germ-line mutation in intron 3 (IVS3-6C > G). This germ-line mutation was also found in nine of his family members. However, none of these relatives have developed any MEN1-related lesion yet, although several are older than 60 years. To our knowledge, a MEN1 family with as few clinical features as this family has not been reported to date. Because MEN1 patients have an increased risk of developing acromegaly, insulin-like growth factor (IGF-I) levels are monitored periodically. We investigated whether IGF-I levels might serve as a presymptomatic marker for acromegaly; 9% (3/33) of MEN1 patients showed temporary IGF-I elevations. One patient (1/3) later developed clinical signs of acromegaly. Possibly, acromegaly in MEN1 is preceded by a transient preacromegalic state. (+info)
A case of a GH-producing pituitary adenoma associated with a unilateral headache with autonomic signs.
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A 66-year-old man suffered from a drug-resistant, left-sided headache with autonomic signs, triggered by the supine position. The acromegalic facies initially suggested a possible increase in basal plasma levels of GH, but routine haematological controls excluded abnormal values of GH. Cerebral and facial CT scan and MRI did not detect any alterations in the nasal sinuses, except for a mucous cyst. Surgical ablation of the cyst did not alleviate the pain. Further endocrinological the pain. Further endocrinological tests demonstrated an increase of IGF-1 (somatomedin C), and another MRI scan of the sellar region confirmed the presence of a pituitary macroadenoma on the left paramedian side. After an initial improvement of the symptomatology due to trans-sphenoidal ablation of a benign GH-producing macroadenoma, the headache worsened again. Pain was well correlated with the increased plasma levels of IGF-1. The patient died suddenly for myocardial infarct. (+info)
Mechanisms of TRH-induced GH release (paradoxical response) in human somatotroph adenoma cells.
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The mechanisms of paradoxical TRH response in human somatotroph adenoma cells were investigated using intracellular calcium measurement and static incubation assay. Intracellular calcium measurement revealed that TRH induces a biphasic response: a transient increase followed by a sustained plateau. The transient phase was due to the calcium release from IP(3)-regulated intracellular calcium store and the subsequent sustained phase was due to the calcium influx through the voltage-gated calcium channels. The signal transduction mechanism of the calcium plateau involved protein kinase C. These calcium responses, especially the second phase, was responsible for the TRH-induced GH release. (+info)
Mechanism of D(2) agonist-induced inhibition of GH secretion from human GH-secreting adenoma cells.
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The mechanism of dopamine D(2) agonist-induced inhibition of GH secretion from GH-secreting adenoma cells was investigated by measurement of intracellular calcium concentration ([Ca(2+)] (i)) and static incubation experiment. Bromocriptine decreased [Ca(2+)](i) in a concentration-dependent manner through D(2) receptor. The inhibition was abolished by pertussis toxin pretreatment. Bromocriptine did not decrease [Ca (2+)](i) after nitrendipine had decreased it. 8Br-cAMP increased [Ca(2+)](i) but application of bromocriptine decreased it, suggesting that bromocriptine-induced inhibition of [Ca(2+)](i) is not dependent on bromocriptine-induced inhibition of adenylyl cyclase. Static incubation experiment revealed that bromocriptine inhibited GH secretion in a concentration-dependent manner. The inhibition was through D(2) receptor and was abolished by pertussis toxin pretreatment. 8Br-cAMP increased GH secretion. Bromocriptine decreased GH secretion even after 8Br-cAMP pretreatment. However, the GH release from cells incubated with bromocriptine alone was significantly less than that from cells incubated with bromocriptine after 8Br-cAMP pretreatment, suggesting a modulatory action of cAMP system in bromocriptine response. (+info)
Short-term preoperative octreotide treatment of GH-secreting pituitary adenoma: predictors of tumor shrinkage.
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We reviewed the cases of 32 patients with growth hormone (GH)-secreting macroadenoma who underwent short-term octreotide treatment before transsphenoidal surgery to determine which types of adenoma the preoperative treatment were sensitive and whether predictors of tumor shrinkage could be identified. The effects of preoperative octreotide treatment, endocrinologic effect and effect on tumor volume in 32 patients were evaluated retrospectively in relation to tumor features on magnetic resonance images and responses to endocrinologic challenge tests. At a daily dose of 300 microg for 2-3 weeks, octreotide reduced serum GH and insulin-like growth factor-1 (IGF-1) levels to 31.9 % and 51.6% of pretreatment values, respectively, and led to a mean tumor volume of 68% of pretreatment volume in 52% of the patients. The endocrinologic effect and the effect on tumor volume were larger in Knosp grades 0-2 than in Knosp grades 3-4. Tumor shrinkage occurred significantly more often among patients that had a good response to both octreotide and bromocriptine challenge tests. For surgical removal of the tumor, the effect of reducing tumor to 68% of pretreatment volume will be beneficial for the macroadenomas of Knosp grades 1-2. Preoperative short-term octreotide treatment is effective for GH-secreting macroadeomas of Knosp grades 1-2 and a good response to both octreotide and bromocriptine challenge tests is a predictor of subsequent tumor shrinkage. These results will lead to more effective selection of patients for preoperative octreotide treatment. (+info)
Subclinical adenomas in postmortem pituitaries: classification and correlations to clinical data.
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OBJECTIVE: The aim of this study was to examine pituitary adenomas in a series of postmortem pituitaries by use of modern technologies of immunostaining, to classify the adenomas according to the current WHO classification and to analyse the possible associations to the available clinical data. METHODS: In this study, pituitaries of 3048 autopsy cases obtained from autopsy series of the years 1991-2004 were examined. RESULTS: A total of 334 pituitary adenomas were found in 316 pituitaries. One hundred and thirty-two sparsely granulated prolactin cell adenomas (39.5%), 75 null cell adenomas (22.5%) and 31 oncocytomas were diagnosed. Forty-six ACTH cell adenomas (13.8%, 27 densely granulated, 19 sparsely granulated) and one adenoma composed of Crooke's cells were detected. Twenty-two gonadotroph cell adenomas (6.6%), seven GH cell adenomas (four sparsely granulated, three densely granulated), one mixed GH cell-PRL cell adenoma, two TSH cell adenomas, five plurihormonal adenoma type I, four plurihormonal adenoma type II and two alpha-subunit-only adenomas were seen. Six adenomas remained unclassified because the tissue was not contained in all sections for immunohistochemistry. Seventeen pituitaries included multiple tumours. The overall tumour size ranged from 0.1 to 20 mm in diameter. Among 76 adenomas (22.7%), which had a tumour size of > or = 3 mm, only three tumours were macroadenomas corresponding to a tumour size of more than 10 mm. The evaluation of the available clinical data showed 99 cases of hypertension, 65 cases of diabetes mellitus, six patients with hyperthyroidism and four with hypothyroidism. No symptoms of adenohypophyseal hormone hypersecretion were reported. The statistical correlations to clinical data were discussed. CONCLUSIONS: Adenomas in postmortem pituitaries differ from those in surgical series in proportion of adenoma types and biological behaviour. (+info)