Criteria of cure and follow-up of central hyperthyroidism due to thyrotropin-secreting pituitary adenomas

The recorded number of patients with central hyperthyroidism due to TSH-secreting pituitary adenoma doubled in the last few years after the introduction of ultrasensitive TSH assays in the assessment of thyroid function; however, information about the results and the criteria for cure after pituitary surgery is scanty. Seventeen patients with a TSH-secreting adenoma, diagnosed on the basis of detectable TSH levels in the face of high free thyroid hormone concentrations and pituitary lesion at neuroimaging, underwent pituitary surgery. Hypersecretion of other pituitary hormones was diagnosed in 5 of 17 patients. Four patients were initially misdiagnosed and treated with thyroid surgery or radioiodine therapy. The majority (86%) of hyperthyroid patients normalized thyroid hormone concentrations and regained euthyroidism, although pituitary imaging, alpha-subunit, and alpha-subunit/TSH molar ratio normalized in only 47%, 54%, and 58% of patients, respectively. Moreover, TSH secretion was normally suppressed by T3 in 40% of the patients. Interestingly, the finding of undetectable TSH levels 7 days after surgery was highly predictive of successful outcome. During long term follow-up, there was one relapse of hyperthyroidism. Early diagnosis of TSH-secreting adenomas permits a high rate of remission of hyperthyroidism after surgery. However, normalization of thyroid function alone does not necessarily reflect complete removal of the tumor, and more comprehensive criteria of cure based on pituitary imaging, hormone measurement, and suppression of TSH during T3 administration should be used. Lastly, all patients need an accurate long term follow-up to monitor the possible recurrence of the adenoma.     

Recurrent hyperparathyroidism due to parathyroid autografts: incidence, presentation, and management

Recurrent hyperparathyroidism (HPT) occurs in a small percentage of patients undergoing parathyroidectomy for primary HPT and is usually due to inadequate excision of hyperfunctioning parathyroid tissue in the neck, a missed ectopic and hyperplastic parathyroid, or, less commonly, parathyroid carcinoma and parathyroid autografts. In order to determine the incidence, clinical characteristics, and outcome of patients with recurrent HPT due to parathyroid autografts, we reviewed our experience with 604 consecutive patients operated on for primary HPT between 1965 and 1989. One hundred of these patients received parathyroid autografts consisting of portions of one or more parathyroid glands. Three patients with autografts, placed in the sternocleidomastoid muscle, developed recurrent HPT due to their autografts for an incidence of 3 per cent. Recurrent disease was diagnosed between 62 and 113 months with an average of 89 months. The autotransplants in all three of these patients were from hyperplastic or adenomatous parathyroid tissue. Two patients had a history of neck irradiation. Preoperative thallium scans accurately localized the hyperfunctioning parathyroid tissue in all three patients. At operation, the hyperfunctioning autografts had grown into a discrete mass with a single vascular pedicle and were resected. Histologic examination disclosed either hyperplastic or adenomatous tissue, and corresponded to the histology and location of the original tissue transplanted in each case. Follow-up ranges from 12 to 67 months, with an average of 48 months. All patients remain cured and none require oral calcium supplementation. We conclude that graft-dependent recurrent HPT is due to the autotransplantation of hyperplastic or adenomatous parathyroid tissue and that thallium scanning is instrumental for diagnosis and localization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent Cushing's syndrome due to recurrent adrenocortical tumor--fragmentation or tumor in ectopic adrenal tissue?

A 33-yr-old woman was found to have Cushing's syndrome due to a left adrenal cortical tumor. The tumor and the surrounding adrenal gland were removed intact and in toto. Four years later, she noticed recurrent symptoms of Cushing's syndrome, and 6 yr postoperatively, an adrenal tumor was demonstrable on computed tomography. Fourteen years after the initial procedure, a left adrenal tumor, presumably arising in ectopic adrenal tissue, was removed with relief of her symptoms of Cushing's syndrome. The site and functional capacity of ectopic adrenal tissues are reviewed.     

Prolactin and thyrotropin responses to thyrotropin-releasing hormone in patients with secondary amenorrhea: the effect of bromocriptine

Prolactin (PRL) and thyrotropin (TSH) responses to a 200 mug intravenous thyrotropin-releasing hormone (TRH) bolus were measured by radioimmunoassay in 11 women with hyperprolactinemic amenorrhea and 9 with normoprolactinemic amenorrhea. In all cases, the tests were carried out under basal conditions and repeated during bromocriptine treatment. In women whose basal PRL level was normal; TRH caused a maximal PRL increment of 85 +/- 25.2 mug/l (mean +/- SE), while those women whose basal PRL level was raised showed a smaller increase (5.2 +/- 11.9 mug/l) (P=0.02). The peak levels were not significantly different in these two groups (95.0 +/- 26.7 and 134.6 +/- 35.9 mug/l) (P is greater than 0.1). During bromocriptine treatment, the raised PRL levels decreased in all cases, but levels over 30 mug/l remained in 3 patients, one of whom turned out to have a pituitary tumor. Prolactin responses to TRH were markedly inhibited in normoprolactinemic patients by the dose of bromocriptine used. The mean maximal net increase of PRL was 2.0 +/- 0.9 mug/l in normoprolactinemic patients and 11.0 +/- 8.1 mug/l in hyperprolactinemic patients taking bromocriptine. After TRH stimulation during bromocriptine, the peak PRL levels in hyperprolactinemic patients were higher (32.7 +/- 10.5 mug/l) than in normoprolactinemic patients (7.2 +/- 1.5 mug/l). Unlike what has been described for hypothyroid patients, the basal TSH level in euthyroid amenorrhea patients was not affected by bromocriptine, and we found that bromocriptine has no effect on the TRH-TSH response.     

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.     

Recurrent pericarditis due to mesalamine hypersensitivity: a pediatric case report and review of the literature

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.     

Increase in plasma thyrotropin levels in hypothyroid patients during treatment due to a defect in the commercial preparation

Around mid-1995, the Molecular Endocrinology Laboratory of the Regional Hospital (Malaga, Spain) began detecting an increase in TSH levels in the serum of patients under study to control the treatment of hypothyroidism with levothyroxine. Over a period of 5 months, of a total of 467 hypothyroid patients treated with Levothyroid, 53% had TSH levels higher than 6 microU/mL. The reliability of the biochemical results was verified by duplicating 56 randomly chosen samples from all those with high TSH levels and by an external control performed in four different laboratories. The amount of levothyroxine in the tablets was analyzed by RIA, high performance liquid chromatography, and their iodine contents. The lowest levels of levothyroxine found in the 50 micrograms Levothyroid tablets were those determined by RIA, with a mean value of 32.3 micrograms, resulting in a 35.3% loss of activity. The mean value of levothyroxine found in these same tablets by high performance liquid chromatography was 39.3 micrograms, amounting to a 21.3% loss in activity. The iodine showed no significant loss in these tablets, with a mean experimental value of 48 micrograms. The commercial laboratory withdrew lot J from the market, the one in which these deficiencies were found.     

Thyroxine, thyrotropin, and age in a euthyroid hospital patient population

The diagnosis of thyroid disease now often can be achieved reliably by measuring thyrotropin (TSH) alone. Thyroxine (T4), triiodothyronine, and other analytes are only needed if TSH and the accompanying clinical condition are discordant. We describe here work that confirms the age independence of TSH in both inpatient and outpatient euthyroid hospital populations between ages 20 and at least 80 years, and demonstrates that although free T4 does vary with age, the range of variation remains within the T4 reference interval. On this basis, TSH-based thyroid diagnostic algorithms can be used reliably in adults without reference to age-related reference intervals.     

Symptom resolution, tumor control, and side effects following postoperative radiotherapy for pituitary macroadenomas

This study reports the outcome of 70 patients who were treated by a consistent treatment plan of surgery and postoperative radiotherapy (RT) for pituitary macroadenomas in the modern era [computed tomographic scan or magnetic resonance imaging (MRI), dopamine agonist therapy (DA) added as indicated, and immunohistochemical staining]. Sixty-two patients underwent transsphenoidal surgery (vs. transcranial surgery) and 61 received 45-Gy/25 fractions postoperatively (vs. other dose fractionation schemes). Twenty-four patients received DA for prolactin-secreting tumors. With a median follow-up of 8 years (range 2-15), 68 patients have experienced continuous control of their tumors. Most symptoms related to mass effect abated, while physiologic symptoms such as amenorrhea from markedly elevated prolactin levels tended to persist. Treatment-induced hypopituitarism occurred in 42% of the patients at risk. No patients in this series have died as a result of their pituitary tumor. No gross neuropsychologic dysfunction after treatment has been noted. While it is possible at this time with serial MRI to withhold postoperative RT and observe some patients who have had a "gross total" resection of a macroadenoma, the therapeutic ratio for surgery and adjuvant radiotherapy for patients with nonfunctional tumors as well as select patients with secretory macroadenomas is favorable.     

Recurrent torticollis due to cervical osteochondroma. Case report and review of the literature]

A patient is presented who had bilateral abductor vocal fold paralysis pathologically proven to be due to multiple system atrophy (MSA) in the absence of other neurological features. MSA is a degenerative neurological condition that includes olivopontocerebellar atrophy, Shy-Drager syndrome and striatonigral degeneration. The usual predominant features of MSA are cerebellar ataxia, autonomic dysfunction and Parkinsonism. Stridor is present in over one third of patients and has been reported previously as a presenting symptom in MSA: however previously reported patients have always gone on to develop other neurological symptoms. The usual investigations of bilateral abductor vocal fold paralysis caused by MSA will not reveal the pathological process and we believe that magnetic resonance imaging (MRI) of the medulla and brain stem and autonomic function tests are probably the investigations of choice. It is a worthwhile exercise attempting to identify MSA as the cause of stridor as the prognosis is good in the medium term if appropriate support is offered.     

Breastfeeding, amenorrhea, and abstinence in Javanese village: a case study of Mojolama

Factors that contribute to low fertility rates among Javanese women were investigated in a survey of 772 ever-married women in the village of Mojolama. The average duration of breast-feeding was 25.6 months, with the median being just over 26 months. 39% of the women reported that postpartum amenorrhea lasted not quite 27 months. More than 60% of the women believed, for various reasons, that they should abstain from sexual intercourse until weaning. Older women tended to abstain longer, as was the case with breast-feeding. On the average, breast-feeding for 17 months corresponded to a birth interval of 18-23 months, while breast-feeding for 28 months corresponded to a birth interval of 48 months or more. Certain cross-cultural comparisons regarding these factors are made, and the implications of the findings for family planning programs are discussed.     

Acute tumor lysis syndrome due to mono-therapy with a corticosteroid in a patient with non-Hodgkin lymphoma

A 20-year-old man was hospitalised because he nearly suffocated when lying on his back. After bronchoscopy which revealed severe external compression of the airways, suddenly respiratory insufficiency developed. Because a malignant lymphoma was suspected chemotherapy was started, using monotherapy with prednisolone as the risk of acute tumour lysis syndrome (ATLS) is high with polychemotherapy of bulky tumours. Nevertheless ATLS developed, for which haemodialysis had to be applied. The tumour, a T-cell lymphoblastic non-Hodgkin lymphoma with high grade malignancy, was treated successfully with cyclophosphamide, doxorubicin, vincristine en prednisone. ATLS is characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, hypocalcaemia, lactate acidosis and acute renal failure. It can occur in the course of aggressive cytoreductive therapy in rapidly growing lymphoproliferative malignancies with large tumour size, due to massive tumour cel lysis. Corticosteroid monotherapy is a very rare cause of ATLS.     

Heterogeneity of tumor oxygenation: relationship to tumor necrosis, tumor size, and metastasis

Analysis of serum samples from patients with acute jaundice by means of enzyme-linked immunosorbent assay and polymerase chain reaction testing provided the first profile of this condition in Vientiane, Lao PDR, in 1995 and 1996. In a case-control, hospital-based study, evidence of acute infections due to hepatitis A and B viruses was found in 14% and 10% of cases, respectively. Hepatitis E virus, however, did not appear to contribute to clinically recognized acute jaundice. Similarly, antibody to hepatitis C virus was recognized in almost equal proportions of cases (8%) and controls (6%), thus representing probable background infections. The detection of hepatitis G virus marks the first report of this virus in Lao PDR. The large proportion (21%) of new leptospiral infections in cases without acute hepatitis A or B was notable. This finding suggests significant regional underreporting of leptospirosis as a cause of acute jaundice. The limited laboratory diagnostic capabilities for confirming a differential diagnosis of leptospirosis contribute to the lack of attention paid to this important health problem.     

Falls, injuries due to falls, and the risk of admission to a nursing home

BACKGROUND: Falls warrant investigation as a risk factor for nursing home admission because falls are common and are associated with functional disability and because they may be preventable. METHODS: We conducted a prospective study of a probability sample of 1103 people over 71 years of age who were living in the community. Data on demographic and medical characteristics, use of health care, and cognitive, functional, psychological, and social functioning were obtained at base line and one year later during assessments in the participants' homes. The primary outcome studied was the number of days from the initial assessment to a first long-term admission to a skilled-nursing facility during three years of follow-up. Patients were assigned to four categories during follow-up: those who had no falls, those who had one fall without serious injury, those who had two or more falls without serious injury, and those who had at least one fall causing serious injury. RESULTS: A total of 133 participants (12.1 percent) had long-term admissions to nursing homes. In an unadjusted model, the risk of admission increased progressively, as compared with that for the patients with no falls, for those with a single noninjurious fall (relative risk, 4.9; 95 percent confidence interval, 3.2 to 7.5), those with multiple noninjurious falls (relative risk, 8.5; 95 percent confidence interval, 3.4 to 21.2), and those with at least one fall causing serious injury (relative risk, 19.9; 95 percent confidence interval, 12.2 to 32.6). Adjustment for other risk factors lowered these ratios to 3.1 (95 percent confidence interval, 1.9 to 4.9) for one noninjurious fall, 5.5 (95 percent confidence interval, 2.1 to 14.2) for two or more noninjurious falls, and 10.2 (95 percent confidence interval, 5.8 to 17.9) for at least one fall causing serious injury, but the association between falls and admission to a nursing home remained strong and significant. The population attributable risk of long-term admission to a nursing home for these three groups (the proportion of admissions directly attributable to the three categories of falls) was 13 percent, 3 percent, and 10 percent, respectively. CONCLUSIONS: Among older people living in the community falls are a strong predictor of placement in a skilled-nursing facility; interventions that prevent falls and their sequelae may therefore delay or reduce the frequency of nursing home admissions.     

Effects of divalent cations and of a calcimimetic on adrenocorticotropic hormone release in pituitary tumor cells

The calcium sensing receptor (CaSR), a member of the G-protein coupled receptor family, is expressed on a variety of cell types and responds to extracellular calcium. We have characterized pharmacological properties of (+/-)NPS 568, a calcimimetic, toward cloned rat brain extracellular Ca2+-sensing receptor (CaSR) expressed in Chinese hamster ovary (CHO) cells and constitutive mouse CaSR in AtT-20 cells. In the presence of 1.3 mM Ca2+, the calcimimetic displayed a potency in the micromolar range in augmenting the inositol phosphates (IP) response in both cell lines and behaved as a full agonist. (+/-)NPS 568 stimulated formation of arachidonic acid release in CHO(CaSR) with a similar potency. The IP dose response curves of (+/-)NPS 568 were shifted to the left in the presence of increasing Ca2+, indicating that the potency of the drug is dependent on extracellular Ca2+ in both cells. In AtT-20 cells, Ca2+ and Ba2+, two CaSR agonists, induced a potent stimulation of adrenocorticotropic hormone (ACTH) secretion. In the presence of 1.8 mM Ca2+, (+/-)NPS 568 led to a dose dependent secretion of ACTH with an EC50 of 0.3 microM and a maximal effect comparable to Ca2+. The similar potency of the calcimimetic on IP and ACTH responses and the sensitivity of these responses to extracellular Ca2+ indicate that the Ca2+-sensing receptor expressed in AtT-20 cells is implicated in ACTH release. These data further characterize the pharmacology of the Ca2+-sensing receptor and argue for a role for extracellular Ca2+ and CaSRs in controlling ACTH secretion, a hormone implicated in several types of stress.