T2-weighted magnetic resonance imaging characterization of prolactinomas and association with their response to dopamine agonists.

PURPOSE: Recent work supports the use of T2-weighted MRI intensity as a tool for treatment stratification in acromegaly. Our study aimed to establish if the pattern of T2 intensity could be a predictor of hormonal and/or tumoral response to dopamine agonists (DAs) in prolactinomas. METHODS: This was a retrospective study performed in two academic centers. We characterized the magnetic resonance T2-weighted aspect of prolactinomas (signal intensity and homogeneity in the whole tumors) before DA therapy and correlated this pattern to the prolactin (PRL) concentration at diagnosis and to hormonal and tumoral responses after 1 year of medical treatment. We separately analyzed a subgroup of prolactinomas visually very bright in more than 50% of the surface ("cystic" tumors). RESULTS: Out of 70 prolactinomas, 80% were T2 hyperintense and 40% were heterogeneous. At diagnosis, heterogeneous prolactinomas were more frequent in men (68% vs. 28.9%, p ≤ 0.011), larger (median area 304.5 mm2 vs. 56.5 mm2, p ≤ 0.021), taller (mean height 18.6 mm vs. 9.9 mm, p < 0.001), more secreting (median PRL ULN_area 23 µg/L/cm2 vs. 12.6 µg/L/cm2, p ≤ 0.032) and had poorer hormonal response to DA as compared with homogeneous prolactinomas. "Cystic" tumors were diagnosed almost exclusively in women and secreted less prolactin, but showed similar hormonal and tumoral response as "non-cystic" tumors. In homogeneous prolactinomas, the T2-weighted intensity ratio was correlated to prolactin secretion, although not significantly, and did not predict hormonal and tumoral response to DA. CONCLUSIONS: Our study confirms that hypo/isointense prolactinoma is a rare finding and suggests for the first time that the heterogeneity of prolactinoma T2 signal at diagnosis might be correlated with a different clinical behavior and could be used as a negative predictor factor of hormonal response to DA.

From pituitary adenoma to pituitary neuroendocrine tumor (PitNET): an International Pituitary Pathology Club proposal.

The classification of neoplasms of adenohypophysial cells is misleading because of the simplistic distinction between adenoma and carcinoma, based solely on metastatic spread and the poor reproducibility and predictive value of the definition of atypical adenomas based on the detection of mitoses or expression of Ki-67 or p53. In addition, the current classification of neoplasms of the anterior pituitary does not accurately reflect the clinical spectrum of behavior. Invasion and regrowth of proliferative lesions and persistence of hormone hypersecretion cause significant morbidity and mortality. We propose a new terminology, pituitary neuroendocrine tumor (PitNET), which is consistent with that used for other neuroendocrine neoplasms and which recognizes the highly variable impact of these tumors on patients.

Anticonvulsant hypersensitivity syndrome mimicking a viral illness with skin rash: a case report.

Anticonvulsant hypersensitivity syndrome (ACHSS) is rare and defined by a group of systemic symptoms: a typical clinical triad with skin rash, high fever and lymphadenopathy, with or without multiple organ dysfunctions. Its variable presentation renders diagnosis particularly difficult yet important, as delayed diagnosis can lead to serious complications. We describe a 31-year-old woman sent to the emergency department with symptoms of high fever, peripheral lymphadenopathy, arthralgia, nausea, vomiting and a vesiculobullous eruption resembling measles. First diagnostic hypothesis was that of a viral illness. However, thorough second anamnesis pointed towards a possible drug aetiology, as the patient had been prescribed lamotrigine 8 days prior to admission. Blood analysis showed an inflammatory syndrome, thrombocytopenia and moderate lymphopenia. A few days later, results indicated old immunisation for measles. Skin biopsy revealed dermal inflammation with presence of hypereosinophilia, thereby confirming ACHSS. It is important to recognise and treat this rare reaction to anticonvulsants as early as possible in order to prevent its potentially life-threatening complications.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Vertebral osteomyelitis with spinal epidural abscess in two patients with Bacteroides fragilis bacteraemia.

We report 2 cases of vertebral osteomyelitis and contiguous epidural abscess due to Bacteroides fragilis with no concomitant or past intra-abdominal infection. Decompressive surgery with laminectomy was required for both patients due to the occurrence of neurologic deficits. Clinical recovery was achieved after 8 weeks of antibiotic therapy. It included 3 weeks of intravenous therapy with clindamycin followed by an oral regimen of clindamycin for 1 patient and oral metronidazole for the other. In both cases, magnetic resonance imaging (MRI) has proved to be essential for diagnostic. The primary source of infection remained unknown despite careful investigations.

Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance.

BACKGROUND: Prolactinomas usually exhibit a benign course and can be safely and effectively managed by dopamine agonists (DA). However, some are locally invasive and may show resistance to DA therapy, and the management of such cases remains controversial. The aim of the present study was to determine whether histological features and markers of cell proliferation correlated to the clinical behaviour of prolactinomas and with DA resistance. METHOD: This retrospective study included 74 cases (36 men and 38 women) who had monohormonal prolactinomas removed by transsphenoidal surgery. The prolactinomas were categorized on the basis of tumour size (48 macroadenomas), invasion of the cavernous sinus (n = 31), and resistance to bromocriptine (BRC) therapy (n = 14). Group 1 consisted of non-invasive microprolactinomas (n = 24), group 2 of non-invasive macroprolactinomas (n = 19), group 3 of invasive non-BRC-resistant tumours (n = 19), and group 4 of invasive BRC-resistant tumours (n = 12). The later group included one case of carcinoma with bone and lung metastases. Seven additional parameters were studied, these being age, sex, basal prolactin (PRL) levels, the Ki-67 and PCNA labelling indices (LI), mitotic count, and cellular atypia. FINDINGS: Age and preoperative PRL levels did not correlate to the histological parameters studied. Tumour size and invasion were related to cellular atypia and the Ki-67 LI. BRC-resistant tumours were more frequently invasive (12/14) than BRC-responsive tumours (11/30; p = 0.002) and were more frequent in men than in women (33 versus 5%; p = 0.003). BRC-resistant tumours had a higher Ki-67 LI and mitotic count (4.2+/-2.0% and 4+/-1, respectively) than other tumours (0.7+/-0.2% and 1+/-0, respectively; p<0.05). The strongest correlations with tumoural staging were seen with male sex and high mitotic activity. Six out of the 12 invasive BRC-resistant macroprolactinomas, including the PRL secreting carcinoma, exhibited histological features of aggressiveness (a mitotic count >/=3 [i.e. in the fourth quartile] and/or a high Ki-67 LI and cellular atypia). CONCLUSIONS: In this surgical retrospective series, histological signs of aggressiveness are present in 50% of invasive and BRC-resistant prolactinomas, which are more frequent in men than in women. This fits with the behaviour of BRC-resistant prolactinomas, which can continue to grow despite DA treatment. These findings justify the long-term follow up of these tumours, and the use of surgery and/or radiotherapy if there is concern about the control of tumour growth.

Late-onset primary hyperoxaluria triggered by hypothyroidism and presenting as rapidly progressive renal failure--description of a new mutation.

Primary hyperoxaluria type 1 (PH1) is a rare autosomal metabolic recessive disease, caused by the deficiency of the liver peroxysomal alanine:glyoxylate aminotransferase (AGT), characterized by accumulation of calcium oxalate crystals in kidneys and others organs. We present the case of an elderly woman with PH1, presenting as acute renal failure. Precipitation of calcium oxalate crystals was probably due to amiodarone-induced severe hypothyroidism. Residual AGT activity is associated with the G170R (G630A) mutation. A new mutation of AGT, called R36C, was also discovered; the role of this new mutation is actually not known.

Antiproliferative effect of octreotide in somatotroph pituitary adenomas: discussion from a single case report.

The case of a 20-year-old man presenting with a rapidly expanding pituitary somatotrophic adenoma with a tumour volume doubling time of 426 days is reported. Preoperative octreotide therapy induced a 45% tumour shrinkage and proliferating cells were absent at the time of tumoural resection. The correlation between clinical and proliferation markers data in this single case report affords an opportunity to discuss the antitumoral effect of octreotide on somatotrophic adenomas which may result from a suppression of cell proliferation.

Minor alterations in thyroid-function tests associated with diabetes mellitus and obesity in outpatients without known thyroid illness.

Thyroid function tests might be affected by diabetes and obesity. To evaluate the influence of these parameters in routine conditions, 72 diabetic and 53 non-diabetic outpatients without known thyroid diseases or severe chronic illness were recruited over a 7-month period. For each patient, dosages of thyrotropin (TSH), total and free thyroxine (TT4 and FT4, respectively), total and free triiodothyronine (TT3 and FT3) and T3 resin uptake (T3RU) were performed by radioimmunoassays. The simultaneous influence of various parameters known to affect thyroid-function tests was evaluated by multivariate linear regression. The studied variables included gender, age, glucosteroids, estrogens, tobacco habits, iodine contacts, body mass index (BMI) and diabetes mellitus. Tobacco habits and iodine contacts did not influence any tests. As expected, estrogens induced an increase in TT4 and TT3 values (p < 0.001 and 0.020, respectively) associated with a decrease in T3RU (p < 0.001). Consequently, females had lower T3RU than males (p < 0.0001). Corticotherapy was associated with decreased TSH values (p = 0.022). TT3 and FT3 decreased with age (p < 0.001), whereas T3RU and FT4 increased (p = 0.020 and 0.004, respectively). In contrast to an increase in TSH (p = 0.006), TT4 and FT4 decreased at higher BMI levels (p = 0.018 and 0.004, respectively), which is consistent with subclinical hypothyroidism. In diabetic patients, TSH was lower than in nondiabetic subjects (p = 0.039). Thus, the present study indicates that besides known parameters such as age and drugs, thyroid-function tests can also be altered by diabetes mellitus and obesity.

Hantavirus infections: clinical presentation in the emergency room.

We present a retrospective review of Hantavirus infection in the emergency department. Thirteen cases of Hantavirus infections with renal syndrome from July 1989 to August 1999 were analysed. The diagnosis was confirmed by detection of Hantavirus antibodies in all cases. Fever, chills and headaches were universally present. Intense back pain was associated in 77% of the patients. Thrombocytopenia, abnormal urinalysis, hypertransaminasaemia, increased lactate dehydrogenase were the principal biological patterns. All these parameters returned to their normal level, and all the patients recovered a normal renal function without sequels. The management is supportive. Only one patient in our series had to be dialysed. Hantavirus disease should be included in the differential diagnosis of acute renal failure with thrombocytopenia, particularly in patients with suspected exposure in known endemic areas. The differential diagnosis of any perplexing case of undifferentiated febrile illness with acute renal failure and thrombocytopenia should include Hantavirus infection.

Hyperoxaluria: an underestimated cause of rapidly progressive renal failure.

Hyperoxaluria is rarely considered as a cause of rapidly progressive renal failure. A case is reported of a patient in whom rapidly renal failure developed after subtotal small bowel resection. A diagnosis of calcium oxalate deposits nephropathy was confirmed by renal biopsy. This cause of renal failure may be underestimated and should be systematically searched for in all patients with malabsorption.

Usefulness of [99mTC]MIBI and [18F]fluorodeoxyglucose for imaging recurrent medullary thyroid cancer and hyperparathyroidism in MEN 2a syndrome.

We report the case of a MEN 2a patient with a history of medullary thyroid cancer (MTC) treated by total thyroidectomy, who presented an increasing calcitonin level, suggesting tumor recurrence. Conventional radiographic and radionuclide imaging failed to localize the responsible lesions. A planar and tomographic (SPECT) [99mTc]MIBI scan, performed in order to investigate a recent hyperparathyroidism localized a parathyroid adenoma and revealed an abnormal uptake in the left lateral neck region, corresponding to apparently banal lymph nodes on MRI. This abnormal uptake was also observed on a [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) study and was proven to be an uptake in MTC lymph nodes metastases as confirmed by histopathologic analysis. We conclude that, using an adequate acquisition protocol (i.e. SPECT), [99mTc]MIBI scan is potentially able to localize both parathyroid adenoma and recurrent MTC at one and the same time, particularly in case of non-diagnostic conventional imaging techniques. In this setting, the potential usefulness of FDG-PET is also discussed.

[Prolactinoma in man: clinical and histological characteristics]. / Le prolactinome de l'homme: caractères cliniques et histologiques.

Prolactinoma usually occurs a small intrasellar tumor in women or as a large tumor in men. To determine whether the predominance of macroprolactinomas in men is due to a delay in diagnosis as has been suggested, or whether there is a sex-related difference in growth rate we conducted a retrospective study in 45 men and 51 women with prolactinomas. Preoperative prolactin level (PRL) was 2,789 573 ng/ml and mean tumor size was 26 2 mm. Prolactin levels and tumor size were significantly higher in women (292 74 ng/ml and 10 1 mm; p<0.01). There was no correlation with age at diagnosis or duration of symptoms. Giant tumors were only observed in men (n=8). Frequency of resistance to bromocriptine (30% vs 5%, p<0.01) and invasive tumors (52% vs 27%, p<0.001) were significantly higher in men than in women. Likewise, proliferation rate was higher for the prolactinomas in men (Ki-67: 2.6 1.1% positive nuclei vs 0.4 0.2%; p=0.08; PCNA: 5.0 2.3% vs 3.7 1.1%). In conclusion, prolactinomas in men are more aggressive than in women. They grow rapidly, often invade the cavernous sinus and are resistant to bromocriptine; proliferation rates can be increased.

Ingestion of antacid tablets (Rennie) and acute confusion.

The authors describe a case of milk-alkali syndrome in a man who consumed antacid tablets (Rennie) for chronic epigastric pain. Simultaneous occurrence of hypercalcemia, metabolic alkalosis, and renal insufficiency, in conjunction with the appropriate history of ingestion of calcium carbonate-containing antacids, was suggestive of the syndrome. The syndrome became uncommon with the advent of modern ulcer therapy, but currently is increasing in frequency with the calcium supplementation drugs taken to prevent osteoporosis. This syndrome may produce life-threatening hypercalcemia.