A patient with thyrotropinoma cosecreting growth hormone and follicle-stimulating hormone with low alpha-glycoprotein: a new subentity?

BACKGROUND: Thyrotropinomas are rare pituitary tumors. In 25 percent of cases there is autonomous secretion of a second pituitary hormone, adding to the clinical complexity. We report a patient with thyrotropin (TSH)-dependant hyperthyroidism along with growth hormone (GH) and follicle-stimulating hormone (FSH) hypersecretion but low alpha-glycoprotein (alpha-subunit) concentrations, a hitherto unique constellation of findings. SUMMARY: A 67-year-old Scottish lady presented with longstanding ankle edema, paroxysmal atrial fibrillation, uncontrolled hypertension, fine tremors, warm peripheries, and agitation. Initial findings were a small goiter, elevated serum TSH of 7.37 mU/L (normal range, 0.30-6.0 mU/L), a free-thyroxine concentration of 34.9 pmol/L (normal range, 9.0-24.0 pmol/L), a flat TSH response to TSH-releasing hormone, and serum alpha-subunit of 3.1 IU/L (normal, <3.0 IU/L). There was no evidence of an abnormal thyroid hormone beta receptor by genotyping. Serum FSH was 56.8 U/L, but the luteinizing hormone (LH) was 23.6 U/L (postmenopausal FSH and LH reference ranges both >30 U/L) Basal insulin-like growth factor I was elevated to 487 microg/L with the concomitant serum GH being 14.1 mU/L, and subsequent serum GH values 30 minutes after 75 g oral glucose being 19.1 mU/L and 150 minutes later being 13.7 mU/L. An magnetic resonance imaging pituitary revealed a macroadenoma. Pituitary adenomectomy was performed with the histology confirming a pituitary adenoma, and the immunohistochemistry staining showed positive reactivity for FSH with scattered cells staining for GH and TSH. Staining for other anterior pituitary hormones was negative. After pituitary surgery she became clinically and biochemically euthyroid, the serum IFG-1 became normal, but the pattern of serum FSH and LH did not change. CONCLUSION: This case of plurihormonal thyrotropinoma is unique in having hypersecretion of TSH, GH, and FSH with low alpha-subunit. Such a combination may represent a new subentity of TSHomas.

Implications of full compliance with the computed tomography scanning recommendations of the National Institute for Clinical Excellence and Scottish Intercollegiate Guidelines Network guidelines for the management of head injury.

A prospective study was conducted to examine clinical practices in the management of head-injured patients preinception and postinception of the Scottish Intercollegiate Guidelines Network guidelines. Comparison was made between the Scottish Intercollegiate Guidelines Network and National Institute for Clinical Excellence guidelines on their indications for computed tomography scanning. Information was available on 2827 adult patients. Two hundred and thirty-two patients satisfied one or more Scottish Intercollegiate Guidelines Network criteria for computed tomography scanning. Four hundred and seventy-eight patients fulfilled one or more National Institute for Clinical Excellence criteria for scanning. No patient with Scottish Intercollegiate Guidelines Network or National Institute for Clinical Excellence indications for computed tomography scanning and who was not scanned, subsequently required neurosurgical treatment for a complication related to their injury. Full compliance with the scanning recommendations in the Scottish Intercollegiate Guidelines Network and National Institute for Clinical Excellence guidelines will require a significant increase in scanning resource and is unlikely to lead to the identification of a significant additional number of patients with intracranial lesions requiring neurosurgical intervention.

Premorbid intelligence and brain injury.

OBJECTIVES: To determine whether NART scores are associated with severity of brain injury and therefore presumably affected by brain injury. In addition, to compare the Cambridge Contextual Reading Test (CCRT) with injury severity in head-injured individuals. DESIGN AND METHODS: Participants were 55 survivors of traumatic head injury, who completed the NART and the CCRT. The scores on these premorbid measures were then compared with indices of injury severity from their initial neurosurgical admission. RESULTS: The NART was significantly correlated with Glasgow coma scale, with greater severity of injury associated with poorer performance. Poorer NART performance was also significantly more likely amongst those whose injury resulted in coma. The CCRT was preferred by patients, though it was also significantly associated with Glasgow coma scale and presence of coma. CONCLUSIONS: The data suggest that performance on both the NART and the CCRT are affected by brain injury severity and thus may underestimate true premorbid ability in these individuals. Similar findings would be likely with the conceptually identical WTAR measure. These measures should be used with appropriate caution and may be usefully supplemented by predictions based on demographic information.

Apolipoprotein E polymorphism and neuropsychological outcome following subarachnoid haemorrhage.

OBJECTIVES: To investigate the association between APOE genotype and cognitive and emotional outcome following spontaneous subarachnoid haemorrhage (SAH). MATERIALS AND METHODS: Neuropsychological assessments were conducted with 70 SAH survivors derived from a consecutive series of neurosurgical admissions. Outcomes, including cognitive tests, health questionnaires and Glasgow Outcome Scale at a mean of 16 months after SAH, were compared with presence or absence of the epsilon4 allele. RESULTS: There was no evidence that SAH survivors possessing the epsilon4 allele had poorer outcome. The only suggestion of an association between the epsilon4 allele and outcome was in a subgroup of patients with a Fisher grade 4 haemorrhage, although this trend did not reach statistical significance. CONCLUSIONS: Overall, possession of the APOE epsilon4 allele is not significantly associated with neuropsychological outcome following SAH. However, there may be an effect amongst those with a Fisher grade 4 haemorrhage.

Patients with a head injury who "talk and die" in the 1990s.

BACKGROUND: Patients who "talk and die" after head injury may represent a group who suffer delayed and therefore potentially preventable complications after injury. We have compared the clinical and pathologic features of patients who talk and die with those who "talk and live" after head injury. METHODS: Data collected prospectively by the Scottish Trauma Audit Group were used to identify patients with a head injury and classify them according to verbal response at admission to hospital. All "talking" patients in the catchment area of a regional neurosurgical center were selected and those who died were compared with those who survived. RESULTS: Seven hundred eighty-nine talking patients were identified. Seven hundred twenty-seven patients survived and 62 died. Patients who talked and died were older, had more severe extracranial injuries, had lower consciousness levels, and reached theater more quickly than those who talked and lived. Thirty-one of the patients that died had extra-axial hematomas. CONCLUSION: Even with increased availability of computed tomographic scanning, some patients still talk and die after head injury.

Effect of apolipoprotein E genotype on hematoma volume after trauma.

OBJECT: The apolipoprotein E-epsilon4 (APOE-epsilon4) allele is associated with poor outcome after head injury and spontaneous intracerebral hemorrhage (SICH). The aims of this study were to determine if patients in whom one or more APOE-epsilon4 alleles are present are more likely to sustain intracranial mass lesions after head injury and to determine whether there is an isoform-specific effect on the size of the intracranial hematoma. METHODS: The authors performed a computerized volumetric analysis of 142 hematomas visible on computerized tomography (CT) scans obtained in 129 patients. The APOE genotype was determined by subjecting buccal smear samples to polymerase chain reaction and restriction enzyme digestion. Allele frequencies were similar in head-injured patients with and without intracranial hematomas (p = 0.36). Univariate analysis revealed that in those patients with one or more APOE-epsilon4 alleles hematoma volume was greater (cube root-transformed values) than that found in patients without the APOE-epsilon4 allele (3.1 cm compared with 2.5 cm, p = 0.0039). The results of univariate analysis also suggested significant effects of patient age, injury severity (mild, moderate, or severe according to admission Glasgow Coma Scale scores) and hematoma location (extraaxial, intraaxial, or both) on hematoma volume. The mechanism of injury (assault, fall, or other) was marginally associated with hematoma volume (p = 0.052). Time from injury to CT scan, hypoxia, and hypotension had no significant effect on hematoma volume. The results of multiple linear regression analysis showed that the presence of an APOE-epsilon4 allele and an extraaxial hematoma location were independent predictors of hematoma volume, after adjusting for patient age, hours between injury and CT scan, injury severity, and injury mechanism. CONCLUSIONS: Larger hematomas were found in head-injured patients with one or more APOE-epsilon4 alleles than in patients without the allele. This may contribute to the poorer outcomes observed in these patients.