Endothelial progenitor cells in subclinical hypothyroidism: the effect of thyroid hormone replacement therapy.

CONTEXT: Subclinical hypothyroidism (SCH) is associated with cardiovascular (CV) risk factors, and possibly CV disease. However, its management remains controversial. Endothelial progenitor cells (EPC), expressing both endothelial and stem cell markers, are known to offer a novel CV risk marker. OBJECTIVE: The aim of the study was to ascertain whether EPC count or function is reduced in SCH and whether it improves with T(4) therapy. DESIGN AND INTERVENTION: EPC were studied in peripheral blood by fluorescence-activated cell sorter and following in vitro cultures before and after T(4) together with CV risk factors in 20 SCH and healthy controls (HC). MAIN OUTCOME MEASURE: EPC count was measured at baseline and after T(4) replacement in SCH. RESULTS: EPC count was significantly reduced in SCH compared to HC: median (range)-CD133+/VEGFR-2+, 0.09 (0.02-0.44) vs. 0.47 (0.17-2.12), P < 0.001; CD34+/VEGFR-2+, 0.10 (0.04-0.46) vs. 0.39 (0.11-2.13), P < 0.001; whereas EPC function was similar. There was a significant positive correlation between CD133+/VEGFR-2+ with free T(4) levels (r = 0.38; P = 0.02); high-density lipoprotein cholesterol levels (r = 0.51; P = 0.001); and negative correlation with TSH concentrations (r = -0.64; P < 0.001). After adjustment for conventional CV risk factors, SCH predicted lower EPC count, beta coefficient/P value: CD133+/VEGFR-2+ (-0.77/<0.001), and CD34+/VEGFR-2+ (-0.71/<0.001). In SCH participants, EPC count increased and was similar to HC after T(4); CD133+/VEGFR-2+, 0.32 (0.03-0.94) vs. 0.09 (0.02-0.44), P < 0.001; and CD34+/VEGFR-2+, 0.26 (0.06-0.88) vs. 0.10 (0.04-0.46), P < 0.001. CONCLUSION: SCH predicted lower EPC count, which improved with T(4) treatment, independent of other CV risk factors, providing additional evidence that T(4) replacement may improve CV risk in SCH.

Cardiovascular risk factors predicting the development of distal symmetrical polyneuropathy in people with type 1 diabetes: A 9-year follow-up study.

The aim of the article was to use prospectively collected data on people with type 1 diabetes to examine which routinely collected clinical measures predict the development of peripheral neuropathy in people with type 1 diabetes. Within the Newcastle Diabetes Services, structured data collection at an annual review has been collected since 1985. This includes metabolic measures, cardiovascular risk factors, and markers of complications. From 1990 data collection was standardized and computerized. For this study, all people with type 1 diabetes in the database in both 1992 and 2001 were ascertained. Data were extracted for a diagnosis of peripheral neuropathy (based on neuropathic symptoms, absence of pinprick sensation, and abnormal biothesiometer measurements and/or monofilament sensation) and for the other metabolic and cardiovascular risk measures, as well as markers of other microvascular complications. Associations with the development of neuropathy were sought. Eighteen of 404 people already had peripheral neuropathy in 1992, and 38 others developed neuropathy during follow-up. People who developed neuropathy were older (47 +/- 14 [SD] versus 36 +/- 11 years; P = 0.000), had longer-duration of diabetes (27 +/- 13 versus 18 +/- 10 years; P = 0.001), higher baseline serum cholesterol (5.8 +/- 1.3 versus 5.2 +/- 1.2 mmol/L, P = 0.017), and higher systolic (139 +/- 18 versus 129 +/- 20 mmHg; P = 0.003) and diastolic BP (82 +/- 12 versus 76 +/- 11 mmHg; P = 0.009) than those who remained free of neuropathy. We found no significant difference for BMI and glycated hemoglobin. The multivariate model showed that diastolic BP, duration of diabetes, serum cholesterol, and history of callus/ulcers on the feet predicted the development of peripheral neuropathy. Neuropathy developed in 11.4% of people with type 1 diabetes over a 9-year follow-up, and was predicted by factors normally associated with cardiovascular rather than microvascular disease.

Pituitary apoplexy: a review of clinical presentation, management and outcome in 45 cases.

OBJECTIVE: To review clinical presentation, management and outcomes following different therapies in patients with pituitary apoplexy. METHODS: Retrospective analysis of case-records of patients with classical pituitary apoplexy treated in our hospitals between 1983-2004. RESULTS: Forty-five patients (28 men; mean age 49 years, range 16-72 years) were identified. Only 8 (18%) were known to have pituitary adenomas at presentation. Thirty-four (81%) patients had hypopituitarism at presentation. CT and MRI identified pituitary apoplexy in 28% and 91% cases, respectively. Twenty-seven (60%) patients underwent surgical decompression, whilst 18 (40%) were managed conservatively. Median time from presentation to surgery was 6 days (range 1-121 days). Patients with visual field defects were more likely than those without these signs to be managed surgically (p = 0.01). Complete or near-complete resolution occurred in 93% (13/14), 94% (15/16) and 93% (13/14) of the surgically treated patients with reduced visual acuity, visual field deficit and ocular palsy, respectively. All patients with reduced visual acuity (4/4), visual field deficit (4/4) and ocular palsy (8/8) in the conservative group had complete or near-complete recovery. Only 5 (19%) patients in the surgical group and 2 (11%) in the conservative group had normal pituitary function at follow up. One (4%) patient in the surgical group and 4 (22%) in the conservative group had a recurrence of pituitary adenoma. CONCLUSIONS: This large series suggests that the patients with classical pituitary apoplexy, who are without neuro-ophthalmic signs or exhibit mild and non-progressive signs, can be managed conservatively in the acute stage.

Medical therapy of macroprolactinomas in males: I. Prevalence of hypopituitarism at diagnosis. II. Proportion of cases exhibiting recovery of pituitary function.

Hyperprolactinaemia frequently causes secondary hypogonadism through central suppression of gonadotropin secretion. Macroprolactinomas (> 1 cm diameter) are more common in males and may additionally cause more generalised hypopituitarism. Recovery of the thyrotropic and/or corticotropic axes is well described following selective adenomectomy, but remains poorly defined in relation to medical (dopamine-agonist) therapy of macroprolactinomas. We therefore performed a retrospective examination of case records of male patients who had received medical therapy alone for macroprolactinoma between 1980-2001 (n = 35) and in whom tumor shrinkage was documented by interval pituitary imaging (reported throughout by a single neuroradiologist). Mean prolactin level at baseline was 59,932 mU/L (median 31,400; range 3,215-332,000); mean period of follow up was 4.2 years (median 2.6; range: 1.0-15). Defects of the following axes were evident at diagnosis: LH/FSH-testosterone (n = 27; 77%), TSH-T4 (n = 14; 41%-not including one case with pre-existing 1 degress hypothyroidism), ACTH-cortisol (n = 8; 23%). Overall, 14 men (40%) were deficient in 1 axis, seven (20%) in 2 axes and seven (20%) in 3 axes. Growth hormone secretory status was not systematically evaluated. In all but 6 patients, prolactin levels fell to normal or near-normal levels (mean 764 mU/L; median 260; range: < 10-4,833). Of the patients in whom adequate reassessment had been performed, thyrotroph function recovered in 4/9, corticotroph function in 4/6 and gonadotroph function in 16/26 cases. In four cases (11%) previously described, development of visual impairment as a result of the chiasmal traction syndrome necessitated a dose reduction in medical therapy to allow a degree of controlled tumor re-expansion. The prevalence at diagnosis of TSH and ACTH deficiency in men with macroprolactinomas was 41% and 23%, respectively. Among eight patients with insufficiency of TSH and/or ACTH secretion who underwent complete interval reassessment over several years of treatment, recovery of at least one axis occurred in six cases (75%). This study highlights the importance of screening ACTH- and/or TSH-deficient men during dopamine agonist therapy in order to identify cases where hypopituitarism has resolved.