Transient hyperthyroidism after surgery for secondary hyperparathyroidism: a common problem

Background

Postoperative hyperthyroidism occurs in approximately one third of patients following parathyroidectomy due to primary hyperparathyroidism (PHP), but has only rarely been described in secondary hyperparathyroidism (SHP). The frequency, course, and laboratory markers of postoperative hyperthyroidism in SHP remain unknown. Our purpose was to evaluate the frequency and the clinical course of postoperative hypcrthyroidism following surgery of SHP and to determine the diagnostic value of thyroglobulin in this setting.

Material and Methods

A total of 40 patients undergoing parathyroidectomy because of SHP were included in this study. Thyroid stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fl4), and thyroglobulin (Tg) were determined one day before and on day 1, 3, 5, 10, and 40 after surgery. At each of these visits patients were clinically evaluated for signs or symptoms of hyperthyroidism.

Results

Biochemical evidence of hyperthyroidism was evident in 77% of patients postoperatively despite of preoperatively normal serum levels. TSH dropped from 1.18 ± 0.06mU/L to 0.15 ± 0.07mU/L (p = 0.0015). Free triiodothyronine (fT3) and fT4 levels increased from 2.86 ± 0.02ng/L and 10.32 ± 0.13ng/L, respectively, to their maximum of 4.83 ± 0.17ng/L and 19.35 ± 0.58ng/L, respectively. Thyroglobulin levels rose from 3.8 ± 0.8ng/mL to 111.8 ± 45.3ng/mL (p < 0.001). At day 40 all thyroid related laboratory values were within normal range. Correlation analysis of postoperative values revealed significant correlations for lowest TSH (r = -0.32; p = 0.038), and highest fT3 (r = 0.55; p < 0.001) and fT4 levels (r = 0.67; p < 0.001) with Tg.

Conclusion

Transient hyperthyroidism is frequent after parathyroidectomy for SHP with Tg being a suitable marker. Awareness of this self-limiting disorder is important to avoid inappropriate and potentially harmful treatment.     

CD4 decline and incidence of opportunistic infections in Cape Town, South Africa: implications for prophylaxis and treatment

OBJECTIVES: To determine the rate of CD4 decline and the incidence of opportunistic infections (OIs) among antiretroviral therapy-naive South African HIV-infected patients and inform timing of OI prophylaxis. METHODS: We used mixed-effect models to estimate CD4 cell decline by CD4 cell count strata in HIV-infected patients in the Cape Town AIDS Cohort between 1984 and 2000. Stratum-specific OI incidence per 100 person-years of observation was determined using incidence density analysis. RESULTS: Nine hundred seventy-four patients with 2 or more CD4 cell counts were included. CD4 counts declined by 47.1 cells/microL per year in the stratum with more than 500 cells/microL stratum, 30.6 cells/microL per year in the stratum with 351 to 500 cells/microL, and 20.5 cells/microL per year in the stratum with 201 to 350 cells/microL. Tuberculosis and oral candidiasis were the only OIs that occurred frequently in the stratum with more than 200 CD4 cells/microL. Rates of chronic diarrhea, wasting syndrome, tuberculosis, and oral and esophageal candidiasis increased in the stratum with less than 200 cells/microL, and rates of all OIs were highest in the stratum with 50 cells/microL or less. CONCLUSIONS:: CD4 cell count declines were dependent on CD4 strata and can inform timing of clinic visits and treatment initiation in South Africa. Incidence rates of OIs suggest that targeted OI prophylaxis could prevent substantial HIV-related morbidity in South Africa.     

Adherence to highly active antiretroviral therapy assessed by pharmacy claims predicts survival in HIV-infected South African adults

It is unclear how adherence to highly active antiretroviral therapy (HAART) may best be monitored in large HIV programs in sub-Saharan Africa where it is being scaled up. We aimed to evaluate the association between HAART adherence, as estimated by pharmacy claims, and survival in HIV-1-infected South African adults enrolled in a private-sector AIDS management program. Of the 6288 patients who began HAART between January 1999 and August 2004, 3805 (61%) were female and 6094 (97%) were black African. HAART adherence was >or=80% for 3298 patients (52%) and 100% for 1916 patients (30%). Women were significantly more likely to have adherence>or=80% than men (54% vs 49%, P<0.001). The median (interquartile range) follow-up time was 1.8 (1.37-2.5) years. As of 1 September 2004, 222 patients had died-a crude mortality rate of 3.5%. In a multivariate Cox regression model, adherence<80% was associated with lower survival (relative hazard 3.23; 95% confidence interval: 2.37-4.39). When medication adherence was divided into 5 strata with a width of 20% each, each stratum had lower survival rates than the adjacent, higher-adherence stratum. Among other variables tested, only baseline CD4+ T-cell count was significantly associated with decreased survival in multivariate analysis (relative hazard 5.13; 95% confidence interval: 3.42-7.72, for CD4+ T-cell count200 cells/microL). Pharmacy-based records may be a simple and effective population-level tool for monitoring adherence as HAART programs in Africa are scaled up.     

Phosphorylation alters the pharmacology of Ca2+-activated Cl? channels in rabbit pulmonary arterial smooth muscle cells

Background and purpose:

Ca²⁺-activated Cl⁻ currents (I_Cl(Ca)) in arterial smooth muscle cells are inhibited by phosphorylation. The Ca²⁺-activated Cl⁻ channel (Cl_Ca) blocker niflumic acid (NFA) produces a paradoxical dual effect on I_Cl(Ca), causing stimulation or inhibition at potentials below or above 0 mV respectively. We tested whether the effects of NFA on I_Cl(Ca) were modulated by phosphorylation.

Experimental approach:

I_Cl(Ca) was elicited with 500 nM free internal Ca²⁺ in rabbit pulmonary artery myocytes. The state of global phosphorylation was altered by cell dialysis with either 5 mM ATP or 0 mM ATP with or without an inhibitor of calmodulin-dependent protein kinase type II, KN-93 (10 µM).

Key results:

Dephosphorylation enhanced the ability of 100 µM NFA to inhibit I_Cl(Ca). This effect was attributed to a large negative shift in the voltage-dependence of block, which was converted to stimulation at potentials <−50 mV, ∼70 mV more negative than cells dialysed with 5 mM ATP. NFA dose-dependently blocked I_Cl(Ca) in the range of 0.1–250 µM in cells dialysed with 0 mM ATP and KN-93, which contrasted with the stimulation induced by 0.1 µM, which converted to block at concentrations >1 µM when cells were dialysed with 5 mM ATP.

Conclusions and implications:

Our data indicate that the presumed state of phosphorylation of the pore-forming or regulatory subunit of Cl_Ca channels influenced the interaction of NFA in a manner that obstructs interaction of the drug with an inhibitory binding site.     

Analysis of Gleason grade and scores in 90 Nigerian Africans with prostate cancer during the period 1994 to 2004

Objectives

To determine the relative frequency of prostate cancer among surgical specimens, and among prostate specimens received at the pathology department ,University Hospital Calabar.

Methods

Histology records were reviewed for the following: total number of histology specimens received; total number of prostate specimens; total number of prostate cancer; and the total number of cancers in males during the study period. Histology sections 4–5microns thick were cut from paraffin blocks and stained by Haematoxylin and Eosin (H&E). Histopathologic specimens were classified using the grading system of tumour differentiation described by Gleason and associates.

Results

One hundred and twenty three cancers of the prostate were received, constituting 2% of the total surgical specimens and 31% of prostate specimens. Thirty three cases (27%) could not be analyzed; therefore the study is based on 90 prostate cancer specimens. Eighty nine (99%) cases were epithelial tumours (adenocarcinoma.) There was a single mesenchymal tumour (rhabdomyosarcoma) (1%). The commonest grade in this study was the high grade (Gleason grade IV).

Conclusions

We observed that prostate cancer is a common among males (all sites) diagnosed at the University Hospital Calabar, with a peak incidence between the ages of 61 – 70 years (seventh decade).