Graves' disease associated with HIV disease and late immune reconstitution inflammatory syndrome following the initiation of antiretroviral therapy.

SUMMARY: Both human immunodeficiency virus (HIV) and antiretroviral therapy (ART) are associated with endocrine dysfunction (1). The term 'immune reconstitution inflammatory syndrome' (IRIS) describes an array of inflammatory conditions that occur during the return of cell-mediated immunity following ART. Graves' disease (GD) occurs rarely as an IRIS following ART. In this study, we describe the case of a 40-year-old Brazilian female who was diagnosed with HIV following admission with cryptococcal meningitis and salmonellosis. At this time, she was also diagnosed with adrenal insufficiency. Her CD4 count at diagnosis was 17 cells/µL which rose to 256 cells/µL over the first 3 months of ART. Her HIV viral load, however, consistently remained detectable. When viral suppression was finally achieved 21 months post diagnosis, an incremental CD4 count of 407 cells/µL over the following 6 months ensued. Subsequently, she was diagnosed with a late IRIS to cryptococcus 32 months following initial ART treatment, which manifested as non-resolving lymphadenitis and resolved with high-dose steroids. Following the initiation of ART for 45 months, she developed symptomatic Graves' hyperthyroidism. At this time, her CD4 count had risen to 941 cells/µL. She has been rendered euthyroid on carbimazole. This case serves to remind us that GD can occur as an IRIS post ART and typically has a delayed presentation. LEARNING POINTS: Endocrinologists should be aware of the endocrine manifestations of HIV disease, in particular, thyroid pathology. Endocrinologists should be aware that IRIS can occur following the initiation of ART. Thyroid dysfunction can occur post ART of which Graves' disease (GD) is the most common thyroid manifestation. GD as a manifestation of ART-induced IRIS can have a delayed presentation. Infectious disease physicians should be aware of endocrine manifestations associated with HIV and ART.

Breast implants: is there an association with connective tissue disease?

Following concern over a suggested link between the implantation of silicone gel and connective tissue disease, the Medical Devices Directorate (MDD) of the Department of Health reviewed all available data for submission to a specially convened Expert Advisory Group. Animal studies indicated that silicones are unlikely to stimulate a specific antibody response or cell-mediated immunity, that they have no adverse effect on resistance to infection, and produce minimal effects in the presence of potent adjuvants but can act as adjuvants themselves. The connective tissue disease most commonly claimed to be associated with breast implants is scleroderma. Although one series of patients showed a significantly higher prevalence of this disease than expected, there is no clear indication that the incidence of scleroderma in women with breast implants is any higher than in the general population.

The value of follow-up in stage II carcinoma of the cervix.

The optimal frequency of clinic follow-up after radical radiotherapy to early cervical cancer is not well established. A retrospective analysis was carried out of 392 patients with FIGO Stage IIA and IIB carcinoma of the cervix treated by radical radiotherapy who attended a radiotherapy clinic for follow-up. A total of 38 (43%) of the 87 locoregional and 25 (38%) of the 66 metastatic relapses were detected at routine clinic visits. There were 72 clinic visits per relapse detected. The majority of locoregional and metastatic relapses whether detected at routine or interval visits were symptomatic of the locoregional recurrences 78% (42/54) occurred in the first two years following treatment. The majority were advanced. 7% (4/54) of locoregional relapses occurred after 5 years. Only 17% (9/54) of patients with locoregional relapse underwent salvage surgery. More intensive follow-up in the first two years is recommended.

The value of follow-up in FIGO stage IB carcinoma of the uterine cervix.

The value of hospital follow-up in the detection of first locoregional or metastatic relapse was assessed in 276 patients with histologically confirmed FIGO Stage IB carcinoma of the cervix. All were treated by intracavitary and external beam irradiation. The maximum period of follow-up studied was 10 years (median follow-up was 55 months) during which 3190 routine and interval clinical visits were made. Fifteen (44%) of locoregional relapses (LRR) and eight (38%) of metastatic relapses were detected at routine visits (137 visits per relapse detected). Seventy-five per cent of relapses occurred within the first 5 years. Nine LRR occurred in the second quinquennium. Five (14.7%) of LRR underwent salvage surgery, three of whom were asymptomatic at the time of relapse. If routine visits had been stopped at 5 years the number of clinical visits would have been reduced by 15%, possibly at the cost of one patient whose asymptomatic LRR might not have been amenable to salvage surgery, had she not presented until she was symptomatic. Routine follow-up beyond 5 years is of dubious benefit in the detection of relapse.

Synchronous 5-fluorouracil, mitomycin-C and radiation therapy in the treatment of locally advanced carcinoma of the cervix.

Locally advanced carcinoma of the cervix has a poor prognosis with a high incidence of persistent or recurrent local disease contributing to distressing symptoms and poor survival. This has remained unaltered over the past 30 years in spite of the addition of other therapeutic modalities. Between 1983 and January 1986, 38 patients with locally advanced carcinoma of the cervix were treated with synchronous 5-fluorouracil, mitomycin-C, and radiotherapy. The results of this pilot study indicate both an improvement in pelvic control and in 3-year survival rate for the chemosensitized therapy compared to conventional radiotherapy alone (55% v 28%) using historical controls. Improved survival was only significant for bulky FIGO Stage IIb tumors. The toxicity of this combination was predominantly gastro-intestinal and led to modification of both radiation dose and technique with subsequent improvement in the incidence of side effects. The results suggest that the combination of synchronous chemotherapy with radiotherapy is an improved method of treatment for locally advanced carcinoma of the cervix and that a prospective randomized trial is now justified.

Extramedullary plasmacytoma of the rectum: two cases treated by radiotherapy.

Two cases of extramedullary plasmacytoma of the rectum treated by radiotherapy are reported. In one patient local control of disease was achieved at 36 months. A second patient treated by a palliative course of radiotherapy had initial good local regression and control of symptoms at 3 months. In view of the radiosensitivity of this tumour, consideration should be given to treating extramedullary plasmacytoma of the rectum by primary radiotherapy.

The pathogenesis of post-irradiation chronic diarrhoea: measurement of SeHCAT and B12 absorption for differential diagnosis determines treatment.

The absorption of vitamin B12 and of a synthetic bile acid analogue 75SeHCAT was measured simultaneously in 26 patients presenting with persistent diarrhoea following pelvic irradiation for treatment of carcinoma of the cervix. Four groups were identified, namely patients with isolated bile acid malabsorption, patients with isolated B12 malabsorption, patients with malabsorption of both and those with malabsorption of neither compound. The therapeutic implications are different for each. Measurement of B12 and bile acid absorption comprises an important new test for the management of patients with this disabling and unpleasant complication of radiotherapy.

Surgical aspects of intestinal injury due to pelvic radiotherapy.

Seventy-one patients with intestinal injury secondary to pelvic irradiation had predominantly large bowel lesions. Seventeen cases were treated conservatively and 54 came to surgery, 28 patients having more than one operation. Following this essentially salvage surgery there were more ileal than colonic anastomotic leaks. Thirty-four patients died during the follow-up period (2-12 years), 19 from recurrent malignancy, and nine as a result of continuing radiation effects. Seventy per cent of the patients who had a radiation fistula died as a result of malignancy. Of 42000 cases of pelvic malignancy treated by irradiation over the decade 1972-1982, surgical referrals for complications constituted 1.7%, with an overall radiation-related mortality of 0.2%. It is our opinion that colostomy alone has little part to play in this condition, and a policy based on excisional surgery is suggested.

Five-year results of a controlled study of BCG immunotherapy after surgical resection in bronchogenic carcinoma.

Ninety-two patients with histologically confirmed bronchogenic carcinoma treated by surgical resection of the tumour were subsequently given immunotherapy with BCG (Glaxo). The patients were randomly allocated into three groups. Twenty-nine patients received multipuncture BCG (50 to 250 X 10(6) viable units), and twenty-six patients intradermal BCG (0.4 to 0.9 X 10(6) viable units), treatment being given at 1, 2, 6, 9, 13, 26, and 52 weeks after operation. Thirty-seven control patients did not receive any BCG immunotherapy; two patients in the control group were lost to follow-up. The overall five-year survival in all groups was 37%. Favourable prognostic features were squamous carcinoma (45% five-year survival), the absence of involved mediastinal nodes at operation (46%), and lobectomy (45%), but even the presence of involved mediastinal nodes was associated with a 19% five-year survival. There were no statistically significant differences between the survival of the control group and either group treated by immunotherapy considered individually or in combination. The influence of the presence of positive mediastinal lymph nodes and the extent of surgical resection on survival was not affected by immunotherapy. No serious side-effects of immunotherapy were encountered.

The detection of DNA tumour virus-specific RNA sequences in abnormal human cervical biopsies by in situ hybridization.

We have used the technique of in situ nucleic acid hybridization and autoradiography of thin frozen sections of human tissue to search for virus RNA sequences in human cervical tumours. Of cervical biopsies with abnormal cytology, 67% bound herpes simplex virus type 2 (HSV2) 3H-labelled DNA probes and 39% bound adenovirus type 2 (Ad2) 3H-labelled DNA probes, whereas control experiments with phage lambda 3H-labelled DNA probes, under the same conditions, bound to only 7% of cases. In contrast, normal cervical biopsies bound the three probes in only 23%, 17% and 8% of cases respectively.

Fluorouracil cardiotoxicity.

Our of 140 patients treated with intravenous 5-fluorouracil, four developed ischaemic chest pain within 18 hours of either the second or third dose. In three of these patients the pain recurred after subsequent doses. Predose electrocardiograms in two cases were normal. None of the four patients had a history of ischaemic heart disease, although all had received left ventricular irradiation. Although cardiotoxicity is a rare complication of fluorouracil treatment, it merits wider recognition.