Acute aortic valvular regurgitation with pulmonary haemorrhage in Wegener's granulomatosis presenting as dyspnoea: a rare presentation.

A 40-year-old man with Wegener's granulomatosis with renal and ocular involvement was admitted with symptoms of fever, malaise and cough not responding to oral antibiotics. On initial assessment, he had patchy consolidation but was also found to have a new cardiac murmur. He was mildly anaemic. Within 2 days of hospital stay his haemoglobin dropped and he became tachypnoeic. High-resolution CT found extensive pulmonary infiltrates, which suggested pulmonary haemorrhage, and blood cultures were negative. He was on antibiotics because of suspected infective endocarditis and this made any immunosuppressive treatment for active Wegener's granulomatosis very difficult. After extensive discussion with tertiary centres he had pulse methylprednisolone for 3 days. His echo detected aortic regurgitation but no vegetations. His antibiotics were stopped and he had cyclophosphomide to control his active Wegener's granulomatosis. He improved remarkably with immunosuppression and non-invasive ventilation and was discharged. He had a further echo, which confirmed moderate aortic regurgitation. He is awaiting cardiac catheter studies but the fact is acute aortic regurgitation has happened due to active Wegener's granulomatosis along with pulmonary haemorrhage. This is a very rare presentation.

Presymptomatic diagnosis of bronchogenic carcinoma associated with bilateral diffuse uveal melanocytic proliferation.

A 62-year-old man presented with bilateral diffuse uveal melanocytic proliferations (BDUMP) and painful flexor contractures of the fingers of both hands. All these features were considered paraneoplastic but extensive and repeated investigations revealed no underlying malignancy. Oral steroids and orbital radiotherapy were ineffective. The diagnosis was confirmed by trans-scleral biopsy of the right choroid. Rapidly progressive cataracts were treated by phacoemulsification. Severe exudative retinal detachment with rubeosis and neovascular glaucoma in the left eye were treated successfully by partial choroidectomy. Fifteen months after presentation, investigations detected a 22 mm, poorly differentiated adenocarcinoma, which was resected without complication. The ocular tumours in both eyes regressed, without improvement in vision of Light Perception, and the palmar fasciitis also improved. The patient remained free of tumour recurrence until sudden death from myocardial infarction five years after he first presented.

Effects of growth hormone replacement on parathyroid hormone sensitivity and bone mineral metabolism.

Adult GH deficiency (AGHD) is associated with reduced bone mineral density, and decreased end-organ sensitivity to the effects of PTH has been suggested as a possible underlying mechanism. We investigated the effects of GH replacement (GHR) on PTH circulating activity and its association with phosphocalcium metabolism and bone turnover in 16 (8 men and 8 women) AGHD patients. Half-hourly blood and 3 hourly urine sampling was performed on each patient over a 24-h period before GHR and then after 1, 3, 6, and 12 months of GHR. GH was commenced at a dose of 0.5 IU/d and was titrated to achieve and maintain an IGF-I SD score within 2 SD of the age-related reference range. The target IGF-I SD score was achieved within 3 months and was maintained at 12 months after GHR in all patients. Our results demonstrated a significant decrease in serum PTH at all visits after GHR compared with baseline values (P < 0.001), with a concomitant increase in nephrogenous cAMP excretion at 1 (P < 0.001) and 3 (P < 0.05) months and increases in serum calcium (P < 0.001), serum phosphate (P < 0.001), 1,25-dihydroxyvitamin D(3) (P < 0.001), type I collagen C-telopeptide (a bone resorption marker; P < 0.001), and procollagen type I amino-terminal propeptide (a bone formation marker; P < 0.001). Simultaneously, we observed a significant decrease in urinary calcium excretion (P < 0.001) and an increase in maximum tubular phosphate reabsorption (P < 0.001). Together these results suggest increased end-organ responsiveness to the effects of circulating PTH resulting in increased bone turnover and reduced calcium excretion. Significant circadian rhythms were observed for serum PTH, phosphate, type I collagen C-telopeptide, and procollagen type I amino-terminal propeptide before and after GHR. However, sustained PTH secretion was observed between 1400-2200 h, with a reduced nocturnal rise in untreated AGHD patients, whereas PTH secretion decreased significantly between 1400-2200 h (P < 0.001), with a significant increase in nocturnal PTH secretion (P < 0.001) after 12 months of GHR. Our results demonstrate that GH may have a regulatory role in bone mineral metabolism, and our data provide a possible underlying mechanism for the development of osteoporosis in AGHD patients. The changes observed after GHR may further explain the beneficial effects of GHR on bone mineral density that have consistently been reported.