The prevalence of smoking among Kuwaitimen is very high and a large number of them are heavy smokers.1 The number of women smokers is also steadily going up. Hence the incidence of bronchogenic carcinoma is very high. It is also the cancer with the highest incidence of paraneoplastic syndromes.2 PNS is a constellation of signs and symptoms that are not due to direct effect of the tumour or its metastasis but occurs due to the hormones or other chemicals produced by the tumour. As PNS may be the initial presentation even before the manifestations of the tumour, a high degree of suspicion is required for early diagnosis and treatment leading to a better prognosis.3 The purpose of the study was to determine the pattern of PNS in patients with bronchogenic carcinoma admitted at A1 Jahra hospital - a 480 bed peripheral general hospital in Kuwait.

The Medical records of all confirmed cases of bronchogenic carcinoma admitted to A1 Jahra hospital between January 2000 and June 2004 were reviewed. The clinical and biochemical parameters recorded were : age, sex, underlying medical illness, presentation, complete blood count, blood urea, electrolytes and serum calcium levels. The localization of the tumours was done by chest X-ray and CT scan. Tissue biopsy was obtained by bronchoscopy or under CT scan guidance and histopathological examination of the specimen was carried out. The type of PNS if any was noted. These parameters were entered into a database and later analyzed. The data management and statistical package used was Epi Info version 6 distributed readily by the CDC (Centre for Disease Control) Bethesda, USA.

A total of 52 patients were studied comprising 49 males and 3 females - all of them heavy smokers or ex-smokers. The mean age was 67.46 ± 12.15 years. Associated illnesses were : Diabetes Mellitus 45.5%, Hypertension 63.6%, COPD 27.3%. All the patients presented with cough, 99% with shortness of breath, 42% with haemoptysis, 31.5% with pleural pain, 42% with fever, 75% with weight loss.

The patients who presented with signs symptoms and laboratory evidence of PNS were : 42% with hypercalcemia, 9.6% with thrombocytosis, 5.8% with limbic encephalitis or SIADH, 3.8% with peripheral neuropathy, 1.9% with GBS and 5.8% with pancytopenia.
In our study there were no patients who presented with ectopic ACTH secretion, myasthenia gravis or Lambart - Eaton myasthenic syndrome.
The histopathological type of the bronchogenic carcinoma were : 22.4% small cell carcinoma and 67.6% non-small cell carcinoma.

The fact that bronchogenic carcinoma is caused by carcinogens and tumour promoters ingested by cigarette smoking is fully corroborated in this study where almost 100% patients were either heavy smokers or ex-smokers. The relative risk of developing bronchogenic carcinoma increases 13 fold by active smoking or ~1.5% by passive exposure to cigarette smoke.

Paraneoplastic syndromes which are the distant effect of underlying carcinoma can present early, well before the primary lung lesion produces local symptoms and even when the tumour is undetected or very small. The signs and symptoms of the hormones and biochemical agents produced by the bronchogenic carcinoma can be detected early by clinical and biochemical means.3 Bigger the tumour, more florid are the signs and symptoms of PNS. The diagnosis of occult tumour associated with PNS requires a high degree of suspicion, but still on some occasions it may be difficult and may lead to delay in initiation of treatment.3 Hypercalcaemia is the commonest PNS of bronchogenic carcinoma and is most commonly associated with the squamous cell carcinoma type, but can be associated with the other non-small cell bronchogenic carcinomas. Hypercalcaemia is uncommon at presentation4 but becomes apparent as the tumour progresses.4 Its pathogenesis is related to hormone production and is called humoral hypercalcaemia of malignancy. In our study hypercalcaemia was present in 43% of the patients which correlates well with the other studies. Another hormone that is produced by bronchogenic carcinoma is ADH.5 The syndrome of inappropriate ADH (SIADH) secretion is easily diagnosed by clinical and biochemical means. It results in hypotonic euvolaemic hyponatraemia with urinary hyperosmolarity. It is most commonly associated with small cell bronchogenic carcinoma and is caused by release of argenine vasopression (AVP) hormone. The incidence of SIADH of 5.8% correlates well with the other studies. Sign and symptoms may precede the tumour by many months or years.6,7 In our study limbic encephalitis presented as intractable epilepsy and the small tumours were detected due to the high index of suspicion. There is evidence that neoplastic neurological symptoms are immune mediated (anti-Yo antibodies).8,9 Treatment is directed towards the primary tumour and the PNS may remit with the regression of the tumour.

Thrombocytosis is the commonest paraneoplastic haematological abnormality with some studies reporting incidence up to 50%.10 In our study the incidence of thrombocytosis was 9.1%. Two of our cases had pancytopenia with hypercellular marrow as in the cases reported by Raz et al.12,13 The other haematological PNS reported is Erythrocytosis due to increased Erythropoietin secretion by the tumour.14 We had no report of erythrocytosis in our study. Since PNS can be the presenting feature of bronchogenic carcinoma, it is imperative to have a high index of suspicion and to investigate these patients fully with all available facilities. The use of 18-F fluorodeoxyglucose positron emission tomography ((U8)F-FDG-PET) has further helped in directing small occult tumours.

Paraneoplastic syndromes are common in patients with bronchogenic carcinoma from Al Jahra region of Kuwait. These patients, clinically presented with hypercalcaemia, thrombocytosis, SIADH or limbic encephalitis. It is therefore important to consider the possibility of bronchogenic carcinoma in smokers who present with signs, symptoms and biochemical evidence of paraneopalstic syndromes and to investigate them thoroughly.

We express our thanks to Mr. Sunny J Parackal for his help in typing this manuscript.