To, Professor Dr. Aziz Ahmad, Chief Editor, Journal of Saidu Medical College, Sawat. Subject:- PUBLICATION OF ORIGINAL ARTICLE. It is certified that my research titled, “To Assess the effect of pineapple on Goiter size and TSH level” is an original research, conducted by me and which is approved by the Ethical review committee of P.G.M.I. Lahore. It is further submitted that I have not sent this article for publication to any Journal. Dr. Abdul Rehman Khokhar Assistant Professor of Physiology D.G Khan Medical College Dera Ghazi Khan TO ASSESS THE EFFECT OF PINEAPPLE ON GOITER SIZE AND TSH LEVEL ABDUL REHMAN KHOKHAR1, MUHAMMAD SHAHID FARQUI2, MUHAMMAD ARSHAD QURESHI3 , TANVIR ALI KHAN SHIRWANY4 QURRAT UL AIN REHMAN5. 1. Assistant Professor Physiology D.G Khan Medical College Dera Ghazi Khan 2. Assistant Professor Physiology P.G.M.I Lahore 3. Assistan Professor Pharmacology Sahiwal Medical College Sahiwal 4. Principal/Professor of Physiology Red Crescent Medical College Lahore 5. P.A.E.C. Science College Dera Ghazi Khan ABSTRACT INTRODUCTION Endemic goiter is a major world wide problem and is a preventable disease. More than 12% of world population is affected. Ananas Comosus is a good source of iodine and vitamin c. Which reduce the size of goiter. OBJECTIVES 1.To measure the goiter size reduction between study and control groups at 4, 8, and ten weeks of intervention 2.Suppression of TSH level up to 25% from base line STUDY DESIGN Randomsized control Trial. SAMPLE SIZE 7o, study group 35, control group 35. SAMPLING TECHNIQUE Simple Random sampling. DOSE STANDARDIZATION was done by P.C.S.I.R laboratories complex Lahore. EXCLUSION CRITERIA. Subjects suffering from bleeding disorder, liver disease and thyrotoxicosis. History of thyroid surgery, solitary nodular goiter with history of pain and regional lymphadenopathy. Diabetes mellitis, History of use of iodized salt, contracting marriage. Goitrogenic food/marine foods intake, change in bowel habits DATA COLLECTION Subjects suffering from endemic goiter were selected from teaching hospital D.G Khan. Goiter size measurement and TSH estimation was done at 0, 4, 8 and 10 weeks of study. DATA ANALYSIS Goiter size reduction from baseline 4.41±0.86cm to 2.00±1.02 after eight week of intervation was highly significant among study group P<0.000, and TSH suppresses from baseline 2.63±0.95 to 0.94±0.84 after eight week P< 0.000. While changes in control group were non significant. CONCLUSION Ananas Comosus is good alterneture remely for endemic goiter patients and a valuable goiter shrinkage agent. KEY WORDS: PCSIR Goiter Ananas Comosus PEI TRIAC TSH Pakistan Council of Scientific & Industrial Research enlarged Thyroid gland Pineapple Percutaneous Ethanol injection Thri-iodo thyro acetic acid Thryoid Stimulating hormone INTRODUCTION: World Health Organization has declared endemic goiter a major world-wide problem and public health priority1. It is a preventable disease, and threat to social and economic development of poor countries. More than 12% of world population is affected2. Endemic goiter is more prevalent in hilly areas3. The fact that iodine deficiency plays a major role in the genesis of endemic goiter4 . In Pakistan an alarming high prevalame of endemic goiter has been reported from Northern Areas of country in laps of Himalyas5. Unreliable assessment of iodine deficiency, poor iodine supplementation, inadequate education, publicity, cost affective are deadly sins, to be avoided in order to achieve sustainable elimination of iodine deficiency1. National Utilization level of iodized salt is only 17% as projected in the Econmic Servey of Pakistan. Which is drastically lower than W.H.O recommending level > 90% level due to non availability and high priece6. People residing in goitrous areas can only obtain enough iodine by consuming sustainable protion of their food in form of marine food, foods from iodine rich regions and using iodized salt7. Iodine is unstable and has largely been replaced by iodate due to sublimation8. Effects of iodine deficiency are worsened if selenium level is low9. Ananas comosm has been used for its medicinal properties for hundred of years. It has broad specturm of actions and a good source of iodine and vitamin C10. Bromelain is an enzyme complex, present in fruit and stem of pineapple, which is key to pineapple medicinal use11. Bromelain is an effective anti-inflammatory agent. Pineapple juice is used to treat morning sickness and sea sickness. Two slices of fresh pineapple (25mg) contain 1 mg of iodine and 100 mg of vitamin C is a recommended adult dose per day12. It enhances the absorption and permeability of Amoxicallin and Tetracycline in diseased tissue so it is synergistic effect is documented13. Contact dermatitis is reported side effect of prolong use of pineapple. Safety during pregnancy and lactation is not documented yet14. Data Collection Procedure Planned visits were made to subjects homes, along with a female nurse, to explain criteria/requirements of study. Lists of foods/fruits of high iodine content was provided to subjects and advised not to consume these foods during study period. Seventy female were selected from medical outpatient department of teaching hospital D.G. Khan. After selection, subjects were randomized and divided into 2 groups, study and control groups. 5 ml of blood was drawn aseptically for base-line, Hb and TSH estimation from all subjects and was allowed to clot for 15-20 minutes. Then it was centifuged for ten minutes at 5,000 rpm. Serum was sucked and stored , at -20 C in serum cups. Microlab-300 Analyzer was used for serum TSH estimation by ELISA kits Human Germany. All subjects of study group had taken 27 gm of fresh. Ananas comosus daily for period of eight weeks. Control group was given Placebo to be eaten during study period Blood samples were drawn aseptically from both study and control group for TSH estimation at 04, 08 and ten weeks of study Goiter size was measured with vernier caliper at onset of study and subsequently at four, eight and ten weeks. Findings were recorded on evaluation proforma. RESULTS Seventy female subjects with newly diagnosed endemic goiter were randomized. Eleven subjects dropped out during follow up. At onset of study no significant difference was noted between TSH, T3, T4 levels and goiter size of both groups. (Table 1). After four and eight weeks of pineapple ingestion goiter size reduction was 2.38% and 2-98% respectively. Within control group changes in goiter size were non significant P=0.06, (Table 2). While highly significant goiter size reduction was noted among study group, P=0.000, (Table 3). Serum TSH level comparison by paired sample t test, with in control group, resulted no significant suppression of TSH level. P> .704, which was 0.94% and 4.3% only at four and eight weeks (Table 4). While TSH suppression was high significant at four and eight weeks of pineapple ingestion among study group P=0.000, (Table 5). When compared between two group by Independent sample t test, highly significant goiter size reduction was noted P=0.000, (Table 6) and TSH suppression was also highly significant P=0.000, (Table 7) which indicates that pineapple is a good goiter size reducing agant. Table 1 Baseline Characteristic on 1st day No. of females Age in years Goiter size T3 T4 TSH Hb% Study group n = 29 (82.9%) 19.86 + 3.96 4.41 + 0.86 cm 1.29 + 0.46 ng/ml 7.78 + 1.96 ug/dl 2.63 + 0.95 miu/l 11.10±2.19gm% Control group n =30 (85.7%) 19.27 + 3.17 4.33 + 1.05 cm 1.45 + 0.46 ng/ml 6.84 + 2.17 ug/dl 2.74 + 1.44 miu/l 10.91±2.35gm% Results are expressed as mean ± SD Table 2 Comparison of goiter size within control group (non-treated) by paired samples t-test Control group (n=30) Time Base line 4 week 8 week 10 week Goiter size (cm) 4.33 ± 1.05 4.23 ± 1.09 4.22 ± 1.04* 4.21 ± 1.15 p-value Reduction 0.066 0.018 0.097 2.38% 2.47% 2.98% Results are expressed as mean ± SD Table 3 Comparison of goiter size within study group (treated) by paired samples t-test study group (n=29) Time Base line 4 week 8 week 10 week goiter size 4.41 ± 0.86 2.99 ± 0.53*** 2.00 ± 1.02*** 2.17 ± 1.09*** p-value Reduction 0.000 0.000 0.000 31.25% 54.83% 50.03% Table 4 Comparison of serum TSH within control group (non-treated) by paired samples t-test Control group (n=30) Time Base line 4 week 8 week 10 week TSH (miu/l) 2.74 ± 1.44 2.73 ± 1.37 2.72 ± 1.30 2.69 ± 1.57 p-value Reduction 0.704 0.735 0.259 0.945% 2.447% 4.363% Table 5 Comparison of serum TSH within study group (treated) by paired samples t-test study group (n=29) Time Base line 4 week 8 week 10 week TSH (miu/l) 2.63 ± 0.95 0.41 ± 0.19*** 0.94 ± 0.84*** 2.44 ± 0.70 p-value Reduction 0.000 0.000 0.353 82.31% 56.61% 3.17% Table 6 Comparison of Goiter size (cm) between control group (non-treated) versus study group (treated) by Independent Samples t-test Time Base line 4 week 8 week 10 week Control group Mean ± SD 4.33 ±1.05 4.23 ±1.09 4.22 ±1.04* 4.21 ±1.15 Study group Mean ± SD 4.41 ± 0.86 2.99 ± 0.53*** 2.00 ± 1.02*** 2.17 ± 1.09*** p-value 0.750 0.000 0.000 0.000 Table 7 Comparison of serum TSH between control group (non treated) versus study group (treated) by Independent Samples t-test Time Base line 4 week 8 week 10 week Control group Mean ± SD 2.74 ± 1.44 2.73 ± 1.37 2.72 ± 1.30 2.69 ± 1.57 Study group Mean ± SD 2.63 ± 0.95 0.41 ± 0.19*** 0.94 ± 0.84*** 2.44 ± 0.70 p-value .720 .000 .000 .433 DISCUSSION Visible goiter causes cosmetic disfigurement of neck. Iodine deficiency results decrease serum T3, T4, which leads to high TSH level, which resulting in hyperactivity of thyroid leading to goiter15. Fresh pineapple, ingestion (fresh) resulted significant goiter size reduction within eight weeks, while no significant change in goiter size was reported in control group. Numerous studies have been carried out, using various chemical substances to determine their effects on thyroid goiters. But evidently no study appears to evaluate effects of natural substance especially fruits like pineapple and strawberries on development or otherwise of goiters. Guglielmi et al (2004) established the role and efficiency of per-cutaneous Ethanol injection(PEI) in benign thyroid lesions. Fifty eight recurrent cystic nodules and soft autonomous functioning nodules were treated by PEI for six years16 while in our study seventy female patents having goiter were studied. Iqbal et al concluded that significant TSH suppression was noted with thyroxin supplementation for one year which was given 50-100 ug/day among interventional group which was highly significant while in Placebo group TSH level remain persistent till the end of study17. While in our study significant TSH suppression was noted in study group just after four weeks of intervention. No TSH suppression was observed in control group. Brenta et al (2003) described comparison of therapeutic efficacy between L- Thyroxin and Tri-iodo-Thyro acetic acid (TRIAC) in non toxic and nodular goiters. Thirty six women were studies for eleven month after randomization. While in our study endemic goiters females were treated with fresh pineapple for short period. Goiter volume was assessed by Three dimensional sonography, while we used vernier caliper for goiter size measurements and patients were evaluated a four, eight and ten weeks of intervention. After II months thereby goiter size was reduced – 42% in TRIAC group, while in our study goiter size reduction was more than 50% of initial size. Our findings like goiter size reduction and TSH Suppression are in accordance with those of Brenta et al18, but more effective with less duration. Finding of our study also confirm to recommendation of Food and Drug Administration (2013) for TSH monitoring at 6-8 weeks interval unit normalization19. While our study showed significant improvement in serum T3 T4 and TSH levels and highly significant goiter size reduction with 8 weeks of intervention. Anderson et al concluded after double blind household base interventional study of 5-15 years old, randomly assigned in Three groups; Intervention was iodized salt, dual fortified salt with iron as micronized ground ferric pyrophosphate (MGFEPP) or iron as ferrous fumarate both at 2mg/gm of salt. Dual fortification improved, serum ferritin, Hemoglobin, urinary iodine, status first day, five and ten month were estimated20, while in our study we estimated Hemoglobin level only at first day of study and comparatively lesser goiter size reduction was reported among anemic patients. Loss of iodine in salt with 1.8% moisture were high, which caused colour changes in some local foods, while no iodine loss or any sort of color changes was not noted in our study. Zimmermann et-al reported that goiter size reduction was poor among anemic children after oral iodine supplementation. Goiter rate was persistent even after iodine supplementation. Our study results are in accordance with Zimmermann et al regarding comparatively less goiter size reduction was noted among anemic females21. Zimmermann MB (2008) While tracing history various studies during last century or so, referred to a study of Marine and Kimball involving iodine intervention in school children of Akren and Ohio, USA They treated young girls by 200 mg of sodium iodide for 10 days, equivalent to 1700 mg of iodine in total, while double dose was given to older girls, while in our study 26.64 gm / day of fresh pineapple containing 1 mg iodine was ingested by young females for eight weeks. No case of goiter was reported from treated group, while control group show +25% goiter at final examination22. In our study goiter size was reduced significantly with a given safe dose. Zimmernnann et-al reported That iodine intake for short period in doses 500-1000mg/day have inhibitory effect on Thyroid function. In our study safe but effective dose of iodine (1 mg/day) as fresh pineapple was given for short period of eight weeks, which resulted significant goiter size reduction and significant TSH inhibition23. Fresh pineapple, which is a food item and cost effective in quantity required for therapeutic use. It act as a good therapeutic agent for endemic goiter patients. Our study has some limitations, because it is contraindicated in pregnancy, lactation and bleeding disorders etc. Address for correspondence:Dr. Abdul Rehman Khokhar Assistant Professor of Physiology D.G. Khan Medical College Dera Ghazi Khan Email: drarkhokhar@yahoo.com Cell # 0323-7877375 Certain Explanation Females were selected, became endemic goiter is more common among females. Pineapple is freely available but people are ignorant about its health benefits, solicits not commonly used. Tables shows different comparisons, within group and between two groups so cannot be combined. Reason for increase in size/TSH elevation, at ten weeks. Because pineapple ingestion was withheld two weeks before.