Milestones in European Thyroidology (MET)

François Delange (1935-2007)

François was born in Ixelles (Brussels) in 1935 and passed away in June 2007. After a rather difficult youth, due mainly to the consequences of World War II (where he lost his father) and a complicated personal family history in the years immediately thereafter, François decided to go to medicine with the aim of devoting his life to social aspects of the medical profession. François studied medicine at the Free University of Brussels (ULB) from where he graduated as M.D. in 1960. He then trained in pediatrics at the University Hospital Saint Pierre (Pr. R. Dubois) in Brussels, and obtained his recognition as pediatrician in 1965. Later on in 1981, he was to become one of the rare examples - in Belgium - to obtain a double specialty recognition in both pediatrics and nuclear medicine. He completed his Ph.D. thesis in 1973, entitled "Etude d'une endémie goitreuse en Afrique Centrale: Influence de la croissance et des facteurs d'environnement sur la fonction thyroïdienne". François' thesis remains today one of the very few examples of a Belgian Ph.D. thesis to have been integrally translated into Chinese, under the title "Endemic goitre and thyroid function in Central Africa".

François spent most of his professional career in the Department of Pediatrics at the University Hospital Saint Pierre (Pr R. Dubois, Pr H. Vis, & Pr J. Levy), where he eventually became Chief of Clinic and Professor of Pediatrics at the ULB, until he retired at the age of 60 years, in 1995. François was renowned for his remarkable clinical qualities as pediatric care provider and also as an excellent supervisor and mentor of both the clinical and research activities of many fellows and young pediatricians. He was responsible for the outpatient clinic of pediatrics and despite his many scientific activities that took him out of his country some times for prolonged periods of time, François always managed to remain an active senior member in the department of pediatrics. As a compassionate and warm physician, he was personally and deeply involved in the problems of his patients and their family.

For François, his retirement from hospital life did not mean stopping work altogether, on the contrary, it allowed him to pursue and develop his life long interests in iodine deficiency disorders (IDD), within the International Council for the Control of Iodine Deficiency Disorders (ICCIDD). François was a member of ICCIDD and member of its board since its foundation in 1986. He acted as the regional coordinator of ICCIDD for Europe between 1986 and 2001. Finally, he was appointed as the Executive Director of ICCIDD between 1995 and 2001. His last position within the ICCIDD was that of Honorary Executive Director.

His research activities began already in 1960, immediately after his MD graduation. He started by collaborating with Pr Paul Bastenie in the Laboratory of Experimental Medicine, Pr Jacques Dumont in the Laboratory of Nuclear Medicine and finally joined Pr André Ermans in the Laboratory of the Department of Radioisotopes in the University Hospital Saint-Pierre. In the team of investigators constituted and mentored by André Ermans for the study of goiter and iodine deficiency in Central Africa, François was undoubtedly one of the most active and one of the first 'spiritual children' of André Ermans. His main interest was the study of iodine deficiency disorders (IDD) and, from the start, his main fields of interest were to associate clinical and experimental aspects of the physiopathology of thyroid disorders with pediatrics.

Between 1965 and 1982, François accomplished 30 research journeys to the former Zaire, actually named the Democratic Republic of Congo. This he did even when war was tearing the country apart. Several times, François was physically confronted by dangerous encounters with drunken trigger happy uncontrolled soldiers. John Stanbury still recalls an incident when such soldiers decided to requisition the boat which had to bring their field team back from Idjwi island; François said "no, this boat is used for medical purposes and I shall not let you take it away"! Impressed by this firm but unarmed physician, the soldiers yielded. Each time he came out of it thanks to his coolness, his sense of humor and his moral strength. During that time he concluded the demonstration of the myxedematous form of endemic cretinism, showed the role of cassava (manioc) and thiocyanate in endemic goiter, developed the use of iodized oil in IDD prevention, etc. He developed and generalized the methodology of population studies of iodine deficiency and iodine prophylaxis. After John B. Stanbury, François is among the very few who have most contributed to our current knowledge and understanding of endemic goiter. Subsequently, his research and public health studies on IDD continued in Albania, Algeria, Austria, Bosnia, Bulgaria, Burundi, Cameroon, the Czech Republic, China, Colombia, Croatia, Ecuador, France, Germany, Hungary, India, Italy (Sicily), Nepal (see below), Peru, the Philippines, Poland, Portugal, Romania, Russia, Spain, Venezuela, Zimbabwe, and last but not least Belgium and Luxembourg.

In 1976, François received a proposal to participate in an inquiry on endemic goiter in the Himalayas, namely in the Northern part of Nepal close to the Chinese border. The day before his departure (from Paris by Aeroflot), François recalls walking alone on the Champs-Elysées, thinking loudly (and he told us this later) that he was not sure at all why he had accepted this terribly difficult challenge. In fact, this field trip eventually proved to be an extraordinary event for François, first scientifically because he discovered the severity of iodine deficiency in this part of the world, which became the basis for organizing later on a national program of iodine supplementation in Nepal. It was also important on a personal basis, because he had to walk in the mountains for seven to ten hours a day in order to reach the most isolated villages, only sustained by cups of hot tea and bowls of rice during the seven weeks that the mission lasted, and at altitudes between 700 and 4,200 meters. François lost fifteen Kg during that mission but he regained both physical fitness and emotional strength and equilibrium, at a difficult personal time for him. It is after he returned from this trip that he met Nicole, his beloved second wife for the next thirty years.

When mentioning the impact of François in the field of iodine deficiency and endemic goiter, we can safely use the expressions 'worldwide field experience', 'excellence in clinical investigation', and 'idealistic & pragmatic dedication to the eradication of IDD' in most countries in the world affected by this scourge, including Europe. After John Stanbury retired from ICCIDD, François was, with John Dunn, the scientific conscience of ICCIDD to which he gave a new impetus.

François was also a pioneer in the development of neonatal screening for congenital hypothyroidism (CH). Under his leadership, systemic screening for CH was initiated in Europe at the end of the 1970s, using serum TSH determination in the first days of life as the prime target. Therefore, he had to fight hard with his American colleagues who, at that time, advocated total T4 determination as the main target of screening for CH. Confident that his scientific reasoning was correct (i.e. that elevated neonatal serum TSH would provide a more sensitive marker to detect early thyroid insufficiency), he maintained this position in Europe, resisting all those who thought, without real scientific argument, that Europe should follow the US fashion. François much contributed to the detection, diagnosis and therapy of permanent sporadic congenital hypothyroidism. He was among the first to describe the epidemiology and significance of transient abnormalities of thyroid function in the neonatal period, and the first to report on the exquisite sensitivity of the premature/neonatal thyroid gland to the effects of iodine excess and to propose avoidance of iodine-rich solutions for skin disinfection around the time of parturition.

François was the promoter of the ThyroMobil story, an initiative sponsored by Merck KGaA. The company purchased a van suitable for equipment with an ultrasound scanner and a deep freeze to store urine samples, with the objective to investigate the prevalence of goiter in Europe (originally), determined by ultrasound-measured thyroid volume in school-aged children using identical examination methods and standardized study protocols. Furthermore, the urine samples taken from all examined subjects allowed to measure urinary iodine concentrations and eventually yielded an excellent view of the prevalence of goiter in young age and its relationship with iodine deficiency. The initial step took place in Cardiff, at the annual meeting of the ETA in 1993. This remarkable project constituted a strong scientific basis to launch field studies of IDD in Europe first, followed by similar studies in Latin America, Africa, Indonesia and, last but not least, Australia. Altogether, 32 countries and 432 sites were investigated, including more than 38.000 school-age children, and more than 5.500 salt samples analyzed for their iodine content. These studies provided an accurate picture of IDD in the world, and allowed to monitor progresses in the eradication of IDD through the introduction of iodized salt. Only one month before his death, François finished writing and published the 'Story of the ThyroMobil' in Thyroid International.

François received many professional awards, among which the Herman Houtman Belgian Foundation award in 1997 (for his research in pediatrics), the ETA Merck prize in 1997, and the ICCIDD award in 2007 for his continuous effort to eradicate iodine deficiency disorders worldwide. François received the degree of Doctor Honoris Causa from the Charles University (Prague, Czech Republic) in 1998 and the Jagiellonian University (Krakow, Poland) in 1999.

François Delange authored or co-authored 12 books, 361 publications including original articles, reviews, several chapters in textbooks, monographs, and proceedings of international congresses. In his long and fruitful career, he presented more than two hundred communications at international meetings. He also organized several international meetings, mainly devoted to advances in pediatric thyroidology, congenital hypothyroidism, and iodine deficiency.

François used to say that his life has been a "hard" one, having followed non classical pathways throughout his career, from pediatrics to nuclear medicine, and from endocrinology to public health issues. He considered that he had accomplished what he had set out to become when he was only 18 years of age, trying to provide medical care of the highest academic level to the poor and deprived populations, with the protection of the children as his main goal, a constant reminder of his own difficult youth. A great clinical scientist, François was a personage full of wisdom, courage, idealism, scientific honesty, and witty sense of humor. His untimely and recent death at a still young age will be regretted by all those who knew him well, his many friends in Brussels and around the world, and probably even his few enemies. We feel honored to have been his lifelong friends.

Daniel Glinoer (1) & Jacques Dumont (2)
(1) University Hospital Saint Pierre (Brussels)
(2) IRIBHM (Université Libre de Bruxelles)


Bibliography

1. Delange F, Thilly C, & Ermans AM: Iodine deficiency, a permissive condition in the development of endemic goiter. J.Clin. Endocr. Met. 1668, 28:114-116.
2. Delange F, Ermans AM, Vis HL, & Stanbury JB: Endemic cretinism in Idjwi Island (Kivu Lake, Republic of the Congo). .J. Clin.Endocr. Met. 1972, 34:1059-1066.
3. Delange F, Thilly Ch, & Ermans AM: Endemic goitre in Kivu area, Africa: Focus on cassava. In: The role of Cassava in the etiology of endemic goitre & cretinism. (Ermans AM, Mbulamoko NM, Delange F, & Ahluwalia R, Eds). I.D.R.C., Ottawa; pp 29-36, 1980.
4. Delange F, Bastani S, Benmiloud M, De Maeyer E, Isayama MG, Koutras D, Muzzo S, Niepomniszcze H, Pandav CS, & Riccabona G: Definitions of endemic goiter and cretinism, classification of goiter size and severity of endemias, and survey techniques. Pan American Health Organization Scientific Publications, Washington (DC); pp 373-376, 1986.
5. Delange F: Endemic cretinism. In: The thyroid. A fundamental and clinical text. (Ingbar SH & Braverman LE, Eds). Lippincott; pp 722-734, 1986.
6. Delange F, Fisher DA, & Glinoer D: Research in Congenital Hypothyroidism. Plenum Press, New York; pp 1-367, 1989.
7. Delange F, Dunn JT, & Glinoer D: Iodine Deficiency in Europe - A continuing concern. Plenum Press, New York; pp 1-491, 1993.
8. Delange F & Lecomte P: Iodine supplementation: benefits outweigh risks. Drug Safety. 2000, 22: 89-95.
9. Delange F, de Benoist B, Pretell E, & Dunn JT: Iodine deficiency in the world: where do we stand at the turn of the Century? Thyroid. 2001, 11: 437-447.
10. Delange F: Optimal iodine nutrition during pregnancy, lactation and the neonatal period. Int.J.Endocr Met. 2004,2:1-12.