MIGUEL BOYAYANRoutine exams of the thyroid (between the tweezers): in search of more serious alterationsMIGUEL BOYAYAN
In 1910, the doctor from the state of Minas Gerais, Carlos Chagas, journeyed through Brazil to get to know the living conditions of the riverside and backcountry populations. In one of his expeditions to the north of the Minas Gerais State he found lots of people with goiter, which results from the abnormal growth of the thyroid gland. Almost a century later, in 2000, four researchers from the University of São Paulo (USP) repeated Chagas’ journey over a two month period, covering 12,000 kilometers in the regions North, Northeast, Central-West and Southeast, aboard a van equipped with an ultrasound machine, computer and a refrigerator. In places as different as Zé Doca, in the state of Maranhão, and Cachoeiro de Itapemirim in the state of Espírito Santo, and Nova Roma in Goiás, they set out to verify the quantity of iodine consumed – both excess of and lack of harms the working of the thyroid gland – and to investigate if there were still Brazilians suffering from goiter, caused by a chronic shortage of iodine.
On examining the size of the thyroid of 2,013 students in twenty one villages and settlements in the States of Pará, Maranhão, Tocantins, Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais and Espírito Santo, at the same locations where the deficiency of iodine had previously been detected, the USP doctors concluded that there were no longer any cases of goiter in these hamlets, thanks to the obligatory addition of potassium iodide to kitchen salt throughout the country. Nevertheless, the examination results on the urine samples of children and youngsters between the ages of 6 and 14 years, led to another conclusion: in the cities of the Northeast, the North and Central-West the population is ingesting an elevated quantity of iodine salt, higher than the 10 milligrams per day recommended by the World Health Organization (WHO).
In this study, which is part of the Thyromobil Project – coordinated by the International Council for the Control of Iodine Deficiency Disorders (ICCIDD) and funded by the Merck laboratory -, the researchers realized that that almost nine out of every ten students showed levels of iodine in their urine higher than the values considered normal: up to 300 micrograms of iodine per liter. And that their level was one of the highest recorded among the fifteen Latin American and African countries covered between 1998 and 2001 by the Thyromobil Project.
Another country with one of the highest levels is Chile, in which the urine of 69.5% of the students contains more than 300 micrograms and 39% more than 500. Bolivia, with 10% of the samples above 300 micrograms, is among the countries with the lowest levels. “Populations that live in places with hot and humid climates have the habit of consuming more salty foods than the inhabitants of the Southeast and South regions”, says the medical endocrinologist Geraldo Medeiros, the coordinator of the Thyroid Unit of the Medical Faculty of USP. “The reason is that the excessive heat makes the body transpire a lot and it then loses salt.”
As the symptoms are slow to appear, those who may well feel the consequences of consuming excess iodine – found in food, in multivitamin complexes and in some medicines – are not children, but adults and the elderly. According to the WHO, the ingestion of iodine in excess over a prolonged period of time – three to four years – can bring about in young adults, mainly among women with some genetic predisposition, an increase in the auto-immune diseases of the thyroid, which occurs when the organism itself begins to manufacture antibodies that destroy the gland. For reasons s yet not fully understood, this infirmity, known as chronic thyroiditis, is seven times more common among women than men. In Brazil it strikes between 3% and 7% of people between the ages of 19 and 45 years and is much higher in the group of women going through menopause – around 13%. Thyroiditis – or chronic inflammation of the thyroid – can lead the gland to produce hormones in insufficient quantities – called hypothyroidism, which, it is estimated, affects around 6% of the population.
Among people older than sixty years, an exaggerated level of iodine in the body increases – and considerably – the occurrence of another type of problem: hyperthyroidism, as is called the excessive production of the hormones T3 (triiodothyronine) and T4 thyroxine of the thyroid, a gland situated in the front part of the neck, which normally weighs between 10 and 16 grams and produces hormones that control the consumption of oxygen in the cells and the level of cholesterol in the blood. After sixty years of age, hypothyroidism, which afflicts less than 1% of Brazilians, increases the already high risk of developing cardiovascular problems. And, it is the production of these hormones at higher than normal levels that leads to the acceleration of heartbeats or an irregularity in the cardiac rhythm, among other symptoms, placing the person’s life at risk.
During the Brazilian stage of the Thyromobil Project, as well as children and youngsters, samples of kitchen salt used in homes were examined. Half of these contained more than 60 milligrams of iodine per kilogram of salt, but within the range acceptable at that time: from 1999 until the beginning of 2003 the concentration allowed in Brazil varied between 40 and 100 milligrams. Based on the research and the technical recommendations of the Ministry of Health, in March of 2003 the National Sanitary Vigilance Agency (Anvisa), an organ of the ministry responsible for the control of medicines and food, has gone on to consider appropriate for human consumption only salt with a level equal to or above 20 milligrams and with an upper limit of 60 milligrams of iodine per kilogram of product.
Four years after their journey into the interior of Brazil, the researchers dedicated themselves to another trek, this time within the state of São Paulo itself. Some two years ago, Medeiros’ team examined 844 pupils, between 6 and 14 years of age, from the cities of Araçatuba, Presidente Prudente, Ribeirão Preto, São José do Rio Preto, Taubaté and Cananéia. Just like the children and teenagers of the first journey, the São Paulo students were submitted to thyroid gland examinations using ultrasound scans and they provided samples of urine and of the salt used in their homes.
The research showed similar results to those previously obtained: there were no cases of goiter in the regions visited and the size of the thyroid was normal in 98% of the pupils. In a general manner, the problem again consists in an exaggerated ingestion of iodine. According to Eduardo Tomimori, from the USP team, the substance is consumed in excess in six of the towns. Half of the students had iodine in a quantity above the normal in their system, and one third of them more than double the acceptable quantity. “As the level of iodine in the salt samples analyzed had been within the standard (from 20 to 60 milligrams per kilogram of product), we concluded that the São Paulo population is taking in a lot of salt”, says Medeiros. But there are exceptions, which as well could be harmful, emphasizes Tomimori. In the farms of the interior of the state many people consume the same salt that is given to cattle. As this product is poor in iodine, this population runs the risk of developing problems associated with a chronic shortage of iodine – for example, goiter, mental retardation and deafness.
In a second stage of the project, the team intends to revisit the six São Paulo towns and to discover the prevalence of alterations in the thyroid of the students’ families. In the opinion of the Brazilian Society of Endocrinology and Metabolism Studies, close to 10% of women above 40 years, and 20% of those who are older than 60 years show some problem with their thyroid gland. One in every five women who seek out a gynecologist to initiate therapy for the reposition of estrogen actually have problems with the functioning of this gland.
When they are not out on the road, the Thyroid Unit researchers, installed at the Hospital das Clinicas, in the city of São Paulo, study the most serious alterations of the gland, such as chronic cases of goiter and of hypothyroidism, which specially affect the elderly. Through a relatively simple measure, the Thyroid Unit team and that of the Nuclear Medical Center, also from USP, have managed to increase by 50% the efficiency of the therapy based on radioactive iodine, which destroys the thyroid cells that are multiplying in an exaggerated manner. Described in an article published in March of this year in Clinical Endocrinology, the innovation consists of inducing the working of the gland with doses of thyroid stimulant hormone (TSH) one day before the radioactive treatment. There is logic to this. In the cases of goiter and chronic hypothyroidism, normally the gland absorbs only a little radioactive iodine because it is already saturated with this chemical element, consumed in kitchen salt or in medicines that contain iodine. The injection of TSH turns the intake of radioactive iodine more efficient.
In this study, carried out between 1998 and 2002, Medeiros’ team evaluated the new treatment in thirty-four patients, of average age 63 years and with well advanced goiter – thyroid of mass between 140 and 728 grams -, which in some cases put pressure on the trachea and even the heart. These patients were separated into two groups of seventeen each: the first were treated only with the dose of radioactive iodine, whilst the second received a hormone injection of synthetic TSH twenty-four hours before therapy with radioactive iodine. After a year, 57.8% of the patients treated with the combination demonstrated a reduction in the volume of the thyroid, as against 39.7% of the group medicated only with the radioactive iodine.
New mutations
At the Molecular Thyroid Laboratory the doctors looked for genetic mutations that had brought about the congenital hypothyroidism, an illness that affects one in every 4,000 newly born children in Brazil – 1,500 per year. It is one of the causes of permanent mental retardation, which can be avoided if the child were to be treated within the first forty days of life. Currently, the defective genes can only be recognized in 20% of the cases of congenital hypothyroidism. In conjunction with the Reference Service for Neonatal Selection of Minas Gerais, the USP team managed to identify nine new genetic mutations.
Minas Gerais was the state chosen because of the high level of children with genetic thyroid illnesses, around 27% of the total. In other regions this rate is considerably lower: in the state of Parana it varies between 10% and 12%. According to Medeiros, the reason for the high occurrence would be the population’s low miscegenation. “In states such as Paraná and Santa Catarina there was intense immigration and integration of Italians, Portuguese, Japanese, Spanish, Ukrainian and Croatians”, he says. “However, in Minas Gerais the miscegenation was almost nil, and the current population are the descendants of the first colonials who arrived in the 18th century, favoring close blood relationships.”
The ongoing studies are confirming this hypothesis. On examining children with congenital hypothyroidism, coming from families apparently without any kinship, the researchers identified the same mutation in a gene of five of eight newly born children from five families apparently unrelated to each other. This genetic alteration induces the production of a defective version of the protein thyroglobulin (Tg), responsible for the storage of the thyroid hormones. “The fact that we had found this mutation in these families suggests that they had common ancestors, a phenomenon known as the founder g effect”, the USP researcher comments. The DNA test, which looked for common genes back to the seventh generation, confirmed that the five families had the same ancestors. They were kin and did not know it. Each family had transported a defective gene for many generations.
The Project
Evaluation of the urine excretion of iodine and the level of iodine in the salt
consumed in the State of Sao Pauloand ambulatory treatment with radioactive iodine of patients suffering from multi-nodular goiter, pre-stimulated with humane recombinant thyroid stimulant hormone (TSH)
Modality
Regular Line of Research Assistance
Coordinator
Geraldo Antonio de Medeiros Neto – USP
Investment
R$ 26,997.79 and R$ 62,382.50 (FAPESP)
