Effect of environmental iodine deficiency (EID) on foetal growth in Nigeria.

BACKGROUND & OBJECTIVES: There is scarcity of information on impact of iodine deficiency on growth and development of newborns, both pre-term and term babies. The present study was carried out to see the impact of iodine deficiency (ID) on the intrauterine foetal growth and development in terms of birth weight (BW) in an African population living in an iodine deficient zone. METHODS: The maternal and cord serum thyroid parameters at term delivery (38-40 wk of gestation) were measured and correlated with the birth weights of the corresponding newborns, and the results compared between those assessed in an ID zone (Jengere region of Bassa district, Plateau State, Nigeria) and with that of non ID (Control) zone, Jos, the State capital. RESULTS: The level of maternal and neonatal thyroid function were significantly reduced in the group with low birth weights (<2.5 kg) as compared to the level seen in normal birth weights category in both control (Jos) and ID (Jengere) regions. Both in non ID and ID regions the maternal serum thyroxine (T4), thyroxine binding globulin (TBG) and free thyroxine index (FT4I) were positively correlated (P<0.005) with BW of term babies while thyroid stimulating hormone (TSH) (P<0.005) and thyroxine binding capacity (TBK) (P<0.05) showed negative correlation. Maternal T3 and T3/T4 ratio did not show any correlation with BW in Jos, while in the ID region of Bassa the BW showed a positive correlation (P<0.005) with the maternal serum T3 and T3/T4 ratio. Cord serum analysis of the term babies revealed that the BW was positively correlated with its T4, triiodothyronine (T3), TBG, FT4I and T4/TBG ratio (Jos only) (P<0.005) in both ID region of Bassa and non ID control zone of Jos. Cord serum TSH and TBK showed negative correlation (P<0.005) with BW. Thyrotrophin releasing hormone (TRH) stimulation test revealed that mothers with small for date (SFD) babies at term were more hypothyroid compared to the level of thyroid function seen in the women delivering normal babies. INTERPRETATION & CONCLUSION: Maternal thyroid hormone plays a significant role in the intrauterine foetal growth and development, and the smaller babies and their corresponding mothers, in an ID affected area are functionally sub-thyroid in greater proportion due to prevailing long standing environmental iodine deficiency (EID). Maternal T3 is an important factor in the defence of foetus in ID regions.

Neonatal chemical hypothyroidism in Nigeria.

To investigate the level of neonatal chemical hypothyroidism (NCH), thyroid function was measured in the cord blood of 271 neonates in an area with a high prevalence of endemic goitre, Bassa (n = 140), and a nonendemic area, Jos (n = 131), in Plateau State, Nigeria. NCH was defined as T4 < 40 nmol/L and TSH > 49 mU/L and borderline compensated NCH as T4 31-50 nmol/L and TSH 41-49 mU/L. NCH was detected in 16.4% of neonates in Bassa and in 3.8% in Jos. Borderline compensated NCH was detected in an additional 18.6% in Bassa and 8.4% in Jos. Contamination of foodstuffs and water by iodine-containing antiseptics and disinfectants during the antenatal period, in addition to factors responsible for endemic goitre, e.g. iodine deficiency and goitrogens, are considered to be responsible for the high prevalence of NCH in the Bassa area. As most infants' thyroid function recovers with time, the former might be a more important factor in the aetiology of NCH.

Iodine deficiency disorders in pre-adolescent and adolescent children in Nigeria, West Africa.

An epidemiological study of iodine deficiency disorders covering 4230 pre-adolescent and adolescent school children, together with biochemical analysis of 741 urinary samples, 26 potable drinking water samples and 56 blood samples was conducted in the Plateau State of Nigeria, West Africa. Results indicate that about 2/3 of the region is goitre endemic due principally to iodine deficiency (ID) prevailing in the region as reflected by a low drinking water iodine (DWI) concentrations throughout most of the areas surveyed as well as by a reduced urinary iodide excretions (UIE) seen among the subjects. Urinary thiocyanate (SCN) level in contrast, was found to be significantly higher (P < .01) in the children from these areas as compared to that in Jos (the State capital), raising a possibility of its association with the increased GP seen for the region. Thyroid profile investigation carried out on the 56 goitrous school children from the iodine deficient Bassa region of the state shows two distinct groups. The major group (41 children) exhibited a low-normal to above normal serum T4, FT41 and T4/TBG levels in association with high-normal to above normal serum T3 and a mildly elevated serum TSH activity, suggesting that the group might be in a state of 'compensated euthyroidism'--due as a result of glandular metabolic adaptation to the prevailing ID. The other minor group (15 children) was in 'euthyroid hyperthyroxinaemia' based on a marked rise in serum T4, T3 TBG levels, while serum FT41, T4/TBG ratio and TSH levels were within mid normal range. Discovery of 9 cretins (0.21%) further signifies the magnitude of the problem in the region. It is concluded that a significant proportion of the children living in these areas may likely to suffer from partial thyroid insufficiency with its attendant consequences.

The role of ions in goitre prevalence in two local government areas of Plateau State, Nigeria.

This study tried to show the contributory role of ions (cations and anions) to great contrast in the goitre prevalence between Bassa and Jos Local Government Areas, both of Plateau State, Nigeria. In pursuance of this, the concentration of cations (Ca++, Fe++, K+, Mg++, Na+, & Zn++) and anions (C1-, F, I-, & NO-3) in soil and drinking water in the two LGAs were determined and their results compared and correlated with the goitre prevalence of these areas. It was observed that both Bassa and Jos LGAs have very low but similar amounts of iodide ions in their soils. Besides, Bassa LGA contained more ions in both soil and drinking water than Jos LGA. In conclusion, the results appear to suggest that the higher ion contents of both soil and drinking water in Bassa LGA exacerbated the coexisting low iodide condition of the LGA, thus resulting in the higher goitre prevalence found in the LGA.

Endemic goiter in the Jos Plateau region of northern Nigeria.

This study is an endemic goiter survey of 3476 school children in 13 Local Government Councils (LGCs) and 1004 subjects in a whole community of one LGC, Plateau State, Northern Nigeria, to determine the prevalence of goiter as well as to identify some of the etiological agents involved. Results of the survey showed that the disease is highly endemic in the area with prevalence varying in places from 1 to 23% of these subjects. Females showed a markedly higher prevalence of goiter. Analysis of 729 urine samples indicated that iodine excretion ranged from 3.5 to 1.3 microgram/dl (32-154 microgram/g creatinine) and was similar to that in iodine deficient areas in the world, but no relation was observed between the prevalence of goiter and urinary iodine. Urinary thiocyanate levels were less than 0.5 mg/dl, suggesting that the role of the thiocyanate as a goitrogen is not important in the region. Thyroid hormone parameters in village subjects with goiter were similar to those in goiter endemia except serum thyroxine (T4). An interesting result found in village subjects was very high serum thyroxine binding globulin, which leads to an increase in serum T4. This study indicated that Northern Nigeria is an area of endemic goiter. Although some areas in Plateau State are iodine deficient zones, we could not conclude that the etiology of endemic goiter in this area is associated with iodine deficiency. There may be an interplay of multiple factors of etiological importance.

Thyroid function profile and differential serum lipid and lipoproteins in Africans with endemic goitre.

Serum total thyroxine (TT4), total triiodothyronine (TT3), thyrotrophine (TSH), thyroxine binding globulin (TBG), total lipids, triglycerides, total cholesterol, beta lipoprotein and beta lipoprotein cholesterol level were measured in 68 goitrous subjects and 4 agoitrous cretins by the techniques based on enzyme immunoassay (ELISA) (for thyroid parameters) and enzyme substrate principle (for lipid and lipoproteins) using commercial test kits (Boehringer Mannheim, W. Germany) and the results were matched with those derived from 59 clinically normal control subjects. The mean values of serum TT3, TBG, TSH and T3/T4 ratio showed positive correlations with the goitre size (r > 0.8, P < 0.005) while mean serum TT4 was negatively correlated (r > -0.9, P < 0.005). Typical biochemical features of hypothyroidism on serum lipid and lipoprotein profile were seen throughout, the changes being more marked in cretins. However, the serum lipid and lipoproteins were also, to some extent, found to be positively related to the thyroid size. In addition, a number of patients also showed variations in the serum lipid and lipoprotein levels appropriate to their compensated thyroid functional status in endemic goitre (as reflected by low TT4, raised TT3 and raised T3/T4 quotients).

A study on transplacental transfer of thyroid hormones in pregnant Nigerian women of Jos-Plateau State.

Knowledge of transplacental passage of thyroid hormones in pregnant women is very scanty. Seventy paired 'maternal-cord' blood samples were obtained at term (40 week) deliveries from the Nigerian women from Jos Plateau and its environment, and the level of serum T4, T3, TSH, TBG and TBK (thyroxine binding capacity) were determined by 'ELISA' technique (Boehringer). The serum level of FT41 (free thyroxine index) was determined subsequently by dividing the serum values of T4 with those of TBK. The results obtained were compared with those derived from a similar group assessed among white Americans, as well as with an age-matched non pregnant control group selected from Jos metropolis. Results show that the level of thyroid activity in the present group of 'mothers and neonates' assessed were lower compared to the level seen in the corresponding American group. Correlation studies carried out in this work indicated that the maternal and corresponding neonates have significant degree of positive correlations between the serum levels of T4 (r > .9; p < .005); FT4I (r > .88; p < .005); TBK (r > .8; p < .005); TBG (r > .89; p < .005) and TSH (r > .87; p .005), while T3 did not show any correlation. It is concluded, that during pregnancy there is probably significant transplacental passage of iodine (I) from the mother to the growing foetus, in an attempt to build the necessary foetal Iodine pool, and TRH (thyrotrophin releasing hormone) probably acts as mediator between the foetal and maternal 'hypothalamus--pituitary--thyroid' axis, which are, otherwise independent of each other.

Serum trehalase activities in controlled and uncontrolled diabetes and the impact of oral glucose, high carbohydrate and glycosuria on serum levels.

Nineteen healthy volunteers, made up of two groups were subjected to an extended oral glucose tolerance study. In one group, each had 50g glucose and in the other a high carbohydrate meal. Blood glucose and serum trehalase activities were determined on fasting blood samples and specimens collected half-hourly for 4 hours. The values obtained for both at each stage of the investigations were compared with one another. Correlation coefficient (r) between blood glucose and serum trehalase were 0.4923 for the fasting samples and 0.4762 at 1 hr. The impact of diabetes and glycosuria on serum trehalase activities in 50 diabetics consisting of treated (controlled) and untreated (uncontrolled) cases was also studied. Our study reveals a slight fall in serum trehalase values from the initial fasting level, but thereafter a gradual and progressive rise during the course of the glucose tolerance investigations. Serum trehalase values were higher in diabetics compared to normal subjects (t = 7.0168, P = 0.005). Diabetics with glycosuria had a significantly higher mean serum trehalase compared to the controlled group (t = 5.233, P = 0.005). High serum trehalase values were seen in diabetics with renal glycosuria at comparatively low levels of blood glucose. The significance of these findings is discussed in relation to the possible place of serum trehalase assay in the management of diabetes, especially when this is made difficult by renal glycosuria.

Aberrations in serum proteins and thyroid size in Nigerians on the Jos Plateau and their relation to thyrometabolic function.

Controlled serum protein and thyroid function studies were carried out among 208 African patients with endemic goitre. The changes seen in the serum protein constituents were studied and evaluated in relation to thyroid hormone levels, goitre grade and the clinical state of the patient. Mean serum TBG and thyroglobulin values rose sharply in the early phase of goitre, and remained elevated throughout. Although the mean serum total T4 was statistically and significantly higher in endemic goitre compared with the normal subjects (t = 3.72. P = 0.005), the free thyroxine index was significantly lower and serum T4 fell progressively (r = 0.975) with increasing thyroid grade. In contrast, mean serum T3 rose continuously (r = 0.910) but appeared inflated due to a proportionate increase in TBG in several cases, giving a misleading picture of T3--thyrotoxicosis in otherwise clinically normal subjects. An increase in T3/T4 ratio and consequently in thyroid function, therefore occurs with advancing thyroid size. Inconsistent binding of T4 to TBG causes wide variations in thyroxine index. Mean serum albumin and betalipoprotein appeared inversely related to thyroid function. These changes imply that in order to evaluate a patient with endemic goitre accurately a detailed biochemical investigated of the thyroid may be necessary.

The "feto-maternal" thyroid function interrelationships in an iodine-deficient region in Africa--the role of T3 in possible fetal defence.

The thyroid status was investigated in 26 pregnant African women at term delivery in an iodine-deficient region (Jengere) of Nigeria, West Africa including the measurement of serum T4, T3, TSH, thyroxine binding capacity, TBG, free thyroxine index (FT4I) and the results were matched with those obtained in a corresponding group of 46 women at delivery in Jos, the non-iodine-deficient region which was used as a control. Corresponding cord-blood samples were obtained from all the neonates of the two groups. Twenty-three urinary samples in the former and 14 in the latter group were analysed for iodide levels to ascertain the degree of iodine deficiency. The results demonstrate that compared to the values seen in the Jos group the maternal serum T4, T3 and FT4I levels were significantly reduced in the iodine-deficient group, while TSH, TBG and thyroxine binding capacity were elevated. Cord serum samples showed a corresponding fall in T4 and FT4I levels in the group from the iodine-deficient region, while the T3 levels were significantly elevated with a concurrent significant rise in TSH and TBG levels. Significant correlations were found between the maternal and cord serum T4, TSH, TBG, thyroxine binding capacity and FT4I levels, but not T3. From these findings we suggest that fetal T3 plays an important defensive role against the danger of long-standing environmental iodine deficiency.

Central cretinism in four successive siblings.

A study of four successive siblings, age 9, 12, 14 and 16 years with cretinism associated with congenitial central hypothyroidism (central cretinism), born to a mother in the endemic goitre region of the Jos Plateau, Nigeria, is presented. Biochemically, the defects were characterized by abnormally low basal thyroxine, triiodothyronine and thyroid stimulating hormone, as well as refractory TSH response to thyrotrophin releasing hormone and gross hyperlipidaemia. Clinically, the intellectual, physical and neurological impairment varied from moderate in the youngest to very severe in the oldest. Contrasting clinical pictures of cretinism, which appeared related to age and previous treatment were found with a spectrum ranging from predominantly myxoedematous in the youngest to predominantly neurological in the 16 year old male. Response to adequate treatment was dramatic, with restoration of severe gait disturbance occurring almost completely, but the imprints of thyroid hormone deficiency on mental defects and intellectual performance remained almost unaltered. The parents and two older sisters were normal with normal thyroid function.

Cations and anions in drinking water as putative contributory factors to endemic goitre in Plateau State, Nigeria.

The prevalence of endemic goitre in Plateau State, Nigeria was established and an attempt was made to identify some of the possible environmental goitrogenic agents in the region to establish their likely relationship with the goitre endemicity. Iodine deficiency appears to be a major aetiological factor for the disease as indicated by low iodine levels observed in portable drinking water and in daily urinary excretion. The carbonate (CO3-) content of drinking water supply was found to bear a significant positive correlation with the goitre rate for the entire state (p less than 0.005). The calcium (Ca++) and magnesium (Mg++) levels of the drinking water also exhibited relatively good linear direct correlations with the percentage goitre distribution in a region, nearly 2/3 of the state. It is concluded that there is possibly an interplay of several factors and in particular the carbonate content of drinking water which, in association with a state of iodine deficiency, may be regarded as responsible for the goitre endemic seen in this part of the Continental Africa.

Serum and thyroid tissue lipids in patients with thyroid tumors in euthyroidism.

Plasma lipids of 24 euthyroid subjects with thyroid adenoma and non-toxic primary differentiated thyroid carcinoma (papillary and follicular types) were assessed and compared with a similar investigation conducted on 20 normal subjects. A parallel study with thyroid tumor tissues examined the lipid changes which occurred in the same group of patients. These were compared with the picture seen in 5 normal thyroids. The investigations examined the changes in total lipids; total, free and esterified cholesterol; total phospholipids; lecithin; cephalin and sphingomyelin; triglycerides and free fatty acids in both serum and thyroid tissue. Compared with normal subjects, the serum lipids were almost identical except for the concentration of free fatty acids which showed significantly lower values in the group with neoplastic changes. Tissue analysis of the cancerous thyroid however revealed a marked rise in virtually all lipid fractions but the cholesterol seemed to dominate the picture. The differential studies of total phospholipids for thyroid tissue membrane lipids further revealed a significant increase in the lecithin and sphingomyelin components of total phospholipids as well as the esterified cholesterol fraction in thyroid carcinoma. The changes in thyrophospholipids were more marked in females normal thyroids than males. An attempt has been made through evaluation of the results derived from differential lipid studies to elucidate the role of some of the various fractions determined and the possible effect of the changes described on thyroid hormone metabolism.

Zinc depletion and menorrhagia in Nigerians using copper T-200 intrauterine device.

PIP: A 12-month followup study was undertaken to evaluate the effect of using the copper T-200 IUD on hemoglobin in trace element levels in Nigerian women. A total of 45 women were studied, including 20 who were using that IUD and 25 controls. The results indicated that after 12 months, the mean serum zinc and iron levels in the study group were significantly lower (p0.01) than initial concentrations and that of normal nonusers. This was true for both hemoglobin and hematocrit values (p0.05). However, serum copper increased significantly in the study group (p0.01). It is suggested that the low zinc status was probably responsible for the menorrhagia which was common among the study group using copper IUDs, which in turn was responsible for the anemia seen in more than 50% of the IUD users. However, the decreased in iron and zinc as well as the increase in copper levels may be a result of alterations during the acute phase response associated with the insertion of the Cu T-200. The monitoring of hemoglobin and serum iron levels as well as zinc levels may thus enhance the prophylactic use of IUDs to control menorrhagia, which leads ultimately to the development of anemia in this group.^ieng

Hyperuricaemia in sickle cell disease.

The serum uric acid level of 69 children below the age of 11 years with homozygous sickle cell disease was determined by the uricase method. The values were compared with those seen in normal children in the same age group who were used as a control. A statistically significant difference was seen in their mean values; 28% of children with sickle cell disease exceeded the upper normal limit of the control group. The implications of the comparatively high uric acid levels are discussed.

Calcium metabolism in African primigravids.

Serum calcium inorganic phosphorus, protein and alkaline phosphatase as well as urine calcium were studied in fifty-five primigravid Nigerian women during pregnancy and postnatal period. Each patient was seen at the various stages of pregnancy and thus acted as her own control. Serum calcium levels fell with progressing pregnancy. Urine calcium showed a highly significant decrease throughout pregnancy and in the puerperium. Alkaline phosphatase showed a continuous rise with advancing gestation which was statistically highly significant, with a return towards normal values in the postnatal period. Serum inorganic phosphorus showed no significant alteration right through the pregnancy period. The normoproteinaemia seen in the group studied suggests that albumin did not make any contribution to the fall in the serum calcium levels seen during the study.

Liver function and the diagnostic significance of biochemical changes in the blood of African children with sickle cell disease.

The blood biochemistry of 84 young homozygous sickle cell patients aged 1 to 11 years was analysed for evidence of liver disease. A comparison of the values found in their blood with those seen in normal children from an identical age group, assessed at the same time, shows no convincing evidence of liver cell damage except in 12% of cases. The normal transaminase observed in many of the patients assessed, together with the high alkaline phosphatase activity which seemed to be out of proportion to plasma bilirubin, is a picture compatible with localised obstructive lesions of the liver or bone lesions, both of which are common in sickle cell disease. This biochemical pattern suggests that the conjugated bilirubin, which dominates the picture in 40% of patients who have 'haemolytic jaundice', is due largely, not to liver cell damage, but to a combination of two factors, namely, intrahepatic cholestasis and the presence of actively functioning liver cells. Adequate albumin synthesis found in these patients, together with normal thymol reactions, provides further evidence of the absence of severe liver cell damage.