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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.

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 comparative study of the incidence of alcoholism and 175 associated psychopathological disorders, in 202 patients, was conducted in Castrop-Rauxel, F.R.G., and in Jos, Nigeria. The results of the study indicate that in relative terms the involvement of the females (36.6%) in Castrop-Rauxel was well over double the number in Jos (11.9%). The pattern of alcoholism in Jos was associated more with gradual personality deterioration rather than with the more frequent delirium tremens found in Castrop-Rauxel. The rate of hallucinosis and schizophreniform psychosis in Castrop-Rauxel were found to be more than double the incidence in Jos. Cases of depressive psychoses and suicidal ideas in Jos were double the incidence established in Castrop-Rauxel. A comparison of the gamma-GT of the two centres showed that in Jos 88.1% of the patients had pathological serum values compared with 61.4% in Castrop-Rauxel. This points to a higher frequency of liver impairment in the Jos cohort. The enzyme constellation established in this work is in correlation with clinical experience in Jos of a relatively higher level of terminal liver disease (cirrhosis) in patients with a history of alcohol misuse.

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.

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.

Endogenous and xenobiotic sulphur-containing convulsant and non-convulsant compounds containing structural moieties of, or bearing a structural resemblance to, GABA and homocysteine were tested in binding studies for their potency in displacing the GABA-mimetic [3H]muscimol from specific, high-affinity sites (Kd = 3.6 nM; Bmax = 3.94 pmol/mg protein) on freeze-thawed, Triton-treated calf-brain synaptic membranes. The xenobiotic convulsants, 4-mercaptobutyric acid (MBA), 3-mercaptopropionic acid (3-MPA) and 2-mercaptopropionic acid (2-MPA) were found to be two-site competitive inhibitors exhibiting apparent inhibition affinity constants (Kiapp) of 5000 microM, 3750 microM, and 4800 microM, respectively; while homocysteic acid (Kiapp = 4800 microM) was shown to be a one-site partial competitive inhibitor. Intermediary metabolites of methionine: S-adenosyl-L-homocysteine, L-cysteine, the convulsant L-homocysteine, and its non-convulsant disulphide oxidation product, homocystine, were found to be one-site partial competitive inhibitors exhibiting Kiapp values of 5750 microM, 8350 microM, 5000 microM, and 510 microM, respectively. The endogenous anticonvulsant neuroeffector, taurine, and the tripeptide, reduced glutathione (GSH) were shown to be, respectively, one-site (Ki = 20 microM) and two-site (Kiapp = 4300 microM) competitive inhibitors of [3H]muscimol binding. These findings are discussed with regard to a previously proposed mechanism for the convulsant action of homocysteine.

The simultaneous action of pyridoxal 5'-phosphate (PLP) and L-homocysteine on specific [3H]muscimol binding to the gamma-aminobutyric acid receptor on freeze-thawed, Triton-treated calf-brain synaptic membranes was examined kinetically by double inhibition analysis. PLP was found to be a pure inhibitor and L-homocysteine, a partial inhibitor, with respect to [3H]muscimol. Diagnostic analysis of the experimental data showed that the interaction constant (alpha) of the two inhibitors for the free receptor is between 0 and 1, confirming that the two inhibitors act synergistically. Further double inhibition analysis showed that no quaternary receptor-[3H]muscimol-homocysteine-PLP complex is formed although the ternary receptor-homocysteine-PLP complex is present. The localization and relationship of binding groups for both inhibitors is discussed as in their association with the ligand binding site.