Postgraduate Medical Journal (October 1972) 48, 609-615.

CLINICAL REVIEW

Thyrotoxicosis in Nigeria-a study of forty-six patients

E. 0. OLURINF.R.C.S.E., F.R.C.S.

Department of Surgery, University College Hospital, Ibadan, Nigeria

SummaryIn a review of 874 Nigerian patients with various typesof thyroid gland disorders, forty-six patients werefound to be thyrotoxic (5-3y.), supporting the commonobservation of many authors that thyrotoxicosis israrer in the African than in Europe and NorthAmerica where thyrotoxicosis accounts for 20-500,of all thyroidectomies. The incidence of thyrotoxi-cosis is higher in the female than male though there isa higher proportion of males in this series than in theUnited Kingdom. There is a higher incidence of secon-dary thyrotoxicosis than has been reported elsewhere.The clinical features of hyperthyroidism in the

Nigerian are no different from those reported in othercountries, though our patients tend to report ratherlate. Primary thyrotoxicosis occured a decade earlierin this series than in Britain. Two of the forty-sixpatients had adenocarcinoma of the thyroid althoughonly in twenty-seven patients was thyroid tissue avail-able for histological examination. Laboratory investi-gations were essential in borderline cases, especiallyestimation of the PBI in those with multinodulargoitres.The standard methods of treatment by antithyroid

drugs, 13'I and surgery were employed with immediate-ly satisfactory results, though the follow-up was sopoor that it is impossible to evaluate the late effects oftreatment.

IntroductionIt is generally accepted that the indicence of thy-

roid disease is subject to geographic variation.Thyrotoxicosis is rare in the African (Blacklock,1925; de Smet, 1954; Kihn, 1957). Trowell (1960) inhis 29 year's service in East Africa reported only twocases of thyrotoxicosis. In Southern Rhodesia,Gelfand (1962) reported one case of primary thyro-toxicosis. Patel (1962) reported a series of five casesin Uganda and Wright reported eight cases fromKenya in 1967. There has also been a number ofreports from Nigeria. Davey & Ogunlesi (1963)described seven cases in Ibadan. Adesola (1968) re-ported seven cases in Lagos, Nigeria. The purposeof this study is to review all cases of thyrotoxicosis

seen in a large teaching hospital in Nigeria with theaim to determine the characteristics and the problemsof this disease as seen in this community. It is hopedthat the analysis of the largest series, so far, fromAfrica will supply sufficiently educative and statisti-cally significant data and illustrate the points ofdifferences and similarities with thyrotoxicosis asseen in other lands.

Material and methodsThe University College Hospital in Ibadan is the

largest and oldest teaching hospital in NigeriaSince its inception in 1957 it has served practicallythe whole country until newer teaching hospitalswere established less than 10 years ago. Naturally, avast majority of the patients came from areas nearerthe hospital. All patients with any type of thyroiddisease seen and treated in the hospital from 1957 to1970 were reviewed. The hospital records, viz. case-notes, operation and histological records and chemi-cal pathological reports were studied in detail. Athorough prosepctive study of ten patients wascarried out over a period of 5 years. Only cases withadequate information in their case-notes and thosestudied prospectively were included. Thyrotoxicpatients who were diagnosed solely clinically andwho, on retrospective review, satisfied Wayne'sdiagnostic index were included. Patients with aclinical diagnosis of thyrotoxicosis which was sup-ported by special thyroid function laboratory testswere also included. Non-Nigerians were not includedin this study. Children under the age of 5 years wereexcluded from this series. The follow-up of somepatients was carried out personally. A few defaultingpatients were traced to their homes for the purposeof this study.

ResultsIncidence

In the 14-year period between 1957 and 1970,about 1000 patients with all varieties of thyroiddisease were treated in this hospital. There was anoticeable yearly increase in the number of new casesfrom about twenty in 1958 to just over 120 in 1970

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610 Clinical review

with an annual average of about seventynew patients.Out of the 1000 patients, 874 had sufficiently ade-quate information to form the basis of this study.Thyrotoxicosis was the final diagnosis in forty-sixof 874 patients, an incidence of 5 3%4. The age ofthe patients ranged from 8 to 70 years with a peak inthe third and fourth decade. There were thirty-sixfemales and ten males giving a ratio of 3 6: 1. Table1 shows the age and sex distribution, and it alsoshows that the female predominates in all age groupsexcept at the extremes of life when the numbers weretoo few to be significant.

TABLE 1. Age and sex distribution in forty-six patients withthyrotoxicosis

Sex Primary SecondaryAge Grand(year) F M F M Total F M Total total

5-10 2 - 2 - 2 - - - 211-20 5 2 5 2 7 - - - 721-30 10 2 8 1 9 2 1 3 1231-40 8 3 3 3 6 5 - 5 1141-50 7 1 2 - 2 5 1 6 851-60 4 - - - - 4 - 4 461-70 - 2 - 1 1 - 1 1 2

Total 36 10 20 7 27 16 3 19 46

Clinical featuresThe duration of thyrotoxic symptoms varied from

3 months to about 2 years. There was a history ofpre-existing goitre in nineteen patients, the dura-tion of the goitre varying from 4 to 35 years beforethe onset of toxicity. The symptomatology includedloss of weight, increased appetite, excessive sweating,heat intolerance, protruding eyes, diarrhoea, palpi-tation, nervousness and irritability, tiredness, diffi-culty in breathing especially on exertion, polyuria,insomnia and amenorrhoea. There were sevensevere cases including one neglected patient in verysevere drug-resistant thyrotoxicosis who died somedays after admission. The signs included the presenceof visible and palpable goitre, bilateral exophthal-mos, fine to gross tremours of the hands, warmmoist hands, tachycardia during sleep, bruit overthe gland and auricular fibrillation. Table 2 gives adetailed analysis of the symptoms and signs and thepercentage incidence of each feature. There weretwenty-seven patients with primary thyrotoxicosis:twenty-five had diffuse goitres and two had no goitresat all (Fig. 1). Nineteen patients had secondarythyrotoxicosis with pre-existing multinodular goitres(Fig. 2). Exophthalmos occurred in 81% of primaryand 42% of secondary thyrotoxic patients. It wasbilateral in all cases. Four patients with secondarythyrotoxicosis had auricular fibrillation and were incongestive heart failure.

FIG. 1. Primary exophthalmic thyrotoxicosis in a boyof 11 years. The thyroid gland was only very slightlyenlarged.

FIG. 2. Secondary thyrotoxicosis in a huge multinodulargoitre with extensive calcification. Note the moderateexophthalmos.

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Clinical review 611

Two patients had follicular carcinoma with thyro-toxicosis. One of them was an unexpected histo-pathological finding in one of the nodules of a multi-nodular goitre. It was neither a 'cold' nor 'hot'nodule in the scintigram. The other was a 47-year-oldwoman who presented in 1963 with clinical simplenodular goitre. At operation the right lobe was en-larged and nodular but the left was visually andpalpably normal, A right lobectomy and biopsy ofthe left lobe were performed. Both showed 'nonmalignant foetal adenoma' features. She was nextseen again in 1970 with severe exophthalmic thyro-toxicosis and osteolytic thyroid carcinomatous de-posits in the skull and ribs (Fig. 3). The left lobe was,in 1970, slightly enlarged and nodular; both thislobe and the bone deposits took up radio-activeiodine (131I). There was no 'cold area' in the leftlobe scintigram.

InvestigationsThe basal metabolic rate (BMR) was determined

in eight patients in the earlier part of the period underconsideration. Thyrotoxicosis was confirmed in allthe patients. Serum protein-bound iodine (PBI) esti-mation was carried out in twenty-two patients andit was elevated in nineteen patients (86%), and

iiil:ii:i ·:::::;::;::

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FIG. 3. Secondary exophthalmic thyrotoxicosis in apatient with secondary carcinomatous deposits. Notethe huge skull deposit. All the secondary deposits showactive iodine uptake.

within normal limits (3-15-9 g.g/100 ml for Nigerians)in three patients. The radio-active iodine (131I)studies were carried out in twenty-five patients. The131I uptake values were raised in twenty patients(80%/), and within normal values in five patients.In eleven patients both the PBI and 131I uptakevalues were raised to thyrotoxic levels. In one patientthe PBI was normal and the 131I was raised. In an-other patient the PBI was elevated and 131I uptakewas normal. The serum cholesterol values were with-in the normal range in twenty-four patients and belownormal in five. The non-specific investigations in-cluded radiological studies of the neck and chest and,in one patient, skeletal survey. There was a soft-tissue shadow in the neck in the forty-four goitrouspatients; the trachea was displaced laterally intwenty-four patients and compressed to varyingdegrees in eight patients. Calcification of the goitrewas radiologically present in five patients, all ofwhom had moderate to large multinodular goitres.The patient with thyrotoxic carcinomatosis hadosteolytic secondary deposits in the skull and ribs.

DiagnosisThe diagnosis of thyrotoxicosis was based solely

on clinical assessment in ten patients. The clinicaldiagnostic index of Wayne was applied retrospec-tively to arrive at this figure. In another twenty-ninepatients, the diagnosis of thyrotoxicosis was basedon clinical and specific thyroid function tests. TheBMR confirmed the clinical diagnosis in ten patients.The 1311 uptake and the PBI together confirmed theclinical diagnosis inelevenpatients. Wheretheclinicaldiagnosis was supported by either the PBI or 131Iuptake values but not by both, thyrotoxicosis wasaccepted for the purpose of this study. In threepatients with multinodular goitres there was noclinical suspicion of thyrotoxicosis at first attendancein the out-patients department but subsequent in-patient reviews and the laboratory results made iteasier to diagnose thyrotoxicosis. Two patients wereonly diagnosed postoperatively when they developedsevere thyroid crisis. The two patients had multi-nodular goitres of many years' duration.The diagnosis of primary and secondary thyro-

toxicosis was based on the retrospective analysis ofthirty-one patients and prospective study of fifteenpatients. Where there was definite evidence of anodular goitre antedating the onset of thyrotoxicsymptoms by at least 4 years, secondary thyrotoxi-cosis was accepted. All patients with secondarythyrotoxicosis had multinodular goitres and weremostly middle-aged or older (Table 1). The patientswith primary thyrotoxicosis were younger people;they had a relatively shorter duration of symptoms,and twenty-five of the twenty-seven patients hadgoitres which appeared about the same time as the

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612 Clinical review

TABLE 2. Symptoms and signs in forty-six thyrotoxic patients

No. of patients No. of patientsSymptoms Signs

Primary (27) Secondary (19) Primary (27) Secondary (19)

Loss of weight 20 (7454) 10 (53%Y) Goitre 25 (93%) 19 (100%/)Excessive sweating 19 (70/.) 12 (6354) Tremors of hands 16 (59%4) 10 (5354)Increased appetite 18 (6754) 4 (2154) Exophthalmos 22 (814%) 8 (4254)Palpitation 17 (6354) 14 (7454) Sleeping tachycardia 25 (9354) 16 (8454)Nervousness/irritability 17 (63%) 8 (4254) Warm moist hands 21 (7854) 8 (4254)Diarrhoea 12 (4754) 8 (4254) Bruit over goitre 9 (3354) 1 (5%)Tiredness 11 (41%Y) 11 (585) Thyrocardiac Nil 4 (215)Dyspnoea on effort 5 (1954) 10 (5354)Insomnia 5 (1954) 3 (18%)Polyuria 4 (1554) NilAmenorrhoea 2 (754) Nil

symptoms. Their thyroid glands were diffusely en-larged, and relatively smaller in weight than thosewith secondary thyrotoxicosis. Exophthalmos oc-curred in both groups though twice as often inprimary as in secondary thyrotoxicosis. Thyro-cardiac disease occurred only in secondary thyro-toxicosis in this series (Table 2).

Treatment with resultsAntithyroid drugs alone were used for treating

sixteen patients. Propylthiouracil was exhibited forthree and carbimazole for thirteen patients who hadprimary thyrotoxicosis. One of the latter group wasbeing prepared for thyroidectomy but she failed toreturn for the operation, probably because she feltbetter! The immediate effects of the drugs weregratifying in fifteen cases but none of these patientsreported for further assessment for more than 8months. It was thus impossible to assess the long-time effects of the drugs. One of the patients proveduncontrollable and she died of severe thyrotoxicosis.

Three patients were treated with radio-activeiodine; two were about 60 years of age and the third,a 35-year-old woman, had had two previous opera-tions for recurrent goitrous thyrotoxicosis. None ofthem was seen in the follow-up clinics after 9 months.

Subtotal thyroidectomy was performed on fifteenprimary and twelve secondary thyrotoxic patients.All except two patients had adequate pre-operativeantithyroid drug preparation. The two exceptionsescaped correct pre-operative diagnosis and bothhad a postoperative thyroid crisis. There was nooperative mortality. The immediate postoperativeresults were satisfactory in so far as thyrotoxicosiswas concerned. The postoperative follow-up waspoor because none of the patients returned after3 years. Seven patients were traced to their homesin various parts of the country 4-9 years afterthyroidectomy. They were all clinically euthyroid.The patient with thyroid carcinomatosis and thyro-

toxicosis was treated with carbimazole and thyroxine,the latter being later replaced with thyroid extract.

She improved tremendously. The ideal treatment forher would have been 131I, but this was not available.

PathologyThe weight of the excised goitrous tissue in twenty-

seven patients varied considerably. It weighed under100 g in seven patients; between 100 and 200 g in tenpatients and between 200 and 300 g in four patients.The weight was between400and 600g in four patients.In one patient the excised gland weighed 1200 g andin another it weighed 1750 g. The weight of thegoitre was not recorded in two patients. The excisedthyroid tissue macroscopically showed diffuse en-largement in fifteen patients and was multinodular inten patients; solitary nodules were recorded in twopatients. Relevant information was not available inthe others. Microscopically, fifteen patients showedactive hyperplastic goitres with features typical oftreated thyrotoxicosis. 'Active solitary adenoma'was described in two patients and nodular colloidgoitre in eight patients. There was a mixed follicularand papillary carcinoma in one patient and follicularcarcinomatosis in another.

DiscussionAll the patients in this series are Nigerians. The

significant finding is that thyrotoxicosis is a relativelyrare disease in Nigeria, an incidence of 5-3%° ofpatients with thyroid disorders. Reports from manyobservers in other parts of Africa also indicate thatthyrotoxicosis is rare in the African: Wilson et al.(1954), Davidson (1954), Bowesman (1960) and Shee& Houston (1963). Recently, however, Wright (1967)and Nevill & Kunga (1969) indicate that thyrotoxi-cosis might not be as rare in the African as has beenpreviously reported. Wright (1967) found eight caseswithin 6 months in Kenya although he did not indi-cate how many patients with other thyroid diseaseshe saw within that period. Thyrotoxicosis is muchmore common in Europe and North America wherethe incidence varies from 20 to 50%° of all thyroidec-tomies according to Montgomery & Welbourne

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TABLE 3. Incidence of thyrotoxicosis in several series of thyroid disorders

United Kingdom Africa

Authors No. of Y. of total Authors No. of % of totalcases cases

Young & Meachim (1964) 313 24-4 Patel (1962) 5 Not givenTill (1969) 517 46 5 Davey & Ogunlesi (1963) 7 ,,Kennedy (1970) 163 49 Wright (1967) 8 ,,

Nevill & Kungu (1969) 17 8Kennedy (1970) 9 4Present series 46 5 3

(1963), Young & Meachim (1964), Till (1965) andKennedy (1970) (Table 3). The factors responsiblefor the low incidence of thyrotoxicosis in the Africanare not known, thought environmental and racialfactors have been suggested by Trotter (1962) andPatel (1963).

Thyrotoxicosis, as a whole, has a peak age-incidence at 21-40 years in this series as shown byTable 1. When, however, primary is separated fromsecondary thyrotoxicosis, it becomes evident thatthe peak age-incidence for primary thyrotoxicosis is21-30 years and the peak for secondary thyrotoxi-cosis is the 41-50 decade. The former is in agreementwith the finding of Patel in Uganda. It is probablysignificant that the peak age-incidence in 1000 casesof all types of thyroid diseases seen in this hospital,in which 87% constitutes simple goitres, is 31-40years (Olurin et al., 1971). Primary thyrotoxicosisthus appears to occur a decade earlier in this seriesthan in Britain, according to Young & Meachim(1964). Thyrotoxicosis is commoner in the femalethan in the male but the male incidence appears tobe higher in this series than in the European andAmerican patients.The symptoms and signs of thyrotoxicosis in many

of these patients are so marked that there is no diffi-culty in the diagnosis. This is particularly so inprimary thyrotoxicosis because patients do not,generally, seek medical advice in the early phase ofillness in this community. In some patients withsecondary thyrotoxicosis the clinical features are notalways unequivocal. The picture is further compli-cated by the finding, in these patients, that manymultinodular simple goitres in euthyroid patientstake up iodine avidly. The bigger the goitre the higherthe iodine uptake. Indeed they behave very muchlike endemic goitres (Stanbury, 1958). It is probablyrelevant to point out that the majority of patientswith multinodular goitres and secondary thyro-toxicosisis live in areas where goitres are locallyknown to be endemic.

Thus, in mild secondary thyrotoxicosis occurringin multinodular goitres both the clinical assessmentand radio-active uptake studies may not be of greathelp in diagnosis. The serum protein-bound iodine

estimations, however, have provided values whichgive a more sensitive index of thyroid function irre-spective of size in these mild cases. It would appea.that a number of patients with secondary thyrotoxi-cosis are indeed cases of Basedow thyrotoxicosis.During the last 5-10 years there has been an im-provement in the standard of living in many ruralareas: the diet is better balanced, pipe-borne wateris available in many areas, travelling is easier andilliteracy is gradually diminishing. It is thereforeplausible to argue that the iodine content of foodand water is gradually increasing in areas which hadhad a low iodine supply. More iodine is being madeavailable to multinodular goitres, which show -avidiodine uptakes under laboratory conditions. Thelarge proportion of secondary thyrotoxicosis in thisseries is thus explained. On this basis, it is to beexpected that the number of secondary thyrotoxicpatients will increase in future if improvement in thestandard of living continues in areas where simplemultinodular goitre is common. In favour of thisphenomenon is the fact that endemic thyrotoxicosishas been observed by Stewart and his co-workers(1971) following iodination of bread in NorthernTasmania which is known to be a goitrous area.The association of thyrotoxicosis and carcinoma

of the thyroid in two cases (7%°) in this series isinteresting. Although it was once thought thatthyrotoxicosis was a sort of insurance against carci-noma of the thyroid (Mean, 1948) yet in recentyears there has been a number of reports on theoccurrence of both diseases co-existing, as shown inTable 4. Thyroidectomy was performed in twenty-seven offorty-sixpatients and only theexcised goitroustissues of these patients were subjected to histo-pathological examination. The rest of the patientshad either antithyroid drugs or 1311 therapy. It wouldnot be known whether any of these contained carci-noma. It is thus possible that carcinoma of the thy-roid occurring in thyrotoxic patients treated medi-cally is being missed, and therefore the incidence ofcarcinoma in the thyrotoxic gland may be greaterthan has been found.The management of thyrotoxicosis in this hospital

does not differ significantly from that in practice

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614 Clinical review

TABLE 4. Incidence of association of thyrotoxicosis andthyroid cancer

Total no.Authors of cases incidence

Leoutsakos (1963) 362 0-5Olen & Klinok (1965) 2114 2 5Georgiadis, Leoutsakos & Katsas

(1970) 500 3-8Beahrs & Sakulsky (1968) 377 2-0Willis (1960) 1348 1Kilpatrick, Blomfield & Nea

(1957) 100 7Present seties 46 7*

* 4% associated with carcinoma.

elsewhere (Riddell, 1965). But it is impossible toassess the late effects of any form of therapy becauseof the poor follow-up. This is a phenomenon whichmakes scientific assessment of the natural course of adisease and the effects of treatment almost impossiblein this community. Many of the patients are poorpeasants who live in distant rural areas and who haveno relations to stay with in this largest city in BlackAfrica. Most cannot finance frequent visits to thehospital. It is no wonder then that once they feelrelieved of their symptoms they cannot indulge inthe luxury of further expensive and difficult journeysto the 'unfriendly city'. This is probably why veryfew patients are seen regularly in follow-up clinicsa few years after the commencement of treatment.On the other hand, it is too expensive, difficult andtime-consuming to carry out regular visits, howeverinfrequent, to the homes of these patients.

ConclusionThyrotoxicosis is a rarer disease in Nigeria than

in Europe and North America. There is a high inci-dence of secondary thyrotoxicosis in the multi-nodular goitre in this series, probably as a result ofgradual improvement in the socio-economic situationof the patients, especially those from rural areaswhere goitre is known to be endemic. Thyrotoxi-cosis is four times as common in the female as inthe male. It would appear that primary thyrotoxi-cosis occurs mostly in the third decade in the Nigerianpatients but a decade later in Britain. Secondarythyrotoxicosis occurs predominantly in the fifthdecade in this series. The Nigerian patients presentwith the same symptoms and signs of thyrotoxicosisas those recorded in other countries. It is not alwayspossible to apply the standard modern laboratoryinvestigations to all the patients regularly because oftechnical deficiencies and the inevitable delays inprocessing imported reagents and isotopes. How-ever, the PBI values give a better indication of thethyroid gland function than the 1311 uptake studies.This is particularly so in borderline cases of primarythyrotoxicosis and also in multinodular goitre of

several years' duration with non-exophthalmic mildtoxicity. In the latter patients, the 13lJ uptake valuesare not often helpful. Retrospective clinical diagnosisof hyperthyroidism by the application of Wayne'sdiagnostic index is quite easy in the establisheddisease but very difficult indeed in the borderlinecases. Wayne's method is best used in prospectivestudies if understood and faithfully but criticallyapplied. The co-existence of hyperthyroidism andadenocarcinoma of the thyroid in two patients (4¶/4)in this series is a pointer and it deserves serious con-sideration in dealing with all thyrotoxic patients.The immediate effects of treatment with antithyroiddrugs, 1311 and surgery are gratifying but the poorfollow-up in this series does not allow full assessmentof the late effects of these different methods oftherapy.

AcknowledgmentsI am grateful to all my colleagues who have looked after

some of these patients. Professor Adadevoh of the Depart-ment of Chemical Pathology has been of great help in theinvestigations of these patients and for his help and adviceto me personally. I owe much to Mr Odeyale for the excellentsecretarial efforts.The work is supported in part by the University of Ibadan

Senate Research Fund and in part by a grant from the WestAfrican Medical Research Council.

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