Walter Sisulu University

Benedicta Ngwenchi Nkeh-Chungag

Antihypertensive effects of the hydroethanol extract of Senecio serratuloides DC in rats

Oladele Vincent Adeniyi

Inequality in uptake of isoniazid prevention therapy and Mantoux test among pregnant women with HIV in the Eastern Cape, South Africa

Norah L. Katende-Kyenda

Undetermined

A Study on Demographic Factors Affecting Quality of Life among HIVInfected People Attending a Public Primary Health Clinic in South Africa

Wilson Akpan

Factors associated with consistent condom use: a cross-sectional survey of two Nigerian universities

Ekpebegh, Chukwuma

Elmezughi, Khaled

Mtingi, Lungiswa

Page number not for citation purposes 1 
 
 
 
Graves’ disease following hypothyroidism due to Hashimoto’s  
thyroiditis in a black South African lady: a case report 
 
Chukwuma Ekpebegh1, Khaled Elmezughi1,&, Lungiswa Mtingi1 
 
1Department of Internal Medicine, Walter Sisulu University, Mthatha, South Africa 
 
&Corresponding author: Khaled Elmezughi, Department of Internal Medicine, Walter Sisulu University, Mthatha, South Africa 
 
Key words: Graves´ disease, hyperthyroidism, Hashimoto´s thyroiditis, hypothyroidism, autoimmune thyroid disease, South Africa 
 
Received: 22/03/2019 - Accepted: 10/04/2019 - Published: 17/04/2019 
 
Abstract  
Graves' disease and Hashimoto's thyroiditis are autoimmune thyroid disorders with distinct pathological and histopathological features. The 
conversion from Hashimoto's thyroiditis to Graves' disease has been rarely reported throughout the world with no reports in the African race to our 
knowledge. We here report an African lady who was initially diagnosed with primary hypothyroidism following Hashimoto's disease but later 
became thyrotoxic due to Graves' disease. 
 
 
Pan African Medical Journal. 2019;32:186. doi:10.11604/pamj.2019.32.186.18713  
This article is available online at: http://www.panafrican-med-journal.com/content/article/32/186/full/ 
 
© Chukwuma Ekpebegh et al. The Pan African Medical Journal - ISSN 1937-8688. This is an Open Access article distributed under the terms of the Creative Commons 
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original 
work is properly cited. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pan African Medical Journal – ISSN: 1937- 8688   (www.panafrican-med-journal.com) 
Published in partnership with the African Field Epidemiology Network (AFENET). (www.afenet.net) 
 
Case report 
 
Open Access 
 
 
 
 
Page number not for citation purposes 2 
Introduction 
 
There are few reports in the literature of hyperthyroidism after an 
initial period of hypothyroidism [1-4]. These have been mainly in 
Asian and Western populations. It is important to identify the rare 
patients who develop hyperthyroidism after initial treatment for 
hypothyroidism to enable prompt discontinuation of thyroxine and 
institution of appropriate treatment for hyperthyroidism. We found 
no reports in the English literature of hyperthyroidism following 
hypothyroidism in an African patient. We herein, report on a middle 
aged black South African female, who was initially diagnosed with 
hypothyroidism due to Hashimoto's thyroiditis but later developed 
Graves' disease after 5 years of thyroxine replacement. 
  
  
Patient and observation 
 
A 54-year-old black South African female from the Eastern Cape 
Province was initially diagnosed in 2011 with primary 
hypothyroidism secondary to Hashimoto's thyroiditis when she 
presented with progressive weight gain, constipation and cold 
intolerance. She had no goiter. Laboratory test results at diagnosis 
revealed extremely low thyroid hormone levels: serum free T4 of 
1.3 pmol/L (12-22) and free T3 of < 0.4 pmol/L (2.8-7.1). This was 
accompanied with markedly elevated TSH of 86.71 miu/L (0.27-4.2). 
Thyroid peroxidase antibody level was elevated at 153 iu/ml (0-35). 
She was subsequently started on thyroxine replacement and the 
dose was gradually increased to150 mcg daily. 
  
In June 2016, she presented with history of palpitations, heat 
intolerance, tremors, exertional dyspnoea and bilateral pitting 
oedema. She had sinus tachycardia of 135 beats per minute with 
elevated blood pressure of 150/105 mmHg. Thyroid function tests 
(TFT) at presentation in June 2016 showed markedly elevated free 
T4 (72.2 pmol/L) and free T3 (30.8 pmol/L) with suppressed TSH of 
< 0.01 miu/L. She was diagnosed with a thyrotoxic heart failure and 
thyroxine replacement was stopped. She also received furosemide 
40 mg BD, bisoprolol 5mg daily, enalapril 5 mg BD and was later 
commenced on carbimazole 20 mg daily when her thyrotoxicosis 
persisted. Subsequently Graves' disease was confirmed by the 
finding of elevated TSH receptor antibody levels of 6.83 u/L (< 
1.75). The TFT results in July 2016 revealed free T4 and free T3 of 
20.6 pmol/L and 6.4 pmol/L respectively with suppressed TSH < 
0.01 miu/L. 
  
Carbimazole was stopped in July 2018 when follow up biochemistry 
showed frank hypothyroidism: low serum free T4 of 10.1 pmol/L 
(12-22) and elevated TSH of 13.9 miu/L (0.27-4.2). She was 
biochemically euthyroid on follow up visits of September 2018: 
serum free T4 of 14.9 pmol/L (12-22) and TSH of 2.35 miu/L (0.27-
4.2) and February 2019: serum free T4 of 12.3 pmol/L (12-22) and 
TSH of 0.39 miu/L (0.27-4.2). She has neither been treated with 
carbimazole nor thyroxine since July 2018. She however remains on 
antihypertensive medications. 
  
Consent 
 
Written informed consent for this case report was obtained from the 
patient. A copy of the written consent is available for review by the 
editorial board on request. 
  
  
Discussion 
 
Our patient initially had clinical and laboratory features of 
hypothyroidism due to Hashimoto's thyroiditis. When she became 
thyrotoxic and presented in heart failure after 5 years of 150 mcg 
daily thyroxine replacement for hypothyroidism, the initial thinking 
was that of thyroxine induced thyrotoxic heart failure. However, 
with the finding of elevated serum TSH receptor antibody titers and 
persistent thyrotoxicosis despite withdrawal of thyroxine, her 
diagnosis was revised from hypothyroidism due to Hashimoto's to 
hyperthyroidism due to Graves' disease. Chronic hypothyroidism 
with inadequate thyroxine replacement can result in pituitary 
hyperplasia and eventual thyrotoxicosis secondary to an 
autonomous secretion of TSH [5]. This is however, unlikely in our 
patient as an elevated and not suppressed TSH would be expected. 
  
Although the transition from thyrotoxicosis to hypothyroidism is 
rare, it occurs in the setting of Hashitoxicosis where following 
thyroid follicular cells destruction an initial phase of thyrotoxicosis 
due to leakage of preformed thyroid hormones is followed by 
permanent hypothyroidism [6]. Thyrotoxicosis following 
hypothyroidism is also rare and is often described in Asian and 
western populations [1-4]. This scenario has been described 
predominantly in middle aged females [7]. It may occur up to 20 
years after an initial period of hypothyroidism [8]. Our case is 
similar to other reports in literature in being a middle-aged female, 
Page number not for citation purposes 3 
the exception is that she is of black race and we have not found 
reports describing it in the black ethnicity in the English language 
literature. The factors that have been associated with the transition 
from hypothyroid Hashimoto's to Graves' disease include thyroxine 
treatment which may promote the elaboration of TSH receptor 
stimulating antibodies [1]. Treatment with immunomodulatory 
agents such as interferon and alemtuzumab have also been 
implicated in the switch from hypothyroidism to thyrotoxicosis 
[9, 10]. Our patient, however, neither received interferon nor 
alemtuzumab. She expectedly received thyroxine replacement for 
chronic primary hypothyroidism. 
  
In all reports of transition from thyrotoxicosis to hypothyroidism and 
vice versa, it has been in the setting of autoimmune thyroid disease. 
The postulated mechanism includes a switch from TSH receptor 
blocking to TSH receptor stimulating antibodies [11]. Indeed, 
circulating levels of TSH receptor inhibiting and stimulating 
antibodies have been reported in the same patient [12]. The clinical 
manifestation will be determined by which antibody predominates 
and this may vary with time with the same patient clinically 
manifesting as Hashimoto's thyroiditis or Graves' disease [13]. 
Alternating episodes of hypothyroidism and hyperthyroidism may be 
ultimately stopped with thyroidectomy or radioactive ablation of the 
thyroid [8, 12]. 
  
This case report is not without limitations; we did not test our 
patient for TSH receptor antibodies when she was diagnosed with 
hypothyroidism as it is not the standard of care. Our practice is to 
perform thyroid peroxidase antibody testing in primary 
hypothyroidism when Hashimoto's is suspected. Thyroid peroxidase 
antibody; which is positive in 90-95% of patients with Hashimoto's 
is the preferred test in autoimmune primary hypothyroidism 
[14, 15]. We also did not perform radionuclide imaging in our 
patient when she became thyrotoxic to demonstrate the expected 
pattern of diffusely increased uptake in Graves' disease because of 
the limited resources in our setting. We are aware that TSH receptor 
antibodies may be falsely positive in patients with thyrotoxicosis not 
due to Graves' disease [13]. However, we do not expect this to be 
the case in our patient. 
  
  
 
 
 
Conclusion 
 
In conclusion, our case extends the rare reports of Graves's disease 
following hypothyroidism to include the black African population. 
  
  
Competing interests 
 
The authors declare no competing interests. 
  
  
Authors’ contributions 
 
Chukwuma Ekpebegh, Khaled Elmezughi and Lungiswa Mtingi, all 
contributed equally to the conception, design, drafting and revising 
the manuscript. All authors read and approved the final manuscript. 
  
  
Acknowledgments 
 
The authors are grateful to the staff of the Department of Internal 
Medicine and the Medical Out Patients Department of the Nelson 
Mandela Academic Hospital (NMAH) for their kind assistance and 
collaboration in successfully treating this patient. 
  
  
References 
 
1. Takasu N, Yamada T, Sato A, Nakagawa M, Komiya I, 
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2. Kamath C, Young S, Kabelis K, Sanders J, Adlan MA, Furmaniak 
J et al. Thyrotropin receptor antibody characteristics in a 
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disease and pretibial myxedema. Clin Endocrinol. 2012; 77 
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thyroiditis to Graves' disease. Res Rev Insights. 2017; 1(3): 1-
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4. Furqan S, Haque NU, Islam N. Conversion of autoimmune 
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P et al. Alentuzumab related thyroid dysfunction in a phase 2 
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Graves’ disease following hypothyroidism due to Hashimoto’s thyroiditis in a black South African lady: a case report

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CORRESPONDENCE
198       April 2019, Vol. 109, No. 4
Eligibility for co-trimoxazole 
prophylaxis among adult HIV-infected 
patients in South Africa 
To the Editor: Co-trimoxazole (fixed-dose trimethoprim-sulfa-
methoxazole) is a broad-spectrum antibiotic used to prevent 
opportunistic infections in patients with HIV infection. Primary 
prophylaxis with co-trimoxazole has been shown to decrease 
hospitalisation, morbidity and mortality among people living with 
HIV, primarily by decreasing rates of malaria, pneumonia, diarrhoea, 
Pneumocystis pneumonia, toxoplasmosis and severe bacterial 
infections.[1-4] Co-trimoxazole is inexpensive and widely available. In 
standard adult treatment guidelines and essential medicine lists in 
South Africa (SA), the current recommendation is that co-trimoxazole 
should be provided for HIV-infected patients with a CD4+ count 
˂200 cells/µL, HIV/tuberculosis (TB) co-infection and/or advanced 
HIV disease (World Health Organization (WHO) stage 3 or 4).
Because of expanded access and progression towards initiation of 
antiretroviral treatment (ART), the WHO issued updated guidelines 
for co-trimoxazole prophylaxis in 2014.[5] These guidelines recommend 
co-trimoxazole prophylaxis for adults (including pregnant women) 
with severe or advanced HIV clinical disease (WHO stage 3 or 4) 
and/or with a CD4+ count ≤350 cells/µL. In settings with a high 
prevalence of malaria and/or severe bacterial infections, prophylaxis 
is recommended for all patients regardless of WHO clinical stage 
or CD4+ cell count. However, the timing of discontinuation of 
co-trimoxazole prophylaxis may vary and is dependent on the malarial/
bacterial infection burden in different settings.[5] Therefore, the current 
WHO guidance should be adapted in the context of a country-specific 
epidemiological profile and priorities. 
The impact and benefit of co-trimoxazole prophylaxis on morbi-
dity and mortality among HIV-infected patients with a CD4+ count 
≤350 cells/µL in regions with high infectious disease burdens (irre-
spective of CD4+ count) have been shown in a good- quality syste matic 
review and meta-analysis that included both rando m ised controlled 
trials (RCTs) and observational cohort studies.[6] This extensive syste-
matic review by Suthar et al.[6] showed that co-trimoxazole prophy laxis 
reduced the rate of death when initiated at CD4+ counts ≤350 cells/ µL 
with ART in populations in Africa and Asia. Co-trimoxazole prophy-
laxis in ART-naive patients with CD4+ counts >350 cells/ µL reduced 
the rate of death and malaria, and continu ation of prophylaxis after 
ART-induced recovery with CD4+ counts >350 cells/µL reduced hos-
pital admission, pneumonia, malaria and diarrhoea in African popula-
tions (SA, Zimbabwe, Uganda, Malawi, Mozambique and Ethiopia).[6] 
While this review largely informed the 2014 WHO guideline update, 
the findings need to be interpreted in the context of studies included 
and the varied epidemiological profile across middle- and low-income 
countries. There were only 2 relatively small RCTs with very few events 
of key endpoints; therefore, the finding of non-significance was likely 
(e.g. total of ~5 deaths in both arms from both trials).[7,8] One of the 
2 studies was unblinded, and the follow-up in the other study was 
only 4 months. Ongoing co-trimox azole prophylaxis was better than 
discontinuation of the drug at CD4+ counts >200 cells/µL for 3 end-
points with an adequate number of events (pneumonia, diarrhoea and 
malaria). Furthermore, 8 of 9 studies were conducted in countries with 
a high burden of malaria and bacterial and parasitic diseases, which is 
generalisable to the SA context.[9] Although season al malaria occurs in 
the north-eastern parts of SA, the incidence of malaria mortality and 
morbidity has declined remarkably over time (˂10 000 cases annually 
for the past 10 years).[10] In contrast, in Uganda, >9 million confirmed 
cases of malaria were reported in the public health sector in 2015.[9] In this 
review, further stratification of the impact of co-trimoxazole prophylaxis 
at CD4+ counts ˂200 cells/µL v. 200 - 350 cells/µL was not available. 
Lower bacterial resistance to co-trimoxazole is possible among popu-
lations included in this review, while resistance to co-trimoxazole in 
SA is common in patients with community-acquired bacterial 
infections.[11-13] This potential risk of resistance compounded by 
the lack of long-term toxicity data needs to be weighed against 
recommending prophylaxis in populations where benefit has not 
been established.
Local observational studies suggest no benefit of co-trimoxazole 
prophylaxis with a CD4+ count >200 cells/µL or in patients who 
were not WHO clinical stage 3 or 4.[14,15] In an observational cohort 
of patients attending the adult HIV clinics at the University of Cape 
Town, SA, the effect of prophylactic low-dose co-trimoxazole on 
survival and morbidity was examined over a 5-year follow-up period. 
Co-trimoxazole reduced the hazards of mortality by ~44% and the 
incidence of severe HIV-related illnesses by ~48% in patients with 
evidence of advanced immunosuppression (WHO stage 3 or 4) or 
laboratory measurement of total lymphocyte count ˂1 250 × 106/L or 
CD4+ count ˂200 cells/µL. However, no beneficial effect was seen in 
patients with WHO clinical stage 2 or CD4+ count 200 - 500 cells/µL. 
A potential limitation of this study was that the sample size of patients 
with a CD4+ count 200 - 500 cells/µL receiving co-trimoxazole was 
small and may have been underpowered to observe a significant 
benefit. In this study, patients on ART were excluded.[14] In another 
SA cohort study by Hoffmann et al.,[15] examining co-trimoxazole 
effectiveness in reducing mortality risk during ART among persons 
with a CD4+ count >200 cells/µL and varying WHO clinical stages, 
overall co-trimoxazole prophylaxis reduced mortality by 36% across 
all CD4+ count strata. Analysis stratified by baseline CD4+ count 
showed a similar reduction in mortality risk among persons with a 
CD4+ count ˂200 cells/µL, but no statistically significant association 
was found between co-trimoxazole prophylaxis and survival in the 
subgroup of persons with a CD4+ count >200 - 350 cells/µL, CD4+ 
count >350 cells/µL and WHO stage 1 or 2 disease. However, the 
findings of this study need to be interpreted cautiously for the following 
reasons: the group with a CD4+ count >350 cells/µL was small (n=917) 
and might not have had enough events to draw inferences; the study 
population was a cohort of miners and might not have been potentially 
representative of the SA population; and, being a non-randomised 
study, residual confounding might have been a potential limitation. 
An earlier Cochrane review established the benefit of initiating 
prophylaxis at a CD4+ count ˂200 cells/µL in those with stage 2, 3 or 4 
HIV disease (including TB), and discontinuation once the CD4+ count 
was >200 cells/µL for >6 months.[16] There was a reduction of ~31% in 
mortality, 27% in morbid events and 55% in hospitalisation. Significant 
reductions were also detected for bacterial and parasitic infections and 
for Pneumocystis jirovecii pneumonia. 
Considering the above-mentioned evidence gaps and lack of 
generalisability of studies to SA, the current National Essential 
Medicines List Committee and Adult Hospital-Level Technical 
Sub-committee do not support the implementation of the updated 
guidance by the WHO for co-trimoxazole prophylaxis among adult 
HIV-infected patients. Efforts should be directed towards exploring 
several research gaps. The impact of co-trimoxazole prophylaxis on 
morbidity and mortality at higher CD4+ counts in low-malaria-
burden areas needs to be investigated further. More data are needed 
on timing of co-trimoxazole cessation in HIV and TB co-infection 
in our context. 
Simbarashe Takuva
Perinatal HIV Research Unit, Faculty of Health Sciences,  
University of the Witwatersrand, Johannesburg; and School of Health 
Systems and Public Health, Faculty of Health Sciences,  
University of Pretoria, South Africa
simbataks1@gmail.com
This open-access article is distributed under 
Creative Commons licence CC-BY-NC 4.0.
199       April 2019, Vol. 109, No. 4
CORRESPONDENCE
Johnson M Nabyoma 
Department of Pharmacy, Lehurutshe Hospital, North West Province 
Department of Health, Zeerust, South Africa
Halima Dawood 
Centre for the AIDS Programme of Research in South Africa 
(CAPRISA), University of KwaZulu-Natal, Durban; and Department 
of Internal Medicine, Grey’s Hospital, Pietermaritzburg, South Africa 
Andrew Black
Department of Internal Medicine, School of Clinical Medicine,  
Faculty of Health Sciences, University of the Witwatersrand, 
Johannesburg, South Africa
Gary Maartens 
Division of Clinical Pharmacology, Department of Medicine,  
Faculty of Health Sciences, University of Cape Town, South Africa
Andy Parrish 
Department of Medicine, Faculty of Health Sciences, Walter Sisulu 
University, Mthatha; and Department of Internal Medicine, Frere and 
Cecilia Makiwane hospitals, East London, South Africa
Trudy D Leong
Essential Drugs Programme, National Department of Health, Pretoria, 
South Africa
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S Afr Med J 2019;109(4):198-199. DOI:10.7196/SAMJ.2019.v109i4.13877 


Eligibility for co-trimoxazole prophylaxis among adult HIV-infected patients in South Africa

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