A challenging case of a pituitary macroadenoma and toxic thyroid adenoma with inappropriate TSH secretion.

Summary: Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas) are rare, accounting for less than 1% of all pituitary adenomas. We present a case of hyperthyroidism secondary to a likely TSHoma and coexisting functional thyroid adenoma. Laboratory errors and familial abnormalities in thyroid function tests were ruled out, and a diagnosis of the toxic thyroid adenoma was confirmed on a thyroid uptake scan. However, the triiodothyronine suppression test was contraindicated due to the patient's cardiovascular disease, and the thyrotropin-releasing hormone stimulation test, measurement of glycoprotein hormone alpha-subunit, and genetic testing were unavailable. Magnetic resonance imaging of the brain revealed a suprasellar pituitary macroadenoma measuring 40 mm × 20.3 mm × 17 mm. The patient was initiated on carbimazole; however, thyroid stimulating hormone and thyroxine levels remained elevated. The patient declined trans-sphenoidal surgery and was treated with radioactive iodine to manage the toxic thyroid adenoma, leading to reduced thyroxine levels and symptom improvement. Unfortunately, the patient passed away before long-acting somatostatin analogs became available. This case highlights the diagnostic and therapeutic challenges involved in managing thyrotoxicosis with dual etiology. Learning points: Hyperthyroidism can have multiple etiologies, which can coexist in the same patient. Persistent discordant thyroid function tests warrant further investigation. The gold standard for diagnosis of TSHomas remains immunohistochemical analysis of the tumor tissue.

Unraveling the Whipple Triad: Non-Islet Cell Tumor-Induced Hypoglycemia.

Tumor-induced hypoglycemia (TIH) is a rare paraneoplastic phenomenon resulting from several tumor types and mechanisms. Insulinomas are the most common cause of TIH. However, non-islet cell tumors can also trigger hypoglycemia by releasing insulin-like growth factor 2 (IGF-II) or its precursor. We present a case of a 56-year-old woman experiencing spontaneous hypoglycemia due to a pleural-based solitary fibrous tumor. Diagnostic evaluations revealed diminished C-peptide levels, increased IGF-II, and a 4-fold increase in the IGF-II: IGF-I ratio, indicative of non-islet cell tumor hypoglycemia. Localization imaging identified a left pleural mass, confirming the diagnosis. Preoperatively, the patient received intravenous dextrose and corticosteroids, but surgical resection was essential for the resolution of symptoms. The identified tumor, a benign solitary fibrous tumor, was successfully removed, leading to an immediate postoperative cessation of hypoglycemia. Six years post resection, the patient remains symptom free. Managing TIH necessitates an early diagnosis aiming for complete tumor resection, with alternative approaches considered when complete resection is not possible. This case highlights the importance of a systematic diagnostic and management approach for TIH, emphasizing the need to identify the underlying cause, particularly in people without diabetes.

COVID-19: An evaluation of predictive scoring systems in South Africa.

Background: | The Coronavirus Disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2, has resulted in more than 700 million cases worldwide. Sepsis and pneumonia severity scores assist in risk assessment of critical outcomes in patients with COVID-19. This allows healthcare workers to triage patients, by using clinical parameters and limited special investigations, thus offering the most appropriate level of care. Methods: | A retrospective cohort study of 605 adult patients hospitalised with moderate to severe COVID-19, at a tertiary state hospital in South Africa. Evaluating the utility of the CURB65, NEWS2 and ISARIC-4C Mortality Score, in predicting critical outcomes, using clinical characteristics on admission. Outcomes included in-hospital mortality, invasive mechanical ventilation, and intensive care unit admission (ICU). Performance of severity scores and risk factors was assessed by area under the receiver operator characteristics (AUROC) analysis and logistic regression. Findings |: A total of 605 records were used, 129 (21 %) non-survivors, 101 (17 %) ICU admissions and 77 (13 %) requiring invasive ventilation. Greater odds of mortality was associated with moderate and severe risk groups of the CURB65, ISARIC-4C and NEWS2 score. Mortality AUROC curve analysis for the CURB65 score was 0·76 (95 % CI: 0·71-0·8), 0·77 (95 % CI: 0·73-0·81) for the ISARIC-4C and 0·77 (95 % CI: 0·73-0·82) for the NEWS2 score. The CURB65 score had a sensitivity of 86 % with 12·8 % mortality, ISARIC-4C score a sensitivity of 87·6 % with 8 % mortality and NEWS2 score a sensitivity of 92·2 % with 8·6 % mortality. Interpretation |: In 605 hospitalised patients with moderate to severe COVID-19, predominantly infected by the ancestral strain, good performance of the NEWS2 and ISARIC-4C score in predicting in-hospital mortality was noted. The CURB65 score had a high mortality rate in its low-risk group suggesting unexplained risk factors, not accounted for in the score, thus limiting its utility in the South African setting.

Point-of-care testing compared to gold-standard laboratory methods in the measurement of serum lipids.

BACKGROUND: Cardiovascular disease is the leading cause of mortality worldwide, with dyslipidaemia being one of the major risk factors. Point-of-care testing (POCT) allows for the rapid measurement of serum lipids. The aim of this study was to assess the accuracy of serum lipid measurement by the Fujifilm™ NX700 POCT compared to a gold-standard clinical laboratory method (Medpace, Leuven, Belgium). METHODS: This was a prospective, observational study conducted at the Lipid Clinic at Charlotte Maxeke Johannesburg Academic Hospital from July to September 2022. Participants were known to have a lipid disorder, most commonly, familial hypercholesterolaemia. Samples sent for lipid measurement by standard laboratory methods were simultaneously measured by the Fujifilm™ NX700 POCT. RESULTS: Lipograms evaluating total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and calculated low-density lipoprotein cholesterol (LDL-C) were obtained from 115 participants. No statistically significant difference was noted between the parameters tested on the different platforms. The Fujifilm™ NX700 POCT correctly identified > 91% of serum lipid results as normal or abnormal, as defined by NCEP-ATP III criteria, and exhibited good sensitivity and specificity for each parameter. Lin's concordance correlation coefficient demonstrated a strong correlation for all parameters; TC (ρc = 0.9861), HDL-C (ρc = 0.95919), LDL-C (ρc = 0.98134) and TG (ρc = 0.92775). Bland-Altman plots identified low bias and a good level of agreement between the two test methods. CONCLUSION: The Fujifilm™ NX700 POCT compared favourably with gold-standard laboratory methods in the determination of serum lipid measurements, allowing for rapid screening at the primary healthcare level.

Targeting PCSK9 and Beyond for the Management of Low-Density Lipoprotein Cholesterol.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is crucial to the prevention of atherosclerotic cardiovascular disease (ASCVD). However, many patients, especially those at very high ASCVD risk or with familial hypercholesterolemia (FH), do not achieve target LDL-C levels with statin monotherapy. The underutilization of novel lipid-lowering therapies (LLT) globally may be due to cost concerns or therapeutic inertia. Emerging approaches have the potential to lower LDL-C and reduce ASCVD risk further, in addition to offering alternatives for statin-intolerant patients. Shifting the treatment paradigm towards initial combination therapy and utilizing novel LLT strategies can complement existing treatments. This review discusses innovative approaches including combination therapies involving statins and agents like ezetimibe, bempedoic acid, cholesterol ester transfer protein (CETP) inhibitors as well as strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and angiopoietin-like protein 3 (ANGPTL3) inhibition. Advances in nucleic acid-based therapies and gene editing are innovative approaches that will improve patient compliance and adherence. These strategies demonstrate significant LDL-C reductions and improved cardiovascular outcomes, offering potential for optimal LDL-C control and reduced ASCVD risk. By addressing the limitations of statin monotherapy, these approaches provide new management options for elevated LDL-C levels.

ANGPTL3 as a Drug Target in Hyperlipidemia and Atherosclerosis.

PURPOSE OF REVIEW: Elevated low-density lipoprotein cholesterol (LDL-C) and triglyceride-rich lipoproteins (TRLs) or remnants are important risk factors for the development of atherosclerotic cardiovascular disease (ASCVD). The ongoing challenge of not being able to achieve recommended LDL-C targets despite maximally tolerated lipid-lowering therapy (LLT) has led to the development of novel therapeutic agents including angiopoietin-like 3 (ANGPTL3) inhibitors. RECENT FINDINGS: ANGPTL3 is a glycoprotein produced by the liver that inhibits lipoprotein lipase and endothelial lipase. Data from genetic and clinical studies have shown that a lower ANGPTL3 level is associated with lower plasma LDL-C, triglyceride (TG), and other lipoproteins. Pharmacological inactivation of ANGPTL3 with the monoclonal antibody, evinacumab, results in a 50% reduction in LDL-C, even in patients with homozygous familial hypercholesterolemia (HoFH). The safe and effective targeted delivery of nucleic acid-based therapies will shape the future of the lipid arena. ANGPTL3 is a novel target in lipoprotein metabolism, targeting not only LDL-C via an LDL-receptor (LDLR) independent mechanism but also TRLs and carries a significant promise for further ASCVD risk reduction.

Acute Suppurative Thyroiditis Secondary to Escherichia coli Infection.

Infections of the thyroid gland are rare. Its innate resistance to infections can be attributed to its unique anatomical features and rich blood supply. High clinical suspicion is required as a delay in diagnosis can lead to significant morbidity and mortality. Major pathogens include the Gram-positive Staphylococcus aureus and Streptococcus species; however, Gram-negative organisms have been found especially in immunocompromised hosts. We present a rare case of acute suppurative thyroiditis (AST) secondary to Escherichia coli (E. coli) infection in a woman known to be infected with human immunodeficiency virus (HIV). LEARNING POINTS: Thyroid abscesses are rare and can be confused with more common pathologies involving the neck such as a goitre, adenoma, intracystic haemorrhage, pharyngeal abscess and subacute thyroiditis.A high index of suspicion for a thyroid abscess is required for patients who present with an anterior neck swelling to avoid a late diagnosis, which is associated with significant morbidity and mortality.Acute suppurative thyroiditis is more commonly caused by Gram-positive organisms. Gram-negative organisms such as E. coli remain a rare cause. However, if a thyroid abscess is suspected clinically, broad-spectrum antibiotics can be lifesaving before definite culture and sensitivity results are available.

Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19.

BACKGROUND: South Africa has the highest prevalence of HIV in the world and to date has recorded the highest number of cases of COVID-19 in Africa. There is uncertainty as to what the significance of this dual infection is, and whether people living with HIV (PLWH) have worse outcomes compared to HIV-negative patients with COVID-19. This study compared the outcomes of COVID-19 in a group of HIV-positive and HIV-negative patients admitted to a tertiary referral centre in Johannesburg, South Africa. METHODS: Data was collected on all adult patients with known HIV status and COVID-19, confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR), admitted to the medical wards and intensive care unit (ICU) between 6 March and 11 September 2020. The data included demographics, co-morbidities, laboratory results, severity of illness scores, complications and mortality, and comparisons were made between the HIV-positive and HIV negative groups. RESULTS: Three-hundred and eighty-four patients, 108 HIV-positive and 276 HIV-negative, were included in the study. Median 4C score was significantly higher in the HIV-positive patients compared to the HIV-negative patients, but there was no significant difference in mortality between the HIV-positive and HIV-negative groups (15% vs 20%, p = 0.31). In addition, HIV-positive patients who died were younger than their HIV-negative counterparts, but this was not statistically significant (47.5 vs 57 years, p = 0.06). CONCLUSION: Our findings suggest that HIV is not a risk factor for moderate or severe COVID-19 disease neither is it a risk factor for mortality. However, HIV-positive patients with COVID-19 requiring admission to hospital are more likely to be younger than their HIV-negative counterparts. These findings need to be confirmed in future, prospective, studies.

Hyperlipidemic myeloma, a rare form of acquired dysbetalipoproteinemia, in an HIV seropositive African female.

Dysbetalipoproteinemia (DBL) is an uncommon condition characterized by a mixed hyperlipidemia due to accumulation of remnant lipoproteins and is highly atherogenic. Typically, DBL is an autosomal recessive condition requiring an additional metabolic stress with reduced apolipoprotein E (apoE) function. However, DBL is also described in patients with multiple myeloma without the characteristic apoE2/E2 mutation seen in familial DBL. Although the underlying pathogenesis in these cases is not fully characterized, it is thought to occur due to interference with apoE function by antibodies produced from clonal plasma cells. Such cases are referred to as hyperlipidemic myeloma (HLM) and have rarely been described in the literature. To our knowledge there is no prior description of HLM in HIV positive patients in Africa. We describe a case of HLM in an African woman with underlying HIV infection who presented with phenotypic and biochemical features of DBL that responded poorly to lipid lowering therapy.

Inhibition of angiopoietin-like 3 for the management of severe hypercholesterolemia.

PURPOSE FOR REVIEW: Despite the therapeutic advances for patients with severe hypercholesterolemia, particularly those with homozygous familial hypercholesterolemia (HoFH), most patients are unable to achieve target low-density lipoprotein cholesterol (LDL-C) levels with the current available standard lipid-lowering therapy (LLT). We review the role of angiopoietin-like 3 (ANGPTL3) inhibition as an additional therapeutic option for severe hypercholesterolemia, particularly HoFH. RECENT FINDINGS: Evinacumab is a monoclonal antibody against ANGPTL3, and reduces LDL-C independent of LDL-receptor activity. ANGPTL3 inhibitors are effective in lowering LDL-C in patients with FH, with a 50% reduction in LDL-C in those with HoFH. Longer-term efficacy and safety have been demonstrated with reductions in LDL-C maintained following 48 weeks of therapy. Gene silencing strategies directed against ANGPTL3 include antisense oligonucleotide and small-interfering ribonucleic acid (siRNA). ARO-ANG3 is a siRNA directed against ANGPTL3 messenger ribonucleic acid and is associated with up to a 42% reduction in LDL-C. SUMMARY: With the promise of these emerging novel therapeutics directed against ANGPTL3 on the horizon, achieving acceptable target LDL-C levels in HoFH without the need for lipoprotein apheresis may finally be a realistic goal and we can anticipate a decrease in cardiovascular morbidity and mortality in these difficult to treat patients.

Novel therapies for familial hypercholesterolemia.

PURPOSE OF REVIEW: Familial hypercholesterolemia is a genetic disorder of defective clearance and subsequent increase in serum LDL cholesterol (LDL-C) with a resultant increased risk of premature atherosclerotic cardiovascular disease. Despite treatment with traditional lipid-lowering therapies (LLT), most patients with familial hypercholesterolemia are unable to achieve target LDL-C. We review current and future novel therapeutic options available for familial hypercholesterolemia. RECENT FINDINGS: The use of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are effective in lowering LDL-C in patients with familial hypercholesterolemia, with a reduction in LDL-C of 60% in heterozygous familial hypercholesterolemia (HeFH) and up to 35% in homozygous familial hypercholesterolemia (HoFH). Inclisiran, another novel agent, is a small-interfering ribonucleic acid that reduces hepatic production of PCSK9 to provide a prolonged and sustained reduction in LDL-C of nearly 50% in HeFH. However, both agents require LDL receptor (LDLR) activity. Evinacumab, a novel monoclonal antibody against angiopoetin-like 3 (ANGPTL3), reduces LDL-C by 50% independent of LDLR activity. SUMMARY: Achieving a target LDL-C in familial hypercholesterolemia can be challenging with standard LLT; however, novel therapeutic modalities show remarkable reductions in LDL-C allowing nearly all patients with HeFH and a significant proportion of patients with HoFH to achieve acceptable LDL-C levels.