Characteristics and outcome of surgically treated acromegaly patients attending an endocrinology clinic at a tertiary referral centre in Durban, South Africa over a period of 10 years

Background: The mode of presentation, clinical, radiologic and laboratory characteristics of patients with acromegaly and the outcome following various modalities of treatment are not well documented in South Africa.Aim: To evaluate treatment outcome and follow-up of patients with acromegaly over a period of 10 years.Methods: The study is a retrospective record review of patients with acromegaly attending Inkosi Albert Luthuli Central Hospital, Durban, 2003–2013.Results: The study included 27 patients (16 female and 11 male) with a mean age at diagnosis of 44.2 ± 14.0 years. The mean growth hormone (GH) at diagnosis was 51.8 ± 32.6 μg/l and mean IGF-1 956.8 ± 432.9 μg/l. In 25 patients (92.5%) pituitary macroadenoma was identified; microadenoma was present in 2 (7.4%) patients. Trans-sphenoidal surgery was employed in 26 (96.3%) as the initial therapy; only 1 patient was treated medically. Adjunctive medical therapy was used in 23 (88.5%) and radiotherapy in 6 (22.2%). After a mean follow-up of 4.4 ± 3.4 years, 9 (33.3%) subjects were cured (normal age-matched and gender-matched IGF-1 and random GH < 1.0 μg/l). No deaths were recorded and post-procedural hypopituitarism developed in 22 (84.6%) patients.Conclusions: Patients with acromegaly in KwaZulu-Natal present with advanced clinical features and large pituitary adenomata. The overall cure rate is lower than reported from developed countries.Keywords: acromegaly, diagnostic criteria, medical and radiotherapy, modes of treatment (surgery

Rickets mimicker: A report of two cases of primary hyperparathyroidism in adolescence

The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of ‘stones, bones, and groans’ to becoming increasingly asymptomatic as a result of more frequent serum calcium screening. However, many developing countries are still reporting predominantly symptomatic PHPT with the classic complications of skeletal disease and nephrolithiasis still being quite common. Furthermore, the exact prevalence of PHPT in children is not known but it is thought to be uncommon and the clinical presentation and outcomes in this subgroup of patients are not well described in the literature. Two cases of PHPT occurring in adolescent boys are reported. Both cases initially presented with chronic bone pain involving the lower limbs and had a long delay before the diagnosis of PHPT was confirmed. They developed progressive deformities of the lower limbs, which resembled rickets clinically. Radiological features were also suggestive of rickets. However, biochemistry confirmed parathyroid hormone mediated hypercalcaemia in both cases and after parathyroid surgery a parathyroid adenoma was confirmed histologically as the aetiology of hypercalcaemia. Therefore, PHPT occurring in adolescence may have a clinical presentation almost identical to that of rickets. All patients presenting with skeletal deformities including a rickets phenotype must have serum calcium and phosphate levels measured as part of the diagnostic workup

Characteristics and outcome of patients with pheochromocytoma at a tertiary endocrinology clinic in Durban, South Africa over 14 years

Objectives: To evaluate the characteristics and outcomes of treatment of patients with pheochromocytoma at Inkosi Albert Luthuli Central Hospital (ILACH) in Durban, South Africa over 14 years.Design: Retrospective chart review.Setting and subjects: Patients with pheochromocytoma attending the endocrinology clinic at IALCH between 2012 and 2016 were studied.Outcome measures: Clinical, biochemical and radiological data were collected at presentation, on discharge, one year and five years after surgical intervention; tumour characteristics, histopathological features and surgical outcome were also assessed.Results: The analysis included 35 patients (mean age 33.2 ± 15.7 years; 60% female). Headache (68.6%), palpitation (60%) and sweating (57.6%) were the three most common presenting symptoms; hypertension was the predominant clinical finding (85.7%). Most pheochromocytomas were sporadic (82.9%), adrenal gland tumours (68.6%) and benign (77.1%); of eight patients with malignant tumours, two were familial. Adrenalectomy was undertaken in the majority (n = 34; 97.1%); 55.2% were large tumours. The use of adjunctive radiotherapy (n = 4; 11.4%) and chemotherapy (n = 1; 2.9%) was low. There was low overall mortality (5.7%), but 57.6% developed intraoperative hypotension. At one year postoperatively, 80% (n = 28) of patients were defined as cure, biochemically in 23 (82.1%) and with radiology in five (17.9%).Conclusions: Most patients presenting to IALCH had large intra-abdominal tumours with high cure rate, low mortality but a high rate of perioperative complications. Late presentation and large tumour size was a feature.Keywords: pheochromocytoma , South Africa, surgical outcom

Microvascular complications in South African patients with long duration diabetes mellitus

Objective. To determine the prevalence of microvascular complications in South African black and Indian patients with long-duration diabetes mellitus (DM).Design. A retrospective analysis was undertaken of clinical records of 219 OM patients (132 black, 87 Indian) with longduration OM (over 10 years) attending a diabetes clinic in Durban. Data recorded on each subject included demographic details (age, gender, ethnic group, type of diabetes, age of onset and duration of diabetes), presence of retinopathy, markers of nephropathy and biochemical variables. The prevalence of complications and the clinical and biochemical parameters were evaluated for type 1 and type 2 diabetes and for each ethnic group.Results. Of the 219 patients, 47 had type 1 OM (36 blacks, 11 Indians) and 172 were classified as type 2 OM (96 blacks, 76 Indians). The mean age of onset of OM wa later in blacks than Indians, both for type 1 (P < 0.05) and type 2 OM (P < 0.01). In patients with type 1 OM, the prevalence of retinopathy was 53.2% (blacks 55.6%, Indians 45.5%), persistent proteinuria was found in 23.4% (blacks 25%, Indians 18.2%) and hypertension in 34%. 0 ethnic difference was found except for the prevalence of hyperten ion which was higher in blacks than Indians (41.7% v. 9.1%, P < 0.5). Onset of retinopathy from time of diabetes diagno is occurred earlier in blacks than Indians (13.0 ± 4.6 yrs v. 18.0 ± 4.6 yrs, P < 0.05). For the type 2 DM group, retinopathy was found in 64.5% (black v. Indian 68.8 v. 59.2%) and per istent proteinuria in 25% (black v. Indian 30.2 v. 1 .4%). Hypertension wa observed in 68% and wa more prevalent in blacks (84.4 v. 47.,*%, P < 0.01) There was an earlier onset of retinopathy (P < 0,05) and hypertension (P < 0.01) from time of diabetes diagnosis in blacks than Indians. In the type 1 OM group retinopathy was a sociated with a ignificantly longer duration of diabetes (P < 0.05) and higher glycated haemoglobin (HbA1) (P < 0.05). For type 2 DM subjects there was a significant association between retinopathy and longer duration of diabetes (P < 0.05) and higher systolic blood pressure (P < 0.05).Conclusion. 1his study has shown that there is a high prevalence of microvascular complications in South African patients with long-duration diabetes mellitus

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.Main funding: This work was funded by the Wellcome Trust, The Wellcome Sanger Institute (WT098051), the U.K. Medical Research Council (G0901213-92157, G0801566, and MR/K013491/1), and the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS core funding

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Trends in glycaemic control and morbidity over 10 years in patients with type 1 diabetes mellitus at Inkosi Albert Luthuli Central Hospital

Aim: To assess control and morbidity in patients with type 1 diabetes mellitus (T1 attending a tertiary adult diabetes clinic in Durban, South Africa.Methods: A retrospective chart review of all patients with T1D who attended clinic in the years 2006, 2012 and 2015. Clinical and laboratory changes were assessed at an individual patient-level follow-up (IPLF) and whole clinic level (n = 231).Results: In the IPLF study arm (n = 58; 45% Black patients; 62% female; median age 18 years), mean HbA1c [% (mmol/mol)] decreased from 9.9 ± 2.6% (85 ± 28) in 2006 to 8.7 ± 1.5% (72 ± 16) in 2012 (p &lt; 0.001) and to 9.1 ± 1.7% (76 ± 19) in 2015 (p = 0.03); target HbA1c &lt; 7.0% (&lt; 53 mmol/mol) was achieved in 7.1%, 5.3% and 8.3%, respectively. Compared with 2006, in 2015 there was a higher prevalence of retinopathy (10.3% vs. 29.3%, p = 0.004), abnormal glomerular filtration rate (0% vs. 6.9%, p = 0.04) and abnormal serum creatinine (0% vs. 8.6%, p = 0.02). Predictive risk factors for new retinopathy included diabetes duration (OR 1.4; 95% CI 1.0–1.3; p = 0.03) and diastolic blood pressure (OR 1.15; 95% CI 1.0–1.3; p = 0.04).Conclusion: Glycaemic control improved over 10 years, but fell short of recommended targets. Intensive efforts are required to achieve current targets for glycaemic and non-glycaemic control

Identification of a subgroup of black South Africans with type 1 diabetes who are older at diagnosis but have lower levels of glutamic acid decarboxylase and islet antigen 2 autoantibodies

AIMS : To compare the age at diagnosis and prevalence of islet autoantibody [glutamic acid decarboxylase (65 kDa) 65 and islet antigen 2] positivity in black and white participants with type 1 diabetes in South Africa, and to analyse the relationship between age at diagnosis and the presence of autoantibodies. METHODS : Participants were recruited from diabetes outpatient departments and autoantibodies to glutamic acid decarboxylase (65 kDa) and islet antigen 2 were measured by enzyme‐linked immunosorbent assay. RESULTS : We recruited 472 (353 black and 119 white) participants with type 1 diabetes. Age at diagnosis of diabetes was later in black (19.7 ± 10.5) than in white participants (12.7 ± 10.8 years; P < 0.001) with a median (interquartile range) disease duration of 5.0 (2.0–10.0) and 8.5 (4.0–20.0) years (P < 0.001), respectively. An older age at diagnosis (≥ 21 years) was more frequent in black (152 of 340, 45%) than in white participants (24 of 116, 21%; P < 0.001). The prevalence of islet antigen 2 autoantibodies was 19% (66/352) in black and 41% in white participants (48/118; P < 0.001). There was no significant difference in glutamic acid decarboxylase (65 kDa) autoantibody positivity between black (212/353, 60%) and white participants (77/117, 66%; P = 0.269). In black, but not white, participants the prevalence of both glutamic acid decarboxylase (65 kDa) and islet antigen 2 autoantibody positivity was significantly lower in participants diagnosed at age ≥ 21 years (P < 0.001 for both comparisons). CONCLUSIONS : The older age at diagnosis, lower prevalence of islet antigen 2 autoantibodies and a distinct subgroup of participants with type 1 diabetes with age at diagnosis of > 20 years in the black compared to white population suggest a difference in the immunological aetiology of type 1 diabetes in these two population groups.The South African Medical Research Council and the National Health Laboratory Service Research Trust (94472).https://onlinelibrary.wiley.com/journal/146454912020-12-06hj2020Internal Medicin