Journal of the ASEAN Federation of Endocrine Societies

Intentional Hyperglycemia at work, Glycemic Control, Work-related Diabetes Distress and Work Ability among Workers with Diabetes

Samah Saleh Elhadidy — 2024-08-02

Background. Work life of individuals with diabetes differs from that of those without diabetes. Work may interfere with diabetes self-management tasks, resulting in intentional hyperglycemia at work (IHW) and poor glycemic control. Diabetes also can affect work productivity due to work-related diabetes distress (WRDD) and impaired work ability (WA).

Methodology. A cross-sectional study was done at the Specialized Medical Hospital Mansoura University, which included 323 working patients with diabetes. They were subjected to personal interviews to collect socio-demographic data, occupational, diabetes and other pertinent medical histories. Questionnaires for measuring IHW, WRDD and WA were completed. Clinical and A1c data were obtained from their records.

Results. The prevalence of always high IHW, poor/very poor glycemic control, high WRDD and poor/moderate work ability was: 23.8%, 60.1%, 34.7% and 74.6%, respectively. The predictors of always high IHW were: 1) below university education; 2) treatment with insulin only or combined with oral drugs and 3) high WRDD. The predictors of poor/very poor glycemic control were urban residence, always and almost high IHW. The predictors of high WRDD were mentally-requiring jobs or both mentally- and physically-requiring jobs, duration of diabetes greater than 14 years and treatment with insulin. The predictors of poor/moderate WA were 'high' WRDD, 'almost high' and 'high a few times' IHW ratings.

Conclusions: Most of the studied population suffered mainly from poor/very poor glycemic control and poor/moderate work ability, while a lower proportion had high WRDD. This highlighted the need for workplace modifications and interventions to help workers with diabetes control their diabetes, improve their work ability and reduce WRDD to increase productivity.

Risk Factors for Perioperative Complications, Treatment Outcomes and Aggressive Behavior of the Tumor in Patients with Pheochromocytoma

Gopinath Narayanaswamy — 2024-08-05

Introduction. Pheochromocytomas are catecholamine-secreting tumors arising from chromaffin cells of the adrenal gland. Surgery is the only curative treatment with a high biochemical cure rate, low mortality and high risk of perioperative complications.

Objectives. To study the demographic characteristics of patients with pheochromocytoma and to identify the risk factors for perioperative complications, treatment outcomes, and aggressive behavior of the tumor.

Methodology. We retrospectively studied the data of pheochromocytoma patients registered from 2012 to 2022.

Results. In our study, a total of 30 patients with pheochromocytoma were included. The mean age of presentation was 35 ± 12.8 years. Fifty-six percent were females, and the sex ratio was 1.3:1. Pheochromocytoma spells (60%) was the most common complaint, followed by abdominal pain (53%), orthostatic complaints (10%) and incidentalomas (6%). The baseline mean 24-hour urinary total metanephrines was 2963.7 ± 2658 mcg/24 hours, and the mean tumor size was 7.3±0.53 cm. Forty-three percent of patients underwent laparoscopic adrenalectomy, while the rest underwent open surgery. The mean Pheochromocytoma of Adrenal gland Scaled Score (PASS) was 3.41 ± 0.28, and 23% had a high risk for malignancy. Among perioperative complications, hypertension crisis (17%) was the most common, followed by posoperative hypotension (13%), hypoglycemia (3%) and right-sided pneumothorax (3%). These patients with complications had higher metanephrine levels (5490 vs. 1880mcg/24 hours, p=0.001). Blood pressure normalized in 50%, and this was associated with male sex, younger age (29.5 vs. 40 years, p=0.03), higher metanephrines (4619 vs. 1855mcg/24 hours, p=0.001) and smaller tumors (5.91 vs. 8.61cm, p=0.046). PASS score greater than or equal to 4 was associated with higher metanephrine levels (5104 vs. 2312mcg/24 hours, p=0.021) and larger tumors (9.28 vs. 6.68 cm, p=0.024). Biochemical cure rate was achieved in 76% of patients after surgery and was associated with older age (37.7 years vs. 27.7 years, p=0.047) and absence of pheochromocytoma spells (100% vs. 61%, p=0.014).

Conclusion. Young age, smaller tumor size and higher metanephrine concentrations were associated with normalization of blood pressure post-surgery. On the other hand, older patients and those without pheochromocytoma spells had better biochemical cure rates. Patients with higher baseline metanephrine levels had increased perioperative complications. More aggressive tumor behavior was associated with higher metanephrine levels and larger tumors. Sex, baseline blood pressure and mode of surgery did not have any influence on treatment outcomes.

Initiating or Switching to Insulin Degludec/Insulin Aspart in Adults With Type 2 Diabetes in the Philippines

Nemencio Nicodemus Jr. — 2024-08-04

Objectives. Blood glucose levels of the majority of Filipino patients with type 2 diabetes (T2D) remain uncontrolled. Insulin degludec/insulin aspart (IDegAsp) is a fixed‑ratio co-formulation of the long‑acting basal insulin degludec and the rapid-acting prandial insulin aspart. The real-world ARISE (A Ryzodeg^® Initiation and Switch Effectiveness) study investigated clinical outcomes across six countries in people with T2D who initiated IDegAsp. This publication presents the clinical outcomes of the Filipino cohort from a subgroup analysis of the ARISE study.

Methodology. This 26-week, open-label, non-interventional study examined outcomes in adults with T2D initiating or switching to IDegAsp (N=185) from other antidiabetic treatments per local clinical guidance.

Results. Compared with baseline, there was a significant improvement in glycated hemoglobin at the end of study (EOS) (estimated difference [ED] −1.4% [95% confidence interval −1.7, −1.1]; P<0.0001). Fasting plasma glucose (ED −46.1 mg/dL [−58.2, −34.0]; P<0.0001) and body weight (ED −1.0 kg [−2.0, −0.1]; P=0.028) were significantly reduced at EOS compared with baseline. IDegAsp was associated with a decrease in the incidence of self-reported healthcare resource utilization. Adverse events were reported in eight (4.3%) participants.

Conclusions. Initiating or switching to IDegAsp was associated with improved glycemic control, lower body weight, and lower HRU for people with T2D in the Philippines. No new, unexpected AEs were reported.

Cushing Disease in a Patient with Double Pituitary Adenomas Complicated with Diabetes Insipidus

Wei Hang Kang — 2024-07-31

Managing a patient with both pituitary hypersecretory and hyposecretory manifestations may be perplexing. We report a 14-year-old female who presented with weight gain, polyuria and polydipsia. Biochemical results were consistent with Cushing disease with central diabetes insipidus. Pituitary magnetic resonance imaging showed right adenoma with stalk thickening. The immunohistochemistry staining of both adenomas was positive for adrenocorticotropic hormone, thyroid stimulating hormone, growth hormone and luteinizing hormone. Postoperatively, the patient developed panhypopituitarism with persistent diabetes insipidus. The coexistence of double adenomas can pose diagnostic and management challenges and is a common cause of surgical failure. Intraoperative evaluation is important in the identification of double or multiple pituitary adenomas in a patient presenting with multiple secretory manifestations.

A Focal Form of Diazoxide-Resistant Congenital Hyperinsulinism with Good Response to Long-Acting Somatostatin

Suhaimi Hussain — 2024-07-30

A four-year-old female who was born term via spontaneous vaginal delivery with a birth weight of 3.4 kg had an onset of persistent hypoglycaemia at the 6^th hour of life. She was diagnosed with congenital hyperinsulinism based on high glucose load, negative ketone and a good response to glucagon. Genetic workup revealed the presence of ATP Binding Cassette Subfamily C Member 8 (ABCC8 genes) mutation which indicated a focal form of congenital hyperinsulinism. She was resistant to the standard dose of oral diazoxide but responded to subcutaneous somatostatin. At the age of 3 years and 6 months, multiple daily injections of somatostatin were replaced with a long-acting monthly somatostatin analogue. With the present treatment, she had better glycaemic control, normal growth and was able to stop tube feeding.

Aggressive Synchronous Papillary and Likely Follicular Thyroid Carcinomas in a Patient with Graves’ Disease

Gerald Gui Ren Sng — 2024-07-31

We report a case of an uncommonly aggressive presentation of the rare entity of synchronous papillary (PTC) and follicular thyroid carcinomas (FTC) in a 67-year-old woman initially presenting with thyrotoxicosis from Graves’ disease. She was found to have two thyroid nodules with extensive intra-cardiac tumour thrombus, symptomatic left pelvis bony metastasis with pathological fracture, pulmonary metastases and mediastinal lymph node metastases. Further investigations suggested a diagnosis of synchronous papillary and metastatic follicular thyroid cancer. Treatment with radical surgery followed by adjuvant therapeutic radioiodine ablation was proposed, but the patient declined all forms of cancer-specific therapy and was elected solely for a palliative approach to treatment. We discuss the diagnostic considerations in arriving at the diagnosis of synchronous thyroid malignancy – in this case the clear features of PTC and the strong probability of FTC due to invasiveness and metastatic follicular lesions. This case underscores potential limitations of the ACR TI-RADS system, notably with certain ultrasonographic features suggesting malignancy that might not be adequately captured. Notably, the aggressive presentation of DTC in this case may be contributed by the concurrent presence of Graves’ Disease, suggesting heightened vigilance when assessing potential thyroid malignancies in such patients.

R243W Mutation in Thyroid Hormone Resistance Syndrome Beta

Jia Cheng Ong — 2024-07-30

A three-year-old female with a history of recurrent tonsillitis was investigated for failure to thrive and global developmental delay. Clinically, she had a triangular face with low-set ears and intermittent tachycardia. She had growth failure with her weight under the third centile while her height was within normal limits. Other systemic examinations were unremarkable. The presence of an elevated free T4 (FT4) with an inappropriately high thyroid stimulating hormone (TSH) in this patient raised the clinical suspicion of Thyroid Hormone Resistance Syndrome. DNA sequencing confirmed the diagnosis, which showed R243W gene mutation in Thyroid Hormone Receptor-Beta1 (THRB1).

Windswept Deformity

Pankaj Ferwani — 2024-07-31

Primary hyperparathyroidism (PHPT) in adolescents is rare and has severe manifestations as compared to adults. Skeletal involvement in primary hyperparathyroidism in the form of deformities like genu valgus, genu varus and cubitus varus is rare and limited to case reports and case series. There is only one case of genu varus with genu valgus on the contralateral extremity (windswept deformity) that has been reported to date in the literature. We report the case of a 19-year-old male who presented with isolated progressive bending of his legs at the knee (windswept deformity) for three years. He was found to have hypercalcemia, hypophosphatemia, high alkaline phosphatase, high intact parathyroid hormone (iPTH), normal 25-hydroxy vitamin D level and a normal kidney function test. A diagnosis of primary hyperparathyroidism was made. On imaging studies, a left inferior parathyroid adenoma was localized and was successfully removed surgically. Serum calcium and iPTH normalized post-operatively. The patient is being planned for corrective osteotomy after stabilization of alkaline phosphatase levels.

Before Low Serum Cortisol Can Be Attributed to SARS-Cov-2 Infection, Alternative Causes Must Be Ruled Out

Josef Finsterer — 2024-07-30

We read with interest Banu et al.,’s article about a cross-sectional study of adrenal function using blood levels of cortisol and adrenocorticotropic hormone (ACTH) in 91 patients with acute SARS-CoV-2 infection. It was found that 27% of patients with severe COVID-19, 26% with mild COVID-19 and 4% with moderate COVID-19 had adrenal insufficiency. Decreased cortisol reserve was found in 6.6% of all patients. It was concluded that the adrenocortical response was impaired in a significant number of non-critically ill COVID-19 patients, with the percentage being highest in patients with severe COVID-19 disease.¹ The study is impressive, but some points should be discussed.

The major limitation of the study is that imaging of the pituitary gland and hypothalamus was not performed. To rule out pituitary adenoma, hypophysitis, pituitary apoplexy, pituitary abscess, sellar tuberculoma, or hypothalamic stroke or bleeding, magnetic resonance imaging (MRI) of the pituitary gland and the hypothalamus with contrast agent must be performed. Like any other infection, SARS-CoV-2 infection can trigger the appearance of symptoms of a pituitary pathology.²

A second limitation is that imaging of the suprarenal glands was not performed. To assess whether there was adrenal atrophy, adenoma, ischemia, bleeding, or carcinoma, adrenal imaging is mandatory. ³

A third limitation is that current medication was not reported. Several medications are known to affect serum cortisol levels, making it imperative to know all medications regularly taken by the included patients. Ketoconazole, isilodrostat, vitamin D and omega-3 fatty acids in particular are known to be able to reduce cortisol levels in the blood.⁴

A fourth limitation is that no ACTH stimulation test was performed to determine whether primary or secondary suprarenal insufficiency was present. Determining cortisol levels alone without ACTH stimulation testing is not reliable with regard to cortical adrenal function.

A fifth limitation is that serum dehydroepiandrosterone (DHEA) levels were not measured. Since DHEA is the antagonist of cortisol and decreases with age, it is conceivable that high levels of DHEA promoted the reduction of serum cortisol.⁵

Since low thyroxine levels may be associated with low cortisol levels,⁶ it would also be desirable to know whether thyroid function was normal or abnormal in the included patients.

In summary, the excellent study has limitations that should be addressed before drawing final conclusions. Clarifying the weaknesses would strengthen the conclusions and could improve the study. Serum cortisol levels may be low not only due to SARS-CoV-2 infection but also due to several other causes. Before adrenal insufficiency can be attributed solely to inadequate cortical cortisol production, the entire hypothalamic-pituitary-adrenal axis must be thoroughly examined.