Steroid-induced diabetes mellitus in children: A case series from Nigeria

Ibironke J Akinola; Gbenga Akinyosoye; Adaobi U Solarin; Motunrayo O Adekunle

doi:10.4103/ajem.ajem_3_22

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CASE REPORT

Year : 2022 | Volume : 12 | Issue : 1 | Page : 53-55

Steroid-induced diabetes mellitus in children: A case series from Nigeria

Ibironke J Akinola¹, Gbenga Akinyosoye², Adaobi U Solarin¹, Motunrayo O Adekunle²
¹ Department of Paediatrics and Child Health, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria; Lagos State University College of Medicine, Ikeja, Lagos, Nigeria
² Department of Paediatrics and Child Health, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria

Date of Submission	27-Mar-2022
Date of Decision	14-Jul-2022
Date of Acceptance	16-Jul-2022
Date of Web Publication	02-Sep-2022

Correspondence Address:
Dr. Ibironke J Akinola
Department of Paediatrics and Child Health, Lagos State University Teaching Hospital, Lagos State University College of Medicine, Ikeja, Lagos
Nigeria

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ajem.ajem_3_22

Abstract

Steroid-induced diabetes mellitus is rarely reported in the pediatric population. In children, high doses of corticosteroids are often used in the treatment of acute leukemias, lymphomas, connective tissue disorders, and rheumatological disorders. One of the many complications of corticosteroid toxicity is transient hyperglycemia and by extension diabetes mellitus. We describe three cases involving Nigerian children managed in a tertiary center for systemic juvenile idiopathic arthritis, acute leukemia, and nephrotic syndrome. Management necessitated the use of high dose steroids, and the development of diabetes mellitus ensued. One child died from complications of the primary disease. Steroid-induced diabetes can be easily diagnosed in the presence of a high index of suspicion and just as easily missed if the focus is only on the primary condition.

Keywords: Autoimmune, diabetes, high-dose steroids, pediatric

How to cite this article:
Akinola IJ, Akinyosoye G, Solarin AU, Adekunle MO. Steroid-induced diabetes mellitus in children: A case series from Nigeria. Afr J Endocrinol Metab 2022;12:53-5

How to cite this URL:
Akinola IJ, Akinyosoye G, Solarin AU, Adekunle MO. Steroid-induced diabetes mellitus in children: A case series from Nigeria. Afr J Endocrinol Metab [serial online] 2022 [cited 2023 Jun 10];12:53-5. Available from: http://www.ajemjournal.org/text.asp?2022/12/1/53/355333

Introduction

The use of steroids in the management of pediatric conditions such as malignancies and rheumatological diseases is on the increase because of increasing awareness and diagnosis of these disorders.^[1] Steroids are associated with complications such as cataract, growth faltering, hypertension, obesity, and diabetes mellitus (DM). DM is possibly the least reported of these complications in children. DM is a group of metabolic diseases with varying etiology characterized by persistent hyperglycemia resulting from a defect in action and/or the excretion of insulin. Diagnosis of steroid-induced diabetes mellitus (SIDM) is based on the presence of either a fasting blood glucose level of ≥7.0 mmol/L (126 mg/dL) or a random blood glucose (RBG) level of ≥11.1 mmol/L (200 mg/dL) on at least two different occasions. A glycated hemoglobin value of ≥6.5% is strongly supportive of the diagnosis.^[2],[3]

The mechanism by which systemic steroid causes diabetes is multifactorial and includes opposing glucose action, decreasing glucose utilization, increasing protein breakdown, and the activation of lipolysis, thereby providing amino acids and glycerol for gluconeogenesis.^[4] The risk of occurrence of SIDM rises with an increasing dosage and the duration of steroid use.^[5] SIDM in children may present with nonspecific symptoms and may be missed as there are no separate guidelines for the diagnosis of SIDM. Apparent underdiagnosis and a paucity of data in children may be attributable to these factors. Even though SIDM often resolves after the withdrawal or reduction of the offending drug,^[5] children with SIDM have an increased risk of developing type 2 diabetes (T2DM) in the future.^[5] It is important to be cognizant of the risk of development of SIDM in children placed on high-dose steroids for other conditions.

Three cases of SIDM who presented between 2019 and 2021 are described. Informed consent to publish the reports was obtained from the parents of the children.

Case series

Case 1

OA, a 12-year-old male patient, presented with complaints of fever, bone and joint pain, and pallor of a month duration. He had severe right hypochondriac abdominal pain and multiple evanescent skin eruptions. He had multiple blood transfusions, antibiotics, and analgesics prior in a private hospital where he had been on admission before referral. There was no family history of similar illness nor DM. Weight and height were 45 kg (65th centile, 1 z score) and 149 cm (36th centile, >1 z score), respectively. He was pale and had generalized lymphadenopathy and hepatosplenomegaly. Peripheral blood film was normal, and chest radiograph revealed cardiomegaly with a cardio-thoracic ratio of 65% and left-sided pleural effusion, whereas echocardiography showed a 28 mm circumferential pericardial effusion. The initial diagnosis of acute leukemia was revised to systemic juvenile idiopathic arthritis considering the age, the duration of joint pain, and systemic clinical features based on International League of Association for Rheumatology (ILAR) criteria.^[4] RBG was 75 mg/dL and urinalysis was normal. Further investigations are shown in [Table 1].

Table 1: Summary of laboratory results

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He received high-dose steroids from the 18th day of admission (intravenous methylprednisolone, 250 mg daily) along with intravenous meropenem, aspirin, and omeprazole. Five days later, he complained of excessive urination and had a urine output of 6 mL/kg/h. RBG ranged between 565 mg/dL and 600 mg/dL with HbA1C of 17.5%. Repeat urinalysis showed 2+ glucose and negative ketones. The diagnosis of SIDM was made, and he was commenced on subcutaneous soluble insulin initially at 0.1 u/kg/h until blood glucose was 250 mg/dL at which time insulin regimen was changed to premixed insulin at 18 IU (am) and 9 IU (pm). Steroid was changed to oral prednisolone 20 mg 12 hourly and then tailed downward over 2 weeks. All symptoms including those of the primary disease subsided, and he was subsequently discharged home on the 30th day of admission on insulin and other ancillary medications. Insulin was discontinued in clinic 2 weeks later, and he has being followed up in view of the risk of developing T2DM later in life.

Case 2

BA, a 7-year-old male patient, presented at our facility with complaints of recurrent fever, generalized bone pains, weakness, and weight loss of a month duration. There was a history of bleeding gums and multiple skin rashes. There was no family history of malignancies or family history of diabetes. He was in anemic heart failure with respiratory rate of 80 cpm, heart rate of 160 bpm, and tender hepatomegaly. Weight and height were 18 kg (<3rd centile, >−2 z score) and 160 cm (>99th centile, >6 z score), respectively. He was transfused with two units of packed red cells and four units of platelet concentrates as packed cell volume was 10% and platelet count was 35 × 10⁹ cells. Urinalysis was negative for glucose and RBG was 80 mg/dL at admission. Peripheral blood film showed the presence of 35% lymphoblasts, which was confirmed with bone marrow aspiration. The diagnosis of acute lymphoblastic leukemia was made. Chemotherapy was started on the third week of admission with high-dose steroids (oral dexamethasone at 6 mg/m²/day for 28 days) as a part of the regimen. He developed polydipsia and polyuria 3 weeks after commencing steroids. RBG and HbA1C were 680 mg/dL and 19.5%, respectively, at this time. Urinalysis showed 3+ of glucose and was negative for ketones. He was commenced on subcutaneous soluble insulin initially at 0.1 u/kg/h until blood glucose reached 250 mg/dL when insulin regimen was changed to premixed insulin at 8 IU (am) and 5 IU (pm). Steroid was tapered down cautiously, and RBG over the next 4 days ranged between 240 mg/dL and 365 mg/dL. He achieved remission after 1 month of induction chemotherapy while still on subcutaneous insulin therapy with RBG in the range of 185 mg/dL and 198 mg/dL. He however died from complications of febrile neutropenia, while he was being worked up for the consolidation phase of his chemotherapy.

Case 3

OT, a 12-year-old female patient, presented with a 4-month history of recurrent facial and body swelling and a week history of reduced urinary output and frothy urine. There was no family history of diabetes. On examination, she had generalized edema and weighed 60 kg (94th centile, >1 z score) with height of 151 cm (36th centile, <−1 z score). Urinalysis showed 3+ protein and negative for both blood and glucose. Serum albumin, total cholesterol, and RBG were 14 g/L (low), 350 mg/dL (high), and 68 mg/dL (normal), respectively. A diagnosis of nephrotic syndrome was made, and she was commenced on oral corticosteroids at 60 mg/m² daily for 6 weeks. She defaulted from the clinic and represented 15 weeks later with polyuria and progressive weight loss of 2 weeks duration. Urinalysis showed glucose of 2+, negative ketones, and trace protein. RBG and HbA1C were 578 mg/dL and 8.1%, respectively. She was admitted and commenced on subcutaneous soluble insulin initially at 0.1 u/kg/h until blood glucose reached 250 mg/dL when insulin regimen was changed to premixed insulin at 10 IU (am) and 6 IU (pm). Hyperglycemia gradually subsided, and urine glucose became negative within a week. She is currently on cyclosporine for her nephrotic syndrome and is being followed up in the clinic.

Discussion

SIDM is defined as the abnormal rise in blood glucose associated with glucocorticoid use in patients with or without previous diabetes.^[6] SIDM is quite common in the adult population.^[6] This is different in children where it is reported to be rare.^[5] In our patients, arriving at the diagnosis of SIDM did not pose difficulty probably because the patients presented to a tertiary center where clinicians had a high index of suspicion once symptoms of diabetes mainly polydipsia and polyuria were noticed in the cases presented especially because they were recently placed on steroids. In other centers where experience with SIDM may be low, the diagnosis may not be made as easily until much later in the disease progression. In our patients, the laboratory findings of hyperglycemia, glucosuria, and high HbA1C were consistent with the diagnosis of DM.^[6]

Our patients did not have peculiar predisposing features to developing diabetes such as positive family history of diabetes or obesity. Unlike in earlier reported cases,^[7],[8] our patients did not develop diabetic ketoacidosis (DKA). This is probably because diagnosis was made early in the progression of the diabetes before the complication of DKA could set in. As demonstrated in our patients, SIDM is often transient and may be easier to treat if diagnosed early. Generally, there are no clear and separate guidelines to the treatment of SIDM; however, some authors have recently provided protocols for adults.^[9] Insulin therapy is considered the treatment of choice in children^[5] probably because it is safer, and oral hypoglycemic agents are largely unlicensed for use in this age group. Our patients were managed in the acute phase with soluble insulin and thereafter maintained on subcutaneous premixed insulin until resolution. This was similar to the approach to management by earlier authors.^[7],[8] The two cases described by Nigerian authors primarily had nephrotic syndrome and responded well to treatment for the complicating SIDM. Although one of our case series had the same diagnosis and a good outcome, we lost one patient to complications of acute leukemia, the primary disease.

Conclusion

Our series shows that SIDM may not be as rare in the pediatric population as once thought. With the increasing use of high-dose steroids for rheumatological, renal, and malignant conditions, it is important to be aware of the possibility of the development of SIDM. High index of suspicion should be maintained in any child on high-dose steroids while monitoring for signs and symptoms of SIDM. Obtaining a simple point of care, random glucose checks at baseline and in the course of treatment should be a standard practice for children receiving steroids for various conditions.

Acknowledgments

The authors are thankful to the study participants and their parents for granting permission to report the cases.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Authors’ contributions

IJA conceptualized the study; IJA and GA drafted the initial report; IJA, GA, AUS, and MOA revised the report and approved the final draft.

References

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