Diagnosis and Treatment > Signs and Symptoms
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Summary
We describe the case of an African woman who was diagnosed with ketosis-prone diabetes with diabetes-associated autoantibodies, after being admitted for diabetic ketoacidosis (DKA) precipitated by her first presentation of systemic lupus erythematosus (SLE). She had a seven-year history of recurrent gestational diabetes (GDM) not requiring insulin therapy, with return to normoglycaemia after each pregnancy. This might have suggested that she had now developed type 2 diabetes (T2D). However, the diagnosis of SLE prompted testing for an autoimmune aetiology for the diabetes, and she was found to have a very high titre of GAD antibodies. Typical type 1 diabetes (T1D) was thought unlikely due to the long preceding history of GDM. Latent autoimmune diabetes of adults (LADA) was considered, but ruled out as she required insulin therapy from diagnosis. The challenge of identifying the type of diabetes when clinical features overlap the various diabetes categories is discussed. This is the first report of autoimmune ketosis-prone diabetes (KPD) presenting with new onset of SLE.
Learning points:
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DKA may be the first presentation of a multi-system condition and a precipitating cause should always be sought, particularly in women with a history of GDM or suspected T2D.
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All women with GDM should undergo repeat glucose tolerance testing postpartum to exclude frank diabetes, even when post-delivery capillary blood glucose (CBG) tests are normal. They should also be advised to continue CBG monitoring during acute illness in case of new onset diabetes.
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KPD comprises a spectrum of diabetes syndromes that present with DKA, but subsequently have a variable course depending on the presence or absence of beta cell failure and/or diabetes autoantibodies.
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KPD should be considered in a patient with presumed T2D presenting with DKA, especially if there is a personal or family history of autoimmune diabetes.
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LADA should be suspected in adults presumed to have T2D, who do not require insulin therapy for at least six months after diagnosis and have anti-GAD antibodies.
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Patients with autoimmune diabetes have an increased risk of other autoimmune diseases and screening for thyroid, parietal cell, coeliac and antinuclear antibodies should be considered.
Search for other papers by Bronwen E Warner in
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NIHR Biomedical Research Unit in Nutrition, Diet & Lifestyle, University Hospitals Bristol NHS Foundation Trust, Education Centre, Bristol, UK
Search for other papers by Christine P Burren in
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Summary
This case, presenting with bilateral impalpable testes, illustrates the relevance of a broad differential disorders of sex development case management. It provides new insights on hypothalamic–pituitary–gonadal (HPG) axis and testicular function abnormalities in the multisystem disorder of Lowe syndrome. Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare disorder characterised by eye abnormalities, central nervous system involvement and proximal renal tubular acidosis. There are a handful of reports of pubertal delay, infertility and cryptorchidism in Lowe syndrome. Biochemistry aged 72 h: testosterone 6.4 nmol/L, LH <0.5 IU/L and FSH <0.5 IU/L. Gonadotropin-releasing hormone stimulation test identified significantly raised baseline LH = 45.4 IU/L (contrasts with earlier undetectable LH), with a 20% increase on stimulation, while baseline FSH = 4.3 IU/L with no increase on stimulation. Day 14 HCG stimulation test produced an acceptable 50% increase in testosterone. The constellation of further abnormalities suggested Lowe syndrome: hypotonia, bilateral cataracts (surgical extraction and intraocular lens implantation) and renal tubular acidosis (microscopic haematuria, hypercalciuria, proteinuria, generalised aminoaciduria, hypophosphataemia and metabolic acidosis). DNA sequencing identified de novo hemizygous frameshift mutation OCRL c.2409_2410delCT in exon 22. Interpretation of initial and repeat GnRH and HCG testing indicates the likelihood of testicular failure. Partial testicular descent occurred but left orchidopexy was required. Improving long-term gonadal function in Lowe syndrome assumes increased importance for current cohorts as advances in renal replacement therapy have greatly improved life expectancy. Noting HPG axis abnormalities in Lowe syndrome in infancy can identify cases requiring increased surveillance of pubertal progress for earlier detection and management.
Learning points:
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Clinical endocrine problems in Lowe syndrome has been reported, but has focused on abnormalities in adolescence and young adulthood: pubertal delay and infertility.
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We present an infant with isolated LH elevation at baseline and on GnRH stimulation testing who also had bilateral impalpable testes.
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Early testing of the HPG axis in patients with Lowe syndrome may help predict gonadal abnormalities from a younger age, which will enhance the overall case management into adolescence.
