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Gaayathri Krishnan Endocrinology Unit, Department of Internal Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

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Nur Hidayah Mohd Makhatar Endocrinology Unit, Department of Internal Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

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Tee Hwee Ching Endocrinology Unit, Department of Internal Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

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Serena Khoo Endocrinology Unit, Department of Internal Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, Malaysia

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Summary

Pituitary tuberculoma is extremely rare and may pose as a diagnostic challenge especially when encountered as an isolated lesion without other systemic manifestation of tuberculosis. A 21-year-old female was admitted for diabetic ketoacidosis. On the third day of admission following the resolution of diabetic ketoacidosis she developed a sudden onset of headache and blurring of vision suggestive of pituitary apoplexy. An urgent MRI brain revealed a large sellar mass with erosion into the sphenoid sinus and intracranial vasculitis. Transphenoidal surgery was done for tumour debulking which allowed histopathological examination of the sellar mass. Immunohistochemical examination of the sellar mass was positive for Gene Xpert MTB/Rif suggesting a tuberculoma. Anti-tuberculous therapy was commenced with full recovery of pituitary hormonal profile seen 7 months post-treatment. In regions with a high incidence of tuberculosis, a tuberculoma should be a considered in a diagnostic evaluation of a sellar lesion.

Learning points

  • In an endemic area of tuberculosis, tuberculoma should be considered as a differential diagnosis when evaluating sellar lesions.

  • Pituitary tuberculoma can present with pituitary apoplexy-like symptoms.

  • Prompt diagnosis and treatment may lead to recovery of pituitary function.

Open access
Debby Christiana Soemitha Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Deshinta Putri Mulya Division of Allergy and Immunology, Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Hemi Sinorita Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

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Summary

Diabetes foot ulcer (DFU) is a common long-term complication of diabetes. Intractable chronic wounds to standard care of diabetic foot raise the question of whether other factors intervene in disease development. We report a case of a 54-year-old male patient who came to Sardjito General Hospital with leg pain and previous history of multiple debridement and amputation for DFU referred from a remote hospital yet no improvement was evident in the surrounding lesion following treatment. Consequently, a histopathological examination was carried out proving the presence of other aetiologic factors, vasculitis and panniculitis existing in the lesion. In this case, we report a rare type of causative factor of foot ulcers among diabetic patients. Vasculitis suspected for polyarteritis nodosa accompanied by panniculitis is considered in this patient. The treatment of choice is corticosteroids or immunosuppressants based on the clinical condition, contrary to usual wound care in DFU. Based on the evidence, clinicians need to consider other causes than only macrovascular complications in a diabetic patient with DFU that is intractable to standard wound care. In this patient, vasculitis may be considered in forming diabetic foot ulcers alongside macrovascular complications.

Learning points

  • A thorough examination is essential to rule out other processes in intractable DFU patients.

  • Prompt management based on proper diagnosis is crucial to prevent peripheral arterial disease complications.

  • Vasculitis and macrovascular complication are inseparable processes forming DFU in this patient.

Open access
Hendra Zufry Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia
Innovation and Research Center of Endocrinology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Putri Oktaviani Zulfa Innovation and Research Center of Endocrinology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Rosdiana Rosdiana Department of Internal Medicine, Tengku Abdullah Syafii Hospital, Beureunuen, Pidie, Aceh, Indonesia

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Krishna Wardhana Sucipto Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Agustia Sukri Ekadamayanti Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Sarah Firdausa Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Summary

Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient’s Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient’s good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome.

Learning points

  • Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland.

  • Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings.

  • Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities

Open access
Natalie Below Diabetes Centre, Gartnavel General Hospital, Glasgow, UK
University of Glasgow, Glasgow, UK

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Deborah Morrison Diabetes Centre, Gartnavel General Hospital, Glasgow, UK

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Ruth McGowan West of Scotland Centre for Genomic Medicine, Glasgow, UK

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Gregory C Jones Diabetes Centre, Gartnavel General Hospital, Glasgow, UK

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Summary

A 20-year-old South Asian male presented with polyuria, polydipsia, HbA1c 81 mmol/mol, BMI 28.8 and family history of both type 1 and type 2 diabetes mellitus. As autoantibody testing was negative and c-peptide level demonstrated significant endogenous insulin secretion, type 1 diabetes was excluded. Given his age and family history, the differential diagnosis included maturity-onset diabetes of the young (MODY), a rare form of diabetes caused by a single-gene variant. A high probability of MODY was calculated and he was subsequently referred for genetic testing. Although a useful tool, the pre-test probability calculator for MODY is only validated in White Europeans. A heterogenous variant of unknown clinical significance of the NEUROD1 gene was detected, leading to gliclazide use with poor response. The patient responded well to metformin. Type 2 diabetes was considered the most likely diagnosis. This case highlights the diagnostic challenges in young patients of Asian ethnicity and the importance of interpreting genetic results of unknown significance within the clinical context. Ethnicity-specific BMI thresholds should be used when classifying patients as overweight or obese.

Learning points

  • Variants of unknown significance detected by genetic sequencing should be interpreted within the context of the patient’s other clinical parameters.

  • It is important to use ethnicity-specific BMI thresholds for obesity.

  • Diagnosis of type 2 diabetes mellitus at younger ages is becoming increasingly common.

  • The pre-test probability calculator for MODY is only validated in White Europeans; although a useful guide, results should be interpreted with caution in patients of other ethnicities.

Open access
Bruno Bouça Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Mariana Cascão Intensive Care Unit - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

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Pedro Fiúza Department of Internal Medicine, Unit 7.2 - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal

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Sara Amaral Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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Paula Bogalho Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal

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José Silva-Nunes Department of Endocrinology, Diabetes and Metabolism - Centro Hospitalar Universitário de Lisboa Central, Lisbon, Portugal
Nova Medical School/ Faculdade de Ciencias Medicas, Universidade Nova de Lisboa, Lisbon, Portugal
Health and Technology Research Center (H&TRC), Escola Superior de Tecnologia da Saude de Lisboa, Lisbon, Portugal

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Summary

17-Alpha-hydroxylase deficiency (17OHD) is a rare autosomal recessive disease, representing 1% of cases of congenital adrenal hyperplasia. A 44-year-old female presented to the emergency department complaining of generalized asthenia and polyarthralgia for about 2 weeks. On examination, she was hypertensive (174/100 mmHg), and laboratory results revealed hypokalemia and hypocortisolism. She had an uncharacteristic morphotype, BMI of 16.7 kg/m2, cutaneous hyperpigmentation, and Tanner stage M1P1, with normal female external genitalia. She reported to have primary amenorrhea. Further analytical evaluations of her hormone levels were performed CT scan revealed adrenal bilateral hyperplasia and absence of female internal genitalia. A nodular lesion was observed in the left inguinal canal with 25 × 10 mm, compatible with a testicular remnant. Genetic analysis identified the c.3G>A p.(Met1?) variant in homozygosity in the CYP17A1 gene, classified as pathogenic, confirming the diagnosis of 17OHD. Karyotype analysis was compatible with 46,XY. The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favored the diagnosis of 17OHD, confirmed by genetic testing. As in other published clinical cases, diagnosis outside pediatric age is not rare and should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

Learning points

  • The association of severe hypokalemia, hypertension, hypocortisolism, and oligo/amenorrhea and the absence of secondary sexual characteristics favor the diagnosis of 17-alpha-hydroxylase deficiency (17OHD).

  • Diagnosis outside pediatric age is not rare.

  • 17OHD should be considered when severe hypokalemia occurs in hypertensive adults with a lack of secondary sexual characteristics.

Open access
Samuel R Miller Medical Oncology, Royal North Shore Hospital, Sydney, Australia

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Shejil Kumar Endocrinology, Royal North Shore Hospital, Sydney, Australia

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Alexander Yuile Medical Oncology, Royal North Shore Hospital, Sydney, Australia

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Alexander M Menzies Melanoma Institute Australia; The University of Sydney; Faculty of Medicine and Health; The University of Sydney, Royal North Shore and Mater Hospitals, Sydney, Australia

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Summary

Hypercalcaemia is a common complication seen in malignancy, frequently due to paraneoplastic parathyroid hormone-related peptide production or osteolytic bony metastases. We present a 58-year-old female with immunotherapy-mediated hypophysitis causing secondary cortisol deficiency resulting in severe glucocorticoid-responsive hypercalcaemia. Whilst hypophysitis is a well recognised adverse event in those receiving immunotherapy for advanced malignancy, it does not typically present with hypercalcaemia. The mechanism responsible for hypercalcaemia due to hypocortisolaemia has not been fully elucidated although hypotheses include the effects of volume depletion and thyroxine’s action on bone. Prompt treatment with glucocorticoids caused an improvement in the patient’s symptoms and corrected her hypercalcaemia which later returned after an attempted glucocorticoid wean. With the increasing uptake of immunotherapy, clinicians should be aware of this unusual presentation of immunotherapy-related hypophysitis and secondary hypocortisolaemia which can be life-threatening if the diagnosis is delayed.

Learning points

  • Immunotherapy can cause inflammation of the pituitary gland resulting in secondary hypocortisolaemia, which can, though rarely, present as hypercalcaemia.

  • Secondary hypocortisolaemia requires prompt recognition and treatment with glucocorticoids. Glucocorticoid replacement leads to rapid clinical and biochemical improvement in these patients.

  • The differential diagnosis for glucocorticoid-responsive hypercalcaemia extends beyond granulomatous disorders (e.g. sarcoidosis, tuberculosis) to adrenocorticotrophic hormone and cortisol deficiency, particularly in patients receiving immunotherapy.

  • Hypocortisolaemia can lead to hypercalcaemia through various proposed mechanisms. Low serum glucocorticoids are associated with reduced blood volume, thus reducing renal calcium excretion. In addition, without glucocorticoid’s inhibitory action, thyroxine appears to drive calcium mobilisation from bone.

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Jananie Suntharesan Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

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Louise Apperley Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

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Senthil Senniappan Department of Endocrinology, Alder Hey Children’s Hospital, Eaton Road, Liverpool, UK

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Summary

A male phenotype accompanied by a 45,X karyotype is rare. It may occur due to Y chromosomal translocation or insertion to X/autosome. Clinical presentation may vary depending on the presence of the Y chromosomal locus and the degree of loss of autosome material. 45,X males can present with short stature and Turner syndrome phenotype due to haploinsufficiency of genes which are normally expressed in both X and Y chromosomes. The presence of the sex-determining region Y (SRY) gene leads to the differentiation of bipotential gonads to testis. Most individuals go through puberty normally, but some may need pubertal induction for delayed puberty. Rarely some can have a pubertal arrest. The risk of gonadoblastoma is minimal in these individuals due to functioning testicular tissue. The azoospermia factor (AZF) region is found on the long arm of the Yq chromosome and is needed for spermatogenesis. In a 45,X male with unbalanced translocation of Y chromosome, spermatogenesis can be affected due to the lack of AZF leading to Sertoli cell-only syndrome. This will have an implication on fertility in adult life. We present a 14-year-old boy with developmental delay, learning difficulties and subtle dysmorphic features who was diagnosed with 45,X,der(2)t(Y:2)(?:p25). Fluorescence in situ hybridisation analysis revealed translocation of SRY (Yp11.3) to the terminal part of the short arm of chromosome 2 resulting in the deletion of most of the Y chromosome (Yp11.2-q12) and part of chromosome 2(2p25.3). This is the first case where SRY translocation to chromosome 2 presents with the above clinical presentation.

Learning points

  • 45,X karyotype is rare in male.

  • It may occur due to SRY translocation or an insertion to X/autosome.

  • SRY gene translocation to chromosome 2 has been not reported in the literature.

  • Clinical presentation can be varied due to degree of loss of chromosomal material.

  • Due to loss of AZF region found on the long arm of the Yq, spermatogenesis can be affected. Loss of 2p25 leads to learning difficulty and obesity.

Open access
Cody Harper Faculty of Medicine, Dalhousie University, Saint John, NB, Canada

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James Michael Division of Medical Oncology, Department of Oncology, Saint John Regional Hospital, Saint John, NB, Canada

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Tarek Rahmeh Department of Pathology, Saint John Regional Hospital, Saint John, NB, Canada

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Vicki Munro Division of Endocrinology & Metabolism, Department of Medicine, Dalhousie University, Halifax, NS, Canada

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Summary

The most common sites of distant metastases of papillary thyroid carcinoma (PTC) are lung and bone. Widespread distant metastases of PTC are rare and associated with poor overall prognosis. Metastases to sites such as liver and pancreas are extremely rare, and literature is sparse on overall survival. In this report, we present a 57-year-old man whose initial presentation of PTC was with pancreatic, liver, and lung metastases, and subsequently developed metastases to bone and brain. He underwent a total thyroidectomy, neck dissection, and tracheal resection. Pathology revealed a predominant columnar cell variant PTC with focal areas of tall cell variant, and genomic sequencing showed both PIK3CA and BRAF gene mutations. Radioactive iodine ablation with I-131 did not show any uptake in metastatic sites and he had progression of the metastases within 6 months. Therefore, therapy with lenvatinib was initiated for radioactive iodine refractory disease. Our patient has tolerated the lenvatinib well, and all his sites of metastases decreased in size. His liver and pancreatic lesions took longer to respond but showed response 6 months after initiation of lenvatinib, and he remains on full dose lenvatinib 18 months into treatment.

Learning points

  • Papillary thyroid carcinoma (PTC) usually metastasizes to lung and bone but can rarely occur in many other sites.

  • Patients with distant metastases have significantly worse long-term prognosis.

  • Lenvatinib can be an effective treatment of radioactive iodine refractory PTC with rare sites of distant metastases.

  • Lenvatinib can be an effective treatment of PTC with BRAF V600E and PIK3CA mutation.

Open access
Mike Lin Department of Endocrinology, Concord Repatriation General Hospital, Concord NSW, Australia

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Kirtan Ganda Department of Endocrinology, Concord Repatriation General Hospital, Concord NSW, Australia
The University of Sydney Concord Clinical School, Concord NSW, Australia.

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Summary

We present the case of a 60-year-old female who developed repeated atraumatic stress fractures. She was initially diagnosed with osteoporosis based on her dual-energy X-ray absorptiometry (DXA) scan bone mineral density (BMD) T-scores and started on denosumab therapy. Secondary osteoporosis screen revealed abnormal myeloma screen and low serum phosphate levels. It was thought that the patient had multiple myeloma with associated Fanconi-related tubular dysfunction. However, fibroblast growth factor-23 (FGF-23) levels were grossly elevated, making Fanconi syndrome unlikely. The patient was subsequently diagnosed with two separate conditions, namely cardiac amyloid light-chain (AL) amyloidosis and FGF-23-related hypophosphataemia, likely due to tumour-induced osteomalacia. This case highlights the importance of excluding osteomalacia as a cause of low BMD and checking FGF-23 levels in the workup for hypophosphataemia.

Learning Points

  • Tumour-induced osteomalacia is a difficult diagnosis as the tumour is often small and slow growing. Imaging may fail to identify a tumour, and treatment therefore consists of calcitriol and phosphate replacement.

  • Tumour-induced osteomalacia should be suspected in the adult presenting with new-onset hypophosphataemia, elevated FGF-23 levels and isolated renal phosphate wasting.

  • Serum phosphate is not part of the routine chemistry panels. Routinely checking phosphate levels prior to initiating antiresorptive therapy is warranted.

  • DXA cannot distinguish low bone mineral density due to osteoporosis from osteomalacia. Antiresorptive therapy should be avoided in osteomalacia due to the risk of clinical and radiographic deterioration.

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Yotsapon Thewjitcharoen Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand

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Soontaree Nakasatien Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand

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Tsz Fung Tsoi Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

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Cadmon K P Lim Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China

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Thep Himathongkam Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand

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Juliana C N Chan Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China
Asia Diabetes Foundation, Shatin, Hong Kong SAR, China

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Summary

Hepatocyte nuclear factor 1β (HNF1B) gene is located on chromosome 17q12. It is a transcription factor implicated in the early embryonic development of multiple organs. HNF1B-associated disease is a multi-system disorder with variable clinical phenotypes. There are increasing reports suggesting that the 17q12 deletion syndrome should be suspected in patients with maturity-onset diabetes of the young type 5 (MODY5) due to the deletion of HNF1B gene. In contrast to classical 17q12 syndrome in childhood with neurological disorders and autism, patients with HNF1B-MODY deletion rarely had neuropsychological disorders or learning disabilities. The diagnosis of 17q12 deletion syndrome highlighted the phenotypic heterogeneity of HNF1B-MODY patients. In this study, we report the clinical course of a Thai woman with young-onset diabetes mellitus and hypertriglyceridemia as a predominant feature due to HNF1B deletion as part of the 17q12 deletion syndrome. Our findings and others suggest that hypertriglyceridemia should be considered a syndromic feature of HNF1B-MODY. Our case also highlights the need to use sequencing with dosage analyses to detect point mutations and copy number variations to avoid missing a whole deletion of HNF1B.

Learning points

  • Maturity-onset diabetes of the young type 5 (MODY5) may be caused by heterozygous point mutations or whole gene deletion of HNF1B. Recent studies revealed that complete deletion of the HNF1B gene may be part of the 17q12 deletion syndrome with multi-system involvement.

  • The length of the deletion can contribute to the phenotypic variability in patients with HNF1B-MODY due to whole gene deletion.

  • Using next-generation sequencing alone to diagnose MODY could miss a whole gene deletion or copy number variations. Specialized detection methods such as microarray analysis or low-pass whole genome sequencing are required to accurately diagnose HNF1B-MODY as a component of the 17q12 deletion syndrome.

  • Molecular diagnosis is necessary to distinguish other acquired cystic kidney diseases in patients with type 2 diabetes which could phenocopy HNF1B-MODY.

  • Hypertriglyceridemia is a possible metabolic feature in patients with HNF1B-MODY due to 17q12 deletion syndrome.

Open access