Browse

You are looking at 1 - 10 of 78 items for :

  • Publication Details x
  • Patient Demographics x
Clear All
Maha Khalil Abass Pediatric Endocrinology Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

Search for other papers by Maha Khalil Abass in
Google Scholar
PubMed
Close
,
Aisha Al Shamsi Clinical Genetics Department, Tawam Hospital, Al Ain, United Arab Emirates

Search for other papers by Aisha Al Shamsi in
Google Scholar
PubMed
Close
,
Iftikhar Jan Paediatric Surgery Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates

Search for other papers by Iftikhar Jan in
Google Scholar
PubMed
Close
,
Mohammed Suhail Yasin Masalawala Clinical Trial Unit, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates

Search for other papers by Mohammed Suhail Yasin Masalawala in
Google Scholar
PubMed
Close
, and
Asma Deeb Pediatric Endocrinology Division, Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates
College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates

Search for other papers by Asma Deeb in
Google Scholar
PubMed
Close

Summary

The most frequent causes of pancreatitis classically have been known to be gallstones or alcohol. However, genetics can also play a key role in predisposing patients to both chronic and acute pancreatitis. The serine protease inhibitor Kazal type 1 (SPINK 1) gene is known to be strongly associated with pancreatitis. Patients with these underlying genetic mutations can have severe diseases with a high morbidity rate and frequent hospitalization. We report an Arab girl who presented with acute pancreatitis at the age of 7 years progressing to recurrent chronic pancreatitis over a few years. She had severe obesity from the age of 4 years and developed type 2 diabetes at the age of 12. She had a normal biliary system anatomy. Genetic analysis showed that she had combined heterozygous mutations in the SPINK1 gene (SPINK1, c.101A>G p.(Asn34Ser) and SPINK1, c.56-37T>C). Her parents were first-degree cousins, but neither had obesity. Mother was detected to have the same mutations. She had type 2 diabetes but never presented with pancreatitis. This case is the first to be reported from the Arab region with these combined mutations leading to recurrent chronic pancreatitis. It illustrates the importance of diagnosing the underlying genetic mutation in the absence of other known causes of pancreatitis. Considering the absence of pancreatitis history in the mother who did not have obesity but harboured the same mutations, we point out that severe obesity might be a triggering factor of pancreatitis in the presence of the mutations in SPINK1 gene in this child. While this is not an assumption from a single patient, we show that not all carriers of this mutation develop the disease even within the same family. Triggering factors like severe obesity might have a role in developing the disease.

Learning points

  • Acute recurrent pancreatitis and chronic pancreatitis are uncommon in children but might be underdiagnosed.

  • Biliary tract anomalies and dyslipidaemias are known causative factors for pancreatitis, but pancreatitis can be seen in children with intact biliary system.

  • Genetic diagnosis should be sought in children with pancreatitis in the absence of known underlying predisposing factors.

  • SPINK1 mutations can predispose to an early-onset severe recurrent pancreatitis and acute pancreatitis.

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

Search for other papers by Yotsapon Thewjitcharoen in
Google Scholar
PubMed
Close
,
Soontaree Nakasatien Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand

Search for other papers by Soontaree Nakasatien in
Google Scholar
PubMed
Close
,
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

Search for other papers by Tsz Fung Tsoi in
Google Scholar
PubMed
Close
,
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

Search for other papers by Cadmon K P Lim in
Google Scholar
PubMed
Close
,
Thep Himathongkam Diabetes and Thyroid Center, Theptarin Hospital, Bangkok, Thailand

Search for other papers by Thep Himathongkam in
Google Scholar
PubMed
Close
, and
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

Search for other papers by Juliana C N Chan in
Google Scholar
PubMed
Close

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
Carolina Chaves Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

Search for other papers by Carolina Chaves in
Google Scholar
PubMed
Close
,
Teresa Kay Department of Medical Genetics, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, EPE, Lisbon, Portugal

Search for other papers by Teresa Kay in
Google Scholar
PubMed
Close
, and
João Anselmo Department of Endocrinology and Nutrition, Hospital Divino Espírito Santo de Ponta Delgada, EPER, Azores Islands, Portugal

Search for other papers by João Anselmo in
Google Scholar
PubMed
Close

Summary

Leptin is secreted by adipocytes in response to fat storage and binds to its receptor (LEPR), which is ubiquitously expressed throughout the body. Leptin regulates energy expenditure and is anorexigenic. In this study, we describe the clinical and hormonal findings of three siblings with a personal history of rapid weight gain during the first months of life. They had delayed puberty, high levels of FSH (15.6 ± 3.7 mUI/mL; reference: 1.5–12.4) and LH (12.3 ± 2.2 mUI/mL; reference: 1.7–8.6), normal oestradiol and total testosterone and successful fertility. None of the patients had dyslipidemia, diabetes or thyroid disease. Next-generation sequencing identified a pathogenic homozygous variant c.2357T>C, p.(Leu786Pro) in LEPR. Their parents and children were heterozygous for this mutation. We compared clinical and biochemical findings of homozygous carriers with first-degree heterozygous family members and ten randomly selected patients with adult-onset morbid obesity. Homozygous carriers of the mutation had significantly higher BMI (32.2 ± 1.7 kg/m2 vs 44.5 ± 7.1 kg/m2, P = 0.023) and increased serum levels of leptin (26.3 ± 9.3 ng/mL vs 80 ± 36.4 ng/mL, P = 0.028) than their heterozygous relatives. Compared with the ten patients with adult-onset morbid obesity, serum levels of leptin were not significantly higher in homozygous carriers (53.8 ± 24.1 ng/mL vs 80 ± 36.4 ng/mL, P = 0.149), and thus serum levels of leptin were not a useful discriminative marker of LEPR mutations. We described a rare three-generation family with monogenic obesity due to a mutation in LEPR. Patients with early onset obesity should be considered for genetic screening, as the identification of mutations may allow personalized treatment options (e.g. MC4R-agonists) and targeted successful weight loss.

Learning points

  • The early diagnosis of monogenic forms of obesity can be of great interest since new treatments for these conditions are becoming available.

  • Since BMI and leptin levels in patients with leptin receptor mutations are not significantly different from those found in randomly selected morbid obese patients, a careful medical history is mandatory to suspect this condition.

  • Loss of leptin receptor function has been associated with infertility. However, our patients were able to conceive, emphasizing the need for genetic counselling in affected patients with this condition.

Open access
Adam I Kaplan Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia

Search for other papers by Adam I Kaplan in
Google Scholar
PubMed
Close
,
Catherine Luxford Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia

Search for other papers by Catherine Luxford in
Google Scholar
PubMed
Close
, and
Roderick J Clifton-Bligh Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia
Cancer Genetics Laboratory, Kolling Institute, Royal North Shore Hospital, Sydney, Australia

Search for other papers by Roderick J Clifton-Bligh in
Google Scholar
PubMed
Close

Summary

Biallelic pathological variants in the thyroid stimulating hormone (TSH) subunit β gene (TSHB) result in isolated TSH deficiency and secondary hypothyroidism, a rare form of central congenital hypothyroidism (CCH), with an estimated incidence of 1 in 65 000 births. It is characterised by low levels of free thyroxine and inappropriately low serum TSH and may therefore be missed on routine neonatal screening for hypothyroidism, which relies on elevated TSH. We describe a patient with CCH who developed recurrence of pituitary hyperplasia and symptomatic hypothyroidism due to poor compliance with thyroxine replacement. She was diagnosed with CCH as a neonate and had previously required trans-sphenoidal hypophysectomy surgery for pituitary hyperplasia associated with threatened chiasmal compression at 17 years of age due to variable adherence to thyroxine replacement. Genetic testing of TSHB identified compound heterozygosity with novel variant c.217A>C, p.(Thr73Pro), and a previously reported variant c.373delT, p.(Cys125Valfs*10). Continued variable adherence to treatment as an adult resulted in recurrence of significant pituitary hyperplasia, which subsequently resolved with improved compliance without the need for additional medications or repeat surgery. This case describes a novel TSHB variant associated with CCH and demonstrates the importance of consistent compliance with thyroxine replacement to treat hypothyroidism and prevent pituitary hyperplasia in central hypothyroidism.

Learning points

  • Pathogenic variants in the TSH subunit β gene (TSHB) are rare causes of central congenital hypothyroidism (CCH).

  • c.217A>C, p.(Thr73Pro), is a novel TSHB variant, presented in association with CCH in this case report.

  • Thyroxine replacement is critical to prevent clinical hypothyroidism and pituitary hyperplasia.

  • Pituitary hyperplasia can recur post-surgery if adherence to thyroxine replacement is not maintained.

  • Pituitary hyperplasia can dramatically reverse if compliance with thyroxine replacement is improved to maintain free thyroxine (FT4) levels in the middle-to-upper normal range, without the need for additional medications or surgeries.

Open access
Inês Vieira Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

Search for other papers by Inês Vieira in
Google Scholar
PubMed
Close
,
Sofia Lopes Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

Search for other papers by Sofia Lopes in
Google Scholar
PubMed
Close
,
Margarida Bastos Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

Search for other papers by Margarida Bastos in
Google Scholar
PubMed
Close
,
Luísa Ruas Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

Search for other papers by Luísa Ruas in
Google Scholar
PubMed
Close
,
Dírcea Rodrigues Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Faculty of Medicine of the University of Coimbra, Coimbra, Portugal

Search for other papers by Dírcea Rodrigues in
Google Scholar
PubMed
Close
, and
Isabel Paiva Endocrinology Diabetes and Metabolism Department of Coimbra Hospital and Universitary Centre, Coimbra, Portugal

Search for other papers by Isabel Paiva in
Google Scholar
PubMed
Close

Summary

The coexistence of neurofibromatosis type 1 (NFT1) and Turner syndrome (TS) has only been reported in a few patients and may represent a diagnostic challenge. We describe the case of a 16-year-old girl, with a prior clinical diagnosis of NFT1, who was referred to Endocrinology appointments for the etiological study of primary amenorrhea. Evaluation of the anterior pituitary function was requested and hypergonadotropic hypogonadism was detected. During the etiological study, a 45X karyotype was found and TS was diagnosed. The fact that NFT1 can also be associated with short stature, short broad neck and hypertelorism was likely responsible for TS being diagnosed in late adolescence. As both TS and NFT1 are relatively common genetic disorders, it is important to be alert to the possibility that the presence of one disease does not invalidate the other.

Learning points

  • The concomitant presence of two syndromes in the same patient is unlikely and represents a diagnostic challenge.

  • Some phenotypic characteristics and clinical manifestations may be shared by several syndromes.

  • Some syndromes, such as neurofibromatosis type 1 may have very heterogeneous presentations.

  • It is important to be alert to the characteristics that are not explained by the initial diagnosis.

  • If such features are present, diagnostic work-up must be performed regardless of the initial syndromic diagnosis.

Open access
Eimear Mary O’Donovan Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

Search for other papers by Eimear Mary O’Donovan in
Google Scholar
PubMed
Close
,
Begona Sanchez-Lechuga Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

Search for other papers by Begona Sanchez-Lechuga in
Google Scholar
PubMed
Close
,
Emma Prehn Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

Search for other papers by Emma Prehn in
Google Scholar
PubMed
Close
, and
Maria Michelle Byrne Department of Endocrinology, Mater Misericordiae University Hospital, Dublin, Ireland

Search for other papers by Maria Michelle Byrne in
Google Scholar
PubMed
Close

Summary

The coexistence of autoimmune diabetes and maturity-onset diabetes (MODY) is rare. The absence of pancreatic autoantibodies is a key factor prompting MODY genetic testing. In this study, we report three cases of young-onset diabetes with progressive beta-cell dysfunction, strongly positive glutamic acid decarboxylase (GAD) antibodies, and genetic confirmation of pathogenic gene variants of HNF-1A, HNF-4A, and ABCC8-MODY. The first case is a woman diagnosed with HNF-1A-MODY diabetes more than 30 years after her diagnosis of adult-onset diabetes at 25 years. She required insulin after her fourth pregnancy. She became ketotic on oral hypoglycaemic agents (OHAs) and subsequently, her GAD antibodies tested positive. The second case is a woman diagnosed with diabetes at 17 years who was subsequently diagnosed with HNF-4A-MODY after many hypoglycaemic episodes on low-dose insulin. GAD antibodies were strongly positive. The last case is a man diagnosed with diabetes at 26 years who was well controlled on OHAs and required insulin years later due to sudden deterioration in glycaemic control. His ABCC8-MODY was diagnosed upon realisation of strong family history and his GAD antibodies tested positive. All subjects are now treated with insulin. Less than 1% of subjects with MODY have positive autoantibodies. These cases highlight individuals who may have two different types of diabetes simultaneously or consecutively. Deterioration of glycaemic control in subjects with MODY diabetes should highlight the need to look for the emergence of autoantibodies. At each clinic visit, one should update the family history as MODY was diagnosed in each case after the development of diabetes in their offspring.

Learning points

  • These cases highlight the rare coexistence of autoimmune diabetes and MODY.

  • Deterioration of glycaemic control in subjects with MODY diabetes should highlight the emergence of autoantibodies.

  • One should revise and update the family history as the diagnosis of MODY was made after the development of diabetes in offspring.

  • Understanding the spectrum of diabetes allows for precision medicine.

Open access
Mone Murashita Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Mone Murashita in
Google Scholar
PubMed
Close
,
Norio Wada Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Norio Wada in
Google Scholar
PubMed
Close
,
Shuhei Baba Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Shuhei Baba in
Google Scholar
PubMed
Close
,
Hajime Sugawara Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Hajime Sugawara in
Google Scholar
PubMed
Close
,
Arina Miyoshi Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Arina Miyoshi in
Google Scholar
PubMed
Close
, and
Shinji Obara Department of Diabetes and Endocrinology, Sapporo City General Hospital, Sapporo, Japan

Search for other papers by Shinji Obara in
Google Scholar
PubMed
Close

Summary

We report a 26-year-old Japanese man who visited our outpatient clinic presenting fever immediately after i.m. injection of the second dose of a coronavirus disease 2019 (COVID-19) vaccine (Moderna®). At the first visit, the patient had a fever of 37.7°C and a swollen thyroid gland with mild tenderness. He was diagnosed with subacute thyroiditis (SAT) based on the presence of thyrotoxicosis (free tri-iodothyronine, 32.3 pg/mL; free thyroxine, >7.77 ng/dL; and thyroid-stimulating hormone (TSH) < 0.01 μIU/mL), high C-reactive protein level (7.40 mg/dL), negative TSH receptor antibody, and characteristic ultrasound findings. His HLA types were A*02:01/24:02, B*15:11/35:01, Cw*03:03, DRB1*09:01/12:01, DQB1*03:03, and DPB1*05: 01/41:01. He was initially administered prednisolone 15 mg/day, following which the fever subsided. After 10 days, he developed limb weakness and could not walk. The serum potassium level decreased to 1.8 mEq/L, which confirmed the diagnosis of thyrotoxic periodic paralysis (TPP). Potassium supplementation was initiated. The muscle weakness gradually decreased. Prednisolone therapy was terminated 6 weeks after the first visit. His thyroid function returned to normal 5 months after the first visit, through a hypothyroid state. To our knowledge, this is the first reported case of TPP-associated SAT following COVID-19 vaccination. Persistent fever following vaccination should be suspected of SAT. Additionally, TPP may be associated with SAT in Asian male patients.

Learning points

  • Following coronavirus disease 2019 (COVID-19) vaccination, subacute thyroiditis may develop regardless of the vaccine type.

  • If persistent fever, anterior neck pain, swelling and tenderness of thyroid gland, and symptoms of thyrotoxicosis are observed immediately after the COVID-19 vaccination, examination in consideration of the onset of subacute thyroiditis is recommended.

  • HLA-B35 may be associated with the onset of subacute thyroiditis after the COVID-19 vaccination.

  • Although rare, subacute thyroiditis can be associated with thyrotoxic periodic paralysis, especially in Asian men.

  • Glucocorticoid therapy for subacute thyroiditis may induce thyrotoxic periodic paralysis through hypokalemia.