Diagnosis and Treatment > Investigation > Uric acid (blood)
You are looking at 1 - 3 of 3 items
Search for other papers by Maria P Yavropoulou in
Google Scholar
PubMed
Search for other papers by Efstathios Chronopoulos in
Google Scholar
PubMed
Search for other papers by George Trovas in
Google Scholar
PubMed
Search for other papers by Emmanouil Avramidis in
Google Scholar
PubMed
Search for other papers by Francesca Marta Elli in
Google Scholar
PubMed
Search for other papers by Giovanna Mantovani in
Google Scholar
PubMed
Search for other papers by Pantelis Zebekakis in
Google Scholar
PubMed
Search for other papers by John G Yovos in
Google Scholar
PubMed
Summary
Pseudohypoparathyroidism (PHP) is a heterogeneous group of rare endocrine disorders characterised by normal renal function and renal resistance to the action of the parathyroid hormone. Type 1A (PHP1A), which is the most common variant, also include developmental and skeletal defects named as Albright hereditary osteodystrophy (AHO). We present two cases, a 54- and a 33-year-old male diagnosed with PHP who were referred to us for persistently high levels of serum calcitonin. AHO and multinodular goitre were present in the 54-year-old male, while the second patient was free of skeletal deformities and his thyroid gland was of normal size and without nodular appearance. We performed GNAS molecular analysis (methylation status and copy number analysis by MS-MLPA) in genomic DNA samples for both patients. The analysis revealed a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1, in the patient with the clinical diagnosis of PHP1A. This amino acid change appears to be in accordance with the clinical diagnosis of the patient. The genomic DNA analysis of the second patient revealed the presence of the recurrent 3-kb deletion affecting the imprinting control region localised in the STX16 region associated with the loss of methylation (LOM) at the GNAS A/B differentially methylated region and consistent with the diagnosis of an autosomal dominant form of PHP type 1B (PHP1B). In conclusion, hypercalcitoninaemia may be encountered in PHP1A and PHP1B even in the absence of thyroid pathology.
Learning points:
-
We describe a novel missense variant c.131T>G p.(Leu44Pro) affecting GNAS exon 1 as the cause of PHP1A.
-
Hypercalcitoninaemia in PHP1A is considered an associated resistance to calcitonin, as suggested by the generalised impairment of Gsα-mediated hormone signalling.
-
GNAS methylation defects, as in type PHP1B, without thyroid pathology can also present with hypercalcitoninaemia.
Search for other papers by Elena Carrillo in
Google Scholar
PubMed
Search for other papers by Amparo Lomas in
Google Scholar
PubMed
Search for other papers by Pedro J Pinés in
Google Scholar
PubMed
Search for other papers by Cristina Lamas in
Google Scholar
PubMed
Summary
Mutations in hepatocyte nuclear factor 1β gene (HNF1B) are responsible for a multisystemic syndrome where monogenic diabetes (classically known as MODY 5) and renal anomalies, mostly cysts, are the most characteristic findings. Urogenital malformations, altered liver function tests, hypomagnesemia or hyperuricemia and gout are also part of the syndrome. Diabetes in these patients usually requires early insulinization. We present the case of a young non-obese male patient with a personal history of renal multicystic dysplasia and a debut of diabetes during adolescence with simple hyperglycemia, negative pancreatic autoimmunity and detectable C-peptide levels. He also presented epididymal and seminal vesicle cysts, hypertransaminasemia, hyperuricemia and low magnesium levels. In the light of these facts we considered the possibility of a HNF1B mutation. The sequencing study of this gene confirmed a heterozygous mutation leading to a truncated and less functional protein. Genetic studies of his relatives were negative; consequently, it was classified as a de novo mutation. In particular, our patient maintained good control of his diabetes on oral antidiabetic agents for a long period of time. He eventually needed insulinization although oral therapy was continued alongside, allowing reduction of prandial insulin requirements. The real prevalence of mutations in HNF1B is probably underestimated owing to a wide phenotypical variability. As endocrinologists, we should consider this possibility in young non-obese diabetic patients with a history of chronic non-diabetic nephropathy, especially in the presence of some of the other characteristic manifestations.
Learning points:
-
HNF1B mutations are a rare cause of monogenic diabetes, often being a part of a multisystemic syndrome.
-
The combination of young-onset diabetes and genitourinary anomalies with slowly progressive nephropathy of non-diabetic origin in non-obese subjects should rise the suspicion of such occurrence. A family history may not be present.
-
Once diagnosis is made, treatment of diabetes with oral agents is worth trying, since the response can be sustained for a longer period than the one usually described. Oral treatment can help postpone insulinization and, once this is necessary, can help reduce the required doses.
Search for other papers by Ruben H Willemsen in
Google Scholar
PubMed
Search for other papers by Violeta Delgado-Carballar in
Google Scholar
PubMed
Search for other papers by Daniela Elleri in
Google Scholar
PubMed
Search for other papers by Ajay Thankamony in
Google Scholar
PubMed
Search for other papers by G A Amos Burke in
Google Scholar
PubMed
Search for other papers by James C Nicholson in
Google Scholar
PubMed
Search for other papers by David B Dunger in
Google Scholar
PubMed
Summary
An 11-year-old boy developed severe syndrome of inappropriate antidiuretic hormone secretion (SIADH) after diagnosis of an intracranial B-cell lymphoma. His sodium levels dropped to 118–120 mmol/L despite 70% fluid restriction. For chemotherapy, he required hyperhydration, which posed a challenge because of severe hyponatraemia. Tolvaptan is an oral, highly selective arginine vasopressin V2-receptor antagonist, which has been licensed in adults for the management of SIADH and has been used in treating paediatric heart failure. Tolvaptan gradually increased sodium levels and allowed liberalisation of fluid intake and hyperhydration. Tolvaptan had profound effects on urinary output in our patient with increases up to 8 mL/kg/h and required close monitoring of fluid balance, frequent sodium measurements and adjustments to intake. After hyperhydration, tolvaptan was stopped, and the lymphoma went into remission with reversal of SIADH. We report one of the first uses of tolvaptan in a child with SIADH, and it was an effective and safe treatment to manage severe SIADH when fluid restriction was not possible or effective. However, meticulous monitoring of fluid balance and sodium levels and adjustments of fluid intake are required to prevent rapid sodium changes.
Learning points:
-
Tolvaptan can be used in paediatric patients with SIADH to allow hyperhydration during chemotherapy.
-
Tolvaptan has profound effects on urinary output and meticulous monitoring of fluid balance and sodium levels is therefore warranted.
-
Tolvaptan was well tolerated without significant side effects.
