Diagnosis and Treatment > Signs and Symptoms
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Search for other papers by A Chinoy in
Google Scholar
PubMed
Search for other papers by N B Wright in
Google Scholar
PubMed
Search for other papers by M Bone in
Google Scholar
PubMed
Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Search for other papers by R Padidela in
Google Scholar
PubMed
Summary
Hypokalaemia at presentation of diabetic ketoacidosis is uncommon as insulin deficiency and metabolic acidosis shifts potassium extracellularly. However, hypokalaemia is a recognised complication of the management of diabetic ketoacidosis as insulin administration and correction of metabolic acidosis shifts potassium intracellularly. We describe the case of a 9-year-old girl with newly diagnosed type 1 diabetes mellitus presenting in diabetic ketoacidosis, with severe hypokalaemia at presentation due to severe and prolonged emesis. After commencing management for her diabetic ketoacidosis, her serum sodium and osmolality increased rapidly. However, despite maximal potassium concentrations running through peripheral access, and multiple intravenous potassium ‘corrections’, her hypokalaemia persisted. Seventy two hours after presentation, she became drowsy and confused, with imaging demonstrating central pontine myelinolysis – a rare entity seldom seen in diabetic ketoacidosis management in children despite rapid shifts in serum sodium and osmolality. We review the literature associating central pontine myelinolysis with hypokalaemia and hypothesise as to how the hypokalaemia may have contributed to the development of central pontine myelinolysis. We also recommend an approach to the management of a child in diabetic ketoacidosis with hypokalaemia at presentation.
Learning points:
-
Hypokalaemia is a recognised complication of treatment of paediatric diabetic ketoacidosis that should be aggressively managed to prevent acute complications.
-
Central pontine myelinolysis is rare in children, and usually observed in the presence of rapid correction of hyponatraemia. However, there is observational evidence of an association between hypokalaemia and central pontine myelinolysis, potentially by priming the endothelial cell membrane to injury by lesser fluctuations in osmotic pressure.
-
Consider central pontine myelinolysis as a complication of the management of paediatric diabetic ketoacidosis in the presence of relevant symptoms with profound hypokalaemia and/or fluctuations in serum sodium levels.
-
We have suggested an approach to the management strategies of hypokalaemia in paediatric diabetic ketoacidosis which includes oral potassium supplements if tolerated, minimising the duration and the rate of insulin infusion and increasing the concentration of potassium intravenously (via central line if necessary).
Search for other papers by Bidhya Timilsina in
Google Scholar
PubMed
Search for other papers by Niranjan Tachamo in
Google Scholar
PubMed
Search for other papers by Prem Raj Parajuli in
Google Scholar
PubMed
Search for other papers by Ilan Gabriely in
Google Scholar
PubMed
Summary
A 74-year-old woman presented with progressive lethargy, confusion, poor appetite and abdominal pain. She was found to have non-PTH-mediated severe hypercalcemia with renal failure and metabolic alkalosis. Extensive workup for hypercalcemia to rule out alternate etiology was unrevealing. Upon further questioning, she was taking excess calcium carbonate (Tums) for her worsening heartburn. She was diagnosed with milk-alkali syndrome (MAS). Her hypercalcemia and alkalosis recovered completely with aggressive hydration along with improvement in her renal function. High index of suspicion should be maintained and history of drug and supplements, especially calcium ingestion, should be routinely asked in patients presenting with hypercalcemia to timely diagnose MAS and prevent unnecessary tests and treatments.
Learning points:
-
Suspect milk-alkali syndrome in patients with hypercalcemia, metabolic alkalosis and renal failure, especially in context of ingestion of excess calcium-containing supplements.
-
Careful history of over-the-counter medications, supplements and diet is crucial to diagnose milk-alkali syndrome.
-
Milk-alkali syndrome may cause severe hypercalcemia in up to 25–30% of cases.
Search for other papers by Kewan Hamid in
Google Scholar
PubMed
Search for other papers by Neha Dayalani in
Google Scholar
PubMed
Division of Pediatric Endocrinology, Hurley Children’s Hospital, Flint, Michigan, USA
Search for other papers by Muhammad Jabbar in
Google Scholar
PubMed
Division of Pediatric Hematology and Oncology, Hurley Children’s Hospital, Flint, Michigan, USA
Search for other papers by Elna Saah in
Google Scholar
PubMed
Summary
A 6-year-old female presented with chronic intermittent abdominal pain for 1 year. She underwent extensive investigation, imaging and invasive procedures with multiple emergency room visits. It caused a significant distress to the patient and the family with multiple missing days at school in addition to financial burden and emotional stress the child endured. When clinical picture was combined with laboratory finding of macrocytic anemia, a diagnosis of hypothyroidism was made. Although chronic abdominal pain in pediatric population is usually due to functional causes such as irritable bowel syndrome, abdominal migraine and functional abdominal pain. Hypothyroidism can have unusual presentation including abdominal pain. The literature on abdominal pain as the main presentation of thyroid disorder is limited. Pediatricians should exclude hypothyroidism in a patient who presents with chronic abdominal pain. Contrast to its treatment, clinical presentation of hypothyroidism can be diverse and challenging, leading to a delay in diagnosis and causing significant morbidity.
Learning points:
-
Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.
-
In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.
-
In pediatric population, treatment of hypothyroidism varies depending on patients’ weight and age.
-
Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.
Wolfson Diabetes and Endocrinology Clinic, Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Box 281, Cambridge, CB2 0QQ, UK
Search for other papers by Benjamin G Challis in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, DK-2200, Denmark
Search for other papers by Nicolai J Wewer Albrechtsen in
Google Scholar
PubMed
Search for other papers by Vishakha Bansiya in
Google Scholar
PubMed
Search for other papers by Keith Burling in
Google Scholar
PubMed
Search for other papers by Peter Barker in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, DK-2200, Denmark
Search for other papers by Bolette Hartmann in
Google Scholar
PubMed
Search for other papers by Fiona Gribble in
Google Scholar
PubMed
Wolfson Diabetes and Endocrinology Clinic, Institute of Metabolic Science, Cambridge University Hospitals NHS Foundation Trust, Addenbrookes Hospital, Box 281, Cambridge, CB2 0QQ, UK
Search for other papers by Stephen O'Rahilly in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Blegdamsvej 3B, Copenhagen, DK-2200, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Search for other papers by Helen L Simpson in
Google Scholar
PubMed
Summary
Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia, constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickening and hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improved the rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perineal rash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs were elevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1 (GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to a pancreatic α-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneous clinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patient with symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part, a proglucagon-expressing pNET.
Learning points
-
PGDPs exhibit a diverse range of biological activities including critical roles in glucose and amino acid metabolism, energy homeostasis and gastrointestinal physiology.
-
The clinical manifestations of proglucagon-expressing tumours may exhibit marked phenotypic variation due to the biochemical heterogeneity of their secreted peptide repertoire.
-
Specific and precise biochemical assessment of individuals with proglucagon-expressing tumours may provide opportunities for improved diagnosis and clinical management.
Search for other papers by Reiner Jumpertz von Schwartzenberg in
Google Scholar
PubMed
Search for other papers by Ulf Elbelt in
Google Scholar
PubMed
Search for other papers by Manfred Ventz in
Google Scholar
PubMed
Search for other papers by Knut Mai in
Google Scholar
PubMed
Search for other papers by Tina Kienitz in
Google Scholar
PubMed
Search for other papers by Lukas Maurer in
Google Scholar
PubMed
Search for other papers by Thomas Rose in
Google Scholar
PubMed
Search for other papers by Jens C Rückert in
Google Scholar
PubMed
Search for other papers by Christian J Strasburger in
Google Scholar
PubMed
Search for other papers by Joachim Spranger in
Google Scholar
PubMed
Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.
Learning points
-
Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.
-
The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.
-
Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.
