Diagnosis and Treatment > Investigation > Haemoglobin A1c
You are looking at 41 - 50 of 78 items
Search for other papers by Ali A Zaied in
Google Scholar
PubMed
Search for other papers by Halis K Akturk in
Google Scholar
PubMed
Search for other papers by Richard W Joseph in
Google Scholar
PubMed
Search for other papers by Augustine S Lee in
Google Scholar
PubMed
Summary
Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.
Learning points:
-
Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).
-
Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop de novo following administration of anti-PD-1.
-
Because anti-PD-1 works by the activation of T-cells and reduction of ‘self-tolerance’, other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.
Search for other papers by Mirjam Eiswirth in
Google Scholar
PubMed
Search for other papers by Ewan Clark in
Google Scholar
PubMed
Search for other papers by Michael Diamond in
Google Scholar
PubMed
Summary
We present the case of an adult female with type 1 diabetes, whose HbA1c was trending at 58 mmol/mol (7.5%) for the past 3 years. In August 2016, she reduced her total daily carbohydrate intake to 30–50 g and adjusted her other macronutrients to compensate for the calorific deficit. Her HbA1c fell to 34 mmol/mol (5.3%) by January 2017 and average daily blood glucose readings decreased significantly from 10.4 to 6.1 mmol/L. Moreover, she observed a marked reduction of average daily glucose variability. Notably, there were no significant episodes of hypo- or hyperglycaemia and her lipid profile remained static. Subjectively, she described an improvement in her quality of life and the dietary transition was extremely well tolerated. We discuss these findings in detail and the potential clinical benefits for patients with type 1 diabetes that can be gained by following a low carbohydrate diet.
Learning points:
-
A low carbohydrate diet was found to substantially reduce HbA1c values and blood glucose (BG) variability, as well as causing a significant reduction in average daily glucose values in a patient with T1DM.
-
Although further research is warranted, low carbohydrate diets in patients with T1DM have the potential to positively impact long-term morbidity and mortality through reduction of BG variability and average daily BG values.
-
The diet was well tolerated and not associated with any adverse effects within this study.
Search for other papers by Ploutarchos Tzoulis in
Google Scholar
PubMed
Search for other papers by Richard W Corbett in
Google Scholar
PubMed
Search for other papers by Swarupini Ponnampalam in
Google Scholar
PubMed
Search for other papers by Elly Baker in
Google Scholar
PubMed
Search for other papers by Daniel Heaton in
Google Scholar
PubMed
Search for other papers by Triada Doulgeraki in
Google Scholar
PubMed
Search for other papers by Justin Stebbing in
Google Scholar
PubMed
Summary
Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.
Learning points:
-
Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.
-
Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.
-
Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.
-
Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.
Search for other papers by Florence Gunawan in
Google Scholar
PubMed
Search for other papers by Elizabeth George in
Google Scholar
PubMed
Search for other papers by Adam Roberts in
Google Scholar
PubMed
Summary
Immune checkpoint inhibitors are the mainstay of treatment for advanced melanoma, and their use is being increasingly implicated in the development of autoimmune endocrinopathies. We present a case of a 52-year-old man with metastatic melanoma on combination nivolumab and ipilumimab therapy who developed concurrent hypophysitis, type 1 diabetes mellitus (T1DM) and diabetes insipidus. He presented prior to third cycle of combination treatment with a headache, myalgias and fatigue. Biochemistry and MRI pituitary confirmed anterior pituitary dysfunction with a TSH: 0.02 mU/L (0.5–5.5 mU/L), fT4: 5.2 pmol/L (11–22 pmol/L), fT3: 4.0 pmol/L (3.2–6.4 pmol/L), cortisol (12:00 h): <9 nmol/L (74–286 nmol/L), FSH: 0.7 IU/L (1.5–9.7 IU/L), LH: <0.1 IU/L (1.8–9.2 IU/L), PRL: 1 mIU/L (90–400 mIU/L), SHBG: 34 nmol/L (19–764 nmol/L) and total testosterone: <0.4 nmol/L (9.9–27.8 nmol/L). High-dose dexamethasone (8 mg) was administered followed by hydrocortisone, thyroxine and topical testosterone replacement. Two weeks post administration of the third cycle, he became unwell with lethargy, weight loss and nocturia. Central diabetes insipidus was diagnosed on the basis of symptoms and sodium of 149 mmol/L (135–145 mmol/L). Desmopressin nasal spray was instituted with symptom resolution and normalization of serum sodium. Three weeks later, he presented again polyuric and polydipsic. His capillary glucose was 20.8 mmol/L (ketones of 2.4 mmol), low C-peptide 0.05 nmol/L (0.4–1.5 nmol/L) and HbA1c of 7.7%. T1DM was suspected, and he was commenced on an insulin infusion with rapid symptom resolution. Insulin antibodies glutamic acid decarboxylase (GAD), insulin antibody-2 (IA-2) and zinc transporter-8 (ZnT8) were negative. A follow-up MRI pituitary revealed findings consistent with recovering autoimmune hypophysitis. Immunotherapy was discontinued based on the extent of these autoimmune endocrinopathies.
Learning points:
-
The most effective regime for treatment of metastatic melanoma is combination immunotherapy with nivolumab and ipilumimab, and this therapy is associated with a high incidence of autoimmune endocrinopathies.
-
Given the high prevalence of immune-related adverse events, the threshold for functional testing should be low.
-
Traditional antibody testing may not be reliable to identify early-onset endocrinopathy.
-
Routine screening pathways have yet to be adequately validated through clinical trials.
Search for other papers by Ken Takeshima in
Google Scholar
PubMed
Search for other papers by Hiroyuki Ariyasu in
Google Scholar
PubMed
Search for other papers by Tatsuya Ishibashi in
Google Scholar
PubMed
Search for other papers by Shintaro Kawai in
Google Scholar
PubMed
Search for other papers by Shinsuke Uraki in
Google Scholar
PubMed
Search for other papers by Jinsoo Koh in
Google Scholar
PubMed
Search for other papers by Hidefumi Ito in
Google Scholar
PubMed
Search for other papers by Takashi Akamizu in
Google Scholar
PubMed
Summary
Myotonic dystrophy type 1 (DM1) is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA) axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.
Learning points:
-
DM1 patients could be affected by a variety of multiple endocrinopathies.
-
Our patients with DM1 presented rare combinations of multiple endocrinopathies; diabetes mellitus, combined form of primary and secondary hypogonadism and dysfunction of HPA axis.
-
Testosterone treatment of hypogonadism in patients with DM1 could improve body composition.
-
The patients with DM1 should be assessed endocrine functions and treated depending on the degree of each endocrine dysfunction.
Search for other papers by Mads Ryø Jochumsen in
Google Scholar
PubMed
Search for other papers by Peter Iversen in
Google Scholar
PubMed
Search for other papers by Anne Kirstine Arveschoug in
Google Scholar
PubMed
Summary
A case of follicular thyroid cancer with intense focal Methionine uptake on 11C-Methionine PET/CT is reported here. The use of 11C-Methionine PET in differentiated thyroid cancer is currently being investigated as a surrogate tracer compared to the more widely used 18F-FDG PET. This case illustrates the potential incremental value of this modality, not only in the localizing of parathyroid adenoma, but also indicating that 11C-Methionine PET might have a potential of increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.
Learning points:
-
11C-Methionine PET/CT and 18F-Fluorocholine PET/CT often visualizes the parathyroid adenoma in case of negative Tc-99m-MIBI SPECT/CT.
-
A cold nodule in Tc-99m Pertechnetat thyroid scintigraphy with a negative Sestamibi scintigraphy has a very low probability of being malignant.
-
However, the pretest likelihood of thyroid cancer in a cold nodule with increased Sestamibi uptake is low.
-
11C-Methionine PET might have a potential incremental value in increasing the pretest likelihood of thyroid malignancy in a cold nodule with highly increased Sestamibi uptake.
Search for other papers by Joseph Cerasuolo in
Google Scholar
PubMed
Search for other papers by Anthony Izzo in
Google Scholar
PubMed
Summary
Acute hyperglycemia has been shown to cause cognitive impairments in animal models. There is growing appreciation of the numerous effects of hyperglycemia on neuronal function as well as blood–brain barrier function. In humans, hypoglycemia is well known to cause cognitive deficits acutely, but hyperglycemia has been less well studied. We present a case of selective neurocognitive deficits in the setting of acute hyperglycemia. A 60-year-old man was admitted to the hospital for an episode of acute hyperglycemia in the setting of newly diagnosed diabetes mellitus precipitated by steroid use. He was managed with insulin therapy and discharged home, and later, presented with complaints of memory impairment. Deficits included impairment in his declarative and working memory, to the point of significant impairment in his overall functioning. The patient had no structural lesions on MRI imaging of the brain or other systemic illnesses to explain his specific deficits. We suggest that his acute hyperglycemia may have caused neurological injury, and may be responsible for our patient’s memory complaints.
Learning points:
-
Acute hyperglycemia has been associated with poor outcomes in several different central nervous system injuries including cerebrovascular accident and hypoxic injury.
-
Hyperglycemia is responsible for accumulation of reactive oxygen species in the brain, resulting in advanced glycosylated end products and a proinflammatory response that may lead to cellular injury.
-
Further research is needed to define the impact of both acute and chronic hyperglycemia on cognitive impairment and memory.
NHMRC Clinical Trials Centre, The University of Sydney, Sydney, Australia
Search for other papers by E S Scott in
Google Scholar
PubMed
University of Sydney, Sydney, Australia
Search for other papers by G R Fulcher in
Google Scholar
PubMed
University of Sydney, Sydney, Australia
Cancer Genetics Laboratory, Hormones & Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, Sydney, Australia
Search for other papers by R J Clifton-Bligh in
Google Scholar
PubMed
Pancreatogenic diabetes is characterised by recurrent severe hypoglycaemia due to changes in both endocrine and exocrine functions. There are no guidelines to manage these individuals. Herein, we describe the post-operative management of two people who developed pancreatogenic diabetes following total pancreatectomy for neuroendocrine malignancy. In both individuals, diabetes was managed using sensor-augmented predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII). We demonstrate the benefit of sensor-augmented CSII in averting hypoglycaemia whilst optimising glycaemic control. Expected rates of severe hypoglycaemia in individuals with pancreatogenic diabetes can be averted with the use of continuous glucose monitoring (CGM) technology, optimising quality of life and reducing the risk of diabetes-related complications.
Learning points:
-
There are no clear guidelines to manage people with pancreatogenic diabetes.
-
We describe the use of CGM with predictive low-glucose suspend continuous subcutaneous insulin infusion (CSII) in the management of two individuals post-pancreatectomy.
-
Predictive low-glucose suspend technology can achieve excellent glycaemic control whilst avoiding recurrent and severe hypoglycaemia in people with pancreatogenic diabetes.
-
Predictive low-glucose suspend CGM should be considered as an effective therapeutic option for the management of pancreatogenic diabetes.
Search for other papers by Ahmad Haider in
Google Scholar
PubMed
Search for other papers by Karim S Haider in
Google Scholar
PubMed
Research Department, Gulf Medical University, Ajman, UAE
Search for other papers by Farid Saad in
Google Scholar
PubMed
Summary
In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM) patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes.
Learning points:
-
Hypogonadism occurs frequently in men with T2DM.
-
In case of pronounced abdominal fat deposition and T2DM, the male patient should be evaluated for testosterone deficiency.
-
Untreated hypogonadism can complicate the successful treatment of patients with T2DM.
-
Under testosterone therapy, critical laboratory values are facilitated to return back to normal ranges and even complete remission of diabetes can be achieved.
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by W K M G Amarawardena in
Google Scholar
PubMed
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by K D Liyanarachchi in
Google Scholar
PubMed
Department of Endocrinology, Royal Hallamshire Hospital, University of Sheffield, Sheffield, UK
Search for other papers by J D C Newell-Price in
Google Scholar
PubMed
Search for other papers by R J M Ross in
Google Scholar
PubMed
Search for other papers by D Iacovazzo in
Google Scholar
PubMed
Search for other papers by M Debono in
Google Scholar
PubMed
Summary
The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test. Insulin-like growth factor 1 (IGF1) was 1710 µg/L (103–310 µg/L) and mean growth hormone (GH) was >600 U/L. MRI scan showed a 4 cm pituitary macroadenoma with suprasellar extension and right-sided cavernous sinus invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for GH. Postoperative investigations showed uncontrolled disease (IGF1:1474 µg/L, mean GH:228 U/L) and residual tumour in the cavernous sinus. She received external beam fractionated radiation. Over the years, she received octreotide LAR (up to 30 mg), lanreotide (up to 120 mg) two weekly, cabergoline, pegvisomant and stereotactic radiosurgery to no avail. Only pegvisomant resulted in an element of disease control; however, this had to be stopped due to abnormal liver function tests. Fifteen years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a month, her IGF1 dropped and has remained within the normal range (103–310 µg/L). Pasireotide has been well tolerated, and there has been significant clinical improvement. Somatostatin receptor subtyping revealed a positivity score of two for both sst5 and sst2a subtypes.
Learning points:
-
Age, size of the tumour, GH levels on presentation, histopathological type and the somatostatin receptor status of the tumour in acromegaly should be reviewed in patients who poorly respond to first-generation somatostatin receptor ligands.
-
Tumours that respond poorly to first-generation somatostatin receptor ligands, especially sparsely granulated somatotroph adenomas, can respond to pasireotide and treatment should be considered early in the management of resistant tumours.
-
Patients with membranous expression of sst5 are likely to be more responsive to pasireotide.