Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: HDR is a rare autosomal dominant genetic disorder characterized by the triad of hypoparathyroidism, sensorineural deafness and renal anomalies caused by haploinsufficiency loss of function of the GATA-binding protein 3 (GATA3) gene. We present a case of a 56-year-old male diagnosed with hypoparathyroidism, sensorineural deafness, renal hypoplasia and epilepsy. Genetic testing revealed a novel GATA3 heterozygous mutation c.860C>A with a predicted amino acid substitution p.Ala287Asp. This hitherto unreported missense GATA mutation was characterized by a relatively late-onset and milder phenotype of the HDR triad.

Learning points: GATA3 gene mutations located on chromosome 10p cause haploinsufficiency of the GATA3 protein affecting fetal development of the parathyroid glands, inner ear and renal anomalies, resulting in HDR syndrome with an autosomal dominant inheritance pattern.Also known as Barakat syndrome, it has been reported in less than 200 cases with an identified mutation, each having a varied phenotypic presentation without consistent genotypic correlation.We present a patient with HDR syndrome who tested positive for a novel mutation c.860C>A, resulting in a missense substitution of amino acids p.Ala287Asp in the GATA3 gene.Clinicians who identify this rare triad of hypoparathyroidism, sensorineural deafness and renal anomalies should further investigate with genetic testing for GATA3 mutations.

Summary: Maturity-onset diabetes of the young (MODY) is a subtype of monogenic diabetes and a rare type of diabetes, which accounts for 1-5% of cases and is often underdiagnosed. The importance of its diagnosis lies in the potential implications that it can have on disease management and offspring. We report a de novo KCNJ11-MODY case and the process of transition from insulin to sulfonylureas. A 24-year-old Caucasian woman was referred to the Endocrinology Department on account of newly diagnosed diabetes mellitus. Her past medical history was unremarkable; however, her family history was relevant, as three grandparents had diabetes. Blood tests showed elevated haemoglobin A1c (10.7%) and fasting glucose (278 mg/dL), prompting the initiation of insulin therapy. Further tests revealed a normal C-peptide level (2.75 ng/mL) and negative anti-glutamic acid decarboxylase and anti-insulin antibodies. The examination of past medical records revealed pre-diabetes since the age of 13. Genetic testing identified a heterozygous pathogenic variant p.(Glu227Lys) in the KCNJ11 gene. Excellent glycaemic control was achieved upon initiation of gliclazide, leading to the withdrawal of insulin treatment. KCNJ11-MODY is an extremely uncommon subtype of MODY, with only a few reported cases worldwide. This case is important, as it supports the use of sulfonylureas as an effective treatment for KCNJ11-MODY.

Learning points: De novo KCNJ11 variants challenge MODY calculators.Gliclazide is safe, is effective in the long term and improves quality of life.Precision medicine is essential in the management of diabetes.

Summary: A 56-year-old woman with cervical pain with a history of ovarian clear cell carcinoma stage IIIC was admitted to a primary care doctor. Ultrasonography revealed a microhyperechoic nodule in the thyroid gland and cervical lymph node enlargement, and fine-needle aspiration was performed. The results showed malignancy, and she was admitted to our hospital. The differential diagnoses included primary thyroid neoplasms and thyroid metastases from ovarian clear cell carcinoma. A needle biopsy of the thyroid gland was performed. Immunohistochemistry revealed that the tumor cells were positive for cytokeratin AE1/AE3, hepatocyte nuclear factor-1-beta and PAX8 and negative for thyroglobulin and thyroid transcription factor-1. Therefore, we diagnosed the patient with thyroid metastasis from ovarian clear cell carcinoma. There were no compressive symptoms at the time of the visit to our hospital, and surgery was considered unnecessary. Systemic treatment for ovarian clear cell carcinoma was continued. Three months later, she died of a stroke due to Trousseau's syndrome.

Learning points: Metastasis of ovarian carcinoma to the thyroid gland is extremely rare.Using histology and immunostaining, we were able to accurately diagnose thyroid metastasis of ovarian clear cell carcinoma.

Summary: Adrenocortical carcinoma (ACC) is a rare malignant tumour arising from the adrenal cortex, with an estimated annual incidence of one to two patients per million. Ectopic ACCs are extremely rare. The majority of ACCs are sporadic; however, ACC has been linked with genetic disease processes, including multiple endocrine neoplasia type-1 (MEN-1). We present the case of a 66-year-old lady referred with newly diagnosed diabetes on a background of primary hyperparathyroidism. Examination revealed Cushingoid features, and hormonal evaluation confirmed ACTH-independent Cushing's syndrome. Morning cortisol after a 1 mg overnight dexamethasone suppression test was 548 nmol/L with an undetectable ACTH <3.0 pg/mL. Dehydroepiandrosterone sulphate was 5.3 μmol/L and androstenedione 3.49 nmol/L, both of which were normal. Testosterone was suppressed at <0.4 nmol/L. Imaging revealed a 6 × 6 × 4.5 cm right-sided presumed adrenal lesion, a pancreatic lesion (2.5 × 1.6 cm), and bilateral pulmonary nodules (0.9 × 0.8 cm, 0.7 × 0.6 cm, 0.3 cm). Right adrenalectomy was performed, and histology was consistent with an extra-adrenal ACC (Weiss score 5/9) within the peri-adrenal adipose tissue. The resected adrenal gland was normal. Lung biopsy confirmed metastatic ACC tissue, and endoscopic ultrasound-guided biopsy of the pancreatic lesion revealed a pancreatic neuroendocrine tumour, which was confirmed biochemically to be an insulinoma. Genetic assessment confirmed MEN-1. This case highlights the importance of screening for MEN-1 in at-risk patients and the need for close clinical follow-up. To our knowledge, this is the first case report of extra-adrenal ACC in MEN-1 syndrome.

Learning points: Adrenal lesions in MEN-1 syndrome have significant malignant potential. Newly diagnosed lesions should be followed closely with short-interval imaging, and a lower threshold for surgical removal is suggested. Primary hyperparathyroidism is often the earliest laboratory or clinical manifestation of MEN-1 syndrome. A detailed medical and family history is vital in order to appropriately identify patients at risk of MEN-1. To our knowledge, this is the first case report of extra-adrenal adrenocortical carcinoma in MEN-1 syndrome.

Summary: Adrenocortical insufficiency is defined as the clinical manifestation of chronic glucocorticoid and/or mineralocorticoid deficiency due to failure of the adrenal cortex. It may result in an adrenal crisis, which is a life-threatening disease; thus, prompt initiation of therapy with hydrocortisone is necessary. Symptoms such as hypotension, weight loss, or fatigue are not specific, which is why diagnosis is delayed in many cases. Our patient suffered from immune thrombocytopenia (ITP), an acquired thrombocytopenia caused by an autoimmune reaction against platelets and megakaryocytes. Primary ITP, in which no triggering cause can be identified, must be distinguished from secondary forms (e.g. in the context of systemic autoimmune diseases, lymphomas, or (rarely) by drugs). Patients may be asymptomatic at presentation or may present with a range of mild mucocutaneous to life-threatening bleeding. Here, we report on a 43-year-old woman who had developed adrenocortical insufficiency due to bilateral hemorrhage in the adrenal glands. Because of anticoagulation with phenprocoumon after pulmonary embolism and thrombocytopenia on the basis of ITP, the patient had an increased risk of bleeding. Due to the nonspecific and ambiguous symptoms of adrenocortical insufficiency, prompt diagnosis remains a challenge.

Learning points: Hypocortisolism or adrenal crisis with nonspecific symptoms, especially abdominal and gastrointestinal, is often misinterpreted. Diagnosis of adrenal insufficiency is often delayed because of the initial ambiguous presentation; physicians must be aware to avoid adrenal crisis. Especially in patients with several risk factors for bleeding, unusual bleeding manifestations, such as adrenal hemorrhage, must be considered. Immediate treatment is necessary by substituting hydrocortisone in a higher dosage, and in most cases, fludrocortisone. During the course of treatment, the amount of hydrocortisone can be reduced to a substitution dosage (15-25 mg/day divided into two to three doses/day). Fludrocortisone should be continued at a dosage of 0.05-0.1 mg/day, depending on blood pressure and sodium and potassium levels. All patients should carry a medical alert notification or a steroid emergency card. In the case of trauma, surgery, or other stressful events, hydrocortisone must be administered in higher dosages (e.g. 100 mg i.v.).

Summary: Relative energy deficiency in sport occurs in athletes who have limited energy availability. Its typical features include reversible suppression of the hypothalamic-pituitary-gonadal axis. In addition, it may be accompanied by hepatic resistance to growth hormone, leading to a decrease in insulin-like growth factor 1 and dysregulation of the hypothalamic-pituitary-thyroid axis. We present the clinical case of a 33-year-old athlete previously treated effectively for hypothyroidism, who presented with low thyroid-stimulating hormone, low free triiodothyronine, and normal free thyroxine. Based on diet and training interviews and further laboratory tests, dysregulation of the hypothalamic-pituitary-thyroid axis and reversible hypogonadism due to insufficiency of energy available to support energy expenditure were revealed. We also discuss here challenging diagnostic dilemmas that may appear in athletes of normal body weight but result from insufficient energy supply in relation to demand, and review the literature for the clinical course and possible mechanisms underlying the relative energy deficiency.

Learning points: Atypical thyroid function tests in athletes may be the first manifestation of reversible pituitary dysfunction due to relative energy deficiency. Typical symptoms of relative energy deficiency include reversible suppression of the hypothalamic-pituitary-thyroidal axis and hypothalamic-pituitary-gonadal axis. Relative energy deficiency may occur in all people who train intensively, regardless of their body weight and BMI, as well as in people who have rapidly lost weight as a result of a low-calorie diet and intense exercise.

Summary: Cushing's disease (CD) is characterized by distinct syndromic features, often accompanied by obesity and depression. However, considering its gradual onset of symptoms, it is usually associated with diagnostic delays. In rare instances, CD may lead to severe infections due to the observed immunosuppression in affected individuals. We present a rare case of an undiagnosed CD in a 20-year-old male with a medical history of depression and obesity, complicated by severe COVID-19 infection. He presented to the Emergency Room with respiratory distress, hypertensive crisis, and fever, ultimately receiving the diagnosis of SARS-CoV-2 pneumonia. The patient required mechanical ventilation and intensive care unit (ICU) admission due to severe acute respiratory distress syndrome (ARDS). During ICU care, he received remdesivir and dexamethasone, subsequently developing severe hyperglycemia and worsened hypertension, requiring insulin and multiple antihypertensive agents to manage metabolic disruption. Upon physical examination, classic signs of hypercortisolism were noted. Subsequent laboratory tests and pituitary magnetic resonance imaging confirmed the diagnosis of CD. The patient underwent surgical resection with significant improvements in body composition and metabolic parameters postoperatively. After surgery, remission of hypercortisolism was evident, accompanied by notable improvements in mood and overall health. This case underscores the importance of recognizing hypercortisolism in the context of metabolic, physical, and mood changes. Timely diagnosis of CD is crucial to mitigate complications such as severe opportunistic infections and their outcomes.

Learning points: Despite some hallmark features such as proximal myopathy, easy bruising, purple striae, and facial plethora, Cushing's disease (CD) is a challenging diagnosis due to its nonspecific signs and symptoms and gradual onset. The case emphasizes the importance of recognizing subtle signs of CD, such as social isolation, depressive symptoms, and changes in body composition, which may be confounded by external factors like the COVID-19 pandemic. Patients with CD are prone to severe infections due to chronic hypercortisolism-induced immunosuppression. CD diagnostic delays are common, leading to worsening of metabolic and immune dysfunction over time. Heightened clinical suspicion and early intervention are essential to prevent diagnostic delays and optimize patient outcomes.

Summary: Delayed arginine vasopressin deficiency (AVP-D) can present in patients following traumatic brain injury (TBI) and may occur years after the trauma, presenting with nonspecific symptoms. The objective of this case is to highlight the importance of considering the delayed onset AVP-D in patients with a history of TBI. We report a case of a patient who had sustained severe traumatic brain injury 8 years before and who presented with polydipsia, behavioural disorder and frequent falls during the last 3 months. The diagnosis of AVP-D was confirmed by water restriction with a positive response to desmopressin, and pituitary MRI showed an absent spontaneous posterior hyperintensity on T1WI. Follow-up confirmed permanent diabetes insipidus as well as a suspected anterior pituitary deficiency. Pituitary dysfunction occurs following TBI and is correlated with severity. As in our case, symptoms are generally non-specific and are difficult to explore given the patient's neurologic sequelae. MRI 8 years post trauma showed changes in pituitary morphology. Some authors have proposed the need for active screening of post-TBI patients. This case highlights the need for clinicians to be aware that AVP-D can occur years after traumatic brain injury.

Learning points: Delayed onset post-traumatic arginine vasopressin deficiency may occur in patients with TBI and is correlated with the severity. The clinical picture is usually non-specific and diagnosis of AVP-D is challenging in non-verbal patients. An active screening for pituitary dysfunction is warranted in TBI patients and should be extended should one hormone deficit be identified.

Summary: We describe and characterise the case of a 26-year-old female undergoing surgery for a right-sided sinonasal alveolar rhabdomyosarcoma who developed profound, transient arginine vasopressin deficiency (AVP-D, formerly central diabetes insipidus (DI)) associated with anaesthesia. In this case report, we characterise the development of AVP-D with serial copeptin and paired urine and serum osmolality measurements. Based on the anaesthetic agent's profile and the literature, we attribute this presentation to propofol exposure. We present a description of the literature on anaesthesia-associated DI as well as poignant learning points.

Learning points: Exposure to anaesthetic agents is a rare cause of self-limited but sudden and profound arginine vasopressin deficiency (AVP-D) or arginine vasopressin resistance (AVP-R). Sevoflurane has been associated with AVP-R and propofol with AVP-D, although the responsible agent may be difficult to identify. Differentiation of AVP-R and AVP-D can be made based on copeptin concentration, where available, or clinical response to desmopressin. Whilst the patient is anaesthetised, intravenous fluid replacement should be targeted to match urine output until the patient is able to drink to thirst. This should be clearly communicated to staff and the patient. Rapid resolution of AVP-R/AVP-D when the causative agent is discontinued has been reported with both propofol and sevoflurane. As such, switching the agent used to maintain anaesthesia may terminate increased urine output in a clinically meaningful timeframe.

Summary: Diabetic ketoacidosis (DKA) is a complication of diabetes mellitus (DM) that can theoretically occur in people of any age. While DKA can typically be the first presentation of type 1 DM in younger people, a first presentation is rare in older adults. Pancreatic cancer often manifests with new DM or hyperglycaemia, but very rarely as DKA. We report a case of an 89-year-old woman who was incidentally diagnosed with DKA during workup for an unwitnessed fall. Her DKA was promptly managed, and she was subsequently diagnosed with metastatic pancreatic cancer. Given the advanced stage of her malignancy, the multidisciplinary team consensus was for a palliative approach. She passed away on day 10 of the admission. To our knowledge, this is the first report of a first DKA presentation as a manifestation of pancreatic cancer in an adult aged over 70 years. To date, there is no effective screening test for pancreatic cancer in the general population. However, new-onset DM in the appropriate context might indicate the need for further evaluation. While it is possible that unresectable tumours are identified, earlier diagnosis of DM with pancreatic cancer may facilitate more timely management, including earlier advanced care planning.

Learning points: A higher clinical suspicion for pancreatic cancer is required for older adults presenting with diabetic ketoacidosis without a previously diagnosed diabetes mellitus. A bi-directional relationship exists between diabetes and pancreatic cancer. Pancreatic cancer generally has a very poor prognosis due to its advanced stage at diagnosis and the lack of an effective screening test. New-onset diabetes in the appropriate context (such as weight loss) can indicate the need for further evaluation for underlying pancreatic cancer.