Endocrinology, Diabetes and Metabolism Case Reports最新文献

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.

Summary: We present the case of a 50-year-old Japanese woman who was transferred to our hospital with a 2-day history of fever, sore throat, and malaise. She was diagnosed with acromegaly 9 months ago while being treated for diabetic ketoacidosis, for which she underwent pituitary surgery. She was diagnosed with hypopituitarism postoperatively and was prescribed hydrocortisone and levothyroxine. Her glycemic control was good on metformin. Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza were positive in the emergency room. Other laboratory findings included thyrotoxicosis (free T3: 9.13 pg/mL; free T4: 3.64 ng/dL; and thyroid-stimulating hormone (TSH): <0.01 μIU/mL) and a high C-reactive protein (CRP) level (3.84 mg/dL). The test for the TSH receptor antibody was negative. She had no apparent goiter and reported no tenderness in response to thyroid palpation. 99m-Technetium scintigraphy revealed decreased tracer uptake. Ultrasonography showed no hypoechoic lesions. Her thyrotoxicosis spontaneously resolved after 6 weeks. Although both anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) were negative 9 months ago, TgAb was positive at admission. The test for TPOAb became positive 6 weeks later. These findings were suggestive of painless thyroiditis. In this patient, painless thyroiditis was believed to be caused by SARS-CoV-2 and influenza infections. Screening tests of thyroid function in patients with viral infections such as SARS-CoV-2 or influenza are recommended, even when thyroid gland pain or tenderness is not observed.

Learning points: We describe a case of painless thyroiditis associated with SARS-CoV-2 and influenza infections. Although a few cases of painless thyroiditis associated with COVID-19 have been reported, no cases of painless thyroiditis associated with influenza have been reported. In this case, thyrotoxicosis developed immediately after the viral infection. In addition, tests for anti-thyroglobulin antibody and anti-thyroid peroxidase antibody were negative before the onset of symptoms. Tests for the former became positive at the time of onset of symptoms, whereas tests for the latter became positive several weeks after the onset of symptoms. Patients with viral infections such as SARS-CoV-2 and influenza, who had no goiter or thyroid tenderness, may develop painless thyroiditis; screening tests for thyroid function are recommended.

Summary: Delayed puberty in girls is often related to late maturation but is occasionally the first sign of premature ovarian insufficiency (POI). POI is a condition that affects ovarian function and fertility, and its etiology is unknown in most cases. Genetic factors have recently been identified in 20-25% of women with POI, involving genes that regulate various aspects of ovarian development and maintenance. We report a case of delayed puberty due to POI in an adolescent from a non-consanguineous family who carried two variants in the MCM9 gene. MCM9 is essential for DNA replication and repair, and its dysfunction can lead to chromosomal instability and ovarian failure. Our case highlights the importance of targeted gene panel analysis, particularly in POI patients with negative autoimmunity screening, and evidence of ovarian or uterine dysgenesis on pelvic imaging.

Learning points: Delayed puberty in girls is often self-limiting, but it can also indicate underlying conditions with lifelong implications, such as premature ovarian insufficiency (POI). Patients with POI, negative autoimmune screening, a normal karyotype, and no FMR premutation should undergo further genetic testing, preferably through targeted gene panels. Compound heterozygous variants in MCM9 can cause POI, presenting with delayed puberty and primary amenorrhea in girls without a consanguineous family.

Summary: Assessment of hormone concentrations can be subjected to laboratory pitfalls. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormones' concentrations. Macro-prolactin and macro-thyroid-stimulating hormone (TSH) are most frequently encountered while macro-follicle-stimulating hormone (FSH) has been rarely reported. We describe the case of a 30-year-old woman who had a gynaecological consultation due to failure in achieving pregnancy after 8 months of unprotected intercourse. She had regular menses, did not complain of climacteric symptoms and her medical history was unremarkable. Antral follicle count and anti-mullerian hormone concentrations were normal, and regular ovulation was documented. Unexpectedly, high early follicular phase FSH concentrations were confirmed on two occasions (57 and 51 IU/L), raising the suspicion of primary ovarian insufficiency. After excluding Turner's syndrome and autoimmune oophoritis, a laboratory artifact was hypothesized. Following polyethylene glycol precipitation, FSH levels dropped from 41.1 IU/L to 6.54 IU/L (recovery 16%) and the presence of macro-FSH was concluded. Laboratory interference can lead to misdiagnosis and unnecessary treatments. A laboratory artifact should be suspected when inconsistency exists between clinical presentation and laboratory results. Only five other cases of macro-FSH have been reported to date. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure.

Learning points: Hormone quantification is a cornerstone in the diagnostic workup of endocrine disorders, but it can be subjected to laboratory interferences which can lead to unnecessary investigations and inappropriate treatments. A laboratory artifact should be suspected when a discrepancy is observed between clinical presentation and laboratory results, when extremely unusual analyte concentrations are observed and when inconsistent results are obtained by different analytical methods. Macro-hormones are hormone-autoantibody complexes which are cleared slowly from circulation and cause a false elevation in hormone concentrations. Macro-prolactin and macro-TSH are most frequently encountered, while macro-FSH has been rarely reported. Macro-hormones can be detected by polyethylene glycol precipitation, gel filtration chromatography, or by using protein G or protein A columns. Although macro-hormones generally have low biological activity and do not require treatment, the role of anti-FSH antibodies has been hypothesized in primary ovarian insufficiency and in vitro fertilization failure.

Summary: Phosphatidylinositol-3 kinase (PI3K) is a critical intracellular pathway that regulates cell growth, metabolism, and survival and has been implicated in most human cancers. Targeting this pathway has been approved as a therapeutic option for breast cancer and lymphoma (e.g. alpelisib, idelalisib), and there are several clinical trials underway in additional types of cancer. However, PI3K is an important mediator of the action of insulin, and the use of PI3K inhibitors has been associated with hyperglycemia. We report the case of a 53-year-old female with metastatic breast cancer who developed acute grade 3 hyperglycemia from a novel PI3K inhibitor, inavolisib. We review the treatment options for PI3K inhibitor-associated hyperglycemia. Treatment strategies that minimize hyperinsulinemia may be preferable considering animal models have demonstrated that hyperinsulinemia may result in partial reactivation of the PI3K pathway and counter the anti-cancer effectiveness of PI3K inhibitors.

Learning points: Phosphatidylinositol-3 kinase (PI3K) is an intracellular pathway that regulates a range of physiological functions, including cell growth, metabolism, survival, and angiogenesis. Hyperactivation of the PI3K pathway is associated with almost all human cancers, and thus PI3K inhibition has been proposed as a treatment option for selected cancers. The action of insulin after binding to the insulin receptor on the cell surface (e.g. glucose uptake in skeletal muscle, inhibition of glycogenolysis and gluconeogenesis) is mediated by the intracellular PI3K pathway, and thus PI3K inhibition may lead to hyperinsulinemic hyperglycemia. All patients treated with PI3K inhibitors should receive pre-treatment screening for hyperglycemia, lifestyle advice, and a glucometer to measure fasting BGL and 2-h post-dinner BGL levels twice per week for at least the first 30 days of treatment. Insulin or insulin secretagogues (e.g. sulfonylurea) may inhibit the anti-tumor activity of PI3K inhibitors, and thus treatment of PI3K inhibitor-associated hyperglycemia should prefer alternative approaches such as a low carbohydrate diet, metformin, SGLT2i, or dose reduction of the PI3K inhibitor.