Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: This case report describes a 54-year-old woman with multiple endocrine autoimmune pathologies and recurrent mucocutaneous Candida spp. infections that were inappropriately attributed to her glycemic control. Following an allergic reaction over four decades later, the patient was referred to clinical immunology. The combination of persistent Candida infections, autoimmune endocrinopathies, and a positive family history prompted investigation for an inborn error of immunity (IEI). Genetic testing revealed a novel, missense mutation in STAT1. Functional analysis confirmed enhanced STAT1 protein phosphorylation, confirming a gain-of-function phenotype that explained her infectious and autoimmune manifestations. She was started on the JAK inhibitor, ruxolitinib, with clinical improvement. This case underscores the shared molecular mechanisms between IEIs and autoimmune endocrinopathies and highlights the importance of early recognition of IEI in patients with unusual or treatment-refractory infections alongside autoimmune disease. Endocrinologists and primary care providers may be the first to encounter such patients and should consider referral for immunologic and genetic evaluation. Early diagnosis can reduce long-term morbidity and open the door to targeted therapies that address the root cause of immune dysregulation.

Learning points: Persistent mucocutaneous candidiasis in patients with autoimmune endocrinopathies warrants evaluation for underlying IEI: while candidiasis is common in individuals with diabetes, recurrent or treatment-refractory infections - particularly in the presence of additional autoimmune conditions - should prompt consideration of IEI, including STAT1 gain-of-function mutations. Autoimmunity and immunodeficiency represent overlapping spectra of immune dysregulation: genetic syndromes such as STAT1 GOF may manifest with both autoimmune endocrinopathies and increased susceptibility to fungal infections, underscoring the importance of a unifying diagnostic approach to seemingly disparate clinical features. Early referral to clinical immunology and genetic testing can enable timely diagnosis and targeted therapy: early recognition of IEI allows for disease-modifying treatment, such as JAK inhibition, which may alleviate infectious susceptibility and autoimmune manifestations, ultimately reducing morbidity and improving the quality of life. A thorough family history can provide critical diagnostic clues in cases of immune dysregulation: subtle patterns of autoimmunity or recurrent infections in family members - particularly in non-consanguineous pedigrees - may indicate heritable immunologic disorders and should inform the clinical threshold for pursuing genetic evaluation.

Summary: A 38-year-old man was admitted because of transient somnolence. Five weeks previously, he had suffered a subarachnoid hemorrhage from a ruptured aneurysm of the anterior communicating artery (ACOM), which was treated by craniotomy and clipping. He had recovered well, although loss of short-term memory and a forehead paresis on the side of craniotomy persisted. Clinical examination on admission showed no new neurological deficits. Cerebral computed tomography with angiography revealed no bleeding or infarction and correctly positioned clips. Laboratory examination showed severe hypernatremia (179 mmol/L). The patient was admitted to the intensive care unit (ICU) and treated with oral fluids and 5% glucose intravenously. Remarkably, he denied being thirsty and had to be encouraged to drink. Urine osmolality quickly fell to 294 mOsm/kg, polyuria of up to 400 mL/h was measured, and serum sodium remained elevated. Therefore, diabetes insipidus (DI) was obvious. After application of desmopressin acetate, urine output dropped to around 50 mL/h, confirming central DI or vasopressin deficiency (VD). Desmopressin acetate dose and volume management were continuously adjusted to blood sodium to restore euvolemia. Drinking volume needed to be supervised because of persistent lack of thirst and amnesia of being told to drink. Adipsic VD (aAVP-D) is a rare syndrome characterized by the combination of VD and loss of thirst in response to hypernatremia. It usually occurs within days after cell damage of osmoreceptors, for example after disruption of blood supply as in clipping of an ACOM aneurysm. Management includes titrated desmopressin acetate replacement, fixed water intake, weight monitoring, patient education and sodium monitoring.

Learning points: Adipsic vasopressin deficiency (aAVP-D) is a rare form of vasopressin deficiency (VD) characterized by additional loss of thirst in response to hypernatremia due to impaired function of periventricular osmoreceptors. Bleeding from ACOM aneurysm and, possibly, therefore the performed frontal craniectomy with aneurysm clipping are the most frequent causes of aAVP-D. Other causes include craniopharyngioma, head trauma, germinoma or neurosarcoidosis. Management of aAVP-D includes replacement of titrated desmopressin acetate, fixed water intake, daily weight tracking, good patient education and regular sodium monitoring.

Summary: We used the sodium-glucose cotransporter 2 inhibitor, luseogliflozin in two patients with diabetes mellitus with Child-Pugh classification B cirrhosis and cirrhotic ascites. In each case, luseogliflozin was safely used for over three years and was also considered effective in reducing ascites. In one of the patients in particular, when luseogliflozin was discontinued and switched to insulin treatment before colorectal cancer surgery, ascites accumulation was observed within two weeks, which subsequently decreased rapidly when luseogliflozin was restarted. In this case, the effect of luseogliflozin on ascites was evident by the clear increase and decrease in ascites over a short period of time, as evaluated using body weight, abdominal circumference and CT scan, without changing her other diuretic medication. Although sodium-glucose cotransporter 2 inhibitors need to be used with caution, they might be an option for the treatment of diabetes in patients with cirrhosis.

Learning points: Luseogliflozin, a sodium-glucose cotransporter 2 inhibitor, is effective for glycemic control and safe in patients with cirrhosis. Luseogliflozin administration reduced ascites in patients with diabetes mellitus. Caution is warranted, as discontinuation of sodium-glucose cotransporter 2 inhibitors might lead to an increase in ascites.

Summary: Gestational diabetes mellitus (GDM) is a known risk factor for dyslipidaemias. Insulin resistance and the associated dyslipidaemia, particularly hypertriglyceridaemia, have been less frequently linked to peripheral nerve dysfunction, including small fibre sensory neuropathy. The relationship between metabolic disturbances, such as hypertriglyceridaemia, and neuropathy warrants further exploration and has gained increasing recognition in recent studies. This case highlights the potential neurological consequences of lipid abnormalities in women with a history of GDM. A 38-year-old woman presented to an endocrinologist with a 4-week history of paraesthesias and incidental findings of significantly elevated triglycerides (78.4 mmol/L) and total cholesterol (14.7 mmol/L). Initially, numbness began in her left first toe, spreading to other toes on the left foot, and then to the right foot, accompanied by hyperalgesia in fifth fingers bilaterally. She had no history of trauma or back injuries. Her medical history included insulin-dependent GDM and HELLP syndrome 4 years prior, endometriosis, and adenomyosis. With persistently high lipid levels (cholesterol: 12.1 mmol/L; triglycerides: 18.5 mmol/L), she was admitted to ICU for urgent lipid-lowering treatment but experienced hypoglycaemia on an insulin-dextrose infusion. Repeat triglycerides the next day were 13.1 mmol/L. A neurologist diagnosed her with small fibre sensory neuropathy secondary to hypertriglyceridaemia. Treatment with fenofibrate, high-dose fish oil, and a low-fat, low-carbohydrate diet was initiated with outpatient endocrinologist follow-up. Hypertriglyceridaemia is a significant health concern, potentially leading to severe complications such as peripheral neuropathy. Early intervention to optimise lipid levels is essential to prevent adverse outcomes.

Learning points: GDM is known to be a risk factor for dyslipidaemias. Hypertriglyceridaemia can contribute to small fibre sensory neuropathy via mechanisms including microvascular ischaemia, oxidative stress, and inflammation affecting peripheral nerves. Diagnosis requires clinical correlation with lipid profiles and neurological findings, and exclusion of other causes through targeted investigations such as nerve conduction studies and autoimmune screening. Early recognition of hypertriglyceridaemia is essential to prevent complications such as neuropathy. Acute management may involve insulin-dextrose infusion in cases of severe elevation, while long-term treatment includes fibrates, omega-3 fatty acids, and dietary modifications.

Summary: Pancytopenia associated with hypopituitarism has been reported in the literature as a rare occurrence limited to isolated case reports, predominantly associated with Sheehan syndrome. We present the case of a 31-year-old woman who showed hematological features of pancytopenia and normal cellularity of bone marrow. Hematological investigation disclosed no other cause for pancytopenia. Her physical findings (generalized weakness, slow speech and no pubic or axillary hair) and history of a previous massive postpartum hemorrhage suggested Sheehan's syndrome, and the pituitary hormonal studies revealed panhypopituitarism. Her blood cell accounts were completely recovered after 5 months of glucocorticoid and thyroxine replacement therapy. We hereby report our experience of a cure of pancytopenia and the normal marrow originating from hypopituitarism after corticosteroid and thyroid hormone replacement therapy.

Learning points: Sheehan's syndrome correlates with postpartum hemorrhage and causes pancytopenia. It could be successfully treated with glucocorticoid. It could be successfully treated with thyroxine replacement therapy.

Summary: Levothyroxine is the backbone of hypothyroidism treatment. The dosage of levothyroxine varies; however, as an estimate, an average adult patient will require 1.6 micrograms per kilogram of body weight. We present the case of a patient with hypothyroidism, controlled on a stable dosage of levothyroxine, who subsequently began semaglutide therapy for obesity. She developed rapid weight loss and presented with palpitations as her main symptoms. Both clinical and biochemical analyses demonstrated new hyperthyroidism. With the weight loss, it was deemed that her levothyroxine dosage was no longer appropriate for her new weight and was over-suppressing her thyroid function (iatrogenic hyperthyroidism), requiring a dosage reduction. With follow-up, both clinical assessment and biochemical studies noted a reduction in the suppression of the thyroid axis. This case highlights the importance of considering a dosage reduction of levothyroxine when patients lose significant weight (such as with concurrent obesity medications), to prevent iatrogenic hyperthyroidism.

Learning points: Weight loss (pharmacological or surgical) can be associated with a reduction in TSH; it is unclear whether this is directly related to the reduction in body mass index. Hypothyroid patients on levothyroxine who are treated for obesity should be monitored for clinical and biochemical evidence of hyperthyroidism, and clinicians should anticipate that a dosage reduction may be required. The mechanism leading to iatrogenic hyperthyroidism in hypothyroid patients with weight loss therapy is unknown but believed to occur either from increased absorption of the medication or as a result of the weight loss itself (posing a supratherapeutic level of levothyroxine).

Summary: This report describes the case of a 37-year-old woman diagnosed with a craniopharyngioma during pregnancy. The patient initially presented with visual impairment at 15 weeks of gestation, and MRI revealed a cystic suprasellar tumor. Endocrine evaluation indicated central hypothyroidism, and central adrenal insufficiency could not be definitively ruled out based on a basal 08:00 h cortisol, as the patient was pregnant and treatment with hydrocortisone was initiated empirically. Hydrocortisone 10 mg/day and levothyroxine 25 µg/day were initiated, but rapid visual deterioration and polyuria by 21 weeks necessitated surgical intervention. She underwent successful treatment with endoscopic transsphenoidal surgery during the second trimester. Adrenal function was assessed on postoperative day 7 based on baseline values, but hydrocortisone was maintained given the risk during pregnancy. At 6 weeks after surgery, pituitary hormones were reassessed, and hydrocortisone, levothyroxine, and desmopressin were continued. Arginine vasopressin deficiency was diagnosed based on polyuria, hypotonic urine, and response to desmopressin, as formal testing was high risk both before and after surgery. Postoperatively, endocrine status was monitored, and pregnancy progressed uneventfully. She underwent an elective cesarean section at 38 weeks of gestation. At 6 months postpartum, MRI revealed residual tumor along the pituitary stalk extending from the right optic chiasm. At 9 months postpartum, the patient had persistent central hypothyroidism, hypogonadism, and newly diagnosed adult GH deficiency. Normal adrenal function allowed discontinuation of hydrocortisone. GH therapy was planned pending tumor assessment. This case underscores the importance of a multidisciplinary approach involving obstetrics, neurosurgery, and endocrinology in managing craniopharyngiomas during pregnancy.

Learning points: Regardless of pregnancy planning, central hypogonadism should always be investigated with a brain MRI to determine its etiology, including the potential presence of a craniopharyngioma or other sellar/parasellar lesions. If a craniopharyngioma enlarges during pregnancy and causes visual impairment, surgical intervention can be performed through multidisciplinary collaboration. The mode of delivery in patients with panhypopituitarism should be carefully determined through multidisciplinary consultation between obstetricians and endocrinologists, with consideration of planned cesarean section as a potential option.

Summary: Congenital hyperinsulinism is a rare disorder characterized by hypoglycemia and inappropriately elevated insulin levels. The genetics of congenital hyperinsulinism is complex, with the most common cause being pathogenic variants in the ATP-sensitive potassium channel. Depending on the parent of origin, patients may present with focal or diffuse hyperinsulinism. Typically, patients with focal hyperinsulinism are non-responsive to diazoxide and likely progress to surgical therapy. However, there can be exceptions to these rules. We evaluated two siblings with congenital hyperinsulinism. Genetic testing identified a paternally inherited variant in ABCC8. One sibling had significant neonatal hypoglycemia requiring diazoxide for several years before weaning off daily diazoxide, whereas the second sibling experienced transitional hypoglycemia in the neonatal period but only requires diazoxide therapy during periods of intercurrent illness. This case highlights the importance of genetic testing for congenital hyperinsulinism.

Learning points: The most common genetic cause of hyperinsulinism is gain-of-function variants in ABCC8 and KCNJ11, which make up the ATP-sensitive potassium channel (KATP). First-degree relatives of affected individuals should be considered for genetic testing. Parent-of-origin testing should be done to determine if the patient is likely to have focal or diffuse hyperinsulinism. Diazoxide is helpful for many patients with diffuse hyperinsulinism, and some patients with focal hyperinsulinism.

Summary: Pycnodysostosis (PYCD) is an osteosclerotic skeletal dysplasia caused by mutations in the CTSK gene. We describe four cases, highlighting their clinical progression and therapeutic responses. Case 1 is a 2-year-old girl with non-consanguineous parents exhibiting short stature (Z-score: -3.23), slow growth (3 cm/year), wide fontanelles, small hands, and no fractures. She received cholecalciferol and calcium. Two CTSK variants (c.436G>C; p.Gly146Arg and c.721C>T; p.Arg241*) were identified. At age three, somatropin was initiated, leading to improved growth (8 cm/year) and a stature Z-score of -2.21, without fractures until age six. Case 2 is a 2-year-old boy, sibling of Case 1, presenting with similar findings (Z-score: -1.81). Carrying the same CTSK variants, he showed improved growth (3 cm/4 months) after growth hormone therapy. Case 3 is a 3-year-old boy with consanguineous parents having short stature (Z-score: -3.75), slow growth (2 cm/year), exophthalmos, bluish sclera, and multiple tibial fractures. A homozygous CTSK variant (c.953G>A; p.Cys318Tyr) was identified. Growth hormone at age six, alongside cholecalciferol and calcium, increased growth (7 cm/year) and improved stature (Z-score: -2.65). Case 4 is an 8-year-old girl with consanguineous parents having multiple fractures, exophthalmos, and severe growth impairment. Misdiagnosed with osteogenesis imperfecta, she received bisphosphonates, further compromising bone integrity. While genotype defines PYCD, early intervention can modulate its phenotype. Growth hormone, calcium, and cholecalciferol improved growth, whereas bisphosphonates negatively impacted bone quality.

Learning points: CTSK mutations define PYCD, but patients exhibit diverse skeletal features, necessitating individualized management. Despite normal IGF-1, growth hormone therapy enhances growth velocity and final height in selected PYCD cases. Bisphosphonates may worsen bone remodeling in PYCD, increasing fracture risk and impairing growth. The CTSK c.953G>A (p.Cys318Tyr) variant correlates with severe skeletal manifestations and variable treatment response.

Summary: We present the case of a 51-year-old man who was referred to our hospital due to abnormal thyroid function tests. Laboratory evaluations showed elevated serum free (F) T3 and free (F) T4 levels (9.05 pg/mL and 4.21 ng/dL, respectively), with a normal serum thyroid-stimulating hormone (TSH) level of 1.49 μIU/mL, indicating central hyperthyroidism. An 18 × 17 × 14 mm T1-weighted hypointense tumor was found on the left side of the pituitary gland, with low contrast enhancement during a cranial MRI. The TRH stimulation test revealed no TSH response. The administration of a single dose of octreotide reduced TSH levels. Following these findings, the patient was clinically diagnosed with a TSH-producing pituitary tumor (TSHoma). The patient was directed to our hospital's neurosurgery department for pituitary surgery and began preoperative treatment with lanreotide autogel (90 mg, subcutaneous injection). Four days after administration, FT3 and FT4 levels returned to normal. Seven days after administration, an MRI revealed a 50% reduction in tumor volume. Endoscopic pituitary surgery was performed 15 days after the initial administration and resulted in complete tumor resection. A histopathological examination confirmed the presence of a TSH-producing pituitary neuroendocrine tumor. Postoperatively, FT3 and FT4 levels stayed within the normal ranges. This case demonstrates how a single dose of lanreotide autogel not only normalized thyroid hormone levels but also resulted in rapid shrinkage of the pituitary tumor in TSHoma.

Learning points: Preoperative treatment with somatostatin analogs for TSH-producing pituitary adenomas (TSHomas) aims to control thyroid function, preventing thyroid storm during surgery, and to reduce tumor size. We report a case of a TSHoma treated preoperatively with a single subcutaneous injection of lanreotide autogel (LAN-ATG). In this patient, thyroid function normalized and significant tumor shrinkage was observed within 1 week of LAN-ATG administration. This case demonstrates that significant therapeutic effects can be achieved within days after a single injection of LAN-ATG. This approach could facilitate earlier surgical intervention, potentially improving patient outcomes and optimizing preoperative management strategies.