Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: We presented a case of a 72-year-old male with severe hypercalcaemia of 3.84 mmol/L following the second cycle of immunotherapy with ipilimumab and nivolumab in the setting of metastatic melanoma with known bone metastases. Further investigations demonstrated hilar lymphadenopathy, which was not present in previous imaging, and subsequent hypercalcaemia work-up demonstrated a significantly elevated serum calcitriol level as high as 429 pmol/L. A diagnosis of drug-induced sarcoid-like reactions or DISRs was made on the basis of hypercalcaemia and hilar lymphadenopathy following immunotherapy. Hypercalcaemia was effectively treated with intravenous fluids and medical therapy including a short course of subcutaneous calcitonin, a total of 120 mg of denosumab and oral prednisolone.

Learning points: DISRs are a rare complication of immunotherapy and may mimic metastases. A temporal relationship between commencement of therapy and progression on clinical imaging is important in making an accurate diagnosis.Calcitriol-mediated hypercalcaemia secondary to DISRs is an important differential diagnosis to hypercalcaemia of malignancy and should be considered in patients who have undergone immunotherapy.Prednisolone should be considered as the next line of treatment after fluid therapy in patients with calcitriol-mediated hypercalcaemia. Prednisolone and denosumab both reach maximum clinical efficacy between 7 and 10 days. Therefore, treatment administration should be spaced out by at least five days to avoid iatrogenic hypocalcaemia.

Summary: A 17-year-old girl presented with recurrent attacks of acute pancreatitis, associated with severe hyperglycemia and hypertriglyceridemia, despite being on intensive insulin therapy for the last 10 years. She had severe acanthosis nigricans, generalized loss of subcutaneous fat and prominent veins over extremities. The serum levels of glucose and triglyceride did not reduce significantly, even with maximally tolerated doses of metformin (2 g), pioglitazone (45 mg) and fenofibrate (160 mg), not uncommonly seen in poor rural families in West Bengal, India. A detailed dietary recall revealed a very high carbohydrate intake (70% of total calorie) with very low protein and fat intake. A switch to a very low carbohydrate (30% of total calorie) diet led to a remarkable improvement in glucose and lipid profiles (the daily insulin requirement came down by 50% and triglyceride level came down to 600 mg/dL from 950 mg/dL). A whole-exome sequencing study confirmed congenital generalized lipodystrophy type 4. A carbohydrate restriction strategy may improve difficult-to-control glycometabolic profile in lipodystrophic subjects on high-carbohydrate diet.

Learning points: Lipodystrophy should be suspected in patient presenting with hyperglycemia, hypertriglyceridemia and low BMI. A very low carbohydrate diet (30% of total daily calorie intake) may significantly improve glucose and lipid profiles in patients with lipoatrophic diabetes. Blood glucose may be the most important initial step to control hypertriglyceridemia and risk of pancreatitis in this group of patients.

Summary: Hypophosphatasia (HPP) is a genetic disorder due to pathological variants in ALPL, the gene encoding tissue-nonspecific alkaline phosphatase (ALP). HPP is typically associated with bone-related symptoms, such as bone deformity, fractures and bone pain in children, but can appear in adults with symptoms resembling arthritis. A 22-year-old male experienced repeated and severe sudden attacks of joint pain in the elbows and knees. Magnetic resonance imaging and joint ultrasonography showed joint effusions indicating chronic inflammation. Blood biochemical tests revealed a remarkably low serum ALP level, and repeated examination confirmed a sustained low ALP level; urine phosphoethanolamine, plasma inorganic pyrophosphate and plasma pyridoxal-5'-phosphate levels were elevated, raising concern for HPP. While the patient had no history of premature loss of primary teeth, fragility fractures, muscle weakness or abnormalities in growth, genetic testing revealed a likely pathogenic and a pathogenic heterozygous variant in the ALPL gene, i.e., c.979T>C (p.Phe327Leu) and c.1559del (p.Leu520Argfs), confirming HPP. Additional genetic testing of his parents showed a heterozygous c.1559del variant in his father and a heterozygous c.979T>C variant in his mother. A diagnosis of adult HPP due to compound heterozygous mutations was therefore confirmed. Enzyme replacement therapy with asfotase alfa was then introduced; no attacks of arthralgia occurred in the 1-year period since then. This case highlights the possibility of HPP in adults who present clinically with repeated joint symptoms and low serum ALP levels but without bone-related symptoms.

Learning points: A diagnosis of adult HPP without bone-related symptoms can be challenging. A reduction in tissue-nonspecific ALP activity leads to an accumulation of pyrophosphate in the joints, which can cause arthralgia. Some cases of adult HPP have arthralgia as the only presenting symptom. At one-year follow-up, enzyme replacement therapy with asfotase alfa might lead to a reduction in arthralgia attacks due to HPP.

Summary: Oral levothyroxine (LT4) is prescribed worldwide for hypothyroidism. Bariatric surgery for patients with obesity has shown a substantial, long-term weight loss and considerable improvement of obesity-related diseases. LT4 malabsorption represents a significant cause of refractory hypothyroidism, well known after malabsorptive bariatric surgery such as Roux-en-Y gastric bypass. However, few studies have shown an increase in oral LT4 needed after sleeve gastrectomy. We present a 47-year-old woman with class III obesity and a history of papillary thyroid cancer, with an excellent biochemical and structural response after total thyroidectomy and radioactive iodine. She underwent sleeve gastrectomy 3 years later and developed refractory hypothyroidism despite taking high doses of oral LT4 and ensuring compliance. The T4 absorption test confirmed gastrointestinal LT4 malabsorption. She was initiated on intramuscular LT4 and oral T3 (liothyronine) with improving symptoms and levels of thyroid-stimulating hormone.

Learning points: Monitoring thyroid function tests is essential after bariatric surgery, including sleeve gastrectomy. Oral LT4 malabsorption should be considered in cases of refractory hypothyroidism. The T4 absorption test is a useful tool for distinguishing true malabsorption from pseudo-malabsorption. Decreased LT4 absorption after bariatric surgery might be explained by higher gastric pH and reduced stomach volume (impaired dissolution) and by interference with food, vitamin/mineral supplements or other drugs. When LT4 malabsorption is confirmed, a trial of other oral formulations (LT4 tablet crushed, soft gel or liquid preparation) or parenteral administrations is suggested.

Summary: Short stature is a common complaint among pediatric visits and the differential diagnosis is extensive. Although some variations in growth are normal, deviation from normal growth is often the first symptom of chronic disease in children. This is true for hormone abnormalities including growth hormone deficiency, hypothyroidism and glucocorticoid excess. However, reduced growth velocity can also occur as the first sign of chronic anemia, malnutrition, deprivation (psychosocial dwarfism), chromosomal abnormalities, genetic syndromes and inflammatory bowel diseases. For the primary care provider, simple measures of standing height, sitting height, arm span, weight, body mass index (BMI) and bone age (BA) will lead to the correct diagnosis in most short children. Screening laboratory studies for endocrine disorders, a skeletal survey if skeletal disproportion is evident, a karyotype or microarray (microarray favored if developmental delay is also present) and genetic testing for monogenic disorders will lead to a specific diagnosis in an additional subset of short children. This case presented a diagnostic dilemma that spanned all these possibilities and served as a focal point for the review of normal growth and growth abnormalities.

Learning points: Variations in growth can be normal variants (constitutional delay of growth and puberty or familial short stature) but deviation from normal growth can also be the first sign of an underlying pathological process. Measures of standing height, sitting height, arm span, weight, body mass index (BMI) and bone age (BA) will lead to the correct diagnosis in 50-80% of short children. Screening laboratory studies for endocrine disorders, a skeletal survey if skeletal disproportion is evident, a karyotype or microarray (microarray is favored if developmental delay is also present) and genetic testing will lead to a specific diagnosis in another 35% of short children. Pseudohypoparathyroidism (PHP) type 1A is due to a mutation in the alpha subunit of the stimulatory G protein of the guanine nucleotide-binding protein gene. Multiple hormone resistance often affects thyroid-stimulating hormone and, when presenting in the newborn period, can be misdiagnosed as common forms of congenital hypothyroidism. Molecular testing is an important component of confirming the diagnosis and PHP subtype, which can help guide management.

Summary: Vitamin D is commonly recommended for daily intake as dietary sources are often insufficient. However, prolonged high-dose use can lead to serious complications. We present a rare case of a 2-month-old infant who developed severe hypercalcemia and hypertriglyceridemia due to an accidental overdose of 25-OH vitamin D, leading to hypertriglyceridemia and pancreatitis. The management challenges encountered while managing this case were the need for high glucose infusion rate fluids with insulin for hypertriglyceridemia, electrolyte imbalances secondary to forced diuresis, difficulties in providing fat-free formula, gradual introduction of maternal breastfeeding due to pancreatitis and rebound hypercalcemia requiring steroid treatment. These complications, rarely reported in hypervitaminosis D, highlight the need for careful vitamin D dosing in the pediatric population. Potential areas leading to vitamin D intoxication include improper formulation, lack of clarity in prescribing, concurrent use of other vitamin D-containing supplements, parental access to the internet for health supplements and easy availability.

Learning points: Children presenting with polyuria and failure to thrive should be screened for hypercalcemia as one of the causes. Hypertriglyceridemia with pancreatitis can be managed with IV insulin infusion, high dextrose-containing fluids and gradual feed establishment as pancreatitis improves. The case report underscores the serious and potentially life-threatening complications associated with vitamin D intoxication while emphasizing the importance of educating parents on safe dosage practices.

Summary: Palmoplantar keratoderma (PPK), characterised by excessive epidermal thickening of the skin on the palms and/or plantar surfaces of the feet, can be hereditary or acquired. Here, we report a case of a 53-year-old woman with a history of sub-optimally controlled diabetes mellitus presenting with fevers and decreased Glasgow Coma Scale (GCS) to a tertiary hospital. She was diagnosed with diabetic ketoacidosis (DKA), with blood glucose at 40 mmol/L and ketones at 7 mmol/L, in the setting of a methicillin-sensitive Staphylococcus aureus necrotising soft tissue back infection. Her medical history included diabetes managed with insulin but no engagement with an endocrinologist or allied health support. Examination revealed an infected, necrotic back wound on her left mid-upper back that required surgical debridement and broad-spectrum IV antibiotics. In addition, she exhibited marked plantar keratoderma and onychogryphosis, reportedly present and worsening over approximately two years. She was prescribed 40% urea cream twice daily, resulting in gradual sloughing of the hyperkeratotic skin within a few weeks. Her HbA1c was 10.4%, and she tested negative for diabetes antibodies, indicating type 2 diabetes. Treatment included an insulin-dextrose infusion until DKA resolved, followed by twice daily insulin degludec/aspart (Ryzodeg 70/30) and metformin. The PPK was attributed likely secondary to sub-optimally managed diabetes.

Learning points: Diabetes mellitus has multiple complications, including rare dermatologic manifestations such as PPK.This case illustrates the importance of thorough skin assessments in patients with diabetes, particularly those that have a history of sub-optimal diabetes control.A multidisciplinary approach, integrating dermatology, endocrinology and allied health services such as podiatry, is essential in managing diabetes-related complications, improving patient quality of life and preventing further complex manifestations.

Summary: Paediatric pituitary adenomas are rare in children and adolescents and differ from adults in both clinical presentation and management. We present the case of a 14-year-old female with primary amenorrhoea secondary to a macroprolactinoma, showing a modest radiological and biochemical response to dopamine agonist (DA) therapy. Despite a 10-month duration of increasing DA therapy, initial symptoms of primary amenorrhoea and hyperprolactinaemia persisted, with new symptoms of weight gain, lethargy and low mood. A transsphenoidal resection of the macroprolactinoma was successfully performed, followed by the initiation of additional hormonal therapy. This case explores the unique challenges of treating a macroprolactinoma refractory to medical management in adolescence.

Learning points: Management of macroprolactinomas in childhood and adolescence can bring unique challenges, including a delay in sexual development, often presenting with primary or secondary amenorrhoea in girls.DA therapy is typically the first-line therapy in treating macroprolactinomas; however, resistance in paediatric and adolescent patients is associated with tumour size and initial prolactin levels.Surgical resection should be considered as a second-line therapy for adolescents unable to tolerate high-dose DA therapy or have inadequate response to DA therapy.There are a range of potential surgical complications, including permanent or transient diabetes insipidus, meningitis, cerebrospinal fluid leakage and hypopituitarism.Timely management of macroprolactinomas is important for secondary sex characteristics, bone development and psychological well-being.

Summary: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant condition characterized by multiple cutaneous and uterine leiomyomas and renal cell cancer (RCC). HLRCC is caused by germline pathogenic/likely pathogenic (P/LP) variants in the fumarate hydratase (FH) gene on chromosome 1q42.3, encoding the mitochondrial enzyme responsible for the conversion of fumarate to malate in the Krebs cycle. 0.6-3.1% of individuals with pheochromocytoma/paraganglioma (PCC/PGL) carry a germline variant in the FH gene. Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do. We described a female-to-male transgender with HLRCC who presented with large symptomatic uterine leiomyomas in the third decade of life and was diagnosed with a PCC 19 years after hysterectomy and with cutaneous leiomyomas and an aggressive form of RCC in the sixth decade of life. With the publication of this case and the review of the existent literature, and until more information becomes available, we would like to emphasize that clinicians should be aware of the possible connection between HLRCC and PCC/PGL, that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and finally that patients with HLRCC should be screened for PCC/PGL.

Learning points: HLRCC, an autosomal dominant condition caused by germline P/LP variants in the fumarate hydratase (FH) gene, is characterized by multiple cutaneous and uterine leiomyomas and RCC.0.6-3.1% of individuals with PCC/PGL carry a germline P/LP variant in the FH gene.Most of these patients have no personal or family history of HLRCC-associated manifestations, but some of them do.Preliminary evidence suggests that genetic testing for susceptibly genes for PCC/PGL should include the FH gene and that patients with HLRCC should be screened for PCC/PGL.Until more information becomes available, we suggest doing a full history, physical, family history, and screen for HLRCC-associated manifestations when there is an FH variant.Screening for PCC/PGL in patients with HLRCC could potentially include a baseline whole-body MRI and plasma fractionated metanephrines.

Summary: An oral contraceptive pill (OCP)-induced increase in total cortisol lead to reversible suppression of the hypothalamic-pituitary-adrenal (HPA) axis and insulin resistance (IR) in a patient with Addison's disease. We suggest that this might influence the choice of an OCP in such patients. A 20-year-old female was diagnosed with Addison's disease (cortisol: 44 nmol/L, adrenocorticotropic hormone (ACTH): >500 pg/mL) and started on hydrocortisone (HC). Few months later, an OCP (30 μg ethinyl oestradiol (EE) and 3 mg drospirenone) was added. Total cortisol was above the upper assay detection limit (UADL), while ACTH was inappropriately 'normal': cortisol 8:00 (pre-dose) 83 nmol/L, post-dose 10:00 >1757 nmol/L, ACTH 8:00 (pre-dose) 24.1 pg/mL and post-dose 10:00 3.8 pg/mL. Even 5 mg of oral HC induced an increase in cortisol above UADL. The glucagon stimulation test (GST) showed brisk growth hormone secretion. The corticotropin-releasing hormone (CRH) test showed partial hypothalamic suppression of CRH release: minimal ACTH 42.4 pg/mL and maximal ACTH 87.3 pg/mL, i.e. relatively low levels for all cortisol concentrations <69 nmol/L. Withdrawal of the OCP resulted in the return of high ACTH concentrations typical for patients with Addison's disease on HC replacement. There was also a marked improvement in insulin resistance (a fall in homeostasis model assessment - insulin resistance (HOMA-IR) from 3.64 to 1.69 and a marked decline in mean insulin concentrations during GST). EE administration resulted in a massive increase in total cortisol with suppression of the HPA axis and IR suggestive of relative hypercortisolaemia. This raises the question of whether EE should be avoided as a contraceptive agent in women with adrenal failure.

Learning points: An OCP containing 30 μg EE induced relative and reversible hypercortisolaemia in a patient with Addison's disease with evidence of suppression of ACTH secretion on dynamic pituitary function tests.We suggest that, in some patients with adrenal failure, EE administration may lead to unrecognised relative hypercortisolaemia and IR.There is literature evidence that, in patients with Addison's disease, EE may decrease cortisol clearance.These alterations are reversible upon EE withdrawal and may have implications for the choice of a contraceptive agent in women with Addison's disease.