Case Reports in Endocrinology最新文献

Background: Cribriform morular thyroid carcinoma has been recently renamed in the 2022 WHO classification as a thyroid tumor of uncertain histogenesis. The epidemiologic, pathological, and pathophysiological characteristics distinguish it from papillary thyroid carcinoma (PTC). Preoperative genetic testing plays a role in facilitating the differential diagnosis.

Methods: This report presents a confirmed case of cribriform morular thyroid carcinoma. Initially, fine-needle aspiration cytology suggested a diagnosis of PTC. However, a genetic analysis did not reveal the typical mutations associated with follicular-cell-derived neoplasms.

Results: A 31-year-old woman was found to have a thyroid nodule at the left lobe measuring 11.8 × 10.2 × 12.4 mm. Ultrasonography indicated a hypoechoic, solid nodule with regular margins. Cytology revealed a papillary structure of tall cells, leading to a PTC diagnosis. Nevertheless, the genetic analysis failed to detect mutations such as BRAF V600E, NRAS Q61R, NRAS Q61K, HRAS Q61R, or HRAS Q61K mutation or the fusion of CCDC6-RET, NCOA4-RET, PAX8-PPARG, ETV6-NTRK3, TPM3-NTRK1, IRF2BP2-NTRK1, or SQSTM1-NTRK1 in the aspirated follicular cells. The patient subsequently underwent total thyroidectomy with central lymph node dissection. Pathological examination revealed a cribriform pattern of spindle-shaped cells with morular areas. Immunohistochemical staining showed positive results for β-catenin and TTF-1, except in the morular regions, and negative results for PAX8, thyroglobulin, and BRAF (clone VE1). The diagnosis was confirmed to be cribriform morular thyroid carcinoma.

Conclusion: Significant cytological similarity exists between PTC and cribriform morular thyroid carcinoma. Preoperative genetic analysis is important to differentiate these two diseases. Cribriform morular thyroid carcinoma can be differentiated from common follicular-cell-derived tumors by the absence of typical mutations; the presence of nuclear and cytoplasmic expressions of β-catenin; the presence of TTF-1, except in morular areas; and the absence of thyroglobulin.

Mauriac syndrome is a rare disorder that occurs in patients with type 1 diabetes mellitus (T1DM) with glucose levels significantly above target, characterized by hepatomegaly, growth delay, and cushingoid features. Another distinguishing feature of Mauriac syndrome is persistent lactatemia during diabetic ketoacidosis (DKA) management. We present a case of an 18-year-old patient with T1DM who presented in DKA and then developed elevated lactate levels leading to a diagnosis of Mauriac syndrome. The cause of the persistent lactatemia is not well understood though it is likely related to glycogenic hepatopathy causing hepatomegaly, abnormalities in glucose metabolism, and subsequent inappropriate lactate production. Since the liver changes seen in Mauriac syndrome are reversible with optimal blood glucose control, these patients should be connected to intensive psychosocial and medical support to help them improve their blood glucose levels.

Production of the high-molecular-weight forms of adrenocorticotropic hormone (big-ACTH) has been reported in a small number of ectopic ACTH syndrome and ACTH-producing pituitary macroadenoma. However, perioperative changes in big-ACTH in patients with subclinical Cushing's disease have not been reported. A 63-year-old woman presented 25 × 20 × 20-mm-sized macroadenoma in the pituitary gland. Her early morning plasma ACTH and cortisol levels were 111 pg/mL and 11.6 μg/dL, respectively. Cushingoid features and diurnal variation in plasma cortisol levels were not observed. The patient's urinary free cortisol (UFC) was 59.3 μg/day. The corticotropin-releasing hormone (CRH) test showed that plasma ACTH levels were 1.5 times higher than the preload value. The overnight dexamethasone suppression test (DST) showed that the plasma cortisol level was not suppressed by 0.5 mg of dexamethasone (DEX) but was suppressed by 8 mg of DEX. Inferior pyramidal sinus sampling was consistent with Cushing's disease. Taken together, the patient was clinically diagnosed with subclinical Cushing's disease caused by an ACTH-producing pituitary adenoma. Endoscopic transsphenoidal adenomectomy was performed. In the postoperative CRH test, plasma ACTH levels showed six-fold increase. The postoperative DST showed cortisol suppression at 0.5 mg of DEX. The UFC levels decreased to 35.1 μg/day. Pituitary contrast-enhanced MRI revealed no residual tumor, and plasma ACTH and cortisol levels remained within normal ranges. Gel filtration of preoperative and postoperative plasma ACTH was performed, and a high molecular weight fraction of ACTH was detected, which markedly decreased postoperatively. The absence of Cushingoid features and the lack of significant cortisol hypersecretion in this case were thought to be due in part to big-ACTH, which has low bioactivity. By careful evaluation of laboratory and clinical findings, we identified it as a big-ACTH-producing adenoma. This is the first report of a case in which the big-ACTH transition was observed perioperative and is a valuable case.

Background: The COVID-19 pandemic has caused major impacts in various aspects of our life. In Malaysia, a Movement Control Order was imposed in March 2020. For almost two years, school going children and adolescents were not able to attend school physically, and their physical activity was confined within their room or house on most days. Case Description. We describe a case of a 14-year-old boy who was previously active in sports and sustained a low trauma fracture at the right neck of the femur following a prolonged period of extreme sedentary life along with poor dietary intake during the COVID-19 pandemic period. He underwent open reduction and screw fixation for the right neck femur fracture. He was thin with a low BMI (15.62 kg/m²) and a significant loss of muscle bulk in all limbs. Laboratory tests showed vitamin D deficiency (15.3 nmol/L) and the dual energy X-ray absorptiometry (DXA) showed a low Z-score for the total spine (-2.2) and total hip (-3.9). He was treated with activated vitamin D and vitamin D3 replacement. Sports physician was involved for individualized postoperative rehabilitation. Successive clinic visits showed remarkable improvements in physical fitness, sports participation, and normalization of vitamin D levels.

Conclusion: A high degree of suspicion is needed to rule out secondary causes in adolescents who present with unusual fragility fractures.

A 74-year-old patient with type 2 diabetes mellitus received basal-bolus insulin, insulin secretagogues, and sodium glucose transporter 2 (SGLT2) inhibitors. After immune checkpoint inhibitor treatment for lung cancer, he suffered from depressed consciousness with a urinary ketone body (3+). When all hypoglycemic treatments were discontinued, his serum blood glucose remained at 121 mg/dL. He was diagnosed with euglycemic diabetic ketosis. Endocrine loading tests revealed isolated adrenocorticotropic hormone (ACTH) deficiency as an immune-related adverse event. It was suggested that euglycemic diabetic ketosis was induced by the self-suspension of insulin and insulin secretagogues, adrenal insufficiency, SGLT2 inhibitors, and carbohydrate intake shortage.

Introduction: The triad of hypercalcemia, metabolic alkalosis, and acute kidney injury associated with ingesting high doses of calcium and absorbable bases characterizes the calcium-alkali syndrome. Clinical Case. We report the case of a patient with postthyroidectomy hypoparathyroidism 15 years ago due to differentiated thyroid cancer who presented with severe hypercalcemia. He had adequate control of calcemia for many years on treatment with calcitriol and calcium carbonate and hypertension treated with amlodipine, losartan, and hydrochlorothiazide. After a period of loss to follow-up, he suddenly presents with severe hypercalcemia, metabolic alkalosis, and loss of renal function. Upon hydration and withdrawal of calcitriol and calcium replacements, hypercalcemia resolved. The etiological investigation identified no granulomatous or neoplastic diseases, but an aldosterone-producing adrenal incidentaloma was found. The cause of hypercalcemia in this patient was calcium-alkali syndrome due to calcium carbonate replacement potentiated by hydrochlorothiazide and primary aldosteronism. Six months after the hospitalization and suspension of calcium and vitamin D, the patient returned to hypocalcemia, reinforcing the diagnosis.

Conclusion: Although seldom described, the calcium-alkali syndrome is an expected complication for individuals with postoperative hypoparathyroidism, as they require lifelong calcium and vitamin D supplementation. This case also shows the importance of hydrochlorothiazide use and primary aldosteronism as possible triggers of life-threatening hypercalcemia.

Background: Primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcaemia (FHH) are common causes of hypercalcaemia. Patients are mostly asymptomatic in the case of FHH and often so in the case of PHPT. In addition, biochemical parameters show considerable overlap, making differential diagnosis difficult. Genetic screening for inactivating variants in the calcium-sensing receptor (CASR) gene that are causative of FHH assists with the diagnosis since such variants are not generally associated with PHPT. However, novel CASR variants must undergo functional assessment before they can be definitively assigned a causative role in FHH. Case Presentations. We describe a 73-year-old female (patient A) who presented with mild parathyroid hormone (PTH)-dependent hypercalcaemia and a history of osteoporosis. Family history revealed that her sister (patient B) had presented a decade earlier with symptoms of PHPT including a history of mild hypercalcaemia and multiple renal calculi, prompting parathyroid surgery. However, a subtotal parathyroidectomy did not resolve her hypercalcaemia long term. On this basis, genetic screening was performed on patient A. This identified a heterozygous variant in the CASR, NM_000388.4:c.T101C: p.Leu34Pro (L34P). Functional analysis showed that the L34P variant was unable to produce mature, dimerized receptor and did not respond to Ca⁺⁺ ions. Adopting American College of Medical Genetics-based guidelines, the variant was classified as 'Pathogenic (II)'. Patient B was subsequently found to carry the L34P variant heterozygously, confirming a diagnosis of FHH, not PHPT.

Conclusion: This study shows the importance of examining patient's family history in providing clues to the diagnosis in isolated cases of hypercalcaemia. In this case, history of a sister's unsuccessful parathyroidectomy prompted genetic screening in a patient who might otherwise have undergone inappropriate parathyroid surgery. Screening detected an inactivating CASR variant, firming up a diagnosis of FHH. These studies reaffirm the requirement for functionally assessing novel CASR variants prior to assigning causality to FHH.

Hypocalcemia following denosumab administration is well described. Hypophosphatemia following an intravenous iron infusion is an increasingly recognized adverse effect. Intravenous iron preparations increase fibroblast growth factor 23 (FGF23) levels. This both stimulates renal phosphate excretion and reduces 1,25-dihydroxyvitamin D (1,25(OH)₂D) levels, resulting in reduced calcium absorption. Both osteoporosis and iron deficiency are common and frequently co-occur. The convenience and efficacy of both denosumab, a subcutaneous injection, and ferric carboxymaltose (Ferinject®), a 15-minute intravenous infusion, both of which can be given in the primary care setting, make these preferred treatment options. However, prescribers are often unaware of potential adverse outcomes, especially when these medications are given in tandem. We present a case of symptomatic hypocalcemia and hypophosphatemia in a 29-year-old woman with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and normal renal function, in the setting of concurrent denosumab and ferric carboxymaltose administration for treatment of glucocorticoid-induced osteoporosis and iron deficiency anemia.

Natural desiccated thyroid (NDT) is a treatment option for many patients with hypothyroidism, but some still exhibit symptoms despite achievement of normal levels of thyroid stimulating hormone (TSH). In this retrospective case series, 13 patients with hypothyroid symptoms were switched from NDT to a liquid formulation of levothyroxine (LT4; Tirosint®-SOL). Laboratory values ≥4 weeks following the switch showed a decrease in TSH levels, maintenance of free triiodothyronine (fT3) levels, and significant increases in free thyroxine (fT4) levels. Patients reported good tolerability, and case summaries are presented for four patients. In summary, this small retrospective case series showed that patients who still had hypothyroid symptoms despite use of NDT can respond well to oral LT4 liquid formulation, including patients who are intolerant of gluten and/or lactose or on hormone replacement therapy or iron supplementation.

Introduction: Cystic fibrosis transmembrane regulator (CFTR) modulator therapies improve respiratory function and glycaemic control in patients with cystic fibrosis (CF). The direct effect of CFTR modulator therapies on pancreatic function in patients without preexisting diabetes remains unclear. Case Presentation. An 18-year-old female with CF caused by F508del/F508del mutation, who had no diabetes, developed postprandial hypoglycaemias 6 months after initiation of elexacaftor, tezacaftor, and ivacaftor combination therapy (ETI). Symptoms were persisted after brief discontinuation of ETI, but her symptoms and time-in-hypoglycaemia had improved remarkably by avoiding high glycaemic index-foods. Discussion. This case of hypoglycaemia associated with CFTR modulator therapy in a patient without preexisting diabetes suggests that CFTR modulator therapy has the potential to directly affect glucose homeostasis. There might be an improvement in insulin secretion as well as a reduction in systemic insulin resistance.

Conclusion: Treatment of CF patients without diabetes with CFTR modulator therapies can cause recurrent hypoglycaemic episodes which resolve with dietary measures.