Ectopic thyroid is a rare developmental anomaly. In ectopic thyroid, thyroid tissue develops outside its normal position (anterior to the trachea), and it can occur within or outside the migratory pathway of the thyroid gland primordium. Ectopic thyroid tissue located in two sites is referred to as dual ectopic thyroid. This report describes a case of transient congenital hypothyroidism (CH) who had dual ectopic thyroid glands: one located at the base of the tongue (within the migratory pathway) and the other in the left parapharyngeal space (outside the migratory pathway). A 24-year-old woman, diagnosed with CH in the neonatal period, had been treated with levothyroxine. Since levothyroxine was discontinued at the age of 7 years, her thyroid function has remained normal. At 24 years of age, she was reevaluated because of throat discomfort. Although her thyroid function remained normal, ultrasonography revealed two ectopic thyroid masses. 99mTc thyroid scintigraphy confirmed thyroid tissue in both locations. Genetic analysis did not reveal any suspicious genetic changes related to CH. Currently, she is under observation without treatment. This rare case of dual ectopic thyroid with transient CH underscores the importance of anatomical evaluation and long-term follow-up in patients with neonatal thyroid disorders.
Hyperglycemia is an adverse effect of targeted cancer therapies; however, the mechanisms underlying B-Raf proto-oncogene, serine/threonine kinase (BRAF)/mitogen-activated protein kinase kinase (MEK) inhibitor-associated hyperglycemia remain unclear. We describe an 80-year-old man who developed severe hyperglycemia during combination therapy with dabrafenib and trametinib for BRAF V600E-positive lung adenocarcinoma. Before treatment, he was obese and had unrecognized mild diabetes. Seven months after treatment initiation, he presented with hyperglycemia accompanied by a reduced insulin secretory capacity. Serial measurements of the C-peptide index revealed that the temporary withdrawal of dabrafenib-trametinib resulted in the recovery of insulin secretion, which gradually decreased again upon reinitiation. This case underscores the clinical importance of monitoring both the glycemic status and insulin secretion in patients receiving BRAF/MEK inhibitors.
Thyroid nodules are increasingly detected with advanced imaging. Although most are benign, accurate preoperative risk stratification remains essential. Fine-needle aspiration is central to evaluation, yet Bethesda III nodules remain challenging because of the variable malignancy risk. Thyroid carcinoma generally has a favorable prognosis, but certain molecular subtypes are associated with higher mortality. Therefore, surgical resection remains the standard treatment for indeterminate and malignant thyroid tumors. However, the thyroid's rich vascular supply, along with comorbidities and factors such as age and mediastinal extension, can increase operative risk. Preoperative transarterial embolization has emerged as an adjunct to reduce tumor vascularity and improve surgical outcomes. We report a case of a 72-year-old African American male with multiple comorbidities who presented with an indeterminate thyroid neoplasm harboring a TERT promoter pathogenic variant, indicating high malignancy risk. The patient underwent pressure-enabled thyroid artery embolization followed by thyroidectomy 72 hours postembolization. Lesion histopathology showed nuclear debris and ghost cells consistent with complete pathologic necrosis. This case supports the feasibility of embolization as an adjunct in the multidisciplinary management of high-risk patients and provides a foundational basis to further study embolotherapy in unresectable tumors or nonsurgical candidates.
Postbariatric hypoglycemia (PBH) represents a challenging complication of bariatric surgery. This case series describes 3 patients with PBH following Roux-en-Y gastric bypass who were treated with tirzepatide, a glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (RA). All patients presented with symptomatic hypoglycemia characterized by episodes of diaphoresis, visual disturbances, confusion, and documented low blood glucose levels occurring postprandially. Conventional management strategies, including dietary modifications, acarbose, and other pharmacotherapies, were either partially effective or limited by side effects. Initiation of tirzepatide led to increased time in range, reduced number and severity of hypoglycemic episodes, and decreased glucose variability. This report suggests that GLP-1 and GIP RA can be a promising adjunct in managing PBH; however, further studies to confirm their efficacy and establish optimal dosing strategies are needed.
Parathyroid carcinoma is a rare cause of primary hyperparathyroidism (PHPT) and is often difficult to distinguish from benign parathyroid disease in its early stages. We describe a nearly 20-year clinical course of recurrent PHPT requiring 4 surgical interventions, ultimately culminating in the diagnosis of parathyroid carcinoma in a nonorthotopic supraclavicular location. The patient was followed continuously at our institution, allowing longitudinal assessment of biochemical, imaging, and histopathological findings. The initial surgery resulted in biochemical remission following removal of a parathyroid adenoma; however, hypercalcemia and elevated intact parathyroid hormone levels recurred over time. Subsequent resections demonstrated parathyroid-type proliferation with increasing Ki-67 index, and the final surgery revealed capsular and venous invasion consistent with carcinoma. Notably, technetium-99 m methoxyisobutylisonitrile uptake became progressively weaker over time and eventually appeared as faint uptake in a nonorthotopic location. These findings may reflect changes in tumor biology over time. Although it remains uncertain whether the supraclavicular lesion represented an ectopic primary carcinoma or metastatic disease from an occult orthotopic lesion, this case highlights the diagnostic challenges of recurrent PHPT and the importance of long-term follow-up, reassessment of atypical locations, and careful interpretation of changing imaging and proliferative indices.
We report a paradoxical case of a 40-year-old man with class 2 obesity (body mass index 39.8 kg/m2) and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] 5.0; reference <2.0) who achieved minimal weight loss (<5%) despite tirzepatide dose escalation to 15 mg weekly over 6 months. Following switch to semaglutide 2.4 mg weekly, the patient achieved 20% weight loss over 6 months, with normalization of fasting glucose, resolution of insulin resistance, and marked improvement in appetite control. This case challenges the assumption that dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonism is universally superior to selective GLP-1 receptor agonism for weight management. Mechanistic analysis suggests that adipose tissue GIP receptor downregulation in the context of class 2 obesity and insulin resistance, combined with intact central GLP-1 receptor signaling, may explain the differential response in some individuals. Key learning points include: markedly elevated baseline insulin resistance (HOMA-IR ≥4-5) may be associated with poor tirzepatide response, though prospective validation is required; persistent hyperphagia during tirzepatide treatment is an early warning sign; and nonresponse to tirzepatide does not preclude semaglutide response. This case supports precision medicine approaches in obesity pharmacotherapy, including pretreatment phenotyping and early response assessment.
Circulating tumor DNA (ctDNA) can be detected in adrenocortical carcinoma; however, its detectability in benign adrenal tumors, such as aldosterone-producing adenoma (APA), remains unclear. We investigated whether tumor-specific mutations could be detected in plasma cell-free DNA (cfDNA) obtained from peripheral and adrenal venous blood in a 34-year-old man with APA. The patient was evaluated for secondary hypertension, and screening and confirmatory tests established the diagnosis of primary aldosteronism. Computed tomography revealed an 11-mm left adrenal mass, and adrenal venous sampling demonstrated left-sided aldosterone hypersecretion. The patient subsequently underwent left adrenalectomy, and pathological examination confirmed an APA. Targeted next-generation sequencing of 18 adrenal disease-related genes identified a somatic KCNJ5 mutation in the tumor tissue. However, the corresponding mutation was not detectable in cfDNA from either peripheral or adrenal venous plasma, despite sampling under clinically favorable conditions. Postoperatively, blood pressure and serum potassium levels normalized. This case illustrates the challenges of detecting tumor-derived mutations in plasma from small benign adrenal tumors using standard sequencing approaches and highlights how tumor burden, sampling conditions, and assay sensitivity influence ctDNA detectability. Further studies employing highly sensitive, mutation-targeted methods are warranted to elucidate the biological and technical factors affecting ctDNA detection in APA.
Acromegaly, caused by excessive growth hormone secretion from a pituitary tumor, is associated with characteristic acral changes and multiple comorbidities. Changes in physical appearance, particularly involving the face and extremities, are the most common triggers for the diagnosis of acromegaly. Since the COVID-19 pandemic, widespread mask wearing in medical settings may interfere with the recognition of acromegaly by obscuring key facial features such as the lips and nose. We report the case of a 74-year-old woman referred for poorly controlled diabetes mellitus (DM). She exhibited disproportionate insulin resistance and excessive insulin secretion despite the absence of obesity or visceral fat accumulation. These metabolic abnormalities prompted further physical examination, which revealed characteristic facial changes that had previously been concealed by mask wearing, ultimately leading to the diagnosis of acromegaly. This case highlights that while mask use is essential for infection control, it may inadvertently delay recognition of acromegaly. Clinicians should therefore remain vigilant and carefully evaluate facial features, particularly in patients with conditions commonly associated with acromegaly, such as DM and hypertension. These findings also underscore the importance of careful facial examination in future pandemics or public health emergencies requiring widespread mask use.
Lipoprotein X is an abnormal lipoprotein formed in cholestatic liver disease that causes artifactual elevation of calculated and measured direct low-density lipoprotein cholesterol (LDL-C). A 40-year-old man with chronic pancreatitis presented with hyperglycemic hyperosmolar state secondary to type 3c diabetes. He was jaundiced, with total bilirubin of 9.4 mg/dL (SI: 161 µmol/L) (reference range, 0.3-1.4 mg/dL [SI: 5-24 µmol/L]). Abdominal computed tomography showed severe common bile duct stricturing causing obstructive cholestasis. Laboratory results revealed a physiologically implausible lipid profile: total cholesterol (TC) of 1531 mg/dL (SI: 39.6 mmol/L) (desirable concentration, <200 mg/dL [SI: <5.2 mmol/L]) and direct LDL-C of 1636 mg/dL (SI: 42.3 mmol/L) (desirable concentration, <100 mg/dL [SI: <2.6 mmol/L]). Low-density lipoprotein cholesterol exceeding TC indicated analytical interference. Apolipoprotein B (ApoB) was elevated: 278 mg/dL (SI: 2.78 g/L) (reference range, 66-144 mg/dL [SI: 0.66-1.44 g/L]). The TC:ApoB ratio was 6.9 mmol/g (reference range, 3.8-6.3 mmol/g), supporting coexistent ApoB-negative lipoprotein. Liver and lipid parameters improved post-biliary stenting. ApoB normalized at 6 weeks, supporting a transient, insulin-deficiency-related ApoB-containing lipoprotein excess. Clinicians should suspect lipoprotein X when LDL-C exceeds TC in the setting of cholestasis; if ApoB is also elevated, transient ApoB-mediated dyslipidemia may coexist. Management centers on correcting underlying biliary and metabolic pathology.
Cushing syndrome (CS) is a major cause of secondary osteoporosis, and postpartum fractures associated with CS have occasionally been reported. However, fractures occurring during pregnancy in patients with CS are exceptionally rare. Additionally, several cases of adrenal CS that became apparent or worsened during pregnancy have been reported. A 31-year-old pregnant woman developed leg edema, subcutaneous bleeding, and a moon face at 17 weeks of gestation. At 24 weeks, she was diagnosed with a fragility fracture of the left pelvis and was admitted to our hospital. She exhibited cushingoid features that were not present before pregnancy. Endocrinological evaluation revealed elevated serum cortisol, suppressed adrenocorticotropic hormone, disrupted diurnal cortisol rhythm, and markedly elevated 24-h urinary free cortisol levels. Abdominal magnetic resonance imaging revealed a 30-mm left adrenal tumor consistent with an adenoma. Based on these findings, a diagnosis of CS due to a left adrenal adenoma was established. Robot-assisted laparoscopic adrenalectomy was performed at 28 weeks and 5 days without complications. Bone mineral density measured postpartum showed severe osteoporosis. This case highlights that adrenal CS may manifest or be exacerbated during pregnancy and increase the risk of various complications, including fragility fractures, emphasizing the importance of early diagnosis and management.
Non-classic P450 oxidoreductase deficiency (NC-PORD) is a rare form of congenital adrenal hyperplasia that may remain unrecognized until adulthood. While infertility in patients already diagnosed with P450 oxidoreductase deficiency (PORD) has been described, cases in which unexplained infertility directly leads to the diagnosis of NC-PORD are rare. We report 2 women who presented with unexplained infertility and persistent elevation of progesterone levels. Rapid adrenocorticotropic hormone stimulation testing showed marked increases in progesterone and 17α-hydroxyprogesterone with suboptimal cortisol response, suggesting impaired steroidogenesis. Genetic analysis identified P450 oxidoreductase variants previously reported in PORD, supporting the diagnosis of NC-PORD. These cases suggest that persistent progesterone elevation may serve as an important clinical clue for NC-PORD in patients with infertility. In contrast to non-classic 21-hydroxylase deficiency, the broader impairment of steroidogenesis in NC-PORD may result in a more complex reproductive phenotype. Recognition of this endocrine pattern may facilitate timely diagnosis and enable mechanism-based management strategies in reproductive medicine.
Severe hypercalcemia is commonly attributed to malignancy. Maintaining a broad differential diagnosis is important in patients with end-organ disease. We present a 47-year-old man with end-stage alcoholic cirrhosis who presented to the outpatient clinic with profound hypercalcemia. His albumin-corrected calcium was 16.8 mg/dL (SI: 4.2 mmol/L) (reference range, 8.5-10.1 mg/dL [SI: 2.1-2.5 mmol/L]) and he had an acute kidney injury. Laboratory evaluation revealed a suppressed parathyroid hormone. Imaging excluded malignancy. Workup for adrenal insufficiency suggested partial secondary disease as a contributing factor. With aggressive fluid hydration and corticosteroids, his symptoms and biochemistry improved. His calcium remained mildly elevated consistent with ongoing cirrhosis-related hypercalcemia. This case underscores the importance of maintaining a broad differential for severe hypercalcemia and considering cirrhosis itself as an etiologic factor.
Hyperinsulinism-hyperammonemia (HI/HA) syndrome is a rare metabolic disorder caused by mutations in GLUD1, which encodes the mitochondrial enzyme glutamate dehydrogenase (GDH). This condition is characterized by recurrent hypoglycemia, elevated plasma ammonia, and potential neurological complications. We report the case of a 12-month-old male who presented with episodic hypoglycemia, hyperammonemia, and seizures. Family history was notable for childhood-onset hypoglycemia and seizures in the patient's mother and sister. The patient's laboratory findings during hospitalization were significant for markedly elevated C-peptide level of 4.9 ng/mL (SI: 1.63 nmol/L) (reference range; 1.1-4.4 ng/mL [SI: 0.36-1.46 nmol/L]). Insulin was inappropriately detectable at 20.2 µIU/mL (SI: 124.92 pmol/L) during hypoglycemia (reference range; 4.00-30.00 µIU/mL [SI: 24.0-180.0 pmol/L]). Genetic testing identified c.1491A>G (p.Ile497Met) in GLUD1. Following initiation of diazoxide therapy, he experienced symptomatic improvement with a marked reduction in hypoglycemic episodes. This case expands the literature on autosomal dominant HI/HA syndrome associated with an inherited GLUD1 p.Ile497Met mutation.
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors, typically secreting norepinephrine and/or epinephrine. A distinct and uncommon variant is the dopamine-secreting PPGL, often presenting asymptomatically, relatively large, and frequently extra-adrenal. Dopamine-excess may independently indicate a higher malignancy risk. We report the case of a 22-year-old man with an incidentally discovered right adrenal lesion. Biochemical evaluation revealed markedly elevated urinary dopamine and 3-methoxytyramine (3MT). Imaging showed a lipid-poor adrenal mass with minimal [18F]-fluorodeoxyglucose (FDG) avidity. Six months later, the lesion had significantly grown and increased in density, with further elevation of dopamine metabolites. The patient underwent robotic-assisted adrenalectomy following preoperative preparation with oral calcium channel blockers (CCB). Surgery was uneventful, and postoperative catecholamine levels normalized. Histopathology confirmed a pheochromocytoma without features of malignancy. This case highlights the importance of age-specific management in individuals under 40 years, even when the lesion presents benign at first. Noncontrast computed tomography (CT) remains the initial imaging modality of choice. Standard treatment consists of surgical resection. In case of dopamine excess in PPGL, CCB, rather than α-blockers, may be recommended for hemodynamic management.
Adipsic arginine vasopressin deficiency (AAVP-D) is a rare hypothalamic disorder, with inadequate vasopressin production and impaired thirst, resulting in sodium and water dysregulation. It poses multiple challenges, including increased morbidity and mortality. We present a 24-year-old female who developed confusion after neurosurgical debulking of a central neurocytoma. Investigations revealed hypernatremia alongside raised plasma osmolality, low urine osmolality, polyuria, and adipsia. Transient AAVP-D was suspected; it was successfully treated with intravenous desmopressin, which resolved predischarge. One week later, she re-presented to the hospital with confusion. Recurrence of hypernatremia, plasma hyperosmolality, and polyuria occurred and permanent AAVP-D was suspected. She was commenced on oral desmopressin 50 mcg/day, titrated to 150 mcg/day, with strict oral fluid regime of 2 L/day. She remains adipsic 24 months postoperatively. Her case highlights the multiple challenges of AAVP-D. Management includes calculating a daily fluid intake goal and titration with desmopressin to ensure consistent urine output, patient weight, and plasma sodium levels with careful outpatient monitoring.
Long-acting growth hormone (LAGH) formulations improve medication adherence in children with growth hormone deficiency. Although transient insulin resistance and mild hyperglycemia are recognized effects of growth hormone therapy, diabetic ketoacidosis (DKA) in patients without prior diabetes is rare. We report a case of severe DKA shortly after initiation of lonapegsomatropin in an adolescent with hypopituitarism without preexisting glucose abnormalities. A 13-year-old boy with obesity, normal fasting glucose, and hypopituitarism receiving levothyroxine, hydrocortisone, and desmopressin replacement therapies following treatment of a suprasellar nongerminomatous germ cell tumor initiated treatment with lonapegsomatropin at 0.23 mg/kg/week. Two days after the administration of the first dose, he presented critically ill with hyperglycemia, severe metabolic acidosis, and ketonuria consistent with DKA. Hemoglobin A1c was 5.7% (reference range, <5.7%), type 1 diabetes autoantibodies were negative, and C-peptide was elevated, suggesting preserved endogenous insulin secretion. Diabetic ketoacidosis resolved with insulin and fluid therapy, and the patient remained normoglycemic after discontinuation of growth hormone therapy. This case suggests that acute LAGH-induced insulin resistance, potentially compounded by glucocorticoids and obesity, may precipitate transient DKA even in patients without prior glucose abnormalities. Close glucose monitoring should be considered when initiating LAGH therapy in high-risk patients.
We report the case of a 48-year-old man with type 2 diabetes with severe insulin resistance, requiring more than 1000 units of insulin per day. Our case highlights the challenges in treating patients with severe insulin resistance, including ruling out secondary causes and using less-commonly prescribed therapies such as U-500 insulin.
A 22-year-old man with untreated congenital adrenal hyperplasia (CAH) developed an acute adrenal crisis following bilateral orchiectomy for testicular adrenal rest tumors. The patient survived into adulthood without treatment until progressive testicular masses led to surgery due to misinterpretation of malignancy. Eighteen days postoperatively, he presented with severe asthenia, hyponatremia, and hyperkalemia. Diagnostic evaluation revealed markedly elevated 17-hydroxyprogesterone, androstenedione, and adrenocorticotropic hormone levels, with bilateral adrenal hyperplasia on imaging. Genetic testing identified a homozygous pathogenic variant in the CYP21A2 gene. Following glucocorticoid and mineralocorticoid replacement, the patient achieved clinical stability. This case illustrates that surgical removal of testicular adrenal rest tumors in untreated individuals can precipitate severe acute adrenal insufficiency, highlighting these tumors as a critical sentinel finding for late-diagnosis congenital adrenal hyperplasia.
Lymphocytic hypophysitis (LYH), attributed to autoimmune mechanisms, typically causes multiple anterior pituitary hormone deficiencies, with corticotroph dysfunction occurring earliest; predominant thyrotroph dysfunction is uncommon. A 65-year-old woman presented with headache, fever, and diplopia. Laboratory tests revealed marked systemic inflammation and cerebrospinal fluid (CSF) pleocytosis. Pituitary magnetic resonance imaging (MRI) demonstrated diffuse enlargement and homogeneous contrast enhancement of the pituitary gland and stalk. Endocrinological evaluation showed paradoxically decreased thyroid-stimulating hormone (TSH) despite low thyroid hormone levels, contrasting with elevated adrenocorticotropic hormone (ACTH) levels. Endocrinological stimulation tests revealed a markedly blunted TSH response, with preserved gonadotropin and growth hormone responses, indicating predominant thyrotroph dysfunction despite preserved corticotroph function. Glucocorticoid therapy resulted in prompt improvement of clinical, laboratory, and MRI findings, with complete recovery of anterior pituitary functions. A presumptive diagnosis of LYH with reversible predominant thyrotroph dysfunction and meningitis secondary to direct extension of pituitary inflammation was established. This case demonstrates that LYH can present with atypical anterior pituitary hormone dysfunction, may be complicated by aseptic meningitis, and requires prompt glucocorticoid therapy for favorable outcomes.
Painless thyroiditis is a destructive disorder associated with immune dysregulation. Although an abrupt reduction in corticosteroid activity has been implicated, the precipitating role of endogenous adrenal insufficiency remains unclear. A 66-year-old woman was admitted to a referring hospital with anorexia, vomiting, and hyponatremia and was diagnosed with syndrome of inappropriate antidiuresis (SIAD). Despite correction of serum sodium levels, anorexia persisted. Two months later, she developed fever, tachycardia, impaired consciousness, and severe hypercalcemia and was transferred to our institution. Laboratory evaluation revealed marked thyrotoxicosis with suppressed thyroid-stimulating hormone and elevated free thyroxine levels, along with inappropriately low adrenocorticotropic hormone (ACTH) and cortisol levels. The patient met the diagnostic criteria for thyroid crisis. Thyroid antibody testing and imaging findings were consistent with painless thyroiditis. Secondary adrenal insufficiency was confirmed by a blunted cortisol response to a rapid ACTH stimulation test. Treatment with intravenous hydrocortisone and empiric potassium iodide resulted in rapid clinical improvement. This case suggests an association between unrecognized secondary adrenal insufficiency initially diagnosed as SIAD and the subsequent occurrence of painless thyroiditis and thyroid crisis. Evaluation of adrenal function should be considered in patients with hyponatremia and thyrotoxicosis.
