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Christina Lee Department of Pediatrics, University of Maryland Children’s Hospital, Baltimore, Maryland, USA

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Leah Hirschman Department of Pediatrics, University of Maryland Children’s Hospital, Baltimore, Maryland, USA

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Teresa York Department of Pediatric Hematology/Oncology, University of Maryland Children’s Hospital, Baltimore, Maryland, USA

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Paula Newton Department of Pediatric Endocrinology, University of Maryland Children’s Hospital, Baltimore, Maryland, USA

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Summary

Neonatal adrenal hemorrhage (NAH) occurs in up to 3% of infants and is the most common adrenal mass in newborns. The most common presentation of NAH is an asymptomatic palpable flank mass which resolves over time without intervention. In rare cases, NAH can present as hemorrhage, shock, or adrenal insufficiency. This case describes a preterm infant born with severe anemia in the setting of bilateral adrenal hemorrhages with resulting adrenal insufficiency. The infant was successfully treated with blood transfusions and steroids. This is a unique presentation of NAH as it was bilateral, presented with severe anemia, and resulted in prolonged adrenal insufficiency.

Learning points

  • Consider adrenal hemorrhage for cases of severe anemia at birth.

  • Adrenal insufficiency is a rare complication of adrenal hemorrhage.

  • Adrenal recovery can take months, if not years.

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Noor Alnasrallah Department of Internal Medicine, Adan Hospital, Kuwait

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Khaled Aljenaee Department of Internal Medicine, Endocrine and diabetes division, Adan Hospital, Kuwait

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Maryam AlMurshed Department of Laboratory Medicine, Anatomical Pathology/Neuropathology Division, Sabah Hospital, Kuwait

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Sulaiman Hajji Department of Internal Medicine, Endocrine and diabetes division, Adan Hospital, Kuwait

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Summary

Gonadotroph adenomas are the most common type of nonfunctional pituitary adenomas. However, functioning gonadotroph adenomas causing clinical manifestations are rare. We present the case of a 42-year-old man with an incidental finding of a pituitary gland mass. A pituitary MRI revealed a 3 cm macroadenoma, and laboratory investigations revealed elevated follicle-stimulating hormone (FSH) and total testosterone levels. A diagnosis of functioning FSH-secreting pituitary adenoma was considered, with possible concomitant luteinizing hormone secretion, given the elevated testosterone, prompting further evaluation. Testicular ultrasound showed bilaterally enlarged testicles, and visual field testing revealed a monocular superior temporal defect. Transsphenoidal resection of pituitary adenoma was the treatment of choice. Histopathology assessment confirmed the diagnosis of gonadotroph-secreting adenoma, with positive staining for FSH. Within the 12-week postoperative period, FSH and testosterone levels normalized, and the patient experienced significant improvement in vision, along with the resolution of macroorchidism. While functional gonadotroph adenomas are rare, patients can present with a wide range of symptoms that are often unnoticeable due to their slow development. Careful evaluation can help guide multidisciplinary management to achieve full remission.

Learning points

  • Endocrine evaluation is indicated in all cases of pituitary incidentalomas to determine functional status.

  • Clinically functioning gonadotroph adenomas, while rare, pose a diagnostic challenge and require careful clinical evaluation.

  • Transsphenoidal surgery is the mainstay of treatment of functioning gonadotroph adenomas, with the involvement of a multidisciplinary team to achieve desirable outcomes.

Open access
Hendra Zufry Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia
Innovation and Research Center of Endocrinology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Putri Oktaviani Zulfa Innovation and Research Center of Endocrinology, School of Medicine, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Rosdiana Rosdiana Department of Internal Medicine, Tengku Abdullah Syafii Hospital, Beureunuen, Pidie, Aceh, Indonesia

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Krishna Wardhana Sucipto Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Agustia Sukri Ekadamayanti Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Sarah Firdausa Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, School of Medicine/Dr. Zainoel Abidin Hospital, Universitas Syiah Kuala, Banda Aceh, Indonesia

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Summary

Symptoms of primary adrenal insufficiency (PAI) are commonly nonspecific, causing the disease to be misdiagnosed or often delayed, and patients may present to the hospital with a life-threatening crisis. Previous case reports have documented that patients in this condition often require lifelong glucocorticoid replacement therapy. This study aimed to present a noteworthy outcome of PAI caused by adrenal tuberculosis infection, demonstrating complete recovery after six months of glucocorticoid replacement therapy. A 38-year-old Indonesian man presented to the endocrinology clinic in a tertiary hospital with a chief complaint of epigastric pain. The patient experienced nausea, vomiting, loss of consciousness, weight loss, excessive sweat, decreased appetite, weakness, and dizziness in the past 2 weeks. Laboratory examinations revealed hyponatremia, elevated adrenocorticotropic hormone, and suppressed morning plasma cortisol level. A non-contrast-enhanced abdominal MRI showed unilateral right-side adrenal enlargement and calcification. The patient’s Mantoux test was positive. Corticosteroids and anti-tuberculosis therapy were administered. After 6 months, hydrocortisone was discontinued due to the patient’s good clinical condition and normal morning plasma cortisol levels. After a 1-year follow-up, the patient remained asymptomatic with normal cortisol levels. We hypothesized several reasons for this unique outcome: (i) the patient was relatively young compared to previous cases, suggesting an adequate immune system may play a role; (ii) despite a 1-month delay in diagnosis and treatment, the absence of skin hyperpigmentation suggested an acute presentation, potentially contributing to the favorable outcome; and (iii) the absence of comorbidities potentially positively impacted the patient's outcome.

Learning points

  • Symptoms of adrenal insufficiency are often nonspecific and may only become apparent once significant damage has occurred to the adrenal gland.

  • Clinical adjustments and a comprehensive understanding of epidemiological knowledge are necessary for diagnosing patients with endocrine diseases in limited-resource settings.

  • Complete recovery in primary adrenal insufficiency caused by tuberculosis infection might be due to younger age, acute presentation, and absence of comorbidities

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Sandra Martens Ghent University Hospital, Ghent, Belgium

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Bruno Lapauw Ghent University Hospital, Ghent, Belgium
Ghent University, Ghent, Belgium

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Summary

Mitotane is used for treatment of advanced adrenocortical carcinoma. It is administered when the carcinoma is unresectable, metastasized, or at high-risk of recurrence after resection. In addition, mitotane is considered to have direct adrenolytic effects. Because of its narrow therapeutic–toxic range, therapeutic drug monitoring (TDM) is warranted. In 2020, a left-sided adrenal gland tumor was found (5.8 cm) in a 38-year-old man. Considering the size of this lesion and inability to exclude an adrenocortical carcinoma on imaging, a laparoscopic adrenalectomy was performed. Histopathologic examination determined presence of an adrenocortical carcinoma (pT2N0M0 ENSAT stadium II; ki67 10–15%). There was no evidence for residual or metastatic disease but given the high risk of recurrence, adjuvant therapy with mitotane was initiated. During TDM, a sudden and spuriously high level of mitotane was observed but without signs or symptoms of toxicity. After exploration, it was found that this high concentration was completely due to uncontrolled hypertriglyceridemia. After correction thereof, mitotane levels were again in the therapeutic range. This observation underscores the importance of TDM sampling in a fasting state with concurrent control of prevalent or incident dyslipidemia.

Learning points

  • TDM of mitotane is advocated to achieve therapeutic levels while avoiding toxicity. For correct TDM, sampling should be done at least 12 h after last intake of mitotane.

  • Although sampling in fasting conditions in not explicitly mentioned in the guidelines, fasting state should be considered as elevated serum triglyceride levels might cause spuriously high mitotane levels.

  • In patients undergoing treatment with mitotane and presenting with too high or unexplained fluctuating mitotane levels without signs or symptoms of toxicity, hypertriglyceridemia as a possible cause should be investigated.

  • If dyslipidemia occurs in patients under mitotane treatment, other causes than mitotane (e.g. alcohol abuse and diabetes) should be considered and appropriate treatment should be initiated.

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Laura González Fernández Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Alejandra Maricel Rivas Montenegro Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Noemí Brox Torrecilla Endocrinology and Nutrition Department, Hospital Ramón y Cajal, Madrid, Spain

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María Miguélez González Endocrinology and Nutrition Department, Hospital Fundación Jiménez Díaz, Madrid, Spain

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Jose Atencia Goñi Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Elisa Fernández Fernández Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Olga González Albarrán Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Juan Carlos Pércovich Hualpa Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Marcel Sambo Salas Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Rogelio García Centeno Endocrinology and Nutrition Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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Summary

Ectopic Cushing’s syndrome (ECS) is a rare disease associated with significant comorbidity. Among the causes of Cushing's syndrome, adrenocorticotropic hormone-producing extrapituitary tumours are rarely reported. This low frequency makes it difficult for the physician to acquire experience in its management.

In this report, we aimed to describe the clinical presentation, diagnostic approach and treatment modalities of 12 patients with ECS treated in a single tertiarycentre over a 17-year period. Although they can appear in different locations through the neuroendocrine system, lung tumours are the most frequently reported, as it occurs in our series. They can show different levels of aggressiveness and mild to severe clinical course. Therefore, distinguishing Cushing's disease can be challenging and sometimes requires more specific techniques such as invasive tests or no conventional imaging. Treatment includes controlling both hypercortisolism and neoplastic disease, and multidisciplinary management is recommended.

Learning points

  • Ectopic Cushing's syndrome (ECS) accounts for 15% of endogenous Cushing's syndromes. Its infrequency implies that both diagnosis and treatment can be a challenge for clinicians without experience in its management.

  • The most common location is the lung. Although older series reported small cell lung carcinoma (SCLC) as the main ECS-producing tumour, currently most cases are attributed to lung carcinoids.

  • Low-grade tumours (lung carcinoids) present themselves with a more subtle and gradual hypercortisolism, and clinically this can be difficult to differentiate from hypercortisolism due to CD. In contrast, high-grade tumours (SCLC) show severe hypercortisolism with rapid evolution.

  • The diagnostic approach is complex especially when the tumour is not previously known and the clinical presentation is subtle. Functional tests are mandatory in these cases, and nuclear medicine imaging can help when conventional imaging tests fail to identify the tumour.

  • ECS treatment includes a wide variety of modalities oriented to treat both the excess of cortisol and the tumour itself. The tumour prognosis depends fundamentally on the type of adrenocorticotropic hormone-secreting tumour.

  • Expert and multidisciplinary team is essential for successfully treating these complex and ill patients.