Endocrinology, Diabetes and Metabolism Case Reports最新文献

Summary: Ovarian hyperstimulation syndrome (OHSS) usually occurs in patients undergoing assisted reproduction techniques and ovulation induction. Its variant, spontaneous ovarian hyperstimulation syndrome, a potentially life-threatening disorder, is uncommon and only a few cases have been reported in association with hypothyroidism. This study analysed five patients with untreated chronic hypothyroidism presenting with multicystic ovaries, isosexual precocious puberty, and delayed bone age; subsequently, the follow-up and regression of ovarian pathology was assessed. Two patients had presented to the emergency department with menorrhagia and hypotension, of these, one had ovarian torsion at presentation. Three patients presented to the outpatient department: one for evaluation of short stature, one for premature menarche, and another with polycystic ovaries. They were all diagnosed with long-standing, untreated chronic hypothyroidism. There was regression of the size of the cystic ovaries on subsequent follow-up. In all these patients, long-standing hypothyroidism had resulted in ovarian hyperstimulation syndrome. The potentially life-threatening complications of this syndrome may be prevented by careful screening and a strong index of clinical suspicion at the outset.

Learning points: Long-standing, untreated primary hypothyroidism may result in spontaneous ovarian hyperstimulation syndrome. A high index of suspicion is required for an early and accurate diagnosis. The requirement for interdepartmental collaboration between gynaecology and endocrinology departments is essential for the successful management of this life-threatening but easily treatable disorder.

Summary: Multiple endocrine neoplasia type 1 (MEN1) requires a high level of suspicion, and late diagnosis can lead to dire outcomes. Genetic counselling is an important part of management, with a lack of evidence surrounding an optimal approach in Aboriginal Australian populations. Our case surrounds a remote-dwelling 48-year-old Aboriginal Australian female who was reviewed by an inpatient endocrine team in 2020 for persistent hypercalcaemia on a background of a parathyroidectomy in 2011 for primary hyperparathyroidism (PHPT), while she was admitted to a local hospital for acute chronic abdominal pain. Relevant medical history included multiple pulmonary embolisms/deep vein thrombosis, myocardial infarction, atrial fibrillation, chronic thromboembolic pulmonary hypertension, right heart failure, human T-lymphotropic virus 1, recurrent abdominal pain, and gastro-oesophageal reflux disorder. Gastroscopies from 2013 and 2015 demonstrated chronic gastritis with hundreds of gastric polyps. Subsequent laboratory studies, neuroendocrine tumour (NET) screening, and CT imaging demonstrated a recurrence of PHPT and a new diagnosis of Zollinger-Ellison syndrome. A 68-gallium-DOTATATE PET/CT was in keeping with metastatic NET. Pituitary studies were normal. Genetic testing confirmed a rare heterozygous variant of c.207dupC in exon 2 of the MEN1 gene. Treatment was symptom based due to terminal comorbidities. Genetic counselling was attempted; however, cultural and logistical barriers were identified and the family declined further testing. Unfortunately, she died in 2021 from multifactorial respiratory failure. This case highlights the need for better approaches to genetic counselling systems for remote Aboriginal Australians and emphasizes the importance of early recognition and the challenges faced in remote areas in making such rare diagnoses.

Learning points: Remote healthcare systems often lack access to adequate specialist care, resulting in delayed diagnosis of rare conditions and leading to morbidity and mortality. Further research and work need to be done to provide culturally appropriate genetic counselling systems in remote Aboriginal Australians. A high index of suspicion is required to diagnose MEN1. Consider MEN1 in any patient diagnosed with primary hyperparathyroidism, with age <40, and/or with the presence of multiglandular disease or with the presence of Zollinger-Ellison syndrome. MEN1 may be under-recognized in Aboriginal Australians.

Summary: Brain metastases as the first clinical presentation of a papillary thyroid carcinoma (PTC) are exceptional, while cavernous angiomas are common cerebral malformations. We report the case of a 36-year-old male with an incidental brain lesion mimicking a cavernous angioma on MRI. Gamma knife radiosurgery was performed, but after 6 months, the patient developed neurological symptoms, and a repeat brain MRI revealed a significant increase in the mass. The patient underwent neurosurgery, and the histological examination of the lesion revealed metastatic carcinoma of thyroid origin. PET-CT and neck ultrasound, subsequently performed, were concordant for the presence of a right lobe nodule and ipsilateral lymph nodes, both with ultrasound features suspicious of malignancy. Total thyroidectomy with central and right lateral neck dissection was performed, and histology confirmed an intrathyroidal multifocal PTC with lymph node metastases. Postoperative radioiodine was administered, and focal uptake within the thyroid bed, without distant metastases or brain remnants, was found on the post-therapeutic whole-body scan. At 2 years from diagnosis, the patient is in good health and undergoes clinical and imaging follow-up.

Learning points: Brain cavernous angiomas are common cerebral vascular malformations that are usually diagnosed by MRI. Despite the high accuracy of MRI, the exam is not pathognomonic, and misdiagnosis cannot be excluded. Brain metastases from PTC are very rare; however, they can mimic a cavernous angioma. Therefore, the differential diagnosis should always be considered.

Summary: Pregnancy in the setting of metastatic paraganglioma is challenging, particularly in the context of tyrosine kinase use. We describe a 26-year-old female with a background of metastatic paraganglioma harboring a pathogenic SDHB variant, requiring sunitinib, which was withheld to facilitate the safe conception and delivery of a healthy baby. She required no alpha- or beta-blockade during her pregnancy and exhibited no signs of tumor progression or symptoms throughout this period. Historically, higher rates of fetal and maternal morbidity and mortality have been experienced in the setting of pregnancy. Although limited data exist on the management of metastatic paraganglioma in pregnant patients, this case suggests that careful treatment modifications, such as temporary tyrosine kinase therapy cessation and vigilant monitoring, can result in successful pregnancies without compromising maternal or fetal well-being.

Learning points: Paraganglioma in pregnancy has been associated with poor fetal and maternal morbidity and mortality. Many of the treatment modalities for metastatic paraganglioma, including tyrosine kinase inhibitors, can affect fertility or cannot be utilized in pregnancy, necessitating the temporary suspension of these treatments. This case exemplifies that careful clinical and biochemical monitoring during pregnancy is required to avoid maternal and fetal harm while balancing the risk of disease progression off treatment.

Summary: A 52-year-old female patient with breast cancer presented with a history of fatigue and malaise 1 year prior. She was diagnosed with isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) on endocrinological examination. Her pituitary gland showed normal morphology. Paraneoplastic IAD associated with breast cancer was suspected; however, immunofluorescence staining revealed no ectopic ACTH or proopiomelanocortin expression in the tumor tissue. Subsequently, the patient was diagnosed with idiopathic acquired IAD concurrent with breast cancer, ruling out paraneoplastic syndrome. Although malignancy should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic syndrome.

Learning points: Several adrenal insufficiency symptoms are similar to the nonspecific symptoms associated with malignancies, and therefore, the diagnosis of IAD remains challenging, especially in patients with cancer. When we encounter a case of IAD accompanied by a malignant tumor, it is important to suspect that paraneoplastic IAD, a novel clinical condition as secondary hypophysitis, may be the etiologic agent. Although malignant tumours should be considered a potential cause of IAD, not all patients with concurrent IAD and malignancy necessarily develop paraneoplastic autoimmune hypophysitis.

Summary: Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation.

Learning points: Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality. Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy. Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required. Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

Summary: Multiple endocrine neoplasia type 2 (MEN2) is a hereditary cancer syndrome caused by germline-activating pathogenic variants in the RET proto-oncogene. MEN2A is the most common subtype, with a risk for medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT), whereas MEN2B is less common and associated with MTC and PHEO along with mucosal neuromas. Little is known about the specific RET germline heterozygous variant K666N. This variant has been described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. There is one case of MTC and bilateral PHEO. The RET K666N variant is not stratified yet by the American Thyroid Association, and data are limited on pathogenicity; therefore, appropriate screening and treatment of asymptomatic RET K666N carriers are unclear. Here, we report a family with a heterozygous germline RET K666N variant. The proband was identified when she experienced cardiogenic shock and multi-organ failure after an elective hysterectomy and subsequently was found to have PHEO, with genetic testing revealing the RET K666N germline variant. Patient consent was obtained through IRB protocol COMIRB #15-0516.

Learning points: The specific RET germline heterozygous variant K666N is rare and described in very few families, and in most cases, patients were diagnosed with a very indolent MTC as the only feature. Our proband is much younger and has PHEO, MTC, and PHPT. The RET K666N germline variant appears to be a low penetrance variant for MEN2.

Summary: At the end of the 19th century, an 18-year-old lady gave birth to a well-proportioned, though very small, son. After delivery, the mother developed a full-grown beard, whereas the son always remained of small stature. The mother developed diabetes mellitus and died, aged 59, from a complicated severe cold. The son died at the age of 91 because of chronic kidney disease. The differential diagnosis in the son is isolated growth hormone deficiency. The mother might have suffered luteoma of pregnancy, polycystic ovary syndrome (PCOS), or Sertoli-Leydig cell tumor(s). The two cases are apparently coincidental/not related in pathophysiology.

Learning points: Hirsutism occurring directly postpartum can have several causes. Patients with isolated growth hormone deficiency can live a long life without the substitution of growth hormone. Coincidence does not necessarily imply correlation. In the past, patients with endocrine disorders like severe hirsutism or small stature were employed at circuses and fairs to entertain the audience as curiosities.

Summary: Congenital hyperinsulinism is the leading cause of persistent hypoglycaemia in infants and children; however, it is uncommon to be diagnosed in adulthood. We describe the cases of two sisters who presented with hyperinsulinaemic hypoglycaemia aged 47 and 57 years old, who were subsequently diagnosed with compound heterozygous likely pathogenic variants in the ABCC8 gene, a known cause of monogenic congenital hyperinsulinism. We discuss the typical presenting features, investigation findings, and treatment strategies for patients with this condition.

Learning points: Congenital hyperinsulinism is a rare cause of hyperinsulinaemic hypoglycaemia diagnosed in adulthood. Clinical presentation is similar to an insulinoma, and imaging modalities may assist in differentiation. There are minimal medical therapies currently available for patients non-responsive to diazoxide (such as those with ABCC8 and KCNJ11 variants). Continuous glucose monitoring can be helpful in giving patients autonomy in managing their disease, as well as relieving anxiety and fear associated with hypoglycaemia.

Summary: A 6.6-year-old female presented to endocrinology with precocious puberty for evaluation and management. Workup was initiated, and a diagnosis of central precocious puberty was confirmed. A decision was made to initiate pubertal blockade using gonadotropin-releasing hormone agonist (GnRHa) therapy with depot leuprolide acetate injections every 3 months. The patient received the first depot leuprolide acetate injection in the right ventrogluteal area. Six hours following the injection, the patient was reported to be inconsolable in pain, which was localized to the right hip site of the earlier injection and associated with a refusal to ambulate. The pain and discomfort continued to progress over the next 24 h despite an alternating regimen of Tylenol and ibuprofen prompting admission to the emergency department. Vital signs demonstrated a low-grade fever and elevated C-reactive protein. An ultrasound of the right hip demonstrated fluid accumulation within the joint. Over the next week, the patient was unable to walk independently and required assistance for activities of daily living. By 2 weeks after the injection, the pain began to remit, and the patient resumed activities of daily living. Following consultation with allergy, a decision was made to continue GnRHa suppressive therapy with an alternative analog (Triptodur). The patient tolerated subsequent treatment without reaction.

Learning points: Although gonadotropin-releasing hormone agonists (GnRHa) have a generally good safety profile, there is a history of both local and systemic hypersensitivity reactions associated with their use. Despite the long-acting formulation of depot leuprolide acetate, the systemic reaction in this case appears to be self-limited. Discontinuation of therapy or a change to an alternative formulation of GnRHa analog should be considered based on the need for therapy versus the potential risk of rechallenge.