Summary

Oncogenic osteomalacia secondary to glomus tumor is extremely rare. Localization of causative tumors is critical as surgical resection can lead to a complete biochemical and clinical cure. We present a case of oncogenic osteomalacia treated with resection of glomus tumor. A 39-year-old woman with a history of chronic sinusitis presented with chronic body ache and muscle weakness. Biochemical evaluation revealed elevated alkaline phosphatase hypophosphatemia, increased urinary phosphate excretion, low calcitriol, and FGF23 was unsuppressed suggestive of oncogenic osteomalacia. Diagnostic studies showed increase uptake in multiple bones. Localization with MRI of paranasal sinuses revealed a sinonasal mass with concurrent uptake in the same area on the octreotide scan. Surgical resection of the sinonasal mass was consistent with the glomus tumor. The patient improved both clinically and biochemically postoperatively. Along with the case of oncogenic osteomalacia secondary to a glomus tumor, we have also discussed in detail the recent development in the diagnosis and management of oncogenic osteomalacia.

Learning points

• Tumor-induced osteomalacia is a rare cause of osteomalacia caused by the secretion of FGF23 from mesenchymal tumors.

• Mesenchymal tumors causing TIO are often difficult to localize and treat.

• Resection of the tumor can result in complete resolution of biochemical and clinical manifestations in a very short span of time.

• Glomus tumor can lead to tumor induced osteomalacia and should be surgically treated.

Summary

Systemic pseudohypoaldosteronism type 1 (PHA1) is a rare genetic syndrome of tissue unresponsiveness to aldosterone caused by mutations affecting the epithelial Na channel (ENaC). The classical presentation is life-threatening neonatal/infantile salt-losing crises that mimic congenital adrenal hyperplasia (CAH). Consistently, extra-renal manifestations, including respiratory symptoms that resemble cystic fibrosis, are well reported. Clinical diagnosis is made by the presence of hyponatremia, hyperkalemia, metabolic acidosis, respiratory symptoms, evidence of high renal and extra-renal salt loss in addition to high plasma renin and aldosterone levels. We herein report a novel manifestation of PHA1: episodic dyslipidemia in a 7-month-old Sudanese boy that occurred during the salt-losing crises. Whole exome sequencing of the patient revealed one homozygous missense variant c.1636G>A p.(Asp546Asn) in the SCNN1B gene, confirming our clinical and laboratory findings that were compatible with PHA1. This report aims to highlight the possible explanation of dyslipidemia in PHA1 and its expected consequences in the long term.

Learning points

• A child presenting with features that mimic salt-losing congenital adrenal hyperplasia (CAH) crises that do not respond to glucocorticoid and mineralocorticoid therapy should alert the pediatricians to the possibility of end-organ resistance to aldosterone.

• Pseudohypoaldosteronism type 1 (PHA1) can be diagnosed even in the absence of advanced laboratory investigations.

• To our knowledge, this is the first case of systemic PHA1 to have a documented episodic dyslipidemia (primarily as marked hypertriglyceridemia).

Summary

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH – classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0–1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients’ quality of life.

Learning points

• Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis.

• CAH may be divided into two major forms: classic and non-classic CAH.

• If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood.

• Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients.

• Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.

Summary

An 82-year-old female was admitted to a general hospital due to progressive bilateral lower limb weakness. A T8–T9 extramedullary meningioma was diagnosed by MRI, and the patient was referred for excision of the tumour. During the patient’s admission, she was noted to have persistent hyperkalaemia which was refractory to treatment. Following a review by an endocrinology team, a diagnosis of pseudohyperkalaemia secondary to thrombocytosis was made. This case demonstrates the importance of promptly identifying patients who are susceptible to pseudohyperkalaemia, in order to prevent its potentially serious consequences.

Learning points

• Pseudohyperkalaemia should be considered in patients with unexplained or asymptomatic hyperkalaemia. It should also be considered in those patients who are resistant to the classical treatment of hyperkalaemia.

• A diagnosis of pseudohyperkalaemia is considered when there is a difference of >0.4 mmol/L of potassium between serum and plasma potassium in the absence of symptoms and ECG changes.

• In patients who are presenting with consistently elevated serum potassium levels, it may be beneficial to take venous blood gas and/ or plasma potassium levels to rule out pseudohyperkalaemia.

• Pseudohyperkalaemia may subject patients to iatrogenic hypokalaemia which can be potentially fatal.

• Pseudohyperkalaemia can occur secondary to thrombocytosis, red cell haemolysis due to improper blood letting techniques, leukaemia and lymphoma.

Summary

Adrenocortical carcinoma (ACC) is a malignant disorder with rapid evolution and severe prognosis in adults and most produce cortisol and androgen. Estrogen-secreting adrenocortical carcinomas are extremely rare, especially in women, tend to be larger and have worse prognosis compared with other types of ACCs. We report the case of a 58-year-old woman who presented with bilateral breast enlargement and postmenopausal genital bleeding. She presented high estradiol (818 pg/mL – 25 times above upper normal limit for postmenopausal women) and testosterone (158 ng/dL – 2 times above upper normal limit) levels and no suppression of cortisol after overnight 1 mg dexamethasone test (12.5 µg/dL; normal reference value: < 1.8 µg/dL). The patient had no clinical features of cortisol excess. MRI showed a 12 cm tumor in the right adrenal. Clinical findings of bilateral breast enlargement and postmenopausal genital bleeding with no signs of hypercortisolism associated with hormonal findings of elevated estradiol and testosterone levels would indicate either an ovarian etiology or an adrenal etiology; however, in the context of plasma cortisol levels non-suppressive after dexamethasone test and the confirmation of an adrenal tumor by MRI, the diagnosis of an adrenal tumor with mixed hormonal secretion was made. The patient underwent an open right adrenalectomy and pathological examination revealed an ACC with a Weiss’ score of 6. Estradiol and testosterone levels decreased to normal range soon after surgery. She was put on mitotane treatment as adjuvant therapy, but due to side effects, we were unable to up-titrate the dose and she never achieved serum mitotane dosage above the desired 14 µg/mL. The patient remained in good health without any local recurrence or metastasis until 5 years after surgery, when increased levels of estradiol (81 pg/mL – 2.5 times above upper normal limit) and testosterone (170 ng/dL – 2.1 times above upper normal limit) were detected. MRI revealed a retroperitoneal nodule measuring 1.8 × 1.2 cm. The pathological finding confirmed the recurrence of the estrogen-secreting ACC with a Weiss’ score of 6. After the second procedure, patient achieved normal estrogen and androgen serum levels and since then she has been followed for 3 years. The overall survival was 8 years after the diagnosis. In conclusion, although extremely rare, a diagnosis of an estrogen-secreting ACC should be considered as an etiology in postmenopausal women presenting with bilateral breast enlargement, genital bleeding and increased pure or prevailing estrogen secretion.

Learning points:

• Estrogen-secreting adrenocortical carcinomas are exceedingly rare in adults and account for 1−2% of adrenocortical carcinomas.

• Estrogen-secreting adrenal tumors can be present in females, but are even more rare, we found few cases described in the literature. In women, they present with precocious puberty or postmenopausal bleeding.

• Feminization in the context of an adrenal tumor is considered almost pathognomonic of malignancy. Feminizing ACCs tend to be larger and with worse prognosis compared with nonfeminizing ACCs.

Learning points:

• The value of a therapeutic trial of octreotide to identify responders.

• Control of GH and IGF-1 secretion using octreotide LA.

• The report of the successful use of octreotide for more than 16 years irrespective of age.

Summary

Well-differentiated thyroid cancer (WDTC), including papillary, follicular, and Hurthle-cell types, is characterized by a slow course and usually remain localized to the thyroid. However, a minority of these cases develop distant metastases with the most common sites being lungs, bones, and lymph nodes. Liver metastases of WDTC are rare and are usually found along with other distant metastases sites and in a multiple or diffuse pattern of spread. The recognition of distant metastasis in WDTC has a significant impact on the treatment and prognosis. However, because of their low incidence and awareness, distant metastases are often diagnosed late. Herein, we describe a case of a 71 years old woman who during routine surveillance of a follicular variant of papillary thyroid cancer (FV-PTC), 5 years after being treated for her primary thyroid tumor, was found to have a single liver metastasis and underwent liver segmental resection. This case highlights the importance of maintaining vigilant surveillance of patients with WDTC, and illustrates the possibility of unique metastasis at unexpected sites. Further studies are needed to understand the organ tropism of some WDTC leading to distant metastases development and to better prediction of an aggressive course.

Learning points:

• WDTC patients with distant metastases have a poor prognosis with a 10-year survival of about 50%. The most common sites of distant metastases are lung, bone and lymph nodes.

• Liver metastases are rare in WDTC, are usually multiple or diffuse and are found along with other distant metastases sites.

• Single liver metastasis of WDTC is an unexpected pattern of spread, and very few cases are reported in the literature.

• Rare sites of distant metastases in WDTC can manifest many years after the primary tumor, stressing the importance of maintaining vigilant surveillance.

• More studies are needed to predict which WDTC tumors may develop a more aggressive course, allowing clinicians to individualize patient management.

Summary

Brown tumors (BTs) are expansile osteolytic lesions complicating severe primary hyperparathyroidism (PHPT). Clinical, radiological and histological features of BTs share many similarities with other giant cell-containing lesions of the bone, which can make their diagnosis challenging. We report the case of a 32-year-old man in whom an aggressive osteolytic lesion of the iliac crest was initially diagnosed as a giant cell tumor by biopsy. The patient was scheduled for surgical curettage, with a course of neoadjuvant denosumab. Routine biochemical workup prior to denosumab administration incidentally revealed high serum calcium levels. The patient was diagnosed with PHPT and a parathyroid adenoma was identified. In light of these findings, histological slices of the iliac lesion were reviewed and diagnosis of a BT was confirmed. Follow-up CT-scans performed 2 and 7 months after parathyroidectomy showed regression and re-ossification of the bone lesion. The aim of this case report is to underline the importance of distinguishing BTs from other giant cell-containing lesions of the bone and to highlight the relevance of measuring serum calcium as part of the initial evaluation of osteolytic bone lesions. This can have a major impact on patients’ management and can prevent unnecessary invasive surgical interventions.

Learning points:

• Although rare, brown tumors should always be considered in the differential diagnosis of osteolytic giant cell-containing bone lesions.

• Among giant cell-containing lesions of the bone, the main differential diagnoses of brown tumors are giant cell tumors and aneurysmal bone cysts.

• Clinical, radiological and histological characteristics can be non-discriminating between brown tumors and giant cell tumors. One of the best ways to distinguish these two diagnoses appears to be through biochemical workup.

• Differentiating brown tumors from giant cell tumors and aneurysmal bone cysts is crucial in order to ensure better patient care and prevent unnecessary morbid surgical interventions.

Summary

A 19-year-old female presented at 25-weeks gestation with pancreatitis. She was found to have significant hypertriglyceridaemia in context of an unconfirmed history of familial hypertriglyceridaemia. This was initially managed with fasting and insulin infusion and she was commenced on conventional interventions to lower triglycerides, including a fat-restricted diet, heparin, marine oil and gemfibrozil. Despite these measures, the triglyceride levels continued to increase as she progressed through the pregnancy, and it was postulated that she had an underlying lipoprotein lipase defect. Therefore, a multidisciplinary decision was made to commence therapeutic plasma exchange to prevent further episodes of pancreatitis. She underwent a total of 13 sessions of plasma exchange, and labour was induced at 37-weeks gestation in which a healthy female infant was delivered. There was a rapid and significant reduction in triglycerides in the 48 h post-delivery. Subsequent genetic testing of hypertriglyceridaemia genes revealed a missense mutation of the LPL gene. Fenofibrate and rosuvastatin was commenced to manage her hypertriglyceridaemia postpartum and the importance of preconception counselling for future pregnancies was discussed. Hormonal changes in pregnancy lead to an overall increase in plasma lipids to ensure adequate nutrient delivery to the fetus. These physiological changes become problematic, where a genetic abnormality in lipid metabolism exists and severe complications such as pancreatitis can arise. Available therapies for gestational hypertriglyceridaemia rely on augmentation of LPL activity. Where there is an underlying LPL defect, these therapies are ineffective and removal of triglyceride-rich lipoproteins via plasma exchange should be considered.

Learning points:

• Hormonal changes in pregnancy, mediated by progesterone,oestrogen and human placental lactogen, lead to a two- to three-fold increase in serum triglyceride levels.

• Pharmacological intervention for management of gestational hypertriglyceridaemia rely on the augmentation of lipoprotein lipase (LPL) activity to enhance catabolism of triglyceride-rich lipoproteins.

• Genetic mutations affecting the LPL gene can lead to severe hypertriglyceridaemia.

• Therapeutic plasma exchange (TPE) is an effective intervention for the management of severe gestational hypertriglyceridaemia and should be considered in cases where there is an underlying LPL defect.

• Preconception counselling and discussion regarding contraception is of paramount importance in women with familial hypertriglyceridaemia.

Summary

Measurement of glycated haemoglobin (HbA1c) has been utilised in assessing long-term control of blood glucose in patients with diabetes, as well as diagnosing diabetes and identifying patients at increased risk of developing diabetes in the future. HbA1c reflects the level of blood glucose to which the erythrocyte has been exposed during its lifespan, and there are a number of clinical situations affecting the erythrocyte life span in which HbA1c values may be spuriously high or low and therefore not reflective of the true level of glucose control. In the present case series, we describe the particulars of three patients with diabetes who had spuriously low HbA1c levels as a result of dapsone usage. Furthermore, we discuss the limitations of HbA1c testing and the mechanisms by which it may be affected by dapsone in particular.

Learning points:

• Various conditions and medications can result in falsely low HbA1c.

• Dapsone can lead to falsely low HbA1c by inducing haemolysis and by forming methaemoglobin.

• Capillary glucose measurement, urine glucose measurements and fructosamine levels should be used as alternatives to HbA1c for monitoring glycaemic control if it was falsely low or high.