Summary

Acute illness-related stress can result in severe hypercortisolism and bilateral adrenal enlargement in certain patients. We report a case of stress-induced hypercortisolism and bilateral adrenal enlargement in a patient admitted for acute respiratory distress and cardiogenic shock. Bilateral adrenal enlargement and hypercortisolism found during hospitalization for acute illness resolved 3 weeks later following the resolution of acute illness. Acute illness can be a precipitating factor for stress-induced hypercortisolism and bilateral adrenal enlargement. We hypothesize that increased adrenocorticotrophic hormone mediated by corticotrophin-releasing hormone from physical stress resulted in significant adrenal hyperplasia and hypercortisolism. This mechanism is downregulated once acute illness resolves.

Learning points

• Adrenal enlargement with abnormal adrenal function after stress is uncommon in humans; however, if present, it can have self-resolution after the acute illness is resolved.

• Stress induces enlargement of the adrenals, and the degree of cortisol elevation could be very massive. This process is acute, and the absence of cushingoid features is expected.

• Treatment efforts should be focused on treating the underlying condition.

Summary

A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and ⁶⁸Gallium-DOTATATE PET–CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome.

Learning points

• Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described.

• Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload.

• Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer.

• More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome.

• Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

Summary

Iron metabolism and markers hereof are altered in anorexia nervosa (AN) but far from completely understood. We report a case of extreme hyperferritinemia in a patient with AN and discuss the possible mechanisms and current knowledge about the association between hyperferritinemia and AN. A 20-year-old woman with a history of AN presented with bradycardia, weariness, and malaise in addition to an incidentally very high ferritin level. The symptoms disappeared spontaneously after a short admission. There were no signs suggestive of systemic, hematological, or malignant disease causing the very high concentration of ferritin. Her body weight was in decline, leading up to admission, but did initially increase after discharge accompanied by declining ferritin concentration. However, a clear association between ferritin dynamics and weight changes or physical activity was not identified and neither were other causes of the hyperferritinemia. Around one in four patients with AN have increased ferritin concentrations. Our case represents the highest ferritin concentration reported in a patient with AN without other underlying causes or comorbidities.

Learning points

• Perturbed iron metabolism is frequent in restrictive type anorexia nervosa but incompletely understood.

• Altered ferritin in anorexia nervosa may be linked to nutritional status.

Summary

A 47-year-old man was diagnosed with a left adrenal incidentaloma at 40 years of age. The tumor had irregular margins and grew from 18 mm to 30 mm in maximum diameter over 7 years. On computed tomography scan, the mass appeared to localize within the tip of the lateral limb of the left adrenal gland, and between the left adrenal gland and the posterior wall of the stomach. The plasma corticotropin and cortisol concentrations and the 24-h urine fractionated metanephrine levels were normal. ¹²³I-metaiodobenzylguanidine scintigraphy showed tumor avidity consistent with a hormonally inactive pheochromocytoma. A laparoscopic left adrenalectomy was performed; however, no tumor was present in the resected specimen. Abdominal computed tomography postoperatively showed that the tumor remained intact and appeared to connect to the posterior wall of the stomach. A laparotomy was performed and the tumor was removed. The tumor was localized to the intraperitoneal space and isolated from the posterior wall of the stomach. The pathological diagnosis was a gastrointestinal stromal tumor. Clinicians need to be aware of the limitations of diagnostic imaging studies in diagnosing non-functioning adrenal incidentalomas, which require a pathological analysis for the final diagnosis. Moreover, clinicians need to provide patients with sufficient informed consent when deciding on treatment strategies.

Learning points

• Anatomic structures and tumors that develop in neighboring tissues to the adrenal glands may be confused with primary adrenal tumors.

• ¹²³I- metaiodobenzylguanidine (MIBG) scintigraphy is specific for diagnosing pheochromocytomas and paragangliomas; however, it has been reported that ¹²³I-MIBG may accumulate in neuroendocrine tumors as well as other tumors.

• Clinicians should recognize the limitations of imaging studies and the uncertainty of an imaging-based preoperative diagnosis.

Summary

Hypercalcaemia is a common complication seen in malignancy, frequently due to paraneoplastic parathyroid hormone-related peptide production or osteolytic bony metastases. We present a 58-year-old female with immunotherapy-mediated hypophysitis causing secondary cortisol deficiency resulting in severe glucocorticoid-responsive hypercalcaemia. Whilst hypophysitis is a well recognised adverse event in those receiving immunotherapy for advanced malignancy, it does not typically present with hypercalcaemia. The mechanism responsible for hypercalcaemia due to hypocortisolaemia has not been fully elucidated although hypotheses include the effects of volume depletion and thyroxine’s action on bone. Prompt treatment with glucocorticoids caused an improvement in the patient’s symptoms and corrected her hypercalcaemia which later returned after an attempted glucocorticoid wean. With the increasing uptake of immunotherapy, clinicians should be aware of this unusual presentation of immunotherapy-related hypophysitis and secondary hypocortisolaemia which can be life-threatening if the diagnosis is delayed.

Learning points

• Immunotherapy can cause inflammation of the pituitary gland resulting in secondary hypocortisolaemia, which can, though rarely, present as hypercalcaemia.

• Secondary hypocortisolaemia requires prompt recognition and treatment with glucocorticoids. Glucocorticoid replacement leads to rapid clinical and biochemical improvement in these patients.

• The differential diagnosis for glucocorticoid-responsive hypercalcaemia extends beyond granulomatous disorders (e.g. sarcoidosis, tuberculosis) to adrenocorticotrophic hormone and cortisol deficiency, particularly in patients receiving immunotherapy.

• Hypocortisolaemia can lead to hypercalcaemia through various proposed mechanisms. Low serum glucocorticoids are associated with reduced blood volume, thus reducing renal calcium excretion. In addition, without glucocorticoid’s inhibitory action, thyroxine appears to drive calcium mobilisation from bone.

Summary

The spectrum of endocrine-related complications of COVID-19 infection is expanding; one of the most concerning of which is adrenal haemorrhage due to the risk of catastrophic adrenal crisis. In this study, we present a case that highlights the challenging management of a large, indeterminate unilateral adrenal mass during pregnancy and draws attention to a rare yet probably underestimated complication of COVID-19. During hospitalization for severe COVID-19 pneumonia, a 26-year-old woman was incidentally found to have a 12.5 cm heterogeneous left adrenal mass. Soon after the discovery, she became pregnant and upon referral, she was in the seventh week of gestation, without clinical or biochemical features of hormonal excess. The uncertainty of the diagnosis and the risks of malignancy and surgical intervention were discussed with the patient, and a period of radiological surveillance was agreed upon. An MRI scan performed 3 months later showed a size reduction of the adrenal lesion to 7.9 cm, which was against malignancy. A Doppler ultrasound showed a non-vascular, well-defined round lesion consistent with an adrenal haematoma, likely a complication of the recent COVID-19 infection. The multidisciplinary team recommended further radiological follow-up. The patient then spontaneously had miscarriage at 12 weeks gestation. Subsequent radiological surveillance showed a further size reduction of the adrenal lesion to 5.5 cm. The patient conceived again during follow-up, and the repeated Doppler ultrasound showed stable appearances of the adrenal mass, and thus, it was agreed to continue radiological monitoring after delivery. The pregnancy was uneventful, and the patient delivered a healthy baby. An MRI scan performed after delivery showed a stable but persistent lesion consistent with a likely underlying adrenal lesion.

Learning points

• Unilateral adrenal haemorrhage can occur as a complication of COVID-19 and should be considered in the differential diagnosis of heterogeneous adrenal masses if there is a history of recent infection.

• Management of large indeterminate adrenal masses during pregnancy poses several challenges and should be led by an experienced multidisciplinary team.

• Underlying adrenal tumours may trigger non-traumatic haemorrhages, especially if exacerbated by stressful illness.

Summary

Large-cell neuroendocrine carcinoma (LCNEC) is a rare neuroendocrine prostatic malignancy. It usually arises after androgen deprivation therapy (ADT), while de novo cases are even more infrequent, with only six cases described. The patient was a 78-year-old man with no history of ADT who presented with cervical lymphadenopathy. Diagnostic approaches included PET/CT, MRI, CT scans, ultrasonography, biopsies, and cytological and immunohistochemical evaluations. Results showed a poorly differentiated carcinoma in the thyroid gland accompanied by cervical lymph node enlargement. Thyroid surgery revealed LCNEC metastasis to the thyroid gland. Additional metastases were identified in both the adrenal glands. Despite appropriate treatment, the patient died of the disease. De novo LCNEC of the prostate is a rare, highly aggressive tumor with a poor prognosis. It is resistant to most therapeutic agents, has a high metastatic potential, and is usually diagnosed at an advanced stage. Further studies are required to characterize this tumor.

Learning points

• De novo LCNECs of the prostate gland can metastasize almost anywhere in the body, including the thyroid and adrenal glands.

• LCNECs of the prostate are usually associated with androgen-depriving therapy, but de novo cases are also notable and should be accounted for.

• Further studies are required to fully understand and treat LCNECs more effectively.

Summary

We describe a case of a 47-year-old patient who presented with severe lactic acidosis, troponinemia, and acute kidney injury after receiving 8 mg of intramuscular dexamethasone for seasonal allergies in the setting of an undiagnosed epinephrine-secreting pheochromocytoma. This case was atypical, however, in that the patient exhibited only mildly elevated noninvasive measured blood pressures. Following a period of alpha-adrenergic blockade, the tumor was resected successfully. Steroid administration can precipitate pheochromocytoma crisis that may present unusually as in our patient with mild hypertension but profound lactic acidosis.

Learning points

• Steroids administered via any route can precipitate pheochromocytoma crisis, manifested by excessive catecholamine secretion and associated sequelae from vasoconstriction.

• Lack of moderate/severe hypertension on presentation detracts from consideration of pheochromocytoma as a diagnosis.

• Lactatemia after steroid administration should prompt work-up for pheochromocytoma, as it can be seen in epinephrine-secreting tumors.

• Noninvasive blood pressure measurements may be unreliable during pheochromocytoma crisis due to excessive peripheral vasoconstriction.

Summary

Congenital lipoid adrenal hyperplasia (CLAH) is characterized by a defect in the STAR protein-encoding gene that attenuates all steroidogenesis pathways. Herein, we present the first reported case in Saudi Arabia of a 46 XY, phenotypically female infant with an unfamiliar, darkened complexion compared to the family’s skin color. Based on the clinical and biochemical findings, CLAH was diagnosed and glucocorticoid replacement therapy was initiated. As a result, we suggest that pediatricians should always investigate the possibility of adrenal insufficiency when encountering unusual dark skin.

Learning points

• Pediatricians should be prompted to rule out adrenal insufficiency in unexpectedly dark skin neonates.

• In such patients, pediatricians should not wait until the neonate develops an adrenal crisis.

• A low level of 17-hydroxyprogesterone does not always rule out the possibility of inherited adrenal gland disorders, and additional tests should be performed for early detection.

Summary

Hiccups are a common symptom characterized by intermittent spasmodic contraction of the diaphragm. Most hiccups are transient, but some are refractory. Patients with intractable hiccups often have abnormalities of the diaphragm, medulla oblongata, and lesions affecting nerve fibers connecting them. Moreover, electrolyte abnormalities, including hyponatremia, are frequently observed in patients with intractable hiccups. Adrenal insufficiency (AI) is one of the causes of hyponatremia. However, hiccups are not commonly the first presentation. Herein, we describe a case of a 45-year-old woman complaining of refractory hiccups. The patient was initially diagnosed with hiccups associated with cervical cancer metastasis to the liver and peritoneum. The administration of chlorpromazine did not have a beneficial effect on her hiccup. Fasting hypoglycemia and hyponatremia were later found. Her serum cortisol level was low without an elevation of adrenocorticotropic hormone level. MRI of the pituitary gland showed metastatic lesion in the pituitary gland and stalk. Thus, the patient was diagnosed with secondary AI due to cervical cancer metastasis to the pituitary gland and stalk. Administration of hydrocortisone improved her hiccups with the normalization of serum sodium level. Therefore, differential diagnosis in advanced cancer patients with hiccups should include AI-induced hyponatremia.

Learning points

• Hiccups could be the first manifestation of adrenal insufficiency (AI).

• Hiccups in patients with AI are often mediated by hyponatremia.

• Hyponatremia is less frequent in secondary AI than in primary AI. However, hyponatremia can result from increased antidiuretic hormone due to loss of cortisol.

• The differential diagnosis should include AI-induced hyponatremia if hiccups occur in patients with advanced cancer, as metastasis to adrenal gland or pituitary gland could cause AI.