Summary

Doege–Potter syndromeis a paraneoplastic syndrome characterized by nonislet cell tumor hypoglycemia due to a solitary fibrous tumor, which produces insulin-like growth factor II. In this report, we present the case of a 67-year-old male with recurrent and refractory hypoglycemia due to DPS successfully treated with imatinib. He initially presented with neuroglycopenic symptoms and dyspnea secondary to a giant tumor in the left hemithorax, which was totally resected. During follow-up, 7 years later, he presented with thoracoabdominal tumor recurrence associated with severe hypoglycemia and underwent subtotal tumor resection, with a subsequent improvement of symptoms. The following year, he had a recurrence of his intra-abdominal tumor, which was unresectable, associated with severe hypoglycemia refractory to dextrose infusion and corticosteroids, thus receiving imatinib with a favorable response. The clinical presentation, diagnostic approach, progression of the disease, and response to treatment with imatinib in the management of a patient with large, recurrent, and unresectable mesenchymal tumors with insulin-like growth factor-2 secretion causing hypoglycemiahighlight the importance of this case report.

Learning points

• Doege–Potter syndrome (DPS) is a rare cause of tumoral hypoglycemia of non-pancreatic origin.

• Some malignant or benignant neoplasms have ectopic secretion of insulin-like growth factor-2.

• Total surgical removal is the principal treatment in patients with DPS.

• Tyrosine kinase inhibitors management in DPS may contribute to improved tumor control in patients with unresectable tumors and severe hypoglycemia.

Summary

Postoperative (PO) complications after transsphenoidal surgery (TSS) are rare when performed in pituitary referral centers. Partial hypopituitarism is more frequent and somewhat expected. Meningitis, cerebrospinal fluid leaks, and visual deficits are unusual. Cerebrovascular complications, including cerebral vasospasm are rare, usually under-appreciated and not mentioned to the patient prior to the surgery. This is a report of a 51-year-old male with a non-functioning pituitary macroadenoma presenting with partial hypopituitarism and visual field loss. The patient was submitted to an uneventful TSS. On the first PO day, he developed a left palpebral ptosis with unequal pupils and impaired consciousness (12 points on Glasgow Coma Scale). CT scan revealed a perimesencephalic subarachnoid hemorrhage (SAH) grade 1 according to the modified Fisher scale. High-dose dexamethasone (16 mg/day) was initiated and the patient became more alert (Glasgow 14). On the fifth PO day, due to progression of the neurological deficits (left III, IV, and VI cranial nerves palsy, ataxia, dysdiadochokinesia, right dysmetria, and dysarthria), a magnetic resonance angiography was obtained and revealed a recent mesencephalic infarct without evident vasospasm. Nevertheless, nimodipine 60 mg 4/4 h was initiated. No improvement was seen after 3 days of treatment. The patient was discharged and put on rehabilitation, returning to normal gait and balance after 7 months. This, therefore, is a case of an unexpected mesencephalic infarct probably due to vasospasm induced by minor SAH. Although exceptionally rare, informing the patient about this event prior to TSS is important due to its significant neurological impact. More data are needed considering preventive treatment with nimodipine as soon as SAH is detected after TSS and whether it would improve neurological outcomes.

Learning points

• Whenever neurological deficits arise after transsphenoidal surgery (TSS), systemic infection, meningitis, electrolyte imbalance, and evident hemorrhage must be promptly investigated.

• Although rare, cerebral vasospasm (CVS) after TSS is associated with high morbidity and high mortality rates.

• Vigilance for vasospasm is necessary for patients undergoing TSS for pituitary adenoma, especially those with significant suprasellar extension.

• Informing this event to the patient prior to TSS is essential due to its significant morbidity and mortality.

• Post-TSS subarachnoid hemorrhage and hemiparesis may be important clues indicating CVS and infarction.

• There is limited evidence in the literature regarding post-TSS CVS surveillance and treatment strategies which could have an impact on clinical decisions.

Summary

We present the case of a 23-year-old patient with maturity-onset diabetes of the young type 3 (MODY 3) and premature ovarian insufficiency (POI). There is no known correlation between MODY 3 and POI, although POI can impair glucose metabolism, and MODY can cause microvascular complications such as POI. We did not find literature describing a correlation between these two pathologies nor did we find similar cases described in the literature.

Learning points

• Maturity-onset diabetes of the young type 3 (MODY 3) is an infrequent cause of diabetes that should be considered in young patients with atypical presentation of type 1 or type 2 diabetes.

• MODY 3 can be associated with microvascular complications of diabetes, which is why it is important to diagnose as early as possible.

• Impairment of glucose metabolism has been demonstrated in patients with premature ovarian insufficiency and menopause.

Summary

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) induce osmotic diuresis by inhibiting the proximal renal tubular reabsorption of the filtered glucose load, which in turn can occasionally lead to severe dehydration and hypotension amidst other adverse effects. We present a case of a 49-year-old man with type 2 diabetes mellitus (T2D) on canagliflozin, a SGLT2i. The patient was brought to the emergency room following a motor vehicle accident. He was confused and had an altered mental status. His blood alcohol and urine toxicology screens were negative. Initial investigations revealed that he had severe hyponatremia with euglycemic ketoacidosis. The adverse condition was reversed with close monitoring and timely management, and the patient was eventually discharged. This is the first report to suggest hyponatremia as a potentially serious adverse effect following SGLT2i therapy. Its impact on the renal tubule handling of sodium and water is not yet well characterized. While further studies are warranted to understand better the pathophysiological mechanisms associated with SGLT2i-induced adverse effects, timely dose reduction or perhaps even its temporary discontinuation may be recommended to prevent complications.

Learning points

• Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are usually well-tolerated, but some serious adverse effects have been documented.

• Our case report suggests hyponatremia as a potential, rare side effect of SGLT2i and makes physicians aware of the occurrence of such life-threatening but preventable complications.

• Timely and close monitoring of the patient, with temporary discontinuation of this drug, may be recommended towards effective management.

• Studies demonstrating a comprehensive understanding of SGLT2i-related electrolyte derangements are warranted.

Summary

Hypoglycemia is an uncommon clinical problem in non-diabetic patients or patients not being treated for diabetes mellitus. It is a rare, but well-established complication of bariatric surgery and, in some cases, it can be the only symptom of another medical problem. A 50-year-old woman with a history of partially recovered hypopituitarism after transsphenoidal surgery for a non-functioning pituitary macroadenoma complained about symptomatic hypoglycemia after sleeve gastrectomy surgery. Our initial studies failed to determine the cause for these episodes and treatment with acarbose (suspecting a dumping syndrome) was not helpful. Finally, laboratory findings revealed growth hormone (GH) deficiency. The patient received treatment with GH, with the resolution of symptoms after 3 months of treatment. Our case suggests that all causes of hypoglycemia should be considered and studied after bariatric surgery. An improvement in insulin-resistance following bariatric surgery can trigger clinical manifestations of GH deficiency.

Learning points:

• Postprandial hypoglycemia after bariatric surgery is usually due to dumping syndrome.

• Even after bariatric surgery, all causes of hypoglycemia should be considered and studied.

• After significant weight loss, insulin sensitivity is usually restored and can trigger clinical manifestations of GH deficiency.

• Hypoglycemia is a rare symptom of GH deficiency.

Learning points:

• Axillary metastases in differentiated thyroid carcinoma are uncommon.

• In patients with high-risk thyroid carcinomas, a decline in thyroglobulin antibody may not signal disease improvement, but rather a progression to a poorly differentiated form of cancer.

• PAX8 staining can be used to differentiate thyroid carcinomas from lung adenocarcinomas.

Summary

Cushing’s syndrome is an endocrine disorder that causes anovulatory infertility secondary to hypercortisolism; therefore, pregnancy rarely occurs during its course. We present the case of a 24-year-old, 16-week pregnant female with a 10-month history of unintentional weight gain, dorsal gibbus, nonpruritic comedones, hirsutism and hair loss. Initial biochemical, hormonal and ultrasound investigations revealed hypokalemia, increased nocturnal cortisolemia and a right adrenal mass. The patient had persistent high blood pressure, hyperglycemia and hypercortisolemia. She was initially treated with antihypertensive medications and insulin therapy. Endogenous Cushing’s syndrome was confirmed by an abdominal MRI that demonstrated a right adrenal adenoma. The patient underwent right laparoscopic adrenalectomy and anatomopathological examination revealed an adrenal adenoma with areas of oncocytic changes. Finally, antihypertensive medication was progressively reduced and glycemic control and hypokalemia reversal were achieved. Long-term therapy consisted of low-dose daily prednisone. During follow-up, despite favorable outcomes regarding the patient’s Cushing’s syndrome, stillbirth was confirmed at 28 weeks of pregnancy. We discuss the importance of early diagnosis and treatment of Cushing’s syndrome to prevent severe maternal and fetal complications.

Learning points:

• Pregnancy can occur, though rarely, during the course of Cushing’s syndrome.

• Pregnancy is a transient physiological state of hypercortisolism and it must be differentiated from Cushing’s syndrome based on clinical manifestations and laboratory tests.

• The diagnosis of Cushing’s syndrome during pregnancy may be challenging, particularly in the second and third trimesters because of the changes in the maternal hypothalamic-pituitary-adrenal axis.

• Pregnancy during the course of Cushing’s syndrome is associated with severe maternal and fetal complications; therefore, its early diagnosis and treatment is critical.

Summary

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant condition characterized by parathyroid, anterior pituitary and enteropancreatic endocrine cell tumors. Neuroendocrine tumors occur in approximately in 5–15% of MEN1 patients. Very few cases of ovarian NETs have been reported in association with clinical MEN1 and without genetic testing confirmation. Thirty-three-year-old woman with MEN1 was found to have right adnexal mass on computed tomography (CT). Attempt at laparoscopic removal was unsuccessful, and mass was removed via a minilaparotomy in piecemeal fashion. Pathology showed ovarian NET arising from a teratoma. Four years later, patient presented with recurrence involving the pelvis and anterior abdominal wall. She was treated with debulking surgery and somatostatin analogs (SSAs). Targeted DNA sequencing analysis on the primary adnexal mass as well as the recurrent abdominal wall tumor confirmed loss of heterozygosity (LOH) at the MEN1 gene locus. This case represents to our knowledge, the first genetically confirmed case of ovarian NET arising by a MEN1 mechanism in a patient with MEN1. Extreme caution should be exercised during surgery as failure to remove an ovarian NET en masse can result in peritoneal seeding and recurrence. For patients with advanced ovarian NETs, systemic therapy options include SSAs, peptide receptor radioligand therapy (PRRT) and novel agents targeting mammalian target of rapamycin (mTOR) and vascular endothelial growth factor (VEGF).

Learning points:

• Ovarian NET can arise from a MEN1 mechanism, and any adnexal mass in a MEN1 patient can be considered as a possible malignant NET.

• Given the rarity of this disease, limited data are available on prognostication and treatment. Management strategies are extrapolated from evidence available in NETs from primaries of other origins.

• Care should be exercised to remove ovarian NETs en bloc as failure to do so may result in peritoneal seeding and recurrence.

• Treatment options for advanced disease include debulking surgery, SSAs, TKIs, mTOR inhibitors, PRRT and chemotherapy.

Learning points:

• Hypothyroidism can have a wide range of clinical presentations that are often nonspecific, which can cause difficulty in diagnosis.

• In pediatric patients presenting with chronic abdominal pain as only symptom, hypothyroidism should be considered by the pediatricians and ruled out.

• In pediatric population, treatment of hypothyroidism varies depending on patients’ weight and age.

• Delay in diagnosis of hypothyroidism can cause significant morbidity and distress in pediatrics population.

Learning points:

• When a toxic ingestion is suspected, direct visualization of the patient’s pills is advised in order to rule out the possibility of patient- or pharmacist-related medication errors.

• Though sending a specimen for determination of the plasma metformin concentration is important when a metformin-treated patient with diabetes presents with lactic acidosis, complex relationships exist between metformin accumulation, hyperlactatemia and acidosis, and the drug may not always be the precipitating factor.

• Intermittent hemodialysis is recommended as the first-line treatment for metformin-associated lactic acidosis (MALA).

• An investigational delayed-release form of metformin with reduced systemic absorption may carry a lower risk for MALA in patients with renal insufficiency, in whom metformin therapy may presently be contraindicated.