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Faculty of Electrical Engineering, Mathematics and Computer Science, University of Twente, Enschede, the Netherlands
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Faculty of Electrical Engineering, Mathematics and Computer Science, University of Twente, Enschede, the Netherlands
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Summary
This study compares the effects of metformin, sulfonylurea derivative (SU) and no treatment in HNF4A-MODY on glycemic control. In two patients with HNF4A-MODY, we changed the existing metformin treatment to SU derivative. The effect on the glycemic control was registered with a Freestyle Libre Flash glucose monitoring device. Each treatment period had a duration of 2 consecutive weeks, and in between, an intermediate period without medication. Data from the first 2 days after changing medications were excluded. We calculated time in range (TIR), and differences in the mean glucose level were tested with a one-way ANOVA test. The 24-h average glucose levels were significantly lower with either metformin (7.7 mmol/L; P < 0.001 and 6.3 mmol/L; P < 0.001) or gliclazide (7.6 mmol/L; P < 0.001 and 5.8 mmol/L; P < 0.001) compared to no treatment (9.4 and 8.9 mmol/L). The TIR with metformin or gliclazide was higher than without treatment (patient 1: 87 and 83 vs 61% and patient 2: 83 and 93 vs 67%). Treatment with either metformin or gliclazide effectively decreases blood glucose, rendering both drugs appropriate for treating HNF4A-MODY.
Learning points
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HNF4A-MODY has a mild phenotype.
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Blood glucose was responsive to long-term metformin treatment in HNF4A-MODY.
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Metformin and gliclazide seem appropriate treatments for HNF4A-MODY.
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Summary
Von Hippel–Lindau’s disease (VHL) is a hereditary tumor syndrome characterized by its prototype lesions, hemangioblastomas, and renal cell carcinomas. Treatment for renal cell carcinomas can ultimately result in long-term dialysis. Pancreatic neuroendocrine tumors (pNET) can also occur in the course of the disease. Currently, peptide receptor radionuclide therapy (PRRT) is the standard treatment for progressive neuroendocrine tumors. However, little is known about treatment with PRRT in patients on dialysis, an infrequent presentation in patients with VHL. We present a 72-year-old man with VHL on hemodialysis and a progressive pNET. He received four cycles of PRRT with a reduced dose. Only mild thrombopenia was seen during treatments. The patient died 9 months after the last PRRT because of acute bleeding in a hemangioblastoma. Hemodialysis is not a limiting factor for PRRT treatment and it should be considered as it seems a safe short-term treatment option for this specific group.
Learning points
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Von Hippel–Lindau disease (VHL) is a complex disease in which former interventions can limit optimal treatment for following VHL-related tumors later in life.
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Metastasized pancreatic neuroendocrine tumors occur as part of VHL disease.
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Peptide receptor radionuclide therapy seems a safe short-term treatment option in patients on hemodialysis.
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Search for other papers by Johannes Hofland in
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Summary
Middle ear adenomas with neuroendocrine features (ANEF) are rare, with an estimated 150 reported cases. They usually pursue an indolent clinical course. Four reported cases of middle ear ANEF with distant metastases were treated with surgery, external beam radiation therapy (EBRT) and chemotherapy. To date, no successful systemic treatment for malignant behaviour of this rare tumour has been reported. Long-acting somatostatin analogues (SSAs) and peptide receptor radionuclide therapy (PRRT) have been used in well-differentiated metastatic neuroendocrine tumours (NETs), but their use has never been described in cases of metastatic middle ear ANEF. We report two patients with grade 1 middle ear ANEF treated with surgery and EBRT. They had stable disease for several years, until clinical symptoms appeared and extensive metastases were detected on 68Ga-DOTA0-Tyr3-octreotate (DOTATATE) PET/CT. Treatment with long-acting SSA was started, with stable disease for 1 year. Afterwards, despite undergoing local treatments, both patients presented progressive disease. Due to high-uptake metastases at 68Ga-DOTATATE PET/CT, both cases underwent four cycles of PRRT with 177Lu-DOTATATE, which secured disease control and improvement of quality of life in both. Similar to other well-differentiated NETs, SSA and PRRT could constitute efficacious therapeutic options in metastatic middle ear ANEF. Its neuroendocrine differentiation, potential to metastasize and somatostatin receptor type 2 expression prompt consideration and management of this disease as a neuroendocrine neoplasm.
Learning points
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Our cases oppose the 2017 WHO classification of middle ear adenoma with neuroendocrine features as a benign disease.
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This entity warrants long-term follow-up, as local recurrence or persistence of disease is reported in up to 18% of surgically treated patients.
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PET/CT scan with 68Ga-labelled somatostatin analogues (SSA) can be used for staging of metastatic middle ear adenoma with neuroendocrine features.
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Unlabelled SSA and peptide receptor radionuclide therapy (PRRT) with radiolabelled SSA can be the first systemic therapeutic options for patients with advanced middle ear adenoma with neuroendocrine features.
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Summary
Gynecomastia is a symptom with a potential high disease burden. It has a variety of underlying causes, such as malignant, drug-related or hormonal. The presence of gynecomastia can be explained in thyrotoxicosis due to a concomitant disbalance of sex hormones. Interestingly, it rarely is the presenting symptom of Graves’ disease. A 49-year-old man presented to our outpatient clinic with right-sided gynecomastia. After thorough history taking, more symptoms of thyrotoxicosis were present. Treatment was started with thiamazole and later levothyroxine. Three months after this treatment the gynecomastia and other symptoms resolved completely. A disbalance of sex hormones due to an increased expression of the protein sex hormone-binding globulin (SHBG) caused by thyrotoxicosis could result in gynecomastia. In vitro and in vivo research in mice suggest that the pathophysiology of thyrotoxicosis-associated gynecomastia is due to upregulation of hepatocyte nuclear factor-4α (HNF4A) in liver cells. Subsequent increase of SHBG results in a decrease of free testosterone levels.
Learning points
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Gynecomastia is a common finding (up to almost 40%) on physical examination in patients with hyperthyroidism.
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In gynecomastia, thyroid function tests should be examined on initial presentation because of the relative simple treatment.
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The pathophysiology of thyrotoxicosis-associated gynecomastia is well understood by a sex-hormonal disbalance due to an increased expression of SHBG.
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Due to the well explainable pathophysiology, reduction of symptoms can be expected after treatment.
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The underlying mechanism of an increased expression of SHBG is not well understood. However, in vitro and in vivo research in mice suggests that thyrotoxicosis causes an increased expression of HNF4A in liver cells. Thus, upregulating the expression of SHBG.
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Interestingly, HNF4A is suspected to play an important role in MODY. Future research will clarify the importance of this gene and might open up new insights for therapy.
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Summary
This paper reports on two patients with a long-standing diagnosis of an ENETS stage IV neuroendocrine tumour (NET) of the small intestine who developed neurological symptoms. The first patient only had bulbar symptoms and tested positive for acetylcholine receptor antibodies. The second patient had more classical symptoms of fatigable diplopia and muscle weakness of the legs, but no detectable antibodies. The diagnosis of paraneoplastical myasthenia gravis (MG) was postulated. Both patients were treated with pyridostigmine for MG and octreotide for the NETs. Interestingly, treatment of the NETs resulted in improvement of myasthenic symptoms. Paraneoplastic MG has been described to occur with certain malignancies, mainly thymoma. Herein, we prove that the association with gastrointestinal NETs, however, rare, is also one to be considered by clinicians dealing with either of these diseases. The pathogenesis has yet to be elucidated.
Learning points
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NETs are rare malignancies with a wide variety of symptoms.
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Paraneoplastic MG can occur with various types of malignancies.
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Herein, we provide evidence of paraneoplastic MG in association with a grade IV NET of the small intestine.
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Treatment of the NETs resulted in remission of myasthenic symptoms in one patient.
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Summary
A 53-year-old male presented with recurrent calcium oxalate kidney stones as a first sign of underlying acromegaly, which vanished when his acromegaly was controlled. The exact mechanism behind hypercalciuria and urolithiasis in acromegaly is not yet clear. By discussing this case, a short overview of the pathophysiology of hypercalciuria in acromegaly and practical insights are given.
Learning points
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Hypercalciuria is a common finding in acromegaly.
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There are only few reports describing hypercalciuric kidney stones in acromegaly.
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We assume that in acromegaly there is a primary role of IGF1-mediated, PTH-independent increase in calcitriol synthesis resulting in hypercalciuric kidney stones.
