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Open access

Fructose-induced severe hypertriglyceridemia and diabetes mellitus: a cautionary tale

Ana Dugic, Michael Kryk, Claudia Mellenthin, Christoph Braig, Lorenzo Catanese, Sandy Petermann, Jürgen Kothmann, and Steffen Mühldorfer

Summary

Drinking fruit juice is an increasingly popular health trend, as it is widely perceived as a source of vitamins and nutrients. However, high fructose load in fruit beverages can have harmful metabolic effects. When consumed in high amounts, fructose is linked with hypertriglyceridemia, fatty liver and insulin resistance. We present an unusual case of a patient with severe asymptomatic hypertriglyceridemia (triglycerides of 9182 mg/dL) and newly diagnosed type 2 diabetes mellitus, who reported a daily intake of 15 L of fruit juice over several weeks before presentation. The patient was referred to our emergency department with blood glucose of 527 mg/dL and glycated hemoglobin (HbA1c) of 17.3%. Interestingly, features of diabetic ketoacidosis or hyperosmolar hyperglycemic state were absent. The patient was overweight with an otherwise unremarkable physical exam. Lipase levels, liver function tests and inflammatory markers were closely monitored and remained unremarkable. The initial therapeutic approach included i.v. volume resuscitation, insulin and heparin. Additionally, plasmapheresis was performed to prevent potentially fatal complications of hypertriglyceridemia. The patient was counseled on balanced nutrition and detrimental effects of fruit beverages. He was discharged home 6 days after admission. At a 2-week follow-up visit, his triglyceride level was 419 mg/dL, total cholesterol was 221 mg/dL and HbA1c was 12.7%. The present case highlights the role of fructose overconsumption as a contributory factor for severe hypertriglyceridemia in a patient with newly diagnosed diabetes. We discuss metabolic effects of uncontrolled fructose ingestion, as well as the interplay of primary and secondary factors, in the pathogenesis of hypertriglyceridemia accompanied by diabetes.

Learning points

  • Excessive dietary fructose intake can exacerbate hypertriglyceridemia in patients with underlying type 2 diabetes mellitus (T2DM) and absence of diabetic ketoacidosis or hyperosmolar hyperglycemic state.

  • When consumed in large amounts, fructose is considered a highly lipogenic nutrient linked with postprandial hypertriglyceridemia and de novo hepatic lipogenesis (DNL).

  • Severe lipemia (triglyceride plasma level > 9000 mg/dL) could be asymptomatic and not necessarily complicated by acute pancreatitis, although lipase levels should be closely monitored.

  • Plasmapheresis is an effective adjunct treatment option for rapid lowering of high serum lipids, which is paramount to prevent acute complications of severe hypertriglyceridemia.

DOI:
https://doi.org/10.1530/EDM-21-0110
Volume 2021: Issue 1
Open access

Rapid response to leptin therapy in a FPLD patient with a novel PPARG missense variant

Fiona Melzer, Corinna Geisler, Dominik M Schulte, and Matthias Laudes

Summary

Familial partial lipodystrophy (FPLD) syndromes are rare heterogeneous disorders especially in women characterized by selective loss of adipose tissue, reduced leptin levels and severe metabolic abnormalities. Here we report a 34-year-old female with a novel heterozygotic c.485 thymine>guanine (T>G) missense variant (p.phenylalanine162cysteine; (Phe162Cys)) in exon 4 of the peroxisome proliferator-activated receptor gamma (PPARG) gene, developing a non-ketotic diabetes and severe hypertriglyceridemia with triglyceride concentrations >50 mmol/L. In this case, a particular interesting feature in comparison to other known PPARG mutations in FPLD is that while glycaemic control could be achieved through standard anti-diabetic medication, hypertriglyceridemia did neither respond to fibrate nor to omega-3-fatty acid therapy. This might suggest a lipid metabolism driven phenotype of the novel PPARG c.485T>G missense variant. Notably, recombinant leptin replacement therapy (metreleptin (Myalepta®)) was initiated showing a rapid and profound effect on triglyceride levels as well as on liver function tests and satiety feeling. Unfortunately, severe allergic skin reactions developed at the side of injection which could be covered by anti-histaminc treatment. We conclude that the heterozygous PPARG c.485T>G variant is a yet undescribed molecular basis underlying FPLD with difficulties predominantly to control hypertriglyceridemia and that recombinant leptin therapy may be effective in affected subjects.

Learning points

  • Heterozygous c.485T>G variant in PPARG is most likely a cause for FPLD in humans.

  • This variant results in a special metabolic phenotype with a predominant dysregulation of triglyceride metabolism not responding to standard lipid lowering therapy.

  • Recombinant leptin therapy is effective in rapidly improving hypertriglyceridemia.

DOI:
https://doi.org/10.1530/EDM-21-0082
Volume 2021: Issue 1
Open access

An unusual case of struma ovarii

Viktoria F Koehler, Patrick Keller, Elisa Waldmann, Nathalie Schwenk, Carolin Kitzberger, Kathrin A Schmohl, Thomas Knösel, Christian Georg Stief, and Christine Spitzweg

Summary

Struma ovarii is a teratoma of the ovaries predominantly composed of thyroid tissue. Hyperthyroidism associated with struma ovarii is rare, occurring in approximately 8% of cases. Due to the rarity of struma ovarii, available data are limited to case reports and small case series.We report on a 61-year-old female patient with known Hashimoto’s thyroiditis on levothyroxine replacement therapy for years with transition to clinical and biochemical hyperthyroidism despite antithyroid medication with carbimazole (10 mg/day), new diagnosis of urothelial carcinoma and an adnexal mass suspicious of ovarian cancer. The patient underwent resection of the adnexal mass and histopathology revealed a mature teratoma predominantly composed of thyroid tissue showing high levels of sodium iodide symporter protein expression. Following struma ovarii resection and disappearance of autonomous production of thyroid hormones, the patient developed hypothyroidism with severely decreased thyroid hormone levels fT4 and fT3 (fT4 0.4 ng/dL, reference interval 0.9–1.7 and fT3 < 1.0 pg/mL, reference interval 2.0–4.4). This has previously been masked by continued thyroid-stimulating hormone suppression due to long-term hyperthyroidism pre-surgery indicating secondary hypothyroidism, in addition to primary hypothyroidism based on the known co-existing chronic lymphocytic thyroiditis of the orthotopic thyroid gland. Levothyroxine administration was started immediately restoring euthyroidism.This case illustrates possible diagnostic pitfalls in a patient with two concurrent causes of abnormal thyroid function.

Learning points:

  • Struma ovarii is an ovarian tumor containing either entirely or predominantly thyroid tissue and accounts for approximately 5% of all ovarian teratomas.

  • In rare cases, both benign and malignant struma ovarii can secrete thyroid hormones, causing clinical and biochemical features of hyperthyroidism.

  • Biochemical features of patients with struma ovarii and hyperthyroidism are similar to those of patients with primary hyperthyroidism. In such cases, thyroid scintigraphy should reveal low or absent radioiodine uptake in the thyroid gland, but the presence of radioiodine uptake in the pelvis in a whole body radioiodine scintigraphy.

  • We give advice on possible diagnostic pitfalls in a case with two simultaneous causes of abnormal thyroid function due to the co-existence of struma ovarii.

DOI:
https://doi.org/10.1530/EDM-20-0142
Volume 2021: Issue 1
Open access

Continuous rhPTH (1–34) treatment in chronic hypoparathyroidism

Carmina Teresa Fuss, Stephanie Burger-Stritt, Silke Horn, Ann-Cathrin Koschker, Kathrin Frey, Almuth Meyer, and Stefanie Hahner

Summary

Standard treatment of hypoparathyroidism consists of supplementation of calcium and vitamin D analogues, which does not fully restore calcium homeostasis. In some patients, hypoparathyroidism is refractory to standard treatment with persistent low serum calcium levels and associated clinical complications. Here, we report on three patients (58-year-old male, 52-year-old female, and 48-year-old female) suffering from severe treatment-refractory postsurgical hypoparathyroidism. Two patients had persistent hypocalcemia despite oral treatment with up to 4 µg calcitriol and up to 4 g calcium per day necessitating additional i.v. administration of calcium gluconate 2–3 times per week, whereas the third patient presented with high frequencies of hypocalcemic and treatment-associated hypercalcemic episodes. S.c. administration of rhPTH (1–34) twice daily (40 µg/day) or rhPTH (1–84) (100 µg/day) only temporarily increased serum calcium levels but did not lead to long-term stabilization. In all three cases, treatment with rhPTH (1–34) as continuous s.c. infusion via insulin pump was initiated. Normalization of serum calcium and serum phosphate levels was observed within 1 week at daily 1–34 parathyroid hormone doses of 15 µg to 29.4 µg. Oral vitamin D and calcium treatment could be stopped or reduced and regular i.v. calcium administration was no more necessary. Ongoing efficacy of this treatment has been documented for up to 7 years so far. Therefore, we conclude that hypoparathyroidism that is refractory to both conventional treatment and s.c. parathyroid hormone (single or twice daily) may be successfully treated with continuous parathyroid hormone administration via insulin pump.

Learning points:

  • Standard treatment of hypoparathyroidism still consists of administration of calcium and active vitamin D.

  • Very few patients with hypoparathyroidism also do not respond sufficiently to standard treatment or administration of s.c. parathyroid hormone once or twice daily.

  • In those cases, continuous s.c. administration of parathyroid hormone via insulin pump may represent a successful treatment alternative.

DOI:
https://doi.org/10.1530/EDM-20-0009
Volume 2020: Issue 1
Open access

Unusual high blood glucose in ketoacidosis as first presentation of type 1 diabetes mellitus

Sebastian Hörber, Sarah Hudak, Martin Kächele, Dietrich Overkamp, Andreas Fritsche, Hans-Ulrich Häring, Andreas Peter, and Martin Heni

Summary

Diabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy.

Learning points:

  • Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients.

  • Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes.

  • First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes.

  • Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.

  • In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.

DOI:
https://doi.org/10.1530/EDM-18-0094
Volume 2018: Issue 1
Open access

Selective blood sampling for FGF-23 in tumor-induced osteomalacia

Hans-Christof Schober, Christian Kneitz, Franziska Fieber, Kathrin Hesse, and Henry Schroeder

Summary

Tumor-induced osteomalacia (TIO) is caused by the hormone fibroblast growth factor 23 (FGF-23). It is mainly produced in the tissue of mesenchymal tumors. Patients with TIO frequently suffer from a chronic decompensated pain syndrome and/or muscle weakness with postural deformity. Despite the severity of the disease, the diagnosis is frequently established late. In some cases, it takes several years to establish the condition. This case report concerning a 68-year old woman demonstrates the selective blood sampling for FGF-23 as path-breaking diagnostics to confirm the diagnosis of a neuroendocrine tumor.

Learning points:

  • Tumor-induced osteomalacia is a rare condition compared to other paraneoplastic syndromes.

  • It causes complex symptoms such as progressive reduction of physical capacity, exhaustion, fatigue, a decompensated pain syndrome of the musculoskeletal system and fractures of several bones.

  • Elevated serum levels of FGF-23 implicate massive phosphate elimination and resulting hypophosphatemia.

  • The diagnosis is often established over a period of several years because the localization of small FGF-23-producing tumors is complicated.

  • It is the combination of MRI and selective blood sampling for FGF-23 which permits reliable identification of tumors causing TIO and leads to accurate localization.

  • In a patient with generalized pain and reduced physical capacity, osteological parameters such as phosphate, 25-OH vitamin D3 and 1,25-(OH)2D3, as well as bone-specific alkaline phosphatase levels in serum should be determined. Hypophosphatemia should always lead to further diagnostic investigations aiming at the detection of an FGF-23-producing tumor.

DOI:
https://doi.org/10.1530/EDM-17-0006
Volume 2017: Issue 1
Open access

A novel stop mutation (p.(Gln22*)) of DAX1 (NR0B1) results in late-onset X-linked adrenal hypoplasia congenita

Judith Gerards, Michael M Ritter, Elke Kaminsky, Andreas Gal, Wolfgang Hoeppner, and Marcus Quinkler

Summary

DAX1 (NR0B1) is an orphan nuclear receptor, which plays an important role in development and function of the adrenal glands and gonads. Mutations in DAX1 cause X-linked adrenal hypoplasia congenita (X-linked AHC), which is characterized by adrenal insufficiency (AI) and hypogonadotropic hypogonadism (HHG). Affected boys present with adrenal failure usually in childhood and, later in life, with delayed puberty. However, patients with a late-onset form of X-linked AHC have also been described in the past years. We report a male patient who presented with symptoms of an adrenal crisis at the age of 38 years and was later diagnosed with HHG. Family history was positive with several male relatives diagnosed with AI and compatible with the assumed X-chromosomal inheritance of the trait. Direct sequencing of DAX1 of the patient revealed a hemizygous cytosine-to-thymine substitution at nucleotide 64 in exon 1, which creates a novel nonsense mutation (p.(Gln22*)). In order to compare the clinical presentation of the patient to that of other patients with X-linked AHC, we searched the electronic database MEDLINE (PubMed) and found reports of nine other cases with delayed onset of X-linked AHC. In certain cases, genotype–phenotype correlation could be assumed.

Learning points:

  • X-linked AHC is a rare disease characterized by primary AI and hypogonadotropic hypogonadism (HHG). The full-blown clinical picture is seen usually only in males with a typical onset in childhood.

  • Patients with a late-onset form of X-linked AHC have also been described recently. Being aware of this late-onset form might help to reach an early diagnosis and prevent life-threatening adrenal crises.

  • Adult men with primary AI of unknown etiology should be investigated for HHG. Detecting a DAX1 mutation may confirm the clinical diagnosis of late-onset X-linked AHC.

  • In relatives of patients with genetically confirmed X-linked AHC, targeted mutation analysis may help to identify family members at risk and asymptomatic carriers, and discuss conscious family planning.

DOI:
https://doi.org/10.1530/EDM-17-0054
Volume 2017: Issue 1
Open access

Remission of type 2 diabetes in a hypogonadal man under long-term testosterone therapy

Ahmad Haider, Karim S Haider, and Farid Saad

Summary

In daily practice, clinicians are often confronted with obese type 2 diabetes mellitus (T2DM) patients for whom the treatment plan fails and who show an inadequate glycemic control and/or no sustainable weight loss. Untreated hypogonadism can be the reason for such treatment failure. This case describes the profound impact testosterone therapy can have on a male hypogonadal patient with metabolic syndrome, resulting in a substantial and sustained loss of body weight, pronounced improvement of all critical laboratory values and finally complete remission of diabetes.

Learning points:

  • Hypogonadism occurs frequently in men with T2DM.

  • In case of pronounced abdominal fat deposition and T2DM, the male patient should be evaluated for testosterone deficiency.

  • Untreated hypogonadism can complicate the successful treatment of patients with T2DM.

  • Under testosterone therapy, critical laboratory values are facilitated to return back to normal ranges and even complete remission of diabetes can be achieved.

DOI:
https://doi.org/10.1530/EDM-17-0084
Volume 2017: Issue 1
Open access

Palliative treatment of uncontrollable hypercalcemia due to parathyrotoxicosis: denosumab as rescue therapy

Reiner Jumpertz von Schwartzenberg, Ulf Elbelt, Manfred Ventz, Knut Mai, Tina Kienitz, Lukas Maurer, Thomas Rose, Jens C Rückert, Christian J Strasburger, and Joachim Spranger

Parathyroid carcinoma is a rare disease leading to severe hypercalcemia due to hyperparathyroidism. Surgery is the primary treatment option. A more progressive form of the disease is characterized by parathyrotoxicosis, and subsequent hypercalcemia is the most common cause of death. We report a case presenting with severe hypercalcemia due to parathyrotoxicosis from parathyroid carcinoma treated for the first time using the monoclonal antibody denosumab as a rescue therapy and present long-term follow-up data. The 71-year-old patient presented with severe hypercalcemia due to metastatic parathyroid carcinoma. Despite undergoing treatment with bisphosphonates, cinacalcet hydrochloride, and forced diuresis, the patient`s condition deteriorated rapidly due to resistant hypercalcemia. Surgery performed because of spinal metastasis and forced diuresis lowered calcium levels, albeit they remained in the hypercalcemic range and significantly increased when forced diuresis was stopped. Considering a palliative situation to overcome hypercalcemia, we decided to administer denosumab, a monoclonal antibody that binds to the receptor activator of nuclear factor-kappa B ligand. After a single subcutaneous administration of 60 mg denosumab, calcium levels normalized within one day. Subsequent denosumab injections led to permanent control of serum calcium for more than 2 years despite rising parathyroid hormone levels and repeated surgeries. Together with recent cases in the literature supporting our observation, we believe that denosumab is relevant for future trials and represents an effective tool to control hypercalcemia in patients with advanced stages of parathyroid cancer.

Learning points

  • Severe hypercalcemia is the most common cause of death in patients with parathyroid carcinoma.

  • The monoclonal antibody denosumab rapidly lowered severely elevated serum calcium levels due to parathyrotoxicosis.

  • Denosumab was effective in the long-term treatment of hypercalcemia despite progression of parathyroid carcinoma.

DOI:
https://doi.org/10.1530/EDM-15-0082
Volume 2015: Issue 1
Open access

A patient with novel mutations causing MEN1 and hereditary multiple osteochondroma

Hanna Remde, Elke Kaminsky, Mathias Werner, and Marcus Quinkler

Summary

We report of a male patient aged 32 years who presented with primary hyperparathyroidism. Three parathyroid glands were resected. At the age of 46 years, nervus facialis irritation was noted, and an MRI scan incidentally revealed a non-functioning pituitary adenoma with affection of the chiasma opticum. The patient underwent transsphenoidal operation resulting in pituitary insufficiency postoperatively. At the same time, primary hyperparathyroidism reoccurred and a parathyroid adenoma located at the thymus was resected. The mother of the patient died early due to multiple tumors. The patient was suspected to have multiple endocrine neoplasia type 1 (MEN1) and genetic analysis was performed. In addition, on clinical examination, multiple exostoses were noticed and an additional genetic analysis was performed. His father was reported to have multiple osteochondromas too. MEN1 was diagnosed in the patient showing a novel heterozygote mutation c.2T>A in exon 2, codon 1 (start codon ATG>AAG;p.Met1?) of the MEN1 gene. In genetic mutational analysis of the EXT1 gene, another not yet known mutation c.1418-2A>C was found in intron 5 of the EXT1 gene (heterozygotic). In conclusion, we report novel mutations of the EXT1 and the MEN1 genes causing hereditary multiple osteochondromas and MEN1 in one patient.

Learning points

  • It is important to ask for the patient's family history in detail.

  • Patients with MEN1 are characterized by the occurrence of tumors in multiple endocrine tissues and nonendocrine tissues, most frequently parathyroid (95%), enteropancreatic neuroendocrine (50%), and anterior pituitary (40%) tissues.

  • Familiar MEN1 has a high degree of penetrance (80–95%) by the age over 50; however, combinations of the tumors may be different in members of the same family.

  • Patients with EXT1 gene mutations should be monitored for possible transformation of bone lesions into osteochondrosarcoma.

DOI:
https://doi.org/10.1530/EDM-14-0120
Volume 2015: Issue 1