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Betty Korljan Jelaska, Sanja Baršić Ostojić, Nina Berović, and Višnja Kokić

hyperuricaemia. She came to our clinic at the age of 22 years for the diagnostic evaluation of arterial hypertension and dyslipidaemia. Her weight was initially 80 kg, height was 157 cm and BMI was 32.5. The levels of uric acid were 425 nmol/l, LDL 3 mmol/l, HDL

Open access

Aoife Garrahy, Matilde Bettina Mijares Zamuner, and Maria M Byrne

.7%). HbA1C improved to 77 mmol/mol (9.2%) after 3 months on insulin therapy. Hypertension and dyslipidaemia were treated. Investigation From 2002 to 2008, HbA1C failed to improve to target, average 73 mmol/mol (8.8%) on 44–62 units of insulin per

Open access

Angelo Paci, Ségolène Hescot, Atmane Seck, Christel Jublanc, Lionel Mercier, Delphine Vezzosi, Delphine Drui, Marcus Quinkler, Martin Fassnacht, Eric Bruckert, Marc Lombès, Sophie Leboulleux, Sophie Broutin, and Eric Baudin

Summary

Mitotane (o,p′-DDD) is the standard treatment for advanced adrenocortical carcinoma (ACC). Monitoring of plasma mitotane levels is recommended to look for a therapeutic window between 14 and 20mg/L, but its positive predictive value requires optimization. We report the case of an ACC patient with a history of dyslipidemia treated with mitotane in whom several plasma mitotane levels >30mg/L were found together with an excellent neurological tolerance. This observation led us to compare theoretical or measured o,p′-DDD and o,p′-DDE levels in a series of normolipidemic and dyslipidemic plasma samples to explore potential analytical issues responsible for an overestimation of plasma mitotane levels. We demonstrate an overestimation of mitotane measurements in dyslipidemic patients. Mitotane and o,p′-DDE measurements showed a mean 20% overestimation in hypercholesterolemic and hypertriglyceridemic plasma, compared with normolipidemic plasma. The internal standard p,p′-DDE measurements showed a parallel decrease in hypercholesterolemic and hypertriglyceridemic plasma, suggesting a matrix effect. Finally, diluting plasma samples and/or using phospholipid removal cartridges allowed correcting such interference.

Learning points

  • Hypercholesterolemia (HCH) and hypertriglyceridemia (HTG) induce an overestimation of plasma mitotane measurements.
  • We propose a routine monitoring of lipidemic status.
  • We propose optimized methodology of measurement before interpreting high plasma mitotane levels.

Open access

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.
Open access

Ana Marina Moreira and Poli Mara Spritzer

Summary

Primary ovarian insufficiency (POI) is the condition of intermittent or permanent gonadal insufficiency that occurs in women before the age of 40. We describe three cases of POI referred to the outpatient endocrinology clinic of a university hospital. The three patients met diagnostic criteria for POI and were managed by specific approaches tailored to individualized goals. In the first case, the main concern was fertility and the reproductive prognosis. The second patient was a carrier of a common genetic cause of POI: premutation of the FMR1 gene. The third case was a patient diagnosed with a POI and established osteoporosis, a common complication of estrogen deprivation. This study reports the treatment and follow-up of these cases, with an emphasis on relevant aspects of individualized management, alongside a brief literature review.

Learning points

  • A diagnosis of POI should be considered in patients presenting with amenorrhea or irregular menses and high serum follicle-stimulating hormone (FSH) levels before age 40 years.
  • Patients with POI without an established cause, especially in familial cases, should be tested for FMR1 mutations.
  • Estrogen/progestin replacement therapy is indicated since diagnosis until at least the estimated age of menopause, and is the cornerstone for maintaining the good health of breast and urogenital tract and for primary or secondary osteoporosis prevention in POI.
  • Fertility should be managed through an individualized approach based on patient possibilities, such as egg or embryo donation and ovarian cryopreservation; pregnancy can occur spontaneously in a minority of cases.
  • Women with POI should be carefully monitored for cardiovascular risk factors.

Open access

Sharmin Jahan, M A Hasanat, Tahseen Mahmood, Shahed Morshed, Raziul Haq, and Md Fariduddin

Summary

Silent corticotroph adenoma (SCA) is an unusual type of nonfunctioning pituitary adenoma (NFA) that is silent both clinically and biochemically and can only be recognized by positive immunostaining for ACTH. Under rare circumstances, it can transform into hormonally active disease presenting with severe Cushing syndrome. It might often produce diagnostic dilemma with difficult management issue if not thoroughly investigated and subtyped accordingly following surgery. Here, we present a 21-year-old male who initially underwent pituitary adenomectomy for presumed NFA with compressive symptoms. However, he developed recurrent and invasive macroadenoma with severe clinical as well as biochemical hypercortisolism during post-surgical follow-up. Repeat pituitary surgery was carried out urgently as there was significant optic chiasmal compression. Immunohistochemical analysis of the tumor tissue obtained on repeat surgery proved it to be an aggressive corticotroph adenoma. Though not cured, he showed marked clinical and biochemical improvement in the immediate postoperative period. Anticipating recurrence from the residual tumor, we referred him for cyber knife radio surgery.

Learning points:

  • Pituitary NFA commonly present with compressive symptoms such as headache and blurred vision.
  • Post-surgical development of Cushing syndrome in such a case could be either drug induced or endogenous.
  • In the presence of recurrent pituitary tumor, ACTH-dependent Cushing syndrome indicates CD.
  • Rarely a SCA presenting initially as NFA can transform into an active corticotroph adenoma.
  • Immunohistochemical marker for ACTH in the resected tumor confirms the diagnosis.
Open access

Lourdes Balcázar-Hernández, Guadalupe Vargas-Ortega, Yelitza Valverde-García, Victoria Mendoza-Zubieta, and Baldomero González-Virla

Summary

The craniopharyngiomas are solid cystic suprasellar tumors that can present extension to adjacent structures, conditioning pituitary and hypothalamic dysfunction. Within hypothalamic neuroendocrine dysfunction, we can find obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, imbalances in the regulation of body temperature, thirst, heart rate and/or blood pressure and alterations in dietary intake (like anorexia). We present a rare case of anorexia–cachexia syndrome like a manifestation of neuroendocrine dysfunction in a patient with a papillary craniopharyngioma. Anorexia–cachexia syndrome is a complex metabolic process associated with underlying illness and characterized by loss of muscle with or without loss of fat mass and can occur in a number of diseases like cancer neoplasm, non-cancer neoplasm, chronic disease or immunodeficiency states like HIV/AIDS. The role of cytokines and anorexigenic and orexigenic peptides are important in the etiology. The anorexia–cachexia syndrome is a clinical entity rarely described in the literature and it leads to important function limitation, comorbidities and worsening prognosis.

Learning points:

  • Suprasellar lesions can result in pituitary and hypothalamic dysfunction.
  • The hypothalamic neuroendocrine dysfunction is commonly related with obesity, behavioral changes, disturbed circadian rhythm and sleep irregularities, but rarely with anorexia–cachexia.
  • Anorexia–cachexia syndrome is a metabolic process associated with loss of muscle, with or without loss of fat mass, in a patient with neoplasm, chronic disease or immunodeficiency states.
  • Anorexia–cachexia syndrome results in important function limitation, comorbidities that influence negatively on treatment, progressive clinical deterioration and bad prognosis that can lead the patient to death.
  • Anorexia–cachexia syndrome should be suspected in patients with emaciation and hypothalamic lesions.
Open access

Takuya Higashitani, Shigehiro Karashima, Daisuke Aono, Seigoh Konishi, Mitsuhiro Kometani, Rie Oka, Masashi Demura, Kenji Furukawa, Yuto Yamazaki, Hironobu Sasano, Takashi Yoneda, and Yoshiyu Takeda

Summary

Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and low-level autonomous cortisol secretion. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of a disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg, pulse rate was 132 beats/min, and plasma glucose level was 712 mg/dL. Abdominal CT scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. His left adrenal lobular mass was over 40 mm and it was clinically suspected the potential for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed, resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, the activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy.

Learning points:

  • Concomitant activation of the renin-angiotensin-aldosterone system and cortisol overproduction may contribute to the development of severe hypertension and lead to lethal cardiovascular complications.
  • Treatment with simultaneous unilateral nephrectomy and adrenalectomy markedly improves BP and blood glucose levels.
  • CYP11B2 immunohistochemistry staining revealed the existence of aldosterone-producing cell clusters (APCCs) in the adjacent non-nodular adrenal gland, suggesting that APCCs may contribute to aldosterone overproduction in patients with RVHT.
Open access

Hiroaki Iwasaki

extensive serological and biochemical analysis was performed, along with a renal biopsy. Laboratory examinations revealed hypoalbuminaemia with massive proteinuria and dyslipidaemia. Light microscopy of the initial renal biopsy specimen showed a slight

Open access

Ana Gonçalves Ferreira, Tiago Nunes da Silva, Sofia Alegria, Maria Carlos Cordeiro, and Jorge Portugal

Summary

Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that can secrete catecholamines. The authors describe a challenging case who presented as stress cardiomyopathy and myocardial infarction (MI). A 76-year-old man, with a medical history of Parkinson’s disease, type 2 diabetes mellitus, hypertension, dyslipidaemia and a previous inferior MI in 2001, presented to the emergency department due to chest pain, headaches and vomiting. He also reported worsening blood glucose levels and increasing constipation over the preceding weeks. BP was 185/89 mmHg (no other relevant findings). EKG had ST segment depression in leads V2-V6, T troponin was 600 ng/L (<14) and the echocardiogram showed left ventricular hypokinesia with mildly compromised systolic function. Nevertheless, he rapidly progressed to severe biventricular dysfunction. Coronary angiogram showed a 90% anterior descendent coronary artery occlusion (already present in 2001), which was treated with angioplasty/stenting. In the following days, a very labile BP profile and unexplained sinus tachycardia episodes were observed. Because of sustained severe constipation, the patient underwent an abdominal CT that revealed a retroperitoneal, heterogeneous, hypervascular mass on the right (62 × 35 mm), most likely a paraganglioma. Urinary metanephrines were increased several fold. 68Ga-DOTANOC PET-CT scan showed increased uptake in the abdominal mass (no evidence of disease elsewhere). He was started on a calcium-channel blocker and alpha blockade and underwent surgery with no major complications. Eight months after surgery, the patient has no evidence of disease. Genetic testing was negative for known germline mutations. This was a challenging diagnosis, but it was essential for adequate cardiovascular stabilization and to reduce further morbidity.

Learning points:

  • PPGL frequently produces catecholamines and can manifest with several cardiovascular syndromes, including stress cardiomyopathy and myocardial infarction.
  • Even in the presence of coronary artery disease (CAD), PPGL should be suspected if signs or symptoms attributed to catecholamine excess are present (in this case, high blood pressure, worsening hyperglycaemia and constipation).
  • Establishing the correct diagnosis is important for adequate treatment choice.
  • Inodilators and mechanical support might be preferable options (if available) for cardiovascular stabilization prior to alpha blockade and surgery.
  • Laboratory interference should be suspected irrespective of metanephrine levels, especially in the context of treated Parkinson’s disease.