Longitudinal Monitoring of Hair Cortisol Using Liquid Chromatography-Mass Spectrometry to Prevent Hypercortisolism in Patients Undergoing Glucocorticoid Replacement Therapy.

OBJECTIVE: Currently available methods for endogenous cortisol monitoring in patients with hormonal insufficiency rely on measurements of plasma levels only at a single time point; thus, any kind of chronic exposure to cortisol is challenging to evaluate because it requires collecting samples at different time points. Hair cortisol levels acquired longitudinally better reflected chronic exposure (both cortisol synthesis and deposition) and may significantly contribute to better outcomes in glucocorticoid replacement therapies. DESIGN: Twenty-two patients on cortisol substitution therapy were monitored for plasma, urinary, and hair cortisol levels for 18 months to determine whether hair cortisol may serve as a monitoring option for therapy setting and adjustment. METHODS: Plasma and urinary cortisol levels were measured using standardized immunoassay methods, and segmented (∼1 cm) hair cortisol levels were monitored by liquid chromatography coupled to mass spectrometry. A log-normal model of the changes over time was proposed, and Bayesian statistics were used to compare plasma, urinary, and hair cortisol levels over 18 months. RESULTS AND CONCLUSIONS: Hair cortisol levels decreased over time in patients undergoing substitutional therapy. The residual variance of hair cortisol in comparison to plasma or urinary cortisol levels was much lower. Thus, longitudinal monitoring of hair cortisol levels could prove beneficial as a noninvasive tool to reduce the risk of overdosing and improve the overall patient health.

PRIMARY HYPERPARATHYROIDISM, WITH A FOCUS ON MANAGEMENT OF THE NORMOCALCEMIC FORM: TO TREAT OR NOT TO TREAT?

OBJECTIVE: The aim of this study was to determine reasonable care for normocalcemic primary hyperparathyroidism (NCPHPT) patients treated at the endocrine clinic. METHODS: The study is based on 218 outpatient cases of primary hyperparathyroidism (PHPT), 187 (86%) of whom were NCPHPT. Subjective complaints, biochemical tests, imaging, and treatment outcome for NCPHPT patients were monitored and compared with the same parameters in patients with hypercalcemic hyperparathyroidism. The number of patients with newly diagnosed NCPHPT who became hypercalcemic and the time period in which it happened were also recorded. RESULTS: Over 6 years of study, in total, 36 of 187 originally normocalcemic patients became hypercalcemic (19%); 24 of 36 within 2 years and 2 of 36 later than after 4 years. Sestamibi scintigraphy was performed in 103 normocalcemic patients (adenoma was detected in 5 cases) and in 46 hypercalcemic patients with pathologically elevated serum calcium levels at the time of assessment (adenoma was detected in 32 of 46 cases). Surgery was performed in 33 patients, 11 of whom were originally normocalcemic (i.e., 6% of all 187 originally normocalcemic patients), and 22 were hypercalcemic from the outset (i.e., 71% of all 31 originally hypercalcemic patients). CONCLUSION: Some NCPHPT patients converted to hypercalcemic, mostly within 2 years, but some after 4 years or later. Normocalcemic patients should be monitored on a long-term basis, as it is impossible to anticipate when and which normocalcemic patients will become hypercalcemic. Imaging is much less effective in normocalcemic than in hypercalcemic patients.

[Symptomatic and asymptomatic primary hyperparathyroidism in outpatient care - current issues]. / Péce o nemocné se symptomatickou a asymptomatickou primární hyperparatyreózou v ambulantní praxi dnes.

OBJECTIVE: To assess the diagnostic and therapeutic options in the care of patients with primary hyperparathyreosis in outpatient practice.Cohort and methods: The study included all the patients with primary hyperparathyroidism treated at the 2nd Internal Medicine Department, Masaryk University and the University Hospital of St. Anne in Brno in the period from Jan 1, 2008 to Dec 31, 2013. The sample consisted of 218 patients, including 41 men and 177 women. Patients with secondary hyperparathyroidism, especially patients with underlying hypovitaminosis D, renal insufficiency and those taking medications with possible effects on parathyroid hormone levels, have not been included in the study. A special attention was paid to differences between the normocalcaemic and hypercalcaemic patients. Ultrasound scanning was performed in all patients, while scintigraphy was indicated in patients who are considered for possible surgical treatment. RESULTS: In the group of 218 patients, serum calcium levels at the baseline were pathologically elevated in 31 patients (14 %) and normal in 187 patients (86 %). One fifth of patients with normocalcaemic primary hyperparathyroidism developed long-term hypercalcaemia - within two years in two thirds of the patients from the onset of the disease and sporadically also after more than four years of follow-up. Parathyroid adenoma was found and removed in 30 hypercalcemic patients (in 97 % of all 31 hypercalcemic patients operated on) and in 2 normocalcemic patients (40 % of all 5 the normocalcemic patients operated on). Pharmacological treatment was administered to 22 patients, of which 9 patients received long-term treatment and 13 patients received pharmacotherapy only during the preoperative preparation for patients with very high serum calcium levels. CONCLUSION: The results support the opinion that primary hyperparathyroidism is a biphasic disease. The initial normocalcemic period is often asymptomatic or associated with symptoms of little importance. Severe complications, however, may already be present also in normocalcemic patients. The decision of when patients with normocalcemic primary hyperparathyroidism should be monitored and when initiation of treatment is needed should also require more detailed information.Key words: hypercalcaemia - hyperparathyroidism asymptomatic and primary - normocalcaemia - outpatient care - parathyroid hormone - surgery and pharmacotherapy.

[Akromegaly and pharmacotherapy]. / Akromegalie a medikamentózní lécba.

Acromegaly is a rare and serious disease. A successful and rational therapy of acromegaly ought to combine surgery, radiotherapy and pharmacotherapy. The submitted article presents a case of acromegaly that was only diagnosed at the stage when total pituitary adenoma removal was impossible. Even so, the long-term stabilisation of the disease was reached by way of repeated surgery through transfenoidal and transcranial approach, by linear accelerator radiation therapy and Leksell Gamma Knife radiotherapy and by pharmacotherapy with somatostatin analogon octreotide and growth hormone receptor antagonist pegvisomant. The octreotide and pegvisomant dosage has been repeatedly changed according to IGF1 levels. The contemporary somatostatin analogon Sandostatin LAR 30 mg is given once every 3 weeks and the growth hormone receptor antagonist Somavert 20 mg is applied daily. Despite this serious disease, the patient has already been living contentedly for 10 years. From the ethical point of view, the financials costingness of the therapy should be considered as reasonable.