Agata Zygmunt-Gorska

Mutations and pituitary morphology in a series of 82 patients with PROP1 gene defects.

Background/Aims: Defects of the PROP1 gene are the most prevalent genetic cause of combined pituitary hormone deficiency. Previous observations in affected patients have shown pituitary size ranging from hypoplasia to overt pituitary mass and evolution of size over the lifespan. Methods: We evaluated pituitary size and morphology in PROP1-mutation carriers who originated from Central and Eastern Europe. We analyzed 112 pituitary magnetic resonance imaging (MRI) scans from 82 patients (42 males) aged 2.5–72.7 (median 16.6) years from 60 kindreds. Results: Among the 120 independent PROP1 alleles, the most prevalent mutations were delGA301/302 (99 alleles) and delA150 (13 alleles). Median pituitary height at first MRI was 4.7 mm (range 1.0–20.7) and median volume was 127.6 mm3 (range 7.5–3,087.0). Pituitary size did not differ between sexes and did not correlate with hormonal phenotype, but significantly decreased with increasing age. However, evaluation of individual values suggested a biphasic mode with increasing volume during childhood, peak in adolescence, and subsequent regression in adulthood. Conclusion: Although pituitary size was increased in a number of PROP1-deficient patients, none of them suffered permanent damage from pituitary mass; therefore, any proposed surgery should be postponed as long as possible and ultimately may not be necessary due to the self-limiting nature of the pituitary enlargement.

High Incidence of Abnormal Circadian Blood Pressure Profiles in Patients on Steroid Replacement Therapy due to Secondary Adrenal Insufficiencyand Congenital Adrenal Hyperplasia without Overt Hypertension - InitialResults

Patients on steroid replacement therapy are at an increased risk of cardiovascular complications owing to the fact that disruptions in the cortisol diurnal rhythm may affect the blood pressure (BP) profile. Aim: To evaluate the circadian BP profiles of patients with secondary adrenal insufficiency (SAI) and congenital adrenal hyperplasia (CAH) on steroid replacement therapy and to compare BP profiles of patients receiving hydrocortisone (HC) in different dosing schedules. Methods: The study included 33 patients: 15 SAI and 18 CAH (mean age 13.2 years 95CI 11.3-15.1). There were no patients with previously diagnosed overt hypertension. Patients with SAI received a mean of 7.39 mg/m2 of HC in 3 daily doses (in the morning (M) 50%, in the afternoon (A) 25%, in the evening (E) 25%), CAH patients 17.9 mg/m2 of HC in the following dosing schedules: 5 patients in 3 equal doses, 7 patients received M: 40% A: 40% E: 20%, the remaining 6 patients had the same dosing schedule as patients with SAI. Fludrocortisone (FC) was given to 13 patients with CAH in 2 equal daily doses. The total dose of HC/FC as well as the dosing schedule of HC was adjusted individually based on clinical and biochemical outcomes. Standard 24-hour BP monitoring (ABPM) was performed using an Ambulatory BP Monitor (Space labs 90217, USA). Results: The majority of the patients (almost 70% SAI, 80% CAH) presented with an abnormal 24-hour BP profile. There were no significant differences in ABPM results between SAI and CAH patients, and no differences between CAH patients treated with and without FC. There was no correlation between HC and FC doses [mg/m2] and ABPM results except that mean night SBP values increased with greater HC doses (r=0.51, p<0.05). Among the CAH group the highest percentage of abnormal ABPM results was observed in patients who received HC in doses: M: 50% A: 25% and E: 25%, the most favorable BP profile was observed in patients with dosing schedule: M: 40%, A: 40%, E: 20%.However there were no significant differences between patients with different treatment protocols, the results suggest that observed disruptions of the BP profile could be related to the HC dosing schedule. Conclusions: The incidence of abnormal BP profiles in patients on steroid replacement therapy due to SAI and CAH without overt hypertension is high. The disruptions of the BP profiles are not associated with the dose of HC or FC. The abnormal BP profiles in patients with SAI or CAH may be related to the HC dosing schedule. 24-hour ABPM seems to be a useful, non-invasive and safe method for the monitoring of HC and FC replacement therapy in patients with adrenal insufficiency. Further investigations in the larger groups of patients are needed.

Atypical Clinical Presentation of ACTH-Dependent Cushing's Syndrome in a Patient Treated with Retinoic Acid

OBJECTIVE The leading signs and symptoms of Cushings syndrome (CS) in adolescents, which depend on the duration and the severity of hypercortisolemia, are: a decrease in growth velocity with an increase in body weight, redistribution of fat tissue (round face), and less commonly, acne due to hyperandrogenization. A widely used antiacne drug, retinoic acid, can change the clinical presentation of CS and delay the diagnosis. METHODS We report an atypical presentation of adrenocorticotropic hormone (ACTH)-dependent CS in a patient treated with retinoic acid due to severe acne. RESULTS Three months after the discontinuation of retinoic acid treatment (at a dose of 40 mg daily for 6 months, with a 4 month break and then for an additional 6 months), a 17.5-year-old male presented with short stature (-3.0 SD), muscle weakness, difficulty concentrating, insomnia, and depressed mood. Body weight (body mass index, 22 kg/m2), fat tissue distribution, pubertal status (testicular volume equal to 20 mL, pubarche V, axillarche present), and blood pressure were normal, and the patients bone age was equal to his chronologic age. His bone mineral density was decreased (Z-score, -3.5 SD). The morning serum cortisol level was normal (8:00 AM, 171.9 ng/mL) and did not decrease in the evening (8:00 PM, 178.9 ng/mL) or after 1 mg of dexamethasone (100.4 ng/mL). The patients urinary free cortisol was elevated on 3 occasions (274.5, 217.3, and 253.7 μg/day). Increased ACTH levels in the morning (97.5 to 141.1 pg/mL) and postcorticoliberine (577.6 pg/mL) pointed to ACTH-dependent CS. A magnetic resonance imaging scan of the pituitary gland confirmed the presence of a microadenoma. CONCLUSION Retinoic acid treatment may alter the clinical presentation of ACTH-dependent CS and consequently delay the diagnosis.