Acromegaly versus hypogonadism: Bone fragility and evaluation.

INTRODUCTION: Osteopathy in patients with acromegaly is characterized by increased prevalence of vertebral fragility fractures (VF). However, the diagnostic criteria for osteoporosis are seldomly met in terms of bone mineral density (BMD), as patients with acromegaly frequently present normal BMD for age and gender. METHODOLOGY: We performed a cross-sectional study on 71 patients with acromegaly and 75 patients with hypogonadism. Turnover markers comprised alkaline phosphatase, osteocalcin, the C-terminal telopeptide of type I collagen and total procollagen type-1 amino-terminal propeptide; imaging comprised dual x-ray absorptiometry for BMD, T and Z scores of the lumbar spine, femoral neck and total hip, trabecular bone score (TBS), and x-ray scans of the thoracic and lumbar spine. RESULTS: Vertebral fractures (VF) in subjects with acromegaly were significantly more frequent than in subjects with hypogonadism, with a prevalence of 29.6% compared to 9.3%. Patients with acromegaly had significantly higher BMD at all skeletal sites but lower TBS than hypogonadal subjects. This difference remained statistically significant after grouping patients with acromegaly according to gonadal status and comparing them with patients with hypogonadism. However, presence of hypogonadism in patients with acromegaly did not influence BMD, TBS or VF prevalence. Moreover, patients with active acromegaly did not have significantly different BMD, TBS and VF prevalence compared to patients with controlled disease. Patients with acromegaly with VF had significantly lower BMD at all skeletal sites than those without VF, but no difference in TBS. CONCLUSIONS: Vertebral fractures are frequent in acromegaly, and are associated with lower BMD but not with TBS. Patients with acromegaly, regardless of gonadal status, have significantly higher BMD but lower TBS than hypogonadal patients. Moreover, disease activity and hypogonadism do not influence BMD, TBS or VF in acromegaly.

Clinical features and complications of acromegaly at diagnosis are not all the same: data from two large referral centers.

PURPOSE: The number of international acromegaly related registries is increasing; however, heterogeneity of acromegaly symptoms and signs across countries is not well described. We compared clinical disease manifestations at diagnosis between two large University referral centers from two continents. METHODS: Retrospective, comparative epidemiological study of acromegaly patients at two centers: (i) C. I. Parhon National Institute of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy Bucharest, Romania (Parhon), and (ii) Pituitary Center, Oregon Health & Science University, Portland, Oregon, United States (OHSU) from approved data repositories was undertaken. Data were extracted from medical charts and questionnaires. Binary logistic regression analysis was undertaken for the most frequently noted symptoms and clinical signs. RESULTS: The study included 216 patients (87 Parhon, 129 OHSU). Age, sex, and median delay in diagnosis were similar between centers. IGF-1 index was higher in patients at Parhon (3.3 vs 2.1, P < 0.001). The top five symptoms at both centers were enlarged hands/feet, headache, arthralgia, fatigue, and irregular menses in women. A significant difference was noted for multiple signs and symptoms frequency, often > 20 percentage points between centers. Center was a predictor of many signs and symptoms, independent of acromegaly biochemical severity or disease duration. CONCLUSION: We show in the first comparative study that differences in medical practice, documentation, and likely cultural differences can influence patients' symptom(s) reporting and screening patterns in geographically different populations. Pooling data into large multicenter international registry databases may lead to loss of regional characteristics and thus a mixed overall picture of combined cohorts.

Acromegaly treatment in Romania. How close are we to disease control?

INTRODUCTION: In Romania, no nationwide data for acromegaly treatment and control rate are available. Our objective was to assess the acromegaly control rate in a tertiary referral centre, which covers an important part of Romanian territory and population of patients with acromegaly. MATERIALS AND METHODS: We reviewed the records of all 164 patients (49 males and 115 females; median age 55 [47, 63.5] years) with newly or previously diagnosed acromegaly, who have been assessed at least once in our tertiary referral centre between January 1, 2012 and March 31, 2016. This sample represents 13.6% of the total expected 1200 Romanian patients with acromegaly and covers 82.9% of the counties in Romania. Control of acromegaly was defined as a random serum growth hormone (GH) < 1 ng/mL and an age-normalised serum insulin-like growth factor-I (IGF-I) value. The GH and IGF-I values used for calculation of the control rate were those at the last evaluation. The same assays for GH and IGF-I measurement were used in all patients. RESULTS: There were 147 treated and 17 untreated patients. Of the 147 patients assessed after therapy, 137 (93.2%) had pituitary surgery, 116 (78.9%) were on medical treatment at the last evaluation, and 67 (45.5%) had radiotherapy. Seventy-one (48.3%) had a random GH < 1 ng/mL, 54 (36.7%) had a normalised, age-adjusted IGF-I, and 42 (28.6%) had both normal random serum GH and IGF-I. CONCLUSIONS: In Romania, acromegaly benefits from the whole spectrum of therapeutic interventions. However, the control rate remains disappointing.

SERIAL CHANGES OF LIVER FUNCTION TESTS BEFORE AND DURING METHIMAZOLE TREATMENT IN THYROTOXIC PATIENTS.

OBJECTIVE: Overt hyperthyroidism and methimazole (MMI) treatment are frequently associated with abnormal liver function tests (LFTs). We describe the serial changes of LFTs in MMI-treated hyperthyroid patients. METHODS: We retrospectively analyzed all 77 patients presenting with newly diagnosed overt hyperthyroidism (59 Graves diseases, 11 toxic nodular goiters, 4 toxic adenomas, 3 amiodarone-induced thyrotoxicosis) between 2012 and 2014. All patients started MMI at 10 to 60 mg/day that was gradually tapered. We measured thyroid-stimulating hormone, free thyroxine, alanine aminotransferase (ALT) and aspartate aminotrasnferase (AST) at baseline and at 6 weeks, 4.5 months and 10 months after starting the MMI treatment. The concomitant medication was stable during MMI treatment. RESULTS: At baseline, 25 patients (32.5%) had abnormal LFT, of which 5 had ALT or AST levels >2× the upper limit of normal (ULN). In most patients with baseline abnormal LFT, MMI treatment resulted in a normalization of serum ALT and AST. Thirteen patients with normal baseline LFT had <2× the ULN elevations of LFT sometime during treatment. There was a case of significant hepatotoxicity. During treatment, there were no significant differences in LFT levels between patients with initially normal or abnormal LFT. In a Cox proportional hazard regression model, abnormal LFT at baseline, abnormal thyroid function at the last evaluation, and MMI dose were not predictors of abnormal LFT at the final evaluation. CONCLUSION: MMI treatment can induce insignificant LFT elevation, <2× the ULN. MMI can be safely administered in hyperthyroid patients with abnormal LFT, and normalization of increased AST and ALT levels should be anticipated. ABBREVIATIONS: ALT = alanine aminotransferase AST = aspartate aminotransferase fT4 = free thyroxine HCV = hepatitis C virus LFT = liver function test LOCF = last observation carried forward MMI = methimazole PTU = propylthiouracil TSH = thyroid-stimulating hormone ULN = upper limit of normal.