Acromegalic Arthropathy.

A 30-year-old woman was referred to physical therapy for bilateral shoulder and thoracic spine pain concurrent with loss of range of motion. Notable medical history included surgical removal of a pituitary adenoma that had resulted in excessive growth hormone secretion, developing into acromegaly with hallmark physical features. Following examination, radiographs were requested to evaluate the extent of arthropathies associated with acromegaly. Radiographs revealed advanced arthropathies of the bilateral acromioclavicular and glenohumeral joints, along with loss of disc height and anterolisthesis throughout the thoracic spine. J Orthop Sports Phys Ther 2019;49(11):864. doi:10.2519/jospt.2019.8302.

Explanatory models of muscle performance in acromegaly patients evaluated by knee isokinetic dynamometry: Implications for rehabilitation.

PURPOSE: To evaluate the effects of demographics and hormonal variations on knee muscle performance in patients with acromegaly and develop explanatory models of peripheral muscle function in these individuals. METHODS: This was a cross-sectional study in which 53 acromegalics and 27 healthy subjects underwent knee isokinetic dynamometry to evaluate the peak torque value for leg extension at 75°/s (PTE75) and 240°/s (PTE240). Separate multivariable linear regression models for the prediction of PTE75 and PTE240 were tested using variables commonly used as predictors in the clinical setting and other specific variables related to acromegaly. RESULTS: The final prediction model for PTE75 (R(2)=0.888; adjusted R(2)=0.820, SE of bias=16.2Nm, p<0.001) was -0.221×growth hormone+36.791×sexmale=1-27.407×statusactive=1-0.690×age+148.071. The final prediction model for PTE240 (R(2)=0.816; adjusted R(2)=0.805, SE of bias=8.8Nm, p<0.001) was -0.174×growth hormone+12.522×sexmale=1-0.520×age+98.099. CONCLUSIONS: In acromegalics, high growth hormone levels, female gender, and older age are associated with reduced muscle strength and endurance. Additionally, active disease negatively affects peripheral muscle strength in these patients.

Acromegalia: diagnóstico y tratamiento / Acromegaly: diagnosis and treatment

La acromegalia es una enfermedad crónica multisistémica, de baja prevalencia, cuyo diagnóstico y tratamiento deben adecuarse a las realidades actuales. No obstante, continúa siendo una enfermedad subdiagnosticada, que evoluciona con una elevada tasa de mortalidad, generalmente por causas cardiovasculares y cerebrovasculares, lo cual reduce la esperanza de vida de la persona que la padece. En el presente artículo se describen las formas de presentación del hipersomatotropismo, los métodos de diagnóstico y las modalidades terapéuticas, que incluyen la quirúrgica, la farmacológica y la radioterapia.

Acromegaly is a multisystem chronic disease, of low prevalence which diagnosis and treatment should be adapted to the current realities. Nevertheless, it continues being an underdiagnosed disease with a clinical course of high mortality rate, generally due to cardiovascular and cerebrovascular causes, which reduce the life expectancy of the person suffering it. In this work, the forms of presentation of hypersomatotropism, the methods of diagnosis and the therapeutic modalities are described, that include the surgical one, the pharmacological one and the radiotherapy.

Physical and cardiovascular performance in cases with acromegaly after regular short-term exercise.

OBJECTIVE: Impaired physical performance is a disturbing complication of acromegaly. We aimed to evaluate the role of regular exercise in amelioration of the impaired physical performance in acromegaly. METHODS: Patients with acromegaly were divided into two groups according to their participation in a prescheduled programme of exercise. Participants in the study group were exercised 3 days a week for 3 consecutive months. Exercise tolerance was evaluated by maximal oxygen consumption (VO2 max) and time (T) taken to complete the Bruce protocol, muscle flexibility by the sit and reach test (SRT) and muscle strength by the hand grip strength test (HGST). Concomitantly, anthropometric assessment was performed using body mass index (BMI), waist-to-hip ratio (WHR), skinfold measurements from 8 points, percentage body fat (PBF), fat mass (FM) and lean body mass (LBM). RESULTS: After 3 months of exercise, VO2 max and T were higher in cases that exercised than in cases that did not (P = 0.004 and P = 0.001). Over 3 months, within the exercise group, VO2 max and T of the Bruce protocol increased (P = 0.003 and P = 0.004) and heart rate during warming decreased (P = 0.04). SRT increased within the exercise group after 3 months (P = 0.004). HGSRT did not change significantly (right P = 0.06 and left P = 0.2). The sum of skinfolds, BMI, WHR and LBM remained stable over the study period (P = 0.1, P = 0.08, P = 0.3 and P = 0.09). PBF decreased slightly and FM decreased significantly over 3 months (P = 0.05 and P = 0.03). CONCLUSION: Even short-term exercise may improve impaired physical performance, muscle activity and disturbed body fat composition in acromegaly.

Coping strategies in patients after treatment for functioning or nonfunctioning pituitary adenomas.

CONTEXT AND OBJECTIVE: Coping strategies may affect quality of life, which is decreased in patients after treatment for Cushing's disease, acromegaly, or nonfunctioning pituitary macroadenomas (NFMA). We aimed to explore coping strategies in these patients because this has never been done before. DESIGN: We conducted a cross-sectional study. SUBJECTS: We included patients treated for Cushing's disease (n = 42), for acromegaly (n = 80), and for NFMA (n = 61). These patients were compared with three reference populations: an a-select sample from the Dutch population (n = 712), patients with chronic pain (n = 59), and patients receiving primary care psychology services (n = 525). Furthermore, the three patient groups were compared with each other. Coping strategies were assessed by the Utrecht Coping List. RESULTS: Compared with the a-select sample, patients with pituitary adenomas reported less active coping (P < 0.0001), sought less social support (P < 0.0001), and reported more avoidant coping (P = 0.008). In contrast, patients treated for pituitary adenomas reported somewhat better coping strategies than patients with chronic pain and those with psychological disease. When patients with different pituitary adenomas were compared, patients treated for Cushing's disease sought more social support than patients treated for NFMA (P = 0.035). CONCLUSIONS: Patients treated for pituitary adenomas display different and less effective coping strategies compared with healthy controls. A targeted intervention might help to stimulate patients to use a more active coping strategy and to seek social support instead of an avoiding coping strategy. This might, in turn, improve their quality of life.

Are there gender-specific differences concerning quality of life in treated acromegalic patients?

OBJECTIVE: Acromegaly is associated with deleterious comorbidities that can remain irreversible even after successful cure has been achieved and lead to a persistently impaired Quality of Life (QoL). The aim of the study was to assess frequency and degree of persistent comorbidities and complaints after treatment of acromegaly and to investigate their impact on QoL. Another scope of interest was to determine gender-specific factors that influence perceived QoL in men and women. METHODS: We developed an Acromegaly Comorbidities & Complaints Questionnaire (ACCQ) consisting of 8 items (e. g. acral enlargement, joint complaints, hypertension, diabetes) known to affect QoL in order to assess frequency and degree of comorbidities. Additionally, the Acromegaly Quality of Life Questionnaire (AcroQoL) and the Short-form 36 (SF-36) questionnaire were handed out to 55 treated acromegalic patients. RESULTS: Both genders suffer from a lasting impairment in quality of life to a considerable degree. Complaints impairing manual skills (e. g. acral enlargement, arthralgias) were the most frequent findings (73% of all participants) in both genders. Multivariate analyses revealed that in men numbness of fingers and persistent joint-complaints were decisively responsible for impaired QoL. In women, it was the persistence of hypertension. CONCLUSIONS: Persistent joint complaints have adverse effects on QoL after treatment of acromegaly in men, possibly because they lead to impairment of manual motor skills and a handicap in their working life. Women seem to perceive late effects of hypertension as a manifest health threat.

Acromegaly and pregnancy: a retrospective multicenter study of 59 pregnancies in 46 women.

CONTEXT: Few data are available on pregnancy outcomes in women with acromegaly. STUDY DESIGN: This was a retrospective multicenter study. PATIENTS: The study included 46 women with GH-secreting pituitary microadenomas (n = 7) or macroadenomas (n = 39). Their mean age was 31.7 yr (±4.5 yr). Incomplete transsphenoidal surgical resection (n = 39) and pituitary radiation (n = 14) had been performed, respectively, 2.9 ± 2.6 and 7.3 ± 4.2 yr before pregnancy. The patients were receiving dopamine agonists (n = 25) and/or somatostatin analogs (n = 14), and GH/IGF-I hypersecretion was controlled and uncontrolled in, respectively, 23 and 34 cases. Five pregnancies followed the fertility treatment. RESULTS: Fifty-nine pregnancies resulted in 64 healthy babies. Gestational diabetes and gravid hypertension occurred in four (6.8%) and eight (13.6%) pregnancies, respectively, and both were more frequent when GH/IGF-I hypersecretion was not controlled before pregnancy. Visual field defects were diagnosed during pregnancy in four women, three of whom were diagnosed with acromegaly during the pregnancy. Seven women had isolated headache. Magnetic resonance imaging performed 3.9 ± 0.3 months after delivery showed that the size of the adenoma had increased in three cases, decreased in two cases, and remained stable in 22 cases. Seventeen women breast-fed with no complications. Four women gave birth to a small-for-gestational-age infant; all had received somatostatin analogs, alone or in combination with dopamine agonists, during pregnancy. The mean IGF-I level fell significantly during the first trimester in 12 cases (before conception 588 ± 207 ng/ml, first trimester 319 ± 126 ng/ml, P = 0.002), whereas the GH concentration did not change significantly. CONCLUSION: The following conclusions were reached: 1) pregnancy in women with active or uncontrolled acromegaly may be associated with an increased risk of gestational diabetes and gravid hypertension; 2) pregnancy is occasionally associated with symptomatic enlargement of GH-secreting pituitary macroadenomas; 3) changes in serum GH and IGF-I concentrations are variable during pregnancy, indicating that routine monitoring is not mandatory if the pregnancy is uneventful; and 4) GH-suppressive treatment can be safely withdrawn after conception in most acromegalic women.

Growth hormone deficiency is associated with decreased quality of life in patients with prior acromegaly.

CONTEXT: Both GH deficiency (GHD) and GH excess are associated with a decreased quality of life. However, it is unknown whether patients with GHD after treatment for acromegaly have a poorer quality of life than those with normal GH levels after cure of acromegaly. OBJECTIVE: The aim of the study was to determine whether patients with GHD and prior acromegaly have a poorer quality of life than those with GH sufficiency after cure of acromegaly. DESIGN AND SETTING: We conducted a cross-sectional study in a General Clinical Research Center. STUDY PARTICIPANTS: Forty-five patients with prior acromegaly participated: 26 with GHD and 19 with GH sufficiency. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: We evaluated quality of life, as measured by 1) the Quality of Life Adult Growth Hormone Deficiency Assessment (QoL-AGHDA); 2) the Short-Form Health Survey (SF-36); and 3) the Symptom Questionnaire. RESULTS: Mean scores on all subscales of all questionnaires, except for the anger/hostility and anxiety subscales of the Symptom Questionnaire, showed significantly impaired quality of life in the GH-deficient group compared with the GH-sufficient group. Peak GH levels after GHRH-arginine stimulation levels were inversely associated with QoL-AGHDA scale scores (R = -0.53; P = 0.0005) and the Symptom Questionnaire Depression subscale scores (R = -0.35; P = 0.031) and positively associated with most SF-36 subscale scores. CONCLUSIONS: Our data are the first to demonstrate a reduced quality of life in patients who develop GHD after cure of acromegaly compared to those who are GH sufficient. Further studies are warranted to determine whether GH replacement would improve quality of life for patients with GHD after cure from acromegaly.

Pretreatment insulin-like growth factor-I concentrations predict radiographic osteoarthritis in acromegalic patients with long-term cured disease.

OBJECTIVE: The aim of the study was to identify factors influencing the development of osteoarthritis during long-term control of acromegaly, focusing on disease-specific parameters, GH and IGF-I concentrations, and duration of disease, adjusted for the well-known determinants of primary osteoarthritis. DESIGN: We conducted a follow-up study. METHODS: We studied 67 patients with adequate biochemical control of acromegaly for a mean of almost 13 yr. Study parameters were the results of radiological assessment of the spine, hip, knee, and hand. Osteoarthritis was defined as radiological osteoarthritis using the scoring system developed by Kellgren and Lawrence. Correlations between potential factors of influence and osteoarthritis were performed by analysis of covariance and adjusted for age, gender, and body mass index. RESULTS: Patients with pretreatment IGF-I sd scores in the highest tertile had an almost 4-fold increased risk for radiological osteoarthritis of the hip when compared with patients in the lowest tertile. After adjustment for age, gender, BMI, and disease duration, pretreatment IGF-I sd scores predicted radiographic osteoarthritis in all joint sites. Osteoarthritis was not predicted by other factors, including pretreatment GH levels, type of treatment, and duration of follow-up. CONCLUSION: This is the first study to document pretreatment IGF-I concentration as a predictor of radiographic osteoarthritis in acromegalic patients with long-term disease control.

Reduced basal ATP synthetic flux of skeletal muscle in patients with previous acromegaly.

BACKGROUND: Impaired mitochondrial function and ectopic lipid deposition in skeletal muscle and liver have been linked to decreased insulin sensitivity. As growth hormone (GH) excess can reduce insulin sensitivity, we examined the impact of previous acromegaly (AM) on glucose metabolism, lipid storage and muscular ATP turnover. PARTICIPANTS AND METHODS: Seven AM (4f/3 m, age: 46+/-4 years, BMI: 28+/-1 kg/m(2)) and healthy volunteers (CON: 3f/4 m, 43+/-4 years, 26+/-2 kg/m(2)) matched for age and body mass underwent oral glucose testing for assessment of insulin sensitivity (OGIS) and ss-cell function (adaptation index, ADAP). Whole body oxidative capacity was measured with indirect calorimetry and spiroergometry. Unidirectional ATP synthetic flux (fATP) was assessed from (31)P magnetic resonance spectroscopy (MRS) of calf muscle. Lipid contents of tibialis anterior (IMCLt) and soleus muscles (IMCLs) and liver (HCL) were measured with (1)H MRS. RESULTS: Despite comparable GH, insulin-like growth factor-1 (IGF-I) and insulin sensitivity, AM had approximately 85% lower ADAP (p<0.01) and approximately 21% reduced VO(2)max (p<0.05). fATP was similarly approximately 25% lower in AM (p<0.05) and related positively to ADAP (r = 0.744, p<0.01), but negatively to BMI (r = -0.582, p<0.05). AM had approximately 3 fold higher HCL (p<0.05) while IMCLt and IMCLs did not differ between the groups. CONCLUSIONS: Humans with a history of acromegaly exhibit reduced insulin secretion, muscular ATP synthesis and oxidative capacity but elevated liver fat content. This suggests that alterations in ss-cell function and myocellular ATP production may persist despite normalization of GH secretion after successful treatment of acromegaly.

Long-term basal and dynamic evaluation of hypothalamic-pituitary-adrenal (HPA) axis in acromegalic patients.

OBJECTIVE: Long-term effects of trans-naso-sphenoidal surgery (TNS) or long-acting somatostatin analogs (SSA) on the function of hypothalamic-pituitary-adrenal (HPA) axis have been poorly investigated. Aim of this study was to evaluate HPA axis integrity during the follow-up in patients with GH-secreting pituitary adenomas and preserved HPA function post-TNS or prior SSA. DESIGN AND PATIENTS: This retrospective study investigated 36 acromegalic patients (16M and 20F, age: 47 +/- 13 years), 20 of whom cured by TNS and 16 controlled by SSA therapy (12 previously operated and 4 in primary medical therapy), before and after long-term follow-up (median: 72 months, range: 12-240). No patient previously underwent radiotherapy. MEASUREMENTS: HPA function was studied by morning circulating cortisol and ACTH levels, 24-h urinary free cortisol (UFC) and cortisol response to low-dose short Synacthen test (LDSST, 1 microg) with a peak > 500 nmol/l as cut-off for normal function. RESULTS: Serum basal cortisol, ACTH and UFC levels were in the normal range and did not significantly change over time. As far as the cortisol peak after LDSST is concerned, 12 patients (32%, 8 TNS and 4 SSA) developed biochemical hypoadrenalism. None of the patients in primary medical therapy showed cortisol peak < 500 nmol/l. No significant correlations between HPA axis deterioration and follow-up duration, serum GH/IGF-I levels, occurrence of other pituitary deficiencies, presence of secondary empty sella, changes in tumour or residual volume were observed. CONCLUSIONS: The HPA axis function must be carefully monitored over the time by dynamic testing in all acromegalic patients, independently from the type of treatment.

Previous radiotherapy negatively influences quality of life during 4 years of follow-up in patients cured from acromegaly.

OBJECTIVE: Cross-sectional studies have shown impaired quality of life (QoL) in patients in biochemical control of acromegaly. The aim of this study was to assess longitudinal changes in QoL in a homogenous cohort of patients with sustained biochemical control of acromegaly. DESIGN: Prospective follow-up study. PATIENTS AND METHODS: QoL was assessed using four health-related QoL questionnaires (HADS, Hospital Anxiety and Depression Scale; MFI-20, Multidimensional Fatigue Index; NHP, Nottingham Health Profile; and SF-36, Short Form-36) and one disease-specific acromegaly quality of life (ACRO-QOL) questionnaire in 82 patients (43 men) with strict biochemical control of acromegaly, aged 56 years (range 29-84 years) at baseline and after 4 years of follow-up. The mean duration of controlled disease was 12 years (range 1-26 years). RESULTS: During follow-up, scores in 5 of 26 QoL subscales significantly worsened: physical and social functioning (SF-36), physical fatigue (MFI-20), and psychological well-being and personal relations (ACRO-QOL). Using linear regression analysis, baseline item scores predicted the follow-up scores, indicating individual stability over time. Previous radiotherapy (n = 27, 33%) negatively influenced several QoL subscales at follow-up: energy, pain and social isolation (NHP), physical fatigue and reduction in activity and motivation (MFI-20), depression and total anxiety and depression scores (HADS) and physical performance (ACRO-QOL). CONCLUSION: During 4 years of follow-up in patients with long-term biochemical control of ACRO-QOL is subtly, but progressively impaired. Radiotherapy was the predominant indicator of progressive impairment in QoL.