Circadian Blood Pressure Profile in Patients with Active Cushing's Disease and after Long-term Cure

Abstract

Hypertension is a major feature of Cushing's disease, with the attendant increase in the rate of cardiovascular events. The circadian blood pressure profile also impacts cardiovascular risk and a few studies have shown that patients with Cushing's syndrome do not present the expected nocturnal blood pressure decrease and, further, that this alteration persists in short-range disease remission. These studies were performed by conventional discontinuous ambulatory pressure monitoring, a technique not devoid of limitations. Aim of our study was the assessment of blood pressure and heart rate profile by beat-to-beat noninvasive monitoring in twelve patients with active Cushing's disease (9 women and 3 men, age 33.3±2.36 years) and the assessment of its possible changes at short- (<1 year) and long-term (2-3 years) follow-up after curative surgery. No nocturnal blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in 50% of patients both during active hypercortisolism and within 1 year from surgery. Recovery of blood pressure dipping profile was detected at long-term follow-up in a minority of patients. Daytime heart rate was higher in patients with active Cushing's disease and decreased over time after cure. In conclusion, patients with Cushing's disease present absent nocturnal blood pressure dipping and abnormal heart rate values which do not resolve after short-term remission of hypercortisolism and show only partial improvement in the long run. These findings identify additional cardiovascular risk factors for patients cured of Cushing's disease.

Key words

hypertension - cardiovascular risk - blood pressure dipping - hypercortisolism - treatment

References

• 1 Plotz CM, Knowlton AL, Ragan C. The natural history of Cushing's syndrome.  Am J Med. 1952;  13 577-614
• 2 Ross EJ, Linch DC. The clinical response to treatment in adult Cushing's syndrome following remission of hypercortisolaemia.  Postgrad Med J. 1985;  61 205-211
• 3 Welbourn RB. Survival and causes of death after adrenalectomy for Cushing's disease.  Surgery. 1985;  97 16-20
• 4 Grabner P, Hauer-Jensen M, Jervell J, Flatmark A. Long term results of treatment of Cushing's disease by adrenalectomy.  Eur J Surg. 1991;  157 461-464
• 5 Lindholm J, Juul S, Jørgensen JOL, Astrup J, Bjerre P, Feldt-Rasmussen U, Hagen C, Jørgensen J, Kosteljanetz M, Kristensen LØ, Laurberg P, Schmidt K, Weeke J. Incidence and late prognosis of Cushing's syndrome: a population-based study.  J Clin Endocrinol Metab. 2001;  86 117-123
• 6 Swearingen B, Biller BMK, Barker FG, Katznelson L, Grinspoon S, Klibanski A, Zervas NT. Long-term mortality after transsphenoidal surgery for Cushing disease.  Ann Intern Med. 1999;  130 821-824
• 7 Pikkarainen L, Sane T, Reunanen A. The survival and well-being of patients treated for Cushing's syndrome.  J Intern Med. 1999;  245 463-468
• 8 Fallo F, Sonino N, Barzon L, Pistorello M, Pagotto U, Paoletta A, Boscaro M. Effect of surgical treatment on hypertension in Cushing's syndrome.  Am J Hypertens. 1995;  9 77-80
• 9 Colao A, Pivonello R, Spiezia S, Faggiano A, Ferone D, Filippella M, Marzullo P, Cerbone G, Siciliani M, Lombardi G. Persistence of increased cardiovascular risk in patients with Cushing's disease after five years of successful cure.  J Clin Endocrinol Metab. 1999;  84 2664-2672
• 10 Mancia G, Zanchetti A, Agabiti Rosei E, Benemio G, Cesaris R De, Fogari R, Pessina A, Porcellati C, Rappelli A, Salvetti A, Trimarco B. Ambulatory blood pressure is superior to clinic blood pressure in predicting treatment-induced regression of left ventricular hypertrophy. SAMPLE study group.  Circulation. 1997;  95 1464-1470
• 11 Staessen JA, Asmar R, Buyzere M De, Imai Y, Parati G, Shimada K, Stergiou G, Redón J, Verdecchia P. Task force II: blood pressure measurement and cardiovascular outcome.  Blood Press Monit. 2001;  6 355-370
• 12 Verdecchia P. Prognostic value of ambulatory blood pressure.  Hypertension. 2000;  35 844-851
• 13 Mancia G, Parati G, Rienzo M Di, Zanchetti A. Pathophysiology of hypertension. In: Zanchetti A, Mancia G (eds) Handbook of Hypertension. Philadelphia: Elsevier Science 1997: 117-169
• 14 Verdecchia P, Schillaci G, Porcellati C. Dippers versus non-dippers.  J Hypertension. 1991;  9 ((Suppl 8)) S42-S44
• 15 Cuspidi C, Meani S, Salerno M, Valerio C, Fusi V, Severgnini B, Lonati L, Magrini F, Zanchetti A. Cardiovascular target organ damage in essential hypertensives with or without reproducible nocturnal fall in blood pressure.  J Hypertension. 2004;  22 273-280
• 16 O'Brien E, Sheridan J, O'Malley K. Dippers and non-dippers.  Lancet. 1988;  2 397
• 17 Verdecchia P, Schillaci G, Guerrieri M, Gatteschi C, Benemio G, Boldrini F, Porcellati C. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension.  Circulation. 1990;  81 528-536
• 18 Kotsis V, Stabouli S, Bouldin M, Low A, Toumanidis S, Zakapoulos N. Impact of obesity on 24-hour ambulatory blood pressure and hypertension.  Hypertension. 2005;  45 602-607
• 19 Björklund K, Lind L, Andrén B, Lithell H. The majority of nondipping men do not have increased cardiovascular risk: a population-based study.  J Hypertension. 2002;  20 1501-1508
• 20 Myers MG. Twenty-four-hour blood pressure control: a brief review of aspects of target-organ protection.  J Hypertens Suppl. 1996;  14 S7-S10
• 21 Plaschke M, Trenkwalder P, Dahlheim H, Lechner C, Trenkwalder C. Twenty-four-hour blood pressure profile and blood pressure responses to head-up tilt tests in Parkinson's disease and multiple system atrophy.  J Hypertension. 1998;  16 1433-1441
• 22 Imai Y, Abe K, Sasaki S, Minami N, Nihei M, Munakata M, Murakami O, Matsue K, Sekino H, Miura Y, Yoshinaga K. Altered circadian blood pressure rhythm in patients with Cushing's syndrome.  Hypertension. 1988;  12 11-19
• 23 Zacharieva S, Orbetzova M, Stoynev A, Shigarminova R, Yaneva M, Kalinov K, Nachev E, Elenkova A. Circadian blood pressure profile in patients with Cushing's syndrome before and after treatment.  J Endocrinol Invest. 2004;  27 924-930
• 24 Manning G, Rushton L, Donnelly R, Millar-Craig MW. Variability of diurnal changes in ambulatory blood pressure and nocturnal dipping status in untreated hypertensive and normotensive subjects.  Am J Hypertens. 2000;  13 1035-1038
• 25 Omboni S, Parati G, Palatini P, Vanasia A, Muiesan ML, Cuspidi C, Mancia G. Reproducibility and clinical value of nocturnal hypotension: prospective evidence from the SAMPLE study.  J Hypertension. 2006;  16 733-738
• 26 Imholz BP, Langewouters GJ, Montfrans GA von, Parati G, Goudoever J van, Wesseling KH, Wieling W, Mancia G. Feasibility of ambulatory, continuous 24-hour finger arterial pressure recording.  Hypertension. 1993;  21 65-73
• 27 Invitti C, Pecori Giraldi F, Martin M De, Cavagnini F. the Study Group of the Italian Society of Endocrinology on the Pathophysiology of the Hypothalamic-Pituitary-Adrenal Axis . Diagnosis and management of Cushing's syndrome: results of an Italian multicentre study.  J Clin Endocrinol Metab. 1999;  84 440-448
• 28 Guidelines Committee . European Society of Hypertension - European Society of Cardiology guidelines for the management of arterial hypertension.  J Hypertension. 2003;  21 1011-1053
• 29 Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing.  Hypertension. 1989;  13 647-655
• 30 Omboni S, Parati G, Castiglioni P, Di Rienzo M, Imholz BP, Langewouters GJ, Wesseling KH, Mancia G. Estimation of blood pressure variability from 24-hour ambulatory finger blood pressure.  Hypertension. 1998;  32 52-58
• 31 Gizdulich P, Imholz BP, Meiracker AH van den, Parati G, Wesseling KH. Finapres tracking of systolic pressure and baroreflex sensitivity improved by waveform filtering.  J Hypertension. 1996;  14 243-250
• 32 Westerhof BE, Guelen I, Parati G, Groppelli A, Montfrans GA van, Wieling W, Wesseling KH, Bos WJ. Variable day/night bias in 24-h non-invasive finger pressure against intrabrachial artery pressure is removed by waveform filtering and level correction.  J Hypertension. 2002;  20 1981-1986
• 33 Verdecchia P, Schillaci G, Borgioni C, Ciucci A, Telera MP, Pede S, Gattobigio R, Porcellati C. Adverse prognostic value of blunted circadian rhythm of heart rate in essential hypertension.  J Hypertension. 1998;  16 1335-1343
• 34 Gardner MJ, Altman DG. Confidence intervals rather than P values: estimation rather than hypothesis testing.  Br Med J. 1986;  292 746-750
• 35 Erdogan D, Gullu H, Caliskan M, Yildirim I, Baycan S, Ciftici C, Muderrisoglu H. The influence of circadian blood pressure changes on aortic distensibility and left ventricular diastolic function in hypertensive individuals.  Int J Cardiovasc Imaging. 2006;  22 157-165
• 36 Tsivgoulis G, Vemmos KN, Zakopoulos N, Spengos K, Manios E, Sofia V, Zis V, Mavrikakis M. Association of blunted nocturnal blood pressure dip with intracerebral hemorrhage.  Blood Press Monit. 2005;  10 189-195
• 37 Ohkubo T, Imai Y, Tsuji I, Nagai K, Watanabe N, Minami N, Kato J, Kikuchi N, Nishiyama A, Aihara A, Sekino M, Satoh H, Hisamichi S. Relation between nocturnal decline in blood pressure and mortality. The Osahama study.  Am J Hypertens. 1997;  10 1201-1207
• 38 Nakano S, Fukuda M, Hotta F, Ito T, Ishii T, Kitazawa M, Nishiwama M, Kigoshi T, Uchida K. Reverse circadian blood pressure rhythm is associated with occurrences of both fatal and non fatal vascular events in NIDDM subjects.  Diabetes. 1998;  47 1501-1506
• 39 Stella P, Tabak AG, Zgibor JC, Orchard TJ. Late diabetes complications and non-dipping phenomenon in patients with type 1 diabetes.  Diabetes Res Clin Pract in. 2006;  71 14-20
• 40 Sherwood A, Steffen PR, Blumenthal JA, Kuhn C, Hinderliter AL. Nighttime blood pressure dipping: the role of the sympathetic nervous system.  Am J Hypertens. 2002;  15 111-118
• 41 Staessen JA, Birkenhager W, Bulpitt CJ, Fagard R, Fletcher AE, Lijnen P, Thijs L, Amery A. The relationship between blood pressure and sodium and potassium excretion during the day and at night.  J Hypertension. 1993;  11 443-447
• 42 Noda A, Okada T, Hayashi H, Yasuma F, Yokota M. 24-hour ambulatory blood pressure variability in obstructive sleep apnoea syndrome.  Chest. 1993;  103 1343-1347
• 43 Parati G. Blood pressure reduction at night: sleep and beyond.  J Hypertension. 2000;  18 1725-1729
• 44 Imai Y, Abe K, Sasaki S, Minami N, Munakata M, Nihei M, Sekino H, Yoshinaga K. Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations.  J Hypertension. 1989;  7 113-120
• 45 Fallo F, Fanelli G, Cipolla A, Betterle C, Boscaro M, Sonino N. 24-hour blood pressure profile in Addison's disease.  Am J Hypertens. 2006;  7 1105-1109
• 46 Matsumara K, Abe I, Fukuhara M, Fujii K, Ohya Y, Okamura K, Fujishima M. Modulation of circadian rhythm of blood pressure by cortisol in patients with hypopituitarism.  Clin Exp Hypertens. 2006;  16 55-66
• 47 Panarelli M, Terzolo M, Piovesan A, Osella G, Paccotti P, Pinna G, Angeli A. 24-hour profiles of blood pressure and heart rate in Cushing's syndrome.  Ann Ital Med Int. 1990;  5 18-25
• 48 Kreze A, Mikulecky M. Daily blood pressure profile in Cushing's syndrome before and after surgery.  Braz J Med Biol Res. 1999;  32 1199-1203
• 49 Zelinka T, Strauch B, Pecen L, Widimisky Jr J. Diurnal blood pressure variation in pheochromocytoma, primary aldosteronism and Cushing's syndrome.  J Hum Hypertension. 2004;  18 107-111
• 50 Palatini P, Julius S. Elevated heart rate: a major risk factor for cardiovascular disease.  Clin Exp Hypertens. 2004;  26 637-644
• 51 Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations.  Johns Hopkins Bull. 1932;  50 137-195
• 52 Hermus AR, Huysmans DA, Smals AGH, Corstens FH, Kloppenborg PWC. Remarkable improvement of osteopenia after cure of Cushing's syndrome.  Horm Metab Res. 1994;  26 209-210
• 53 Suzuki T, Shibata H, Ando T, Kurihara I, Kobayashi S, Hayashi K, Hayashi M, Kawabe H, Saito I, Murai M, Saruta T. Risk factors associated with persistent postoperative hypertension in Cushing's syndrome.  Endocrine Res. 2000;  26 791-795
• 54 Reinartz G, Angermaier A, Buchfelder M, Fahlbusch R, Georgieff M. Cushing's disease utilizing stable isotope techniques.  Horm Metab Res. 1995;  27 425-431
• 55 Pivonello R, Faggiano A, Lombardi G, Colao A. The metabolic syndrome and cardiovascular risk in Cushing's syndrome.  Endocrinol Metab Clin North Am. 2005;  34 327-339
• 56 Lindsay JR, Nansel T, Baid S, Gumowski J, Nieman LK. Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission.  J Clin Endocrinol Metab. 2005;  91 447-453
• 57 Pecori Giraldi F, Andrioli M, Marinis L De, Bianchi A, Giampietro A, Martin M De, Sacco E, Scacchi M, Pontercorvi AS, Cavagnini F. Significant GH deficiency after long-term cure by surgery in adult patients with Cushing's disease.  Eur J Endocrinol. 2007;  156 235-241
• 58 Palatini P, Parati G. Modulation of 24-h blood pressure profiles: a new target for treatment?.  J Hypertension. 2005;  23 1799-1801

Correspondence