Diagnosis and Surgical Treatment of Primary Hyperaldosteronism

The dissertation is devoted to the diagnosis and surgical treatment of primary hyperaldosteronism (PA) — one of the important manifestations of secondary arterial hypertension. The research is relevant in connection with the high prevalence of arterial hypertension and the necessity of timely detection of endocrine forms of the disease. The work develops an optimal complex of clinical-laboratory and instrumental methods for PA diagnosis, including evaluation of the sensitivity of ultrasonic, tomographic, and magnetic resonance imaging methods, as well as the role of selective venous blood sampling in the differential diagnosis of disease forms. Special attention is given to the development of a rational examination scheme, the determination of prognostic factors for the efficacy of surgical treatment, and the substantiation of the choice of treatment strategy — conservative or operative — for various forms of PA.

In the structure of morbidity in industrially developed countries, diseases of the cardiovascular system hold a dominant position (55%). In Russia in 2000, 1 million 220 thousand people died from diseases of the circulatory organs [16,43]. Among diseases of the circulatory organs, the principal role belongs to arterial hypertension (AH) as well as ischemic heart disease (IHD). According to data presented in the State Report on the Health Status of the Population in 2001, in Russia more than 40 million people suffer from AH, which constitutes 25–30% of the country's population [16]. Alarming is the fact that only in 20–25% of patients blood pressure (BP) is maintained at a normal level with medication (Chikhladze N. 1992; Duprez R.A. 1993; Freis E.D. 2000). In Russia, AH is adequately controlled in only 8% of patients (Oganov R.G. 1994).

Given the important socio-economic and medical significance of AH, in 2001 the Government of Russia adopted the Federal Target Program «Prevention and Treatment of Arterial Hypertension in the Russian Federation» [16].

Elevated BP is one of the most frequent reasons for seeking medical care. Despite the widespread nature of the disease, the causes of AH are often not recognized in a timely manner, and the patients' condition is erroneously classified as essential AH (hypertensive disease). The main reasons for late diagnosis of symptomatic AH are insufficient knowledge of the clinical picture, including atypical forms of the disease, as well as inadequate material and technical support of medical institutions. Attempts to apply standard approaches to antihypertensive therapy to the treatment of patients with endocrine AH often do not yield the desired result. At the same time, adequate timely pathogenetic therapy makes it possible to normalize the patients' condition in the shortest possible time and prevent the development of life-threatening complications.

The relevance of the problem is also determined by the fact that in the structure of diseases accompanied by elevated BP, up to 25–35% are symptomatic AH (Arabidze G.G. 1981). One of the causes of secondary AH is primary hyperaldosteronism (PA), which accounts for 1–3% (Dedov I.I. 2000; Vetshev P.S. 2002; Biglieri E.G. 1995; Ledingham J.G. 1987; Roake J.A. 1994; Wilson J. 1998), and according to some data, which is apparently more realistic, 9–15% (Gordon R.D. 1994; Gordon R.D. 2001) of all cases of AH, in connection with which some authors report a developing «epidemic» of PA (Connel J.L. 2002; Foo R. 2001; Gordon R.D. 2001).

At present, two main causes of PA are identified:

1) Unilateral aldosterone-producing adenoma (APA) — Conn's syndrome — 60–80%;

2) Idiopathic hyperaldosteronism (IHA) — bilateral zona glomerulosa hyperplasia — 20–40%.

These two dominant forms of the disease constitute approximately 90–95% of all PA observations. Among most researchers, the opinion has taken shape regarding the necessity of surgical treatment for patients with Conn's syndrome and conservative treatment for IHA. Therefore, reliable differential diagnosis of various forms of PA using laboratory tests and topographic diagnostic methods plays a leading role in choosing the optimal treatment strategy. (Kalinin A.P. 2000; Vetshev P.S. 2002; Biglieri E.G. 1995; Gordon R.D. 2001; Young W.F.Jr. 1999).

Analysis of literature data allows the identification of two main problems in PA diagnosis: first, the difficulty of detecting PA due to the frequent absence of typical symptoms, insufficient awareness and vigilance of clinicians (Pavlenko A.K. 2001, Gordon R.D. 2001); second, the necessity of reliable differential diagnosis between APA and IHA to resolve the question of treatment strategy. In this regard, while the first problem is encountered by physicians of therapeutic and endocrinological departments, the resolution of the second is primarily the prerogative of surgeons.

The presence among APA of angiotensin II-sensitive and angiotensin II-insensitive adenomas, the retroperitoneal location of the adrenal glands, and small adenoma sizes are the reasons why, using traditional laboratory (hormonal tests, stimulation tests) and instrumental (ultrasound examination (US), computed tomography (CT), magnetic resonance imaging (MRI) methods of investigation, it is not always possible to reliably verify the forms of PA. This often leads to an erroneous treatment strategy, including unjustified removal of one of the adrenal glands in IHA or refusal of surgery in patients with APA. (Vetshev 2002, 2004, 2006; Kalinin A.P. 1999, 2000; Gordon R.D. 2001; Phillips J.L. 2000; Sohaib S.A. 2000).

According to most researchers (Gordon R.D. 2001; Phillips J.L. 2000; Sohaib S.A., 2000), in some cases the key role in performing the differential diagnosis between APA and IHA is played by selective venous blood sampling directly from the adrenal veins; however, there is no single generally accepted protocol for interpreting the results of this investigation, which also introduces substantial difficulties in making decisions regarding the choice of further treatment strategy.

At present, most specialists involved in the diagnosis and treatment of PA agree that surgical treatment is pathogenetically justified only in APA, aldosterone-producing carcinomas (APC), and primary unilateral adrenal hyperplasia (PUAH), since in these three forms of PA there exists unilateral autonomous aldosterone secretion. Given that APC and PUAH are extremely rare, the greatest significance for clinical practice has the treatment of APA. Potentially, surgical treatment in APA should lead to subsequent normalization of BP in all operated patients. However, the frequency of persistence of arterial hypertension after APA removal ranges from 40 to 70% (Ustinova S.E., 1989, Kalinin A.P., 2000, Simon D., 1993, Siren J., 1998), which does not fully satisfy surgeons and requires further search for ways to improve treatment outcomes in this category of patients.

Consequently, certain questions of differential diagnosis of various forms of PA, the development of an optimal diagnostic algorithm for this category of patients, the determination of well-founded indications and reliable criteria for forecasting the efficacy of surgical treatment remain far from final resolution, which served as the basis for conducting the present work.

RESEARCH OBJECTIVE: to develop an optimal complex of clinical-laboratory and instrumental research methods for the diagnosis of PA and the choice of treatment strategy based on a comparative analysis of the results of modern diagnostic methods compared with morphological investigation data, as well as short-term and long-term outcomes of surgical treatment of patients.

RESEARCH TASKS

1. To evaluate the sensitivity of various instrumental diagnostic methods (US, CT, MRI) in the dominant forms of PA: APA and IHA.

2. To determine the place and role of selective blood sampling in the differential diagnosis between APA and IHA.

3. To develop a rational examination scheme for patients with PA.

4. To determine the prognostic factors of surgical treatment in APA, based on the study of long-term results of operative treatment of APA.

SCIENTIFIC NOVELTY

• Based on a comparative study of the sensitivity of various non-invasive topographic diagnostic methods in combination with functional tests, it has been established that the greatest informativeness in the differential diagnosis of PA is possessed by the combined use of the standing test with computed tomography.

• On a large clinical material, the necessity of calculating the Aldosterone/Cortisol ratio during selective venous adrenal sampling (SVAS) for the objective assessment of adrenal functional activity and the differential diagnosis of various forms of PA with subsequent resolution of the question regarding the necessity of surgical treatment has been demonstrated.

• Based on a comparative evaluation of the informativeness of various diagnostic methods: laboratory research methods, functional tests, instrumental research methods (US, CT, MRI, SVAS), a rational scheme for diagnosis and differential diagnosis of various forms of PA in patients with symptomatic AH has been developed.

• It has been established that left ventricular hypertrophy (LVH) is a prognostic factor for the persistence or recurrence of AH in patients with APA after adrenalectomy.

PRACTICAL SIGNIFICANCE

A diagnostic-therapeutic algorithm scheme for the differential diagnosis of various forms of PA has been developed and substantiated, allowing the majority of patients to choose the correct treatment strategy — conservative or operative — and to avoid performing an unjustified operation.