Adrenal-derived hypertension is one of the most prevalent causes of secondary hypertension. The two main types of pathology include adrenal tumors and hyperplasia. Because adrenal tumors have more significant clinical manifestations, biochemical abnormalities and imaging features, their treatment techniques have become increasingly sophisticated. Adrenal hyperplasia, on the other hand, has been considered to be relatively rare and has not received much attention because of the difficulties in diagnosis and treatment. With the continuous improvement of diagnostic techniques in recent years, the detection rate of adrenal hyperplasia has been increasing, for example, idiopathic adrenal hyperplasia (IAH) has accounted for more than 60 of patients with primary aldosteronism, and the latter accounts for almost all hypertensive people5-13, which makes people realize the importance of adrenal hyperplasia in the diagnosis of secondary hypertension. The importance of adrenal hyperplasia in the diagnosis of secondary hypertension has been recognized.
Adrenal hyperplasia hypertension refers specifically to adrenal-derived hypertension with a pathologic basis in adrenal hyperplasia. This article will provide a systematic review of the concept, diagnosis and surgical management of adrenal hyperplasia.
The concept of adrenal hyperplasia hypertension
The relationship between adrenal hyperplasia and hypertension
Pathological studies have shown a tendency for nodular hyperplasia of the adrenal cortex to occur to varying degrees with age, and it is common in autopsies. in consecutive autopsy studies conducted by Dobbie (1969) and Reinhard at different times and populations, the detection rate of nodular hyperplasia of the adrenal cortex was 64.6 and 53.7, respectively, and it was found that nodular hyperplasia of the adrenal cortex was associated with hypertension, but was associated with adrenal envelope vascular pathology. It is inferred that ageing or other causes of adrenal cortical vascular atherosclerosis lead to focal ischemic lesions and segmental cortical atrophy, which stimulate the hypothalamic-pituitary-adrenal axis and increase compensatory secretion of ACTH, leading to hyperplasia and hypersecretion of peripheral cortical cells and nodules. Adrenocortical function may be normal, hypo- or hyper-secretory where nodular hyperplasia occurs. In Dobbie’s study, the incidence of hypertension in adrenal hyperplasia was 50 . Therefore, adrenocortical nodular hyperplasia can be a manifestation of adrenal aging and does not necessarily lead to the development of hyperadrenalism and hypertension. Hypertension, as a manifestation of hyperadrenalism, is not necessarily associated with the morphological concept of adrenal hyperplasia. The diagnosis of adrenal hyperplasia hypertension must be based on biochemical evidence of increased adrenal hormone secretion.
Type of pathology
Adrenal hyperplastic hypertension consists mainly of Adrenal Cortical Hyperplasia (ACH), Adrenal Medullar Hypcrplasia (AMH) and Adrenal Cortical and Medullar Hyperplasia (ACMH) are three types of pathology.
ACH is the most common. Because the adrenal cortex is regulated by the hypothalamic-pituitary-adrenal axis, its hyperplasia can be secondary to both hypothalamic-pituitary disease and primary adrenal gland disease, and is therefore divided into two major types: secondary and primary cortical hyperplasia. The former mainly includes ACTH-dependent adrenocortical hyperplasia in cortisolism and IAH in primary aldosteronism, which are pathologically manifested as diffuse bilateral adrenal hyperplasia and, in a few cases, nodular hyperplasia at a later stage; the latter mainly includes non-ACTH-dependent macronodular adrenal hyperplasia (Adrenocorticotropin Independent Ma-cronodular Adrenal Hyperplasia (AIMAH), Primary Pigmented Nodular Adrenocortical Disease (PPNAD), and Unilateral Adrenocortical Hyperplasia (UAH), which is mostly nodular hyperplasia.
AMH Wu Jieping (1985), in his long-term clinical practice, based on the pathological differences
AMH is mostly bilateral, but can also occur unilaterally.
AMH has diffuse or nodular changes without an envelope, and its proliferating medullary cells may extend into both flanks and the tail. The medullary/cortical ratio is fundamentally changed, and microscopically the proliferating medullary cells are similar to normal chromophores, without specific changes.
ACMH is rare clinically, but has been reported to be increasing in recent years. Studies have shown that the corticomedullary is closely linked and regulated by a common mechanism, and the two can regulate each other. Increased secretion of one adrenal hormone can stimulate other adrenal [glandular cells, leading to increased secretion of the other hormone as a possible pathogenesis of ACMH.
A review of the literature shows that most of the reported ACMH are mainly AMH, and the clinical manifestations and hormone biochemistry are consistent with it, while the adrenal cortical hyperplasia is only morphological. Therefore, it is possible that a significant proportion of the reported ACMH are AMH complicated by senile changes in the adrenal cortex, the latter not being of particular significance in the development of hyperadrenalism and hypertension, which is another possible explanation for ACMH.
Clinical manifestations and diagnosis
Clinical manifestations
Adrenal hyperplasia is divided into three clinical types: cortisolism, primary aldosteronism, and catecholamine hyperplasia, depending on the hormone overproduced. Hypertension is the common clinical manifestation.
The typical clinical features of each type are not described here. It is worth noting that, compared to adrenal tumors, patients with hyperplasia have a longer disease duration and milder or insidious clinical manifestations. Some patients with cortical hyperplasia may present only with hypertension and no other typical clinical symptoms, called subclinical cortisolism or proaldosteronism. This may be related to the low hormone synthase activity of the hyperplastic cells. This feature places a higher demand on the diagnosis of adrenal hyperplastic hypertension.
Diagnosis
For each patient with adrenal hyperplastic hypertension, three issues need to be clarified and three different levels of diagnosis made: ① clinical diagnosis: whether there is an adrenal hormone excess (hyperfunction) and the type of excess hormone, mainly judged by clinical manifestations and biochemical findings; ② morphological diagnosis: whether the lesion is an adrenal hyperplasia and which side of the adrenal gland is hyperplastic, mainly relying on imaging before surgery (3) Functional diagnosis: whether the adrenocortical hyperplasia is primary or secondary, mainly by using the regulatory characteristics of the hypothalamus-pituitary-adrenal axis and selecting the corresponding test, if the primary focus can be found, the diagnosis is established. The accurate diagnosis and treatment of adrenal hyperplasia hypertension is based on the correct answers to these three questions.
Diagnostic procedure
All patients with clinical suspicion of adrenal hyperplastic hypertension must undergo a comprehensive biochemical examination including the three major adrenal hormones (cortisol, aldosterone and catecholamines) or their metabolites, including both screening tests and confirmatory tests, in addition to routine biochemical tests such as blood potassium and blood glucose, in order to obtain the same biochemical tests as for other hypertension of adrenal origin All patients must also undergo CT-based imaging to determine the presence of adrenal hyperplasia; patients with diagnostic difficulties or conditions may also undergo ECT isotope imaging and interferometry, both of which have very important reference values for establishing the diagnosis.
Morphologic diagnosis is the basis for determining the surgical treatment plan. Adjuvant examinations that can be used include: ① Adrenal imaging: is the main diagnostic basis. The adrenal region is rich in adipose tissue, and CT is the imaging test of choice because it has better resolution than MRI, while MR is mainly used for patients with suspected pituitary tumors; ② ECT isotope imaging can comprehensively determine the function and localization of adrenal hormone secretion, which has special diagnostic significance. At present, the more reliable and popular is the I-MIBG whole-body chromophobe scan, which can show highly functional pheochromocytoma and medullary hyperplasia, and its specificity is reported to be 97-100 in the literature; iodocholesterol adrenal cortical imaging under dexamethasone-suppressed conditions has limited its clinical use because of the difficulty in distinguishing lesions below 1.5 C1TI in diameter. (3) Bilateral adrenal venous sampling (Adrenal Venous Sampling, AVs): It is recognized as the most reliable diagnostic tool for the localization of primary aldosteronism, and can reliably differentiate adrenocortical adenomas and hyperplasia and make a lateral diagnosis with an accuracy rate of more than 95. However, it is an invasive test and it has a high technical difficulty, so it can be used in cases where the diagnosis is difficult to determine, but it should not be used as the first choice or routine test.
In adrenal cortical hyperplasia, determining whether the hyperplasia is primary directly affects the choice of treatment and prognosis of the patient. There are several methods to determine ACTH dependence in cortisolism: (1) high-dose dexamethasone test, where the level of cortisol secretion (blood or urine test) on the second day of oral administration does not drop below 50 on the control day is considered ACTH non-dependent; (2) plasma ACTH measurement, where blood ACTH is elevated in patients with ACTH-dependent hyperplasia; (3) imaging, where imaging of the relevant site (especially MRI) (iii) imaging, with imaging (especially MRI) of the relevant areas supporting ACTH-dependent hyperplasia if an ACTH-secreting tumor is detected. In primary aldosteronism, the distinction between IAH and UAH can be made with the aid of a renin stimulation test. A mild elevation in plasma aldosterone levels when lying down and a rise in levels above 33 when standing up supports the diagnosis of IAH.
Surgical treatment
Principles of surgical treatment
Although some cases of adrenal hyperplastic hypertension can be well controlled over time with simple medications, adrenalectomy remains the treatment of choice for this disease because: (1) adrenalectomy can cure or significantly improve hypertension in most patients with hyperplasia, greatly reducing or eliminating the inconvenience and side effects of long-term antihypertensive medications; (2) the ideal goal of treatment of adrenal hyperplastic hypertension is not limited to control normal blood pressure, but also should eliminate the adverse effects of excessive adrenal hormones on the organism. For example, studies have found that overproduction of aldosterone can promote cardiovascular hypertrophy, remodeling, and fibrosis, in addition to elevated blood pressure. Pharmacological treatments aimed at controlling blood pressure often do not specifically antagonize these effects of excessive hormones, and pathological processes with serious consequences continue under the guise of stable blood pressure. Adrenalectomy directly corrects the adrenal hormone overproduction and interrupts the corresponding pathological processes; (3) from an economic point of view, a long-term follow-up study of patients with primary aldosteronism showed that surgical treatment, although more costly on a one-time basis, significantly reduces the financial burden of patients compared to lifelong pharmacological treatment. Therefore, we advocate the adoption of adrenal surgery in the absence of contraindications.
Relative contraindications are mainly for patients with secondary adrenocortical hyperplasia: ①ACTH-dependent cortisolism: patients should first target the primary cause, such as pituitary radiotherapy or surgery, supplemented by drug therapy, and consider removing the hyperplastic adrenal gland if the effect is not good; ②IHA: some scholars currently believe that its onset may be caused by the pituitary gland, but often do not find concurrent pituitary adenomas, thus unable to target the primary cause. Treatment is mainly pharmacological.
Surgical approach
Since the introduction of retroperitoneoscopic techniques for adrenal surgery at the end of the last century, they have rapidly replaced traditional open surgery with the advantages of being minimally invasive, delicate, rapid and safe. It has become the most ideal treatment option for patients with this disease.
Surgical scope selection and prognosis
For patients with unilateral adrenal hyperplasia (including uAH and some AMH), the affected adrenal gland should be removed; for patients with bilateral adrenal hyperplasia (including most of AIMAH, PPNAD and AMH), the scope of surgery is still inconclusive. The main ideas include: (1) total bilateral adrenalectomy to ensure a surgical outcome with a cure rate of almost 100″”. Addison syndrome can occur after this procedure, requiring lifelong adrenocorticotropic hormone replacement therapy, affecting the quality of life. Once missed or in case of unexpected emergencies or trauma, it is easy to develop adrenal hypofunction or even adrenal crisis, leading to death; ② subtotal adrenalectomy (often preserving 15 0/4-30 of the adrenal gland ) and tipped adrenal autotransplantation, which can preserve certain adrenal function, mostly It is used for the treatment of bilateral AMH and has achieved more satisfactory results. However, related studies have found that blood and urine cortisol levels can be normalized early after subtotal adrenalectomy to avoid long-term hormone replacement, but there is still a risk of adrenal insufficiency if the cortisol rise induced by ACTH stimulation is continuously suppressed; (3) unilateral excision of the adrenal gland on the side of obvious hyperplasia, supplemented by short-term hormone replacement and closely monitored staged surgery may be a more reasonable treatment for bilateral adrenal hyperplasia. (iii) unilateral resection of the significantly enlarged adrenal gland, supplemented by short-term hormone replacement and closely monitored staged surgery may be a more reasonable clinical option for treating bilateral adrenal hyperplasia. A study of AIMAH found that hormone synthase activity in the hyperplastic cortical cells was not significantly elevated and may even be lower than normal, and that excision of one adrenal gland may completely correct hyperadrenalism and the resulting hypertension, even leading to postoperative adrenal insufficiency in a few cases. In a long-term follow-up study of unilateral adrenalectomy for AIMAH? After a mean follow-up of 78.8 (30-137) months, hypertension was cured or improved in all cases, blood and urine cortisol was normal, and no enlargement of the contralateral adrenal gland was observed, demonstrating that removal of the adrenal gland on the side of significant hyperplasia is a safe and effective treatment. Unilateral adrenalectomy has also been shown to be useful in the treatment of bilateral AMH, with good recent results”, but long-term follow-up studies are lacking. In the case of partial adrenalectomy, it should be clear that partial adrenalectomy is only a symptomatic treatment and cannot reverse the pathophysiological changes; therefore, the outcome of the procedure depends largely on the function of the remaining adrenal glands after surgery and whether further hyperplasia, hypersecretion, leads to persistent or recurrent hypertension. Therefore, long-term standardized postoperative follow-up to observe the surgical outcome is extremely important. For those who have poor results after unilateral adrenalectomy and whose hypertension is still not satisfactorily controlled, removal of the other adrenal E gland may be considered.