A case of primary hyperparathyroidism, primary hyperaldosteronism and Cushing's disease

The rare association of parathyroid adenoma with primary hyperaldosteronism, occurring in each of 2 patients, was recently reported from this unit. The present communication records the subsequent development, in one of these patients, of Cushing's syndrome with an anterior pituitary adenoma. Screening for other endocrine abnormalities was negative. A literature search failed to produce any other cases of the association of these three conditions in one patient.     

Localization of primary hyperaldosteronism

After diagnosis of primary aldosteronism on the basis of biochemical evidence, the detection of the tumour is of crucial importance in the management of the disease. We reviewed the efficacy of CT-Scan, Iodo-Cholesterol Scintigraphy, digitalized phlebography, adrenal vein sampling for steroid measurements (AVS), and Nuclear Magnetic Resonance (NMR) in 160 hypertensive patients with primary aldosteronism. Diagnosis of Conn's adenoma (n = 96) or Adrenal Hyperplasia (n = 40) was confirmed by surgery or at least two concordant tumour localization tests. Scintigraphy gave a correct diagnosis in 53% of the 51 exams, CT-Scan in 82% of the 85 exams, and phlebography in 79% of 61 exams. Plasma Aldosterone/Cortisol ratio was 5 times higher on the side of adenoma in 55% of the 47 cases but this ratio was also present in 23% of 22 patients with adrenal hyperplasia. Each procedure exhibited few false positive and false negative cases. NMR performed in 15 patients with Conn's adenoma identified all the cases. But tumours displayed a signal close to the liver signal and identical to the normal adrenal. These results and the risk of invasive procedure (failure of catheterization of the right adrenal vein (n = 6) and adrenal haematoma (n = 2) lead us to propose a schema of exploration of patients with primary aldosteronism. The CT-Scan could be performed at the first step once the biological diagnosis confirmed. Phlebography and AVS will be performed only if tumour was less than 1 cm at the CT-Scan despite important biological abnormalities. This schema requires to be validated by a prospective evaluation.     

Aldosterone in primary hyperaldosteronism

The conditions which must be respected to ensure the validity of the biochemical diagnostic criteria of primary hyperaldosteronism, conditions of blood sampling, timing posture and age of the patient, sodium intake and intercurrent drug therapy. As none of the tests is 100 p. 100 specific in distinguishing adrenal adenoma from hyperplasia, an association of several investigations has to be used. In cases of adenoma, the authors recommend the investigations which demonstrate the autonomy of secretion and the prevalence of circadian rhythm over the influence of change in posture. The measurement of aldosterone levels may be completed by that of its precursor, 18-hydroxy-corticosterone (18 OH CS).     

A patient with concurrent primary hyperaldosteronism and adrenal insufficiency

A 73-year-old man with history of longstanding primary hyperaldosteronism developed adrenal insufficiency after he ruptured an abdominal aortic aneurysm and had a prolonged hypotensive episode. The patient presented as a diagnostic dilemma with recurrent hypotensive episodes and hypokalemia. A cosyntropin (Cortrosyn) stimulation test demonstrated a blunted cortisol response while at the same time having a suppressed plasma renin activity level and an elevated plasma aldosterone value. Diagnosis of Addison disease and concurrent primary hyperaldosteronism resulted in the patient's being treated with an unusual combination of prednisone and spironolactone followed by marked improvement in his symptoms.     

Medical management of primary hyperaldosteronism

Most forms of primary aldosteronism are surgically correctable. However, when surgery is not appropriate, medical management is just as effective in correcting the pathophysiologic abnormalities due to aldosterone excess. A prerequisite for the rational medical management of primary aldosteronism is an understanding of the mechanisms that sustain hypertension. Primary aldosteronism can be associated with severe and resistant hypertension, and persistent hypervolemia is the primary reason for resistance to therapy. Patients with overriding comorbidities or strong preferences have been medically treated over the intermediate term of 5 to 7 years without evidence of escape or evidence of malignant transformation of adrenal adenomas.     

Renal impact of primary hyperaldosteronism

The impact of hyperaldosteronism on target organs, and particularly kidney function, is greater than that of essential hypertension. Hyperaldosteronism provokes a glomerular hyperfiltration and hypertension that may cause renal alterations. Those may explain why elevated blood pressure may persist, even after radical treatment of the cause of hyperaldosteronism.     

A new diagnostic test for primary tumoral hyperaldosteronism

Plasma aldosterone levels were measured during two tests of inhibition in 31 hypertensive patients (13 essential hypertension, 6 bilateral adrenal hyperplasia and 12 documented Conn adenomas) on normal salt diets after withdrawal of all therapy: 1--before and after intravenous infusion of 2 I normal saline in two hours; 2--before and three hours after administration of 1 mg/kg of Captopril. Plasma aldosterone levels greater than 360 pmol/I after salt loading, or greater than 748 pmol/I after Captopril is characteristic of primary tumoral hyperaldosteronism. Apart from the rapidity of the test, Captopril is well-tolerated, does not require acute volume expansion and can be carried out in all forms of hypertension, even in severe cases.     

Cardiac consequences of primary hyperaldosteronism

The activation of the renin-angiotensin system is associated with vascular and cardiac hypertrophy. But there are few data on the renal and cardiac consequences of the hypersecretion of aldosterone. In the experimental setting, hyperaldosteronism leads to an excess of fibrous interstitial tissue and cardiac hypertrophy. In man, these consequences are those of hyperaldosteronism. The aim of this study was to assess the cardiac consequences of hyperaldosteronism in a series of 31 patients with a documented Conn adenoma, in comparison with a matched population of 31 patients with primary hypertension. For the same level of blood pressure, cardiac hypertrophy is more prominent in hyperaldosteronism and there is a positive correlation between the level of plasma aldosterone and left ventricular wall thickness. Left ventricular hypertrophy is of the concentric type. In addition, an increase in myocardial fibrosis (that can now be quantified by echocardiography) is observed, with a positive correlation between plasma aldosterone and reflected ultrasound which might correspond to increased myocardial collagen. These anatomic modifications of myocardial structure result in diastolic dysfunction. Overall, Conn adenoma is associated in accelerated disease, which is partly independent of the level of blood pressure.     

Surgical treatment in primary hyperaldosteronism

From 1994 to 2000, 32 patients (16 men, 16 women; mean age 53 years) underwent laparoscopic adrenalectomy at H?pital l'Antiquaille of Lyon. All but one had systemic arterial hypertension and hypokaliemia was noted in all patients. All patients had unilateral adrenalectomy, and only one required conversion to conventional laparotomy. There were no deaths and complications were rare.     

A rare lung nodule consisting of adenocarcinoma and amyloid deposition in a patient with primary systemic AL amyloidosis

A 60-year-old woman was found to have proteinuria and a lung nodule. The surgically resected left upper lobe contained a nodule, in which the adenocarcinoma was surrounded by a heavy deposition of amyloid. Subsequent renal and gastric biopsies demonstrated amyloid deposition with Aλ immunoreactivity. She was treated with 2 courses of VAD (vincristine, doxorubicin and dexamethasone), resulting in the disappearance of Bence Jones proteinuria. Her nephrotic syndrome has been improving during the subsequent 3 years. The rare lung nodule consisting of adenocarcinoma and amyloid deposition was a diagnostic clue in this primary systemic AL amyloidosis patient.     

Plasma immunoreactive proopiolipomelanocortin-derived peptides in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism

Immunoreactive plasma levels of the proopiolipomelanocortin-derived peptides, ACTH, beta-endorphin-lipotropin, and gamma 3MSH, were measured in patients with primary hyperaldosteronism, idiopathic hyperaldosteronism with bilateral adrenal hyperplasia, and dexamethasone-suppressible hyperaldosteronism. Plasma peptide concentrations in patient groups were not different from those in normal controls. Removal of aldosterone-producing adenomas in three patients and of an aldosterone-producing adrenocortical carcinoma in one patient did not affect plasma peptide concentrations. Furthermore, infusion of the opiate antagonist naloxone (0.2 mg/min) in one patient with bilateral adrenal hyperplasia had no effect on either plasma aldosterone or cortisol. These results suggest that the proopiolipomelanocortin-derived peptides are not overproduced in states of hyperaldosteronism.     

原发性醛固酮增多症临床诊治规范

原发性醛固酮增多症是一种常见的继发性高血压,发病率为10%～20%,与原发性高血压患者相比,原醛症患者心、脑等靶器官损害更为严重,因而此类高血压的早期诊断至关重要。本文将就原发性醛固酮症多症的患病率、筛查指标、确诊试验、分型诊断及治疗方案进行探讨。     

17 alpha-hydroxylase deficiency masquerading as primary hyperaldosteronism

A unique case of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is reported. Initially the patient was misdiagnosed as testicular feminization for 16 years and was thought to have typical primary hyperaldosteronism for 5 years. However, careful detailed endocrine studies showed markedly elevated progesterone, deoxycorticosterone, and 18-hydroxycorticosterone values with low levels of 17-hydroxyprogesterone, 11-deoxycortisol, testosterone, and DHEA-Sulfate. In contrast to the suppressed aldosterone levels that are found in 17 alpha-hydroxylase deficiency, this patient's aldosterone levels were inappropriately elevated before and after ACTH stimulation. Use of glucocorticoid replacement resolved the patient's symptoms and completely corrected the hypokalemia and hypertension. In summary, recognition of 17 alpha-hydroxylase deficiency with steroid-responsive primary hyperaldosteronism is important because hypertension, hypokalemia, and symptoms respond to steroid replacement.