Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas.

OBJECTIVE: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6 to 16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone saline infusion test (DSIT) by applying both tests on the same subjects. METHODS: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls with normal adrenal imaging. Serum cortisol, aldosterone, and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean ± 2 s.d. values from the controls, we defined the upper normal limits for cortisol, aldosterone, and PRC for both the SIT and DSIT. RESULTS: In the controls, the post-DSIT aldosterone levels and the ARR were approximately two-fold and three-fold lower, respectively, than the corresponding post-SIT values (all P = 0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion (ACS). Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. CONCLUSIONS: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk of developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant ACS.

Clinical, Endocrine and Imaging Characteristics of Patients with Primary Hypophysitis.

Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25-75%: 3-60). There was a female predominance with a female/male ratio: 3.4:1. Eight out of 22 patients had another autoimmune disease. Headaches and gonadal dysfunction were the most common symptoms. Five patients presented with panhypopituitarism; 17 patients had anterior pituitary deficiency, and 7 had diabetes insipidus. At presentation, 9 patients were treated surgically, 5 received replacement hormonal treatment, and 8 high-dose glucocorticoids from whom 5 in association with other immunosuppressive agents. Six patients showed complete recovery of pituitary hormonal deficiencies while 6 showed a partial recovery during a 5-year follow-up period. No difference was found between patients treated with surgery and those treated medically. The overall relapse rate was 18%. PH can be manifested with a broad spectrum of clinical and hormonal disturbances. Long-term follow-up is required to define the natural history of the disease and response to treatment, since pituitary hormonal recovery or relapse may appear many years after initial diagnosis. We suggest that surgery and immunosuppressive therapy be reserved for exceptional cases.

Current status and controversies in adrenal incidentalomas.

Adrenal incidentalomas (AI) are serendipitously discovered lesions during abdominal imaging studies that need to be investigated for evidence of hormonal hypersecretion and/or malignancy. Because imaging modalities can reliably identify lesions that carry a high risk of malignancy, we focus on the identification of hypersecretory lesions and those with subclinical activity, particularly Cushing syndrome. Because diverse diagnostic tests and cut-offs are employed, the prevalence of hypersecretory AI varies widely, and there is controversy regarding their long-term sequelae. In this article we provide information regarding current radiological means to define the nature of AI, and the most appropriate biochemical tests for delineating hypersecretory states. We also discuss the duration and intensity of AI follow-up as well as the identification of AI that require specific therapeutic intervention.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension.

BACKGROUND: Previous studies based on standard endocrine testing have generally shown a low prevalence of primary aldosteronism, a form of autonomous aldosterone secretion (AAS), in hypertensive individuals. The purpose of this case-control study was to evaluate whether use of appropriately defined controls and combined testing reveal previously undetected AAS in hypertensives. MATERIALS AND METHODS: We investigated aldosterone secretion in 180 hypertensives with (n = 44) and without (n = 136) adrenal adenomas on computerized tomography (CT) and 72 matched nonhypertensive individuals with normal adrenal CT. Serum aldosterone and active renin were measured, and the aldosterone/active renin ratio was calculated before and after a modified fludrocortisone-suppression test (FST). In the latter, to eliminate any stimulatory effect of endogenous stress-induced adrenocorticotrophin hormone on aldosterone secretion, we administered 1 mg of dexamethasone on the last day of the classical FST fludrocortisone/dexamethasone suppression test (FDST). RESULTS: Using the 97·5 percentiles of serum aldosterone (74 pM L(-1)) and the aldosterone/renin ratio (32 pM L(-1) mU(-1) L(-1)) values obtained from the controls following the FDST, normal cut-off values indicative of adequate aldosterone suppression were established. Using the combination of these cut-offs, the estimated prevalence of AAS in patients with hypertension was 31%. Multiple linear regression analysis revealed a significant correlation between systolic and/or diastolic arterial blood pressure and the aldosterone value (P < 0·0001 and P < 0·01, respectively) and/or the aldosterone/renin ratio (P < 0·0001 and P < 0·01, respectively), which were obtained following the FDST. CONCLUSIONS: By applying new cut-offs obtained following modification of standard testing, AAS is quite prevalent in hypertensive individuals and correlates highly with arterial blood pressure. This may have relevance for both the aetiology of the hypertension and its optimal therapy.

The ice pack test in the differential diagnosis of myasthenic diplopia.

PURPOSE: To investigate the diagnostic value and to establish threshold criteria for the ice pack test as an office preliminary test in the differential diagnosis of myasthenic diplopia in comparison with blepharoptosis. DESIGN: Prospective, comparative cohort study. PARTICIPANTS: Eighty-nine patients with a recent onset of diplopia, blepharoptosis, or both were evaluated with orbital cooling in a prospective manner. Forty-eight patients presented with diplopia, 25 patients with both blepharoptosis and ophthalmoplegia and 16 patients with blepharoptosis. TESTING: All patients had the ice pack applied for 5 minutes on both eyelids at the initial orthoptic evaluation. Increasing the duration of cooling to 10 minutes was investigated in 36 diplopic patients. A complete diagnostic work-up was ordered and patients were followed up for a minimum of 6 months before diagnosis of myasthenia gravis was ascertained. MAIN OUTCOME MEASURES: Difference in cover test measurements in primary position or marginal reflex distance before and after the application of the ice pack, specific cause for diplopia and blepharoptosis. RESULTS: Fifteen patients were diagnosed as myasthenic. The optimal cutoff point for a positive response to the ice pack test proved to be a reduction in ocular deviation in primary position by 50% or by 10 prism diopters (PD) or more for presenting deviations larger than 20 PD. By this criterion, sensitivity for the detection of myasthenic diplopia was 76.9% (95% confidence interval [CI], 49.06%-92.50%) for the 5-minute application, compared with 92.3% (95% CI, 63.5%-98.9%) sensitivity demonstrated for blepharoptosis. Increasing the time of application to 10 minutes did not improve the diagnostic value of the test. Specificity was high (98.3%; 95% CI, 90.3%-99.9%) and was demonstrated even in patients with coexisting myasthenic and dysthyroid ophthalmopathy. Patients with oculomotor nerve paresis and Horner syndrome invariably were nonresponsive to the test. CONCLUSIONS: The ice pack test demonstrated high specificity and an acceptable sensitivity in the differential diagnosis of myasthenic diplopia. Data from this series suggest that a partial rather than a complete response to the ice pack test may be expected for myasthenic diplopia. Standardization of the method of application of the ice pack is critical for the interpretation of its effect.

High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas.

OBJECTIVES: Previous studies based on standard endocrine testing have shown a variable incidence of autonomous cortisol secretion (ACS) or autonomous aldosterone secretion (AAS) in patients with single adrenal adenomas (SAA). We tested whether the use of appropriate controls and modification of standard testing, aiming at eliminating interference from endogenous ACTH, reveals previously undetected subtle ACS and AAS by SAA. DESIGN: Case control study. Patients We investigated 151 patients with SAA and 72 matched controls with normal adrenal computerized tomography. MEASUREMENTS: All participants had arterial blood pressure recorded, and serum cortisol and aldosterone measured before and after intravenous administration of 250 mug of ACTH, and following dexamethasone administration. Eighty-three patients and all the controls had serum aldosterone and renin measured before and after saline infusion, and after a second saline infusion following dexamethasone administration. RESULTS: Using the mean + 2 SD values obtained from controls after dexamethasone administration and saline infusion following dexamethasone administration, normal cut-off values for cortisol (30.11 nM), aldosterone (67.59 pM), and aldosterone/renin ratio (9.74 pM/mU/l) were developed. Using these cut-off values, the estimated incidence of ACS and AAS in patients with SAA was 56.63% and 24.10%, respectively, whereas 12.05% had autonomous secretion of both cortisol and aldosterone. Systolic and diastolic arterial blood pressure correlated significantly with the aldosterone/renin ratio following AlphaCTH stimulation (P < 0.0002 and P < 0.001, respectively), and after saline infusion following dexamethasone administration (P < 0.003 and P < 0.002, respectively). CONCLUSIONS: By applying new cut-offs, ACS and AAS in patients with a SAA is very common, and aldosterone secretion correlates with arterial blood pressure.

Systemic and endocrine manifestations of Langerhans' cell histiocytosis: current concepts in diagnosis and management.

Langerhans' cell histiocytosis (LCH) is a rare disease of unknown etiology and variable biologic behavior and course. Almost every organ can be affected; however, it frequently involves the bones, lungs, skin and lymph nodes. LCH exhibits a particular predilection for involvement of the hypothalamo-pituitary axis resulting in diabetes insipidus and/or other anterior pituitary deficiencies. Although LCH can sometimes resolve spontaneously, it usually follows a chronic course and systemic treatment is mandatory for the management of multisystem disease. However, a significant number of patients will develop at least one permanent sequela as a consequence of the disease, with diabetes insipidus being the most common. A multidisciplinary approach is always needed in diagnosis, treatment and follow-up of all patients with LCH.

Growth without growth hormone (GH): a case report.

Growth without growth hormone (GH) has occasionally been described in patients with organic pituitary pathology, and even more rarely in patients with idiopathic pituitary hormone deficiency. The mechanism of growth without GH remains a mystery. We describe a 17-year old male who grew 38.5 cm in height over a 7-year period, despite the fact that he had established panhypopituitarism. The hypopituitarism was initially attributed to a presumptive hypothalamic hamartoma which was not, however, confirmed on subsequent and prolonged follow-up. Regular endocrine evaluation confirmed persistent anterior and posterior pituitary hormonal deficiencies with severe concomitant hyperinsulinemia as shown by an exaggerated insulin response to a standard oral glucose tolerance test. In our patient, a postulated mechanism could be the severe hyperinsulinemia, acting either through the insulin and/or IGF receptors and thus potentiating the mitogenic effect. This case illustrates that final height attainment within or above target height may occur in patients with idiopathic pituitary hormonal deficiency despite persistent, severe GH insufficiency.