Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas.
OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas. (+info)
Preclinical Cushing's syndrome due to ACTH-independent bilateral macronodular adrenocortical hyperplasia with excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone.
A 64-year-old woman developed hypertension and hypokalemia, due to ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) with excessive secretion of 18-hydroxydeoxycorticosterone and corticosterone. Plasma cortisol did not show a diurnal rhythm, and was not suppressed by dexamethasone (8 mg). Plasma cortisol responded to ACTH and was increased by hypoglycemia without modifying ACTH levels. Radiological studies demonstrated that adrenal glands were enlarged with macronodules. Although the patient exhibited a low plasma renin activity and aldosterone levels, hypokalemia and hypertension were observed. Hormonal findings would support the hypothesis that the tumor of AIMAH originated from cells of the upper zona fasciculata. (+info)
Clinical significance of the solitary functioning adrenal gland.
To assess the compensatory functional and anatomic changes in the remaining adrenal cortex after unilateral adrenalectomy or in the unaffected adrenal in patients with unilateral adrenal destruction by neoplasm, 17 patients with a single, functioning adrenal gland and normal indices of adrenocortical function, nine after adrenalectomy and eight with a unilateral, destructive adrenal lesion were studied with 131I-6 beta-iodomethyl-19-norcholesterol (NP-59) scintigraphy and computed tomography. Adrenal masses with a mean (+/- s.d.) diameter of 2.8 +/- 1.0 cm; (range 1-4 cm; 95% confidence interval (Cl), 2.5-3.1 cm) were identified by computed tomography in seven of nine patients in the remaining adrenal cortex at variable times (6.1 +/- 5.9 y; range 0.5-19 y) after unilateral adrenalectomy. Mean (+/- s.e.m.) NP-59 uptake was elevated (p less than 0.01) in both adrenalectomy and adrenal destruction groups, mean uptake (+/- s.e.m.) was 0.32% +/- 0.04% administered dose (95% Cl, 0.24%-0.4% administered dose) as compared to normal (0.16% +/- 0.05% administered dose, 95% Cl, 0.06%-0.26% administered dose). The remaining adrenal cortex may be anatomically abnormal after unilateral adrenalectomy and demonstrate compensatory, increased NP-59 uptake in the presence of overall, normal adrenocortical function. (+info)
Cellular internalization, transport, and esterification of iodine-125-NP59 by MA-10 Leydig tumor cells.
The present studies were directed toward understanding the cellular processing of the cholesterol analogue, NP59. NP59 readily entered MA-10 Leydig tumor cells. The cholesterol analogue entered the cells by binding to the plasma membrane and becoming internalized along with plasma membrane cholesterol. Internalized NP59 was readily esterified to NP59 ester. Transport of NP59 within the cell was indistinguishable from transport of cholesterol. Cholesterol and NP59 transport were under the control of cAMP, however, only cholesterol entered the mitochondria and was converted into progesterone. Thus, internalized NP59 could not be removed from the cell by conversion into steroid hormones. Esterified NP59 was metabolically inert and could not be converted back to free NP59 and free fatty acid. Since NP59 was not a substrate for the cholesteryl ester hydrolase, it became trapped in the cell as NP59 ester. (+info)
Diagnostic value of I-131 NP-59 SPECT/CT scintigraphy in patients with subclinical or atypical features of primary aldosteronism.
Diagnostic accuracy and pitfalls of [iodine-131]6-beta-iodomethyl-19-norcholesterol (NP-59) imaging.
NP-59 concentrates in steroid hormone synthesizing tissues, enabling scintigraphic localization and characterization of endocrine dysfunction in the adrenal cortex and ovary. Studying 108 consecutive cases from 1982 to 1985 and using clinical, biochemical, radiographic, and pathologic data, we performed a rigorous assessment of the accuracy and pitfalls of NP-59 scintigraphy. The evaluation was divided into categories of abnormal hormone secretion: Cushing's syndrome, primary aldosteronism, and hyperandrogenism. Additional categories included euadrenal tumors (without detectable hormone dysfunction) and sites of residual adrenal cortical tissue. The accuracy of NP-59 scintigraphy ranged from 71% in primary aldosteronism and 75% in euadrenal tumors, to 100% for Cushing's syndrome and hyperandrogenism. However, more than in most nuclear medicine studies, NP-59 imaging requires well-defined indications to be met for it to be efficacious, including the fulfillment of clear clinical, biochemical, and radiographic criteria. The high reproducibility of NP-59 scintigraphic interpretation was demonstrated when 40 random cases underwent interinstitutional exchange and through interobserver evaluation at the University of Michigan. Responses of 85/126 medical centers to questionnaires revealed the high level of NP-59 safety. (+info)
Is there a role for Nuclear Medicine in diagnosis and management of patients with primary aldosteronism?
Primary aldosteronism (PA) is the most common cause of secondary hypertension. The diagnosis of PA is of clinical importance for choosing the appropriate treatment, meaning, surgery for the unilateral disease, and inclusion of aldosterone antagonists in the antihypertensive treatment for the bilateral disease. Current diagnostic approaches showed that the prevalence of PA is much higher than previously estimated. There is still controversy regarding the true prevalence of PA in hypertensive patients. The gold standard for differentiating between unilateral and bilateral disease is the adrenal vein sampling (AVS), a method that is invasive and is performed accurately in only few dedicated centers. Non invasive methods (imaging) for discriminating the two entities are: the CT scan, MRI and iodocholesterol (NP-59) scintigraphy performed under dexamethasone suppression. But the accuracy of imaging compared to AVS is suboptimal and can result in wrong therapeutic decisions. NP-59 scintigraphy is a non-invasive functional imaging technique that reveals the adrenal cortical autonomic function and could have of incremental value over anatomical imaging. In conclusion, in previous years NP-59 scintigraphy was used infrequently, but recently with the advent of hybrid single photon emission tomography (SPET/CT) systems the interest in NP-59 scintigraphy has been renewed. Studies comparing NP-59 SPET/CT imaging with AVS are warranted in order to establish its diagnostic accuracy. (+info)
NP-59 SPECT/CT imaging in stage 1 hypertensive and atypical primary aldosteronism: a 5-year retrospective analysis of clinicolaboratory and imaging features.