Usefulness of adrenal scintigraphy in the follow-up of adrenocortical incidentalomas: a prospective multicenter study

ObjectivesPrognostic factors for progression of benign adrenocortical adenomas (AI) remain poorly known. We assessed the usefulness of 131I-6-β-iodomethylnorcholesterol scintigraphy (IMS) to predict the occurrence of adrenal hyperfunction or mass enlargement.DesignFifty-one consecutive inpatients with unilateral AI and normal 24-h urinary free cortisol (UFC) were enrolled in a multicenter observational prospective study to investigate the relationship between the scintigraphic pattern and the progression of biological abnormalities of the hypothalamo-pituitary–adrenal axis or tumor size.ResultsBiochemically defined ‘subclinical’ Cushing's syndrome (SCS) was found at baseline in 47% of patients. Unilateral uptake (UU) was significantly associated with SCS (P<0.05). During the follow-up (4.3±1.6-year): 53% of patients showed unchanged hormonal evaluation, 29% displayed intermittent SCS and 18% showed definitive hormonal progression of SCS but without overt biochemical hypercortisolism. UU was associated with persistence of SCS and hormonal progression (P<0.01). In multivariate analysis, UU and impaired 1 mg dexamethasone suppression were independently associated with hormonal progression. Three patients with UU developed clinical CS despite persistently normal UFC. Tumor size increased in 10% patients and was not associated with any scintigraphic pattern.ConclusionEvolution of SCS toward overt biochemical CS in patients with AI is a rare event during a 4-year follow-up. UU is predictive for the occurrence of SCS, its persistence and progression within the spectrum of SCS. Further studies aiming to establish the clinical consequences of SCS are needed to recommend IMS as a complementary evaluation in patients with AI and biochemical SCS.

HYPOTENSIVE DRUGS EFFECT AND LIVER MONOOXIGENASE FUNCTION IN ARTERIAL HYPERTENSION PATIENTS AFTER ADRENAL HYPERFUNCTION CORRECTION

Hypotensive drug tolerance and liver monooxygenase activity were investigated in 24 refractory arterial hypertension patients before and after surgical suppression of adrenal hyperfunction. Liver monooxygenase activity was studied using antipyrine test. It was found that hypotensive drug tolerance was decreased after one and two side operations on adrenal glands. In parallels halftime of antipyrine elimination was shown to be prolonged by 88.5% in 3 months - 3 years after suppression of adrenal hyperfunction. Our findings suggest that the hypotensive drug tolerance diminution may be the consequence of liver monooxygenase activity reduction. This assumption is in accordance with well known the hypotensive drug metabolism by microsomal liver monooxygenases

Risk Factors and Long-Term Follow-Up of Adrenal Incidentalomas1

The natural course of adrenal incidentalomas and the risk that such lesions evolve toward hormonal hypersecretion or malignancy are still under evaluation. Of 246 consecutive patients with adrenal incidentaloma studied at our institution in the last 15 yr, 91 underwent surgery. Of the remaining patients, a group of 75 (52 females and 23 males; median age, 56 yr; range, 19–77 yr) with incidentally discovered asymptomatic adrenal masses (60 unilateral and 15 bilateral; median diameter, 2.5 cm; range, 1.0–5.6) was enrolled in an endocrine and morphological follow-up of at least 2 yr after diagnosis (median, 4 yr; range, 2–10). During follow-up, no patients developed malignancy; 9 showed mass enlargement, with appearance of a new mass in the contralateral gland in 2; 3 developed adrenal hyperfunction (overt Cushing’s syndrome in 2, nonclinical hypercortisolism in 1); and 3 showed adrenal mass enlargement associated with adrenal hyperfunction (nonclinical hypercortisolism in 2, pheochromocytoma in 1). The estimated cumulative risks to develop mass enlargement and hyperfunction were 8% and 4%, respectively, after 1 yr, 18% and 9.5% after 5 yr, and 22.8% and 9.5% after 10 yr. Nine risk factors for adrenal mass enlargement or hyperfunction were arbitrarily selected and evaluated: sex, age, presence of obesity, hypertension, diabetes, abnormal endocrine tests, mass size, mass location, and scintigraphic uptake pattern. Three of them attained statistical significance: mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake by the mass at scintigraphy had relevance for the occurrence of adrenal hyperfunction, whereas the presence of endocrine test abnormalities at diagnosis had predictive value for mass enlargement. It is concluded that subtle hormonal abnormalities are risk factors for mass size increase, which is not a sign of malignant transformation. Both mass size of 3 cm or more at diagnosis and exclusive radiocholesterol uptake, indicating higher risks of hyperfunction, should be considered to plan a more thorough endocrine follow-up.

Defective cortisol binding globulin affinity in association with adrenal hyperfunction: a case report

A patient with an apparent abnormality of cortisol binding globulin (CBG) is reported. Investigations showed that while the plasma CBG binding capacity (equivalent to the plasma CBG concentration) was normal, the binding affinity was reduced by a factor of four. The significance of this observation is discussed with regard to its possible role in the development of the adrenocortical hyperfunction also seen in this patient.

STEROID SYNTHESIS IN A HUMAN VIRILISING ADRENAL CARCINOMA – SOME UNUSUAL FEATURES

ABSTRACT A patient presenting at the Universitäts-Frauenklinik, Berlin with a long history of increasing hirsutism and virilism provided an opportunity to study an unusual form of adrenal hyperfunction. It was found that she behaved abnormally with respect to the dexamethasone suppression test since her highly elevated 17-oxosteroid output further increased by approximately 400% with 8 mg/day dosage. Her basal 17-hydroxycorticosteroid output was elevated but not grossly so, nor did she exhibit the usual signs of Cushing's syndrome of weight increase and florid complexion. At operation a »tennis ball« size adrenal carcinoma was removed from the left side. Incubation studies were performed on sliced tumour tissue with substrates [1-14C] acetate, [7α-3H] pregnenolone, [4-14C] progesterone and [4-14C] androst-4-ene-3,17-dione. The frozen incubation mixtures were subsequently flown to Cardiff for steroid analysis by reverse radioisotope dilution techniques. The combined urinary and incubation results suggested that, in vivo, the tumour secreted DHA and not DHA sulphate and that there appeared to be a considerable deficiency of DHA-3β-hydroxysteroid dehydrogenase/Δ5−4-isomerase and of DHA-3β-sulphokinase activities although the steroid-11β-hydroxylase, 17α-hydroxylase and 21-hydroxylase activities seemed unimpaired.