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Ultrasonographic examination of the adrenal gland and evaluation of the hypophyseal-adrenal axis in 20 cats.

The adrenal glands of 20 healthy, non-sedated cats were examined ultrasonographically; visualisation and assessment was possible in all cases. In comparison with the surrounding tissue, the adrenal glands were hypoechoic and two distinct zones could be differentiated in six of the cats. The length and width of the adrenal glands varied from 0.45 to 1.37 cm and 0.29 to 0.53 cm, respectively, and both dimensions could be reliably reproduced. The adrenal glands did not differ between male and female cats, and, in comparison to dogs, those of cats are more easily visualised ultrasonographically. The basal cortisol value ranged from 2.0 to 79 micrograms/litre. Values 30 and 60 minutes after administration of ACTH (0.125 mg/cat intramuscularly) varied from 36 to 126 micrograms/litre. The basal value of aldosterone ranged from 4 to 618 pg/ml. Values 30 and 60 minutes after administration of ACTH varied from 100 to 832 pg/ml. In all cats, suppression of the cortisol value below the level of detection (< 2.0 micrograms/litre) occurred four and eight hours after the administration of dexamethasone (0.1 mg/kg intravenously).

Adrenal Glands↗

An accessory spleen mimicking a nonfunctional adrenal tumor: a potential pitfall in the diagnosis of a left adrenal tumor.

We describe a case of accessory spleen mimicking a left adrenal tumor. A 66-year-old woman was referred to our hospital because of a suspected left adrenal mass detected by US. A laparoscopic adrenalectomy was performed, and examination of the surgical specimen revealed that the resected adrenal gland contained no tumorous lesion. A further investigation of the intraperitoneal space revealed an accessory spleen. This indicates that urologists should be aware of the possible existence of accessory spleens when left adrenal tumors are suspected on CT and MRI.

Adrenal Gland Neoplasms↗

Changes of several adrenal delta 4-steroids measured by HPLC-UV spectrometry in neonatal patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

We have developed an easy and rapid method of reverse-phase high-performance liquid chromatography (HPLC)-UV spectrometry for measuring adrenal delta 4-steroids. Three female neonates with adrenal 21-hydroxylase deficiency (2 salt-losers and 1 simple virilizer), two of whom were recalled by neonatal mass-screening for congenital adrenal hyperplasia (CAH), were diagnosed using this method. Changes of several adrenal steroids were examined in these patients before and after treatment with hydrocortisone. Before treatment, the cortisone and cortisol peaks were very low and those of 17 alpha-hydroxyprogesterone (17-OHP) and 21-deoxycortisol (21-DOF) were high in all 3 patients (17-OHP: 79.9-997 nmol/l, 21-DOF: 83.7-324 nmol/l). The androstenedione peak was also high in 2 of them. A peak produced by 21-deoxycortisone, which is a product of oxidation of 21-DOF at the C-11 position, was also detected in all cases (14.5-297 nmol/l). After treatment, all of these abnormally elevated delta 4-steroids decreased or disappeared. This new method is thought to be valuable for the rapid diagnosis of CAH, and especially for use in neonatal mass-screening for CAH.

17-Hydroxycorticosteroids↗

Neonatal catecholamine content of adrenal and extra-adrenal chromaffin tissue after prenatal exposure to dexamethasone.

We investigated the effects of prenatal exposure to dexamethasone on paraganglia and adrenal catecholamine stores in rabbit neonates. We compared pregnant rabbits injected with 0.01 mg x kg(-1) of dexamethasone (Dex) from day 24 to day 27 of gestation to an untreated group of unmanipulated rabbits. A group injected with 0.9% saline solution was added to evaluate the effect of injection and handling. Catecholamines were assessed by HPLC in offspring paraganglia and adrenal glands on days 0, 1, and 7 after birth. Data were analyzed by a two-factor ANOVA and Bonferroni-Dunn and t tests. Statistical significance was accepted at p < 0.05. Paraganglia catecholamine levels were significantly higher in the Dex animals than in the untreated ones at every maturational stage studied. For saline animals, the levels were lower than in the Dex group and higher than in the untreated one. In adrenal glands, the same pattern was observed for noradrenaline only. These findings suggest that such a treatment has a positive long-term effect on catecholamine levels of both structures with a more marked effect on paraganglia, an extra-adrenal structure exerting a main function during the perinatal period in providing the child with catecholamine stores.

Adrenal Glands↗

Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function.

We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked [125I]iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions [125I]iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less. The enhanced steroidogenic responsiveness of IGF-I and insulin-treated cells were related to an enhanced capacity to produce pregnenolone and an increased activity of several steroid hydroxylases. These results indicate that both IGF-I and insulin, acting through their own receptor, play an important role in the maintenance of specific adrenal cell functions. However, at physiological concentrations IGF-I is more potent than insulin.

Adrenal Glands↗

Elevated serum interferon-gamma-inducible chemokine-10/CXC chemokine ligand-10 in autoimmune primary adrenal insufficiency and in vitro expression in human adrenal cells primary cultures after stimulation with proinflammatory cytokines.

Chemokines are a large family of cytokines involved in the pathogenesis of inflammatory and autoimmune diseases. Among CXC chemokines, CXC chemokine ligand 10 (CXCL10) has been identified to play an important role in several endocrinological autoimmune diseases, such as Hashimoto's thyroiditis, Graves' disease, and type 1 diabetes mellitus. Although the mechanisms leading to glandular autoimmune process may be at least in part shared by different endocrine organs, the role of CXCL10 in autoimmune adrenal insufficiency is unknown. The aim of this study was to evaluate the role of CXCL10 in Addison's disease (AD). Serum CXCL10 levels were assayed in 64 patients with clinically evident autoimmune AD, 20 patients with autoimmune subclinical AD, nine patients with nonautoimmune AD, and 48 healthy volunteers. Clinically evident and subclinical AD, but not nonautoimmune AD patients, showed a significant increase in serum CXCL10 levels compared with healthy subjects: 119.9 pg/ml (range, 39.8-427.6) and 124.0 pg/ml (range, 37.0-384.7) vs. 75.6 pg/ml (range, 22.4-164.0; P < 0.001 for both groups). Comparable serum CXCL10 levels were found between patients with an isolated form of AD and patients with other autoimmune conditions associated with AD, suggesting a specific influence of the adrenal autoimmune process in determining elevated CXCL10 concentrations in such patients. No relationship was found between serum CXCL10 levels and anti-21-hydroxylase or adrenal cortex autoantibody titers or between CXCL10 levels and duration of disease. The role of CXCL10 in the adrenal gland was also evaluated in vitro in human zona fasciculata cells (hZFC). CXCL10, although not basally detected in cultured hZFC, was strongly induced by interferon-gamma and synergistically increased by TNF-alpha addition. Hydrocortisone or ACTH alone had no effect on CXCL10 secretion in hZFC, but they both significantly inhibited cytokine-induced CXCL10 secretion. Taken together, these data suggest a potential role of hZFC, through the production of CXCL10, in regulating the recruitment of specific subsets of activated lymphocytes in autoimmune AD.

Addison Disease↗

Differential zonal expression and adrenocorticotropin regulation of secreted protein acidic and rich in cysteine (SPARC), a matricellular protein, in the midgestation human fetal adrenal gland: implications for adrenal development.

CONTEXT: Matricellular proteins are a group of secreted, multifunctional extracellular matrix glycoproteins that includes thrombospondins (TSPs), tenascin-C, and secreted protein acidic and rich in cysteine (SPARC). They may be implicated in the dynamic developmental processes of the human fetal adrenal (HFA) in which the outer, definitive zone (DZ) cells are postulated to proliferate, migrate centripetally, differentiate, and populate the inner, steroidogenic fetal zone (FZ). OBJECTIVE: The objective of the study was to identify a matricellular molecule that likely plays a major role in HFA development. DESIGN: Studies involved RNA, cryosections, and cell cultures from 14- to 23-wk HFAs and human adult adrenal RNA. MAIN OUTCOME MEASURES: Measures included transcripts encoding matricellular proteins, using real-time quantitative RT-PCR; SPARC localization by immunostaining; and ACTH regulation of SPARC expression and secretion by quantitative RT-PCR and Western blot. RESULTS: SPARC HFA mRNA was 100-, 700-, and 300-fold higher than TSP-1, TSP-2, and tenascin-C mRNA, respectively. HFA SPARC mRNA was 3-fold higher than adult adrenals (P < 0.005), comparable with levels in adult brain (positive control), whereas mRNAs encoding TSP-1 and TSP-2 were lower in fetal than adult adrenals. SPARC immunoreactivity was detected exclusively in the FZ, not DZ. ACTH, a key regulator of HFA growth and function, increased SPARC mRNA (by 1.7-fold at 1 nm, 48 h, P < 0.05) in isolated FZ cells but not DZ cells. ACTH up-regulation of SPARC protein was also detected in FZ cell lysates and culture medium. CONCLUSIONS: Results suggest a possible role for SPARC in development of functional and/or structural zonation of the HFA.

Adrenal Glands↗

A case of ACTH-independent bilateral macronodular adrenal hyperplasia successfully treated by subtotal resection of the adrenal glands: four-year follow-up.

We report ACTH-independent bilateral macronodular adrenal hyperplasia (AIMAH) seen in a 48-year-old male with a history of rectal and skin cancer. Bilateral multiple adrenal nodular lesions on abdominal CT scans, elevated early morning plasma cortisol levels with undetectable plasma ACTH, increased 24-hour urinary free cortisol excretion, and loss of the normal circadian rhythm in cortisol secretion established the diagnosis of AIMAH. Subtotal resection of the adrenal glands preserving lower one third of the left side was performed, considering the unfavorable effects of total adrenalectomy on future treatment of his malignancies. He has been doing well for four years with normal plasma ACTH and cortisol levels. This case suggests that subtotal resection of the adrenal glands may be applicable to selected patients.

Adrenal Glands↗

Conversion of 22S-hydroxy-cholesterol and its effects on the metabolism of other sterols in rat adrenal cells and bovine adrenal mitochondria.

This study provides evidence that 22S-OH-cholesterol inhibits the conversion of 25-OH-cholesterol but has no effect on the conversion of 22R-OH-cholesterol. The latter sterol is an intermediate in the cholesterol side-chain cleavage, whereas for the conversion of 25-OH-cholesterol into pregnenolone the complete side-chain cleaving enzyme system is necessary. This complements a previous study in which it was shown, that 22S-OH-cholesterol has an inhibitory effect on the ACTH-induced conversion of cholesterol into corticosterone in isolated rat adrenal cells. The available evidence thus suggests an inhibition by 22S-OH-cholesterol of the first step in the cholesterol side-chain cleavage. The results, obtained from the experiments with rat adrenal cells and with bovine adrenal mitochondria, allow the hypothesis, that a causal relationship exists between conversion of 22S-OH-cholesterol and production of corticosterone, respectively pregnenolone. We conclude, that 22S-OH-cholesterol is a substrate for steroid production in the adrenal cell. This sterol inhibits the ACTH-stimulated corticosterone production. The site of this inhibition is located at one of the first steps in the cholesterol side-chain cleavage, probably the binding of cholesterol to the cytochrome P450-complex.

Adrenal Glands↗

Postoperative differentiation between unilateral adrenal adenoma and bilateral adrenal hyperplasia in primary aldosteronism by mRNA expression of the gene CYP11B2.

OBJECTIVE: Primary aldosteronism (PA) is characterized by hypertension, hypokalemia and suppressed renin-angiotensin system caused by autonomous aldosterone production. The aim of this study was to localize mRNA expression of the genes coding for steroidogenic enzymes in adrenals from a group of patients with PA and relate this to clinical work-up, histopathology and outcome of adrenalectomy. DESIGN: This was a retrospective study of 27 patients subjected to adrenalectomy for PA. METHODS: Clinical data were collected and follow-up of all patients was performed. Paraffin-embedded specimens were analyzed by the in situ hybridization technique, with oligonucleotide probes coding for the steroidogenic enzyme genes. RESULTS: The resected adrenals had the histopathologic diagnosis of adenoma (11), adenoma and/or hyperplasia (15) or hyperplasia (1). CYP11B2 expression (indicating aldosterone production) was found in a dominant adrenal nodule from 22 patients. Fourteen of these had additional CYP11B2 expression in the zona glomerulosa. All 22 patients were cured of PA by adrenalectomy. One of these patients, who had additional high expression of CYP11B2 in the zona glomerulosa, was initially cured, but the condition had recurred at follow-up. Two patients had a mass shown on computed tomography without CYP11B2 but with CYP11B1 and CYP17 expression (indicating cortisol production). Instead their adrenals contained small nodules with CYP11B2 expression. These patients were not cured. CONCLUSIONS: Clinical data, endocrinologic evaluation and histopathology in combination with mRNA in situ hybridization of steroidogenic enzyme genes provide improved opportunities for correct subclassification postoperatively of patients with primary aldosteronism. At present, the in situ hybridization method is of special value for analysis of cases not cured by adrenalectomy.

Adenoma↗

The natural history of adrenal function in autoimmune patients with adrenal autoantibodies.

Adrenal autoantibodies (AA) were found in 23 of 2571 (0.9%) patients with organ-specific autoimmune diseases, in one of 632 first-degree relatives of insulin-dependent diabetic patients, and in none of 375 normal controls. In AA-positive subjects the prevalence of human leucocyte antigens (HLA)-A1, -B8 and -DR3 was significantly higher with respect to the general population. Two groups were followed (15 subjects persistently positive for AA and 51 negative subjects) for a mean period of 3.2 years. Yearly tests were made for AA and adrenal function. Of the 15 subjects persistently positive for AA, six developed Addison's disease after a period varying from 6 months to 10 years. Of the 51 subjects initially negative, two became positive during follow-up, and one of these developed Addison's disease 15 months later. In contrast, all the remaining 49 persistently negative subjects maintained normal adrenal function tests. Overall, of the 17 positive subjects, seven (41%) developed Addison's disease, three (18%) showed various degrees of subclinical adrenocortical failure and the remaining seven maintained normal glandular function. In the positive patients the yearly incidence of detriment in adrenal function was 19%. Patients who developed Addison's disease showed significant association with HLA-B8 phenotype. The development from normal adrenocortical function to overt Addison's disease seemed to progress through four distinct stages of functional impairment: increased plasma renin activity with normal/low aldosterone (stage 1), low cortisol response after i.v. administration of ACTH (stage 2), increased ACTH (stage 3), and low basal cortisol (stage 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Identification of the adrenal protease that cleaves pro-gamma-MSH: the dawning of a new era in adrenal physiology?

In respect to growth, the adrenal is a dynamic organ that requires constant stimuli from pituitary-derived POMC peptides to maintain its tonic state since either hypophysectomy or dexamethasone treatment results in rapid adrenal atrophy. It has been previously demonstrated that peptides derived from the N-terminus of the 16 kDa fragment of POMC not containing the gamma-MSH sequence are potent adrenal mitogens both in vitro and in vivo. However, since these shorter peptides are not found in the circulation, it has been suggested that they are generated by cleavage of the 16 kDa fragment by a specific protease expressed by the adrenal. This putative enzyme has recently been identified and this commentary describes the findings to date and highlights some of their possible implications.

Adrenal Cortex↗

[A rare form of adrenal tuberculosis presenting as an asymptomatic adrenal mass].

The authors report a case of adrenal tuberculosis discovered during staging of a biopsy-confirmed bladder tumour, in a 70-year-old patient consulting for haematuria. Cystoscopy with biopsy revealed a high-grade papillary urothelial carcinoma invading the detrusor. Staging abdominopelvic computed tomography revealed a necrotic, multilobed right adrenal mass. Histological examination of the adrenalectomy specimen revealed adrenal tuberculosis. Antituberculous therapy was administered for 9 months and comprised streptomycin, isoniazid, rifampicin and pyrazinamide for 2 months, followed by rifampicin and isoniazid for 7 months. In the light of this case and with the increasing incidence of AIDS, the diagnosis of adrenal tuberculosis must be considered in any case of incidentaloma.

Adrenal Gland Diseases↗

The innervation of the adrenal gland. IV. The source of pre- and postganglionic nerve fibres to the guinea-pig adrenal gland.

The pre- and postganglionic sympathetic innervation of the guinea-pig adrenal medulla was investigated using the retrograde neuronal tracers Fast Blue and WGA-HRP. Labelled preganglionic cell bodies were located in the intermediolateral horn of spinal segments T3-L2, the majority (73.9%) were found between T6-T12 representing 70.2% of the total number of labelled cells; the segment T10 contained the largest number of labelled neurons. Labelled postganglionic cell bodies were found in the paravertebral ganglia between vertebral levels T3-T12 (representing 22.6% of the total labelled neurons), the maximum number was found at T10. In addition, labelled neurons were found in the suprarenal ganglion (representing 7.2%). No labelled cells were found in the coeliac ganglia. The labelled neurons were found ipsilateral to the site of injection into the left adrenal gland. It is concluded that the guinea-pig adrenal gland receives both a pre- and a significant postganglionic sympathetic innervation. The destination of these nerve fibres within the adrenal gland has yet to be determined.

Adrenal Glands↗

[Two cases of adrenal cysts--the meaning of imaging in diagnosing adrenal cysts].

Two cases of adrenal cysts are reported. The first case is of a left adrenal cyst in a 19-year-old woman and was incidentally discovered by computed tomography (CT). Its margin was clear, its contents was homogeneous and its signal indicated water contents on magnetic resonance imaging (MRI). It was punctured and is now followed up by CT. The second case is of a left adrenal cyst in a 62-year-old woman, which also happened to be discovered by CT. Its contents was heterogeneous by MRI. It was removed and proved to be a lymphangiomatous cyst. The conclusion is that MRI will be useful in the differential diagnosis of adrenal cysts.

Adrenal Gland Diseases↗

Adrenal myelolipomatous nodules mimicking adrenal neoplasms: report of three cases.

The authors describe three cases of adrenal myelolipoma. In the first two, unilateral adrenal masses, assumed to represent adrenal neoplasms, were found during urologic examination; the correct diagnosis was made by frozen-section examination during operation. The third case involved bilateral adrenal lesions diagnosed at autopsy in a patient suspected to have metastatic cancer. Histologic, immunohistochemical and electron microscopic studies revealed polyclonal lesions composed of hematopoietic cells and fat cells. Radiologic recognition and fine-needle biopsy of these lesions are important to avoid unnecessary surgery in asymptomatic cases. Since the lesions cannot be regarded as true neoplasms, the authors suggest that the name myelolipoma should be replaced by the term myelolipomatous nodule.

Adenoma↗

Adrenic acid content in rat adrenal mitochondrial phosphatidylethanolamine and its relation to ACTH-mediated stimulation of cholesterol side chain cleavage reaction.

We have isolated various phospholipids from adrenal mitochondria of adrenocorticotropic hormone (ACTH)-treated (stimulated) and cycloheximide/ACTH-treated (unstimulated) rats. When the effects of these phospholipids were examined on the formation of pregnenolone from endogenous cholesterol by adrenal mitochondria of unstimulated rats, phosphatidylethanolamine and phosphatidylserine from stimulated mitochondria were effective in enhancing the cleavage reaction in unstimulated mitochondria, whereas these phospholipids from unstimulated mitochondria were all ineffective. Cardiolipins from both stimulated and unstimulated mitochondria were effective. When the compositional changes in fatty acid moiety of phospholipids were examined, a significant increase in C22:4 (adrenic) acid was observed only for phosphatidylethanolamine under the influence of ACTH. A linear relationship between the contents of C22:4 acid in various phospholipids and respective steroidogenic activities was obtained (r = 0.880), suggesting an important role of this fatty acid moiety. The separation of active phosphatidylethanolamine by high performance liquid chromatography revealed that a fraction containing 25% C22:4 acid was most effective in the activation. Based on these results, it is most likely that 1-stearoyl-2-adrenoyl phosphatidylethanolamine is an active species. C22:4 acid was liberated together with C20:4 acid from adrenal triglycerides by the action of ACTH but the liberation was insensitive to cycloheximide inhibition. Finally, cardiolipin which enhances the transfer of cholesterol to cytochrome P-450scc may not be a physiological mediator of ACTH action.

Adrenal Glands↗

[Glucocorticoid and androgenic functions of the adrenal cortex and the state of the sympathetic-adrenal system in thyrotoxicosis with primary organic disease of the central nervous system].

In patients with thyrotoxicosis combined with primary affection of the central nervous system (CNS)-encephalitis, diencephalitis-there was revealed, like in common thyrotoxicosis, an increased production by the adrenal cortex of hydrocortisone, its intensified transformation and inactivation, reduced production of 17-ketosteroid chiefly due to the fall of dehydroepiandrosterone content, an increased urinary excretion of adrenaline and a decreased-of noradrenaline. The use of functional test with the ACTH administration demonstrated organic affection of the CNS to sharply aggravate the weakening and even the exhaustion of the functional reserves of the glomerular and the reticular zones of the adrenal cortex developing during thyrotoxicosis, and also the reserve possibilities of the sympathico-adrenal system. Direction of the changes in the 24-hour excretion of 17-OCS and corticosteriods was the same in the majority of cases. The latter can point to the presence of functional association between the hypothalamus-hypophysis-adrenal cortex systems and adrenergic regulation in these patients.

17-Hydroxycorticosteroids↗