Ultrastructural types of cell in adrenal cortical adenoma with primary aldosteronism.

By means of electron microscopy, three types of cell were identified in the adrenal cortical adenomas obtained by surgery from three patients with primary aldosteronism. They were zona glomerulosa-type cells, compact cells and clear cells. The former two types of cell were quite similar to those found in the zona glomerulosa and the zona reticularis respectively. The clear cell with large lipid vacuoles possessed mitochondria similar to those found in the outer zona fasciculata. The ultrastructure of the vacuoles was rather complex and their relationship to those in the zona fasciculata cell was not clear. Glycogen particles in the beta-form, which were present in the zona glomerulosa and reticularis cell but not in the zona fasciculata cell, were observed within the cytoplasm of this tumour cell. The clear cells of the tumours were therefore considered to possess features of both the zona glomerulosa and the zona fasciculata cell.     

The fine structure of the zona glomerulosa and the zona fasciculata of the adrenal cortex of the opossum

The normal fine structure of the zona glomerulosa and the zona fasciculata of the opossum is described, with emphasis on the structure of the smooth surfaced endoplasmic reticulum (SER) and mitochondria. The cells of the zona glomerulosa are characterized by the presence of numerous rod-shaped mitochondria with shelf-like cristae, small amounts of tubular SER and moderate amounts of rough surfaced endoplasmic reticulum. The cells of the zona fasciculata possess large quantities of SER, spherical mitochondria with tubular cristae and a few profiles of rough surfaced reticulum. A Golgi apparatus is present in cells of both zones as are coated vesicles, coated invaginations of the plasmalemma, lysosomes and lipid droplets. It is concluded that the tubular SER seen in electron micrographs corresponds closely to the form of this membrane system found in the living cell. The functional significance of the associations observed among lipid droplets, mitochondria and SER are discussed.     

The ultrastructural features of secretory cells of some endocrine glands in aging

In the electron microscopic investigation of the secretory cells of adenohypophysis, adrenal cortex, adrenal medulla and pancreatic islets from the adult and old Wistar male rats, certain age-related ultrastructural features have been found. Age changes appeared to be more pronounced in the thyrotrophs, somatotrophs and gonadotrophs of the adenohypophysis and in zona glomerulosa and zona reticularis spongiocytes of the adrenal cortex. They consisted of atrophy of the Golgi apparatus, appearance of the cytoplasmic vacuoles, lipid and lipofuscin granules, secondary lysosomes and damage of the inner mitochondrial membrane. Parallel to these, hypertrophy of the Golgi apparatus and rough endoplasmic reticulum, formation of giant mitochondria and presence of a great number of secretory cells in the cellular cytoplasm were noted in zona fasciculata spongiocytes and chromaffin cells of the adrenal medulla, and in beta cells of the pancreatic islets during aging thus evidencing for the adaptive changes in the ultrastructure of these cells. However, no appreciable age changes have been observed in the ultrastructure of the adrenocorticotropic cells of the adenohypophysis.     

Ultrastructural analysis of the adrenal cortex in rats after bilateral subdiaphragmatic vagotomy

Electron-microscopic investigation of the zona fasciculata and zona reticularis of the adrenal cortex in rats showed that 7 days after bilateral subdiaphragmatic vagotomy the perinuclear space of the adrenocorticocytes and endothelial cells is widened, the tubules of the smooth cytoplasmic reticulum are dilated, the mitochondria edematous, their cristae reduced, and the number and size of the lipid droplets diminished. After 45 days some mitochondria were starting to undergo myelinization, lipid droplets were aggregating, and electron-translucent vacuoles appeared in them. Vagotomy depresses the function of the adrenocorticocytes of the zona fasciculata and zona reticularis of the rat adrenal cortex.Department of Histology and Embryology, Faculty of Internal Medicine, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. P. Avtsyn.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 4, pp. 492–494, April, 1977.     

The adrenal cortex in spontaneously hypertensive rats. A quantitative ultrastructural study.

The adrenal cortex of spontaneously hypertensive rats (SHR) has been examined by quantitative morphologic techniques for electron microscopy. The volume and surface area of smooth endoplasmic reticulum and the volume of Golgi apparatuses in zona glomerulosa cells of SHR was significantly greater than those of Wistar-Kyoto strain (W/KY) normotensive controls; the volume of lipid droplets and nucleus was significantly less in SHR than in W/KY animals. A stimulation of the zona glomerulosa in SHR may well be attributable to the elevation in systolic blood pressure. A distinct lipid-free subglomerulosa was observed in the adrenal gland of W/KY rats; the cell volume was similar to that of the zona glomerulosa although the cells showed a significantly greater volume of mitochondria and surface area of mitochondrial membranes and greater volume of smooth endoplasmic reticulum and lysosomes. In the zona fasciculata, cell volume, volumes and surface area of mitochondria and smooth endoplasmic reticulum, and volume of lipid droplets were significantly lower in SHR than in W/KY rats. The volume of the Golgi apparatus was greater in SHR than in W/KY rats. Glycogen particles were observed in focal areas of some zona fasciculata cells. The adrenal cortex of another strain of normotensive Wistar rat (W/CFN) was compared with that of the W/KY and SHR. Although the relative adrenal weights of SHR and W/KY animals were identical, the weight of that in W/CFN was significantly smaller. The volume of the zona glomerulosa of SHR was significantly greater than that of W/KY although the volume of the zona glomerulosa in W/CFN was significantly greater than the other two groups. The volume of nucleus and lipid droplets of zona glomerulosa in W/KY was significantly greater than that in the S/CFN; the volume of the cell, mitochondria, smooth endoplasmic reticulum, lipid droplets, and lysosomes, and the surface area of smooth endoplasmic reticulum and mitochondrial membranes of W/KY animals was significantly greater than those of W/CFN animals. It is concluded that the W/CFN rat is not an appropriate control for spontaneously hypertensive rats.     

Comparative studies on the effects of aminoglutethimide on hamster and rat adrenal cortex.

Adult female, intact or steroid suppressed hamsters were treated twice daily with 7 mg aminoglutethimide phosphate (AG) for 5 days while intact female rats received 14 mg AG per injection. AG resulted in an increase in adrenal gland weight of both hamster and rat. In the hamster AG had no effect on the amount of lipid droplets while in the rat a slightly higher number of fine lipid vacuoles was seen. In the hamster, enlargement of the gland was due to hyperplasia of the zona reticularis cells while in the rat the number of glomerulosa and fasciculata cells increased. AG had no effect on the adrenal cortex of steroid suppressed hamsters. The serum cortisol level was markedly higher in AG-treated hamsters while the corticosterone level was notably lower in AG-administered rats. In both hamsters and rats, AG-treatment did not change the serum ACTH level. Thus the study demonstrated different responses of the hamster and rat adrenal cortex to AG.     

Heterogeneous levels of oxidative phosphorylation enzymes in rat adrenal glands

Mitochondria are organelles that produce ATP and reactive oxygen species, which are thought to be responsible for a decline in physiological function with aging. In this study, we morphologically and biochemically examined mitochondria in the rat adrenal gland. Immunohistochemistry showed that the rank order for intensity of immunolabelling for complex IV was zona reticularis > zona fasciculata ? adrenal medulla, whereas for complex V α and β subunits, it was zona fasciculata > zona reticularis and adrenal medulla. The immunolabelling for complex I was homogeneous in the adrenal gland. The difference in immunolabelling between complexes I and IV indicates that the ratio of levels of complex I to that of complex IV in the zona reticularis was smaller than that in the zona fasciculata and the adrenal medulla. Electron microscopy revealed that aging rats had zona reticularis cells with many lysosomes and irregular nuclei. The result suggests that the level of proteins involved in oxidative phosphorylation is coordinated within the complex, but differs between the complexes. This might be responsible for degeneration of zona reticularis cells with aging.     

ULTRASTRUCTURAL ZONATION OF THE HUMAN ADRENAL CORTEX

Electron microscopic observations of sections from adrenal cortex obtained from a twenty-four-year-old male with hypertension were made. In the zona glomerulosa the cells showed a large nuclear-cytoplasmic ratio. The mitochondria had a dark matrix and plate-like inner structure. The agranular endoplasmic reticulum revealed a close association with lipid granules. The Golgi apparatus was prominent and frequently accompanied by centrioles. Free ribosomes were abundant. The zona fasciculata can be subdivided into two layers. In the outer layer the cells are characterized by numerous large lipid granules. Two kinds of mitochondria are discernible; one with a pale matrix and tubulo-vesicular or vesicular inner structure and the other with a dark matrix and tubulo-vesicular or lamelllform cristae. In the inner zona fasciculata and reticularis there are two types of cells besides the dark cells. The type 1 cells have a compact cytoplasm, elliptic or irregularly shaped mitochondria with a dark matrix and tubulo-vesicular or vesicular internal structure. The type 2 cells are large and ovoid, having a clear transparent cytoplasm. The mitochondria are numerous having a clear matrix and almost exclusively vesicular inner elements. Abundance in agranular endoplasmic reticulum, decreased lipid granules, and cytoplasmic incisions are common in both the inner fasciculata and reticularis. In addition the zona reticularis is characterized by increased number of dark cells, numerous pigment bodies, and the appearance of huge mitochondria.
On the basis of these observation were discussed the significance of the organelles in steroid biosynthesis, mode of hormone secretion, and cyto-genesls in the adrenal cortex.     

Zur Ultrastruktur der atrophischen Nebennierenrinde bei dissoziierter,sekundärer Nebennierenrindeninsuffizienz

Summary The atrophic adrenal cortex associated with corticosteroid-producing tumours was investigated by electron microscopy in 5 cases. The well-preserved zona glomerulosa was easily distinguished from lipid-rich glomerular cell complexes of the outer zona fasciculata in epoxy sections. Little difference from normal ultrastructure was observed in the cells of the zona glomerulosa. The zona fasciculata-reticularis, however, showed marked changes in the ultrastructure. The mitochondria are diminished, with reduced internal structures. Almost no agranular endoplasmic reticulum is evident. The fasciculata cells contain huge membranebound lipid vacuoles. Comparable ultrastructural changes in animals have been described after hypophysectomy or after treatment with glucocorticoid hormones. The electron microscope findings are considered to be the result of the suppression of ACTH secretion and probably of a direct inhibition of protein synthesis in adrenocortical cells by the elevated steroid hormone levels produced by the adrenal tumours.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft (Sonderforschungsbereich 34 Endokrinologie).     

Effects of exogenous ACTH on the rat fetal adrenal cortex: a histochemical and electron-microscopical observation.

ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be specifically related to the development and differentiation of the cells.     

Fat accumulation in tha adrenal gland: effect of oestradiol benzoate on the zona reticularis of the Mongolian gerbil adrenal gland.

Oestrogen promotes accumulation of abundant lipid droplets in the zona reticularis of the Mongolian gerbil. Lipid was observed in zona reticularis parenchymal cells but droplets were especially numerous in macrophages. Enlargement of lipid droplets was facilitated by an envelopment with lysosomal membranes. Focal areas or entire parenchymal cells may then undergo degeneration and necrosis and be incorporated into large macrophages recognizable by distinct areas of lipid-containing material as well as by small mitochondria with short cristae. Oestrogen may well act directly on zona reticularis cells inasmuch as nafoxidine, an antioestrogen, prevents these changes. Zona fasciculata cells were identical to those in controls and an intermediate region between the zona fasciculata and zona reticularis persists, although concentric whorls of rough endoplasmic reticulum seen in controls were replaced by disorganized, randomly dispersed cisternae of rough endoplasmic reticulum. Oestrogen does not elevate cortisol in the plasma.     

Ultrastructure of the fetal rat adrenal gland at full-term and during prolonged gestation

The ultrastructure of the fetal rat adrenal gland is described at full-term (day 22) and during artificially prolonged gestation (days 23, 24, 25). The latter was achieved by daily subcutaneous injections of seven mg progesterone to gravid females from the twentieth through the twenty-fourth day. Cortical and medullary cells contained well developed organelles at all stages. Nonetheless, zonation of the gland was not yet distinct. Whereas the zona glomerulosa and zona fasciculata were fairly well delineated, the zona reticularis and medulla were as yet poorly defined. The latter regions were intermingled, and thus collectively referred to as the “zona reticulo-medullaris.” During prolonged gestation (days 24 and 25 only), many cells of the zona fasciculata and zona reticulo-medullaris contained dilated smooth endoplasmic reticulum and numerous enlarged mitochondria. Enlarged mitochondria were observed also in medullary cells concurrent with a paucity of catecholamine storage granules. Moreover, meconium staining, which is indicative of fetal stress, was also observed on days 24 and 25. The ultrastructural changes observed were interpreted to be an expression of response by the fetal adrenal gland to fetal stress produced by as yet undetermined factors arising during prolonged gestation.     

ELEKTRONENMIKROSKOPISCHE UND ELEKTRONENMIKROSKOPISCH-HISTOCHEMISCHE UNTERSUCHUNGEN UBER NEBENNIERENRINDE DER RATTE MIT AMINOGLUTÄTHIMID (ELIPTEN, CIBA) ÜND UBER IHREN REPARATURPROZESS.

Amlnoglutethimide blocks the conversion of free cholesterln to 5-pregnenolone. It's effects on the fasciculata cells were studied electron microscopically in Wistar rats fed with this chemical for a maximum of seven days. The animals surviving after this treatment were also examined to follow the process of restoration from the damage. Four to seven days after the initiation of the feeding, the mitochondria were enlarged, variously deformed and contained intramitochondrial vacuoles. The lipid droplets were increased in size. Three to four days after withdrawal of amlnoglutethimide, so-called "Intramitochondrial mitochondria" appeared. The picture suggesting division of the mitochondrial matrx was also occasionally encountered. These features suggested formation of new mitochondria from preexisting mitochondria. The mltohchondrla resumed their normal shape and appearance starting about ten days after withdrawal of amlnoglutethimide. The electron microscopic histochemlcal method demonstrated tubular crystals of digitonin-cholesterid in the intramitochondrial vacuoles as well as in the lipid droplets 4 days after the initiation of the feeding. The withdrawal of amlnoglutethimide was followed with disappearance of these crystals from the sites of deposition.     

Spontaneous or experimentally induced formation of a special zone in the adrenal cortex of the adult brush-tailed possum (trichosurus vulpecula)

The cytology and ultrastructure of the hypertrophied special zone, which is formed spontaneously in the adrenal cortex of adult female brush-tailed possums (Trichosurus vulpecula), was compared to the adrenocortical tissue in adult males in which the special zone, normally absent, was induced following castration alone or by additional treatment with folliclestimulating hormone (FSH). The special zone in females was situated between the zona fasciculata and the zona reticularis, the latter being a rudimentary zone in this species. Special zone tissue extended as a broad band parallel to and on one side of the adrenal medulla. In the luteal phase of the reproductive cycle, the special zone cells showed ultrastructural features commonly associated with steroidogenic tissues, with many mitochondria and compact masses of smooth endoplasmic reticulum. Cytoplasmic lipid inclusions were rarely observed. In lactating females, however, the special zone cells exhibited cytological and ultrastructural features suggestive of a transformation in their morphology broadly divided into two types of cells: (1) cells at the periphery of the special zone (closest to the zona fasciculata) showed variable quantities of lipid inclusions, mitochondria with dispersed cristae, and segregation of the smooth endoplasmic reticulum into compact masses; (2) cells within the more central regions showed an increasing abundance of lipid inclusions which in many cells became the dominant feature of the cytoplasm. These special zone cells contained very little smooth endoplasmic reticulum and their mitochondria contained few cristae together with amorphous granular material within the matrix. In castrated males, special zone tissue developed between the zona fasciculata and the zona reticularis, appearing initially as focal islands of cells (8 months postcastration) and later (11 months postcastration) expanding into a single zone, probably via the proliferation and differentiation of adjacent cells of the zona fasciculata and longitudinal growth of the special zone. Similar focal aggregations of special zone cells were induced after 14 days of FSH treatment given to 2-month castrated males. In all castrated and FSH-treated castrated males, the ultrastructure of special zone cells was similar to that of special zone cells in luteal-phase female possums. The findings suggest that the formation and cellular composition of the special zone is associated with changes in the pituitary-gonadal axis and that FSH plays a primary role in the differentiation of this tissue.     

EFFECTS OF EXOGENOUS ACTH ON THE RAT FETAL ADRENAL CORTEX: A HISTOCHEMICAL AND ELECTRON-MICROSCOPICAL OBSERVATION

ACTH was administered subcutaneously to rat fetus directly at the late stage of fetal development and acute reaction on the fetal adrenal cortex was observed histochemically and electron microscopically. By administration of ACTH the adrenal cortex became remarkably hyperemic and there were swollen cells in all layers, particularly in the middle and inner layers (corresponding to the zona fasciculata and reticularis in adult rat). Marked reduction of lipid, enlarged mitochondria with increased vesicular cristae and increased smooth-surfaced endoplasmic reticulum (SER) were characteristic. The alterations of mitochondria preceded the change of SER, and thereafter mitochondria showed rapid degeneration. The outer layer (corresponding to the zona glomerulosa in adult rat) also showed similar changes by ACTH to those of the other two layers. These results indicated that the fetal adrenal cortex of rats was exogenous ACTH-reactive and its reaction which was different from that of adult cortical cells, seemed to be speciflcally related to the development and differentiation of the cells. ACTA PATH. JAP. 27 : 477–484, 1977.     

Interrenal cell zonation in the adrenal gland of the goose (Anser anser)

The adrenal medulla in mammalian species is surrounded by a cortex that contains three distinct layers, whereas the cortex and medulla are intermingled in poultry species. The objective of the present study was to determine the distinct zonation changes in the adrenal cortex of geese in various ages using both electron and light microscopy. Adrenal glands were obtained from French Geese (Anser anser) under deep ether anesthesia at posthach day 1, 5, 10, 21 and 30 (n= 5 per day). The cytoplasm of interrenal cells located beneath the adrenal capsule (sub-capsular zone, SCZ) were stained lighter than that of interrenal cells located inside the adrenal gland (inner zone, IZ) and contained several vacuoles for each sampling day. Additionally, unlike IZ cells, SCZ cells contained nuclei that were various shapes and surrounded by irregularly arranged membranes, lipid droplets which were not surrounded by a membrane, mitochondria with mostly shelf-like cristae. The arrangement of SCZ cells appears similar to that of zona glomerulosa and also the arrangement of IZ cells to that of zona fasciculata of mammalian adrenal cortex, suggesting the significant signs of zonation in goose adrenal cortex.     

Stereological analysis of the guinea pig adrenal: Effects of dexamethasone and ACTH treatment with emphasis on the inner cortex

This paper describes the morphological responses of adult male guinea pig adrenals to dexamethasone (DEX) and adrenocorticotrophic hormone (ACTH), in both qualitative and quantitative terms. Most organelles and inclusions are affected, but their responses often vary in the different cell types examined: zona fasciculata externa and interna, and zona reticularis. Following DEX the volume of lipid droplets increases in cells of zona fasciculata externa but decreases in zona reticularis; smooth endoplasmic reticulum decreases in fasciculata externa but increases in reticularis. Following ACTH, exactly the opposite occurs. This strongly suggests differing functions for these subcellular entities in each cell type, particularly for the smooth reticulum, as well as for the cells themselves. The volume of the Golgi complex markedly decreases following DEX in all cells but increases only in zona fasciculata interna and zona reticularis following ACTH. These deeper cortical cells are known to secrete at least one sulfated steroid, dehydroepiandrosterone sulfate, and these changes in the Golgi complex strengthen the suggestion that the Golgi plays a role in sulfation of steroids. Mitochondrial volume and number decrease in all cells following DEX, supporting their role in steroidogenesis. Further decreases in their volume, accompanied by increases in their number following ACTH, may be related to a proliferation of mitochondria in response to ACTH. Changes in peroxisome volume and number, following DEX and ACTH, suggest a possible role for these organelles in steroid cell metabolism. Lysosomes decrease in volume in all cells following ACTH. This does not support the recently suggested concept that they play a role in steroid secretion.     

Structure and dynamics of adrenal mitochondria following stimulation with corticotropin releasing hormone

The mitochondria of rat adrenals were investigated qualitatively and quantitatively in different functional states of the adrenal cortex. Following stimulation of the animals with corticotropin releasing hormone (CRH), the corticosterone serum levels reached a maximum 1 hour after stimulation with CRH. The amount of inner mitochondrial membrane within the zona fasciculata increased showing a biphasic time course, with a first maximum 2 hours and a second maximum 8 hours after stimulation. In contrast, a significant rise of mitochondrial volume occurred only 24 hours after CRH stimulation. Therefore, the dense vesicularization of mitochondrial cristae may constitute an early process to enhance the steroidogenic capacity of these cells. Within cells of the transition zone between zona glomerulosa and zona fasciculata, we could depict a special type of mitochondria with characteristic crescent-like cristae only seen after stimulation with CRH. This type of mitochondria may represent an intermediate form between mitochondria of zona glomerulosa and zona fasciculata underlining the impressive transformational capacity of adrenocortical mitochondria. After hypophysectomy, zona fasciculata cells contained mitochondria with tubular inner membranes, representing a hypofunctional state. In contrast, the hypofunctional state after hypophysectomy and the hyperfunctional state after stimulation of the adrenal cortex via CRH injection did not appear to correlate with the morphology of mitochondria from the zona reticularis and adrenal medulla.© Willey-Liss, Inc.     

Structure and dynamics of adrenal mitochondria following stimulation with corticotropin releasing hormone.

The mitochondria of rat adrenals were investigated qualitatively and quantitatively in different functional states of the adrenal cortex. Following stimulation of the animals with corticotropin releasing hormone (CRH), the corticosterone serum levels reached a maximum 1 hour after stimulation with CRH. The amount of inner mitochondrial membrane within the zona fasciculata increased showing a biphasic time course, with a first maximum 2 hours and a second maximum 8 hours after stimulation. In contrast, a significant rise of mitochondrial volume occurred only 24 hours after CRH stimulation. Therefore, the dense vesicularization of mitochondrial cristae may constitute an early process to enhance the steroidogenic capacity of these cells. Within cells of the transition zone between zona glomerulosa and zona fasciculata, we could depict a special type of mitochondria with characteristic crescent-like cristae only seen after stimulation with CRH. This type of mitochondria may represent an intermediate form between mitochondria of zona glomerulosa and zona fasciculata underlining the impressive transformational capacity of adrenocortical mitochondria. After hypophysectomy, zona fasciculata cells contained mitochondria with tubular inner membranes, representing a hypofunctional state. In contrast, the hypofunctional state after hypophysectomy and the hyperfunctional state after stimulation of the adrenal cortex via CRH injection did not appear to correlate with the morphology of mitochondria from the zona reticularis and adrenal medulla.     

Ultrastructural morphometry of normal adrenal cortex and of hyperplastic adrenals in gushing’s disease

Surgical specimens of 4 normal adrenal glands and of 5 hyperplastic ones in Cushing’s disease were studied ultrastructurally. The ultrastructure of the three zones of each adrenal gland was morphometrically and statistically analyzed. Comparing the statistical data of the three zones of the normal gland, the development of smooth endoplasmic reticuium and rough endoplasmic reticuium showed an increase from the outer zona glomerulosa to the inner zona fasciculata and reticularis. Also, the mitochondria were more numerous in the inner zona reticularis than in the outer zones. In Cushing’s disease, the smooth endoplasmic reticuium, the rough endoplasmic reticuium, and the mitochondria were developed to a significantly higher degree than in normal human adrenal glands. The distribution of the cell organelles in the zona fasciculata and zona reticularis is almost alike in normal adrenal glands and in the adrenal cortex in Cushing’s disease, except that the smooth endoplasmic reticuium in the zona reticularis was less extensive than in the zona fasciculata. The volume percentages of lipid vacuoies in the hyperplastic zona fasciculata in Cushing’s disease was strongly and significantly decreased in comparison to normal adrenal glands. Our ultrastructural findings and the statistical data were in accordance with the results from animal experiments with adrenocorticotropic hormone (ACTH) stimulation and confirmed former qualitative ultrastructural findings concerning human adrenal gland changes in ACTH-dependent Cushing’s disease.