Low dose mitotane-induced neurological and endocrinological complication in a 5-year-old girl with adrenocortical carcinoma

A 58-year-old man had adrenocortical carcinoma in the right adrenal gland. The tumour secreted excessive cortisol and dehydroepiandrosterone-sulphate (DHEA-S), and had invaded the right hepatic lobe and vena cava. Eleven months after surgical tumour resection, the serum DHEA-S levels again increased. Local tumour recurrence and a metastasis was found in the lung. Eleven months after surgery chemotherapy with mitotane (o,p'-DDD) was initiated. Twelve weeks of mitotane reduced serum DHEA-S levels and caused these tumours to disappear. The patient was then treated with low-dose mitotane (1.5-2.0 g/day) for 2 years. Serum levels of mitotane remained at less than 10 microg/ml. Although such low serum levels of mitotane and delayed initiation of mitotane after surgery have been proposed to weaken the antineoplastic effect of mitotane, the patient had a remission for 2 years. However, there was then local re-recurrence with an increase in serum DHEA-S and death 4 months later. The histological features of neoplastic cells were quite different comparing tumour resected at surgery and tumour at autopsy. The latter had more frequent mitotic nuclei. This tumour was initially sensitive to mitotane, but later became insensitive.

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Adrenocortical carcinoma: an ominous cause of hirsutism

BMJ Case Reports ◽

10.1136/bcr-2019-232547 ◽

2019 ◽

Vol 12 (12) ◽

pp. e232547

Author(s):

Suhaib Radi ◽

Michael Tamilia

Keyword(s):

Adrenocortical Carcinoma ◽

Low Dose ◽

Urinary Free Cortisol ◽

Early Morning ◽

Provisional Diagnosis ◽

Late Night ◽

Late Night Salivary Cortisol ◽

Morning Cortisol ◽

Free Cortisol ◽

Life Threatening

Hirsutism is a common medical presentation to family physicians, internists and endocrinologists. Although the cause is commonly benign, a more serious or life-threatening one should not be missed. Here we report a 58-year-old woman, assessed for hirsutism and 15-pound weight gain, with associated easy bruising and mood swings. On physical examination, she was hypertensive with central obesity. Laboratory work was significant for erythrocytosis, leukocytosis with lymphopenia and transaminitis. With this initial clinical picture, a provisional diagnosis of cortisol and androgen hypersecretion was suspected. Further investigations revealed non-suppressible early morning cortisol after low-dose dexamethasone, elevated 24 hours urinary-free cortisol and late night salivary cortisol. In addition, serum adrenocorticotropin hormone was low and androgens were elevated. These results supported the provisional diagnosis and imaging of the adrenals showed a large 10.4×7.7×5.2 cm right adrenal mass, consistent with adrenocortical carcinoma, for which she underwent surgical resection.

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LONG-TERM FOLLOW-UP OF ADRENOCORTICAL CARCINOMA PATIENTS TREATED WITH ADJUVANT LOW-DOSE MITOTANE (O, P', -DDD)

European Urology Supplements ◽

10.1016/s1569-9056(06)60515-0 ◽

2006 ◽

Vol 5 (2) ◽

pp. 150

Author(s):

M. Mullerad ◽

G. Dickstein ◽

C. Shechner ◽

G. Meyer ◽

B. Moskovitz ◽

...

Keyword(s):

Adrenocortical Carcinoma ◽

Low Dose ◽

Long Term Follow Up

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Ovarian Dysfunction in Fetally Irradiated Beagles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100080717 ◽

1977 ◽

Vol 35 ◽

pp. 658-659

Author(s):

T. M. Seed ◽

M. H. Sanderson ◽

D. L. Gutzeit ◽

T. E. Fritz ◽

D. V. Tolle ◽

...

Keyword(s):

Gamma Rays ◽

Low Dose ◽

Long Term Effects ◽

Ovarian Dysfunction ◽

Dose Rates ◽

Highly Sensitive ◽

Microscopic Evaluation ◽

Ovarian Pathology ◽

Normal Offspring

The developing mammalian fetus is thought to be highly sensitive to ionizing radiation. However, dose, dose-rate relationships are not well established, especially the long term effects of protracted, low-dose exposure. A previous report (1) has indicated that bred beagle bitches exposed to daily doses of 5 to 35 R 60Co gamma rays throughout gestation can produce viable, seemingly normal offspring. Puppies irradiated in utero are distinguishable from controls only by their smaller size, dental abnormalities, and, in adulthood, by their inability to bear young.We report here our preliminary microscopic evaluation of ovarian pathology in young pups continuously irradiated throughout gestation at daily (22 h/day) dose rates of either 0.4, 1.0, 2.5, or 5.0 R/day of gamma rays from an attenuated 60Co source. Pups from non-irradiated bitches served as controls. Experimental animals were evaluated clinically and hematologically (control + 5.0 R/day pups) at regular intervals.

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High Resolution Microscopy of Multi-Layered Biological Crystals

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010005319x ◽

1982 ◽

Vol 40 ◽

pp. 80-83

Author(s):

H.A. Cohen ◽

T.W. Jeng ◽

W. Chiu

Keyword(s):

High Resolution ◽

Low Dose ◽

Three Dimensional ◽

Data Interpretation ◽

Two Dimensional ◽

Biological Objects ◽

Density Maps ◽

Density Map ◽

Complex Crystal ◽

High Resolution Microscopy

This tutorial will discuss the methodology of low dose electron diffraction and imaging of crystalline biological objects, the problems of data interpretation for two-dimensional projected density maps of glucose embedded protein crystals, the factors to be considered in combining tilt data from three-dimensional crystals, and finally, the prospects of achieving a high resolution three-dimensional density map of a biological crystal. This methodology will be illustrated using two proteins under investigation in our laboratory, the T4 DNA helix destabilizing protein gp32*I and the crotoxin complex crystal.

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Characterization of microtubules by dark-field STEM and replication

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010008506x ◽

1991 ◽

Vol 49 ◽

pp. 152-153

Author(s):

S.B. Andrews ◽

R.D. Leapman ◽

P.E. Gallant ◽

T.S. Reese

Keyword(s):

Protein Interactions ◽

Low Dose ◽

Unit Length ◽

Dark Field ◽

Carbon Films ◽

Microtubule Associated Proteins ◽

Molecular Weights ◽

Freeze Dried ◽

Protein Motors ◽

Associated Proteins

As part of a study on protein interactions involved in microtubule (MT)-based transport, we used the VG HB501 field-emission STEM to obtain low-dose dark-field mass maps of isolated, taxol-stabilized MTs and correlated these micrographs with detailed stereo images from replicas of the same MTs. This approach promises to be useful for determining how protein motors interact with MTs. MTs prepared from bovine and squid brain tubulin were purified and free from microtubule-associated proteins (MAPs). These MTs (0.1-1 mg/ml tubulin) were adsorbed to 3-nm evaporated carbon films supported over Formvar nets on 600-m copper grids. Following adsorption, the grids were washed twice in buffer and then in either distilled water or in isotonic or hypotonic ammonium acetate, blotted, and plunge-frozen in ethane/propane cryogen (ca. -185 C). After cryotransfer into the STEM, specimens were freeze-dried and recooled to ca.-160 C for low-dose (<3000 e/nm2) dark-field mapping. The molecular weights per unit length of MT were determined relative to tobacco mosaic virus standards from elastic scattering intensities. Parallel grids were freeze-dried and rotary shadowed with Pt/C at 14°.

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Structural analysis of the surface-layer protein of spirillum serpens by high-resolution electron microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100077268 ◽

1983 ◽

Vol 41 ◽

pp. 738-739

Author(s):

W. H. Wu ◽

R. M. Glaeser

Keyword(s):

Electron Microscopy ◽

Surface Layer ◽

Structural Analysis ◽

High Resolution ◽

Low Dose ◽

High Resolution Electron Microscopy ◽

Optical Diffraction ◽

Surface Layer Protein ◽

Morphological Unit ◽

Resolution Electron

Spirillum serpens possesses a surface layer protein which exhibits a regular hexagonal packing of the morphological subunits. A morphological model of the structure of the protein has been proposed at a resolution of about 25 Å, in which the morphological unit might be described as having the appearance of a flared-out, hollow cylinder with six ÅspokesÅ at the flared end. In order to understand the detailed association of the macromolecules, it is necessary to do a high resolution structural analysis. Large, single layered arrays of the surface layer protein have been obtained for this purpose by means of extensive heating in high CaCl2, a procedure derived from that of Buckmire and Murray. Low dose, low temperature electron microscopy has been applied to the large arrays.As a first step, the samples were negatively stained with neutralized phosphotungstic acid, and the specimens were imaged at 40,000 magnification by use of a high resolution cold stage on a JE0L 100B. Low dose images were recorded with exposures of 7-9 electrons/Å2. The micrographs obtained (Fig. 1) were examined by use of optical diffraction (Fig. 2) to tell what areas were especially well ordered.

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The Response of Testis Cells to Low Dose X-Irradiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100099155 ◽

1981 ◽

Vol 39 ◽

pp. 542-543

Author(s):

D. E. Philpott ◽

W. Sapp ◽

C. Williams ◽

Joann Stevenson ◽

S. Black

Keyword(s):

Electron Microscopy ◽

Stem Cell ◽

Light Microscopy ◽

Dose Level ◽

Cross Sections ◽

Low Dose ◽

Light And Electron Microscopy ◽

Cellular Responses ◽

Post Irradiation ◽

X Irradiation

The response of spermatogonial cells to X-irradiation is well documented. It has been shown that there is a radiation resistent stem cell (As) which, after irradiation, replenishes the seminiferous epithelium. Most investigations in this area have dealt with radiation dosages of 100R or more. This study was undertaken to observe cellular responses at doses less than 100R of X-irradiation utilizing a system in which the tissue can be used for light and electron microscopy.Brown B6D2F1 mice aged 16 weeks were exposed to X-irradiation (225KeV; 15mA; filter 0.35 Cu; 50-60 R/min). Four mice were irradiated at each dose level between 1 and 100 rads. Testes were removed 3 days post-irradiation, fixed, and embedded. Sections were cut at 2 microns for light microscopy. After staining, surviving spermatogonia were identified and counted in tubule cross sections. The surviving fraction of spermatogonia compared to control, S/S0, was plotted against dose to give the curve shown in Fig. 1.

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