THE MULTIFARIOUS CUSHING'S - LESSONS FROM A CASE SERIES.

Endogenous Cushing's syndrome is rare, with an incidence of 0.7-2.4 per a million people a year. Clinical presentation of Cushing syndrome can be pleomorphic, and establishing diagnosis can be difficult. Early recognition and rapid control of hypercortisolaemia are necessary to decrease morbidity and mortality in these patients. We report a series of 6 endogenous Cushing's syndromes of different etiologies (4 Cushing's disease and 2 adrenal Cushing's syndrome) assessed in our endocrine department over a decade (2009-2019). In order to highlight the diversity of clinical forms, diagnostic tools and specific management of this condition we labelled each case suggestively: the typical Cushing's disease, the Pseudo Cushing's, the elusive Cushing's disease, the mild autonomous cortisol hypersecretion, Cushing's syndrome in pregnancy and Cushing's disease with thromboembolism. We discussed their particularities which were revelatory for the diagnosis, such as dermatologic, cardiovascular, musculoskeletal, neuropsychiatric, or reproductive signs, reviewing literature for each manifestation. We also discuss the commonalities and differences in laboratory and imagistic findings. Therapeutic approach can also differ with respect to the particular condition of each patient and the multiple choices of therapy will be reviewed.

Structural and functional changes of carotid wall properties in patients with acromegaly are not restored after 1 year of GH/IGF1 normalization.

UNLABELLED: Vascular changes are common in acromegaly (ACM). Current therapies can normalise the levels of both growth hormone (GH) and insulin-like growth factor (IGF1). OBJECTIVE: To establish whether the ACM vascular changes in patients with effectively managed disease are different from those in patients with an active condition. METHODS: 64 ACM patients were tested for serum GH (random and during an oral glucose tolerance test) and IGF1. Ultrasonography of the right common carotid (RCC) explored structural (the carotid diameter and intima-media thickness index (IMT)) and functional (the augmentation index (AIx), elastic modulus (Ep), and local pulse wave velocity (PWV)) arterial parameters in the ACM patients (groups A and B) and an age- and sex-matched control group of 21 patients without acromegaly (group C). RESULTS: The ACM patients were divided into 2 subgroups that had similar cardiovascular risk factor profiles: A (n=10, with controlled ACM), and B (n=54, with active ACM). The AIx was higher in groups A (27.7% [2.2-54.3]) and B (20.0% [ - 38.2-97.1]) than in group C (3.5% [ - 11.3-31.1]), p=0.01 and 0.002, respectively. The group B patients presented with poorer functional carotid wall parameters than the control subjects: Ep-95.5 [33-280] KPa vs. 77.5 [39-146] KPa, p=0.01; and PWV-6 [3.6-10.4] m/s vs. 5.4 [3.9-7.2] m/s, p=0.03.The ACM patients had greater RCC diameters (6.4 ± 0.6 mm vs. 5.7 ± 0.6 mm, p<0.001) and IMT values (0.72 ± 0.13 mm vs. 0.58 ± 0.08 mm, p<0.001) than the subjects in group C. CONCLUSIONS: Both the controlled and active ACM patients showed structural arterial changes. After 1 year of disease control, the patients with controlled ACM showed improvements in the functional, but not the structural, arterial parameters compared with the patients with an active condition.

Insulin resistance and insulin secretion in non-diabetic acromegalic patients.

UNLABELLED: Insulin resistance (IR) can be induced by high amounts of growth hormone (GH). AIM: To set up, in acromegaly without diabetes mellitus, a correlation between the disease activity in GH-secreting adenoma (AA) - assessed by minimum GH serum level during an oral glucose tolerance test (OGTT) - and severity of insulin resistance (IR), assessed by HOMA-IR index. METHODS: 75 out of 88 consecutive patients with acromegaly hospitalized in our department were included in this study. 13 patients proved to have diabetes mellitus and were excluded. Serum glucose, GH and insulin levels were measured by immunoradiometricassay basal and at 30, 60 and 120 minutes after a 75 g OGTT in 88 patients with active or cured acromegaly. IR was assessed using HOMA-IR index (Homa-IR=basal serum glucose (mg/dl) x basal serum insulin (mU/L)/22.5 x 18). A value over 2.5 was considered indicating IR. RESULTS: Out of 75 patients without diabetes mellitus, 36 subjects (48%) were presenting with IR (34 with active disease, 2 cured). We found a significant positive correlation (r=0.56, p<0.001) between AA and HOMA-IR. The GH minimal level corresponding to the intersection of the exponential regression curve with the HOMA-IR level of 2.5 was 8.8 ng/mL, a cut-off point indicating IR with 82% specificity and 78% sensitivity. The odds ratio for developing IR becomes significant at a minimum GH level during OGTT of 2 ng/mL (odds ratio 7.6, 95% confidence interval 2-29). CONCLUSIONS: The severity of IR revealed by acromegaly correlates with GH production. A GH serum level higher than 2 ng/mL during OGTT indicates an increased risk for developing IR. This cut-off level of GH can be used as one of criteria of cured disease, regarding the lack of metabolic effects.

Program package for paramedical investigations (EEG, EKG, radiography, biochemical investigations, pathological anatomy, nuclear medicine).

The purpose of this program package is to provide computer-based assistance for the work performed in paramedical investigation laboratories: functional investigations, radiology, biochemical investigations, pathological anatomy, nuclear medicine, in hospitals, polyclinics, medical practices. The common characteristics regarding the management of the work done in such laboratories has made a global approach of the problem possible. The modular design of the program package has allowed its stagewise development, thus offering the possibility of integration with the medical information management in each laboratory. The program package for paramedical investigations has a two level structure. programs and data bases pertaining to the main program; programs and data bases specific to each type of computerised laboratory.

The serum osteocalcin levels in adult and aged hypothyroid patients.

Osteocalcin (OC) or the bone protein containing gamma-carboxyglutamic acid (BGP or Gla-P), is a specific and sensitive marker of bone turnover. A radioimmunoassay (RIA) system for human osteocalcin was developed with the sensitivity of 0.5 ng/ml. The osteocalcin was measured in sera from 33 hormonally and/or clinically hypothyroid patients: 12 adult and 21 aged patients. For comparison, blood samples were collected from 14 hormonally hyperthyroid adult patients in whom the OC levels were 16.23 +/- 7.57 ng/ml (mean +/- SD) and from hormonally euthyroid adult patients (previously treated hyperthyroid patients) having OC 9.76 +/- 5.32 ng/ml. Abnormal low OC levels were noted in the hypothyroid adult patients group: 1.04 +/- 0.23 ng/ml by comparison to the hypothyroid aged patients 3.76 +/- 2.38 ng/ml (p less than 0.001). Moreover, great variability of the OC serum levels was observed in the aged group, four patients hormonally eu- or hypothyroid having high OC levels in the range: 13.29-55.45 ng/ml and other three patients although hormonally euthyroid but clinically hypothyroid had low OC levels 0.88-2.27 ng/ml. The abnormalities of the OC levels in hypothyroid adult and aged patients are discussed.

Zinc and copper in plasma and erythrocytes of Down's syndrome children.

The concentration of zinc and copper in the plasma and the erythrocytes of 24 children with Down's syndrome was measured and compared with the values in a control group of normal children. Zinc and copper were determined in this biologic material by flame atomic absorption spectrophotometry. A significant (p less than 0.001) decrease of the plasma zinc content well as an increase of copper (p less than 0.024) and zinc (p less than 0.001) in the erythrocytes of Down's syndrome patients were found. The possible mechanisms of these changes are discussed.

Significance of high levels of serum malonyl dialdehyde (MDA) and ceruloplasmin (CP) in hyper- and hypothyroidism.

The lipid peroxidation process is enhanced in both hyperoxygenated or underoxygenated tissues though its mechanism of production is different. Because in thyroid functional diseases there are severe disorders in tissue oxygenation we studied the lipid peroxidation process by using the serum level of malondialdehyde (MDA) as indicator. We also determined the serum ceruloplasmin (CP), an enzymatic protein belonging to the circulating system of antioxidative protection and also playing a role in the cell-mediated immunity. We also followed serum level of uric acid (UA). The determinations were performed on serum samples collected from three groups: 1, adult control subjects: 2. adult untreated hyperthyroid patients, and 3. adult hypothyroid thyroidectomized patients to whom replacement therapy was discontinued for at least 15 days. The mean MDA level was significantly higher in both hyperthyroid and hypothyroid patients by comparison to the control group. CP mean level was significantly lower than in controls. It was concluded that in post thyroidectomy hypothyroidism an enhancement of lipid peroxidation does exist and that its consequences are probably aggravated by the low serum CP level. The enhancement of the process occurs by other mechanisms than for hyperthyroid group. At hypothyroid patients there is an ADP excess which is degenerated to xanthine, the substrate of xanthine oxidase resulting in toxic anion superoxide and UA. In contrast with hyperthyroid group, in hypothyroid patients we observed significant higher values of UA in comparison to the controls. The excess of MDA found in hyperthyroid patients is statistically significant, but its consequences are probably less severe because the serum CP is higher than normal, a rather expected finding for an autoimmune disease.

Serum and intracystic levels of thyroxine (T4) and triiodothyronine (T3) in women with breast macrocysts.

In 15 patients with a total of 22 breast macrocysts serum and intracystic T4 and T3 and intracysts TSH were concomitantly radioimmunoassayed (using a technique with polyethylene glycol (PEG) for T3, T4, and a double antibody technique for TSH). While in most cysts (17/22) the T4 values were under those in the serum, in 21 cysts T3 was 2-18 times above the serum values. Intracystic TSH was at the lower limit of the normal serum TSH values whereas prolactin (PRL) and thyroglobulin (TGL) assayed in several cysts were not different from their serum value. It suggests that breast macrocysts are able to concentrate or even produce triiodothyronine.

Results of 131I therapy in hyperthyroidism at 7-18 years of age.

Twenty-seven patients aged 7-18 years, with hyperthyroidism and diffuse goite received 131I and 125I in doses of 200-350 muCi/gm of gland. The drug was given in a unique dose to 14 patients and fractioned (maximum 4 doses) to the rest. The total maximum dose was 15 mCi. Doubtless recovery was obtained in 25 cases and probable improvement in another 2 (the patients were lost track of). Exophthalmometric values did not increase in any of the patients and in 2 cases of edematous exophthalmos the protrusion and edema disappeared after this treatment. Clear improvement in the nutritional state occurred and puberty followed a normal course. The incidence of both early and late transient hypothyroidism was 1/25, while permanent hypothyroidism occurred in 5/25. In 5 cases administration of 125I in doses of 500 muCi/gm of gland was not effective and necessitated 131I readministration. It was concluded that radioactive iodine (131 isotope) is an effective radiopharmaceutical for radical treatment of hyperthyroidism in children and adolescents. The therapeutical innocuity of 131I was perfect and the dose of 200-350 muCi/gm of gland was the most adequate. A follow-up of the functional status is however advocated in these patients for detection of late hypothyroidism.