Lubomir J. Valenta

EFFECTS OF VALPROIC ACID, NALOXONE AND HYDROCORTISONE IN NELSON'S SYNDROME AND CUSHING'S DISEASE

Two patients with Nelsons syndrome and one patient after bilateral adrenalectomy for Cushings disease, without any evidence of Nelsons syndrome, were studied with respect to the effect of hydrocortisone, naloxone and valproic acid (a GABA transaminase inhibitor) on ACTH secretion. Hydrocortisone suppressed plasma ACTH concentrations to normal in the patient without Nelsons syndrome, but failed to do so in the two patients with Nelsons syndrome. Naloxone and valproic acid caused a decline in plasma ACTH concentrations in the patients with Nelsons syndrome, but produced no change in the patient without Nelsons syndrome. Secretion of ACTH may thus be influenced by both opiate peptides and by gamma aminobutyric acid, as well as by the cortisol concentrations, these agents may act at different sites to inhibit ACTH release by the tumour.

Thyroid function studies in the nephrotic syndrome.

Total serum and urinary thyroxine (T4), triiodothyronine (T3), and thyroxine-binding globulin (TBG) as well as serum free T4, thyroid-stimulating hormone (TSH), and T3 resin uptake (T3RU) were measured in seven patients with the nephrotic syndrome. The nephrotic syndrome was defined by proteinuria exceeding 3 g/24 h. All patients were clinically euthyroid. Most values for total serum T4, free T4, T3, T3RU, TBG, and TSH were within normal limits. However, the mean serum T3 and TBG values were significantly lower in patients compared with the control group. The values (mean +/- 2 SD) for urinary T4 were 24.3 +/- 20.3 in the patient group and 1.5 +/- 0.7 microgram/24 h in the control group. Urinary T3 values for patients and the control group were 2100 +/- 856 and 848 +/- 253 ng/24 h respectively. Urinary TBG was 2.1 +/- 1.8 mg/24 h in the patients and undetectable in the control group. There was no correlation between daily urinary T3 and T4 and urinary TBG. There was a weak correlation between daily urinary protein excretion and urinary T4 (r = 0.5).

Ultrastructure and biochemistry of thyroid carcinoma

Thirty‐two thyroid tumors, 9 benign, 23 malignant, and 12 samples of normal thyroid tissue were examined by light and electron microscopy. Thyroglobulin content was also measured in the tissues and, in a limited number of cases, enzymatic activities were determined, such as thyroid peroxidase‐iodinase, acid protease, and deiodinase. The presence of significant amounts of 19S, 27S and 12S thyroglobulin was well correlated with the ability of the tumors to accumulate radioiodine. It is suggested that the presence of thyroglobulin be used as a marker of potential function of thyroid carcinoma. Two types of ultrastructural changes were observed in thyroid carcinoma. The first one was interpreted as accompanying the progressive loss of function of thyroid tumors, and was represented by the modifications of highly specialized structures such as RER, lysosomal dense bodies, colloid, etc. The second one is suspected to reflect the malignant transformation of the follicular cell. This concerned namely the nuclei, mitochondria, and intracytoplasmic inclusions. These changes may have a diagnostic value since they were not observed in benign conditions. Cancer 40:284–300, 1977.

Microfollicular thyroid carcinoma with amyloid rich stroma, resembling the medullary carcinoma of the thyroid (MCT)

A human thyroid tumor is described which, on light microscopy, exhibited the features of medullary carcinoma of the thyroid (MCT). The cells were arranged in solid lobules or trabeculae, and the stroma was abundant and gave positive reaction for amyloid as assessed by congo red, crystal violet and thioflavin T stains. However, there was microfollicular differentiation in certain portions of the tumor even where the tumor was invasively growing. On electron microscopy, numerous microfollicles were identified even where unsuspected by light microscopy. There were junctional complexes, the cells possessed well developed rough endoplasmic reticulum, prominent Golgi and numerous dense bodies obviously derived from the Golgi vesicles, which were of the same morphology as “secretory” granules described previously by some authors in MCT. However, we find this kind of cytology typically in microfollicular thyroid carcinomas. Presence of about 100A thick fibrils in the stroma was consistent with histochemically positive amyloid. The biochemical data were compatible with the differentiated follicular cell origin of the tissue. The homogenate contained poorly iodinated thyroglobulin, and thyroid peroxidase activity. Calcitonin was undetectable by a sensitive radioimmunoassay. It is concluded that this tumor was follicular thyroid carcinoma with amyloid rich stroma. The presence of amyloid and dense bodies with homogenous electron dense contents is insufficient for making conclusions about histogenesis of thyroid tumors. The so called MCT with amyloid stroma probably represents a heterogenous group of thyroid tumors, at least some of them derived from follicular epithelium.

ACTH Stimulation of Adrenal Epinephrine and Norepinephrine Release

Epinephrine (E) and norepinephrine (NE) levels were measured simultaneously in the adrenal veins of 6 patients before and after stimulation with 0.25 mg beta 1-24 ACTH. In 1 patient with Cushings syndrome, E and NE were also measured before and 30 min after dexamethasone. There was a significant increase in NE and E secretion (p less than 0.002) from both adrenal glands after ACTH stimulation. In the patient with Cushings syndrome, there was also a slight increase in plasma E levels after dexamethasone. It is postulated that ACTH stimulated NE and E secretion by augmenting blood flow through the adrenals and by induction of tyrosine hydroxylase and dopamine beta-hydroxylase, although a direct effect of ACTH on NE and E secretion cannot be excluded. It is also possible that the increase in adrenal catecholamine secretion after ACTH may be due to ACTH augmentation of catecholamine secretion by endogenous opioids such as beta-endorphin.

Endocrine studies in heroin addicts

Abstract In 10 heroin addicts actively taking the drug, 5 males, 5 females, a number of endocrine abnormalities were identified. These included especially: (1) Increased thyroid function manifested by high total T 4 (and occasionally T 3 ) and T 3 resin uptake, and by blunted TSH response to TRH. (2) Changes in sex hormones, LH and FSH, and LH/FSH responsiveness to GnRH compatible with either primary gonadal failure or disturbance of the hypothalamopituitary regulations of the reproductive functions. (3) Abnormal increase in growth hormone in response to TRH/GnRH. (4) Occasionally increased baseline prolactin; blunted response or slightly increased responsiveness of PRL to TRH/GnRH. (5) No apparent change in the adrenocortical function. The results are best explained by multiglandular abnormalities due possibly to multiple effects of heroin on the endocrine system and its regulations.

Diagnosis of pituitary tumors by hormone assays and computerized tomography

Abstract One hundred and seventy patients with endocrine abnormalities, 29 males and 141 females, were studied by computerized tomography (CT) scanning of the pituitary and by pituitary hormone assays including basal and stimulated hormone concentrations in the blood. Pituitary macroadenoma was observed in 40 of the 170 patients, microadenoma in 49, primary empty sella in 46, secondary empty sella in 25, including 20 of the 40 patients with macroadenoma after surgical removal or radiation therapy of the tumor. Suprasellar tumor was present in four patients. In 23 women with menstrual abnormalities and 3 men with impotence and hyperprolactinemia, the results of CT scanning were normal. Of the 40 patients with macroadenoma, 24 presented with a hyperfunctioning syndrome (acromegaly or hyperprolactinemia). Among the 49 patients with microadenomas, 46 had the amenorrhea-galactorrhea syndrome, one male presented with acromegaly and one with Cushings disease, and one female also had Cushings disease. Primary empty sella was associated with the amenorrhea-galactorrhea syndrome in females and impotence in males. Only four female patients demonstrating an empty sella were asymptomatic. Distinctive biochemical findings were identified in certain groups of patients with different pituitary pathologic features. CT scanning was found very useful in the assessment of the size of the tumor, its suprasellar or parasellar extension and response to therapy, and in differential diagnosis of tumor and empty sella. Disappointing results were obtained in patients with endocrine abnormalities and normal results of CT scanning, and in patients following surgical treatment for a pituitary tumor, when the identification of recurrent tumor was impossible from a single examination. It is concluded that CT scanning is the most advanced technique in the diagnosis of anatomic pituitary abnormalities, and it should replace the traditional invasive diagnostic procedures.

Use of the artificial beta cell (ABC) in the assessment of peripheral insulin sensitivity: Effect of chromium supplementation in diabetic patients

The artificial beta cell (ABC), a closed-loop insulin delivery system, was used to determine insulin sensitivity. Progressively increasing glucose loads were administered after initial stabilization of the blood glucose at euglycemic levels such that the serum C-peptide was suppressed. The amount of insulin required to maintain euglycemia was considered a measure of sensitivity to insulin. Six stable maturity onset diabetics were studied before and after supplementation with chromium-rich brewers yeast. All patients demonstrated an increase in sensitivity to insulin as indicated by a decrease in the fasting blood glucose concentration and a decrease in insulin requirement during the glucose challenge (P less than 0.02). The data obtained support the hypothesis that chromium or some other factor(s) present in brewers yeast potentiates the peripheral effects of insulin. It remains to be established whether this effect occurs at the receptor or post-receptor level.

Insulin-Induced Lipodystrophy in Diabetic Patients Resolved by Treatment with Human Insulin

Excerpt Lipoatrophy occurs with high frequency in diabetic patients treated with conventional bovine-porcine insulin preparations (1-3), but is rare in patients receiving the highly purified porcin...

Regression of a pituitary adenoma following levothyroxine therapy of primary hypothyroidism

Two patients are described who were suffering from primary hypothyroidism and who developed a pituitary microadenoma and macroadenoma with suprasellar extension, respectively, diagnosed by CT scan of the pituitary. Both patients originally presented with amenorrhea and galactorrhea. In addition to low serum T4 and T3 levels and an elevated TSH level, they also had hyperprolactinemia. The TRH test performed in one of the patients showed an exaggerated response of both TSH and PRL to TRH. Correction of hypothyroidism by prolonged (months) treatment with levothyroxine resulted in normalization of thyroid function tests as well as hyperprolactinemia and in regression of the pituitary tumor. It was concluded that primary hypothyroidism was the cause of the pituitary adenoma and the amenorrhea/galactorrhea syndrome. It is recommended that routine thyroid function tests be obtained for patients with hyperprolactinemia. Demonstrable primary hypothyroidism should be corrected for prolonged periods of time by levothyroxine therapy, and CT scanning of the pituitary should be repeated before any other treatment such as bromocriptine or surgery is attempted.