Vanitha Vaidya

Gas-liquid chromatography in the diagnosis of congenital adrenal hyperplasia☆

Abstract A gas-liquid Chromatographic method to measure 17-hydroxyprogesterone, pregnanetriol, and 17-hydroxypregnanolone in serum is described. This method has been applied to the diagnosis of congenital adrenal hyperplasia with success. All three compounds are elevated and fall rapidly upon treatment. This method, as described, does not detect these steroids in normal human serum, although the levels reported by some radioimmunoassay techniques are high enough to have been discerned.

THE ROLE OF ADRENOCORTICOTROPHIC AND GROWTH HORMONE ON GLUCOCORTICOID SECRETION IN HYPOPITUITARY (HP) PATIENTS

This study in HP was aimed at evaluating the role of Human Growth Hormone (HGH) on effect of Adrenocorticotrophic Hormone (ACTH) on glucocorticoid secretion. The 5 studied included 3 HP (with partial GH, Isolated GH, and GH and TSH deficiency respectively), and 2 normal controls. Urine collections for basal 17-hydroxysteroid (17H) were followed by collections with ACTH and GH alone, and in combination, for 3 consecutive days. The dosage, HGH 2 IU/day, ACTHAR GEL 25 U/M2 q.12 hr. Mean basal 24-hr 17H excretion in the 3 HP was 0.38 mgm. There was a 15-fold rise to ACTH alone, a 37-fold rise with ACTH given a second time, whether given alone or in combination with HGH. The 17H excretion on HSH alone was not different from basal. The controls showed a 4-fold rise to the first stimulus with ACTH, and a 9-fold rise to ACTH given the 2nd time. There was no change with HGH administration. Results indicate no potentiation of HGH on the ACTH and hypopits are relatively deficient in 11-oxido-reductase. Tetrahydro F was a prominent component after ACTH in hypopits whereas Tetrahydro E was in the normal.

LOW LEVELS OF TRIIODOTHYRONINE IN ANOREXIA NERVOSA

There are many biochemical and clinical findings in patients with anorexia nervosa to suggest altered thyroid hormone activity but laboratory tests of thyroid gland function are generally normal or low normal. TSH, total T4, total T3 and the response to TRH were determined in 6 patients with anorexia nervosa in an effort to evaluate discriminately thyroid hormone activity at the physiologic levels of the hypothalamus, pituitary gland, thyroid gland and peripheral tissue. The results, expressed as the mean value ± SEM, are summarized in the following table:The most striking finding was the markedly depressed T3 levels. Animal studies suggest that in acute starvation, peripheral deiodination of thyroxine is increased. Our data suggest that during chronic starvation, peripheral deiodination of T4 to T3 is diminished. Sullivan et al have suggested that severely ill but euthyroid patients have decreased deiodination and decreased intracellular T3. Teleologically, decreased deiodination may be a protective mechanism during chronic stress.

LH & FSH RESPONSE TO LUTEINIZING RELEASING FACTOR (LRF) IN CLYCLOPHOSPHAMIDE TREATED MALES

Testicular damage associated with cyclophosphamide (CX) therapy of steroid-dependent nephrosis prompted assessment of 5 pubertal males, 15-18 yrs, to identify those who may have gonadal injury as a result of medication. 3 who had received CX for 4 months and 2 for a total of 9 and 10 months between the ages of 12-1/2 to 16 yrs (2-4 yrs before testing) received LRF, 100 ugm. Basal serum testosterone (T) values in 4 were within the normal range for age, mean 507 (400-900 ngm/ml) and one was low, 246.Responses to LRF in 3 with normal T showed higher basal levels of LH, mean 46.3 mIU/ml, and peaks to 101-119. Mean basal levels of FSH were 25.7 mIU/ml and had sustained elevation rather than a significant peak. 1 with normal T and 1 with low T had mean basal LH 18.5 mIU/ml and mean basal FSH 1.4. After LRF a 3-4 fold rise of LH and 8-10 fold rise of FSH occurred. The LRF test caused no untoward reactions and does identify those who require further evaluation of their gonadal status. These studies showed that testesin CX-treated males may be under higher LH and FSH stimulation to maintain normal T.

LH & FSH RESPONSES TO LRF IN GONADAL DYSGENESIS (GD) AFTER ETHINYL ESTRADIOL (EE)

Subjects with GD have elevated LH & FSH and achieve greater rise in both after LRF (Silver, Yen 1973). Estrogens exert inhibitory action on FSH & LH release (Yen et al 1972). To ascertain an effect of estrogen on LH and/or FSH to LRF in GD, 8 females 7-20 yrs, were studied; 4 XO, 1 XO/XY, constitutional delay, hypopituitarism, normal female. LRF, 50-100 ugm IV, was followed by 0.1 mgm EE daily 3-7 days, with 1-7 days off EE prior to second LRF test. In 3 young XO GD, 7 days EE decreased basal FSH (mean 17.6 mIU/ml before EE, 6.1 after EE) and the FSH peak to LRF (mean FSH peak 64.1 before EE, 16.1 after); LH was not significantly affected. With 3 days EE, a 7 yr. XO/XY had no change in LH, FSH responses. An older XO had an LH rise to LRF after 3 days EE, with a decreased FSH responsiveness. LH levels with LRF (after EE) were decreased in a normal female and constitutional delay. The younger child with GD lacks ovarian feedback mechanism and may have chronic endogenous secretion of LRF which induces pubertal LH response, as shown in these studies. LH & FSH responses to EE varied with age.

CHRONIC LYMPHOCYTIC THYROIDITIS (CLT) IN THYEOXINE (T4) TREATED CHILDREN

Progression of CLT in T4 treated children has been poorly documented. The response of endogenous T4, T3 and TSH to withdrawal after 2 to 9 yrs of therapy in 6 children, 7-18 yrs, was studied with weekly levels for 4-20 wks. At Dx. of CLT 5 had hypothyroid values. Results indicated 3 patterns of response: 1) clinical and lab evidence of hypothyroidism in 6 wks, 2) increased TSH with normal T4 followed by return of goiter 8 wks off therapy, 3) clinical & chemical euthyroidism in 3 with no return of goiter 12-20 wks off therapy. This group demonstrated a reduction in agglutinating antibody (Ab) titers from initial levels. Two had hypothyroid lab data at dx. of CLT. Normal TSH, T4 & T3 occurred 3 wks after discontinuing therapy. A reduction in Ab titers with normal TSH accompanied euthyroidism. Hypothyroidism coincided with unchanged Ab. In contrast to adults treated for 10 yrs, with deterioration in thyroid function noted 6 wks off therapy (Papapetrou et al, Lancet, Nov.72), these studies indicated that the child may recover function after a period of replacement.

PATTERNS OF LH & FSH RELEASE STIMULATED BY LUTEINIZING HORMONE RELEASING FACTOR (LRF) IN 18 CHILDREN

18 subjects, 5-20 yrs, received LRF to determine if the responses of serum LH & FSH might be useful in specific situations. The subjects who received LRF, 50-100 ugs IV, had hypopituitarism, intrasellar mucocoele (A); constitutional delay, normal female (B); delayed puberty & anosmia, anorchia & encephalocoele (C); obesity (D); anorexia nervosa (E) & gonadal dysgenesis (F).A prepubertal hypopit had FSH 0.7 mIU/ml (peak 4.5); LH was basal 16.0 (peak 31.7). B had no LH, FSH abnormality. LH did not rise in anorchia; C had no FSH peaks. D had no peaks but basal LH, FSH were higher than expected for age. E had low LH & no rise in FSH (N) in one. F had elevated LH, FSH. The LRF test is useful for evaluation of suspected htypothalamic-pituitary disorders.