M. Faggiano

CIRCANNUAL RHYTHMS OF PLASMA LUTEINIZING HORMONE, FOLLICLE‐STIMULATING HORMONE, TESTOSTERONE, PROLACTIN AND CORTISOL IN PREPUBERTY

For a period of four years we have been studying 106 healthy males and 66 healthy females, aged 6–10, by cross‐sectional design, to look for evidence of a circannual rhythm in LH, FSH, testosterone, PRL, and cortisol secretion. Plasma samples were taken at 0800 h and all hormones were measured by RIA. A cosine function was fitted to the single data to indicate any significant circannual (about 1 year) rhythm and to estimate its parameters: mesor, amplitude, and acrophase. Annual changes were validated in the secretion of: LH (annual crest time in January in both sexes), testosterone (studied only in males, annual crest time in July), and PRL (significant rhythm only in females with annual crest time in March). FSH and cortisol did not show an annual rhythm in both sexes. Our data suggest that sex influences the circannual hormonal rhythms from prepuberty onwards.

DYSGERMINOMA IN 45,X TURNER SYNDROME: REPORT OF A CASE

Here we report the fourth case of dysgerminoma in a patient with the syndrome of gonadal dysgenesis and 45,X karyotype. Typical Turners syndrome features were unusually associated with breast development, menarche and secondary amenorrhoea. Exaggerated basal and GnRH stimulated gonadotrophin and low oestradiol levels were typical of post‐pubertal Turners syndrome. Detailed (standard) chromosome and banding analysis excluded the presence of Y chromosome material. This case suggests that the presence of a Y chromosome is not necessary for abnormal differentiation of germ cells and the occurrence of a gonadoblastoma.

Effect of L-dopa on plasma TSH levels in primary hypothyroidism.

Plasma TSH responses after an i.v. injection of 100 mg of L-dopa were evaluated by radioimmunoassay in 4 normal euthyroid subjects and in 8 patients with primary hypothyroidism. In agreement with previous results, no variations to plasma TSH levels were observed in the euthyroid subjects. In contrast, in primary hypothyroidism L-dopa induced a biphasic response in plasma TSH. In fact, we observed a transitory increase witha maximum at 30 min (mean plus or minus SEM equals 54 plus or minus 18%) followed by a decrease reading a minimum level of plasma TSH basal values at 90 min (mean plus or minus SEM equals 15 plus or minus 6%). Thesefindings demonstrate that the plasma TSH response to L-dopa in primary hypothyroidism is time-dependent . Some speculation on the possible mechanism of this action is presented.

Two cases of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) associated with hGH deficiency and marginal impairment of other hypothalamic-pituitary functions.

Plasma hGH response to provocative tests (insulin‐induced hypoglycaemia and arginine infusion) appears normal in Turners syndrome. Two cases are reported of the chromatin positive variety of ovarian dysgenesis (XO/XX mosaicism) with unusual absence of plasma hGH response to provocative tests (arginine infusion, insulin‐induced hypoglycaemia). Study of other pituitary functions supports the view that a hypothalamic‐pituitary impairment is present in these cases. In fact, in these cases we observed low values of gonadotrophin excretion and limited responses of plasma ACTH and plasma corticosteroids to provocative tests (insulin‐induced hypoglycaemia, metopyrone). Moreover, markedly abnormal plasma TSH response to TRF was observed in Case 2. The results are discussed with reference to the significance of this rare association.

Circannual variations of plasma testosterone, luteinizing hormone, follicle-stimulating hormone and prolactin in Klinefelter's syndrome.

To clarify the influence of primary testicular failure upon circannual hormone rhythmicity we have been studying, by cross-sectional design, 93 adult patients with Klinefelters syndrome (KS) and 64 adult healthy males to look for evidence of circannual rhythms in testosterone (T), LH, FSH and PRL plasma concentrations. Plasma samples were taken from 08.00 to 09.00 h and all hormones were measured by radioimmunoassay. The data were assessed by the single cosinor method in order to obtain evidence for any significant rhythm and to estimate its parameters mesor, amplitude and acrophase. In the controls, annual rhythms were validated for the secretion of T (annual crest time in September), LH (annual crest time in February) and FSH (annual crest time in January), whereas PRL did not show a significant annual rhythm. In KS, significant circannual rhythms were validated for the secretion of T (annual crest time in April) and FSH (annual crest time in September), but not for LH and PRL secretion. Our results suggest that in KS the circannual hormone rhythmicity may be influenced by seminiferous tubule dysgenesis.

Isosexual Precocious Pseudopuberty Secondary to a Testosterone‐Secreting Leydig Cell Testicular Tumour: True Isosexual Development Early After Surgery*

Summary:  The paper reports on a 6‐year‐old boy with precocious pseudopuberty due to androgen hypersecretion by a testicular interstitial cell tumour. Steroidogenesis, characterized by high testosterone, dihydrotestosterone, androstenedione, dehydroepiandros‐terone and 17‐hydroxyprogesterone plasma levels, was not modified by ACTH, dexame‐thasone or HCG administration. Gonadotropins were subnormal and unresponsive to LRH stimulation. TSH and prolactin levels were normal both in basal and dynamic conditions. The hormonal profile progressively returned to prepubertal value and persisted normal for 6 months after removal of the tumour. The patient entered puberty spontaneously at 7,6/12 years showing a normal pubertal basal and LRH stimulated FSH and LH and a pubertal circadian rhythm of both gonadotropins and testosterone.

Blindness influences the growth of institutionalized prepubertal subjects.

To investigate if blindness influences the growth rate of young subjects we measured height and weight of 71 prepubertal blind subjects (33 females and 38 males) aged 7–10 yr, in Tanner stage one puberty, living at the Institute “Martuscelli’ for young blind individuals in Naples, Italy. They were divided into two groups: group 1 consisting of 27 subjects (14 females and 13 males) with total blindness; group 2 consisting of 44 subjects (20 females and 24 males) having only a light perception. The distribution in quintiles of their height and weight was compared by X2 test for trend to that of an age-matched large population (7902 subjects: 3808 females and 4094 males) of primary school from the same district. A stature significantly lower than controls was evidenced in both group 1 (p = 0.0006) and in group 2 (p = 0.008). When the comparison is performed taking into account the sex of subjects, the girls of both group 1 (p = 0.0014) and group 2 (p = 0.0004) show a stature significantly lower than female controls, whereas the stature of boys of both groups did not differ from that of male controls. No statistically significant differences in weight distribution were found between controls and either group 1 and group 2. Our results suggest that total or partial blindness could influence negatively the growth of prepubertal subjects; in particular it can cause short stature or growth delay especially in female sex.

Plasma thyrotropin, thyroxine, triiodothyronine, free thyroxine, free triiodothyronine, and cortisol levels in blind prepubertal boys

Findings on thyroid function in blind subjects are lacking. The aim of this study was to investigate the thyroid hormonal pattern in prepubertal blind subjects. Six healthy and 8 blind males, aged 7–10 yr, in Tanner stage one puberty, living at Institute “Martuscelli” for blind young subjects, Napoli, Italy, were studied. Each had a TRH (200 µg) test at 08:00 h after nocturnal rest. Plasma TSH, T4, T3, free T4(FT4), free T3(FT3) and cortisol (F) were measured by RIA. Our blind subjects show levels of TSH (basal values and absolute peak after TRH), T4, T3 and F normal but FT4 and FT3 levels significantly higher than controls (39 pg/ml ± 4.7 vs 12 ± 0.6, p< 0.001; 14 pg/ml ± 1.3 vs 4.7 ± 0.2, p< 0.001, respectively). Our results, similar to those found in some patients with euthyroid hyperthyroxinemia, suggest that the prolonged inability to receive light signal could influence the metabolism of thyroid hormones and/ or cause a tissue resistance to their action, even if this hypothesis must be verified by future more extensive investigations.

Circannual Variations of Plasma Thyrotropin in Klinefelter’s Syndrome

The aim of this study was to explore the occurrence of abnormalities in the circannual thyrotropin (TSH) rhythm in Klinefelters syndrome (KS). For 3 years, 69 healthy adult males and 73 patients with KS, usually living in Sardinia, were studied by a cross-sectional design. Plasma samples were taken between 08.00 and 09.00 h and TSH was radioimmunoassayed. First, the mean (+/- SD) of the data, grouped for each month of the year, was estimated to seek any macroscopic annual variation. Then, a cosine function was fitted to the single serially independent data by the single cosinor method in order to test for any statistically significant rhythm and, if the no-rhythm assumption is rejected, to describe the circannual parameters. Our patients showed circannual mean TSH concentrations lower than controls (p less than 0.001) without any statistically significant circannual rhythm, which was instead apparent in normal subjects with the annual crest time in December (95% CL November-February). Our results support the hypothesis that in KS the impaired TSH secretion may be related to abnormalities in the hypothalamic-pituitary coordination of the circannual rhythmicity of this hormone.

Endocrine Function in Subjects Treated for Childhood Hodgkins' Disease

Six prepubertal children (2 F and 4 M, aged 3-11.5 years, Group I) and six adults (3 F and 3 M, aged 15-21.5 years, Group II), were treated during childhood for Hodgkins Disease (HD). They received contemporary chemotherapy with either ABVD, MOPP or both and mantle or laterocervical irradiation. Three patients also received abdominal irradiation. All subjects were studied off therapy for 0.2—2 years (Group I) and 3—9 years (Group II). Pituitary function was investigated by evaluation of basal plasma levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), Cortisol (F), estradiol (E2), and testosterone (T). In males, Τ was also measured 72h after 100 U/Kg i.m. of human chorionic gonadotropin. Semen analysis in males and pelvic ultrasound in females of Group II were also performed. Our patients showed significantly (P < 0.05-0.001) increased levels of: FSH in females of both groups and in males of Group II, LH in girls of Group I, PRL in girls of Group I and in males of both groups, TSH in females of both groups. Hodgkins patients showed significantly decreased levels of basal (p <0 .005) and stimulated (p < ±0.05) Τ in males of Group II. Moreover, all males of Group II showed oligo-azoospermia. Our results seem to indicate that combined theapy for childhood HD often results in abnormal endocrine function; in particular, increased PRL, FSH and TSH secretion. Reprint Address: Dr. Laura Perrone Via Belisar Corenzio 33 80127 Napoli, Italy INTRODUCTION Abnormal endocrine funct ion is a known complication of combined chemoand radiation-therapy for Hodgkins Disease (HD) /1 /. Most reports have focused on adult subjects and studied with the pituitary-thyroid or pituitary-gonadal axes separately. After therapy for childhood HD data on thyroid /2/ or gonadal /3,4/ function are conflicting, while data on Cortisol and prolactin secretion are scarce. The present study was aimed at evaluating the effects on the endocrine secretion of combined therapy for HD during childhood. PATIENTS AND METHODS We studied 12 subjects treated for HD during childhood with chemotherapy (ABVD: cases 1-3; MOPP: cases 9,12; ABVD plus MOPP: cases 4-8, 10, 11) and mantle (2500-5000 rad, cases 2, 5-9, 11), or laterocervical irradiation (1750-4500 rad, cases 1,3,4,10,12) associated with abdominal irradiation (2500 rad) in 3 cases (4,6,8). In all patients except case 12, lymphoangiography was performed. The age when studied was prepubertal in 6 cases (2 F and 4 M, aged 3-11.5 years, off-therapy since 0.2-2 years Group I) and adult in the other 6 (3 F and 3 M, aged 15-21.5 years, off-therapy since 3-9 years, Group II). Control groups consisted of 63 age and sex-matched subjects, 20 prepubertal (10 F and 10 M) and 43 adult (23 F and 20 M). Clinical data of patients are reported in Table 1. Informed consent of patients or of their parents was obtained. Fasting blood samples were taken after nocturnal rest and plasma stored at -25°C in several tubes to facilitate multiple determinations. Each sample VOL. 3, No. 3,1989 175 176 LPERRONE et al. TABLE 1: Clinical Data of Hodgkins Disease Cases Age at Age at Years therapy Radiation study off No. Sex (yr) Chemotherapy dose field (yr) therapy Group I 1 F 3.0 ABVD 2000 LC 4.7 1.0 2 Ε 9.0 ABVD 2 5 0 0 Μ 11.5 2.0 3 Μ 2.4 ABVD 2000 LC 3.0 0.3 4 Μ 6.7 ABVD+MOPP 2500 LC 9.4 1.2 2 5 0 0 A 5 Μ 10.0 ABVD+MOPP 2500 Μ 10.8 0.2 6 Μ 7.7 ABVD+MOPP 2500 Μ 8.6 0.2 2500 A Group II 7 F 12.2 ABVD+MOPP 4 0 0 0 Μ 15.0 3.0 8 Ε 15.0 ABVD+MOPP 4 0 0 0 Μ 18.2 3.