Plasma 17OH-progesterone Research Articles

Дефицит витаминов и микронутриентов и особенности репродуктивного здоровья у женщин

Aim: to identify the content of vitamins and micronutrients in the blood of young female patients. Patients and Methods: a prospective single-center study included young female patients aged 18–24 years with complaints of menstrual disorders (MD) or manifestations of androgen-dependent dermopathy (acne, seborrhea, alopecia). Clinical, anamnestic and anthropometric parameters, hormonal profile involved in the realization of reproductive function, a number of biochemical blood parameters, and pelvic ultrasound data were evaluated. Results: the study included 133 female patients divided into 4 groups. Group 1 (n=53) consisted of female patients with MD, group 2 (n=44) — women with manifestations of hyperandrogenism (HA; acne and post-acne, alopecia, seborrhea) and MD, group 3 (n=9) — female patients with HA manifestations without MD, group 4 (n=27) — female patients without HA and MD (conditionally healthy). 41% of female patients of the 1st and 2nd groups and 44% of the 3rd group showed signs of an increase in the ovarian volume and changes in their structure (multifollicular or polycystic ovaries). Echographic signs of anovulation were detected in 26.1, 32.3 and 35.0% of female patients in groups 1, 2 and 3, respectively. Comparison of the androgenic steroid level in the groups did not reveal statistically significant differences, however, there were borderline cortisol levels and higher values of plasma 17-OH progesterone (vs the group 1) in groups 2 and 3. Values of gonadotropins did not differ significantly, but the LH/FSH ratio was higher in group 2, although unreliable. Hyperprolactinemia was detected in every fourth female patient of groups 1, 2, 3 (value range from 737 to 1079 mIU/L). 25(OH)D content was reduced in all three groups, amounting to 16.4±8.4, 24.7±13.2 and 11.4±4.5 ng/mL, respectively. Although homocysteine levels were borderline (11.5±2.9, 9.7±2.8 and 9.4±2.7 μmol/L), they differed statistically significantly (p<0.0002) in the groups. Besides, borderline low levels of folic acid, vitamin B12 and serum ferritin were found in groups 1, 2 and 3. Conclusion: the disorders detected in women with MD and HA should be taken into account when forming the treatment tactics. KEYWORDS: menstrual disorders, hyperandrogenism, homocysteine, ferritin, vitamin D, B vitamins. FOR CITATION: Kudinova E.G. Deficiency of vitamins and micronutrients and reproductive health in women. Russian Journal of Woman and Child Health. 2022;5(3):182–187 (in Russ.). DOI: 10.32364/2618-8430-2022-5-3-182-187.

Identification of a novel mutation in DAX1/NR0B1A gene in two siblings with severe clinical presentation of adrenal hypoplasia congenita

To search for mutations in DAX1/NR0B1A gene in siblings to establish the molecular etiology of the adrenal hypoplasia congenita (AHC), a rare potentially life-threatening disorder. We describe two siblings who presented with salt-wasting syndrome in the newborn period and received hormonal replacement for primary adrenal insufficiency. A diagnostic hypothesis of AHC was suspected because the children maintained, during hormonal treatment, low plasma 17-OH progesterone (17-OHP) and androgens, despite high ACTH levels. DAX1 gene was studied by molecular analysis, which showed a mutation, confirming the diagnosis in the siblings and a heterozygous state in the mother. Direct sequencing of DAX1 revealed an insertion of an adenine base (c1382-1383 A ins), which lead to a pMet461Asp substitution. A novel frameshift mutation of DAX1 gene, which established the molecular etiology of the AHC in the siblings, was identified. Obtaining a precise genetic diagnosis of this adrenal disorder, which, sometimes, cannot be confirmed only by clinical aspects, may have important implications for the long-term management of the disease.

Ambiguous genitalia in the newborn.

Ambiguous genitalia in the newborn need immediate and rational management. This complex situation requires a strategy of clinical, hormonal, genetic, molecular, and radiographic investigation to determine the etiology of the intersex state and orient the therapeutic approach. Physical examination is key to diagnosis. Careful palpation to locate gonads at the genital folds or in the inguinal region provides the first element for diagnostic orientation. If gonads are absent, a diagnosis of female pseudohermaphroditism seems advisable; if gonads are palpated, a diagnosis of male pseudohermaphroditism is more appropriate. Karyotyping is systematic while polymerase chain reaction (PCR) analysis of the SRY gene provides information about the presence of a Y chromosome within 1 day. Hormonal investigation should be based on clinical and genetic orientation. Substantially elevated plasma 17-OH progesterone will confirm the diagnosis of congenital adrenal hyperplasia due to deficiency in 21-hydroxylase. Testicular stimulation with human chorionic gonadotropin (hCG) will determine the functional value of testicular tissue. Exploration of the genitourinary axis is principally carried out by ultrasound and genitography. By the end of these investigations, the medical team should be able to give a precise diagnosis. Female pseudohermaphroditism may be due to excess fetal androgens (congenital adrenal hyperplasia), increased androgen production of maternal origin, or placental androgen excess. In male pseudohermaphroditism, if testosterone rises normally after hCG stimulation, androgen resistance is indicated. If it does not rise after this test, either testicular dysgenesis or disturbance in testosterone biosynthesis may be responsible. The assignment of sex for rearing must be guided by the etiology of the genital malformation, the anatomic condition, and family considerations. In cases of female pseudohermaphroditism, the newborn should always be declared to be of female sex at birth. In cases of male pseudohermaphroditism, great care should be taken in the declaration of male sex: the potential for reconstructive surgery and the pubertal "programmed" response of the external genitalia to endogenous and exogenous testosterone are determinant. Management of ambiguous genitalia in the newborn requires an entire multidisciplinary team in every step of the diagnostic procedure, the choice of sex assignment, and the treatment strategy.

17-Hydroxyprogesterone response to ACTH in bilateral and monolateral adrenal incidentalomas.

The aim of our study was to assess the frequency of 21-hydroxylase deficiency, a cause of congenital adrenal hyperplasia (CAH), in incidentally discovered asymptomatic adrenal masses (incidentalomas) and to compare the prevalence of this enzymatic disorder in monolateral (M) and bilateral (B) forms. Twenty-seven patients with incidentalomas (12 M and 15 B) and 16 sex and age-matched controls (C) received synthetic adrenocorticotropin (ACTH, 250 micrograms i.v.). Plasma 17-OHprogesterone (17-OHP) and cortisol were collected in basal conditions and after 30, 60, 90 minutes. Basal plasma 17-OHP in C [1.25 +/- 0.15 (0.61) ng/ml, mean +/- SE (SD)] was not significantly different from that in patients with M [0.85 +/- 0.13 (0.44) ng/ml] or B [0.94 +/- 0.23 (0.90) ng/ml] incidentalomas. After ACTH, 17-OHP levels significantly (p < 0.05) increased in C, in M and B incidentalomas. However, the rise in plasma 17-OHP in C both in terms of peak [2.5 +/- 0.28 (1.1) ng/ml] and of AUC values [174 +/- 16 (64) ng/ml/min] was significantly lower than that observed in M [peak 6.32 +/- 1.66 (5.7) ng/ml, p < 0.01; AUC 410 +/- 111 (385.5) ng/ml/min, p < 0.01] and in B [peak 8.84 +/- 1.98 (7.65) ng/ml, p < 0.001; AUC 613 +/- 149 (579.3), ng/ml/min, p < 0.001] incidentalomas. Individual data indicated that while 17-OHP response to ACTH in C never reached 5 ng/ml (cut-off for normal response), 16 out of 27 patients with incidentalomas (59.2%) exceeded this value. Moreover, the abnormal response was more frequently observed in B (66.6%) than in M (50%) incidentalomas. Basal and stimulated plasma cortisol did not differ among the three groups. In conclusion, our data indicate that in adrenal incidentalomas the endocrine pattern of 21-hydroxylase deficiency is very common and that this enzymatic defect is more frequent in bilateral than in monolateral lesions.

Multiple or single 21-hydroxylases in congenital adrenal hyperplasia?

The objective of this study was to determine whether there is a single 21-hydroxylase in CAH ∗ ∗ In the paper CAH is used as an abbreviation for that form of congenital adrenal hyperplasia (or adrenogenital syndrome) caused by a defect in 21-hydroxylation. that is defective or multiple different 21-hydroxylases that are involved. The activity of the 17-OH progesterone 21-hydroxylase in cortisol biosynthesis was estimated by measuring plasma 17-OH progesterone and cortisol levels simultaneously at frequent intervals throughout the day in two patients with non-saltlosing CAH and three patients with salt-losing CAH. Plasma progesterone and corticosterone concentrations were also measured on the same blood samples as an index to progesterone 21-hydroxylase activity in the corticosterone biosynthetic pathway. During periods of maximal adrenal secretory activity it was found that plasma 17-OH progesterone concentrations were markedly elevated in all patients while cortisol levels were either low normal (in non-salt-losers) or low (in salt-losers). At the same time, plasma progesterone and corticosterone concentrations were normal or elevated in both forms of CAH. Although not conclusive, these results favor the multiple enzyme theory in the pathogenesis of CAH.

Continuing need for mineralocorticoid therapy in salt-losing congenital adrenal hyperplasia.

Four patients with salt-losing congenital adrenal hyperplasia (CAH) who had stopped mineralocorticoid therapy for several years, showed raised plasma concentrations of 17OH-progesterone and plasma renin activity, despite adequate glucoticoid therapy. One patient was able to reduce urinary sodium excretion when the sodium intake was restricted. Another patient who was a salt-loser, developed signs of an adrenal crisis when salt deprived. In comparison, one nonsalt-loser and 2 normal subjects decreased urinary sodium excretion in response to sodium restriction. The addition of fludrocortisone (100 micrograms) to usual maintenance doses of glucocorticoid, resulted in normal levels of plasma 17OH-progesterone and plasma renin activity in all 4 salt-losers. Two female salt-losers, with raised plasma testosterone concentrations, began menstruating when their plasma testosterone concentrations returned to normal after treatment with fludrocortisone. It is recommended that salt-losing CAH patients should be given mineralocorticoid, in addition to glucocorticoid therapy, at least until adult life.

Plasma 17OH-progesterone concentrations in newborn infants.

Plasma concentrations of 17OH-progesterone were determined in 60 normal newborn infants aged between 3 and 36 hours. Mean levels decreased rapidly during this time after removal of the placental contribution of this steroid. A further 70 normal infants, studied between ages 2 and 7 days, showed a mean plasma 17OH-progesterone concentration of 3.5 nmol/1 (1.2 ng/ml). By comparison, plasma concentrations in untreated infants with congenital adrenal hyperplasia were markedly raised. At 36 hours of age, there was an obvious difference between plasma levels of this steroid in normal and affected infants. Determination of plasma 17OH-progesterone concentrations are valuable in the evaluation of disorders of sexual differentiation and electrolyte balance in newborn infants, provided due care is given to the timing of sample collections.

3&amp;beta;-Hydroxysteroid Dehydrogenase Deficiency Follow-Up Study in a Girl with Pubertal Bone Age

Follow-up data on a girl with 3 beta-hydroxysteroid dehydrogenase deficiency at a pubertal bone age are presented. On examination at age 14.7 years (bone age 12 years), there was no spontaneous breast development. On treatment with hydrocortisone and fludrocortisone, most steroids with the exception of increased 17OH-pregnenolone in plasma and delta 5-pregnenetriol and pregnanetriol in urine, were normal. After 1 week off hydrocortisone, plasma 17OH-pregnenolone, DHA and delta5-androstenediol and urinary delta 5-pregnenetriol and pregnanetriol increased markedly, while plasma 17OH-progesterone increased only slightly. On increased hydrocortisone medication, there was no response of plasma estradiol to HMG. This first observation of a pubertal girl with 3 beta-hydroxysteroid dehydrogenase deficiency indicates that in this patient, the defect persists at a pubertal bone age and that it is not limited to the adrenals, but also affects the ovaries. Girls with this type of defect thus require estrogen replacement at a bone age of about 12 years. The large quantities of pregnanetriol in the urine are not due to an incomplete defect or an additional 21-hydroxylase deficiency, but most likely to the peripheral or hepatic conversion of 17OH-pregnenolone or delta 5-pregnenetriol.

Unusual heterozygotes (HE) of congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency

In 3 otherwise healthy relatives of patients with CAH, clinical and/or biochemical findings exceeded those in usual HE : 1 mother and 1 sister (2.8 yrs) of a CAH patient had hirsutism and hypertrichosis and excreted pregnanetriolone (PTL, 1380 and 263 μg/24 h). The mother had increased basal and post-ACTH plasma 17OH-progesterone (17OHP, 296 and 7170 ng per 100 ml) like a homozygote (HO), but normal or only slightly increased plasma and urine testosterone (T, 73 ng/100 ml and 16.4 μg/24 h). 1 adult brother of a patient in a second family also excreted PTL (3160 μg/24 h) and had high plasma 17OHP (1905 ng/100 ml basal and 6352 after ACTH). His plasma-T (758 ng/100 ml) and testicular volume (12-15 ml) were normal. It is concluded that these subjects are unusually marked HE rather than mild HO. In females, this condition has to be included in the differential diagnosis of idiopathic hirsutism. In males, it will pass unnoticed unless relatives of CAH-patients are systematically tested.