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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 2 715-719
Copyright © 2000 by The Endocrine Society

Original Studies

Normal Reproductive Function in Leptin-Deficient Patients with Lipoatropic Diabetes

F. Andreelli, H. Hanaire-Broutin, M. Laville, J. P. Tauber, J. P. Riou and C. Thivolet

Endocrinology and Diabetes Department, Hospital E Herriot (F.A., M.L., J.P.R., C.T.), 69437 Lyon; and the Diabetes Department, Hospital de Rangueil (H.H.-B., J.P.T.), 31403 Toulouse, France

Address all correspondence and requests for reprints to: Dr. F. Andreelli, Pavillon X, Hôpital E Herriot, 69437 Lyon Cedex 03, France.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
To further examine the relationships between leptin and female reproductive axis, we conducted hormonal studies in two patients with lipoatropic diabetes that occurred before puberty. Despite complete atrophy of sc and visceral adipose tissue, menarche occurred in these two patients between 11–12 yr of age, followed by regular menstrual cycles. One patient had been pregnant three times, giving birth to children who did not develop the disease. In our two patients, repeated analysis revealed leptin levels below 1 ng/mL (normal range for 20 insulin-treated diabetic women, 2–23 ng/mL for body mass index of 14–39 kg/m2; personal data). We measured peripheral levels of estradiol, progesterone, FSH, LH, free testosterone, and androstenedione within the first 5 days of the menstrual cycle, and we tested the reactivity of pituitary after iv injection of 100 µg GnRH. The variation in body temperature in the morning before arising was also analyzed. We showed that 1) all measured levels of hormones were in the normal range for both patients; and 2) low levels of leptin did not impair the development of reproductive function in one patient and was associated with normal gonadal function in both patients. We conclude that puberty and fertility can occur despite chronic low serum levels of leptin. This suggests that leptin is not fundamental to the maintenance of normal reproductive function in humans.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
LEPTIN IS A 16-kDa peptide secreted by the adipocyte and acts through specific receptors at the level of the hypothalamus (1). In rodents, leptin has negative effects on appetite and energy expenditure and promotes fertility (2, 3, 4). Data are just beginning to accumulate regarding the role of leptin in the regulation of puberty in humans. It has been suggested that a minimum weight for height is associated with the onset and maintenance of normal menstrual function in young women (5). It is also well established that highly trained athletes, ballet dancers, and women who diet excessively can develop primary or secondary amenorrhea (6). Other studies showed a progressive increase in serum leptin levels with age in prepubertal boys and girls associated with a possible peak of leptin levels before the onset of puberty (7, 8). Lastly, mutation of human genes encoding leptin and its receptor results in severe early onset obesity and failure of initiation of puberty and the establishment of secondary sexual characteristics (9, 10). These data raised the question of the possible involvement of leptin in the onset of puberty and/or the maintenance of reproductive function in humans. However, several important questions remain to be answered. First, it remains to be explained why obese children with high leptin levels have no precocious puberty. In addition, no study demonstrating a feedback loop between leptin and reproductive endocrine axis is available. The secretion of leptin is influenced by many hormones (for review, see Ref. 11), leptin levels are not correlated with gonadal hormone levels in children with central precocious puberty (12), and the circadian rhythm of leptin secretion is independent of pulsatile anterior pituitary hormone secretion, as shown in children with perinatal stalk transsection syndrome (13).

Congenital lipoatropic diabetes (LD) or Seip-Berardinelli syndrome is characterized by the absence of visceral and sc adipose tissue, insulin resistance, hypertriglyceridemia, fatty liver, and low leptin levels (14, 15, 16, 17). Recently, Pardini et al. reported frequent amenorrhea or irregular menstrual cycles in generalized LD women, whereas their menarche occurred between 12–14 yr of age, thus not abnormally delayed (18). However, no evaluation of gonadal function was available in the lipoatropic women described in Pardini’s report. To further investigate the role of leptin in puberty and female reproductive function, we studied two patients with generalized lipoatrophy occurring in early infancy. We conclude from these exceptional cases that leptin is probably not involved in the onset of puberty and/or the maintenance of fertility in humans.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Patients

Two patients with LD were recruited. One woman (case 1) had typical congenital generalized LD, as shown in Fig. 1Go. Her body mass index (BMI) was 17 kg/m2. The absence of sc and visceral fat mass was confirmed by a computed tomography abdominal scan at the level of the second lumbar vertebra (Fig. 2Go) and biphotonic absorptiometry. Hirsutism and ambisexual development were absent. Diabetes was diagnosed at 15 yr of age, and oral antidiabetic treatment was started 1 yr later. A high dose insulin trial of 5 IU/kg·day was started at 35 yr of age, leading to an improvement of metabolic control. Hypertriglyceridemia was treated by fibrates. The other patient (case 2) had a typical sporadic acquired generalized LD. She completely lost her adipose tissue before puberty (at 9 yr of age) during a period of 15 days when she lost 10 kg of body weight. Diabetes mellitus was discovered at 25 yr of age and is being treated by a high dose insulin trial of 3.2 IU/kg·day (association of NPH and lispro insulin analog). Her BMI was 17 kg/m2. The endocrine evaluations of the LD patients were performed on the fifth day of the menstrual cycle. No patient used oral steroidal contraceptives. Despite insulin resistance, the two patients had an acceptable control of their diabetes at the time of endocrine evaluation with hemoglobin A1C values of, respectively, 8% (case 1) and 5.3% (case 2; normal values, 4–6%).



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  		Figure 1. One woman had typical congenital generalized LD (case 1).

 


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  		Figure 2. Absence of sc and visceral fat mass was confirmed by a computed tomography abdominal scan at the level of the second lumbar vertebra and biphotonic absorptiometry.

 
RIAs

Serum levels of the following hormones were measured by radioimmunological methods using commercially available kits: leptin (human leptin RIA kit, Linco Research, Inc., St. Charles, MO) with an intraassay coefficient of variation (CV) of 10% and an interassay CV of 15%, both at the least detectable dose of leptin of 0.5 µg/L); insulin (insulin immunoradiometric assay, Biosource Technologies, Inc., Europe SA, Strasbourg, France) with an intraassay variability of less than 5% and an interassay variability of less than 10%; estradiol (Immunotech, Marseille, France) with intraassay CVs of 3.1% and 15.1% at 511 and 15.7 pg/mL, respectively, and interassay CVs of 4.1% and 14.4% at 202 and 2611 pg/mL; orogesterone (Ortho-Clinical Diagnostics, Amersham, UK) with intraassay CVs of 2% and 5.1% at 12.1 and 0.95 ng/mL, respectively, and interassay CVs of 3.7- 9.4% at 5.53 and 1.02 ng/mL, respectively; free testosterone (Berhing Diagnostic, Marseille, France) with intraassay CVs of 3.2% and 4.3% at 40.3 and 4.6 pg/mL, respectively, and interassay CVs of 3.4% and 5.5% at 42.4 and 4.7 pg/mL; dehydroepiandrosterone sulfate (Immunotech) with intraassay CVs of 3.2% and 7.4% at 52.4 and 26.4 µg/mL and interassay CVs of 3.4% and 10.59% at 213.3 and 24.4 µg/mL, respectively; and androstenedione (Immunotech) with intraassay CVs of 5.6% and 8.1% at 8.72 and 2.75 ng/mL, respectively, and interassay CVs of 6% and 11.9% at 9.05 and 0.92 ng/mL, respectively. The gonadal hypothalamic-pituitary axis was evaluated in patient 1, as determining by measuring plasma LH and FSH levels before and every 15 min for 120 min after iv injection of 100 µg GnRH (Stimu-LH 50, Roussel Laboratories, Paris, France). LH and FSH were measured by radioimmunological methods using commercially available kits: LH (Immunotech), intraassay CVs of 2.7% and 4.3% at 16.9 and 53.5 IU/L, respectively, and interassay CVs of 0.4% and 3.7% at 4.45 and 62.1 IU/L, respectively; and FSH (Immunotech), intraassay CVs of 1.4% and 2.6% at 44.6 and 15.6 IU/L, respectively, and interassay CVs of 4.2% and 6.3% at 37.6 and 7.37 IU/L, respectively.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Leptin levels

Patient 1 had plasma leptin levels below 1 ng/mL (mean ± SEM, 0.9 ± 0.1 ng/mL; n = 3; normal range for 20 insulin-treated diabetic women, 2–23 ng/mL for BMI of 14–39 kg/m2; personal data). Patient 2 also had significantly lower levels than controls (mean ± SEM, 0.8 ± 0.1 ng/mL; n = 3).

Age of onset of puberty and fertility

Patient 1 started menarche at 12 yr of age followed by regular monthly menstrual cycles until now (38 yr of age). The patient was unmarried at the time of the study and never used steroidal contraceptives. In patient 1, the sustained increase in body temperature suggested the occurrence of ovulation during the menstrual cycle. Menarche began in patient 2 at 11 yr of age, a few years after the achievement of generalized lipoatrophy, with regular menstrual cycles until now. She has been pregnant three times, and each pregnancy was complicated by fetal macrosomy because of bad metabolic control during pregnancy. She now uses only barrier methods for contraception. Pelvic ultrasounds in both patients show no polycystic ovarian disease.

Hormonal evaluation

The endocrine studies showed clearly normal gonadal function in the two LD patients and normal reactivity of gonadal axis after GnRH injection (Table 1Go). No hyperandrogenism was noted, and the levels of female hormones were in the normal range.


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  		Table 1. Endocrinological data for the two lipoatrophic diabetes patients

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
A rapidly growing body of research has demonstrated that leptin is an important hormone for both the metabolic and the reproductive axis in rodents. For example, leptin administration restores fertility in ob/ob mice (4). In humans, the main determinant of serum leptin levels is body fat mass. Some researchers suggested that leptin is also necessary to maintain normal reproductive axis in humans. We studied the gonadal axis of two female patients with LD (one of exceptional congenital form and one of acquired complete lipoatrophy in early childhood), as this rare disease is characterized by chronic low leptin levels since early infancy. This disease was first recognized in the 1950s. Even though it has been reported that lipoatropic disease is associated with delayed menarche (16, 18), the literature published during these 40 yr clearly showed that fertility is maintained in these women despite very low fat mass, and some observations of pregnancy have been reported (for review, see Ref. 16). In agreement with the report of Pardini et al. (11 congenital and 11 acquired generalized LD patients), we showed that despite very low serum levels of leptin (<1 ng/mL confirmed different times during the last 3 yr), our two lipoatropic patients had clearly normal puberty and secondary sexual characteristics development (18). The atrophy of the breast can be explained by the general atrophy of fat mass. Patient 1 had normal gonadal evaluation, and the change in body temperature in midcycle was concordant with ovulation. It is interesting to note that patient 2 was sufficiently fertil to begin and proceed with three pregnancies without the need of ovarian stimulation by gonadotropin. Therefore, even if we cannot exclude that in lipoatropic women, very low leptin levels are sufficient for sexual development, our subjects demonstrate that the onset of puberty and normal reproductive function can occur despite chronic low leptin levels. Interestingly, anorexia nervosa is another condition characterized by chronic low plasma leptin levels. It is surprising that despite comparable low serum leptin levels, anorectic patients are amenorrheic, whereas our LD patients are not (19). Leptin levels rise considerably during weight gain in recovered anorectic patients without leading to the rapid reappearance of menstruation. This suggests that normalization of the gonadal axis in this situation takes time and/or involves factors in addition to leptin itself (20).

Results concerning the hypothetical role of leptin during puberty are contradictory. Mantzoros et al. showed a possible brief pulse in leptin levels preceding the onset of puberty (8), but Ahmed et al. were unable to confirm this point in a longitudinal study of prepubertal children (7). Furthermore, it is known that leptin levels are higher in males than females during early puberty and decline thereafter (7, 8). This divergent pattern of serum leptin levels during sexual maturation of boys and girls is interpreted as a negative effect of testosterone on leptin secretion, as confirmed by in vitro studies on adipose tissue (21). According to this point of view, the variation in leptin levels during puberty has been considered independent of changes in body composition measured by body weight (22), BMI (10, 23, 24, 25, 26, 27, 28, 29, 30), skinfold thickness (9, 31), or dual energy x-ray absorptiometry (32). However, it is not excluded that these leptin changes observed throughout puberty could also be linked at least in part with the increase in muscle mass in boys, whereas girls accumulate fat mass. Indeed, it is important to notice that abundant literature from the last years comparing the different techniques of assessment of body composition in children have showed that BMI is not the best marker for body composition in puberty (33). Skinfold thickness measurements (34), dual energy x-ray absorptiometry (35, 36, 37, 38, 39), and bioelectric impedance measurements may not accurately measure body fat mass in children in contrast to total body potassium (40) or the three-component water density model (41). It is therefore difficult to conclude that leptin variations throughout puberty are independent of changes in body composition as reported previously. According to this, the only paper published to our knowledge that reported the body composition of children measured by the H2(18)O dilution principle showed that leptin levels are similar in prepubertal children and pubertal adolescents and are correlated only with body fat content. No gender difference in leptin independent of adiposity was found (42). Considering these data together and because no study of longitudinal follow-up of leptin levels during puberty with assessment of fat mass by the 3C-H2O method (or another istotopic method) is available, it is difficult today to believe that the observed variation in leptin levels during puberty in children is independent of body composition and that leptin per se triggers puberty.

In conclusion, we showed that two LD patients are fertile despite chronically low levels of leptin. Pubertal development and menarche in these patients were normal. This suggests that the critical weight (fat) hypothesis has to be confirmed because confounding factors other than leptin are plausible. This also suggests that the infertility observed in human subjects with morbid obesity associated with mutation of the leptin gene or mutation of the gene encoding for the leptin receptor probably involved a mechanism other than leptin alone, and leptin is probably not the trigger of puberty in humans.

Received August 12, 1999.

Revised November 2, 1999.

Accepted November 5, 1999.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. 1994 Positional cloning of the mouse obese gene and its human homologue. Nature. 372:425–432.[CrossRef][Medline]
  2. Halaas JL, Gajiwala KS, Maffei M, et al. 1995 Weight-reducing effects of the plasma protein encoded by the obese gene. Science. 269:543–546.[Abstract/Free Full Text]
  3. Ahima RS, Prabakaran D, Mantzoros C, et al. 1996 Role of leptin in the neuroendocrine response to fasting. Nature. 382:250–252.[CrossRef][Medline]
  4. Chehab FF, Lim ME, Lu R. 1996 Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin. Nat Genet. 12:318–320.[CrossRef][Medline]
  5. Scott EC, Johnston FE. 1982 Critical fat, menarche, and the maintenance of menstrual cycles: a critical review. Adolesc Health Care. 2:249–260.
  6. Warren MP. 1999 Health issues for women athletes: exercise-induced amenorrhea. J Clin Endocrinol Metab. 84:1892–1896.[Free Full Text]
  7. Ahmed ML, Ong KK, Morrell DJ, et al. 1999 Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition. J Clin Endocrinol Metab. 84:899–905.[Abstract/Free Full Text]
  8. Mantzoros CS, Flier JS, Rogol AD. 1997 A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab. 82:1066–1070.[Abstract/Free Full Text]
  9. Montague CT, Farooqi IS, Whitehead JP, et al. 1997 Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 387:903–908.[CrossRef][Medline]
  10. Clement K, Vaisse C, Lahlou N, et al. 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 392:398–401.[CrossRef][Medline]
  11. Trayhurn P, Hardie L J, Hoggard N, Rayner D V. 1997 Regulation of leptin production. In: Blum WF, Kiess W, Rascher W, eds. Leptin: the voice of adipose tissue. Heidelberg-Leipzig: J A Barth Verlag; 69–77.
  12. Palmert MR, Radovick S, Boepple PA. 1998 The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty. J Clin Endocrinol Metab. 83:1091–1096.[Abstract/Free Full Text]
  13. Pombo M, Herrera-Justiniano E, Considine RV, et al. 1997 Nocturnal rise of leptin in normal prepubertal and pubertal children and in patients with perinatal stalk-transection syndrome. J Clin Endocrinol Metab. 82:2751–2754.[Abstract/Free Full Text]
  14. Berardinelli W. 1954 An undiagnosed endocrinometabolic syndrome: report of 2 cases. J Clin Endocrinol. 14:193–204.
  15. Seip M. 1959 Lipodystrophy and gigantism with associated endocrine manifestations. A new diencephalic syndrome? Acta Paediatr. 48:555–574.[Medline]
  16. Seip M, Trygstad O. 1996 Generalized lipodystrophy, congenital and acquired (lipoatrophy). Acta Paediatr. 85(Suppl 413):2–28.
  17. Vigouroux C, Khallouf E, Bourut C, et al. 1997 Genetic exclusion of 14 candidates genes in lipoatrophic diabetes using linkage analysis in 10 consanguineous families. J Clin Endocrinol Metab. 82:3438–3444.[Abstract/Free Full Text]
  18. Pardini VC, Victoria IMN, Rocha SMV, et al. 1998 Leptin levels, ß cell function and insulin sensitivity in families with congenital and acquired genralized lipoatrophic diabetes. J Clin Endocrinol Metab 83:503–508.
  19. Hebebrand J, Hinney A, Ballauff A, et al. 1997 Leptin synthesis in anorexia nervosa: pathogenetic and therapeutic implications. In: Blum WF, Kiess W, Rascher W, eds. Leptin: the voice of adipose tissue. Heidelberg-Leipzig: J A Barth Verlag; 277–284.
  20. Hebebrand J, van der Heyden J, Devos R, et al. 1995 Plasma concentrations of obese protein in anorexia nervosa. Lancet. 346:1624–1625.
  21. Wabitsch M, Blum WF, Muche R, et al. 1997 Contribution of androgens to the gender difference in leptin production in obese children and adolescents. J Clin Invest. 100:808–813.[Medline]
  22. Garcia-Mayor RV, Andrade MA, Rios M, Lage M, Dieguez C, Casanueva FF. 1997 Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab. 82:2849–2855.[Abstract/Free Full Text]
  23. Giusti M, Guido R, Valenti S, Giordano G. 1999 Serum leptin levels in males with delayed puberty during short-term pulsatile GnRH administration. J Endocrinol Invest. 22:6–11.[Medline]
  24. Palmert MR, Radovick S, Boepple PA. 1998 Leptin levels in children with central precocious puberty. J Clin Endocrinol Metab. 83:2260–2265.[Abstract/Free Full Text]
  25. Falorni A, Bini V, Molinari D, et al. 1997 Leptin serum levels in normal weight and obese children and adolescents: relationship with age, sex, pubertal development, body mass index and insulin. Int J Obes Relat Metab Disord. 21:881–890.[CrossRef][Medline]
  26. Blum WF, Englaro P, Hanitsch S, et al. 1997 Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 82:2904–2910.[Abstract/Free Full Text]
  27. Clayton PE, Gill MS, Hall CM, Tillmann V, Whatmore AJ, Price DA. 1997 Serum leptin through childhood and adolescence. Clin Endocrinol (Oxf). 46:727–33.[CrossRef][Medline]
  28. Giusti M, Guido R, Valenti S, Giordano G. 1999 Serum leptin levels in males with delayed puberty during short-term pulsatile GnRH administration. J Endocrinol Invest. 22:6–11.
  29. Carlsson B, Ankarberg C, Rosberg S, Norjavaara E, Albertsson-Wikland K, Carlsson LM. 1997 Serum leptin concentrations in relation to pubertal development. Arch Dis Child. 77:396–400.[Abstract/Free Full Text]
  30. Blum WF, Englaro P, Hanitsch S, et al. 1997 Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 82:2904–2910.
  31. Kulik-Rechberger B, Rechberger T, Jakimiuk AJ. 1999 Leptin correlates with the skinfold thickness in prepubertal and pubertal girls. Acta Paediatr. 88:103–104.[CrossRef][Medline]
  32. Klein KO, Larmore KA, de Lancey E, Brown JM, Considine RV, Hassink SG. 1998 Effect of obesity on estradiol level and its relationship to leptin, bone maturation and bone mineral density in children. J Clin Endocrinol Metab. 83:3469–3475.[Abstract/Free Full Text]
  33. Clayton P E, Gill M S. 1997 Serum leptin, body mass index and body composition: studies in children, adults and elderly. In: Blum WF, Kiess W, Rascher W, eds. Leptin: the voice of adipose tissue. Heidelberg-Leipzig: J A Barth Verlag; 221–229.
  34. Ferrario M, Carpenter MA, Chambless LE. 1995 Reliability of body fat distribution measurements. The ARIC Study baseline cohort results. Atherosclerosis Risk in Communities Study. Int J Obes Relat Metab Disord. 7:449–457.
  35. Ogle GD, Allen JR, Humphries IR, et al. 1995 Body-composition assessment by dual-energy x-ray absorptiometry in subjects aged 4–26 y. Am J Clin Nutr. 61:746–753.[Abstract/Free Full Text]
  36. Mast M, Kortzinger I, Konig E, Muller MJ. 1998 Gender differences in fat mass of 5–7-year old children. Int J Obes Relat Metab Disord. 22:878–884.[CrossRef][Medline]
  37. Reilly JJ, Wilson J, Durnin JV. 1995 Determination of body composition from skinfold thickness: a validation study. Arch Dis Child. 73:305–310.[Abstract]
  38. Reilly JJ, Wilson J, McColl JH, Carmichael M, Durnin JV. 1996 Ability of biolectric impedance to predict fat-free mass in prepubertal children. Pediatr Res. 39:176–179.[Medline]
  39. Gutin B, Litaker M, Islam S, Manos T, Smith C, Treiber F. 1996 Body-composition measurement in 9–11-y-old children by dual-energy x-ray, absorptiometry, skinfold-thickness measurements, and bioimpedance analysis. Am J Clin Nutr. 63:287–292.[Abstract/Free Full Text]
  40. Schaefer F, Georgi M, Zieger A, Scharer K. 1994 Usefulness of bioelectric impedance and skinfold measurements in predicting fat-free mass derived from total body potassium in children. Pediatr Res. 35:617–624.[Medline]
  41. Roemmich JN, Clark PA, Weltman A, Rogol AD. 1997 Alterations in growth and body composition during puberty. I. Comparing multicompartment body composition models. J Appl Physiol. 83:927–935.[Abstract/Free Full Text]
  42. Arslanian S, Suprasongsin C, Kalhan SC, Drash AL, Brna R, Janosky JE. 1998 Plasma leptin in children: relationship to puberty, gender, body composition, insulin sensitivity, and energy expenditure. Metabolism. 47:309–312.[CrossRef][Medline]



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals