scholarly journals SUN-LB15 A Case of Familial Male-Limited Precocious Puberty With a Novel Mutation

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lindsey L Owens ◽  
Mauri Carakushansky ◽  
Shilpa Gurnurkar
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Novel Mutation ◽  
Elevated Serum ◽  
Bone Age ◽  
Serum Levels ◽  
Pubic Hair ◽  
Normal Serum ◽  
Skeletal Maturation ◽  
Penile Length

Abstract Introduction: Familial Male-Limited Precocious Puberty (FMPP), also known as testotoxicosis, is a rare cause of precocious puberty in males. It is caused by a mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR) gene, resulting in the receptor to be constitutively activated. This results in precocious puberty in males with rapid skeletal maturation and compromised final adult height if not treated. A combination on anti-androgens and aromatase inhibitors are the mainstay of treatment. Case: A 16-month-old male presented to our clinic due to concerns of precocious puberty. Pubic hair was noted at 6 months of age along with rapid growth acceleration. There was no known exposure to testosterone and no family history of early puberty or subnormal adult height. Upon presentation, his height was over the 99th percentile while his target height is at the 50th percentile. Physical examination revealed prepubertal testes with pubic hair at Tanner stage II. A bone age was reported as 12-18 months at a chronologic age of 12 months. Initial lab evaluation revealed normal serum levels of 17 OHP, androstenedione and DHEA-S with a slightly elevated serum LH (0.7mIU/ml), and very elevated serum testosterone level (289ng/dl). Leuprolide and ACTH stimulation tests as well as MRI of the abdomen and pelvis were normal. Serum levels of AFP, β-hCG and IGF-1 were also normal. Bone age advanced to 6 years at a chronological age of 21 months and to 8 years by 26 months of age. At 26 months of age, his stretched penile length measured 11cm. LH receptor testing was obtained, which revealed a novel heterozygous missense mutation in the LHCGR gene (c.1733A>C; p.Asp.578Ala). The mutation was reported to be a variant of unknown significance though likely in the pathological end of the spectrum by variant analysis with SIFT and PolyPhen. He was started on treatment with anastrozole 1 mg daily and bicalutamide 25 mg daily at 2 and 9/12 years of age. Pubertal progression, linear growth and skeletal maturation slowed down with treatment. His bone age remained stable at 13 years from the age of 2 and 10/12 years to 4 years old. Pubertal stage and stretched penile length have also remained stable on treatment. He is tolerating treatment well. Conclusion: We report a novel mutation in the LHCGR gene causing FMPP in a 6-month-old male who is responding very well to a combination of bicalutamide and anastrazole with marked decrease in growth velocity, pubertal progression and skeletal advancement.

scholarly journals Precocious puberty in a 24 month old Nigerian girl: case report

2020 ◽  
Vol 47 (4) ◽  
pp. 358-360
Author(s):  
I.O. Oluwayemi ◽  
A.A. Afolabi ◽  
E.O. Adeniji ◽  
T.O. Ayeni
Keyword(s):  
Precocious Puberty ◽  
Elevated Serum ◽  
Tanner Stage ◽  
Bone Age ◽  
Pubic Hair ◽  
Breast Development ◽  
Endocrine Disorders ◽  
Essentially Normal ◽  
History Of ◽  
Age And Sex

Precocious puberty refers to the appearance of signs of puberty at an earlier age than is considered normal. It occurs ten times more commonly in  girls than in boys. The overall incidence ranged from 1/5000 to 1/10,000 children. The cause is idiopathic in 90% of cases of female precocious  puberty. We present BA a 24 month old female toddler who presented with one year history of progressive breast development and 6 month history of pubic hair growth. There was associated increasing weight, height and vaginal secretion. There was no similar occurrence in the family. Mother attained menarche at 14 years of age. Essential finding at presentation revealed a toddler who is heavy and tall for age with a weight of 17kg (>95th percentile for age and sex), height of 90.5cm (90th percentile for age and sex), Occipito-frontal circumference of 49cm (normal). Her sexual maturityrating was Tanner stage 3 for breasts and stage 2 for pubic hair. An assessment of precocious puberty was made. Her investigation result showed an advanced bone age of 5 years; elevated serum gonadotrophins in the pubertal range; and essentially normal cranial CT. Abdomino-pelvic USS showed an enlarged uterus for age, and a dominant right follicle with internal echo measuring 17.1mm X 15.2mm. Parents were counseled on the need for treatment to arrest the progression of precocious puberty but yet to respond because of financial constraint after 2 years of diagnosis. Female precocious puberty is ten times more common than male precocious puberty. The aetiology is idiopathic in 90% of cases and It is amenable to treatment. Integration of the investigation and treatment of childhood endocrine disorders into the National Health Insurance scheme will be a great panacea to the challenge of prompt management in developing countries. Keywords: Precocious, puberty, 24 months old, female, idiopathic, poverty, Nigeria 

scholarly journals Homozygous SHBG Variant (rs6258) Linked to Gonadotropin-Independent Precocious Puberty in a Young Girl

2021 ◽  
Author(s):  
Victoria C Andriessen ◽  
Marissa Lightbourne ◽  
Chelsi Flippo ◽  
Fabio R Faucz ◽  
Angela Delaney ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Bone Age ◽  
Serum Levels ◽  
Young Girl ◽  
Sex Hormone Binding Globulin ◽  
Polycystic Ovaries ◽  
Shbg Level ◽  
History Of ◽  
Laboratory Investigations ◽  
Peripheral Precocious Puberty

Abstract Sex hormone-binding globulin (SHBG) in the blood is a major determinant of bioactivity for key sex steroids such as testosterone and estradiol. Low serum levels of SHBG have been associated with obesity, polycystic ovaries and metabolic syndrome, and other states associated with hyperandrogenemia. A 9-year, 6-month-old girl presented with a history of peripheral precocious puberty and aggressive behavior. The patient’s SHBG level was remarkably low for her age, at less than 5 nmol/L [reference range for a girl with a bone age of 10 years, 73 nmol/L (SEM= 10)](1). Upon genetic and protein analysis, the patient was found to have a homozygous missense potentially pathogenic variant in the SHBG gene (c.554 C>T, p.P185L); her parents were asymptomatic heterozygote carriers. Laboratory investigations supported the possible involvement of this genetic alteration in the patient’s phenotype. Various analyses of this variant support its pathogenicity, although the exact mechanism remains unclear. In conclusion, we present a genetic SHBG variant in the homozygote state that may have been associated with gonadotropin-independent precocious puberty in a young girl.

Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Carolina O. Ramos ◽  
Ana P M Canton ◽  
Carlos Eduardo Seraphim ◽  
Aline Guimarães Faria ◽  
Flavia Rezende Tinano ◽  
...  
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Bone Age ◽  
Overweight And Obesity ◽  
Leuprorelin Acetate ◽  
The Mean ◽  
Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

scholarly journals Growth and Pubertal Development in Elite Female Rhythmic Gymnasts

1999 ◽  
Vol 84 (12) ◽  
pp. 4525-4530 ◽  
Author(s):  
N. Georgopoulos ◽  
K. Markou ◽  
A. Theodoropoulou ◽  
P. Paraskevopoulou ◽  
L. Varaki ◽  
...  
Keyword(s):  
Body Fat ◽  
Adult Height ◽  
Pubertal Development ◽  
Optimal Growth ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Chronological Age ◽  
Average Height ◽  
Limited Information ◽  
Rhythmic Gymnasts

Optimal growth depends upon both environmental and genetic factors. Among environmental factors that could alter growth and sexual maturation are stress and intensive physical training. The influence of these factors has been documented in a variety of sports, but there is limited information on rhythmic gymnasts, who have entirely different training and performance requirements. The study was conducted during the 13th European Championships in Patras, Greece, and included 255 female rhythmic gymnasts, aged 11–23 yr. The study included measurement of height and weight, assessment of breast and pubic hair development, estimation of body fat and skeletal maturation, and registration of menarcheal age and parental height. Gymnasts were taller than average height for age, with mean height above and mean weight below the 50th percentile. Actual height sd score was positively correlated to weight sd score (P &lt; 0.001), number of competitions (P = 0.01), and body mass index (BMI; P &lt; 0.001). Predicted adult height sd score was positively correlated to weight sd score (P &lt; 0.001) and negatively to body fat (P = 0.004). There was a delay in skeletal maturation of 1.3 yr (P &lt; 0.001). Pubertal development was following bone age rather than chronological age. The mean age of menarche was significantly delayed from that of their mothers and sisters (P = 0.008 and P = 0.05, respectively), was positively correlated to the intensity of training and to the difference between chronological age and bone age (P &lt; 0.001 and P = 0.002, respectively), and was negatively correlated to body fat (P &lt; 0.001). In the elite female rhythmic gymnasts, psychological and somatic efforts have profound effects on growth and sexual development. Despite these aberrations, adult height is not expected to be affected.

scholarly journals A study on relationship between severity of diabetic retinopathy and subclinical hypothyroidism

2017 ◽  
Vol 5 (5) ◽  
pp. 1818
Author(s):  
Mitali Borooah ◽  
Shobhana Phukan
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Subclinical Hypothyroidism ◽  
Elevated Serum ◽  
Serum Levels ◽  
Severe Form ◽  
Normal Serum ◽  
Free Thyroxine ◽  
Serum Tsh

Background: Subclinical hypothyroidism (SCH) is defined as an asymptomatic condition characterized by normal serum levels of free thyroxine and elevated serum concentration of thyrotropin (>4.0µIU/ml). Association between diabetic retinopathy and SCH is unclear. Aim was to study the relationship between severity of diabetic retinopathy and SCH in patients of diabetic retinopathy with type 2 diabetes mellitus.Methods: 120 patients of diabetic retinopathy with known type 2 diabetes mellitus were taken and categorized them according to severity of diabetic retinopathy as per ETDRS classification. Serum thyrotropin (TSH) and free thyroxine (FT4) concentration were measured in all 120 patients. Patients with normal TSH and FT4 values are euthyroid patients and those with normal FT4 but TSH value >4µIU/ml are considered as having subclinical hypothyroidism. Severity of diabetic retinopathy is compared between the euthyroid and subclinical hypothyroid group.Results: Out of the 120 patients included in the study, 72 (60%) were male and 48 (40%) were female. 97 patients (80.83%) were Euthyroid and 23 patients (19.17%) had subclinical hypothyroidism. It was observed that prevalence of more severe form of diabetic retinopathy (severe NPDR and PDR) was higher in SCH group as compared to euthyroid group. Severity of diabetic retinopathy was compared with serum TSH level and it was seen that severity of diabetic retinopathy significantly increases with increase in serum TSH value.Conclusions: Patients with SCH had more severe form of diabetic retinopathy as compared to patients with euthyroidism. Severity of diabetic retinopathy significantly increases with increase in serum TSH value.

scholarly journals The relationship between systolic function and serum NGAL levels in patients with chronic heart failure of ischemic origin

2021 ◽  
Vol 23 (2) ◽  
pp. 184-188
Author(s):  
V. A. Lysenko ◽  
V. V. Syvolap ◽  
M. S. Potapenko
Keyword(s):  
Heart Failure ◽  
Heart Function ◽  
Systolic Function ◽  
Elevated Serum ◽  
Left Ventricular Systolic Function ◽  
Serum Levels ◽  
Left Ventricular ◽  
Normal Serum ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
The Relationship

Neutrophil gelatinase-associated lipocalin (NGAL) is considered one of the most informative biomarkers of chronic kidney disease (CKD). NGAL can also serve as a biomarker of cardiovascular disease and heart failure (HF). However, the relationship between systolic function and serum NGAL concentrations in patients with chronic HF (CHF) of ischemic origin remains insufficiently studied. The aim. To study the influence of tubulo-interstitial injury marker NGAL on systolic function in patients with CHF of ischemic origin. Materials and methods. The study included 51 patients with CHF, stage II AB, NYHA II-IV FC. Doppler echocardiographic examination was performed on the device Esaote MyLab Eight (Italy) according to standard methods. NGAL levels were analyzed using an ELISA kit (E-EL-H0096, Elabscience, USA). Depending to the concentration of serum NGAL, the patients were divided into 2 subgroups. In the first group (n = 37), the NGAL level was higher than 168 ng/ml, in the second (n = 14) – less than 168 ng/ml. Results. The mean serum NGAL concentration in the first subgroup was 192 (183; 200) ng/ml, in the second subgroup – 154 (134; 160) ng/ml. The patients with CHF of ischemic origin with tubulo-interstitial injury (according to the serum concentration of NGAL) did not differ significantly from the patients with CHF of ischemic origin without tubulo-interstitial injury in age (P = 0.950), height (P = 0.983), weight (P = 0.681), body surface area (P = 0.975). Most of left ventricular systolic function indicators showed a downward tendency (S 6.90 ± 2.85 cm/s vs. 7.67 ± 2.83 cm/s (P = 0.536); S lat 7.33 ± 2.08 cm/s vs. 11.00 ± 4.00 cm/s (P = 0.467); TEI LV 0.56 ± 0.26 c.u. vs. 0.49 ± 0.14 c.u. (P = 0.747)) in the patients with CHF of ischemic origin with elevated serum levels of NGAL compared to similar indicators in the patients with CHF of ischemic origin without tubulo-interstitial injury. The index of LVEF was significantly lower in the patients with CHF with elevated serum NGAL compared to that in the patients with CHF with normal serum NGAL (50.43 ± 17.85 % vs. 63.29 ± 13.24 % (P = 0.021)). Conclusions. Serum NGAL was not only the sensitive marker of tubulo-interstitial injury in patients with CHF of ischemic origin, but also appeared to be a predictor of changes in systolic heart function.

scholarly journals Congenital Hypothyroidism with Precocious Puberty-A Case Report

2011 ◽  
Vol 24 (1) ◽  
pp. 48-50
Author(s):  
M Sanaul Haque ◽  
SN Hasnain ◽  
MI Haque ◽  
MA Hossain ◽  
MI Bari
Keyword(s):  
Case Report ◽  
Congenital Hypothyroidism ◽  
Precocious Puberty ◽  
Vaginal Bleeding ◽  
Rare Case ◽  
Rare Condition ◽  
Bone Age ◽  
Pubic Hair ◽  
Breast Development

Congenital hypothyroidism with precocious puberty is a rare condition. In this report a rare case of congenital hypothyroidism with precocious puberty is described. A 10 years old girl presented with feature of hypothyroidism together with breast development, vaginal bleeding, lack of pubic hair and delayed bone age. She also had multicystic ovaries. She was treated with L-thyroxine and improved TAJ 2011; 24(1): 48-50

scholarly journals Should Skeletal Maturation Be Manipulated for Extra Height Gain?

2021 ◽  
Vol 12 ◽  
Author(s):  
Jan M. Wit
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Precocious Puberty ◽  
Adult Height ◽  
Central Precocious Puberty ◽  
Idiopathic Short Stature ◽  
Hormone Deficiency ◽  
Skeletal Maturation ◽  
Gnrh Analogue

Skeletal maturation can be delayed by reducing the exposure to estrogens, either by halting pubertal development through administering a GnRH analogue (GnRHa), or by blocking the conversion of androgens to estrogens through an aromatase inhibitor (AI). These agents have been investigated in children with growth disorders (off-label), either alone or in combination with recombinant human growth hormone (rhGH). GnRHa is effective in attaining a normal adult height (AH) in the treatment of children with central precocious puberty, but its effect in short children with normal timing of puberty is equivocal. If rhGH-treated children with growth hormone deficiency or those who were born small-for-gestational age are still short at pubertal onset, co-treatment with a GnRHa for 2-3 years increases AH. A similar effect was seen by adding rhGH to GnRHa treatment of children with central precocious puberty with a poor AH prediction and by adding rhGH plus GnRHa to children with congenital adrenal hyperplasia with a poor predicted adult height on conventional treatment with gluco- and mineralocorticoids. In girls with idiopathic short stature and relatively early puberty, rhGH plus GnRHa increases AH. Administration of letrozole to boys with constitutional delay of growth puberty may increase AH, and rhGH plus anastrozole may increase AH in boys with growth hormone deficiency or idiopathic short stature, but the lack of data on attained AH and potential selective loss-of-follow-up in several studies precludes firm conclusions. GnRHas appear to have a good overall safety profile, while for aromatase inhibitors conflicting data have been reported.

scholarly journals In Boys with Abnormal Developmental Tempo, Maturation of the Skeleton and the Hypothalamic-Pituitary-Gonadal Axis Remains Synchronous

2004 ◽  
Vol 89 (1) ◽  
pp. 236-241 ◽  
Author(s):  
Armando Flor-Cisneros ◽  
Ellen W. Leschek ◽  
Deborah P. Merke ◽  
Kevin M. Barnes ◽  
Marilena Coco ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Congenital Adrenal Hyperplasia ◽  
Short Stature ◽  
Precocious Puberty ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Chronological Age ◽  
Adrenal Hyperplasia ◽  
Normal Bone ◽  
Primary Mechanism

The primary mechanism that initiates puberty is unknown. One possible clue is that pubertal maturation often parallels skeletal maturation. Conditions that delay skeletal maturation also tend to delay the onset of puberty, whereas conditions that accelerate skeletal maturation tend to hasten the onset of puberty. To examine this relationship, we studied boys with congenital adrenal hyperplasia (n = 13) and familial male-limited precocious puberty (n = 22), two conditions that accelerate maturational tempo, and boys with idiopathic short stature (n = 18) in which maturational tempo is sometimes delayed. In all three conditions, the onset of central puberty generally occurred at an abnormal chronological age but a normal bone age. Boys with the greatest skeletal advancement began central puberty at the earliest age, whereas boys with the greatest skeletal delay began puberty at the latest age. Furthermore, the magnitude of the skeletal advancement or delay matched the magnitude of the pubertal advancement or delay. This synchrony between skeletal maturation and hypothalamic-pituitary-gonadal axis maturation was observed among patients within each condition and also between conditions. In contrast, the maturation of the hypothalamic-pituitary-gonadal axis did not remain synchronous with other maturational processes including weight, height, or body mass index. We conclude that in boys with abnormal developmental tempo, maturation of the skeleton and the hypothalamic-pituitary-gonadal axis remains synchronous. This synchrony is consistent with the hypothesis that in boys, skeletal maturation influences hypothalamic-pituitary-gonadal axis maturation.

scholarly journals Increased Final Height in Precocious Puberty after Long-Term Treatment with LHRH Agonists: The National Institutes of Health Experience

2001 ◽  
Vol 86 (10) ◽  
pp. 4711-4716 ◽  
Author(s):  
Karen Oerter Klein ◽  
Kevin M. Barnes ◽  
Janet V. Jones ◽  
Penelope P. Feuillan ◽  
Gordon B. Cutler Jr.
Keyword(s):  
Precocious Puberty ◽  
Adult Height ◽  
Final Height ◽  
Bone Age ◽  
Chronological Age ◽  
Lhrh Agonist ◽  
Duration Of Treatment ◽  
Long Term Treatment ◽  
Predicted Height

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3± 2.1 yr old at the start of treatment and were treated with either deslorelin (4 μg/kg·d sc) or histrelin (4–10 μg/kg·d) for an average of 6.1 ± 2.5 yr. Final height averaged 159.8 ± 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 ± 9.6 cm) but still significantly less than midparental height (MPH) (163.7 ± 5.6). Final height averaged 171.1 ± 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 ± 14.2 cm) but still significantly less than MPH (178.3 ± 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height sd score correlated positively with duration of treatment (P &lt; 0.01), midparental height (P &lt; 0.001), predicted height at the start of treatment (P &lt; 0.001), and growth velocity during the last year of treatment (P &lt; 0.001) and correlated inversely with delay in the onset of treatment (P &lt; 0.001), age at the start of treatment (P &lt; 0.001), bone age at the start of treatment (P &lt; 0.001), bone age at the end of treatment (P &lt; 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

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