ResearchPad - male-reproductive-case-reports https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[SUN-033 A Rare Case: Bone Pain and Continued Linear Growth in a Young Adult Male Due to Aromatase Deficiency]]> https://www.researchpad.co/article/elastic_article_8545 Introduction:

Aromatase, the product of CYP19A1, catalyzes the conversion of androgens to estrogens. 46, XX infants with aromatase deficiency, due to androgen excess, present with ambiguous genitalia at birth. In 46, XY individuals, however, the subtle phenotypic features make the diagnosis even more difficult. Less than 15 male cases were reported in the literature and we present the first case of aromatase deficiency diagnosed in Taiwan.

Clinical Case:

A 23-year-old man, Burman overseas student of Chinese descent, presented to an orthopedist with a two-year history of left ankle pain, which was diagnosed as gout by his previous physician. Unexpectedly, unfused growth plates were discovered so he was referred to our pediatric endocrine clinic for evaluation. Reviewing his past history, we learned he is the third child of consanguineous parents. His mother experienced deepening of voice during this pregnancy which resolved following parturition. He was 177 cm tall at the age of 19. At the time he presented to our clinic, he weighed 95.3 kg and was 183 cm tall. Physical exam showed the ratio of U/L segment to be 0.82, stretched penile length 6.5 cm, bilateral testes > 25 mL, pubic hair at Tanner stage V, and presence of genu valgum. The skeletal age was 14 years and 6 months. Labs showed FSH 19.7 IU/L (0.7–11.1), LH 8.18 IU/L (0.8–7.6), total testosterone 1335 ng/dL (240–871), estradiol <20 pg/mL, DHEA-S 13.41 μmol/L (6.5–14.6), androstenedione 5.73 nmol/L (3.5–9.8) and 17-OH progesterone 6.55 nmol/L (2–10). GnRH (100 μg i.v) stimulation test showed a supranormal basal FSH level and a normal to higher LH response (FSH at baseline/peak were 23.0/38.6 IU/L; LH at baseline/peak were 8.81/47.7 IU/L). Under the clinical suspicion of aromatase deficiency, we performed genetic sequencing of CYP19A1 (NM_031226) and found a homozygous missense variant c.1108G>A (V370M), a previously reported pathogenic mutation.

A diagnosis of aromatase deficiency was made. He also had hypertension (156/87 mmHg), dyslipidemia (T-cholesterol 236 mg/dL, LDL-C 175 mg/dL) and insulin resistance (AC glucose 87 mg/dL, insulin 23.5 μU/mL, HOMA-IR 5.0, Hb1Ac 5.6%). Bone mineral density of lumbar spine (DXA) showed a T-score of -2.8, consistent with the diagnosis of osteoporosis.

Conclusion:

Estrogen is pivotal for epiphyseal closure in both sexes. As demonstrated in this case, estrogen deficiency in men results in tall stature and eunuchoid habitus, while it is also associated with low bone density and metabolic syndrome. The gonadotropin response in this report suggests the inhibitory role of estrogen in the male HPG axis. Clinicians may consider this rare diagnosis for men in their late teens or early twenties, who have spontaneous initiation of puberty, presenting with bone pain and continued linear growth.

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<![CDATA[SUN-029 Diabetes Mellitus Associated with Klinefelter Syndrome]]> https://www.researchpad.co/article/elastic_article_6409 Background: It has not been clarified why diabetes mellitus develops in patients with Klinefelter’s syndrome. However the association between both diseases is frequent. Clinical Case: A 31-years-old man with type 2 diabetes diagnosed 2 months ago who received metformin for treatment. He presented to the hospital with dysuria, polyuria, polydipsia, weight loss, hyporexia, vomiting and drowsiness. On examination: BP: 110/60 mmHg, HR: 108 lp, FR: 24 rp, T °: 37 ° C, BMI: 31.4 kg / m2, oral mucosa dry, bilateral gynecomastia, subcutaneous cellular tissue of gynecoid distribution. His body hair was thin. His penis was small and both testicles were prepubertal. Laboratory: Glucose: 410 mg / dl; HbA1c 15.2%; creatinine: 1.01 mg / dl; arterial gases: pH 7.14 pCO2: 20, HCO3: 6.6, AG: 29. Normal electrolytes. Ketonuria: 3+. We concluded: diabetic ketoacidosis. In addition, FSH 61.18 μU / ml (RR: 1.5-12.5); LH: 28.47 μU / ml (RR: 0.7-8.6); Total testosterone: 0.41 ng / ml (RR: 2.8-8), compatible with hypergonadotropic hypogonadism. Therefore a karyotype is requested in peripheral blood, resulting in 47, XXY in 20 metaphases analyzed. Klinefelter’s syndrome was diagnosed from his physical characteristics, hormonal findings and his chromosomal aberration. He received testosterone undecanoate every 4 weeks, NPH insulin 12 IU / 8UI plus metformin 850 mg every 12 hours. Three months later: baseline glucose 89 mg / dl and HbA1C of 9.5%. Conclusion: We present the case of a young male with diabetic ketoacidosis and hypogonadism, secondary to Klinefelter syndrome. Klinefelter syndrome is associated with Diabetes mellitus with a RR that varies from 1.64 to 7.06 according to current literature. In addition, we highlight the importance of the medical history and physical examination for an adequate diagnosis of rare conditions such as Klinefelter Syndrome. Reference: 1. Kanakis GA, Nieschlag E. Klinefelter syndrome: more than hypogonadism. Metabolism. Septembere 2018;86:135-44.

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<![CDATA[SUN-031 Megestrol Acetate for Bodybuilding Resulting in Abrupt Hypothalamic-Pituitary Dysfunction]]> https://www.researchpad.co/article/N3a141b94-b689-4efa-86e1-b6e38e349835 Introduction: Megestrol acetate (MA) is a synthetic progestin often used for appetite stimulation and weight gain in patients with cachexia related to AIDS, cancer or terminal illness. MA is frequently implicated in development of both glucocorticoid excess and adrenal insufficiency (AI) in a somewhat unpredictable manner. Less commonly reported adverse effects of MA include dysfunction of the hypothalamic pituitary axis. Few cases in literature exist regarding the use of MA in young, healthy patients and the potential clinical severity of pituitary dysfunction in this population.

Case: A 24-year-old male was previously healthy but frustrated by an inability to gain muscle mass. Evaluation one-year prior was unrevealing and included a total testosterone of 1100ng/dL (264-916ng/dL). In the interim, he was prescribed MA 625/5mg for 2 months with rapid development of abdominal adiposity, depressed mood, low libido and erectile dysfunction. Repeat evaluation revealed a precipitous drop in total testosterone to 66 ng/dL at which point he self-discontinued MA. He then began to experience palpitations, sweats, poor concentration, and undesirable weight loss along with worsening symptoms of sexual and erectile dysfunction.

Three months after MA discontinuation, he appeared well with physical examination and vital signs within normal limits. Surprisingly, repeat studies revealed total testosterone <3, free testosterone <0.2 (9.3 -26.5 pg/mL), LH 1.3 (1.7-8.6 mIU/mL), FSH 2.2 (1.5-12.3 mIU/mL), Prolactin 33.4 (4.0-15.2 ng/mL) as well as 8AM cortisol 2.2 ug/dL and ACTH 22.7 pg/mL. A basic metabolic panel, thyroid function studies and pituitary MRI were unremarkable. The patient was empirically placed on prednisone 5mg daily pending ACTH stimulation testing for HPA axis reassessment. Topical testosterone replacement therapy was initiated due to intolerance of hypogonadal symptoms.

Discussion: MA, by virtue of affinity for glucocorticoid receptors, has the potential to cause hyperglycemia and Cushing’s syndrome. Secondary AI often results from withdrawal of MA however central AI can also occur with active administration by unclear mechanisms. Hypogonadism and hyperprolactinemia are additional under-reported adverse effects of MA with symptoms often masked by AI or elements of chronic illness. In study of men age 60-85 year on MA, a mean percentage change of ACTH -89.5%, LH -49%, TSH -14.7% and Prolactin +150% were seen from baseline after 12 weeks of therapy as was decreased cortisol. Limited data exists in young patients such as ours given limited indications for the agent’s use. Importantly, MA should be prescribed with understanding that weight gain is predominantly adipose rather than muscle mass and that its safety is limited by potential HP axis dysfunction, namely adrenal and gonadal deficiencies.

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<![CDATA[SUN-031 Megestrol Acetate for Bodybuilding Resulting in Abrupt Hypothalamic-Pituitary Dysfunction]]> https://www.researchpad.co/article/Ned330804-72e7-4fff-a065-f9b5a91264e3

Abstract

Megestrol acetate (MA) is a synthetic progestin often used for appetite stimulation and weight gain in patients with cachexia related to AIDS, cancer or terminal illness. MA is frequently implicated in development of both glucocorticoid excess and adrenal insufficiency (AI) in a somewhat unpredictable manner. Less commonly reported adverse effects of MA include dysfunction of the hypothalamic pituitary axis. Few cases in literature exist regarding the use of MA in young, healthy patients and the potential clinical severity of pituitary dysfunction in this population.

: A 24-year-old male was previously healthy but frustrated by an inability to gain muscle mass. Evaluation one-year prior was unrevealing and included a total testosterone of 1100ng/dL (264-916ng/dL). In the interim, he was prescribed MA 625/5mg for 2 months with rapid development of abdominal adiposity, depressed mood, low libido and erectile dysfunction. Repeat evaluation revealed a precipitous drop in total testosterone to 66 ng/dL at which point he self-discontinued MA. He then began to experience palpitations, sweats, poor concentration, and undesirable weight loss along with worsening symptoms of sexual and erectile dysfunction.

Three months after MA discontinuation, he appeared well with physical examination and vital signs within normal limits. Surprisingly, repeat studies revealed total testosterone <3, free testosterone <0.2 (9.3 -26.5 pg/mL), LH 1.3 (1.7-8.6 mIU/mL), FSH 2.2 (1.5-12.3 mIU/mL), Prolactin 33.4 (4.0-15.2 ng/mL) as well as 8AM cortisol 2.2 ug/dL and ACTH 22.7 pg/mL. A basic metabolic panel, thyroid function studies and pituitary MRI were unremarkable. The patient was empirically placed on prednisone 5mg daily pending ACTH stimulation testing for HPA axis reassessment. Topical testosterone replacement therapy was initiated due to intolerance of hypogonadal symptoms.

MA, by virtue of affinity for glucocorticoid receptors, has the potential to cause hyperglycemia and Cushing’s syndrome. Secondary AI often results from withdrawal of MA however central AI can also occur with active administration by unclear mechanisms. Hypogonadism and hyperprolactinemia are additional under-reported adverse effects of MA with symptoms often masked by AI or elements of chronic illness. In study of men age 60-85 year on MA, a mean percentage change of ACTH -89.5%, LH -49%, TSH -14.7% and Prolactin +150% were seen from baseline after 12 weeks of therapy as was decreased cortisol. Limited data exists in young patients such as ours given limited indications for the agent’s use. Importantly, MA should be prescribed with understanding that weight gain is predominantly adipose rather than muscle mass and that its safety is limited by potential HP axis dysfunction, namely adrenal and gonadal deficiencies.

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<![CDATA[SUN-028 Concomitant Mutations in the POR and AR Genes in a Boy Presenting with Micropenis and Premature Adrenarche]]> https://www.researchpad.co/article/N3e89a4bb-7247-4a72-b481-fed845238c3f

Abstract

: Micropenis is caused either by a defect in androgen synthesis, conversion to Dihydrotestosterone, or action due to mutant androgen receptor. Premature adrenarche is caused by excess of adrenal androgens.

: A 6,5-year-old boy presented to our pediatric endocrinology clinic due to increased body weight and hyperthyreotropinemia. Physical examination revealed premature adrenarche with testicular volume 1,5 ml, micropenis (4cm, <-2 SDS) and acanthosis nigricans. His linear growth presented an acceleration the last 2 years from +0.85 to +1.81 SD and his bone age was advanced by 2 years with a statural height at -0.5 SD, not in accordance with the mean parental height (+0.90 SD). At the same time, his BMI was increased from +1,36 to +3,64 SDS.

Laboratory investigations for premature adrenarche with synacthen test revealed mild elevation of compound-S 15,4 ng/dl at 60’, which could be theoretically attributed to partial 11-β-hydroxylase deficiency (CYP11B1). DHEA was also elevated 2,1 ng/ml with an increased DHEA/Δ4 ratio at 20 (normal < 10) which could be explained in the case of partial 3-β-Hydroxysteroid dehydrogenase deficiency.

: Whole exome sequencing was preformed targeted to a gene panel related to premature adrenarche.

: A heterozygous mutation c.[1174C>T]+[1174C>T]; p.[Pro329Ser]+[Pro329Ser] in exon 1 in Androgen Receptor (AR) gene (X-linked) was found to the patient and his mother. The mutation, according to Human Gene Mutation Database, can cause disorder of sex development (DSD), partial androgen insensitivity syndrome (PAIS), infertility and hypospadias. Additionally, sequencing of the coding region of the P450 oxyreductase (POR) gene revealed a heterozygous mutation c.[642-5C>G] in exon 7, which in homozygosity can cause steroidogenesis disorder due to oxyreductase deficiency. This heterozygous POR mutation was found to the patient and his father.

: Our patient caries mutations in the AR and in POR genes. The AR mutation is obviously responsible for micropenis in our patient. CYP11B1 and 3β-Hydroxysteroid dehydrogenase genes were normal. POR deficiency is a disorder of steroidogenesis with phenotypic spectrum ranging from PCOS to ambiguous genitalia and glycocorticosteroid deficiency or even to classic Antley-Bixler syndrome (1).

: The genetic and hormonal results in our case imply a role for POR in the CYP11B1 gene expression, which is reported for the first time to our knowledge.

1.

Concomitant Mutations in the P450 Oxidoreductase and Androgen Receptor Genes Presenting with 46,XY Disordered Sex Development and Androgenization at Adrenarche. J Clin Endocrinol Metab. 2010 Jul; 95(7): 3418-3427

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<![CDATA[SUN-032 Digenic Inheritance of PCSK1 and CHD7 Mutations in PAX4 Homozygous Diabetic Male with Normosmic Hypogonadotropic Hypogonadism]]> https://www.researchpad.co/article/Nbaf65de1-29f2-49aa-a328-bbf2fab5f54d T, p.Pro2036Leu, rs369543203) and PCSK1 gene (c.239G>A, p.Arg80Gln, rs1799904). The missense variants were predicted to have a damaging effect on the encoded protein, by SIFT and PolyPhen-2 analyses. Genetic analyses of his family revealed that his father had the same heterozygote missense mutations of the CHD7 gene, but wild type of PCSK1. Proband’s mother had the same heterozygote missense mutations of PCSK1, but wild type of CHD7. Furthermore, the proband had homozygote missense mutation of PAX4 (c.575G>A, p.Arg192His, rs2233580) known as maturity-onset diabetes of the young (MODY) 9 gene. Both parents have the same but heterozygous mutation of PAX4 p.Arg192His, and pre-diabetic range of hyperglycemia. Conclusion: This is the first case demonstrating digenic inheritance of mutations in PCSK1 and CHD7 as a potential cause of normosmic hypogonadotrophic hypogonadism, interestingly in PAX4 homozygous diabetic male. Reference: (1) Maione L, et al. Genetic counseling for congenital hypogonadotropic hypogonadism and Kallmann syndrome: new challenges in the era of oligogenism and next-generation sequencing. Eur J Endocrinol. 2018;178(3):R55-R80. ]]> <![CDATA[SUN-026 Unusual Presentation of Aromatase Excess Syndrome]]> https://www.researchpad.co/article/N833adc64-9595-4631-946d-c17d1f7da96f 10, he was started on an aromatase inhibitor and his ratio dropped from 1:40 to 1:24, as his estradiol went down to 75 pg/ml. Discussion: Gynecomastia is the benign proliferation of breast tissue due to imbalance between estrogen and testosterone. It could be caused by medications or medical illnesses. Occasionally its presence can harbor a serious endocrine issue especially if presenting in the prepubertal period. Thus, evaluation is often necessary. Among the pathological causes is the Aromatase excess syndrome. In this syndrome there are three types of cryptogenic genomic rearrangements identified. Those rearrangement affect the aromatase gene CYP19 and results in gain of function of the aromatase enzyme. Patients will have high estradiol and estrone level, lower FSH and LH levels that will normalize after treatment with aromatase inhibitor. Their testosterone levels could be low or normal. For the clinical diagnosis, there are four criteria; bilateralgynecomastia, pre or peripubertal onset, exclusion of other causes of gynecomastia and having a genetic trait. The first three criteria are indispensable for diagnosis while fourth one is not obligatory, but rather pathognomonic. An elevated estradiol to testosterone ratio above 1:10 is a supportive finding, as well as having a low FSH with low to normal LH. Genetic identification of the CYP19 A1 mutation remains the definitive method of diagnosis. Our patient met the first three criteria and also had estradiol to testosterone ratio is > 1:10. Genetic confirmation is challenging. Consequently, whole genome sequencing may be required. Though unusual, this case highlights the importance of looking deep in the differential when evaluating gynecomastia. ]]> <![CDATA[SUN-027 Testicular Regression Syndrome, an Underdiagnosed Cause of Hypergonadotropic Hypogonadism]]> https://www.researchpad.co/article/Nd2008c6c-2cf6-4270-98f9-5844f2fcd659 <![CDATA[SUN-030 Tetraorchidism: A Rare Type of Polyorchidism]]> https://www.researchpad.co/article/Ne16cb6a2-d1c9-4cda-acbc-ad776d9a528e

Abstract

Polyorchidism is defined as the presence of two or more testis. We report an interesting case of Tetraorchidism an extremely rare type of Polyorchidism in a 14-year-old boy with short stature due to Growth hormone deficiency. An extensive review of literature yielded only 200 case reports of Polyorchidism [1]. Most of these are case reports on triorchidism (3 testicles). There has been only 9 case reports of patients with (tetraorchidism) 4 testicles [2]. Most of them has been reported as incidental findings in adults.

This case is being reported due to its rarity. Here we elaborate on clinical presentation of Polyorchidism in children and their management plan. More specifically from Pediatric Endocrinology perspective, we discuss the influence of the Polyorchidism on the Tanner staging (by testicular volume), growth and pubertal development in boys.

Reference:

1. Amanda Myers, Bradley Morganstern and Ronnie Fine Urology, 2017-06-01, Volume 104, Pages 196-197,

2. Ibrahim H., Roberts M.J., and Hussey D.: Quadruple orchidopexy for torsion testis in an adolescent with polyorchidism: a case report. Urology 2016; 87: pp. 196-199.

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