Clinical Overview > Gland/Organ
Search for other papers by Mariana Aveiro-Lavrador in
Google Scholar
PubMed
Search for other papers by Adriana De Sousa Lages in
Google Scholar
PubMed
Search for other papers by Luísa Barros in
Google Scholar
PubMed
Search for other papers by Isabel Paiva in
Google Scholar
PubMed
Summary
Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to enzyme deficiencies in the adrenal steroidogenesis pathway leading to impaired corticosteroid biosynthesis. Depending on the extension of enzyme defect, there may be variable severities of CAH – classic and non-classic. We report the case of a 37-year-old male patient with a previously unknown diagnosis of classic CAH referred to Endocrinology evaluation due to class III obesity and insulin resistance. A high diagnostic suspicion was raised at the first Endocrinology consultation after careful past medical history analysis especially related to the presence of bilateral adrenal myelolipomas and primary infertility. A genetic test confirmed the presence of a variant of the CYP21A2 in homozygous with an enzymatic activity of 0–1%, corresponding to a classic and severe CAH form. Our case represents an unusually late definitive diagnose of classic CAH since the definition was established only during adulthood in the fourth decade of life. The missing diagnosis of classic 21 hydroxylase deficiency during infancy led to important morbidity, with a high impact on patients’ quality of life.
Learning points
-
Congenital adrenal hyperplasia (CAH) refers to a group of autosomal recessive enzyme disorders responsible for an impaired cortical adrenal hormonal synthesis.
-
CAH may be divided into two major forms: classic and non-classic CAH.
-
If untreated, CAH may be fatal or may be responsible for important multi-organ long-term consequences that can be undervalued during adulthood.
-
Adrenal myelolipomas are associated with chronic exposure to high ACTH levels and continuous androgen hyperstimulation typically found in undertreated CAH patients.
-
Testicular adrenal rest tumours (TART) and primary infertility can be the first manifestation of the disease during adulthood.
Search for other papers by M A Shehab in
Google Scholar
PubMed
Search for other papers by Tahseen Mahmood in
Google Scholar
PubMed
Search for other papers by M A Hasanat in
Google Scholar
PubMed
Search for other papers by Md Fariduddin in
Google Scholar
PubMed
Search for other papers by Nazmul Ahsan in
Google Scholar
PubMed
Search for other papers by Mohammad Shahnoor Hossain in
Google Scholar
PubMed
Search for other papers by Md Shahdat Hossain in
Google Scholar
PubMed
Search for other papers by Sharmin Jahan in
Google Scholar
PubMed
Summary
Congenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3β-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3β-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3β-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well.
Learning points:
-
Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH.
-
High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3β-HSD enzyme deficiency.
-
Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations.
-
Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism.
-
Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, USA
Search for other papers by Jasmeet Kaur in
Google Scholar
PubMed
Augusta University School of Medicine, Augusta, Georgia, USA
Neonatology Intensive Care Unit, Memorial University Medical Center, Georgia, USA
Search for other papers by Alan M Rice in
Google Scholar
PubMed
Search for other papers by Elizabeth O’Connor in
Google Scholar
PubMed
Neonatology Intensive Care Unit, Memorial University Medical Center, Georgia, USA
Search for other papers by Anil Piya in
Google Scholar
PubMed
Search for other papers by Bradley Buckler in
Google Scholar
PubMed
Anderson Cancer Institute, Memorial University Medical Center, Savannah, Georgia, USA
Search for other papers by Himangshu S Bose in
Google Scholar
PubMed
Congenital adrenal hyperplasia (CAH) is caused by mutations in cytochrome P450 side chain cleavage enzyme (CYP11A1 and old name, SCC). Errors in cholesterol side chain cleavage by the mitochondrial resident CYP11A1 results in an inadequate amount of pregnenolone production. This study was performed to evaluate the cause of salt-losing crisis and possible adrenal failure in a pediatric patient whose mother had a history of two previous stillbirths and loss of another baby within a week of birth. CAH can appear in any population in any region of the world. The study was conducted at Memorial University Medical Center and Mercer University School of Medicine. The patient was admitted to Pediatric Endocrinology Clinic due to salt-losing crisis and possible adrenal failure. The patient had CAH, an autosomal recessive disease, due to a novel mutation in exon 5 of the CYP11A1 gene, which generated a truncated protein of 286 amino acids compared with wild-type protein that has 521 amino acids (W286X). Although unrelated, both parents are carriers. Mitochondrial protein import analysis of the mutant CYP11A1 in steroidogenic MA-10 cells showed that the protein is imported in a similar fashion as observed for the wild-type protein and was cleaved to a shorter fragment. However, mutant’s activity was 10% of that obtained for the wild-type protein in non-steroidogenic COS-1 cells. In a patient of Mexican descent, a homozygous CYP11A1 mutation caused CAH, suggesting that this disease is not geographically restricted even in a homogeneous population.
Learning points:
-
Novel mutation in CYP11A1 causes CAH;
-
This is a pure population from Central Mexico;
-
Novel mutation created early truncated protein.
First Surgical Department of General Hospital of Athens ‘Georgios Gennimatas’, Alpha Institute of Biomedical Sciences (AIBS), Department of Pathology, Mesogeion 154, Athens 15669, Greece
Search for other papers by Marinos C Makris in
Google Scholar
PubMed
Search for other papers by Konstantinos C Koumarelas in
Google Scholar
PubMed
Search for other papers by Apostolos S Mitrousias in
Google Scholar
PubMed
Search for other papers by Giannos G Psathas in
Google Scholar
PubMed
Search for other papers by Athanasios Mantzioros in
Google Scholar
PubMed
Search for other papers by Stratigoula P Sakellariou in
Google Scholar
PubMed
Search for other papers by Panagiota Ntailiani in
Google Scholar
PubMed
Search for other papers by Evripides Yettimis in
Google Scholar
PubMed
Summary
Until now, less than ten cases of extra-adrenal chromaffin cell tumors have been reported to be localized to the spermatic cord area. All published studies report benign tumors with a diameter <2–3 cm and no invasion of the testis. In this article, we present one case of a giant malignant paraganglioma in the testis of a patient who had initially been operated for a giant mass in the scrotum. The mass developed in approximately 4 months. This is the first study reporting the following findings: i) paraganglioma was found exclusively in the testis, invading the testicle and not the spermatic cord, ii) it was malignant with lung metastasis, and iii) its size was 17.5 cm×10 cm×9.5 cm. We present the first – giant – malignant paraganglioma. Moreover, it is the first case report of a paraganglioma in the testis.
Learning points
-
This is the first study reporting the following findings:
-
Paraganglioma found exclusively in the testis, invading the testicle and not the spermatic cord.
-
It is malignant with lung metastasis.
-
It is of the size 17.5 cm×10 cm×9.5 cm.
