Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report
Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting...
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2025-07-01
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| author | Alanna Asgeirsson Eujean Park Vinicius Seidel Mathew Shedd Matheni Sathananthan Tania Arous Kevin Codorniz Silvana Giannelli Justin Do Wyut Yi Thin Arsenije Jelovac Scott Lee |
| author_facet | Alanna Asgeirsson Eujean Park Vinicius Seidel Mathew Shedd Matheni Sathananthan Tania Arous Kevin Codorniz Silvana Giannelli Justin Do Wyut Yi Thin Arsenije Jelovac Scott Lee |
| author_sort | Alanna Asgeirsson |
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| description | Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in <i>PCSK1</i> and <i>HS6ST1</i>, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS. |
| format | Article |
| id | doaj-art-96c3ad3e6b3e400fadccc81c0b635fdb |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Life |
| spelling | doaj-art-96c3ad3e6b3e400fadccc81c0b635fdb2025-08-20T03:58:30ZengMDPI AGLife2075-17292025-07-01157115110.3390/life15071151Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case ReportAlanna Asgeirsson0Eujean Park1Vinicius Seidel2Mathew Shedd3Matheni Sathananthan4Tania Arous5Kevin Codorniz6Silvana Giannelli7Justin Do8Wyut Yi Thin9Arsenije Jelovac10Scott Lee11Department of Internal Medicine, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADepartment of Internal Medicine, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADepartment of Internal Medicine, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USAProvidence Little Company of Mary Medical Center Torrance, Torrance, CA 4101, USADivision of Endocrinology, Loma Linda University Health Consortium, Loma Linda, CA 92354, USAKallmann syndrome (KS) is a form of hypogonadotropic hypogonadism (HH) characterized by gonadotropin-releasing hormone (GnRH) deficiency and anosmia due to defective neuronal migration. While traditionally considered irreversible, cases of spontaneous improvement of HH have been reported, suggesting residual GnRH neuronal function in some individuals. We present a case of a 29-year-old man with KS who exhibited spontaneous recovery of endogenous testosterone production following the cessation of long-term androgen therapy without the use of alternative hormonal agents. After ceasing testosterone therapy for several months, the patient’s total testosterone levels normalized (407–424 ng/dL), accompanied by increased secondary sexual characteristics, stable gonadotropin levels, and normal testicular volume. Persistent anosmia was noted, suggesting that restoration of reproductive endocrine function can occur independently of olfactory recovery. Genetic testing identified heterozygous mutations in <i>PCSK1</i> and <i>HS6ST1</i>, genes implicated in GnRH regulation and KS pathogenesis. This case highlights the potential role of genetic variation in spontaneous HH improvement and underscores the need for individualized management strategies, including periodic reassessment of gonadal function and fertility potential. Further research is needed to elucidate the mechanisms driving spontaneous HH improvement, identify predictive biomarkers of reversibility, and explore therapeutic strategies that may promote endogenous GnRH activity in select patients with KS.https://www.mdpi.com/2075-1729/15/7/1151spontaneous hypogonadotropic hypogonadism reversal<i>PCSK1</i> mutation<i>HS6ST1</i> mutationGnRH neurons |
| spellingShingle | Alanna Asgeirsson Eujean Park Vinicius Seidel Mathew Shedd Matheni Sathananthan Tania Arous Kevin Codorniz Silvana Giannelli Justin Do Wyut Yi Thin Arsenije Jelovac Scott Lee Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report Life spontaneous hypogonadotropic hypogonadism reversal <i>PCSK1</i> mutation <i>HS6ST1</i> mutation GnRH neurons |
| title | Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report |
| title_full | Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report |
| title_fullStr | Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report |
| title_full_unstemmed | Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report |
| title_short | Spontaneous Improvement of Hypogonadotropic Hypogonadism in a Patient with <i>PCSK1</i> and <i>HS6ST1</i> Mutations: A Case Report |
| title_sort | spontaneous improvement of hypogonadotropic hypogonadism in a patient with i pcsk1 i and i hs6st1 i mutations a case report |
| topic | spontaneous hypogonadotropic hypogonadism reversal <i>PCSK1</i> mutation <i>HS6ST1</i> mutation GnRH neurons |
| url | https://www.mdpi.com/2075-1729/15/7/1151 |
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