Category: Pituitary Disorders/Neuroendocrinology
This is the case of a 39 year-old Ecuadorian man with history of growth failure and pituitary hypofunction diagnosed at age 18 years old, for which he was started on parenteral testosterone and oral levothyroxine. He denied any previous treatment with growth hormone (GH). Family history (FH) was significant for consanguinity; his parents, both healthy, were first degree cousins. One sister had short stature, infertility and hypothyroidism. Two of his cousins were diagnosed with pituitary hormone deficiencies during childhood. Furthermore, he has two healthy siblings. Physical exam revealed a short stature, short neck, non-dysmorphic facial features, normal facial and body hair distribution, and small and firm testes. The rest of the exam was unremarkable.
A written report of a brain magnetic resonance imaging (MRI) from 1998 described an atrophic pituitary gland, and a new pituitary MRI confirmed this finding. Ancillaries while on testosterone and levothyroxine therapies revealed a suppressed thyrotropin (TSH) and normal free thyroxine, suppressed follicle-stimulating hormone (FSH) and luteinizing hormone (LH), a low-normal serum prolactin (PrL), and an inappropriately normal ACTH level for a low morning serum cortisol. A spermogram revealed azoospermia.
The clinical data, and FH of panhypopituitarism and consanguinity pointed towards an autosomal recessive (aa) disorder causing combined pituitary hormone deficiency. The patient was initiated on oral hydrocortisone at maintenance dosing, and directed work up was pursued. A karyotype analysis revealed 46XY array and no Y-chromosome microdeletions. Cystic fibrosis testing was negative. Genetic mutation analyses showed presence of a homozygous pathogenic mutation of the PROP1 gene. Fertility options were discussed with the patient and his wife. Testosterone therapy was withheld and human-chorionic gonadotropin (hCG) therapy was started. After months of therapy eighteen spermatozoa were retrieved via percutaneous testicular needle aspiration. Ultimately, the plan is to eventually try in-vitro fertilization.
Discussion : PROP1 gene mutation is the most prevalent etiology of combined pituitary hormone deficiency (CPHD), it is associated with GH, TSH, LH, FSH, PrL and occasionally ACTH deficiency.
Carrier testing for at-risk relatives and prenatal testing is indicated. Nevertheless directed testing is possible when both paternal and maternal PROP1 pathogenic variants are known. Even though there is no history of consanguinity among the patient and his wife, testing for PROP1 mutation and molecular analyses are warranted, especially when exhaustive attempts for conception are being sought.
Chief of Endocrinology
New York City H+H/ Metropolitan, New York Medical College
Dr. Alberto Franco-Akel is an endocrinologist, currently working as chief of the endocrinology section of the department of medicine, at NYC H+H/Metropolitan, New York City. Dr. Franco-Akel graduated from medical school at Universidad Catolica de Santiago de Guayaquil, Ecuador in 2005. He did his internal medicine residency at NYC H+H/Metropolitan after which he served as Chief Medical Resident, until 2014. Dr. Franco-Akel completed his endocrinology fellowship training at Mount Sinai Beth Israel, New York in 2016. Afterwards, he started working as an internist and endocrinologist at NYC H+H/Metropolitan in 2016, taking charge of patients in the general endocrinology clinic, HRT-LGBT clinics, and Diabetes clinics, as well as the inpatient endocrinology consultation services. He was promoted to Chief of Endocrinology in July 2017. Dr. Franco has an academic affiliation with New York Medical College as an Assistant Professor of Medicine. As such, he participates in mentorship of residents and medical students. Dr. Franco-Akel is actively involved in quality improvement projects, performance improvement projects, as well as programs for the enhancement of care for patients at Metropolitan, including the Diabetes Prevention Program, and Diabetes Self Management Program. Dr. Franco-Akel received the award of The Best Physician Teacher In A Sub-specialty Rotation, and the recognition by New York Medical College medical students for teaching and preceptor-ship in 2018.