Thyroid disorders and male sexual dysfunction.

Though early research suggested that thyroid hormones were not involved with the testes, male spermatogenesis, or erectile function, investigations on this topic over the past few decades have increased and shed new light. A literature review of studies conducted between 1963 and 2022 regarding male sexual dysfunction (SD) and thyroid disorders was performed to define the diagnostic consideration, pathophysiology, and management of SD secondary to thyroid dysregulation. This article provides evidence and interpretation of prior clinical and preclinical studies and contextualizes these studies for clinical practice. Clinical manifestations of SDs included erectile and ejaculatory dysfunction, impaired spermatogenesis, and disruption of the hypothalamic-pituitary-gonadal axis. Our aim of this communication was to perform a literature review detailing the impact of thyroid disorders on male SD. We hope to provide a framework for practicing urologists, endocrinologists, or general practitioners when evaluating patients with concurrent thyroid and male SD. It is important to recognize that thyroid disorders can be an important part of the pathophysiology of male SD in patients. Future research studies are needed to further elucidate the mechanisms involved.

Crystal structures of ß-1,4-N-acetylglucosaminyltransferase 2: structural basis for inherited muscular dystrophies.

The canonical O-mannosylation pathway in humans is essential for the functional glycosylation of α-dystroglycan. Disruption of this post-translational modification pathway leads to congenital muscular dystrophies. The first committed step in the construction of a functional matriglycan structure involves the post-translational modification of α-dystroglycan. This is essential for binding extracellular matrix proteins and arenaviruses, and is catalyzed by ß-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2). While another glycosyl transferase, ß-1,4-N-acetylglucosaminyltransferase 1 (POMGNT1), has been shown to be promiscuous in extending O-mannosylated sites, POMGNT2 has been shown to display significant primary amino-acid selectivity near the site of O-mannosylation. Moreover, several single point mutations in POMGNT2 have been identified in patients with assorted dystroglycanopathies such as Walker-Warburg syndrome and limb girdle muscular dystrophy. To gain insight into POMGNT2 function in humans, the enzyme was expressed as a soluble, secreted fusion protein by transient infection of HEK293 suspension cultures. Here, crystal structures of POMGNT2 (amino-acid residues 25-580) with and without UDP bound are reported. Consistent with a novel fold and a unique domain organization, no molecular-replacement model was available and phases were obtained through crystallization of a selenomethionine variant of the enzyme in the same space group. Tetragonal (space group P4212; unit-cell parameters a = b = 129.8, c = 81.6 Å, α = γ = ß = 90°) crystals with UDP bound diffracted to 1.98 Šresolution and contained a single monomer in the asymmetric unit. Orthorhombic (space group P212121; unit-cell parameters a = 142.3, b = 153.9, c = 187.4 Å, α = γ = ß = 90°) crystals were also obtained; they diffracted to 2.57 Šresolution and contained four monomers with differential glycosylation patterns and conformations. These structures provide the first rational basis for an explanation of the loss-of-function mutations and offer significant insights into the mechanics of this important human enzyme.

Surgical Management of Idiopathic Partial Thrombosis of the Corpus Cavernosum.

A 36-year-old African American man presented to the emergency department with 2 days of left-sided perineal pain after sexual activity. He was found to have induration in the left perineum overlying the proximal left corporal body. Clinical picture was suspicious for traumatic corporal rupture; however, advanced imaging showed a proximal segmental thrombosis of the left corpus cavernosum. The patient underwent perineal exploration with evacuation of an intracorporal penile hematoma. In spite of disrupting a fibrous membrane in the proximal corpora and drainage of the corpora, we observed repeat tumescence during the procedure because of an observed arterial high-flow state in the corpora cavernosum. This was resolved with administration of phenylephrine into the cavernosum. The patient had return of normal erectile function 2 days after the procedure with resolution of pain at the site. Singh D, Larson T, Campbell K, et al. Surgical Management of Idiopathic Partial Thrombosis of the Corpus Cavernosum. Sex Med 2021;9:100273.

Asymptomatic Obstructive Ureterolithiasis Due to a Periureteral Venous Ring.

Background: Periureteral venous rings are a rare congenital anomaly involving the inferior vena cava (IVC) and the right ureter, where the ureter courses through a venous ring made by the duplication of the IVC during embryogenesis. This anatomic anomaly is also referred to as a transcaval ureter. Although most patients are asymptomatic and radiographic findings are incidental, some patients can be symptomatic. We present the first reported case of asymptomatic obstructive ureterolithiasis at the level of a periureteral venous ring that was effectively treated with endoscopic management. Case Presentation: A 47-year-old woman was found to have right hydroureteronephrosis on MRI. Further CT imaging showed an obstructing ureteral stone at the level of a periureteral venous ring. After initial decompression with ureteral stenting, she underwent ureteroscopy that revealed the ureteral stone at the level of the venous anomaly. The stone was fragmented and removed with laser lithotripsy and stone basket manipulation. After a period of ureteral stenting and removal, she had improved hydroureteronephrosis, no symptoms of ureteral obstruction, and stable renal function. Given these findings, she elected for surveillance with imaging in lieu of any reconstructive procedure to transpose the ureter around the venous anomaly. Conclusions: We present the first reported case of obstructive ureterolithiasis at the level of a periureteral venous ring. Our experience suggests that, with preoperative ureteral stenting, obstructing ureteral stones in the setting of an IVC anomaly can be managed with retrograde flexible ureteroscopy. Conservative laser settings and minimal torqueing of the ureteroscope are advised given adjacent vascular anomaly. Cases wherein the affected ureteral segment is too constricted or tortuous to allow for stone passage or for ureteroscopy may require management by percutaneous antegrade intervention. Surgical reconstruction of the ureter should also be considered.

Protein O-Linked Mannose ß-1,4-N-Acetylglucosaminyl-transferase 2 (POMGNT2) Is a Gatekeeper Enzyme for Functional Glycosylation of α-Dystroglycan.

Disruption of the O-mannosylation pathway involved in functional glycosylation of α-dystroglycan gives rise to congenital muscular dystrophies. Protein O-linked mannose ß-1,4-N-acetylglucosaminyltransferase 2 (POMGNT2) catalyzes the first step toward the functional matriglycan structure on α-dystroglycan that is responsible for binding extracellular matrix proteins and certain arenaviruses. Alternatively, protein O-linked mannose ß-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1) catalyzes the first step toward other various glycan structures present on α-dystroglycan of unknown function. Here, we demonstrate that POMGNT1 is promiscuous for O-mannosylated peptides, whereas POMGNT2 displays significant primary amino acid selectivity near the site of O-mannosylation. We define a POMGNT2 acceptor motif, conserved among 59 vertebrate species, in α-dystroglycan that when engineered into a POMGNT1-only site is sufficient to convert the O-mannosylated peptide to a substrate for POMGNT2. Additionally, an acceptor glycopeptide is a less efficient substrate for POMGNT2 when two of the conserved amino acids are replaced. These findings begin to define the selectivity of POMGNT2 and suggest that this enzyme functions as a gatekeeper enzyme to prevent the vast majority of O-mannosylated sites on proteins from becoming modified with glycan structures functional for binding laminin globular domain-containing proteins.